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Received: 27 February 2022    Accepted: 17 May 2022

DOI: 10.1111/bjh.18286

REVIEW

Early integration of palliative care for patients with haematological

malignancies

Adir Shaulov1,2   | Ariel Aviv3   | Jacqueline Alcalde4,5   | Camilla Zimmermann4,5,6

1
Department of Haematology, Hadassah
Medical Center, Jerusalem, Israel Summary
2
Faculty of Medicine, Hebrew University of Early palliative care (EPC) significantly improves quality of life, symptoms, and sat-
Jerusalem, Israel
3
Department of Haematology, HaEmek isfaction with care for patients with advanced cancer. International organizations
Medical Center, Afula, Israel have recognized and promoted the role of palliative care as a distinct specialty, ad-
4
Department of Supportive Care, Princess
Margaret Cancer Centre, University Health vocating its involvement throughout the cancer trajectory. Although patients with
Network, Toronto, Ontario, Canada haematologic malignancies (HMs) have a comparable symptom burden to patients
5
Department of Medicine, University of
Toronto, Toronto, Ontario, Canada with solid tumours, they face multiple barriers to EPC integration. In this review, we
6
Department of Psychiatry, University of discuss these barriers, present updated evidence from clinical trials of EPC in HMs
Toronto, Toronto, Ontario, Canada
and propose models to support EPC integration into care for patients with HMs.
Correspondence
Adir Shaulov, Hadassah-­Hebrew University K EY WOR DS
Medical Center, Ein Kerem, Jerusalem, Israel.
cancer, delivery of health care, haematologic oncology, haematology, oncology, palliative care
Email: [email protected]

Funding information
University of Toronto; University Health
Network

I N T RODUC T ION psychosocial and spiritual.”8 This definition emphasizes a

holistic approach to prevent and manage clinical compli-
Palliative care (PC) originated from the modern hospice cations from the disease and its treatments, and is equally
movement in the 1960s, which aimed to provide end-­of-­life applicable to patients with solid tumours as well as haemato-
(EOL) care for patients with terminal illnesses. In the fol- logical malignancies (HMs).
lowing decades, PC evolved from providing exclusively EOL Unlike patients with solid tumours, for whom PC is in-
care to proactively supporting patients and caregivers fac- creasingly integrated early in the disease course, referrals to
ing a life-­threatening disease from the time of diagnosis.1 specialized PC for patients with HMs typically occur late in
Extensive evidence has shown that early palliative interven- the disease course.9–­11 However, the symptom burden expe-
tion significantly improves quality of life, symptoms and rienced in these diseases is similar to that of solid tumours,
satisfaction for patients with advanced cancer and may even and patients and their caregivers experience substantial
prolong survival.2,3 As a result, international cancer orga- psychosocial distress, as well as needs related to navigating
nizations have recognized and promoted the role of PC as a the complexities of the health care system and advance care
distinct specialty, advocating its involvement throughout the planning.12–­14 Thus, patients with HM could benefit greatly
cancer trajectory.4–­7 The World Health Organization now from the interdisciplinary approach offered by PC, which is
defines PC as “an approach that improves the quality of life of focused on improving symptoms, communication, shared
patients and their families facing the problem associated with decision making, psychosocial support, community care re-
life-­threatening illness, through the prevention and relief of sources, advance care planning, and caregiver support.15,16
suffering by means of early identification and impeccable as- Moreover, there is emerging evidence that supports early
sessment and treatment of pain and other problems, physical, specialized PC in HM.17–­19

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited and is not used for commercial purposes.
© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

14  |  wileyonlinelibrary.com/journal/bjh
 Br J Haematol. 2022;199:14–30.
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SHAULOV et al.    |
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In this narrative review, we discuss the PC needs of pa- HMs.6 Lastly, tertiary (specialized) PC is provided by PC
tients with HMs as well as barriers that prevent access to consultants, who may be consulted to provide specialized PC
specialized PC for this population. We also present recent for more complex situations such as refractory symptoms,
evidence from clinical trials demonstrating benefits from severe psychosocial distress or family conflict.
the early integration of PC for patients with HM and discuss
potential models for early integration.
PC syndromes in HMs

PC I N H M In contrast with HMs, the trajectory of disease in solid

tumours is relatively predictable, with metastasis gener-
Domains of PC and levels of care ally heralding incurability and a steady downward trajec-
tory (Figure  2). Previous publications have described the
PC is provided by interdisciplinary teams, which allows for characteristics of various types of HM with respect to PC
the delivery of multidimensional care.20,21 PC addresses needs.24,25 We find it helpful to divide HMs into three main
multiple domains, including not only physical symptoms but groups based on the trajectory of disease, setting of care and
psychosocial, spiritual and EOL care as well as ethical, struc- challenges to PC delivery. These are described briefly below
tural and cultural issues.22 A popular conceptual model clas- and are depicted in Figure 2B–­D.
sifies PC into primary, secondary and tertiary PC, according
to who delivers the care (Figure 1).23 Primary PC is delivered
in the community by primary care clinicians with general Aggressive HMs –­“The rollercoaster”
knowledge about PC. Accordingly, all clinicians should have
basic training in the principles and practice of PC (i.e., basic The first group of HM diseases includes aggressive life-­
pain relief, nausea, mood disorders). Secondary PC is pro- threatening diseases with a high risk of harm alongside a re-
vided in hospitals by specialists who have general knowledge alistic possibility for long-­term cure (Figure 2B). This group
about PC for their specialty. Thus, all oncologists, including includes acute leukaemias, aggressive lymphomas, stem cell
haemato-­oncologists, should have basic PC training, result- transplantation and acute graft-­vs.-­host disease. The razor-­
ing in a good understanding of symptom management, psy- edge character of these diseases make prognostication dif-
chosocial care and advance care planning for patients with ficult until late in the course of disease. Often cure may still

Terary All sengs - Specialized palliave care teams provide

experse for complex situaons

Hospitals and cancer centres – oncology and

Secondary haemato-oncology clinicians have fundamental
knowledge of palliave care

Community – primary care providers have basic

Primary knowledge of general palliave care

F I G U R E 1   A conceptual model of PC delivery based on setting and provider.[Adapted with permission from Kaasa S, Loge JH, Aapro M, Albreht
T, Anderson R, Bruera E, et al. Integration of oncology and palliative care: a Lancet Oncology Commission. Lancet Oncol. 2018 Nov;19 (11):e588–­
653]
 EARLY INTEGRATION OF PALLIATIVE CARE FOR PATIENTS WITH HAEMATOLOGICAL

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16       MALIGNANCIES

F I G U R E 2   (A) Solid malignancy trajectory.[Adapted with permission from Murray SA, Kendall M, Boyd K, Sheikh A. Illness trajectories and
Palliative Care. BMJ. 2005 Apr 28;330(7498):1007–­11. (B) Aggressive HM trajectory –­“The rollercoaster”: acute leukaemia, aggressive lymphoma, stem
cell transplantation, acute graft-­vs.-­host disease [developed by the authors]. (C) Indolent HM trajectory –­“The war of attrition”: indolent lymphoma,
multiple myeloma, chronic lymphocytic lymphoma [developed by the authors]. (D) Bone marrow failure “the transfusion tether”: myelodysplasia,
myelofibrosis [developed by the authors]

be a reasonable and achievable goal until days before death. as a compressive mass or nerve infiltration, pain is a prom-
For example, life threatening sepsis during nadir of salvage inent symptom due to multiple causes related to neutrope-
chemotherapy for refractory double-­hit diffuse large B-­cell nia and infection (e.g., perianal pain) as well as the result
lymphoma may be seen as a terminal event; however, within of treatment (e.g., mucositis, lumbar puncture).26 Patients
days, the reversal of neutropenia may find a patient not only with acute leukaemia report multiple burdensome physi-
recovering from sepsis but indeed in complete remission. cal and psychological symptoms, including lack of energy,
Conversely, the decline before death in such scenarios may drowsiness, dry mouth, pain, weight loss, difficulty sleep-
be very rapid which may be a barrier to transition to hospice ing, worrying, difficulty concentrating and feeling sad.
care in a timely manner. Uncertainty and psychological distress are also prominent
The rollercoaster nature of life in the context of these in patients with these diseases. For example, the acute onset
diseases also presents unique challenges, both physical and of leukaemia coupled with uncertainty regarding prognosis
psychological. While leukaemias do not commonly present as well as high rates of morbidity and mortality may have a
 13652141, 2022, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/bjh.18286 by Cochrane Mexico, Wiley Online Library on [03/07/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SHAULOV et al.    |
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FIGU R E 2  (Continued)

devastating psychological effect.13 Patients referred to spe- harbinger of relapse and increased blast count. It is there-
cialist care for acute leukaemia may undergo multiple blood fore unsurprising that 32% of acute leukaemia patients suffer
tests, bone marrow biopsy, PICC line insertion, whole body from syndromal or subsyndromal acute stress disorder over
imaging, cardiac imaging and fertility preservation followed the course of their disease14,28,29 and 17% suffer from depres-
by intensive inpatient continuous chemotherapy all within sive symptoms.30,31
days. Illness understanding in patients with acute leukaemia
is severely affected by the sheer volume of information they
are asked to process over a short period of time, further com- Indolent HMs –­“The war of attrition”
promising their ability to effectively participate in decision
making.27 The second group includes more indolent diseases such as
Weeks of neutropenia are often complicated by infection chronic lymphocytic leukaemia (CLL), indolent lymphomas
and mucositis, leading to mortality risk and increasing un- and many cases of multiple myeloma (Figure 2C). Although
certainty. Mood and hope vary with fluctuations of daily these diseases are incurable, prognosis may be prolonged,
blood counts, while increasing white blood cell counts may with episodes of decreased function due to multiple relapses
either bring the consolation of resolving neutropenia or the entailing multiple and ever-­expanding lines of treatment,
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18       MALIGNANCIES

alongside prolonged remissions with excellent function. As infections. These infections are both life threatening and de-
increasingly more novel drugs have been found to be ef- bilitating, with no ready solution in the form of transfusion.
fective in the treatment of these diseases, clinically signifi- Treating these infections effectively may entail both identifi-
cant remissions can be achieved even in advanced disease. cation of the cause of infection using cultures, imaging and
Prognostication may therefore be difficult. More impor- invasive procedures, as well as the use of broad-­spectrum
tantly, it is difficult to decide whether further treatment may antibiotics. Thus, the commonly used term, the ‘transfusion
be efficacious or detrimental to quality of life. Even advanced tether’, is but one of many tethers tying these patients to the
stage disease after multiple lines of therapy may have a sig- hospital bed.40 Despite the low risk of transfusion in a home
nificant response to seemingly over-­aggressive treatments. setting41,42 and many patients' wish to receive transfusions at
For example, over the past eight years, the FDA has approved home,43,44 transfusions are not readily available in home or
five new drugs for the treatment of CLL. Each new approval hospice settings, mostly due to cost and regulation. In this
opens the door for single drug treatment as well as combina- group, prognostication is again a challenge, as death is the
tions with other novel agents and with chemotherapy, creat- result of acute complications of cytopenias rather than dis-
ing an exponential amount of treatment possibilities. Stem ease progression.
cell transplantation, a severely debilitating and dangerous Although the three groups mentioned provide a useful
intervention, can attain long term remission and even cure framework to understand the complexities of these dis-
in a significant minority of patients and thus persists as a eases, the behaviour of various HMs is heterogeneous and
wild card treatment option in the eyes of both patients and does not adhere rigidly to this categorization. HMs can
clinicians. CAR-­T cell therapy is an additional treatment also transform from one group to another; for example, low
modality with activity in indolent as well as aggressive HMs grade lymphoma or CLL can transform to aggressive lym-
and data as to quality of life at the EOL with these treatments phoma and MDS can transform to acute leukaemia. Even
is only beginning to emerge.32 without overt morphological transformation, HMs can shift
Physical and psychological challenges are prominent in their behaviour in surprising ways whether due to treat-
this group as well. Multiple myeloma is notorious for causing ment or intrinsic biology, thus aggressive diseases may be-
bone pain and spontaneous fractures33 while lymphomas have as indolent ones and vice versa, further complicating
may behave as solid tumours compressing adjacent organs prognostication.
or nerves causing a variety of symptoms.34 Moreover, vari-
ous HMs, as well as the drugs used to treat them, may cause
debilitating peripheral neuropathy.35 C U R R E N T STAT E OF PC N E E DS
Indolent diseases, such as multiple myeloma, are also as- I N H MS
sociated with psychological distress for patients and fami-
lies, including anxiety and depression associated with fear Patients suffering from HMs have an overwhelming symp-
of inevitable relapse.36,37 Of particular interest are indolent, tom burden, with a burden of pain, dyspnea, nausea and
asymptomatic and premalignant conditions, which need anorexia similar to that of solid tumour malignancies.12,45
no treatment but may portend future symptomatic disease, However, the overall spectrum of symptoms and their
such as monoclonal gammopathy of unknown significance. causes may differ from solid tumours, and a deeper un-
The ‘watch and wait’ approach taken with these patients is in derstanding of these nuances (which may also be disease-­
itself a source of psychological distress and decreased quality related) may be beneficial for the care of these patients. For
of life similar to that of multiple myeloma.38,39 example, some symptoms, such as drowsiness, delirium,
fatigue and loss of appetite, may be more prevalent in HM
patients.12,45,46
Bone marrow failure –­the ‘transfusion tether’ Despite extensive physical and psychological symptoms,
referral to PC remains inadequate in HM patients,9–­11,47 and
The third group is characterized by bone marrow failure re- despite the high incidence of traumatic stress, only a small
sulting in cytopenias (Figure  2D). This group includes the proportion of these patients are referred to psychology or
myelodysplastic syndromes, myelofibrosis, aplastic anaemia psychiatry.48 In one study, 30% of haemato-­oncologists re-
and end-­stage HM with spent marrow due to infiltration by ported never referring to PC while all solid tumour oncolo-
disease or aplasia from treatment. Profound anaemia causes gists had previously referred to PC.49 Patients with HM have
dependence on blood transfusions for improvement of symp- consistently been shown to have decreased referral rates to
toms such as fatigue, dyspnea, chest pain and more. Severe PC services as well as hospice care compared to patients with
thrombocytopenia may result in haemorrhage ranging from solid tumours.9,50,51 Patients with HM are less likely to com-
mild but unsettling mucocutaneous bleeding, which may plete advance directives or DNR orders.11 In comparison
also exacerbate anaemia, to life-­threatening gastrointesti- with solid tumour malignancies, patients with HM have an
nal or intracranial bleeding. These may be partially avoided increased incidence of emergency room visits, hospital ad-
by regular platelet transfusions. Most importantly, severe missions and ICU admissions as well as use of chemother-
neutropenia in the setting of chronic progressive bone mar- apy and targeted therapy at the EOL.10,52–­55 In the opinion of
row failure results in recurrent bacterial and invasive fungal most haemato-­oncologists, EOL discussions occur too late,56
 13652141, 2022, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/bjh.18286 by Cochrane Mexico, Wiley Online Library on [03/07/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SHAULOV et al.    |
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and PC is often discussed only when death is imminent. BA R R I E R S TO T H E I N T E GR AT ION

Further, patients with HM are less likely to have a preexist- OF PC I N H M
ing opioid prescription upon admission to hospice indicat-
ing that symptom management may not be adequate.11 Difficulties with prognostication
Haemato-­oncologists are more likely than solid tumour
oncologists to equate PC with EOL care.31 Not only is the The relative predictability of prognosis in advanced solid
EOL more complex to predict in haemato-­oncology; even tumour malignancies, particularly when combined with
when death becomes a reasonable scenario, haematologists prognostic markers such as performance status,58 has made
often feel less comfortable discussing death and dying or re- it possible to routinely implement models of early PC, in-
ferring to hospice and are more likely to feel a sense of fail- cluding involving PC teams in the outpatient setting at the
ure when disease progresses.57 A previous review reported a diagnosis of advanced cancer. This steady decline is in con-
large difference in the number of published studies regard- trast to the highly unpredictable course of most HMs, as de-
ing palliative care in solid tumours compared with haema- scribed above.
tological malignancies.24 We performed a focused search A systematic review of the literature failed to find ef-
for the terms ‘palliate’, ‘palliation’ or ‘palliative’ in article fective prognostic factors in HM beyond imminently life-­
titles of the five leading journals in haemato-­oncology and threatening events such as multiorgan failure. 59 Factors
medical oncology, as ranked by journal citation reports, is associated with prognosis in solid tumour malignancies
illustrative of this point (Figure 3). Although the number of such as level of performance status, symptom burden, ca-
publications on PC in leading oncology journals has fluctu- chexia and comorbidities are not as strongly correlated
ated, the percentage of PC publications in these journals has with prognosis in HM patients.60 Nonetheless, consensus
consistently been more than ten-­fold higher than in leading may be found among haemato-­oncologists as to potential
haematology journals. signals for transition to the EOL phase of disease which

F I G U R E 3   Comparison of the percentage of publications including the keywords ‘palliative’, ‘palliate’ or ‘palliation’ in the article title, in five
leading haematology journals versus oncology journals over the years 2011–­2021.The leading journals in heamatology and medical oncology were
selected by the yearly impact factor designated by Journal Citation Reports. Haematology journals without an oncology focus were not included (i.e.,
Circulation, Circulation Research). Within each journal, a search for the terms ‘palliate’ ‘palliation’ or ‘palliative’ within the article title, including
meeting abstracts, was conducted using the Web of Science database. Oncology journals included were: CA: A Cancer Journal for Clinicians, Nature
Reviews Clinical Oncology, Nature Reviews Cancer, Journal of Clinical Oncology and Lancet Oncology. Haematology journals included were: Blood, Lancet
Haematology (from 2014), Journal of Haematology and Oncology, Blood Cancer Journal and Leukaemia. Mann–­W hitney–­Wilcoxon test was used to
compare the two groups (p < 0.0001)
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20       MALIGNANCIES

may indicate the need for integration of PC. These in- and blood products, and inpatient hospice rarely have the
clude refractory disease, CNS involvement, and worsening financial ability or philosophy of care to allow for such treat-
performance status.61 It is clear, however, that prognosti- ment.61,68 Many have advocated for policy change including
cation is not the sole barrier to quality EOL care in HM the American Society of Haematology69 and legislation has
patients. Further barriers will be described in the follow- recently been introduced to enable administration of blood
ing sections. products in the hospice setting in the US.70

Attitudinal barriers E V I DE NCE FOR BE N E F I T S OF PC

Haemato-­oncologists are more likely than oncologists to Evidence in patients with solid tumours
prescribe systemic therapy with moderate toxicity and no
survival benefit for patients with a severely impaired per- The benefits of early specialized PC were originally dem-
formance status and an expected survival of 1 month. 57 PC onstrated in randomized controlled trials conducted in pa-
providers may see this as resistance of haemato-­oncologists tients with advanced solid tumours (Table  1).71–­79 Most of
to the core tenets of PC while haemato-­oncologists may these trials were conducted in the outpatient setting, with
see the benefit in these therapies in the palliation of symp- interventions of either free-­standing71 or embedded72,73 PC
toms and complications. This attitude is best expressed in clinics. A study in Canada demonstrated that compared to
the saying by haemato-­oncologists that ‘the best palliation patients who received standard oncologic care alone, those
for HM is chemotherapy’. For example, the presence of se- referred early to a free-­standing specialized PC clinic experi-
vere neutropenia would pose a contraindication for chem- enced better quality of life, symptom control and satisfaction
otherapy in solid tumour patients, however in the setting with care.71 Other trials in the USA and Italy showed that
of bone marrow infiltrated by HM, chemotherapy may be early specialized PC provided by a PC physician or advanced
fully indicated. While some have described the approach practice nurse embedded in an outpatient cancer clinic im-
of haemato-­oncologists as technical rather than holistic,62 proved quality of life, mood, aggressiveness of EOL care, and
haemato-­oncologists may see this as evidence of the in- survival.72–­74
ability of other specialties to comprehend the intricacies
of HM. Similarly, accepted EOL quality measures such as
admission to hospice or time from last chemotherapy to Evidence in patients with HMs
death are often incompatible with the needs of HM pa-
tients and may not be appropriate in the haematology Although the symptom burden of patients with HMs is
setting.63,64 equivalent or higher than that for patients with solid
The differing characteristics of disease may also have a tumours, the evidence from randomized trials study-
varying effect on the doctor-­ patient relationship. While ing the effect of early PC interventions for HM patients
oncologists may see their patients every 3  months, the dy- is only currently emerging.17–­19,75,80,81 Unlike the trials
namic character of many HM necessitate visits at shorter in patients with solid tumours, most trials in patients
time intervals as well as treatment of multiple acute life-­ with HM have been conducted entirely or almost en-
threatening events, commonly with prolonged periods of tirely in the inpatient setting. Some early trials in the
inpatient treatment. It may be argued that this intense and emergency and outpatient setting that included mainly
intimate relationship may result in difficulty for both patient patients with solid tumours also included patients with
and haemato-­oncologist in referral to PC.24,49 Therefore, HMs, 75,82 but results are difficult to interpret given the
haemato-­oncologists may be more inclined to refer to PC if heterogeneity of the patient population and the very
they can maintain clinic visits with their patients.65 small percentage of patients with HMs (less than 5%)
in these trials.
More recently, PC interventions including exclusively pa-
Policy barriers and efforts to overcome them tients with HM have provided conclusive evidence for this
population in the inpatient setting (Table 2).17–­19,32,80,81 In a
Hospice criteria may exclude patients with HM by limiting randomized controlled trial in patients with HM who under-
access to therapies that may improve their quality of life.66 went allogeneic or autologous stem cell transplantation, pa-
PC services have not been traditionally formed to accom- tients assigned to the intervention arm received specialized
modate the more intensive needs of haematology patients PC within 72 hours of hospital admission and twice weekly
at EOL. Real world experience shows that even within a as inpatients.17 Anxiety was reduced and quality of life im-
PC unit the needs of HM patients far exceed that expected proved for patients in the intervention arm after 2 weeks of
including the use of broad spectrum antibiotics and blood enrolment. Moreover, both patients and caregivers had re-
products in most patients as well as parenteral nutrition duced levels of depression. The benefit in patient quality of
and intravascular devices in many.67 Home PC services are life was sustained after 3 months, and at 6 months, there was
not generally able to administer wide spectrum antibiotics a positive impact on post-­traumatic stress disorder (PTSD)
 TA BL E 1  Early palliative care clinical trials including only patients with advanced solid tumours
Intervention
SHAULOV et al.

Clinician providing Timing of early

Setting Study/year Cancer diagnosis palliative care palliative care Control group Favoured PC arm Did not differ
Outpatient: Zimmermann 2014 Advanced lung, GI, GU, Specialized PC Estimated survival Standard care with QOL, symptoms, patient Caregiver QOL
free-­standing McDonald 201771,95 Gyn, breast. physician and nurse 6–­24  months referral on request and caregiver
satisfaction with care
Maltoni 2016, Nonresectable PC physician Within 8 weeks of Standard care with QOL, aggressiveness at Survival, anxiety,
Maltoni 201674,96 or metastatic diagnosis and no prior referral on request the EOL depression
pancreatic cancer chemotherapy
Scarpi 201976 Locally advanced or PC physician Within 8 weeks of Standard care with QOL at 3 months,
metastatic gastric diagnosis and no prior referral on request survival,
cancer chemotherapy aggressiveness at
the EOL
Outpatient: Temel 2010, Metastatic NSCLC Palliative care physician Within 8–­12 weeks of Standard care with QOL, mood,
embedded Greer 2012 and APN diagnosis referral on request communication, less
Temel 201172,97,98 aggressive EOLc,
survival
Temel 2016 Incurable lung or non-­ Palliative care physician Within 8 weeks of Standard care with QOL, mood, decision Illness
El-­Jawahri 201773,99 colorectal GI cancer and APN diagnosis referral on request making, coping, understanding,
EOLc discussions, caregiver
caregiver distress anxiety, QOL at
week 12
Mixed inpatient Vanbutsele 2018 Incurable solid tumour Specialized PC nurse Prognosis ≤1 year, and Multidisciplinary QOL at 3 months Survival, anxiety,
and outpatient Vanbutsele 202077,100 with PC physician within 12 weeks care with nurse depression,
referral if required of diagnosis or specialist, symptoms,
progression psychologist and health care
dietitian. PC utilization,
referral on request aggressiveness at
the EOL
Franciosi 201978 NSCLC (no EGFR), Oncologist specialized Within 8 weeks of Standard care with QOL at 3 months,
pancreatic, gastric, in PC and PC nurse diagnosis referral on request health care
or biliary tract utilization
cancer
Mixed face to face Groenvold 201779 Stage IV lung, GI, Multidisciplinary team Timing not specified Standard care with Nausea/vomiting QOL, depression,
and telephone breast, other with (doctor, nurse, referral on request survival
at least one PC need psychologist, among
and 4 symptoms on others)
EORTC-­QLQ-­C30
Telehealth Bakitas 200975 Lung, GI,GU, breast APN with PC specialty Prognosis ≤1 year and Standard oncology and QOL, mood Symptom intensity,
training within 8 weeks of supportive care Resource use
diagnosis
|  

Abbreviations: EOLc, end-­of-­l ife care; EOL, end-­of-­l ife; QOL, quality of life; GI, gastrointestinal; GU, genitourinary; APN, advance practice nurse; NSCLC, non-­small cell lung cancer; PC, palliative care.
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 T A B L E 2   Early palliative care clinical trials including patients with haematological malignancies
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Intervention
22      

Clinician providing
Type according to multidisciplinary PC and Timing of early
setting Study/year Cancer diagnosis SC palliative care Comparison group Favours PC arm Did not differ
Trials that included only patients with haematologic malignancies
Inpatient El-­Jawahri 202118 High risk AML receiving PC physician, APN or Within 72 h of receiving Standard care with QOL, depression, Symptom burden,
intensive chemotherapy physician assistant chemotherapy referral upon anxiety, PTSD. hospice use and
request EOLc preference length of stay,
discussions, less hospitalization the
chemotherapy near last week of life
EOL
El-­Jawahri 2016, HM receiving allogenic or PC physician or APN Within 72 h of Standard care with -­At week 2: QOL, -­At week 2: fatigue,
El-­Jawahri autologous stem cell admission for referral upon depression, anxiety, caregiver QOL and
201717,80 transplantation transplantation request symptom burden, anxiety
caregiver depression -­At month 3: anxiety,
-­At month 3: QOL, fatigue, symptom
depression burden
-­At month 6: depression, -­At month 6: QOL,
PTSD anxiety
Inpatient, Rodin 2020 Newly diagnosed or recently -­Specialized PC physician -­Triggered by ESAS-­A L Standard care with -­Pain intensity and Symptom severity,
outpatient and (phase II)19 relapsed AML/ ALL and nurse symptoms ≥4 or referral upon pain interference at symptom related
telephone within one month of and upon request request 12 weeks with daily distress, depressive
admission -­Therapist trained in EASE-­ −12 EASE-­psy sessions activities symptoms, QOL,
Psy plus psychiatrist/ over 8 weeks -­Traumatic stress satisfaction with
psychologist at request symptoms at weeks 4 care
and 12
Outpatient Loggers 201681 HM planned for allogenic APN or RN trained in PC During the 2-­week N/A -­69% provided consent No control arm
or autologous stem cell evaluation period Acceptability of to participate in EPC
transplantation immediately EPC consult.
before HCT Comfort with EPC was
high (82%)
Trials that included patients with solid tumours and haematologic malignancies
ED Grudzen 2016 Advanced solid tumour; relapsed Palliative care physician, Same or following day Standard ED care QOL -­Survival, ICU
(phase II)82 stage III/IV lymphoma or nurse practitioner, social of ED admission admission, hospice
myeloma, non-­transplant worker and chaplain discharge
or chemotherapy candidate
(5.1%)
Mixed in person Bakitas 2015101 Advanced solid or HM (5%), PC board certified physician Estimated survival Delayed PC Survival QOL, health care
(outpatient) within 1 to 2 months of (in person), and an APN 6–­24  months intervention utilization,
and telephone diagnosis, prognosis 6 to (telephone) after 3 months chemotherapy in
24 months the last 14 days,
home death

Abbreviations: QOL, quality of life; EOLc, end-­of-­l ife care; PTSD, posttraumatic stress disorder; PC, palliative care; ED, emergency department; ICU, intensive care unit; EPC, early palliative care; APN, advance practice nurse; RN,
registered nurse; N/A, not applicable; AML/ALL, acute myeloid leukaemia and acute lymphocytic leukaemia; HM, haematologic malignancy.
MALIGNANCIES
EARLY INTEGRATION OF PALLIATIVE CARE FOR PATIENTS WITH HAEMATOLOGICAL

13652141, 2022, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/bjh.18286 by Cochrane Mexico, Wiley Online Library on [03/07/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
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SHAULOV et al.    |
   23

and depression for patients receiving the intervention.80 It is palliative care and roles of each level of provider in deliver-
noteworthy that the PC intervention in this study included ing this care are outlined in Table  4, with the recognition
mostly rapport building, symptom management and assis- that the boundaries between providers' roles are ill-­defined
tance with coping while illness understanding, decision-­ and are based on patient need as well as provider skill. As
making and advance care planning received significantly most HM patients are treated in cancer centres, most PC for
less focus. HM patients is secondary, delivered by haemato-­oncology
In Canada, a phase II trial of a combined psychoso- teams. Haemato-­oncologists should therefore have better
cial and PC intervention (EASE –­Emotion And Symptom PC training; specifically, HM residents should complete at
Engagement) delivered mainly in the inpatient setting in least a one-­month rotation in PC, including information
patients with newly diagnosed or relapsed acute leukaemia on symptom management, communication skills, cultural
demonstrated feasibility of this model as well as improved competence, multidisciplinary care, and ensuring timely re-
pain control and decreased traumatic stress symptoms.19 ferrals to PC specialists.6 Haemato-­oncology team meetings
The positive impact of early specialized PC for patients with with a palliative focus have been shown to foster a culture
acute myeloid leukaemia was affirmed by a randomized con- change allowing for more goal-­concordant care and should
trolled trial demonstrating better quality of life and reduced be implemented by haemato-­ oncology teams.85 Tertiary
levels of anxiety, depression and PTSD in high-­risk acute (specialized) PC provided by PC consultants should be avail-
myeloid leukaemia patients randomized to early inpatient able to provide specialized PC for more complex situations
PC compared to usual care.18 such as refractory symptoms, severe psychosocial distress,
Further new intervention studies are underway, includ- or family conflict. The referral process to tertiary PC will be
ing a multi-­centre randomized phase III trial of EASE for discussed below.
patients with newly-­diagnosed acute leukaemia and several
other trials of early PC in patients with leukaemia, multiple
myeloma, lymphoma, myelodysplastic syndrome and mixed Where care is delivered: outpatient, inpatient,
haematologic malignancies (Table  3) (clini​caltr​ials.gov). home and virtual models
These include a trial of funding to receive palliative blood
transfusions while enrolled on hospice for patients with As mentioned above, most models of early PC with
HMs at the EOL83 and a trial of outpatient PC for patients proven benefit for patients with advanced solid tumours
with multiple myeloma.84 involve routine involvement of specialized PC deliv-
ered in the outpatient setting, either through freestand-
ing PC clinics or in an embedded within the oncology
MODE L S FOR PC I N H A E M ATOL OGY clinic (Table  1). The principle for these clinics is that
the PC team provides support with symptom control,
PC is provided by interdisciplinary teams, which allows coping with illness, decision-­m aking and future plan-
delivery of multidimensional care addressing the com- ning, in a model that emphasizes care that is f lexible,
plex supportive care needs of people facing life threaten- attentive, patient-­led and family-­c entred. 86 This outpa-
ing diseases. 20,21 However, there is no single model of PC tient model works well for patients with solid tumours,
that is appropriate for all settings. Instead, the model of who have an illness course that is relatively predictable,
PC provision will depend on national health policies, ac- and for whom referral ideally occurs at the diagnosis of
cess to training and education of specialized PC providers, advanced illness. This model may be of benefit for pa-
availability of resources, societal and health professional tients with indolent HMs or for relatively fit patients
attitudes towards PC, and the setting where PC is deliv- with bone marrow failure. For these groups of patients,
ered. As well, models of care will depend on the disease longer term outpatient involvement of PC may improve
trajectory, such that models developed for patients with symptom control, provide psychosocial support, and as-
solid tumours may not be appropriate for patients with sist with advance care planning. However, to date, there
HMs. Broadly, models of early PC delivery be categorized have been no randomized controlled trials of such an
according to who delivers PC (i.e., primary, secondary and outpatient model for HMs.
tertiary PC, discussed above); where PC is delivered; and For patients with aggressive HMs, inpatient treatment of
how it is determined who receives PC (i.e., the referral their disease is necessary, and a model of concurrent early
process). involvement of PC in the inpatient setting is appropriate.
As mentioned above, there have been several trials that
have demonstrated the feasibility and benefit of involv-
Who delivers care: primary, secondary and ing inpatient PC teams upon admission for treatment of
tertiary PC acute leukaemia or stem cell transplantation, with benefits
demonstrated long after discharge.17,18,80 Providing further
Family physicians, haemato-­oncologists and palliative care ad hoc telephone PC or psychosocial support after discharge
physicians all have important roles in providing primary, may also help to ease the often-­challenging transition from
secondary and tertiary care, respectively. The domains of hospital to home.31
 T A B L E 3   Ongoing early palliative care clinical trials in patients with haematologic malignanciesb
|

[Principal Investigator]; Intervention

24      

status;
phase; Country; Patients; Clinician providing
setting year registered Cancer diagnosis Comparison group PC Timing of early PC Outcomesa
[El-­Jawahri] NCT02975869 >60 years old: Standard leukaemia care Collaborative PC and Newly diagnosed, QOL, psychological distress, symptom
Active, not recruiting USA -­High risk AML leukaemia specialist relapsed, primary burden, PTSD, EOL discussion
N/A 2016 refractory preference, chemotherapy within
inpatient 30 days of death, admission within
7 days of death, hospice utilization
[El Chaer] NCT04482894 ≥18 years old: Standard care with referral PC specialist Newly diagnosed, Place of death, survival, duration,
Recruiting USA -­A ML, ALL, MDS, CMML upon request relapsed, primary admissions duration/type/
Phase II; 2020 refractory frequency, ER visits, hospice
Inpatient and outpatient service use, transfusions, QOL,
code status change, GOC
discussions
[Samala] NCT04248244 ≥18 years old: No comparison group Specialized physician, Within 8 weeks of QOL, anxiety, depression, health care
Recruiting USA -­M M APN, care diagnosis utilization
Phase II 2020 coordinators
Outpatient
[Tanzi]102 NCT03743480 ≥18 years old: Standard care with referral Integrated PC team Soon after decision of Adherence to palliative care program,
Unknown Italy -­Incurable haematological upon request last active treatment QOL, anxiety, depression, PPS.
Phase II 2020 tumour and last line of
Outpatient therapy
[Rodin & Zimmermann] NCT04224974 ≥18 years old: Standard care with referral -­Supportive Within 2 weeks of Traumatic stress symptoms, physical
Recruiting Canada Newly diagnosed AML and upon request psychotherapy: admission for symptom severity, QOL, ASD,
Inpatient & outpatient & 2020 ALL trained therapist treatment of acute depression, satisfaction with care,
telephone -­Symptom triggered leukaemia pain, survival, quality adjusted life
referral: PC years
specialists
[Booker] NCT05190653 ≥18 years old: Standard care with referral PC nurse practitioner Scheduled for SCT QOL, symptom burden, patient
Not yet recruiting Canada -­Haematologic malignancy upon request or physician and caregiver prognostic
N/A 2022 -­Family caregiver understanding, caregiver QOL
Virtually (phone or
zoom)
[Scarfò]103 NCT04370457 ≥ years old: Standard care with PC if MyPal ePRO: Scheduled to receive QOL
Recruiting Italy -­CLL/SLL or MDS needed PROs at baseline, any line of therapy
Open label 2020 -­Users of internet connected monthly times 6, for CLL/SLL or
Virtually (App) device and at 12 months MDS
[Guastella] NCT03800095 ≥70 years old: Standard care with referral Palliative and At diagnosis in AML, QOL, symptoms, survival, satisfaction
Recruiting France -­A ML, MDS, diffuse large B upon request supportive care MDS; after 3rd with care, cost effectiveness
Phase III 2019 cell lymphoma team line therapy in
Not specified lymphoma
MALIGNANCIES
EARLY INTEGRATION OF PALLIATIVE CARE FOR PATIENTS WITH HAEMATOLOGICAL

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SHAULOV et al.    |
   25

Home-­based PC is usually provided later in the course of

QOL, symptom intensity, depression,

advanced disease, when it becomes difficult for patients to

questionnaire; N/A, not applicable; ESAS, Edmonton System assessment system; GDS, Geriatric Depression Scale; AML, acute myeloid leukaemia; ALL, acute lymphocytic leukaemia; MQOL-­E , McGill Quality of Life Questionnaire;
anxiety, quality of EOL, survival

MDS, myelodysplastic syndrome; MM, multiple myeloma; SCT, stem cell transplantation; CLL/SLL, chronic lymphocytic leukaemia and small lymphocytic leukaemia; ASD, acute stress disorder; e-­PRO, electronic patient reported
travel to and from the hospital, and when the focus is exclu-

Abbreviations: QOL, quality of life; PPS, palliative performance scale; EOL, end of life; GOC, goals of care; PTSD, post-­t raumatic stress disorder; ER, emergency room; PC, palliative care; FACT, functional assessment of cancer
sively on EOL care. The further expansion of home-­based
PC earlier into the disease trajectory, particularly in patients
with bone marrow failure, would be much enabled by the
capacity to provide transfusions of blood products in the
home setting. This has been implemented in some countries
with negligible risk.41,42,87 However, in most countries home
Outcomesa

blood transfusions are impossible due to regulatory and fi-

nancial constraints, presenting a substantial barrier for early
PC in the home setting for HM patients.88
A novel mode for PC delivery is telemedicine, in which
Timing of early PC

PC is delivered via telephone or video conference to the

Within 8 weeks of

patient.89 Telemedicine in PC has become increasingly

diagnosis

common during the COVID-­19 pandemic, due to the re-

quirement for social distancing and reluctance of many
patients to come to the hospital.90,91 This model of care is
particularly promising for patients who are receiving care in
outpatient or home settings, to avoid the necessity for travel
palliative care team

on the part of the patient or clinician and provide more ef-

Clinician providing

Multidisciplinary

ficient care. Randomized controlled trials of virtual PC are

needed to determine its effectiveness compared to in-­person
Intervention

models.
PC

How specialized PC referral is determined:

Standard care with referral

clinician-­initiated and automated systems for

aggressive HMs
Comparison group

upon request

Referral to specialized PC can either be based on judge-

ment of the referring clinician or automated in some way.
Referral initiated on clinical judgement by oncologists
or haemato-­ oncologists is currently the most popular
method and remains synonymous with usual care, both
in practice and for clinical trials. 20,92 Oncologists are in-
ALL, transplant ineligible

creasingly making early referrals to PC services at their

-­First relapse on AML or

centres for patients with solid tumours, thanks to the solid

evidence favouring multidisciplinary care and the policies
Cancer diagnosis

and advocacy supporting this approach.93 On the other

≥18 years old:

hand, haemato-­oncologists face several barriers to effec-

Patients;

tively integrating PC into their practice under this model,

as described above.64,92 Therefore, despite the high symp-
tom burden and needs, clinician-­initiated referral results
in most patients diagnosed with HMs being referred very
year registered
NCT02631811

All trials listed are registered in clini​caltr​ials.gov.

late or never to PC. 26,48

Country;

Interventions in most existing randomized controlled

France

trials both in solid tumours and for HMs have consisted of

outcomes; APN, advance practice nurse.
2021

routine referral for all patients shortly after the diagnosis of

Primary outcomes appear in bold.

advanced disease (in solid tumours),72 or shortly after ad-

[Principal Investigator];
T A B L E 3   Continued

mission for autologous or allogeneic haematopoietic stem

cell transplantation or for acute leukaemia treatment.17–­19
Automatic referral to PC upon admission to hospital for
Not specified

treatment led to improved outcomes in two randomized

Completed

controlled trials: one in HMs requiring stem cell trans-

Phase II
[Bénite]
setting
status;
phase;

plantation and the other in acute leukaemia (Table 2).17,18,80

Compared to usual care, patients receiving automatically
b
a
 EARLY INTEGRATION OF PALLIATIVE CARE FOR PATIENTS WITH HAEMATOLOGICAL

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|
26       MALIGNANCIES

T A B L E 4   Domains and providers of palliative care for patients with haematological malignancies

Primary PC –­Primary care Secondary PC –­Haemato-­oncology care Tertiary PC –­Specialty PC

Domain providers teams teams
Domain 1: Structure and • Understanding the value of PC • Basic PC assessment in HM • In-­depth PC assessment and
processes of care • Familiarity with the core • Address common sources of suffering consultation
principles of PC in HM • PC education for other
providers
Domain 2: Physical aspects of • Assessment of symptom • Identify and treat common symptoms • Consult for complex and
care burden, functional status, and associated with HM (nausea and intractable symptoms
quality of life vomiting, cancer pain, fatigue, • Advanced pain and symptom
• Developing a palliative anorexia and cachexia, constipation, management (i.e methadone,
treatment plan consistent with dyspnea, delirium etc.) lidocaine, interventions etc.)
patient and family needs and • Starting opioid treatment, titration,
preferences rotation and managing side effects.
Domain 3: Psychological and • Screen, assess and manage for • Understanding of psychological issues • Expertise in management of
psychiatric aspects of care psychological concerns facing patients with HM (anxiety, refractory symptoms
depression, etc.) • Care coordination for
• Addressing grief and loss of patients patients with extreme mental
and families distress, cognitive and/or
communication disorders
Domain 4: Social aspects of care • Perform and integrate social • Assessment in the context of HM • Address complex family
assessments needs (prolonged admissions, dynamics and intense social
• Identify patient strengths, prognostic uncertainty etc.) needs
availability of caregiving and • Plan care management and delivery
support, access to food housing • Identify and address caregiver burnout
and transportation etc.
Domain 5: Spiritual, religious, • Spiritual screening and • Utilize resources available within • Address complex spiritual
and existential aspects of assessment of spiritual distress HM setting, patient and family, needs
care community, and care setting • Spiritual care specialist care
Domain 6: Cultural aspects of • Knowledge of how culture • Expertise in taking into account • PC specialists and cultural
care influences patient and family and navigating cultural aspects in representatives aid in
decision making and their the context of severe haematological navigating cultural nuances
approach to illness, dying and illness
bereavement.
Domain 7: Care of the patient • Timely hospice referrals • Timely hospice referrals in the setting • Managing difficult EOL
nearing the EOL • Skills in conversations with of HM and prognostic uncertainty conversations
patients and families about • Skills in difficult conversations about • Managing difficult EOL
dying prognosis in the setting of HM and symptoms including
• Skills in managing EOL prognostic uncertainty judicious use of palliative
symptoms • Skills in managing EOL symptoms in sedation
HM
Domain 8: Ethical and legal • Understanding basic ethical • Advance care planning for patients • Specialist PC, ethicists and
aspects of care principles applicable at the EOL with HM ethics committees provide
• Basic advance care planning • Managing common scenarios causing high quality care aligned
ethical and legal conflicts with patient goals

Note: Adapted from Clinical Practice Guidelines for Quality Palliative Care, 4th edition 2018, National Coalition for Hospice and Palliative Care.22
Abbreviations: PC, palliative care; HM, haematological malignancies, EOL, End of life.

specialized PC experienced better quality of life and reduced Symptom screening with Targeted Early PC (STEP) demon-
psychological symptoms, including depression, anxiety, and strated the feasibility of such a model in patients with solid
post-­traumatic stress disorder. Therefore, automatic refer- malignancies.94 Here, patients attending outpatient oncol-
ral upon admission for the group of HMs that includes ag- ogy clinics were screened at each visit for symptoms using
gressive life-­threatening diseases with a high risk of harm the Edmonton Symptom Assessment System; patients with
(alongside a realistic possibility for long-­term cure) would be moderate physical (e.g., pain, dyspnea, nausea) or psycho-
ideal in settings with sufficient PC resources. logical (e.g., depression, anxiety) symptoms, or with severe
An alternate model to automatic referral entails referral constitutional symptoms (e.g., fatigue, appetite), received a
to specialized PC according to specific triggers (e.g., mod- phone call from a PC nurse who discussed their symptoms
erate symptoms, severe psychological distress). As yet, there and offered a formal PC appointment.
is no conclusive evidence for this model in solid tumours or Lastly, the EASE intervention described above in-
HMs. However, a phase II trial of an intervention entitled volved both automated and triggered components.19 In this
 13652141, 2022, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/bjh.18286 by Cochrane Mexico, Wiley Online Library on [03/07/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SHAULOV et al.    |
   27

intervention, patients with newly diagnosed or relapsed integration of PC for HMs with indolent disease and with
acute leukaemia who were randomized to the EASE inter- bone marrow failure.
vention received an automated referral to a psychosocial In addition to further research on models of tertiary
clinician who provided a tailored psychotherapy delivered PC, secondary PC services by haemato-­oncologists need
over 8 weeks, and weekly physical symptom screening over to be improved, both through better training for haemato-­
8 weeks, with a triggered referral to an inpatient PC team oncologists in PC and by expansion of HM research into
if symptoms were scored above a certain threshold. The the PC needs of this population. A PC rotation incorpo-
intervention was found to be feasible, with promising re- rated into residency training for haemato-­oncological on-
sults for several patient-­ reported outcomes: significant cologists would provide insight into the possible benefits
treatment-­group differences favouring EASE were observed of integrating PC earlier in the disease trajectory and pro-
in traumatic stress symptoms at 4 and 12 weeks, and in pain vide basic education in symptom management, commu-
intensity and interference at 12 weeks. nication skills and advance care planning. Importantly,
progress in the integration of PC for patients with HM
will necessitate a mutual understanding and collaboration
Possible models for patients with bone marrow between haemato-­oncologists and PC providers across all
failure and indolent HMs levels of care.
As the understanding of the biology of HM and targeted
To date, all RCTs have included patient with aggressive dis- treatments continue to progress, HM patients will continue
ease: either patients with acute leukaemia or those undergo- to face challenges in maintaining quality of life and in mak-
ing stem cell transplantation. The trajectory as well as the ing treatment decisions in the context of prognostic uncer-
aggressive, high-­risk, high-­gain nature of these diseases are tainty. With its interdisciplinary and holistic approach, PC
mirrored in the models of triggered inpatient PC that have has much to offer these patients. Increased understanding
been proven to be of benefit. For other disease trajectories, of PC by haemato-­oncologists as well as improved models
different models may be needed. In indolent relapsing–­ for integration of tertiary PC will open the door to improved
remitting diseases, there are often challenges of illness un- quality of care for this underserved population.
derstanding and advance care planning due to prognostic
uncertainty, and symptoms such as pain and fatigue may AU T HOR C ON T R I BU T ION S
also be prominent. For this patient population, the early out- Conception and design: AS, AA, CZ. Study implementation,
patient integration of specialized PC, with its expertise in acquisition and/or assembly of data: All authors. Analysis
symptom management as well as complex decision making and interpretation of data: All authors. Manuscript writing:
may be most beneficial. This could occur using preapproved All authors. Final approval of manuscript to be published:
triggers of symptom severity and may also result from im- All authors.
proved referrals due to increased awareness of PC among
haemato-­oncologists. As well, bone marrow failure diseases AC K N OW L E D G E M E N T S
may demand a rethinking and adaptation of home-­based PC CZ holds the Harold and Shirley Lederman Chair in Palliative
and hospice care. The low risk of home transfusion may be Care and Psychosocial Oncology, a joint chair at the Princess
vastly outweighed by cultural, bureaucratic, and financial Margaret Cancer Centre, University Health Network, and
barriers that need to be removed in order to allow for proper University of Toronto. The funders of the study had no role
care at home. For many of these patients, home care may not in study design, data collection, data analysis, data interpre-
be feasible as the need for complex inpatient interventions tation or writing of the report.
may be needed to achieve goals of care. In these cases, hos-
pice or PC units may need to adapt to the patients’ complex C ON F L IC T OF I N T E R E S T
needs. The authors report no conflict of interests.

C OM PL I A N C E W I T H E T H IC A L S TA N DA R D S
C ONC LUSIONS A N D Not applicable (review paper).
F U T U R E DI R E C T IONS
PR IOR PR E S E N TAT ION
As evidence of the benefits of PC in HM continues to evolve, None.
our understanding of the unique needs of this population
continues to grow. Existing models of early tertiary PC for ORC I D
HM are based on specialist PC intervention triggered by ad- Adir Shaulov  https://orcid.org/0000-0002-9620-781X
mission for inpatient treatment for aggressive HMs, and have Ariel Aviv  https://orcid.org/0000-0002-6024-1100
demonstrated benefit in randomized controlled trials.17–­19 Jacqueline Alcalde  https://orcid.
Future trials of outpatient PC for patients with multiple org/0000-0002-7410-8087
myeloma and of enabling blood transfusions in hospice set- Camilla Zimmermann  https://orcid.
tings are underway and will pave the way to enabling better org/0000-0003-4889-0244
 EARLY INTEGRATION OF PALLIATIVE CARE FOR PATIENTS WITH HAEMATOLOGICAL

13652141, 2022, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/bjh.18286 by Cochrane Mexico, Wiley Online Library on [03/07/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
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28       MALIGNANCIES

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