Relapse in Chronic Lymphocytic Leukaemia (CLL)
A Guide for Patients Introduction
A relapse is the return of leukaemia after treatment. Specifically, this booklet is about a relapse in chronic lymphocytic leukaemia (CLL).
The booklet was written by our Patient Information Writer, Isabelle Leach, and peer reviewed by Helen Knight, CLL Clinical Nurse Specialist at the Centre for Clinical Haematology in Nottingham University Hospitals. We are also grateful to our patient reviewer, Amanda Salter, for their contribution.
If you would like any information on the sources used for this booklet, please email [email protected] for a list of references.
Version 2 Printed: 05/2019 2 www.leukaemiacare.org.uk Review date: 05/2021 In this booklet
Introduction 2
In this booklet 3
About Leukaemia Care 4
What is Chronic Lymphocytic Leukaemia? 6
What is relapsed CLL? 8
Symptoms and diagnosis of relapsed CLL 12
How is relapsed CLL treated? 14
Seeing your doctor 24
Telling your family 26
Managing your emotions 28
Survivorship 32
Palliative care 34
End of life care 36
Glossary 38
Useful contacts and further support 43
Helpline freephone 08088 010 444 3 About Leukaemia Care
Leukaemia Care is a national charity dedicated to ensuring that people affected by blood cancer have access to the right information, advice and support.
Our services has been affected by a blood cancer. A full list of titles – both Helpline disease specific and general Our helpline is supported by information titles – can be our Patient Advocacy team from found on our website at www. 8.30am - 5.30pm on weekdays. leukaemiacare.org.uk/support- A nurse is available on Mondays and-information/help-and- from 9.00am - 5.00pm, Tuesdays resources/information-booklets/ to Thursdays 9.30am - 2.00pm Support Groups and Thursday and Fridays evening from 7.00pm - 10.00pm. If you Our nationwide support groups need someone to talk to, call are a chance to meet and talk 08088 010 444 to other people who are going through a similar experience. Nurse service For more information about a We have two trained nurses on support group local to your area, hand to answer your questions go to www.leukaemiacare.org. and offer advice and support, uk/support-and-information/ whether it be through emailing support-for-you/find-a-support- [email protected], group/ over the phone on 08088 010 444. Buddy Support Patient Information Booklets We offer one-to-one phone We have a number of patient support with volunteers who have information booklets like had blood cancer themselves this available to anyone who or been affected by it in some
4 www.leukaemiacare.org.uk way. You can speak to someone information on our website, who knows what you are going www.leukaemiacare.org.uk. through. For more information on how to get a buddy call Campaigning and Advocacy 08088 010 444 or email Leukaemia Care is involved in [email protected] campaigning for patient well- being, NHS funding and drug Online Forum and treatment availability. If you Our online forum, would like an update on any of www.healthunlocked.com/ the work we are currently doing or leukaemia-care, is a place want to know how to get involved, for people to ask questions email advocacy@leukaemiacare. anonymously or to join in the org.uk discussion with other people in a similar situation. Patient magazine Our quarterly magazine Patient and carer conferences includes inspirational patient Our nationwide conferences and carer stories as well as provide an opportunity to informative articles by medical ask questions and listen to professionals. To subscribe go patient speakers and medical to www.leukaemiacare.org.uk/ professionals who can provide communication-preferences/ valuable information and support. Website You can access up-to-date
Helpline freephone 08088 010 444 5 What is Chronic Lymphocytic Leukaemia?
In chronic lymphocytic leukaemia lymphatic vessels, which run (CLL), the lymphocytes in the adjacent to the small blood bone marrow start multiplying vessels in the body, drain lymph excessively leading to large fluid from all over the body to numbers of abnormal, immature clear excess fluid and act as cells called blasts, which prevent a blood filter helping to fight the bone marrow from producing infection with the help of the enough healthy blood cells of all B-cells and T-cells. types. Lymphocytes are a type of CLL is the most common form of white blood cell involved in the leukaemia in adults in Western immune response. countries. Approximately 3,500 There are three types of adults are diagnosed with CLL lymphocytes: each year in the UK alone, which is equivalent to 10 new cases B-cells produce antibodies 1. every day. Slightly more men than that seek out and immobilise women tend to be affected by CLL bacteria, viruses, and toxins and it is often diagnosed in older which invade the body. people, being diagnosed in 59% of 2. T-cells destroy the invading people aged 70 years and over. For organisms that have been reasons that are not understood, tagged by the B-cells as well CLL is more common in White as cells that have become people and less common in Asian cancerous. populations. The disease is rarely, if ever, seen in children. 3. Natural killer (NK)-cells attack cancer cells and viruses. Full details of the characteristics, diagnosis and treatment of All these types of white blood CLL are given in the Patient cell are found in the blood, bone Information Booklet titled marrow, and lymphatic system. chronic lymphocytic leukaemia The lymphatic system is a part (CLL), which is available on of the immune and circulatory the Leukaemia Care website at systems. A network of small
6 www.leukaemiacare.org.uk https://www.leukaemiacare.org. uk/support-and-information/ help-and-resources/ information-booklets/
In this booklet, relapse in CLL will be examined.
Helpline freephone 08088 010 444 7 What is relapsed CLL?
In patients with CLL who require ••Blood and bone marrow at treatment, the mainstay the cell level (cytogenetic of the treatment is chemo remission): Diseased cells immunotherapy, which consists have been greatly reduced, or of chemotherapy to which no longer appear, in the bone immunotherapy is added. Where marrow. the CLL cells have a particular Blood and marrow at the chromosome abnormality, •• molecule level using sensitive such as a 17p deletion or TP53 tests such as polymerase mutation, a novel agent such chain reaction analysis or as ibrutinib is used instead of flow cytometry (molecular chemotherapy. remission): No evidence of The nature of CLL as a chronic disease in the blood cells and/ disease means that it is not or bone marrow is seen at all. a curable disease, and that a relapse is expected to happen Why does relapse at some point. A relapse is when happen? a patient initially responds to While the recent treatment of leukaemia therapy but, after CLL with chemo-immunotherapy six months or more, response has resulted in improved patient to treatment stops. This is also responses and overall survival sometimes called a recurrence. compared to chemotherapy alone, Refractory CLL occurs when the a sizeable number of patients will cancer has not responded to first- still relapse and need subsequent line treatment (first treatment treatment. given). Relapse is often linked to the Remission can be established by cause of the CLL, particularly examining: when chromosome mutations ••Blood samples are involved. These genetic (haematological remission): characteristics are useful for Blood counts return within predicting how the CLL will normal ranges. progress, and which patients will
8 www.leukaemiacare.org.uk respond to therapy or relapse. with standard CLL patients and patients with lower-risk For patients with CLL, analysis chromosomal abnormalities. of chromosomes has detected several reoccurring mutations: Another indication of a reduced survival rate in CLL is an 13q deletion - 55% of patients •• unmutated immunoglobulin ••11q deletion - 18% of patients variable region heavy chain (IgVH) gene. This gene is responsible ••17p deletion - 7% of patients for generating antibodies used previously untreated and 30% of by the immune response. IgVH patients who relapsed mutation status has identified ••Trisomy 12 (3 copies of two subtypes of CLL that have a chromosome 12) - 16% of differing clinical course: patients 1. Patients with a mutated IgVH Patients with 13q deletion tend have a subtype of CLL which is to have good prognoses and slow to progress and with little patients with trisomy 12 have an symptoms. These patients have intermediate prognosis. Therefore, a better prognosis. these patients may be more 2. Patients without a mutated fortunate in avoiding relapses. IgVH have an aggressive Patients with 11q deletion and subtype of CLL with a poorer 17p deletion are known to have a prognosis, a shorter duration shorter time before relapse where of complete remission and a further treatment will be required. greater chance of relapse.
Deletion of chromosomal region The mutation status of IgVH can 17p13 results in the loss of one be detected by DNA sequencing. of the variants of the TP53 gene. DNA sequencing involves This abnormality is predictive of determining the exact order of a poor response to treatment and the four organic molecules (also is associated with the shortest called nucleotides: adenine, time before relapse compared guanine, cytosine, and thymine)
Helpline freephone 08088 010 444 9 What is relapsed CLL? (cont.)
which make up a molecule of DNA. first line treatment is around five years. When it has been identified How often does relapse that the disease has come back, occur? further treatment options will be discussed with you by your doctor. Despite the encouraging Details of these are given in the responses in patients with section ‘How is relapsed CLL CLL who have received chemo- treated?’ immunotherapy, most patients will relapse at some point within the first five years of starting treatment.
The first-line chemo- immunotherapy regimen of FCR (combination of fludarabine, cyclophosphamide and rituximab) is most frequently used in patients with CLL, as long as they are fit and well with little or no other health problems. However, even after this treatment regimen, approximately 6% of patients will relapse within six to 12 months and another 14% will do so within two years.
Patients whose first remission lasts less than three years have a short survival period, whatever treatment they were given subsequently. For patients with a first remission greater than three years, a number of other treatments are available. The average remission after FCR as a
10 www.leukaemiacare.org.uk Helpline freephone 08088 010 444 11 Symptoms and diagnosis of relapsed CLL
What are the ••Bruising and bleeding due to a lack of platelets in the blood symptoms of relapsed (thrombocytopenia) CLL? ••Swollen lymph nodes in the The course of CLL can be very neck, armpits or groin varied. CLL usually develops extremely slowly, and more than ••Swollen abdomen, abdominal half of all patients do not have discomfort, inability to eat large any symptoms in the early stages meals caused by an enlarged of the disease. Over time, CLL spleen or lymph nodes patients often develop symptoms Changes in appetite as a result of lower than normal •• numbers of red blood cells ••Weight loss (anaemia), white blood cells (neutropenia) and/or platelets How is relapsed CLL (thrombocytopenia). diagnosed? In patients with CLL who relapse, The majority of relapses in the symptoms and signs that patients with CLL are diagnosed may occur are similar to those for relatively early on because after newly diagnosed CLL, and include: first-line or second-line treatment, patients are monitored regularly. Feeling tired all the time •• The diagnosis of relapsed CLL (fatigue) is similar to that of the initial ••Infections – these may be diagnosis. frequent, persistent and/or Diagnosis of CLL requires the severe (due to neutropenia) presence of increased levels ••A high temperature (fever) (≥5000 per mm3) of monoclonal (genetically identical) B-cells ••Severe sweating at night in the blood for at least three ••Breathlessness, tiredness and months. The clonal nature of headaches due to a lack of red the circulating B-cells should blood cells (anaemia) be confirmed by flow cytometry (a test that identifies specific
12 www.leukaemiacare.org.uk surface markers on the cell). of proteins on the surface of the lymphoblast cells Diagnosis is achieved using the following tests: Immunophenotyping Complete blood count Immunophenotyping is used primarily to help diagnose Detects the number of red blood and classify leukaemias and cells, white blood cells and lymphomas, and guide their platelets. treatment. Where possible, Peripheral blood smear it may be able to predict the aggressiveness of the leukaemia Blood sample is viewed under and its responsiveness to certain a microscope to count different treatment. circulating blood cells, and see whether the cells look normal. Markers detected on the cells will help characterise any abnormal Bone marrow aspiration and cells present. In conjunction with biopsy the patient’s clinical history, The aspiration procedure removes physical examination, signs and a liquid marrow sample and the symptoms, and laboratory tests, biopsy removes a small amount immunophenotyping can help of bone filled with marrow. make a diagnosis. Medication is given to numb the Immunophenotyping is routinely area, or a general anaesthetic is performed by flow cytometry performed, in order to remove a which processes either blood, sample from the hip bone. These bone marrow fluid or tissue by samples can be examined for: adding specific antibodies that ••Percentage of lymphoblasts in have been tagged with fluorescent the bone marrow markers. These antibodies, also called cell markers, bind to ••Any abnormalities of the corresponding antigens on the lymphocytes lymphocytes. The flow cytometer ••Immunophenotyping: This rapidly measures the size and procedure identifies the types internal cellular structures
Helpline freephone 08088 010 444 13 Symptoms and diagnosis of relapsed CLL (cont.)
of thousands of cells, and benefit from: assesses the type and quantity Lumbar puncture - This is used of fluorescent antigen-antibody •• to determine if the lymphoblast complexes present. For these cells are in your central nervous practical reasons, flow cytometry system (brain and spinal cord). is preferred to immunochemistry for immunophenotyping. ••Imaging tests – Ultrasound Chromosomal or cytogenetic and computed tomography scanning to accurately detect analysis the enlarged lymph nodes, ••Blood smear samples can be liver and spleen before starting used to identify certain changes treatment. in the number and size of chromosomes within cells that ••Lymph node biopsy – This is might have led to the relapse. carried out when lymph nodes are swollen. A lymph node ••This can be achieved easily and biopsy is a minor surgical accurately with fluorescent procedure where a small sample in situ hybridisation (FISH) is taken from a lymph node which uses fluorescent dyes and then examined under a to attach to certain parts of microscope. This is usually chromosomes. FISH analysis performed as a day case and should always be carried out does not require a hospital stay. prior to a patient receiving treatment as it can determine ••Staging - This is a grading types of leukaemia likely to system used by consultants to relapse or their response to describe the extent of the CLL, treatment. in terms of location, its effect on the blood count, and the The following tests and number and size of existing procedures are carried out to lymph nodes. Grading CLL helps confirm the diagnosis, confirm your doctor predict how quickly the stage of the CLL, and enable the cancer may grow and your consultant to determine the spread, as well as decide the treatment you are most likely to best treatment for you. There are
14 www.leukaemiacare.org.uk two main systems used to stage CLL. Most doctors in the UK and Europe use the Binet system, whereas in the USA doctors more commonly use the Rai system.
Helpline freephone 08088 010 444 15 How is relapsed CLL treated?
To date, the FCR treatment response obtained with previous regimen has given the best treatment, length of the response, complete remission rate, longest and their characteristics at the duration of remission, and time of relapse. the most extensive survival for patients with CLL. The Alternative treatment regular chemo-immunotherapy options regimens for the treatment of Most patients with relapsed or patients with CLL are FCR or the refractory CLL require second-line combination of bendamustine therapy (treatment other than the and rituximab. However, with type used the first time around). both these regimens, patients Second-line drug regimens may may experience significant side include: effects, especially older patients or those with other health issues. ••Chlorambucil with a monoclonal antibody (if the patient only Most patients who respond to received chlorambucil on its treatment will eventually relapse own as first line therapy) and require second-line therapy (treatment other than the type ••Targeted therapy: ibrutinib or used the first time around). idelalisib in combination with However, patients who are in rituximab (when the disease remission for less than three has been treated but relapsed years the first time have shorter within 24 months) periods of remission and shorter intervals between treatments, ••Venetoclax whatever treatment regimen they ••Clinical trials may also be were given subsequently. a possibility if suitable and The most appropriate treatment available for relapsed patients depends largely on the characteristics of their CLL, and is also dependent on their prior therapies, best
16 www.leukaemiacare.org.uk Chlorambucil with a Ibrutinib is an inhibitor of monoclonal antibody Bruton’s tyrosine kinase, and (chlorambucil chemo- idelalisib is a selective inhibitor immunotherapy) of the delta phosphatidylinositol 3-kinase enzyme. Both these If patients only received targeted therapies inhibit specific chlorambucil as first-line signalling pathways for B-cells. therapy, then chlorambucil with a monoclonal antibody can be an Idelalisib has regulatory approval, alternative treatment for patients when used in combination with who relapsed. Chlorambucil is a rituximab, in previously-treated type of chemotherapy called an CLL and CLL with 17p deletion or alkylating agent which interferes TP53 mutation that cannot be with DNA and stops cancer cells treated with any other therapy. proliferating. It is approved by the National Institute for Health and Clinical When combined with other Excellence (NICE). monoclonal antibody drugs such as ofatumumab or obinutuzumab, Ibrutinib has regulatory approval chlorambucil was superior to for previously-treated CLL and chlorambucil alone in two large untreated CLL with 17p deletion phase 3 studies. or TP53 mutation, and is also approved by NICE. Targeted therapy Both ibrutinib and idelalisib are Patients with 17p deletions effective in patients with high- or TP53 mutations, for whom risk features and are able to chemo-immunotherapies are control CLL in difficult-to-treat not suitable, can be treated with patients better than currently the targeted therapies B-cell approved therapies. This makes receptors inhibitors such as them the drugs of choice for CLL ibrutinib and idelalisib, or B-cell patients with TP53 mutations lymphoma-2 inhibitors such as and patients resistant to chemo- venetoclax. immunotherapy. Both idelalisib
Helpline freephone 08088 010 444 17 How is relapsed CLL treated? (cont.)
and ibrutinib in combination Ibrutinib with monoclonal antibodies have The approval of ibrutinib as improved survival in relapsed/ initial therapy for CLL patients refractory CLL. was based on the phase 3 Idelalisib in combination with RESONATE 2 trial in which 269 rituximab previously untreated CLL patients >65 years received ibrutinib or Idelalisib is currently only chlorambucil. After a follow-up approved for relapsed/ period of 18.4 months, patients refractory CLL when combined on ibrutinib showed a significant with rituximab, based on the increase in overall survival with pivotal phase 3 trial which an estimated survival rate at 24 compared treatment with the months. Overall response rate combination against rituximab was also significantly improved alone. In this randomised trial, with ibrutinib compared with the investigators recruited 222 chlorambucil. Complete remission patients >65 years, who had been was achieved by five patients treated with first-line treatment receiving ibrutinib compared but relapsed within 24 months, with two patients receiving and had decreased renal function chlorambucil. as well as previous therapy- induced myelosuppression. Positive responses with idelalisib Treatment with the combination and ibrutinib are increasingly of idelalisib and rituximab, when being reported in patients with compared with rituximab alone, relapsed/resistant CLL. However, significantly improved overall for a number of patients with response and overall survival at 12 relapsed CLL, who were classified months in patients with relapsed as high-risk, these therapies do CLL who were less able to undergo not achieve a long-term response. chemotherapy. The clinical benefit of this drug was also present in Venetoclax the high-risk patients with del Venetoclax is an inhibitor of (17p) and/or TP53 mutation. the activity of a protein called
18 www.leukaemiacare.org.uk B-cell lymphoma-2. This protein a complete response achieved in regulates the natural death 20%. of cells, particularly cancer cells. In the United Kingdom, Rechallenge with first- venetoclax has conditional line treatments approval for CLL when other Patients with CLL who have treatments have failed or are relapsed can be re-challenged unsuitable. Conditional approval with the first-line treatments for marketing authorisation of FCR or the combination of (available for prescription) was bendamustine and rituximab, but granted because additional data this is extremely rare. is being considered; however, the use of venetoclax in the interest FCR of public health and the benefit of For patients without the high-risk immediate availability outweighs features for being refractory to the risk from less comprehensive therapy or having chromosome data than normally required. 17 abnormalities, FCR is an NICE recommends the use of effective and safe therapy. For venetoclax in patients with a 17p high-risk and elderly patients, deletion or TP53 mutation, and optimal treatments still need to whose disease has progressed be defined. despite treatment with Bendamustine and rituximab chemo‑immunotherapy and a combination B‑cell receptor inhibitor. For the many CLL patients >65 In a phase 1 study to determine years who experience severe the best dose of venetoclax to toxicity with FCR (because use in safety and efficacy trials of the serious infections and (dose-escalation study), the suppression of the bone marrow), overall response rate across bendamustine combined with all doses of 116 patients who rituximab (BR) is commonly used received venetoclax was 79% with as it is better tolerated.
Helpline freephone 08088 010 444 19 How is relapsed CLL treated? (cont.)
Allogeneic stem cell does not respond to two lines of treatment and shows an transplantation objective response to B-cell The treatment options described receptor inhibitors or to previously may render allogeneic treatment in a clinical trial stem cell transplantation (ASCT) outmoded because patients ••CLL which does not show can now be maintained in a an objective response or prolonged disease-free state progresses after B-cell receptor with these treatments, even if inhibitors, regardless of whether they are not curative. However, an objective response is especially for young healthy achieved patients, ASCT remains the only Supportive therapy potentially curative option if they are fortunate enough to Supportive therapy or palliative have a suitable donor. ASCT is care is valuable during treatment rarely offered to patients aged in each phase of CLL to offset any >70 years. Clinical practice complications, particularly for recommendations for the role of patients with high-risk features. ASCT in the current management Supportive therapies given during of relapsed CLL has relegated treatment for relapsed CLL may its use to later in the disease. A include antibiotics, antivirals, or recent paper summarising the antifungals to combat infection, clinical findings of physicians and leukapheresis to separate out with expertise of ASCT in CLL has large numbers of white blood cells recommended ASCT for patients from the blood. For more details, with the following: see the palliative care section later in the booklet. ••CLL which is refractory or progresses despite treatment Clinical trials with B-cell receptor inhibitors For some patients, including ••CLL in high-risk patients which those with poor treatment responses associated with the
20 www.leukaemiacare.org.uk del17p mutation, TP53 mutation response to treatment and your and a lack of mutated IgVH, state of health. It is possible that participation in clinical trials can your CLL will progress slowly and offer another treatment option, remain controlled with targeted as clinical trials are currently therapy. Alternatively, you may making excellent progress in go into remission for many years, the treatment of CLL. Moreover, during which time you will not clinical trials represent a strong have any symptoms and your contribution to CLL management, blood tests will be clear. as well as access to newer In the event of a relapse, you medications which may not be will be offered further treatment available on the NHS, and the to help you reach a second possibility in the future with the remission. If the new targeted development of new treatments. therapies are not successful, Details of trials in the treatment you may be offered intensive and management of CLL which are treatment with an ASCT, recruiting patients can be found depending on your age and state online at clinicaltrials.gov of health, but this is rare due to the further treatments options Prognosis that are now available.
The majority of patients will The two most important genetic experience a relapse within prognostic markers for CLL that five years of starting chemo significantly affect the course immunotherapy, and for patients of the CLL and the likelihood of with a duration of first remission relapse are: less than three years prognosis is worse. However, on the whole, CLL ••Chromosome 17 deletion 17p, is not seen to have an impact on del(17p), which occurs in 30% of natural lifespan. patients who relapse Your prognosis will vary according ••TP53 mutations and/or no IgVH to the phase of your CLL, your mutation
Helpline freephone 08088 010 444 21 How is relapsed CLL treated? (cont.)
The poor treatment responses, and shorter time before relapse associated with the del17p mutation, TP53 mutation and lack of mutated IgVH are the focus for using new therapies to treat CLL.
22 www.leukaemiacare.org.uk Helpline freephone 08088 010 444 23 Seeing your doctor
Your symptoms Examples of questions to ask the doctor: Whatever symptoms you have, make sure you write a list of all ••How would I know if I my CLL of them to share with your doctor came back? as they may be important to your What tests will I need to have? treatment. •• ••What will the tests show? Your appointment How long will it take to get the Arranging an appointment with •• results back? your general practitioner (GP) or your consultant will be one ••How common is it to have a of the first things you will need relapse? to do when you start to notice symptoms. Pick a time convenient ••What sort of treatment will I for you that you know you will be need? able to attend. If there is a chance ••How long will my treatment that you might be experiencing last? a relapse, you will be referred to the hospital who will be able to ••How will I know if my treatment confirm this through tests. has worked this time? Your preparation ••What will the side effects be? It is important to know exactly ••Are there any foods or what you would like to ask medications I need to avoid? your doctor. Make a list of your ••Will I be able to go back to work? questions and leave spaces for the answers so you can write ••Where can I get help with them down when you see the claiming benefits and grants? doctor. This way you can go into Where can I get help dealing the meeting ready and prepared. •• with my feelings?
24 www.leukaemiacare.org.uk Talking to your doctor that nothing has been missed or forgotten. Be honest with your doctor; they have seen and heard everything The next steps before, so there is no need to feel Always ensure that you leave the embarrassed about anything. If GP surgery, or the hospital, having you saw your healthcare team shared everything you know before seeing your doctor, be about your condition, with all of sure to share with your doctor your questions answered, and everything your healthcare team knowing exactly what the next told you about your relapse, the steps are, whether it is more tests, blood tests you had performed, further treatment or palliative and the next steps in your CLL care. You can ask for a summary journey. letter of the consultation to have If you want to, ask if you will everything in writing. Your doctor receive more intensive treatment will generally send a letter like or palliative care. However, it is this to your GP. important to remember that this Furthermore, be sure to access is only offered if other lines of all of the other support available treatment are exhausted or you to you as this may be able to help decide you no longer want further you with your feelings towards treatment. It is increasingly rare your diagnosis and treatment. for patients to die due to their CLL. Your support If it helps, take a family member or friend in with you for support. Some people take a pen and paper in to make notes, and repeat back to their doctor everything they have been told to ensure that they are both on the same page and
Helpline freephone 08088 010 444 25 Telling your family
Planning who to tell people in an environment where both of you can hear each other Telling your family and friends clearly and where there are likely that you have suffered a relapse to be no interruptions. can be difficult, especially since you already went through it with How to say it your initial CLL diagnosis. One Although it is upsetting that you positive aspect to this is that you have relapsed and the people already have your team in place, you tell may get upset for you, it so once they know what your is important to try and remain situation is, they can help and positive and optimistic when support you like they did before. talking. Even though a relapse You may want to create a list of is unfortunate, it is not the end people you want to tell, starting of the world, as there are further with close family and friends, and treatment and supportive care then extending it beyond, from options available. your colleagues at work to friends in your neighbourhood. How to respond You may receive similar Planning what to say responses to when you told people It is important to know what about your initial diagnosis. you want to say and exactly how Naturally they will feel sad, and much you want people to know. concerned for you. Everyone deals Being clear in your mind about with this type of news in their own that before speaking to anyone way, from shock and silence, to will make this a much smoother questions and support. experience. Know your story that Invariably, people respond you want to tell, the diagnosis, positively, which in turn means the prognosis, the next treatment you will respond back positively. steps, and what you expect to be going through physically and emotionally. Be sure to speak to
26 www.leukaemiacare.org.uk Accepting help You can receive help from Sometimes people feel guilty for us on how to speak to their cancer relapsing, that they weren’t strong enough, and that your friends and family they will be a burden on those following a relapse. around them. This is where your You can visit www. loved ones come in, so make sure leukaemiacare.org.uk, you do ask for and accept offers to or call 08088 010 444, to help and support you in the next find out more. stages of your CLL journey. Do not try to cope on your own. If they offer to help, tell them that you will get in touch when you need them.
Repeating yourself to different people can become burdensome, which is where your network of family and friends can help you out, by telling those beyond them about your current situation.
Helpline freephone 08088 010 444 27 Managing your emotions
Being told that your cancer has relapse and carrying on with your returned may be difficult for life will help ease any anxieties. you to deal with, especially after Help, care, kindness and support all your time and effort during will be available to you from your treatment and remission period. healthcare team, and you will have access to counsellors and Indeed, you may have a positive therapists when you need it. demeanour, which will obviously be helpful to you during the next Isolation steps in the management of your CLL. However, you may experience If you have received a diagnosis of a range of emotions, including relapse, and the next steps don’t uncertainty, isolation, anxiety, involve intensive treatment, you anger, sadness and depression. may feel a break in your routine. Understanding each emotion and You may feel alone because developing ways that help you you will no longer enjoy regular deal with them will help you move meetings with your healthcare forward with your life. team who provide you with information and reassurance, Uncertainty or fellow patients who can provide you with empathy and You may think "What happens compassion. next?". You may be unsure about your health and what the future Alternatively, you may feel this holds for you. You may or may break in routine allows you to not have had meetings with your be around those closest to you, healthcare team to discuss the and follow your regular routine of next steps following your relapse. work and play. Being around those Once you have a clear path set out closest to you, such as your family in front of you, you will be able to and friends, can be positive and develop a clearer picture of where negative. you are headed. Gaining a sensible Let them know what you do and balance between being vigilant don’t want to do, how you do about your symptoms following
28 www.leukaemiacare.org.uk and don’t wish to be treated, help you to cope with the physical and what you do and don’t feel effects of anxiety. Cognitive comfortable talking about. behavioural therapy can help you Sometimes, it is difficult for your deal with your worrying thoughts. family, friends and colleagues to understand what you are Anger feeling and going through. Being Feeling angry after a relapse is clear will help create the kind of natural and normal. You may be positive, supportive, and caring angry with yourself, your body, environment that will help as you with the healthcare team or move forward with your life. with family and friends. You may display your anger as impatience, Anxiety irritability and frustration with Being fearful of the unknown, people and things that would not especially when we are feeling normally bother you. threatened, is natural. You may Understanding exactly what is experience an increased heart making you angry will help you rate, rapid breathing, and muscle deal with your feelings effectively. tension. These things help us to In addition, setting yourself face a danger or run away. These achievable goals that stretch you changes in you are part of the will help reduce the anger and ‘fight or flight’ response. Any impatience you feel, especially feeling of discomfort, pain or even with each passing success. Don’t another appointment with your forget to congratulate yourself for healthcare team may elicit such each successfully completed task, responses, and give you sleepless however small. nights or feelings of worry. This is completely natural. Physical exercise is a great way to release your anger and Such reflexes and responses will frustrations, and channel your ease over time with the building energy positively with no negative of daily routines and planning impact on your body. Talking things for the future, which will
Helpline freephone 08088 010 444 29 Managing your emotions (cont.)
about your feelings, letting them do as much as you can and try out, will also help stop you lashing and talk about your thoughts and out at people and keep you calm. feelings. This will help lighten your burden and put things into Sadness and perspective. If you have made depression any acquaintances or friends in the same position as you, talk Relapsing will bring back some, to them over coffee as they will if not all, of the feelings you felt understand exactly what you are when you were first diagnosed facing. with your CLL. You may feel a sense of loss of the person you Self-confidence used to be, and how safe you felt. You may also feel that your illness Being forced to readjust from your is a heavy burden on those around daily routine during remission you. You might be feeling low, back into one involving multiple which is a natural effect of your visits to the hospital for further illness, treatment and recovery. treatment, or moving into However, if this low mood persists palliative care, can take its toll. for more than several weeks, This interruption of your life, along and you feel hopeless, and with your lack of energy because lose interest and pleasure with of your CLL and the effects of your things in life, then you may have treatment, can impact on how depression. you feel about your appearance and how you feel emotionally. In Your first steps should be to turn, this can knock your self- speak to your loved ones around confidence and self-esteem. you about your mood and state Your feelings of relief, hope, and of mind, and then contact your optimism have just been replaced GP. You may lift the way you feel with their polar opposites. by engaging in activities that you were enjoying before your You can gradually build your self- relapse and initial diagnosis, to confidence and self-esteem back connect back with your life. Only up by engaging in the activities
30 www.leukaemiacare.org.uk you did before your diagnosis, and can help quieten your mind and socialising with family, friends, remove the stress of coming to and fellow patients. This will help terms with your diagnosis, so you create a supportive atmosphere to feel calmer and more relaxed. get you back to your old self. Mindfulness and relaxation Simple practices from mindfulness and relaxation techniques can help you calm the mind, release tension and ease any pain in your muscles. ••Put yourself in a relaxing environment, sitting or lying down comfortably. ••Loosen your clothing so you can move more freely. ••Calmly breathe in through your nose, and out through your mouth, developing a steady natural rhythm, focusing on your chest and abdomen as you do so. ••Visualise that you are inhaling positivity and exhaling negativity.
By taking some time out of your day to do these exercises, you
Helpline freephone 08088 010 444 31 Survivorship
Someone who is living with or is the end of treatment until the end beyond a cancer diagnosis can be of life. At this point, your routine considered a cancer survivor. of meeting frequently with your healthcare professionals also Survivorship can be defined as: ends, so you may feel a mixture "...cover[ing] the physical, of emotions from relief to fear, psychosocial and economic anxiety and uncertainty about the issues of cancer, from diagnosis future. You may wonder how you until the end of life. It focuses will slot back into your life after on the health and life of a coming through the treatment person with cancer beyond the period. diagnosis and treatment phases. Your survivorship pathway began Survivorship includes issues at the point when you were related to the ability to get health diagnosed with CLL. By this point, care and follow-up treatment, late you will have been starting to effects of treatment, secondary receive support for work, finance, cancers and quality of life. Family and personal relationships members, friends and caregivers through to managing pain, fatigue are also part of the survivorship and making positive lifestyle experience." changes, such as starting a When living with cancer, healthy diet and gentle exercising. especially if you are relapsing Your individual needs as a patient after remission, you will face new will be identified and addressed, challenges to cope with from including: physical to psychological and social ones. Survivorship aims ••Dealing with the emotional to provide personalised care impact of receiving a diagnosis based on your need to improve of relapse which may have your health, wellbeing, quality created feelings of uncertainty, of life, and your confidence and fears of recurrence and motivation, to help you manage. difficulties in planning for the Survivorship also focuses on your future. These will be discussed health and life with cancer after with you to develop your
32 www.leukaemiacare.org.uk individualised care plan with ••Preparing you fully for support from social care staff the impact of relapse and and therapists, as you need it. treatment, the physical and physiological side effects Improving your quality of life •• of treatments and the through efficient and co- psychological impact of CLL ordinated care during your relapse in general. You will be treatment, with effective provided physical equipment, communication within the and taught about various treatment team, and a positive coping strategies to adapt to attitude. your new situation. Taking care of any comorbidities •• ••Supporting you with advice – that is, other medical for social and financial conditions and diseases difficulties, including caring – and offering you cancer responsibilities, your inability to rehabilitation based on your participate in social activities, clinical needs as assessed by any debt and financial worries informed professionals, and from not being able to work, and ensuring compliance with the perhaps the need to return to National Cancer Rehabilitation work before you feel ready. Pathways. ••Receiving health and nutrition Providing you with a treatment •• advice from a nutritionist summary from diagnosis of on following a healthy and your relapse to the end of your balanced diet to help improve treatment. This would include your general health and any ongoing medication and wellbeing. The World Cancer noting possible symptoms that Research Fund published a may occur in the future. You report for cancer survivors would also be provided details which suggests that even small of who to contact in addition to dietary and lifestyle changes your GP for any concerns you can produce large health may have. benefits.
Helpline freephone 08088 010 444 33 Palliative care
Palliative care in occupational therapists, complementary therapists, and relapsed CLL religious leaders, if you would like Palliative care, also known as this. Your palliative care services supportive care, involves a holistic may be provided by the NHS, local or "whole person" approach, which council or a charity. You may includes the management of your receive day-to-day care at your pain and symptoms as well as home and at the hospital. psychological, social and spiritual support for you and your loved What is the clinical ones. course? Palliative care aims to reduce You will have experienced a your symptoms, control your CLL, protracted cycle of relapses and extend your survival, and give remissions, and be prone to you and your loved ones the best frequent infections because of quality of life possible. Your doctor the CLL and the impact of your will discuss the options with you treatments. Your chemotherapy in detail before you decide the may continue because of next steps. potential remission and/or useful palliation. Who provides palliative You may experience various pains care? and other clinical complications Your palliative care will be such as: provided by a team of health and social care professionals trained ••Bone pain: Radiotherapy and/ in palliative medicine who will or oral steroids, and sometimes coordinate your care. non-steroidal anti inflammatory drugs (NSAIDs), may be used, These professionals can include although these are used with your GP, hospital doctors and caution because they can nurses, community nurses, interfere with your immune hospice staff and counsellors, system and kidney function. social care staff, physiotherapists, ••Bone marrow failure: Blood
34 www.leukaemiacare.org.uk and platelet transfusions vertebrae of the spinal column: are provided to prevent and Treatments can include fight recurrent infections and analgesics, antidepressants bleeding episodes. and/or anticonvulsant medication used in tandem Oral problems: Analgesic •• with opioids. mouth washes and topical ointments may help with ••Hypercalcaemia: Treatment ulceration. Chewing gum, and is usually with intravenous mouth washes have been shown hydration and intravenous to help with dry mouth, dental bisphosphonates. caries and oral thrush. ••Loss of appetite: Low-dose ••Night sweats and fever: These steroids may temporarily can place a heavy burden on boost the appetite, while small, carers because of so many frequent and appetising meals changes of night clothes and and supplement drinks will also bedding. help. ••Pathological fractures: Orthopaedic intervention and subsequent radiotherapy, with consideration given to prophylactic pinning of long bones and/or radiotherapy to prevent fractures will be performed. This will reduce the likelihood of complex pain syndromes developing. ••Spinal cord compression: Immediate high single daily dose oral steroids will be given. ••Back pain from wedge and crush fractures of the
Helpline freephone 08088 010 444 35 End of life care
When does end of life Who provides end of care begin? life care? If you have relapsed and are going A team of health and social care through palliative care, you may professionals may be involved be offered end of life care. End of in your end of life care, including life care begins when you need it hospital doctors and nurses, your and may last a few days, months GP, community nurses, hospice or years. staff and counsellors, social care staff, physiotherapists, What does end of life occupational therapists or care involve? complementary therapists, and religious leaders, if you would like End of life care is support for this. If you are being cared for at people who are in the last few home or in a care home, your GP months or years of their life. The will have overall responsibility for aim is to help you enjoy a good your care with the support from quality of life until you die, and to community nurses, along with die with dignity. The professionals your family and friends. looking after you will ask you about your wishes and What choices do I have preferences on how to be cared for and put these into action. They in terms of end of life will also provide support to your care? family, carers and loved ones. You Deciding where you want to die will be able to decide where you can be a difficult choice to make. will receive end of life care, be it at Working out what you and your home or in a care home, hospice loved ones want, together with or hospital. The same will be true seeing what services are available of where you would like to die. to you can help to make the Wherever you are, you will receive decision a little easier. high quality end of life care. ••Staying at home - A place of familiarity, surrounded by your loved ones, may be something
36 www.leukaemiacare.org.uk that you will find reassuring. cannot always be tailored to External care professionals will your specific needs. Pressures be able to visit you at home to on the NHS mean that your make sure your symptoms are stay will only be as long as looked after. strictly required. As soon as the condition you were admitted Hospices – Specialised in •• for has been resolved, you will looking after those with life- need to go back to your home limiting illnesses and those or nursing home. However, a who are coming to the end of number of specialists will be their life, hospices are staffed available to help look after you with care professionals who for specific problems, and a are able to keep an eye on you, number of hospitals also have a make sure that your symptoms designated palliative care team are controlled and offer you a for patients who require them. number of services to make your stay as comfortable as Whatever your choice, speak possible. For more information with your GP or healthcare team on the care that they can who will able to help you put provide, go to https://www. everything into place. hospiceuk.org/ ••Residential care/nursing homes - If you think that your stay may be a few months or more, then a nursing home may be more suitable than a hospice. These can be private or run by a charity or the local council so be sure to check if there are any fees. ••Hospitals - Although you may be used to staying in a hospital ward, the care routine
Helpline freephone 08088 010 444 37 Glossary
Allogeneic Stem Cell Transplant cells are not fully developed and (ASCT) are called blasts or leukaemia cells. Stem cell transplant of cells from a matching donor. Bone Marrow Failure Amino Acids Term used when the bone marrow is unable keep up with the body’s Organic molecules which are need for white and red blood cells the building blocks for making and platelets. proteins. Central Nervous System Anaemia Part of the nervous system which Condition where the number of includes the brain and spinal red blood cells, which contain cord. haemoglobin and transport oxygen to body cells, are reduced. Chemotherapy This may be due to a lack of iron, Drugs that work in different ways leukaemia or sickle cell disease. to stop the growth of cancer cells, Antibody either by killing the cells or by stopping them from dividing. Protein produced by the B-cell lymphocytes in response to Chromosomes a specific antigen, such as Thread-like structures which carry a bacteria, virus, or foreign the genes, and are located in the substance in the blood. nuclei of every cell in the body. Antigen There are 46 chromosomes (23 pairs) in humans. Toxin or other foreign substance which induces an immune ClinicalTrials.gov response in the body, especially ClinicalTrials.gov is a database the production of antibodies. of trials and includes details of Blasts 276,190 research studies in 204 countries. Patients with leukaemia have a high number of abnormal white blood cells. These white blood
38 www.leukaemiacare.org.uk Clonal found in the nucleus of each cell in the body which carries genetic Refers to an organism descended instructions used in the growth, from, and genetically identical, to development and functioning of a single common ancestor. the individual’s cells. Complete remission Fatigue Complete remission is said to Tiredness and weakness have occurred when the following rendering the patient unable to conditions have been met: work or perform usual activities. ••Blood cell counts returned to Flow Cytometry normal Technology used to analyse ••Less than 5% of blasts the physical and chemical (abnormal, immature, early characteristics of particles in a lymphocytes) are still present in fluid as it passes through at least the bone marrow one laser. Cell components are fluorescently labelled and then There is no leukaemia present •• excited by the laser to emit light elsewhere in the body at varying wavelengths. Cytogenetics Fluorescence in Situ Branch of genetics that is Hybridisation (FISH) concerned with how the Process using fluorescent chromosomes relate to cell dyes to attach to certain parts behaviour, particularly to their of chromosomes for their behaviour during division and identification. reproduction. Cytotoxic Drugs Genes Genes are made up of DNA which Drugs that are toxic to cancer stores the genetic information cells and prevent their growth and required to make human proteins. replication. DNA (Deoxyribonucleic Acid) Immunophenotyping Process that uses antibodies to Thread-like chain of amino acids
Helpline freephone 08088 010 444 39 Glossary (cont.)
identify cells based on the types system (part of the body’s of antigens or markers on the immune system) that contain surface of the cells. This process lymphocytes which produce is used to diagnose specific types antibodies and macrophages to of leukaemia and lymphoma digest dead cells. Lymph nodes by comparing the cancer cells are swollen with cell fragments in to normal cells of the immune the event of infection or cancer. system. They are located mainly in the spleen but also in the neck, Immunotherapy armpit and groin. Treatment that uses the body’s own immune system to fight the Minimal Residual Disease cancer. (MRD) Measure of the presence of Leukopenia leukaemia at a molecular level Abnormally low number of white rather than at a cell level. It blood cells in the blood. is measured using molecular techniques such as flow Leukaemia cytometry and polymerase chain A group of cancers that usually reaction analysis. begin in the bone marrow and result in high numbers of Morbidity abnormal white blood cells. These Refers to having a disease or a white blood cells are not fully symptom of a disease. developed and are called blasts or leukaemia cells. Depending Phase 1 Trial on the type of white blood cell Small trial (up to 30 volunteers) involved, there are different to confirm if the drug behaves types of leukaemia with varying as expected, determine its side characteristics, such as being effects, and how the body reacts acute (develop quickly) or chronic to the drug. (develop slowly). Phase 2 Trial Lymph Nodes Medium trial (up to 100 Components of the lymphatic volunteers/patients) to confirm
40 www.leukaemiacare.org.uk the drug’s safety, find the best Protein Kinase Inhibitor dose to use, assess the drug’s Protein kinase inhibitors block effectiveness if the trial is in the protein kinase enzymes that patients, and determine the value are involved with cell growth, of studying it in large numbers of thereby preventing the growth of patients in a Phase 3 trial. the cancer cells. Phase 3 Trial Refractory Large clinical trial (more than Refractory CLL occurs when the 100 patients) that collects cancer has not responded to first- information on a drug’s safety line treatment. and effectiveness using different populations and different Relapse dosages, and by comparing it to A relapse is when a patient other known drugs for a condition. initially responds to leukaemia Phase 4 Trial therapy but, after six months or more, response stops. This is also Trial conducted once a drug has sometimes called a recurrence. been granted a licence to find out more about a drug’s side effects, Remission its long-term risks and benefits, Remission occurs when the or how well it works when it’s used following conditions are met: more widely. ••Blood cell counts returned to Platelets normal One of the types of blood cell which helps to stop bleeding. ••Less than 5% of blasts (early stem cells) are still present in Prognosis the bone marrow Indication of how well a patient is ••There is no leukaemia present expected to respond to treatment elsewhere in the body (minimal based on their individual residual disease) characteristics at the time of diagnosis or other timepoint in Salvage Chemotherapy the disease. Chemotherapy given to a patient
Helpline freephone 08088 010 444 41 Glossary (cont.)
when other options are exhausted. Second-line Therapy Treatment other than the type used the first time around (first- line treatment). Targeted Therapy Drugs that specifically interrupt the leukaemia cells from growing in the body. These drugs do not simultaneously harm healthy cells the way conventional chemotherapy drugs do. Thrombocytopenia Low levels of platelets, which are small blood cells that help the body form clots to prevent or stop bleeding. Toxicity Harmful effect.
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42 www.leukaemiacare.org.uk Useful contacts and further support
There are a number of helpful Bloodwise sources to support you during Bloodwise is the leading charity your diagnosis, treatment and into the research of blood cancers. beyond, including: They offer support to patients, ••Your haematologist and their family and friends through healthcare team patient services. ••Your family and friends 020 7504 2200 ••Your psychologist (ask your www.bloodwise.org.uk haematologist or CNS for a Cancer Research UK referral) Cancer Research UK is a leading Reliable online sources, •• charity dedicated to cancer such as Leukaemia Care research. Charitable organisations •• 0808 800 4040 There are a number of www.cancerresearchuk.org organisations, including ourselves, who provide expert Macmillan advice and information. Macmillan provides free practical, Leukaemia Care medical and financial support for people facing cancer. We are a charity dedicated to 0808 808 0000 supporting anyone affected by www.macmillan.org.uk the diagnosis of any blood cancer. We provide emotional support Maggie’s Centres through a range of support Maggie’s offers free practical, services including a helpline, emotional and social support patient and carer conferences, to people with cancer and their support group, informative families and friends. website, one-to-one buddy service and high-quality patient 0300 123 1801 information. We also have a nurse www.maggiescentres.org on our help line for any medical Citizens Advice Bureau (CAB) queries relating to your diagnosis. Offers advice on benefits and Helpline: 08088 010 444 financial assistance. www.leukaemiacare.org.uk [email protected] 08444 111 444 www.adviceguide.org.uk
Helpline freephone 08088 010 444 43 Leukaemia Care is a national charity dedicated to providing information, advice and support to anyone affected by a blood cancer.
Around 34,000 new cases of blood cancer are diagnosed in the UK each year. We are here to support you, whether you’re a patient, carer or family member.
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Helpline: 08088 010 444 (free from landlines and all major mobile networks) Office Line: 01905 755977 www.leukaemiacare.org.uk [email protected]
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