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Incurable but treatable: Understanding, uncertainty and impact in chronic blood cancers—A qualitative study from the UK’s Haematological Malignancy Research Network

Debra a. howell.

1 Department of Health Sciences, University of York, York, United Kingdom

Dorothy McCaughan

Alexandra g. smith, russell patmore.

2 Queens Centre for Oncology and Haematology, Castle Hill Hospital, Cottingham, United Kingdom

Associated Data

All relevant data are within the manuscript and its Supporting Information files. Raw data (i.e. transcripts) cannot be shared publicly due to assurances of confidentiality given to participants at the time of consenting. The authors are unable to make the transcripts available upon request to researchers who meet the criteria to access confidential information for the same reason; also, permission to do this was not sought from participants.

Most blood cancers are incurable and typically follow unpredictable remitting-relapsing pathways associated with varying need for treatment, which may be distressing for patients. Our objective was to conduct a qualitative study to explore understanding among patients with such malignancies, including the explanations given by HCPs and the impact of uncertain trajectories, to generate evidence that could guide improvements in clinical practice.

The study is set within a population-based patient cohort (the Haematological Malignancy Research Network), in which care is delivered across 14 hospitals according to national guidelines. In-depth interviews were conducted with 35 patients with chronic lymphocytic leukaemia, follicular lymphoma, marginal zone lymphoma or myeloma; and 10 accompanying relatives. Purposive sampling ensured selection of information-rich participants and the data were interrogated using reflective thematic analysis.

Rich data were collected and four themes (11 sub-themes) were identified: 1) Knowledge and understanding of chronic haematological malignancies; 2) Incurable but treatable; 3) Uncertainty about the future; and 4) Treatable (but still incurable): Impact on patients. Patients had rarely heard of blood cancer and many expressed difficulty understanding how an incurable malignancy that could not be removed, was treatable, often for long periods. While some were reassured that their cancer did not pose an immediate survival threat, others were particularly traumatised by the uncertain future it entailed, suffering ongoing emotional distress as a result, which could be more burdensome than any physical symptoms. Nonetheless, most interviewees understood that uncertain pathways were caused by the unpredictability of their disease trajectory, and not information being withheld.

Conclusions

Many participants lacked knowledge about chronic haematological malignancies. HCPs acted to reassure patients about their diagnosis, and while this was appropriate and effective for some, it was less so for others, as the cancer-impact involved struggling to cope with ongoing uncertainty, distress and a shortened life-span.

1. Introduction

Arising in blood and lymph forming tissues, haematological malignancies (leukaemias, lymphomas, and myelomas, also known as blood cancers) are collectively the fifth most common cancer grouping in economically developed countries [ 1 , 2 ]. With diverse aetiologies, treatments, and outcomes, more than 100 subtypes are currently recognized by the World Health Organization (WHO) [ 3 ]. Although some of these cancers are potentially curable with intensive chemotherapy (e.g. diffuse large B-cell lymphoma and acute myeloid leukaemia), around 60% are not; the latter typically comprising more chronic or indolent diseases (e.g. chronic lymphocytic leukaemia (CLL), follicular lymphoma (FL), marginal zone lymphoma (MZL) and myeloma) [ 4 ]. These malignancies often have a slow manifestation, in which symptoms may be vague, intermittent and commonly seen in benign, self-limiting conditions, particularly in older age groups, meaning cancer is not always immediately suspected [ 5 , 6 ].

Interestingly, despite being incurable, many indolent blood cancers can be successfully managed, sometimes over many years, on what is considered a remitting-relapsing pathway. This trajectory may include periods of observation (known as ‘active monitoring’ or ‘watch and wait’) usually at diagnosis or when the cancer is in remission, interspersed with treatment at progression or as the disease burden increases (manifested by deteriorating blood results, or new/worsening symptoms), to restore remission. While some patients continue on observation without ever requiring treatment, if/when it is needed (which may occur on multiple occasions) it includes combinations of chemotherapy, radiotherapy, stem cell transplant and targeted agents [ 7 ]. Behaviour is known to differ between indolent blood cancers subtypes, with progression almost certain to occur for some (e.g. myeloma), but much less likely for others (e.g. CLL), as is reflected in the five-year relative survival estimates of 48% for myeloma, compared to 86%, 88% and 80% for CLL, FL and MZL, respectively ( https://hmrn.org/statistics/survival ).

With respect to the experiences of patients with chronic haematological malignancies, much existing literature is limited by the inclusion of individuals with both indolent and acute subtypes, with no differentiation between the two with respect to findings. Such studies have focused on issues such as information satisfaction, decision-making, and quality of life, as well as physician communication styles; identifying considerable scope for improvement [ 8 – 14 ]. Several studies have, however, specifically examined patients with chronic blood cancer subtypes in the last decade or so, with a recent survey identifying poorer diagnostic understanding compared to other malignancies [ 15 ]; a worrying issue given the link between information satisfaction and improved quality of life in cancer generally [ 16 ]. Other difficulties linked to chronic haematological malignancies include the issue of living with uncertainty, which may be associated with psychosocial problems [ 17 – 19 ].

There is, however, little qualitative evidence about patient knowledge and understanding of chronic haematological malignancies, the explanations given to patients by clinical staff and the impact the uncertain trajectories of these cancers have on those affected over time. To address this, we conducted an in-depth interview study, to generate evidence that could be used to guide improvements in clinical practice. Set within a broader UK National Institute for Health Research (NIHR) programme, this paper is one of a forthcoming series dedicated to examining patient experiences of chronic blood cancers, including information needs and preferences for involvement in decision-making.

Methods are described in accordance with COREQ [ 20 ].

2.1 Setting

This qualitative study was set within the infrastructure of the UK’s Haematological Malignancy Research Network (HMRN: www.hmrn.org ), a population based patient cohort initiated in 2004 to inform research and clinical practice; locally, nationally and internationally [ 7 ]. HMRN’s configuration, methods and approvals have been published [ 21 ]; and the present study has additional ethical support (REC:16/LO/0740). Briefly, HMRN has a catchment population of ~4 million, with a similar socio-demographic profile to the UK as a whole; and patient care is provided by a unified clinical network (14 hospitals), working to national guidelines. All haematological malignancies in the study area are diagnosed by a single laboratory (the Haematological Malignancy Diagnostic Service: www.hmds.info ), using the latest ICD-O classification [ 3 ]. Patients enter the cohort at diagnosis (~2,400 annually), and have diagnostic, prognostic and clinical data (including all treatment and responses) collected from their medical records.

2.2 Sampling strategy

In-depth interviews were conducted with patients from HMRN’s established Partnership ( https://yhhn.org/partnership ), who had agreed they could be contacted for research purposes. Purposeful sampling was utilised, in which patients were intentionally selected based on their demographic and diagnostic characteristics, in the likelihood of them being ‘information-rich’ sources, able to provide data that were relevant to the research aims [ 22 ]. In this context, initial inclusion criteria included: diagnosis of CLL, FL, MZL or myeloma (reflecting the spectrum of chronic cancers) in men and women close to the median diagnostic age for each subtype. Variation was then introduced by socio-economic area, age strata and time since diagnosis, to capture more diverse experiences [ 22 , 23 ]. The number of interviews conducted was guided by the concept of information power [ 24 , 25 ], which aligns with our analytical method, outlined in 2.4.

2.3 Recruitment and data collection

After checking with NHS staff that patients were alive, and well enough to participate, potential interviewees were sent an information sheet and asked to contact the research team if they wanted to take part, and to ask a relative/friend to join the interview, if they wished. Interviews were conducted February to October 2019, at a time and place chosen by the patient, usually their home. Informed written consent was obtained (permitting use of direct quotes) following assurances about confidentiality and anonymity, and the opportunity to ask questions. Interviews were conducted by an experienced researcher, lasted ~90 minutes and were digitally audio-recorded. Patients were asked to tell their own story from diagnosis, with a topic guide used to direct questioning ( S1 File ). Recordings were transcribed externally, then checked, corrected and anonymised by the interviewer.

2.4 Data analysis

Data analysis was conducted by the interviewer and a second researcher utilising reflexive thematic analysis, a method commonly used in studies seeking to identify patterns of meaning (‘themes’), which does not adhere to any particular theoretical stance [ 26 , 27 ]. The initial step in this approach involved familiarization and engagement with the data by active (i.e. analytical, critical) reading and re-reading of the transcripts, while constantly attempting to interpret the information provided. This was followed by the generation of useful, meaningful codes, by means of a fluid, organic, active process in which codes evolved, were renamed, divided, collapsed and/or deleted [ 25 ]. The next step was to search for and develop themes from the codes, which were then reviewed within a thematic map, before finally being defined and named.

Thirty-five patients were interviewed, 10 with a relative present (contributing to varying degrees). Pathway overviews and participant characteristics, based on routine HMRN data collection from medical records are shown in Table 1 . The majority were aged in their sixth or seventh decade at interview, nineteen were male, and most resided with a relative, with three living alone. Twelve had myeloma, ten CLL, eight FL, and five MZL. Rich data were accumulated and reflexive thematic analysis resulted in the identification of four themes and 11 sub-themes. Key themes included: 1) Knowledge and understanding of chronic blood cancers; 2) Incurable but treatable; 3) Uncertainty about the future; and 4) Treatable (but still incurable): Impact for patients. Each theme is described below with sub-themes. Quotations are shown in italic and linked to participant numbers (e.g. P1 for the patient, P1R for P1’s relative) and diagnosis. Fig 1 depicts the hierarchy of themes and sub-themes.

1 CLL: Chronic lymphocytic leukaemia; FL: Follicular lymphoma; MZL: Marginal zone lymphoma.

2 Chemotx = Chemotherapy; HPE = Helicobacter pylori eradication; Radiotx = Radiotherapy; SCT = Stem cell transplant (all autografts); SCH = Stem cell harvest (shown for P33 because this patient’s SCT was cancelled as it was considered risk by clinical staff and the patient).

3 Does not include supportive care (e.g. blood product transfusions, plasma exchange, bisphosphonates, cell mobilization products).

4 Patient was diagnosed pre-HMRN; pathway data collected at interview.

Theme 1, knowledge and understanding of chronic blood cancers

This theme contains five sub-themes that focus on patient knowledge, understanding and expectation regarding blood cancers.

Sub-theme 1, prior knowledge

Many people said they had no prior knowledge of their malignancy type, with one saying he knew about ‘ standard cancers ’ but not myeloma (P16). In the context of CLL, P13 said she had known ‘ nothing ’ about her disease; and P29 said she had known leukaemia was a ‘blood cancer’, but no more. P30 said he ‘didn’t even know the word myeloma until I went to the doctors’ . Patients did not always immediately understand the nature of their chronic blood cancer, but initially reported focusing on specific phrases such as ‘not curable’ and ‘leukaemia’, which could be distressing, incurring shock and fear, particularly as there was little awareness about indolent and acute subtypes, or the different pathways and outcomes associated with each of these.

Sub-theme 2, unexpected diagnosis

Some patients had been diagnosed incidentally and otherwise considered themselves well, so were confused to discover they had cancer. In patients with myeloma, for example, P21 was diagnosed at a routine check-up ‘by accident’; and P16 said his diagnosis came ‘ out of the blue ’ as he considered himself fit and active. Others had only minor symptoms and didn’t always feel ill, with P22 (CLL) explaining his surprise at being told he was ‘ a very poorly man’ at his first appointment, as his only prior symptom was tiredness; P15 (FL) declaring ‘ I wasn’t ill…it was just the lumps I found’ ; and P27 (CLL) saying apart from difficulty walking, he felt fine.

This was augmented in a number of patients, as they had actually attended medical appointments for what they presumed to be unrelated symptoms, but which were later attributed to their blood cancer. Examples include diagnosis following screening to assess breast lumps (P15: FL, P20: CLL); a GP visit for leg pains (P29: CLL); an ENT appointment for a neck lump (P17: FL); and a scan for osteoporosis (P35, myeloma). Conversely, however, some individuals had heard of their cancer and knew of its clinical signs, with one saying that the ‘jigsaw fell into place’ (P12: MZL), as he had thought his symptoms were due to lymphoma.

Sub-theme 3, expectations about chronic blood cancers

A number of patients struggled to understand the characteristics of their cancer and why it could not simply be removed. In this context, P5 (MZL) described her main barrier being that what seemed like a stomach problem couldn’t be treated with a simple ‘zap’ ; she did, however, accept that her cancer was different to the type you could just ‘get rid of’ . Similarly, P13 (CLL) said she had found it hard to understand she had leukaemia because the first symptom was a lump in the armpit, which led her to presume that: ‘if it’s a lump they can just take it out’ and resulted in ‘ a bit of a shock ’ when she found this was not possible as the cancer was in her blood, so in her ‘whole body’ .

Based on their knowledge of other cancers, most people expected to start treatment immediately after diagnosis, whereas many were initially observed. While this satisfied some, particularly if a HCP had clearly explained the underpinning rationale, many found it difficult to comprehend. P26 (myeloma), for example, said: ‘it’s hard to understand you have something that is so…really frightening…yet nothing happens’ . P15 (FL), said she found it challenging to understand and accept and was ‘not prepared’ for the situation; she was also unclear about the circumstances that would lead to her starting treatment, saying: ‘ that was always a question I had; how doctors would know when to start treatment : it was almost like you had to become ill… .’. Similarly, P6 (CLL) and her husband described difficulty comprehending that ‘nothing was being done’ , whilst they just waited for things to get worse before: ‘they’ll sock it (treatment) to you’ .

Sub-theme 4, ongoing lack of knowledge

While some later came to have a good grasp of their illness, others didn’t seem to reach this point and were still unclear about their malignancy a number of years post-diagnosis. P32 (MZL), for example, said she could not discuss her diagnosis with family, partly because she didn’t really understand it: ‘we’ve never ever… we’ve got a son and a daughter , we’ve never told them because really , we don’t know what we’re talking about…’ . Knowledge and understanding was found to impact on diagnostic disclosure, with P20 (CLL) saying he told his immediate family, but not his friends as he believed they wouldn’t comprehend why treatment had not started: ‘I don’t publicise it’ . This was echoed by P25 (FL), who said others didn’t understand the characteristics and impact of her cancer.

Sub-theme 5, signs of progression/relapse

Several patients demonstrated clear knowledge of the signs of progression/relapse and how to respond: ‘(I) keep a look out and get in contact with them (HCPs) when…I get any…B symptoms of night sweats…itchy skin , tiredness , you know , problem with breathing and all that’ (P34: FL); with P25 (FL) saying she would ‘ know straightaway if something was wrong ’. Others were, however, worried about their lack of awareness. P19 (FL) for example, said that initially she hadn’t been told what to look for, and was ‘ not convinced that I would know if it was back ’. Having responsibility for recognising potential signs of progression and deciding when to report these was difficult for some, with P35 (myeloma) explaining: ‘That’s why it’s so complicated . So , it’s kind of down to me to tell them if I don’t feel right and I just find , that’s just a massive pressure’ .

Theme 2, incurable but treatable

This theme focuses on the information provided by HCP to promote understanding among patients and families about the characteristics of the chronic haematological malignancies; it also contains a sub-theme about response to this. Patients often mentioned that HCPs had referred to their cancer as being incurable but treatable. Phrases HCPs were said to use include: ‘ it’s very treatable’ (21R, myeloma); and ‘ there’s no cure but it is not life-threatening ’ (P20R, CLL). Similarly, P34 (FL) described being told he had cancer, but that it was: ‘ …low grade…slow growing but harder to get rid of … an incurable cancer; (that) the chemo was probably going to be effective in some way , but… I’d never be in full remission’ .

A number of people said their HCP likened their diagnosis to living with a chronic illness, with comparisons made to ‘ diabetes ’ (P15: FL), and ‘ similar to me COPD’ [sic] (P25: FL). In terms of prognosis, several others said that reassurance emerged via HCPs implying they would die from other causes, not the blood cancer itself, recounting phrases such as: ‘(you) could actually die with it , not because of it’ (P7, CLL). P32 (MZL), described being told she could expect a lifespan that was ‘same as anybody else’ . P32R went on to say ‘…it’s the stigma , with the word cancer and that . Everybody thinks it’s a death sentence , don’t they ? So (doctor) sort of said it , there’s something wrong with you , but you can live with it . It wasn’t life threatening or anything like that…’ .

Sub-theme 1, relief or distress? Many interviewees described feeling relief at hearing their cancer was incurable but treatable, with P7 (CLL) considering this: ‘ a big ray of hope in the distance’ ; and P3 (CLL) feeling ‘positive’ after his haematologist told him he would certainly be attending clinic ten years hence. P12 (MZL) said that after being told ‘it’s more likely you’ll die with it than of it… . that phrase settled me…’ . Another was similarly reassured when their consultant said: ‘ …this could take weeks to develop , months , decades…go and live your life’ (P26: myeloma). P17 (FL) described being ‘ in a bit of state of shock at diagnosis ’, but relieved when the haematologist said: ‘we can treat this’ . The relative of P22 (CLL), said she and her husband coped by focusing on such positive phrases.

While some patients were reassured, however, others were deeply troubled. P35 (myeloma) for example, said progression was always on her mind: ‘ it’s just horrible being in this position where you know (the paraprotein) it’s creeping up’ . Similarly, P34 (FL), said: ‘it’s hard not to think that everything is related to lymphoma . Any time something happens to me I’ve got it in the back of my mind , what’s this ache I’ve got ? ’ . P17 (FL) described the sudden appearance of a neck lump (later diagnosed as a cyst), saying: ‘you obviously think it’s something to do with the lymphoma’ . The need for counselling, or psychological/emotional support was noted by some patients, and also family members. P4 (MZL), P13 (CLL) and P19 (FL), for example, reported accessing such services to help them manage diagnostic distress; although P12 (SMZ), said his diagnosis didn’t affect him ‘ psychologically ’ as he had a ‘ low-grade type ’. This issue of distress is picked up in greater detail in Theme 4, Sub-theme 2.

Theme 3, uncertainty about the future

Uncertainty generally pertained to the occurrence and timing of cancer progression, the need for treatment, and prognosis, as described within the two sub-themes below.

Sub-theme 1, progression

Although patients were told progression might never occur, they were aware it could still happen at any time and on numerous occasions, with the need for multiple lines of increasingly intensive chemotherapy. In the context of myeloma, P28 said ‘ they’ve wanted to put me on a 4 th line of treatment… . my light chains are very high…’ . Changes were said to happen slowly or rapidly, and could lead to altered treatment plans. P18 (myeloma), for example, described gradually ‘getting more and more breathless’ in the post-transplant period as he relapsed, with further chemotherapy given prior to a planned second transplant, which was then abruptly ‘ruled out’ as his ‘free light chains had rocketed back up again’ .

Uncertainty about the timing of progression/relapse was said to be clearly communicated at various time-points on the pathway. At diagnosis, for example, P20 said his CNS ‘went through it very thoroughly’ explaining that his CLL may progress, but that ‘nothing might happen during (his) life-time…you might live with it as long as you live’ ; and P30 (myeloma) noted how one doctor ‘went straight to the point’ , telling him ‘sometime or other chemo will have to come in , but he didn’t say when’ . Uncertainty about future progression/relapse was also conveyed post-treatment, as noted by P34 (FL) whose HCP ‘basically explained…how you cannot predict what’s going to happen . It may never , ever come back . It may come back tomorrow . It’s just completely uncertain and that’s what you have to have in your head…’ . Similarly, P10 (FL), described how after second-line chemotherapy, his consultant had said the cancer: ‘had gone completely , but could come back 5 or 10 years down the line (as there wasn’t) 100% guarantee that it won’t , but in all honesty , we think it probably will at some stage come back…it’s a raffle really…you could be lucky or it could come back’ . P16 (myeloma) said ‘(HCPs) advise you…be prepared it could return…I know mine will…’ .

Sub-theme 2, prognosis

With respect to prognosis, patients described being told that their survival duration was also unclear. Importantly, however, there was often recognition and understanding that this reflected genuine clinical uncertainty, due to the unpredictability of their cancer, rather than the withholding of information by HPCs ( Box 1 ) . P11 (myeloma), for example said he had reached ‘ a plateau ’ and that his clinicians had said: ‘ some people stay on that plateau for quite a long time , others don’t ’. This patient seemed to understand that doctors couldn’t be certain about individual patients, and that nobody can ‘ really know what’s in store down the line ’. P25 (FL) described how she wanted to know more about her prognosis including: ‘what is the likelihood of (the cancer) coming back…what’s the odds ? ’ and ‘ how many people live to a ripe old age and die of something else ? ’ but compared this to asking ‘how long is a piece of string ? ’ ; and P3 (CLL) explained that having an uncertain pathway meant it was difficult to know when was the right time to ask about prognosis.

Box 1. Reflections on genuine clinical uncertainty

○ ‘(HCPs) couldn’t say for sure what my prognosis was because they really didn’t know… everyone is different , that’s what I learned’ (P3: CLL)

○ ‘(HCPs) just don’t know how it will evolve in your body’ (P4: MZL)

○ ‘there aren’t any answers…you’ve just got to wait and see’ (P7R: CLL)

○ ‘everyone is different and so it’s difficult to say , well this is going to happen…it’s not that certain’ (P15: FL)

○ ‘(HCPs) can’t give you a timescale…you accept the worst and hope for the best’ (P16: myeloma)

○ ‘there are a lot questions that people just don’t know the answers to’ (P18: myeloma)

○ ‘(HCP) just said “we don’t know…” , they’ve never actually said “the average is 6 years or the average is… [before relapse]” I don’t think they can’ (P19: FL)

○ ‘(HCP said) we can’t give you an answer (about prognosis) , we don’t know…everybody is different , which I can accept that’ (P25: FL)

○ ‘myeloma is a very individual disease…you get the same treatment , same this , same that , but you have different outcomes’ (P28: myeloma)

Theme 4, treatable (but still incurable): Impact on patients

Having a treatable but incurable chronic haematological malignancy, affected patients differently, with the diagnosis gaining or losing impact over time, and some individuals experiencing particular emotional difficulties coping with uncertain future pathways, as depicted in the sub-themes below.

Sub-theme 1, diminishing impact

For some, the impact of their indolent blood cancer diminished as they became more accustomed to it, especially if they had not required any treatment, and were being monitored less often. This was particularly apparent in CLL, but also to a lesser extent other diagnoses, with one patient (P26, myeloma) starting with 3 monthly monitoring, which reduced to checks every 6 months, before being replaced by telephone appointments. In another example, P29 said she had spoken to her consultant about the future and been told ‘ right at the beginning , maybe 5 years , maybe more ’; 3 years post-diagnosis at interview, she said: ‘ so I’ll just keep going’ , saying she didn’t want to dwell on her disease, as keeping positive helped her cope.

Sub-theme 2, increasing impact and emotional difficulties

For many, having a chronic haematological malignancy had a significant impact on their life. One such group included patients for whom severe emotional distress appeared to be ongoing, causing greater difficulty than any physical effects from the cancer. Such anxiety was clearly portrayed by P35 (myeloma), who said: ‘ …you’re at different stages all the time , and I’m in a bit of a difficult [stage] I think it’s like fear of not knowing what’s going on is harder than like , if someone says , you’ve got to have this and [you can] psych up for it . I’m just in an awful time for me , but then again , I’m constantly wrangling with myself , because then I just think , I’m just so grateful to be here and I do have treatment options , you know , it could be worse…and my quality of life is good at this point and I don’t want to waste it by [being] up and down . Oh , I’m so anxious , you know , I really don’t want to do that . I just want to get on . It’s bloody hard though’ . Similarly, P25 (FL) described distress caused by wondered how long her cancer would be ‘manageable’ , comparing her situation to ‘Russian roulette (where) someone has got a gun against my head…’ . The same patient, who had attended the haematology clinic regularly since diagnosis, reported being anxious when she didn’t receive her usual appointment and ‘kept ringing up’ , only to be told she was on a waiting list. She said she just needed reassuring that she was ‘alright’ , but felt her HCPs were simply ‘ waiting for me to die’ .

Sub-theme 3, survival

Despite being treatable, chronic blood cancers are generally considered incurable, and can potentially effect survival, which was of great concern to some, including younger patients, such as P28 (age 59 at diagnosis; myeloma): ‘it’s a non-curable cancer… certainly , it’s treatable , but nonetheless , that was kind of a big shock in itself , a huge shock (finding) 50% of people survive 5 years’ . In an ‘ unforgettable’ exchange with an HCP, P4 (age 57, MZL) recounted being reassured that her cancer was treatable, but then learning it could significantly limit her life expectancy: ‘the first thing (HCP) said to me was “you might only live 5 years with it…” . I just couldn’t take it in…you’ve just been told you’ve got cancer and she’s saying “you might only live for 5 years ! ”‘ . S ome older patients viewed their prognosis in the context of their life-span, however; P15 (FL, age 72), for example, saying: ‘ 10 years , which at my age is more than you could hope for’ .

Interestingly, P35 (myeloma) noted undue optimism from clinical staff about her treatment and prognosis: ‘They kind of just acted in a positive way . They don’t say : “it might not work” . They’re just being really positive , but…I was in the unfortunate situation of knowing someone really well who had (myeloma) , and he’d had a really bad time and none of the treatment worked’ . P35 went on to describe having asked: ‘… can I live to be an old person ? And (nurse) said…I’ll never forget it , it’s in my mind a lot , she said , “you might have to re-evaluate what you mean by old” , and it really sticks in my mind but I couldn’t bring myself to ask any more questions [became upset]’ . She then demonstrated a mix of fear and hope, saying: ‘ I’ve never dared ask how long I might live and things like that , because they don’t know , because like , what works for one person doesn’t work for another , and you get these people who get long remissions . I always have a few questions , but I don’t ask the things that are sort of on my mind . It’s just too big’ .

Maintaining optimism was considered important by P35 (above) and other interviewees. P24 (FL) said it was important for doctors to give patients hope, and for patients to maintain a positive mental outlook. Patients themselves often placed their hope in new therapies, with P34 (FL) saying he hoped his prognosis had improved since diagnosis: ‘treatments have changed… and obviously it’s going to be a lot better outcome (now) . I know that the outcome would have been different if I hadn’t have had (drug) … you know , I don’t think I would have been told 5 years . But now , who knows . They told me if I went now , they’d give me a different… prognosis . They’d be looking at what I am now…going forward…’ . P11 (myeloma) said: ‘they are constantly improving medication’ ; and the relative of P27 (CLL) reported their consultant saying ‘things are moving on all the time… we can re-treat’ , which gave them ‘a lot of confidence’ .

4. Discussion

This study contributes novel evidence about the experiences of patients with chronic haematological malignancies. Specifically, we identified a distinct lack of knowledge about such cancers among patients, HCP communication strategies that often aimed to reassure individuals about their indolent diagnosis, and an immense amount of uncertainty about the future. The resulting impact on patients varied, with some feeling relieved that although their chronic cancer may not be curable, it could be treated (if treatment was ever required), while others struggled to grasp and deal with this. Living with uncertainty often caused marked ongoing emotional distress, even among patients with the most indolent diseases, who were asymptomatic and did not require treatment; and in many cases this appeared more burdensome than any physical consequences of the cancer.

The unusual pathways of chronic haematological malignancies clearly impacted on the well-being of some patients. Compared to other cancers, for example, where relapse may only need to be considered once or twice, individuals with chronic blood cancers may have to face this repeatedly, on a third, fourth or subsequent occasion, across their remaining life. This is also a crucial difference between the chronic subtypes targeted in the current study and the more aggressive entities that may be potentially curable with intensive treatment; after which (similar to many other cancers) a distinct ‘survivorship’ phase begins. This marks another divergence, as traditional concepts of survivorship denote a phase ‘beyond’ treatment [ 28 – 30 ], a time-point never reached on the remitting-relapsing pathway of chronic blood cancers, meaning resources and national initiatives set-up to meet long-term needs are not always applicable to these patients.

Although communicating information about uncertain pathways is a major component of existing good clinical practice, which was clearly appreciated by participants, some continued to struggle with this constantly being a part of their lives. Described as an ‘ever-shifting perspective between illness and wellness’ in the context of myeloma [ 18 ], this situation has been linked to anxiety, distress, depression, isolation and quality of life levels that match those of patients receiving treatment [ 12 , 17 – 19 , 31 , 32 ]. Indeed, psychological adjustment has been described as more difficult in these cancers than physical effects [ 12 ]. Unfortunately, the very nature of chronic haematological malignancies means patients attend clinic infrequently, or less often those with acute subtypes, so may have little face-to-face time with clinicians [ 19 ], reflecting fewer opportunities for HCPs to identify difficulties, provide reassurance and facilitate interventions.

Interestingly, patients with cancer have been described as experiencing ‘a journey of never-ending making sense’ as they attempt to regain control over their lives, despite changes in their disease and treatment [ 33 ]; a compelling perspective in the context of chronic blood cancers. A further interesting notion pertinent to the inherent uncertainty associated with blood cancers is that discussions about the future and prognosis should adopt an individualized, sensitive and honest approach that achieves a balance between hope and a realism [ 34 – 37 ]. Not a new idea, this concept gained importance in the last decade and may protect patients from over-optimism regarding prognosis, as was noted in our study and is recognised to exist more generally among HCPs providing cancer care [ 38 , 39 ]. It may also improve preparedness for disease progression or relapse, and the need for (more) treatment, or indeed end of life care, where this situation arises.

As noted, patients with chronic blood cancers do not always commence treatment immediately at diagnosis, but may instead be observed, only receiving treatment at disease progression or when they become (more) physically symptomatic; a concept many patients found difficult to process and a factor that contributed to their anxiety. Such anxiety is perhaps unsurprising, however, as preventing delayed cancer diagnosis is at the forefront of NHS policy and, combined with early treatment, is recognised as a means of maximising survival [ 40 , 41 ]. In this context, and as similar initial management strategies may also occur in other cancers (e.g. active surveillance in prostate cancer [ 42 ]), raising awareness among the public that such pathways are evidence-based and set within national guidance may be helpful.

In line with our findings, other studies note a pre-diagnostic lack of knowledge about haematological malignancies, and an ongoing lack of understanding about these diseases, although there was recognition that they differed from other cancers [ 5 , 12 , 43 ]. The patients we interviewed who had been diagnosed with myeloma described what appeared to be particularly difficulty pathways compared to those with the other subtypes of interest, perhaps because disease progression was almost inevitable in myeloma [ 18 ]; complications (e.g. fractures and renal failure) often occurred before and after diagnosis [ 44 ]; and quality of life and physical functioning was considered more problematic than for other blood cancers [ 45 ]. This group of patients is also reported to have limited understanding of their diagnosis, compared to levels of comprehension among people with other cancers [ 15 ].

Worryingly, patients in a UK study of CLL noted how their doctors do not always seem to fully appreciate how they feel, or are affected by their cancer [ 17 ]. The research we present here, however, in conjunction with that of others, has clearly shown that problems (e.g. psycho-social and information needs) may be significant and enduring [ 12 , 17 – 19 , 31 , 32 ]. This is important in the context of clinical practice and health policy (including survivorship), in order to ensure the unmet needs and challenges experienced by patients with chronic blood cancers are not overlooked by HCPs, simply because their disease is less acute than other haematological malignancies, and more long-term. It is also important that further research takes place examining the extent to which HCPs are aware of anxieties and distress; and the availability and effectiveness of interventions to address this.

To our knowledge this is the first study focusing solely on the experiences of patients with chronic haematological malignancies. Purposive sampling ensured information rich participants were included [ 22 ], thereby aligning with the concept of information power [ 24 , 25 ]. The analytical process involved two experienced researchers and quality was ensured via ongoing engagement with the data and reflexive interpretation [ 25 ]. Findings are comprehensively described and provide new insights into an important, under-researched area, which highlights significant challenges for patients. Our results are likely to be transferable [ 46 ] within the UK and countries with similar health-care services, and to other chronic cancers/conditions. Despite significant efforts, we were unsuccessful in recruiting interviewees ethnic minority backgrounds, and future dedicated research is required in this area. Finally, we interviewed patients who consented to further contact via the HMRN Partnership, thus did not capture the experiences of those too ill to be approached.

5. Conclusion

Many participants lacked knowledge about chronic haematological malignancies. HCPs acted to reassure patients about their diagnosis, and while this was appropriate and effective for some, it was less so for others, as the cancer-impact involved struggling to cope with ongoing, uncertainty, anxiety, distress and a shortened life-span, which could be more burdensome than any physical symptoms.

Supporting information

Acknowledgments.

We wish to thank the study participants who openly shared sensitive information about emotive issues.

Patient and public involvement (PPI)

All HMRN studies benefit from significant PPI via a Patient Partnership. The present study arose due to PPI into HMRN’s research agenda. Patients were involved as co-applicants for funding and on the steering committee; they commented on paperwork and provided a ‘Sounding Board’ for findings.

Funding Statement

1. DH, ER, AS and RP: National Institute for Health Research Programme Grant for Applied Research (NIHR PGfAR): RP-PG-0613-2002. https://www.nihr.ac.uk/explore-nihr/funding-programmes/programme-grants-for-applied-research.htm 2. DH, ER, AS: Cancer Research UK (CRUK) 29685. https://www.cancerresearchuk.org/ DH, ER, AS: Blood Cancer UK (BCUK) 15037. https://www.cancerresearchuk.org/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Data Availability

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The Landscape of Blood Cancer Research Today-and Where the Field Is Headed

Affiliation.

• 1 American Association for Cancer Research, Philadelphia, Pennsylvania. [email protected].
• PMID: 34661134
• PMCID: PMC8447268
• DOI: 10.1158/2643-3249.BCD-20-0083

This editorial integrates the views of Blood Cancer Discovery 's editors-in-chief and scientific editors to explore the current and near-future landscape of the study of hematologic malignancies-from the most intriguing new developments in clinical and basic research to the greatest upcoming challenges and how they will be confronted.

©2020 American Association for Cancer Research.

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What is blood cancer and why do we need more research?

Blood cancers are the fifth most common type of cancer in the world and around 1.3 million new cases of blood cancer were diagnosed worldwide in 2020. The good news is that thanks to research, blood cancer diagnosis and treatments are getting better. But what are blood cancers? How are they caused? And how is our research helping to start new blood cancer cures?

What is blood cancer?

Blood cancers affect the cells which make up our blood, causing too many, too few, or faulty cells to be produced. They develop when the cells involved in producing our blood gather cancer-causing DNA changes and stop working properly. 

Because many of our blood cells are involved in keeping our immune system working well, having a blood cancer might make it harder for people to detect and fight off infection. Blood cancers can also affect parts of the body involved in producing and transporting blood cells, like bone marrow and the lymphatic system.

Doctors currently recognise that there are at least 100 different types of blood cancer. Each one comes with different challenges, treatments, and outlook.

Some blood cancers develop quickly, while others can take years. People with some slowly developing types of blood cancer may not need immediate treatment. They may instead be monitored closely over time.

Your blood cancer FAQs:

Researchers are still working out exactly what causes these changes, and how they can lead to blood cancer.

Some DNA changes might be caused by exposure to risk factors in our environment, such as chemicals, or radiation. Other reasons may be genetic, or due to the presence of other health conditions.

DNA changes also occur naturally over time as we age, and our cells become less efficient at picking up and correcting these changes. This is one reason why older people generally have a higher risk of developing any cancer.

For many cases of blood cancer, the underlying cause is not known, but research in this area is already helping us to find out more. We’re proud to be supporting several blood cancer research projects which are investigating how blood cancers begin. 

• Lymphoma is a type of cancer which affects our lymphatic system. This is a network of vessels which runs throughout our body and helps to carry immune cells like white blood cells, waste, and water. It has an important role in our immune system. Lymphoma happens when a type of white blood cell called a lymphocyte does not develop properly. The cells begin to divide out of control and clump together to form solid lumps. Tumours most commonly form in the lymph nodes but they can form in other parts of the body too. Lymphomas are usually classed as Hodgkin lymphoma or non-Hodgkin lymphoma, depending on the type of cell that is affected. Hodgkin lymphoma is more rare in the general population, but is one of the most common cancers diagnosed in younger people.
• Leukaemia is a cancer of white blood cells. It usually begins in the bone marrow when the process of generating new white blood cells goes wrong. Precursor blood cells (called ‘stem cells’) produce too many cells that do not develop fully. This leads to a lack of healthy cells able to work properly. It can also disrupt the balance between white blood cells and other cells in the blood, causing further problems. There are many different types of leukaemia, which are usually named according to the type of cell they affect, and whether they are chronic or acute. Acute types of leukaemia develop quickly and can have more severe symptoms at an earlier stage. Prompt treatment is often needed to help prevent rapid progression. Chronic types of leukaemia tend to develop more slowly, with milder initial symptoms. Treatment is usually still required, but the condition may be managed differently over time.
• Myelomas  develop when a type of bone marrow cell called a plasma cell begins to divide uncontrollably. Plasma cells are usually involved in producing antibodies, which help our immune system recognise and fight off infection. When myeloma develops, plasma cells do not produce antibodies correctly, and this can affect our ability to recover from infection. The overproduction of plasma cells can also lead to problems with production of other cells in the bone marrow, causing further issues.  Myeloma is usually called multiple myeloma because it can affect any bone in the body which contains bone marrow involved in blood cell production. Myeloma can develop in different areas of the body at the same time.
• Other more rare conditions such as myeloproliferative disease (also called myeloproliferative neoplasms or myeloproliferative disorders), and myelodysplastic syndrome (also called myelodysplasia) are also classed as blood cancers. These conditions affect cells of the bone marrow, causing them to produce too many blood cells, or too few healthy blood cells.

People with blood cancer may experience a number of different symptoms. Some are quite general and could be explained by other more common conditions. If you have any symptoms that you are unsure about, it’s always worth talking to your GP.

Some common symptoms of blood cancers include:

• Heavy sweating at night
• Persistent or recurrent infections
• Uncomfortable pain in bones and joints
• Unusual or frequent bruising and bleeding
• Looking very pale or greyish coloured
• Feeling breathless
• Persistent tiredness, or weakness
• Other unexplained general symptoms such as weight loss, rash or itchy skin, lumps or swellings

Several different treatments are available to treat blood cancer. Standard treatments like chemotherapy and radiotherapy have been developed over many years, and are still very effective.

Blood cancer researchers have also made huge progress in developing new effective treatments which can work alongside existing treatments. These include:

• Targeted therapies - which act on specific molecules involved in cancer growth.
• Immunotherapies (including CAR-T therapy) - these work with our immune system to treat cancer.
• Stem cell transplants - where blood stem cells which are affected by cancer are replaced with your own or someone else’s healthy new stem cells.

We cannot fund vital research that will find new ways to prevent, diagnose, and treat blood cancer without the support of Curestarters like you. Together we can save lives by discovering the next cure for cancer. Will you join us today? 

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Explore  CRI’s 2023 Cancer Research Impact

Immune to Cancer: The CRI Blog

Blood Cancer Awareness Month: How Immunotherapy Fights Leukemia, Lymphoma, and Multiple Myeloma

‘Blood cancer’ is an all-encompassing term for cancers that impact millions of people globally every year. The most common blood cancers are leukemia , lymphoma , and multiple myeloma . Each of these cancers is unique, but their common thread is they cause bone marrow and the lymphatic system to produce malfunctioning white blood cells. CRI-funded scientists and CRI ImmunoAdvocates are working hard to improve immunotherapy outcomes for blood cancer patients and to advocate on their behalf. 

“My experience with immunotherapy was truly a miracle.” READ MORE: How Immunotherapy Saved Sonia’s Life

Leukemia: Leukemia is a type of cancer that affects the blood and bone marrow. It begins in the bone marrow, where blood cells are produced, and causes abnormal white blood cells. It is the most common cancer in children under 15 years of age.  

Lymphoma: Lymphoma is a type of cancer that originates in the lymphatic system, which is part of the body’s immune system. It primarily affects lymphocytes, a type of white blood cell that helps fight infections. Lymphoma causes these cells to grow uncontrollably, leading to the formation of tumors in the lymph nodes, spleen, bone marrow, and other parts of the lymphatic system.  

Multiple Myeloma: Multiple myeloma is a cancer that starts in the bone marrow and primarily targets plasma cells, a type of white blood cell that produces antibodies to combat infections. In this condition, abnormal plasma cells multiply excessively, resulting in a range of complications.  

CRI Scientists Share Recent Immunotherapy Progress Against Blood Cancers

In the past decade, CRI-funded scientists have made significant inroads in the fight against blood cancers, including two former CRI postdoctoral fellows who determined how a specific type of leukemia thwarts a proper immune response to the cancer. Immunotherapy research has vastly improved blood cancer patient outcomes for people who have specifically been treated with CAR T therapy. Several CRI-funded scientists focus their current research on CAR T therapy, including Marco Ruella , MD, assistant professor of medicine and scientific director of the Lymphoma Program at the University of Pennsylvania and 2024 CRI CLIP Investigator. Dr. Ruella’s grant focuses on lymphoma , but his clinic services patients for all of the major blood cancers. He said we are living in an exciting time for novel blood cancer immunotherapy research, and CAR T therapy shows promise as an earlier line of treatment. 

“In the last year we have seen the continuous expansion of indications for CAR T immunotherapy to more subsets of B cell leukemia and lymphomas,” Dr. Ruella said. “With the advent of gene editing, we are now able to modify our immunotherapies to make them more effective and potentially safer.”

He aims to unravel resistance mechanisms with CAR T immunotherapy, thereby developing more effective therapies for blood cancer patients. Dr. Ruella has published several research papers so far in 2024, including as the senior author of a Science Immunology publication detailing how the immune checkpoint protein CD5 magnifies the anti-tumor actions of adoptive CAR T cell therapies.

Other CRI-funded scientists share his passion and drive to conquer blood cancers through immunotherapy. Matteo Maria Bellone , MD, head of the Cellular Immunology Unit and medical consultant in clinical immunology at IRCCS Ospedale San Raffaele in Italy, professor of immunology at the Università Vita-Salute San Raffaele in Italy, associate editor at Frontiers in Immunology and Frontiers in Oncology , and CRI CLIP Investigator, expressed a desire to design therapies for patients with smoldering multiple myeloma (SMM) to halt the disease before it becomes incurable. 

“We are investigating how microbes inhabiting our intestinal tract influence the immune response to neoplastic plasma cells, and how to manipulate these microbes to strengthen anti-tumor immunity,” Dr. Bellone told CRI. He described that interactions between cancer cells and the immune system can be large and complex – like a city riot fought in nooks and alleys. “Some cancer cells sneak through the immune cells’ fences, helped by corrupted guards. We need to make immune cells more efficient, to limit collateral damage, and to avoid excessive harm to the healthy tissue.”

Dr. Bellone’s grant project focuses on modulating both the gut microbiota and immune system response to multiple myeloma. In March of 2023, he published a research paper in Leukemia as a co-senior author that presented up-to-date evidence of diet and other lifestyle impacts on the gut microbiome, multiple myeloma incidence, and patient outcomes. 

Conclusion: Blood Cancer Symptoms and Screening

A non-exhaustive list of blood cancer symptoms includes night sweats, unexplained rashes and bleeding, frequent infections, and difficulty breathing. These symptoms do not always present in an early stage, and blood cancer testing can include conducting blood and bone marrow tests, imaging scans, physical exams, and staged surgical lymph node removal. By seeing a doctor if you are experiencing symptoms and encouraging loved ones to do the same, you can help create a world immune to cancer. 

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Advances in Leukemia Research

Human cells with acute myelocytic leukemia.

NCI-funded researchers are working to advance our understanding of how to treat leukemia. With progress in both targeted therapies and immunotherapies, leukemia treatment has the potential to become more effective and less toxic.

This page highlights some of the latest research in leukemia, including clinical advances that may soon translate into improved care, NCI-supported programs that are fueling progress, and research findings from recent studies.

Leukemia Treatment for Adults

The mainstays of leukemia treatment for adults have been chemotherapy , radiation therapy , and stem cell transplantation . Over the last two decades, targeted therapies have also become part of the standard of care for some types of leukemia. These treatments target proteins that control how cancer cells grow, divide, and spread. Different types of leukemia require different combinations of therapies.  For a complete list of all currently approved drugs, see Drugs Approved for Leukemia.

Although much progress has been made against some types of leukemia, others still have relatively poor rates of survival. And, as the population ages, there is a greater need for treatment regimens that are more effective and less toxic  than standard chemotherapy.

Acute Lymphoblastic Leukemia (ALL) Treatment

Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). It usually gets worse quickly and needs rapid treatment. Some recent research includes:

Combining less-toxic therapies

The intensive chemotherapy treatments used for ALL have serious side effects that many older patients cannot tolerate. Targeted therapies may have fewer side effects than chemotherapy. Clinical trials are now testing whether combinations of these types of therapies can be used instead of chemotherapy for older patients with a form of ALL called B-cell ALL.

Immunotherapy

Immunotherapies are treatments that help the body’s immune system fight cancer more effectively. Immunotherapy strategies being used or tested in ALL include:

CAR T-cell therapy

CAR T-cell therapy is a type of treatment in which a patient’s own immune cells are genetically modified to treat their cancer.

• Currently, one type of CAR T cell therapy is  approved for the treatment of some children and young adults with B-cell precursor ALL . This CAR T cell therapy is now being explored for use in older adults with B-cell ALL. 
• A second CAR T-cell therapy has also been approved for adults with B-cell precursor ALL that has not responded to treatment or has returned after previous treatment.

CAR T cell therapies are now being explored for other uses in ALL. For example, scientists hope that it will be possible to use CAR T-cell therapy to delay—or even replace—stem-cell transplantation in older, frailer patients.

Bispecific T-cell engagers

Another immunotherapy being tested in ALL is bispecific T-cell engagers (BiTEs). These drugs attach to immune cells and cancer cells, enabling the immune cells to easily find and destroy the cancer cell by bringing them closer together.

Once such BiTE, called blinatumomab (Blincyto) , was recently shown to improve survival for people with ALL who are in remission after chemotherapy , even when there is no trace of their disease. In 2024, FDA approved blinatumomab for adult and pediatric patients one month and older with a specific type of B-cell precursor ALL. The approval is for use as part of consolidation chemotherapy, which is treatment that is given after cancer has disappeared following initial therapy.

Improving treatment for adolescents and young adults (AYAs)

An intensive treatment regimen developed for children with ALL has been found to also improve outcomes for newly diagnosed AYA patients . The pediatric regimen more than doubled the median length of time people lived without their cancer returning compared with an adult treatment regimen. Further studies are now testing the addition of targeted therapies to the combination .

Acute Myeloid Leukemia (AML) Treatment

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. It can cause a buildup of abnormal red blood cells, white blood cells, or platelets.

AML tends to be aggressive and is harder to treat than ALL. However, AML cells sometimes have gene changes that cause the tumors to grow but can be targeted with new drugs. Researchers are starting to look at whether genomic sequencing of tumor cells can help doctors choose the best treatment (such as chemotherapy, targeted therapy, stem-cell transplant, or a combination of therapies) for each patient. Scientists are also testing other ways to treat AML.

New Treatment Option for Some People with AML

Combining ivosidenib with chemo is effective for AML with an IDH1 gene mutation.

Targeted therapies

Targeted therapies recently approved to treat AML with certain gene changes include  Enasidenib (Idhifa) ,  Olutasidenib (Rezlidhia) ,  Ivosidenib (Tibsovo) ,  Venetoclax (Venclexta) ,  Gemtuzumab ozogamicin (Mylotarg) ,  Midostaurin (Rydapt) ,  Gilteritinib (Xospata) ,  Glasdegib (Daurismo) , and  Quizartinib (Vanflyta) . 

An NCI-sponsored precision medicine study called MyeloMATCH is now enrolling people with newly diagnosed AML or a related but less aggressive cancer called myelodysplastic syndrome (MDS) . Participants will undergo genomic testing of blood and bone marrow samples to see if they have specific genetic alterations that can be matched to corresponding targeted therapies.

Other ways to treat AML

• Testing newer targeted therapies.  Researchers continue to develop new drugs to shut down proteins that some leukemias need to grow. For example, new drugs called menin inhibitors stop cancer-promoting genes from being expressed. 
• Studying ways to target AML cells indirectly. These include testing ways to make cancer cells more vulnerable to new and existing treatments.
• Targeting AML and related conditions. MDS can eventually progress to AML. Researchers are testing HDAC inhibitors and other drugs that alter how genes are switched on and off in both MDS and AML.
• Reducing side effects. Some older adults cannot tolerate the intensive treatments most commonly used for AML. Studies have recently found that several drug combinations can help older people with AML live longer while avoiding many serious side effects. New treatments to relieve symptoms of MDS have also been developed.
• Immunotherapy. CAR T-cells and BiTEs are being tested in people with AML.

Chronic Myelogenous Leukemia (CML) Treatment

Chronic myelogenous leukemia (CML) is a type of cancer in which the bone marrow makes too many granulocytes (a type of white blood cell). These granulocytes are abnormal and can build up in the blood and bone marrow so there is less room for healthy white blood cells, red blood cells, and platelets. CML usually gets worse slowly over time.

Blocking an abnormal protein

Most people with CML have a specific chromosome alteration called the Philadelphia chromosome , which produces an abnormal protein that drives the growth of leukemia cells. Targeted therapies that block this abnormal protein— imatinib (Gleevec) , nilotinib (Tasigna) , dasatinib (Sprycel) , and ponatinib (Iclusig) —have radically changed the outlook for people with CML, who now have close to a normal life expectancy.

Testing new combination therapies

Some people with CML continue to have detectable cancer cells in their body even after long-term treatment with drugs that target the protein produced by the Philadelphia chromosome. NCI-sponsored trials are testing whether the addition of immunotherapy or other targeted therapies to these drugs can reduce the number of CML cells in such patients.

Looking at whether patients can stop taking therapy

Researchers have found that some drugs that target the protein produced by the Philadelphia chromosome can be safely stopped in some CML patients rather than taken for life. These patients must undergo regular testing to ensure the disease has not come back.

Chronic Lymphocytic Leukemia (CLL) Treatment

Like ALL, chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). But unlike ALL, CLL is slow growing and worsens over time.

Targeted therapy

Ibrutinib (Imbruvica) . The targeted therapy ibrutinib (Imbruvica) was the first non-chemotherapy drug approved to treat CLL. It shuts down a signaling pathway called the B-cell receptor signaling pathway, which is commonly overactive in CLL cells. Depending on people’s age , ibrutinib may be given in combination with another targeted drug, rituximab (Rituxan) .

Clinical trials have shown that ibrutinib benefits both younger and older patients with CLL.

Venetoclax (Venclexta) and obinutuzumab (Gazyva) . In 2019, the Food and Drug Administration (FDA) approved the second chemotherapy-free initial treatment regimen for CLL , containing the targeted therapies venetoclax (Venclexta) and obinutuzumab (Gazyva) .

Other combinations of these drugs plus ibrutinib are now being used or tested for CLL, including •    ibrutinib and venetoclax in people with newly diagnosed CLL •    ibrutinib, obinutuzumab, and venetoclax in older adults with newly diagnosed CLL •    ibrutinib and obinutuzumab with or without venetoclax in younger adults with newly diagnosed CLL

An ongoing trial at NCI is also testing whether giving the combination of venetoclax and obinutuzumab to some people with CLL before symptoms develop can help them live longer overall.

Zanubrutinib (Brukinsa) . In early 2023, the FDA approved a drug that works in a similar manner to ibrutinib, called zanubrutinib (Brukinsa) , for people with CLL. A large study showed that zanubrutinib alone has fewer side effects and is more effective than ibrutinib for people whose leukemia has returned after initial treatment. More research is now needed to understand how to best combine zanubrutinib with other newer therapies, such as venetoclax.

CAR T-cell therapy is also being tested in adults with CLL. Researchers would like to know if using this type of immunotherapy early in the course of treatment would be more effective than waiting until the cancer recurs.

Hairy Cell Leukemia (HCL) Treatment

Hairy cell leukemia (HCL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). The disease is called hairy cell leukemia because the abnormal lymphocytes look "hairy" when viewed under a microscope. This rare type of leukemia gets worse slowly, or sometimes does not get worse at all.

Combinations of drugs

Researchers are studying combinations of drugs to treat HCL. For example, in a recent small study, a combination of two targeted therapies— vemurafenib (Zelboraf) and rituximab (Rituxan) — led to long-lasting remissions for most participants with HCL that had come back after previous treatments. More drug combinations are currently being tested in clinical trials.

Leukemia Treatment for Children

For the two most common types of leukemia, AML and ALL, standard leukemia treatments for children have been chemotherapy, radiation therapy, and stem-cell transplant. Despite great improvements in survival for children with many types of leukemia, some treatments don't always work. Also, some children later experience a relapse of their disease. Others live with the side effects of chemotherapy and radiation therapy for the rest of their lives, highlighting the need for less toxic treatments.

Now researchers are focusing on targeted drugs and immunotherapies for the treatment of leukemia in children. Newer chemotherapy drugs are also being tested.

Targeted Therapies

Targeted therapies that have been approved or are being studied for children with leukemia include:

• imatinib (Gleevec) and dasatinib (Sprycel), which are  approved for the treatment of children with CML  as well as those with a specific type of ALL. The approvals are for children whose cancer cells have the Philadelphia chromosome. 
• sorafenib (Nexavar) , which has been studied in combination with standard chemotherapy for children with AML whose leukemia has changes in a gene called FLT3. The addition of sorafenib to standard treatment was safe, and its addition may improve survival time free from leukemia. Other ongoing clinical trials are testing drugs that target FLT3 more specifically than sorafenib (such as gilteritinib).
• larotrectinib (Vitrakvi) , which is being tested in children with leukemia that has a specific change in a gene called NTRK . 

More possible targets for the treatment of childhood cancers are discovered every year, and many new drugs that could potentially be used to treat cancers that have these targets are being tested through the Pediatric Preclinical In Vivo Testing Consortium (PIVOT) .

CAR T-cell therapy has recently generated great excitement for the treatment of children with relapsed ALL. One CAR T-cell therapy, tisagenlecleucel (Kymriah) , was approved in 2017 for some children with relapsed ALL.

Researchers continue to address remaining challenges about the use of CAR T-cell therapy in children with leukemia:

• Sometimes, leukemia can become resistant to tisagenlecleucel. Researchers in NCI’s Pediatric Oncology Branch have developed CAR T cells that target leukemia cells in a different way. An  ongoing clinical trial is testing whether the combination of these two types of CAR T cells can provide longer-lasting remissions.
• CAR T cells are currently only approved for use in leukemia that has relapsed or proved resistant to standard treatment. A clinical trial from the Children's Oncology Group ( COG ) is now testing tisagenlecleucel as part of first-line therapy in children with ALL at high risk of relapse.
• More research is needed to understand which children who receive CAR T cells are at high risk of developing resistance to treatment. Researchers also plan to test whether strategies such as combining CAR T-cell therapy with other immunotherapies may help prevent resistance from developing. 
• Other research, both in NCI’s Pediatric Oncology Branch and at other institutions, is focused on creating CAR T-cell therapies that work for children with other types of childhood leukemia, such as AML. Several clinical trials of these treatments, including one led by NCI researchers , are now under way.

Two other drugs that use the body’s immune system to fight cancer have shown promise for children with leukemia:

• In clinical trials, the drug was shown to be more effective than chemotherapy in treating ALL that has relapsed in children and young adults.
• An NCI-sponsored trial is now testing the drug as part of treatment for newly diagnosed ALL in children, adolescents, and young adults.
• A drug called inotuzumab ozogamicin (Besponsa)  is being tested in children with relapsed B-cell ALL. This drug consists of an antibody that can bind to cancer cells linked to a drug that can kill those cells. An NCI-sponsored trial is also testing the drug as part of treatment for newly diagnosed ALL in children and adolescents at higher risk of relapse.

Chemotherapy

In addition to targeted therapies and immunotherapies, researchers are also working to develop new chemotherapy drugs for leukemia and find better ways to use existing drugs. In 2018, a large clinical trial showed that adding the drug nelarabine (Arranon) to standard chemotherapy improves survival for children and young adults newly diagnosed with T-cell ALL.

Other drugs are being tested that may make standard chemotherapy drugs more effective. These drugs include venetoclax , which has been approved for older adults with some types of leukemia and is now being tested in children .

Survivorship

Children’s developing brains and bodies can be particularly sensitive to the harmful effects of cancer treatment. Because many children treated for cancer go on to live long lives, they may be dealing with these late effects for decades to come.

The NCI-funded Childhood Cancer Survivor Study , ongoing since 1994, tracks the long-term harmful effects of treatments for childhood cancer and studies ways to minimize these effects. NCI also funds research into addressing ways to help cancer survivors cope with and manage health issues stemming from cancer treatment, as well into altering existing treatment regimens to make them less toxic in the long term.

For example, one study found that, in children with ALL, radiation therapy to prevent the cancer from returning in the brain is likely unnecessary . The study found that radiation can even be omitted for children at the highest risk of the cancer coming back, reducing the risk of future problems with thinking and memory, hormone dysfunction, and other side effects of radiation to the brain.

Preventing and Treating Graft Versus Host Disease

Many people with leukemia—both adults and children—have a stem-cell transplant as part of their treatment. If the new stem cells come from a donor, the immune cells they produce may be able to attack any cancer cells that remain in the body.

But sometimes, immune cells produced by donor stem cells attack healthy tissues of the body instead. This condition, called graft versus host disease ( GVHD ), can affect nearly every organ and can cause many painful and debilitating symptoms. 

In recent years, several drugs have been approved by the FDA for the treatment of GVHD, including:

•    ibrutinib, which is also used as a treatment for some types of leukemia •     ruxolitinib (Jakafi) •     belumosudil (Rezurock)

Researchers are also testing ways to prevent GVHD from developing in the first place. For example, a recent study found that removing certain immune cells from donated stem cells before they are transplanted may reduce the risk of chronic GVHD without any apparent increase in the likelihood of relapse.

NCI-Supported Research Programs

Many NCI-funded researchers working at the NIH campus and across the United States and the world are seeking ways to address leukemia more effectively. Some research is basic, exploring questions as diverse as the biological underpinnings of cancer. And some is more clinical, seeking to translate this basic information into improving patient outcomes. The programs listed below are a small sampling of NCI’s research efforts in leukemia.

NCI’s Leukemia Specialized Programs of Research Excellence (SPORE) promotes collaborative, interdisciplinary research. SPORE grants involve both basic and clinical/applied scientists working together. They support the efficient movement of basic scientific findings into clinical settings, as well as studies to determine the biological basis for observations made in individuals with cancer or in populations at risk for cancer.

The Targeting Fusion Oncoproteins in Childhood Cancers (TFCC) Network is forming a collaborative team of investigators to advance the understanding of how fusion proteins contribute to pediatric cancers, and how they might be targeted with new treatments. Fusion proteins, which can occur when parts of different chromosomal regions are joined, may drive the development of many cancers in children.

NCI has also formed partnerships with the pharmaceutical industry, academic institutions, and individual investigators for the early clinical evaluation of innovative cancer therapies. The Experimental Therapeutics Clinical Trials Network (ETCTN) was created to evaluate these therapies using a coordinated, collaborative approach to early-phase clinical trials.

The Pediatric Early-Phase Clinical Trials Network was established to help identify and develop effective new drugs for children and adolescents with cancer. The network’s focus is on phase I and early phase II trials, as well as pilot studies of novel drugs and treatment regimens to determine their tolerability.

NCI’s Pediatric Preclinical In Vivo Testing Consortium (PIVOT) develops mouse models to allow early, rapid testing of new drugs for pediatric cancers, including leukemia. The models are all derived from tissue samples taken from patients’ tumors. The consortium partners both with commercial drug companies and with drug development efforts at universities and cancer centers.

The NCI-supported Children’s Oncology Group develops and conducts both clinical trials of initial treatments and clinical trials for after cancer relapse for children and adolescents with ALL, AML, and CML.

Researchers in NCI’s Division of Cancer Epidemiology and Genetics (DCEG)  investigate novel, molecular biomarkers for leukemia, as well as clarify relationships of established risk factors. Studies include those looking at environmental and workplace exposure, families with multiple leukemia cases, and inherited bone marrow failure syndromes to name a few.

Clinical Trials

NCI funds and oversees both early- and late-phase clinical trials to develop new treatments and improve patient care. Search NCI-Supported Clinical Trials to find leukemia-related trials now accepting patients. 

Leukemia Research Results

The following are some of our latest news articles on leukemia research:

• Quizartinib Approval Adds New Treatment Option for AML, Including in Older Patients
• Blinatumomab Increases Survival for Infants with an Aggressive Type of ALL
• Revumenib Shows Promise in Treating Advanced Acute Myeloid Leukemia
• Help Desk for Oncologists Treating People with a Rare Leukemia Pays Big Dividends
• Zanubrutinib’s Approval Improves Targeted Treatment for CLL
• Trial Suggests Expanded Role for Blinatumomab in Treating ALL

View the full list of Leukemia Research Results and Study Updates .

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Blood Cancer Research Poised for Another ‘Banner Year’ in 2024

More than 25,000 medical professionals from across the world came together in December to discuss the latest blood cancer developments during the annual meeting of the American Society of Hematology (ASH). This annual event gives us the opportunity to think about what advances are on the horizon as LLS works to strengthen cures, care and quality of life for people with blood cancer and their families.   

Study results presented at ASH 2023, including many by LLS-funded investigators and Therapy Acceleration Program partners, showcased an incredible range of treatments that are either currently available or in development for every type of blood cancer. What I heard at ASH, not to mention the recent addition of $65 million in new LLS research investments , set us up for another banner research year in 2024. 

Immunotherapy, targeted therapies remain a cornerstone of blood cancer care 

New data demonstrated that immunotherapy continues to provide substantial and increasing benefits, particularly in the treatment of lymphomas and multiple myeloma.  

Current CAR T-cell treatments target CD19 or BCMA proteins, which are common on lymphoma and myeloma cancer cells, respectively. New CAR targets in development include BAFF-R for mantle cell lymphoma, CD5 and CD7 for T-cell lymphoma, and ddBCMA, which uses a different mechanism to target BCMA on myeloma cells.  

Expect to hear more about each of these new targets in 2024 as well as new insights into why CAR-T stops working—or doesn’t work at all—in some patients. Understanding these mechanisms is step one in finding ways to overcome them and help more patients. 

CAR-T is both an immunotherapy and a targeted treatment that works by helping T cells find and attach to BCMA, CD19 and hopefully soon several other unique targets on cancer cells. But CAR-T is just one type of targeted therapy—most of the treatment data presented at ASH and the work we’re looking forward to hearing about in 2024 has a genetic target. 

Here are just two examples. BTK inhibitors continue to lead the way in the treatment of B-cell cancers, including non-Hodgkin lymphomas and CLL. These targeted drugs cut off the BTK protein defective B cells need to proliferate. Perhaps even more exciting is emerging data about menin inhibitors, work that LLS started supporting nearly 15 years ago in a lab at the University of Michigan.  

We heard some strong results during ASH for menin inhibitors in patients with AML that includes genetic mutations that make outcomes for this already hard to treat disease even worse. Menin inhibitor treatment increased overall survival in patients who have exhausted many other treatment options. I expect at least one, and possibly two menin inhibitors to be approved by the FDA in the next few years. 

Emerging themes to watch in 2024 

We are in a period of building on transformational treatments. After a series of breakthroughs in recent years, including new precision medicines and immunotherapies, researchers are working hard to refine and expand their use so more patients can benefit.  

Breakthroughs appear to the public to be sudden, dramatic discoveries. But in medical research, that’s never quite true. Breakthrough takes years of research, and we owe it to patients to ensure we spend just as much time exploring every avenue after the breakthrough to make sure these new drugs are used optimally. 

Thanks to targeted therapies for so many types of cancer at all stages, more patients can avoid harsh chemotherapies. When chemotherapy is necessary, doctors can use updated versions of chemo drugs, combine and deliver them in new ways, and they have better ways to reduce the serious side effects of chemo that can limit or even prevent treatment in some people, especially older patients. 

New diagnostic and prognostics tools are emerging to guide treatment. For example, simple blood tests are emerging that can predict the best time to stop treatments and when or even if they will need to be started again to keep cancer in check. These so called “peripheral biomarkers” are a big advance. Without them, doctors have to rely on scanning techniques or biopsies, which are not always feasible. 

Progress on all these fronts will continue in 2024 with a wide range of research ongoing in each area. 

We are making meaningful progress in all types of blood cancer 

This is just a sample of what’s coming for half a dozen types of blood cancer. 

Myeloma: Adding the anti CD38 antibody daratumumab to the standard treatment regimen in patients with newly diagnosed multiple myeloma led to significantly higher survival rates without disease progression (84.3%) compared to standard care alone (67.7%) Next up: does this combination improve overall survival? And a big question for this and all combo treatments: will they be affordable and equally available to all patients? LLS Equity in Access Research Grants are helping to find ways to make sure all treatments are. 

Mantle cell lymphoma: Combining the BTK inhibitor ibrutinib with the B-cell lymphoma-2 inhibitor venetoclax for relapsed or refractory mantle cell lymphoma improved progression-free survival to 33 months compared to 22 months for ibrutinib alone. Stay tuned as researchers continue to explore this combination and evaluate whether these results can be replicated with BTK inhibitors that have fewer negative effects on the heart than ibrutinib, such as zanubrutinib, acalabrutinib, and pirtobrutinib, which could also offer additional advantages because it works differently than the other BTK inhibitors. 

Chronic lymphocytic leukemia (CLL): After decades of using a triple combination chemotherapy, the standard of care for CLL has shifted to targeted treatment with ibrutinib and venetoclax. Data at ASH showed that people receiving the targeted combination had 8-fold less deaths than the older chemo regimen. Next up: What do we do when a patient’s disease becomes resistant to the ibrutinib/venetoclax combination? Will a minimal residual disease blood test, which can detect measurable cancer cells during and after treatment, give physicians the information they need to know the right time to stop treatment, and to restart it if necessary? 

Acute myeloid leukemia: LLS dedicates about one-quarter of its research budget to AML, which is one of the most common and most deadly blood cancers. Perhaps the most exciting news coming out of ASH was about a new type of drug called menin inhibitors for people with AML. Patients with an AML mutation called KMT2A fusion, who have among the worst AML outcomes, had improved overall survival and complete hematological response after menin inhibitor treatment. This is one of the two menin inhibitor drugs likely to be evaluated for approval soon by the FDA.  

Myelofibrosis: After years of having nothing but supportive care to offer people with myelofibrosis, there are several late-stage drug trials in progress. One trial reported at ASH showed that combining the kinase inhibitor ruxolitinib with a BET inhibitor called pelabresib significantly improved debilitating symptoms in people with myelofibrosis: anemia and an enlarged spleen. Look for a possible FDA drug approval for pelabresib in 2024. 

CMML: Rare cancers like CMML are difficult to study. There are fewer patients available for clinical trials, median survival time is just 30 months, and up to 3 in 10 patients will convert to having AML. There is a major effort underway, led by LLS and supported by the Segal Family Foundation , to test new treatments and dig deeper into understanding mechanistically how CMML forms and attacks the body. We expect an acceleration in our understanding of CMML in 2024 and beyond. 

I hope after reading this, you are as excited as I am about the progress that we are making across blood cancer.  

Blood Cancers

Cancers of the blood (hematologic malignancies) affect the bone marrow, blood cells, lymph nodes and other parts of the lymphatic system. Malignancies in the blood interfere with normal blood cell production or function. As the cancer cells multiply, they stop your blood from performing essential functions such as fighting off infection.

Decades of scientific research and clinical trials have led to more effective treatments and better outcomes for the more than 150,000 people diagnosed with blood cancers each year.

At the University of Chicago Medicine, we’re at the forefront of leading-edge research, the latest clinical trials and the newest treatments for leukemia, lymphoma and multiple myeloma.

Our patients have access to advanced treatments not available at most medical centers, such as stem cell transplantation  and CAR T-cell therapy , a treatment that supercharges a patient's T cells to recognize and destroy cancer cells. Many patients receive stem cell transplants or CAR T-cell therapy on an outpatient basis, enabling them to return to the comfort of their home or nearby accommodations between treatments and appointments, rather than staying in the hospital. 

Offering the Most Advanced Care for Blood Cancers

We care for more than 300 patients with leukemia, myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) each year, making our program one of the largest in Chicago.

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New medications, targeted therapies and cellular therapies have changed the landscape for patients with multiple myeloma. UChicago Medicine offers all of the latest treatments for this complex condition.

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CAR T-cell therapy supercharges a patient's white blood cells to find and destroy cancer cells. UChicago Medicine research played a key role in the development of this exciting new immunotherapy.

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• Cancer, the blood and circulation

This page tells you about the blood and circulation and how cancer may affect them. 

There is information about 

What the blood does

• How blood circulates

What is in blood?

White blood cells, red blood cells.

• How and where blood cells are made
• Effects of cancer treatments on blood cells

Related information

The blood flows throughout the body. It:

• carries food (nutrients) and oxygen to all the cells of the body
• carries away waste products that the body needs to get rid of

Without a blood supply, cells and body tissues die.

How blood circulates

The blood flows around the body in blood vessels (tubes) called arteries, veins and capillaries. This is the circulatory system. The heart pumps the blood through the circulatory system.

49_diagram_showing_the_circulatory_system_of_the_body.svg

Arteries carry blood that is full of oxygen from the heart to all parts of the body. As the arteries get further and further away from the heart, they get smaller and smaller. Eventually they turn into capillaries.

Capillaries

Capillaries are the smallest blood vessels. They go right into the tissues. Here the blood in the capillaries gives oxygen to the cells and picks up the waste from the cells. The capillaries connect with the smallest veins in the body.

The veins get bigger and bigger as they carry the blood back towards the heart. The blood passes through the right side of the heart and goes to the lungs where it gets rid of carbon dioxide and picks up more oxygen. It then passes through the left side of the heart and gets pumped back around the body.

Blood circulation and cancer spread

The circulation can help to explain how some cancers spread to particular parts of the body. For example, cancers of the colon (large bowel) often spread to the liver. This is because blood circulates from the bowel through the liver on its way back to the heart. So if some cancer cells escape into the circulation, they may stick in the liver as the blood passes through. They can then begin to grow into secondary cancers.

Although blood looks like a red liquid, if left in a test tube it separates out into:

• a pale liquid called plasma
• a solid layer of blood cells

31_diagram_of_what_is_in_blood.svg

The blood is about 55% plasma and 45% cells. Plasma is mostly water with some proteins and other chemicals dissolved in it. There are 3 main types of cells in the blood. These are:

A full blood count (FBC) measures the number of red cells, white cells and platelets in your blood. There are several different types of white blood cells including neutrophils and lymphocytes. 

There isn’t an exact value of normal for blood counts. The range of figures quoted as normal varies slightly between laboratories and also differs between men and women.

03_diagram_of_table_showing_the_normal_values_of_men_and_women.svg

There are several different types of white cells in the blood in differing amounts. They all play a part in the immune response. This is how the body deals with an infection or anything else the body recognises as 'foreign'. The body can make white blood cells very quickly. They have a short life. Some only live for a few hours, others for a few days.

Your white blood cell count may go up if you have surgery or an infection.

Neutrophils

The most common type of white blood cells are the neutrophils (sometimes called leucocytes). 

They are important for fighting infection. Some chemotherapy and targeted cancer drugs can lower the levels of neutrophils for a short time. This reduces your resistance to infection.

Lymphocytes

The next most common type of white blood cell is lymphocytes.

11_diagram_of_a_lymphocyte_1.svg

Lymphocytes help to make antibodies to fight infection. There are B lymphocytes and T lymphocytes.

Other types of white blood cells

Other white blood cells are present in smaller numbers in the circulating blood. 

These are called eosinophils, basophils and monocytes. They are sometimes collectively called granulocytes.

Red blood cells give the blood its red colour. They contain a pigment called haemoglobin. 

14_diagram_of_a_red_blood_cell.svg

Red blood cells attach to oxygen and carry it in the blood to the tissues. When they get to an area that needs oxygen, they give it up and pick up carbon dioxide which they carry back to the lungs. A shortage of red blood cells is called anaemia. The role of the red blood cell in carrying oxygen explains why very anaemic people usually feel breathless.

Platelets are very important in blood clotting. They clump together to form a plug to help stop bleeding. They then release other chemicals to clot the blood and repair the blood vessel.  

13_diagram_of_a_platelet.svg

How and where are blood cells are made.

Your body makes blood cells in the bone marrow. The bone marrow is the soft inner part of your bones. You make blood cells in a controlled way, as your body needs them.

All blood cells start as the same type of cell, called a stem cell. In adults, there are blood stem cells in the bone marrow, inside the skull, ribs, sternum (breast bone), spine and pelvis.

16_diagram_showing_where_blood_cells_are_made_in_the_body.svg

The stem cells divide and multiply to make the blood cells. These cells develop and mature (differentiate) as they grow into white cells, red cells or platelets. The diagram below shows how the different types of cells can develop from a single blood stem cell.

41_diagram_showing_how_blood_cells_are_made_r3.svg

It is possible to collect stem cells from the bone marrow or the blood and freeze them. Doctors can then use stem cells as part of high dose chemotherapy treatment called stem cell transplant or bone marrow transplant.

Effects of cancer drugs on blood cells

Some types of cancer drugs can lower the number of white blood cells, red blood cells and platelets in your blood for some time. Drugs that can cause this include some chemotherapy drugs and some targeted cancer drugs.

Developing blood cells multiply all the time as they mature in the bone marrow and are then released into the blood. Some cancer drugs can slow the production of blood cells by the bone marrow, so they are not released as quickly into the blood. Then the number of circulating blood cells goes down.

Low level of white blood cells

It usually takes a week or 2 for the bone marrow to make more cells and release them back into the blood.

A drop in white blood cells can lead to an increased risk of infection. 

Low level of red blood cells

Mature red blood cells live for about 3 months, so there are fewer multiplying at any one time. So you often don't get low in red cells (anaemic) until further into your cancer treatment. If your red blood cell level gets very low, you may need to have a blood transfusion.

A drop in red blood cells can make you feel tired and you may become breathless. 

Low level of platelets

The platelet level may also drop. If it does, you may get nose bleeds, or notice a red rash on your skin like tiny bruises. You may then need to have a platelet transfusion. After high dose chemotherapy, it can take longer for the platelet count to get back to normal than any other blood cell count.

There is more information about:

• How can cancer spread?
• The blood, bone marrow and cancer drugs : for information about how cancer treatment can affect blood cells
• Cancer drugs : to find out about if a particular cancer drug treatment might affect blood cells
• Stem cell and bone marrow transplants

Next review due : 6 November 2026

Last reviewed

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Yellow food dye can make living tissue transparent—it could improve cancer treatment, blood draws and tattoo removal

by Guosong Hong, The Conversation

Why isn't your body transparent? Some animals such as jellyfish , zebra fish and some glass frogs have see-through bodies. But most mammals, including humans, aren't transparent.

While the idea of a transparent body might seem odd or even a bit creepy, it could actually be really helpful for doctors. If our bodies were transparent, doctors could easily see inside to diagnose diseases in organs such as the liver, spleen and brain. They wouldn't need invasive procedures such as biopsies or expensive machines such as CT scanners and MRIs.

I'm a materials scientist , and my team and I work on how new materials can aid biomedicine. My colleagues and I have wondered whether it's possible to make living tissue transparent temporarily to aid in medical treatments and other uses.

We discovered that by dissolving certain dye molecules , including a food dye commonly used in snacks called FD&C Yellow 5 , into water, we can change the way light travels through the water. We used this phenomenon to make organic tissue—specifically the thin skin of mice—transparent in our study, published in September 2024 in Science .

Refractive indices

Our bodies, like those of most mammals, aren't transparent mainly because of how light interacts with our tissues. Normally, light travels in a straight line through the air. But when light hits the human body, it doesn't go very far before its path gets scattered. The light bounces around in different directions instead of traveling straight through. If light passed through us without scattering, our tissue would be transparent.

This scattering happens because human tissues are made up of many different components, including water, fats and proteins. Each of these components slows down light differently, a property known as the refractive index .

For example, water has a refractive index of about 1.33 , while fats and proteins have a higher refractive index of around 1.45 in the visible spectrum . So, light travels more slowly in lipids than in water.

The key to making living tissue transparent would be to reduce the differences in how light moves through different parts of the tissue—specifically between water and fats and proteins.

Kramers-Kronig relations

A principle in physics known as the Kramers-Kronig relations explains how if a material absorbs more light of one color, such as blue, this increased absorption will change how light of a different color, such as red, moves through it. Kramers-Kronig relations say that the colors of light are not independent of each other but connected.

FD&C Yellow 5 absorbs blue light strongly, which yields its characteristic orange-to-red color when dissolved in water. This happens because the blue part of the light is absorbed, leaving only the orange-to-red part visible. As a result of the Kramers-Kronig relations, this absorption of blue light increases the refractive index of water for red light. The water's refractive index increases from 1.33 and matches that of fats and proteins, around 1.45.

When the refractive indices match, red light no longer scatters as much. It travels in water the same way that it does in fats in the tissue. So, the whole tissue appears as a single, uniform material. This process can make the tissue look transparent, even though it's normally opaque.

Turning tissue transparent

My research team applied this idea in an experiment using a scattering phantom, which is a material designed to mimic the opaqueness of human skin. As we added more FD&C Yellow 5 dye to the phantom, it became more orange-red in color, just as we expected.

However, something else happened. It became more transparent to red light. This increased transparency allowed us to see the grid pattern on the table underneath the phantom.

We then decided to test this idea on a piece of chicken breast from the grocery store. Unless it's sliced very thin, chicken meat usually looks opaque.

When we soaked the chicken breast in a solution containing FD&C Yellow 5 dye, something amazing happened. It became more transparent, allowing us to clearly see a Stanford sign placed underneath.

Finally, we used this idea to make the skin of a mouse optically transparent. We applied the FD&C Yellow 5 dye to different parts of the mouse's body. When we added it to the mouse's scalp, we could see the blood vessels in its brain. When we added it to the mouse's belly, we could see its gut. When we added it to the mouse's limbs, we could see its muscle fibers.

All this experiment took was gently massaging a solution of the dye into the mouse's skin and a bit of patience.

This process is noninvasive because it doesn't require tissue removal or surgery, and the skin returns to its normal opacity once you rinse off the dye with water. Although it's a fascinating technique, we strongly advise against trying this on yourself.

While the use of Yellow 5 is approved by the FDA, some people have raised concerns about its potential health risks . These include allergic reactions—particularly in people with asthma—hyperactivity in children and potential links to cancer. But researchers will need to conduct more tests to determine whether there are any dangers.

Future uses

So what could this approach be used for? Right now, it works best on very thin layers of skin, like that of a mouse.

Unfortunately, human skin is much thicker, so this method isn't quite ready for practical use on people yet. Also, the red color of the dye means that the color balance isn't quite right and the transparency isn't perfect across the entire visible spectrum . The dye still blocks blue light .

My colleagues and I are working on improving this technique to make it more effective for human tissues. We're also trying to shift the dye's absorption toward the ultraviolet spectrum , which would create a more balanced transparency effect across all visible colors.

Looking ahead, this technology one day could make veins more visible, making it easier to perform venipuncture—the process of drawing blood or injecting fluids through a needle—especially in elderly patients with hard-to-see veins.

It could also aid in the early detection of skin cancer , enhance light delivery into deep tissues for photodynamic and photothermal therapies and simplify laser-based tattoo removal .

In photodynamic and photothermal therapies, doctors use a laser to kill cancerous and precancerous cells. But light from the laser penetrates only so far into the tissue, so these therapies aren't suitable for organs deeper in the body—yet.

All of these applications could benefit from a reversible, on-demand transparency window into the body.

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share this!

September 6, 2024

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Low-cost nanomaterial technology can detect cancer genes with ultra-high sensitivity

by National Research Council of Science and Technology

Dr. Min-young Lee and Dr. Sung-gyu Park of the Advanced Bio and Healthcare Materials Research Division at KIMS have developed a technology that can detect cancer mutant genes in blood with the world's highest sensitivity of 0.000000001% based on plasmonic nanomaterials for optical signal amplification. The team tested blood samples from lung cancer patients (stages 1-4) and healthy individuals for EGFR mutations and achieved a diagnostic accuracy of 96%.

The work is published in the journal Small Science .

Previously utilized genetic analysis technologies had low analytical sensitivity to detect mutated genes compared to normal genes, making it difficult to accurately diagnose early-stage cancer patients. In addition, it was difficult to establish a quick treatment strategy and apply it to screening tests due to the high cost and long time required for analysis and the need for special equipment.

To overcome these challenges, the research team developed a low-cost analysis technology that can analyze various cancer mutations within the target gene region within one hour with an ultra-high sensitivity of 0.000000001%. This technology boasts the world's highest level of sensitivity, which is 100,000 times better than the highest level of 0.0001% among reported technologies, and through this, the possibility of early diagnosis was confirmed using the blood of lung cancer patients.

This technology combines nanomaterial technology that significantly improves the fluorescence signal, and primer/probe design that suppresses the fluorescence signal of normal genes, amplifying only the fluorescence signal of cancer mutant genes. This is because the accurate detection of even very small amounts of cancer mutated genes requires not only strong fluorescent signal expression technology but also precise discrimination of fine fluorescent signals.

The team fabricated a biochip in the form of a microarray capable of simultaneously detecting three mutant genes of EGFR (deletion, insertion, and point mutations ) on a plasmonic substrate made of three-dimensional, high-density gold nanostructures. After evaluating the clinical performance of 43 domestic lung cancer patients (stages 1 to 4) and 40 normal groups, a clinical sensitivity of 93% for lung cancer patients and a clinical specificity of 100% for the normal group were confirmed.

This technology can play an important role in not only early diagnosis and detection of recurrence of cancer, but also in monitoring treatment effectiveness and establishing personalized treatment plans. In addition, liquid biopsy using blood is possible as an alternative to surgical tissue biopsy, reducing the burden on patients and simplifying the examination process. It can also serve as a regular screening test, ultimately improving the quality of cancer management and treatment.

Senior researcher Min-young Lee said, "Because it is capable of comprehensively detecting various cancer mutations with the world's highest level of ultra-high sensitivity, it can become a leading player in the early cancer diagnosis and treatment/recurrence monitoring market. We expect that this will greatly improve the survival rate and quality of life of cancer patients."

Provided by National Research Council of Science and Technology

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Local support group 'a comfort' for blood cancer patients and their families

Annual walk in dorchester raised more than $115,700 for multiple myeloma research and treatment.

Social Sharing

A support group for multiple myeloma patients, their families and caregivers in southwestern Ontario, says their fundraising efforts have allowed for greater research and more people to access treatment closer to home, rather than having to travel to other cities.

The London and District Myeloma Support Group has also become a network for families to navigate the illness and medical system, said Ev McDowell, the group's co-founder. 

"It's made a difference for some people who now know others that are living with the same disease. It can affect people differently, but just knowing another person with the disease can really provide a lot of comfort," she said.

Multiple myeloma is the second most common form of blood cancer and approximately eleven Canadians are diagnosed with it every day, according to  Myeloma Canada.  Although there is no known cure, research advancements have allowed people with myeloma to live longer. 

The patient-led group formed in 2002 as a way to educate families about the illness and has now grown into a community of more than 300 members and volunteers from the London area, said McDowell, who was diagnosed with myeloma twenty-four years ago.

Since 2009, the group has raised more than $1 million for myeloma research, clinical trials and equipment at Verspeeten Family Cancer Centre through an annual Walk for Champions in Dorchester, McDowell said. Hundreds attended this year's walk on Sunday which raised more than $115,700.

Dorchester's walk was started by myeloma patients, Dan Childerhouse and Keith Fleming, who wanted a local event for others in the region. Before this, many would attend Toronto's fundraiser for Princess Margaret Cancer Centre.  

• Couple from Echo Bay raises awareness about multiple myeloma
• Manitobans raise about $25,000 for research into a rare form of blood cancer

"Initially, we wanted it to be a get together for families to spread awareness because not too many people knew about myeloma and the first walk had maybe 120 people but every year it's gotten bigger," said Childerhouse. 

"The group is very good for all the new patients, they get to feel more relaxed because as soon as you hear that big scary C-word, you don't know what to do and you have lots of questions so it really helps them out."

Childerhouse was diagnosed in 2008 at age 58 and at the time, doctors told him he had between six months and two years to live. A year later, he underwent a stem cell transplant and said new medication helps him manage the illness and its effects. 

Fleming died in 2013, but received a 10-year life extension with advanced treatments and medicine, said his wife Shelley, wearing a T-shirt that read 'Fleming's Flock' with his photo on it.

"He lived 10 really good years so I just want to carry on and offer hope to other families that have been going through the same cancer treatments as my husband went through and be supportive of this walk," said Shelley Fleming.

• Cancer is 'only a word,' says Moncton city councillor diagnosed with multiple myeloma

It was an emotional event for Sarah Corman and her family as they walked in memory of her dad Craig, who died in February following a 15-year battle with myeloma.

Her son Grayson, 15, has attended the group's events since he was a baby and is now one of their youngest volunteers. Corman said it feels good to give back to a community which has helped her family and others.

"My dad was lucky to get quite a few medical trials that really prolonged his life," she said. "This group also really helped my mom because being a caregiver can be really hard, but she had a strong network that she can lean on and get lots of helpful information."

ABOUT THE AUTHOR

Isha Bhargava is a multiplatform reporter for CBC News and has worked for Ontario newsrooms in Toronto and London. She loves telling current affairs and human interest stories. You can reach her at [email protected]

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• This young Edmonton entrepreneur is helping to reunite families with DNA genealogy
• Northern Manitoba community 'in shock' after hospital sent wrong body to grieving family: Chief
• Grieving families struggle to find funeral services in B.C.

How is Ovarian Cancer Diagnosed?

If a doctor suspects ovarian cancer, they may perform tests such as a pelvic exam, transvaginal ultrasound, CT scan, or CA-125 blood test to learn more. It is important to know, however, that none of these tests are definitive on their own. A surgical biopsy is the only way to make a definitive diagnosis of ovarian cancer.

Understanding Symptoms and Diagnosis

Though symptoms are often what lead an individual to pursue an ovarian cancer diagnosis, it’s important to know that not everyone with ovarian cancer experiences symptoms and the most common symptoms are not unique to ovarian cancer. Family history and risk factors should also be discussed with your physician in conversations about ovarian cancer.

Annual check-ups and pelvic exams are useful for general reproductive health but usually do not detect ovarian tumors, which are often too small. Ovarian cancer also cannot be diagnosed through a Pap smear , which only screens for cervical cancer.

If ovarian cancer is suspected, doctors may conduct blood work or order imaging tests like transvaginal ultrasounds or CT scans. However, a surgical biopsy is the only definitive way to diagnose ovarian cancer.

Physical and Gynecologic Exams

Ovarian cancer is rarely detected during routine physical or gynecologic exams due to its location deep in the body. Without an early detection tool, tumors are usually only found when they are large and more advanced. However, routine physical or gynecologic exams are crucial as initial steps that can lead to more detailed imaging tests and surgical procedures . It’s also important to ask your doctor about genetic counseling and testing , which can help identify if you are high-risk. If you’re concerned about your risk or experiencing symptoms, schedule an exam and discuss your concerns about ovarian cancer with your doctor.

Imaging Tests

If a doctor suspects ovarian cancer, they may order imaging tests such as a CT scan, transvaginal ultrasound, or both. These tests help identify masses in the ovaries or pelvic area and assess whether they might be malignant. However, imaging tests alone cannot confirm an ovarian cancer diagnosis.

CT scans employ x-rays to take multiple cross-sectional images of the tissues and bones in the body. Doctors can analyze the images or use software to make a three-dimensional model of the internal organs. A CT scan can define the boundaries of a tumor and show the extent of tumor spread, helping a doctor determine where to operate.

An x-ray produces cross-body imaging using a type of radiation called electromagnetic waves. X-rays are rarely used in diagnosing ovarian cancer, but they are sometimes used to see if cancer has spread elsewhere in the body. A chest x-ray can display tumors in the lungs and fluid that has collected near the lungs, known as pleural effusion.

An MRI, short for magnetic resonance imaging, is similar to an X-ray, except it does not use radiation. An MRI uses magnetic radio waves to produce images of the inside of the body. MRIs are rarely used to check for ovarian cancer initially, though they can be used to examine the spinal cord and the brain, where cancer can sometimes spread.

Surgical Procedures for Ovarian Cancer

A surgical biopsy is the only way to definitively diagnose ovarian cancer. In some cases, a minimally invasive surgery (laparoscopy or robotic surgery) may be performed first to confirm a diagnosis with biopsy and to determine whether to proceed with a full cancer resection or to administer chemotherapy first.

In a laparoscopy or robotic surgery, a physician can examine the ovaries and other pelvic and abdominal organs using a camera inserted through a small incision in the abdominal wall. Both approaches to minimally invasive surgery can determine how large the tumors have grown and whether they can be completely resected. These procedures allow the surgeon to perform a biopsy to confirm the diagnosis and to collect more information about the tumor that may guide treatment decisions.

The only way to definitively determine if a patient has ovarian cancer is through a biopsy. This is when tissues from a tumor are removed and tested in a lab. A laparoscopy may be performed to evaluate tumor spread and collect tissue for a diagnosis, or a diagnosis may be made by sampling tissue during a more extensive surgery to fully resect the cancer. In some cases, a biopsy may be performed using image guidance with a CT scan or ultrasound.

CA-125 & Blood Tests

No single blood test can diagnose ovarian cancer. However, certain tests can help estimate risk, or monitor its progression. Below is an overview of key tests used in the evaluation process.

OVA1: Purpose: Measures levels of five proteins that may change when ovarian cancer is present. Usage: Helps determine if surgery should be done by a gynecologic oncologist. Not a screening tool, and does not provide definitive evidence of cancer.

Inhibin B and Inhibin A: Purpose: May help detect and monitor granulosa cell tumors. Usage: Assesses risk of presence and progression of these specific tumors.

CA-125: Purpose: CA-125 blood test, or “Cancer Antigen 125” is a test that measures a protein that is elevated in more than 80% of advanced ovarian cancers and 50% of early-stage cancers. Usage: Useful for monitoring the response to treatment or for evidence of cancer recurrence but not recommended as a general screening tool due to the fact that it can often be elevated in benign or unrelated conditions.

Doctors frequently order a CA-125 test when they are concerned that a woman may have ovarian cancer. Because CA-125 levels can fluctuate in response to treatment, the test is also used to monitor how well treatment is working or if alternative treatment should be considered. CA-125 is also frequently used to monitor for recurrence. With evidence that monitoring CA-125 may not impact overall survival, some patients or providers may elect not to follow this marker. Read an article on CA-125 usage .

No, a high CA-125 does not always mean cancer is present. Generally speaking, the normal range of CA-125 is considered to be 0-35 units/mL, while a level above 35 units/mL is considered to be a high CA-125 level. Although a CA-125 blood test can be a useful tool for the diagnosis of ovarian cancer, it is not uncommon for a CA-125 count to be elevated in premenopausal women due to benign conditions since it fluctuates as part of their normal menstrual cycle, or due to benign conditions unrelated to ovarian cancer, such as diverticulitis, endometriosis, liver cirrhosis, pregnancy, or uterine fibroids, as Medscape details here . As a result, the CA-125 is generally only one of several tools used to help diagnose ovarian cancer in a patient with a pelvic mass or other suspicious clinical findings.

There is no evidence to suggest that doing so is beneficial. The CA-125 test is most helpful in postmenopausal women with a pelvic mass. It is also important to note that in about 20 percent of cases of advanced stage disease, and 50 percent of cases of early stage disease, CA-125 is NOT elevated, even though there is ovarian cancer present — and CA-125 can also be elevated by benign conditions. For these reasons, the National Cancer Institute and the United States Preventive Services Task Force do not endorse using it to screen women for ovarian cancer who are at ordinary risk or in the general population. Learn more about their recommendations around CA-125 and screening .

For those undergoing ovarian cancer treatment, CA-125 levels may fluctuate based on treatment response, with lower levels indicating the treatment is working. As mentioned above, CA-125 can also fluctuate because of benign or unrelated conditions — including uterine fibroids, endometriosis, diverticulitis, liver cirrhosis, or pregnancy.

Studies have shown that annual screening with CA-125 tests and transvaginal ultrasounds for average-risk women does not improve survival rates and may lead to unnecessary surgeries, which can increase the risk of complications. The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) found that this approach failed to prevent deaths from ovarian cancer.

The ROCA Test uses changes in CA-125 levels over time, along with factors like age and menopausal status, to predict ovarian cancer risk. It is marketed as part of an annual check-up, costing $295, but there is no evidence it prevents deaths from ovarian cancer. The FDA issued a Safety Guidance in 2016 highlighting potential risks of ovarian cancer screening tests, including the ROCA Test, which is not FDA approved.

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