Haematology and Palliative care

Lisa NewtonBradford Teaching Hospitals NHS Foundation Trust

Palliative care and haematology

Background information Blood product support Bleeding in cancer patients Case studies Myelodysplasia Prognostic factors in lymphoma and

leukaemia

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”

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

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

Blood product support

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

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expensive, invasive, unnatural, artificial, emotionally taxing for the patient, high technology and rapidly fatal when withdrawn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

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

DIC

Underlying disorder

Systemic activation of coagulation

Widespread fibrin deposition Consumption of platelets and clotting factors

Microvascular thrombotic low platelets andobstruction coagulation factors

ORGAN FAILURE BLEEDING

Mucosal bleeding

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

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

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

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?

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

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% longterm survivial

myelodysplasia

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 , decitabine lenalidomide produce major responses in subgroups

prognosis

lymphoma

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

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

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?

Features that may require palliation

Poor prognosis in lymphoma (IPI )

Stage Age, LDH Performance status Extranodal sites – CNS

Comorbidities Chemoresponsiveness Types B/T, HD v NHL