Haematology and Palliative care

1. Lisa Newton Bradford Teaching Hospitals NHS Foundation Trust Haematology and Palliative care

2. Palliative care and haematology • Background information • Blood product support • Bleeding in cancer patients • Case studies • Myelodysplasia • Prognostic factors in lymphoma and leukaemia

3. Haematology and specialist palliative care services • Review by University of York, Palliative Medicine 2011 • Haematological malignancy patients less likely to be referred to specialist palliative care services • IOG recommends integration from time of diagnosis • Current evidence doesn’t support this – Australian – “death in the curative system”

4. Why are they not referred? • Do haematological malignancy patients have unmet needs? • Are the needs met by others – Haem CNS, Drs ? • Haem malignancy patients more drowsiness and delirium and similar overall symptom severity to solid tumour patients • Haem malignancy patients referred late (14 days prior to death v 47 days) • Referral to palliative care – more likely to have a home death – generally preferred place? • Haem patients 2 x as likely to die in hospital

5. Why do more haematology patients die in hospital? • Is it the preferred place? • Is it due specific factors: • Diverse set of conditions with differing pathways for disease type – eg MM – years, elderly AML days • Do the long term patients have appropriate symptom control /supportive care management from haematology team? • But – lots of trips to the wards, day unit – prevents access to community palliative care which could reduce admissions for terminal care • Absence of clear transition between curative, life prolonging and palliative phase of disease : • Difficulty identifying the transition • Timing of death unpredictable even for specific disease types • Because – nature of complications – bleeding, sepsis – may be rapid, variable number of therapies, variable response, unknown time to relapse, will it be the last relapse? efforts focussed on life saving treatment ICU deaths, young patients, Dr emotions, anecdotes

6. Blood product support

7. Physician ranking of forms of life support in order of preference for withdrawal • Blood products • Haemodialysis • Iv vasopressors • TPN • Antibiotics • Tube feeding • Mechanical ventilation • intravenous fluids

8. Other factors influencing withdrawal of support – physician preference • In general prefer to withdraw forms that were scarce, expensive, invasive, unnatural, artificial, emotionally taxing for the patient, high technology and rapidly fatal when withdrawn • Prefer not to withdraw forms that require continuous rather than intermittent administration, forms that cause pain when withdrawn • Less likely to withdraw if supporting iatrogenic complication • Preference for withdrawing a recently implemented support • Timing of death – prefer to withdraw treatment resulting in immediate death • Physician social and professional charas – no assoc with sex, religion (Catholic, Jewish less likely 1 study), rank, specialty • Physician age – more likely if younger • Does a particular specialty feel more comfortable withdrawing its own “form of life” – including haematologists

9. Bleeding in cancer patients LOW PLATELETS, PLATELET DYSFUNCTION, REDUCED CLOTTING FACTORS • Chemotherapy (BM depression, DIC trigger) • Radiotherapy • DIC • Sepsis • Vitamin K deficiency • BM infiltration (haematological, lung, thyroid, renal breast, prostate) • Hypersplenism • TTP • ITP • Liver dysfunction • Mucosal bleeding, bruising

10. DIC Underlying disorder Systemic activation of coagulation Widespread fibrin deposition Consumption of platelets and clotting factors Microvascular thrombotic low platelets and obstruction coagulation factors ORGAN FAILUREBLEEDING

11. Mucosal bleeding

12. Blood product support • Red cells – aim for Hb >8-9 (depends on symptoms, age, comorbidities • Platelets – if febrile transfuse if < 20 otherwise <10. if bleeding transfuse • In patients may get daily platelets, out patients aim for 1-2 x a week • Chronic asymptomatic thrombocytopenia – only transfuse if bleeds • Bleeding more likely AML, MDS v ITP • Platelet refractoriness – fever splenomegaly sepsis, antibodies

13. Withdrawing blood product support • Little guidance in literature: • When goals no longer being met • Blood loss exceeding replacement eg carotid artery erosion from tumour • Inability to obtain venous access • Inability to match blood product due to antibodies • Subjective – fail to improve energy, strength , dyspnoea • Not working – patients may decide its not worth the effort. Try and discuss early that time will come when it will be ineffective/ unable to keep pace/ not want it • Going home/hospice for terminal care forces a decision • Alternatives – optimise clotting with drugs – vitamin K, tranexamic acid (oral/topical), norethisterone. No aspirin, NSAIDs (?), cautery for epistaxis, nurse on dark sheets • Distress for relatives particularly if dying at home

14. Case 1 - Donald • 67 year old man • CML diagnosed in 1999 • Interferon Alpha and Hydroxycarbamide. autologous stem cell transplant. He then was tried on Imatinib, Nilotinib and Dasatinib with no cytogenetic response • T315I mutation. • Not fit for allogeneic transplant • accelerated disease - Hydroxycarbamide • Busulphan - controlled counts to a degree – soldiering on • Ponatinib – Liverpool in Feb 2012 – compassionate use • Increasing transfusion requirement – keen to “keep going while I can” recurrent epistaxis, melaena • Community palliative care referral but little involvement • 2 weekly, weekly 2-3 x week, inpatient – blood product support stopped 27/3, died 28/3

17. Case 2 Joanne • Age 29 • Diagnosed myelodysplasia Dec 2010 – erythroid (rare, poor prognosis - approx 1 year) • 3 months post partum - 2 children, partner • Initially monitored – falling blood counts – treated with azacitidine (nucleoside analogue) – sc as an outpatient every 4 weeks (aiming for allogeneic stem cell transplant long term • BM post 3 cycles – improvement - Completed 6 cycles – due BM, bone pain, sweats • BM – AML • Given 1 x intensive chemo (DA) – in patient for 4 weeks – repeat BM – no response – refractory – poor prognosis • Given further intensive treatment (FLAG) – in patient – complicated by severe perineal sepsis (palliative care involved)– white count increase after 4 weeks – blasts – well enough to go home • Home 12/10, • Hydroxycarbamide to try and control white count, blood product support, day unit 1-2 weekly, got married, day unit – 5 attendances • Increasingly weak – decided to stop coming – last visit 31/10 died at home in her own bed 3/11 • Should blood and platelets be given in hospices?

18. prognostic factors in acute myeloid leukaemia • Cytogenetics – good 69%, standard 50%, poor 20% (33% with BMT) 5 years (<60 years) • Molecular – NPM1, FL3 mutations, core binding factor - drugs • Age >60/<60 • Performance status • Secondary /de novo • White count • Response to cycle 1 (84% CR rates) • Signs/symptoms of progression – deterioration in counts, increased blood product requirements, bone pain, leucostasis

19. Prognostic factors in ALL • Age 2-10, <35) relapse and treatment related mortality much higher • Cytogenetics, philadelphia (25% adults , 3% children), MLL • Male • High white count • B or T cell • Treatment related mortality 5-10% adults, <1% children • 20-40% longtermsurvivial

20. myelodysplasia

21. Myelodysplasia(Bleeding, anaemia, infections) • Myelodysplastic syndromes (MDS) represent a heterogeneous group of myeloid neoplasms characterized by abnormal differentiation and maturation of myeloid cells, bone marrow failure, and a genetic instability with enhanced risk to transform to AML • Older patients, Comorbidities • Types, RA, RARS, RAEB RCMD • only curative treatment approach is stem cell transplantation – only suitable for few patients, relatively high risk of transplant-related morbidity and mortality • Intensive chemotherapy can induce long term disease-free survival in a few, most relapse • non intensive agents – new – azacytidine , decitabinelenalidomide produce major responses in subgroups

22. prognosis

23. lymphoma

24. Lymphoma symptoms • Diverse • B symptoms • Symptoms related to nodes – compression of adjacent structures, local discomfort • Symptoms related to bone marrow failure, bone pain • Symptoms related to extra nodal sites • Asymptomatic - chance finding – lymphocytosis

25. Lymphoma staging • Stage I - the lymphoma is in only one group of lymph nodes • Stage II - two or more groups of lymph nodes are affected, but are on one side of the diaphragm, either all in the chest or all in the abdomen • Stage III - two or more groups of lymph nodes are affected, in both the chest and the abdomen • Stage IV - lymphoma is in at least one organ other than the lymph nodes (for example, the bone marrow, the liver, or the lungs) • A or B

26. Lymphoma treatment • Watch and wait • Chemotherapy • Radiotherapy • Monoclonal antibodies • Steroids • Potential curable, rapid response - very chemo/radiosensitive • When not to treat – comorbidities, performance status, biology, age?

27. Features that may require palliation

28. Poor prognosis in lymphoma (IPI ) • Stage • Age, LDH • Performance status • Extranodal sites – CNS • Comorbidities • Chemoresponsiveness • Types B/T, HD v NHL