lisa newton bradford teaching hospitals nhs foundation trust
TRANSCRIPT
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
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expensive, invasive, unnatural, artificial, emotionally taxing for the patient, high technology and rapidly fatal when withdrawn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
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(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
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?