14.12 Palliative Care Issues in Populations with Hematological Malignancies (HM)

Question 1

List 4 ways in which patients with hematological malignancies receive more aggressive EOL care (vs patients with solid tumours)

Answer 1

1. More use of disease modifying treatment at EOL
2. More ICU utilization in last month
3. Higher likelihood of dying in hospital
4. Failure to use hospice at all or late enrollment (<72 hrs before death)

Question 2

List 2 unique features of hematologic malignancies (vs solid tumours)

Answer 2

1. Unpredictable illness course and outcomes (including possiblity of cure)*
2. Need for intensive treatments for good outcome (risk of early death from toxicity)
3. Non-traditional staging system*
4. In some cases, chronic indolent course punctuated by need for active therapy or continuous oral therapy indefinitely

Question 3

List 3 major categories of hematological malignancies (HM)

Answer 3

1. Leukemias
2. Lymphomas
3. Multiple myeloma

Question 4

How does the underlying cell of origin dictate the manifestations of leukemias and lymphomas

Answer 4

1. Leukemias - cancers of bone marrow cells so involve blood and marrow
   *cancer of bone marrow
   *increase in WBCs
   *ALL, CLL, AML, CML
   *kids

—-

2. Lymphomas - cancers of lymph glands/immune system, so involve lymph nodes and lymphatic organs (i.e. spleen)
   *cancer of lymph system
   *increase in leukocytes
   *Hodgkin and non Hodkin
   *older

Question 5

List 2 major categories of acute leukemias. Which is more common?

Answer 5

1. Acute myeloid leukemia (more common)
2. Acute lymphoid leukemia

Question 6

Acute leukemias are rapid in onset.

What does their rapidly growing nature mean for symptoms, mortality, and response to treatment?

Answer 6

1. Cause significant symptoms and mortality quickly if not treated
2. Rapidly growing = more responsive to chemo (vs. solid tumours) so some can be cured
3. However, require high-dose chemo (vs. solid tumours) +/- SCT so increased hospitalization, risk mortality during treatment
4. Due to high dose therapies, higher burden of:
   - symptoms
   - impaired QOL
   - psychological distress
   - anxiety/depression
   So ++ palliative/supportive care needs!

Question 7

List 2 types of chronic leukemias

How does their onset, symptom burden, and prognosis differ from acute leukemias

Answer 7

1. Chronic myeloid leukemia (CML)
   Chronic lymphoid leukemia (CLL)
2. Insidious onset
   Relatively asymptomatic
   Prognosis measure in years

FS: prognosis

CML (with TKI) > CLL
ALL (may be curable) > AML

Question 8

1. What is the usual treatment course for CML?
2. Expected prognosis in this case?
3. List 2 reasons for shortened survival with CML?
4. List 1 reason for palliative care needs with CML.

Answer 8

1. Usually oral targeted therapy with a TKI (i.e. imatinib)
2. Average expected survival now identical to age-matched population controls
3. i) treatment-refractory CML with resistance mutations
   ii) CML transforms to AML
4. Even if no longer life limiting, may have symptom burden from decades of continuous oral therapy + financial burden

Question 9

1. What is the typical demographic, trajectory, and median survival for CLL?
2. Because it is slow growing, CLL may not need treatment initially, if at all (active surveillance only). List 3 scenarios in which treatment may be started.
3. Name 1 common complication patients with CLL face
4. If CLL presents/becomes more aggressive, what is the prognosis?

Answer 9

1. Older age onset, slow-growing, median survival 10 years
2. End-organ impairment, significant cytopenias, symptoms
3. Infectious complications (sometimes life threatening, unpredictable, but often readily treatable).
4. Once aggressive, can have a 1-2 year terminal phase with risk of “Richter’s transformation” to more aggressive lymphoma with poor prognosis

Question 10

Heme-oncologists rely on info about cytogenetics, molecular abnormalities, genetic mutations to prognositicate leukemias.

PC clinicians should be familiar with some - list 1 positive and 1 negative prognostic factor each for CLL and AML.*

Answer 10

Oxford says we should know this - but memorize at your own discretion

1. CLL:

17p deletion - aggressive

Isolated immunoglobulin heavy chain mutation - favourable prognosis

2. AML:
   Poor prognosis mutations:
   i) complex chromosomal karyotype
   ii) monosomy 7
   iii) FLT3-ITD

Favourable prognosis:
i) Xsome 8 and 21 translocation t(8;21)
ii) inversion 16 abnormality
iii) Acute promyelocytic leukemia has t(15;17) translocation and >90% cure rate (often not even cytotoxic chemo needed)

Question 11

List the 2 main classifications of lymphomas

Which is more common?

Answer 11

1. Hodgkin lymphomas
2. Non-Hodgkin lymphomas (more common, over 40 subtypes)

Question 12

What is the general prognosis for Hodkin Lymphomas?

Answer 12

Typically good prognosis, esp in younger patients

About 90% 5-year survival rate, expectation of cure with multiagent chemotherapy

Question 13

What are the 2 main subtypes of NHL?

What is the general treatment response and prognosis of each?

List 1 prototypical example of each

Answer 13

1. Indolent NHLs
   - generally incurable but median survival decade or more
   - follicular lymphoma
2. Aggressive NHLs
   - very responsive to chemo, sometimes curable
   - diffuse large B cell lymphoma

Question 14

1. What is the most common type of NHL?
2. What is the expected cure rate?
3. What is the treatment/prognosis once a patient has relapse of this lymphoma?
4. Which subtype may have a worse prognosis?*

Answer 14

1. Diffuse large B cell lymphoma or “large cell lymphoma”
2. 40-50% with multiagent outpatient chemo
3. May still be curable with more intensive Rx, including SCT, but some patients pass from multiple relapses or aggressive primary progressive disease
4. “Double hit lymphomas” - genetic abnormality confers resistance to chemo, higher risk of relapse

Question 15

1. Name of the the most common indolent NHLs
2. What is the general course of disease when undergoing treatment
3. What is the general prognosis with this lymphoma?

Answer 15

1. Follicular lymphoma
2. -Intially may be observed
   -Once treated, periods of remission punctuated by disease progression
   -Each relapse treated with another line of therapy
   -Each remission shorter than the last, but remission can last years

3.Most patients die of something else, given long median survival, unless:
- enter terminal stage after multiple relapses
- transformation to large cell lymphoma = poor prognosis

Question 16

1. Name 1 emerging targeted therapy for lymphomas
2. What are its estimated response rates
3. How does this complicate prognostication in patients with lymphoma

Answer 16

1. (CAR) T-cell immunotherapy
   (chimeric antigen receptor)
2. Response rates of 50-80% with durable response in >40-50% of patients
3. Growing uncertainty about patient’s prognoses in many cases of lymphoma:

Novel treatments may provide good outcomes in historically poor prognosis aggressive/indolent lymphomas BUT hard to predict which patients will benefit

Question 17

1. Which cell type does multiple myeloma originate from?
2. What is the pathophysiology of MM?
3. Standard 3 drug treatment regimens for MM confer near 100% response rates. List 3 significant side effects

Answer 17

1. Plasma cell, mature type of B cell
2. The accumulation of monoclonal antibodies (proteins) by plasma cells causes many signs/symptoms of MM
3. Progressive peripheral neuropathy* <- chemo
   Cytopenias
   Steroid-associated side effects* <- steroid
   Viral infections* <- immunomodulatory
   Thrombosis

Question 18

1. What is the median overall survival in “standard risk” myeloma (i.e. without high risk abnormalities)
2. Which system is commonly used to stage MM?
3. List the 3 markers it employs to stratify patients into 3 prognostic groups*
4. What is the median overall survival of ISS stage 1 vs stage 3*
5. What is another known prognostic marker in other risk stratification schemas for MM*

Answer 18

1. 5-10 years
2. ISS: “International staging system”
3. serum albumin
   beta-2-microglobulin
   serum lactate dehydrogenase
4. ISS stage 3 - about 43 months
   ISS stage 1 - has not been reached per published estimates
5. 17p abnormalities - worse prognosis

Question 19

1. Which 3 broad therapies might the management plan for MM involve?
2. Name 1 promising (but not yet approved) therapy for MM

Answer 19

1. Initially immunomodulatory agents (eg thalidomide) with steroids
2. Optimally, autologous stem cell transplantation followed by maintenence therapy to prolong remission
3. Chemotherapy

*Not unusual for patients to receive 5 or more different lines of therapy +/- 1 or 2 ASCT, and multiple 2-3 drug regimens over several years = cumulative toxicity = role for PC specialists to help with QOL

2. CAR T-cell immunotherapy

Question 20

List 4 unmet palliative care needs in patients with hematological malignancies

Answer 20

1. symptom burden
2. psychological distress
3. QOL impairment
4. Poor illness understanding
5. inadequate decision support
6. unmet survivorship care needs
7. poor quality end of life care

Question 21

1. How does physical symptom burden compare in patients with HM vs solid tumours
2. What system level issue complicates symptom management in HM (vs solid tumours)

Answer 21

1. Comparable symptom burden and severity
2. Late referral to PC (i.e. median time from referral to death only 13 days)

Question 22

1. Population level studies show that patients with leukemia experience which symptom at higher level (compared to other cancers)?
2. What immediate effect can this have on newly diagnosed patients with leukemia?

Answer 22

1. Psychological distress
2. Impair patient’s ability to receive and understand prognostic information, and to make urgent decisions about treatment (as is often required with acute leukemia)

Question 23

List 3 psychiatric conditions prevalent among patients undergoing hematopoietic stem cell transplantation

Answer 23

1. Anxiety
2. Depression
3. Post-traumatic stress

Question 24

1. In what way does evidence suggest that patients with HM harbour significant misconceptions about their prognosis
2. List 2 reasons patient participation in treatment decision making may be a challenge in HM

Answer 24

1. They significantly overestimate the likelihood of cure or remission with their disease
2. Exceedingly complex decisional scenarios are inherent in HM care

Rarity of these diseases (vs common solid tumours) means fewer decision support materials/resources

Question 25

List 2 ways in which the burden of treatment can be higher in patients with HM (vs solid tumours)

Answer 25

1. In patients with bone marrow involvement (i.e. MDS, AML) –> higher infection risk and frequent transfusion needs = more monitoring, prophylactic Rx’s, and hospitalization
2. Time spent travelling back and forth for tests/treatments (some HM require complex multi-day treatment regimens)

Question 26

There may be a role for palliative care support of patients who undergo curative, yet aggressive interventions for HM.

List 2 possible chronic conditions patients with HM may face in survivorship.

Answer 26

1. Post-chemotherapy cardiomyopathy or neuropathy
2. Chronic graft versus host disease
3. Physical/psychological complications of allogeneic stem cell transplant

Question 27

List 3 “illness-specific” barriers to palliative care in hematologic malignancies.

Answer 27

1. Prognostic uncertainty
2. Lack of a clear transition from curative to palliative phases of treatment

(i.e. difficult to know when very ill patient could have treatment response vs. is in terminal stage)

3. Unique illness complications (i.e. infections, bleeding, need for transfusion support)
   (i.e. even if long term prognosis is poor, these complications may be readily treatable)

Question 28

List 5 “cultural and clinician barriers” to palliative care in hematological malignancies

Answer 28

1. Bias due to diverse range of outcomes in HM
   - hematologists have seen unexpected/dramatic positive treatment responses, so recall bias
   - PC clinicians only exposed to EOL, so may assume hematologists are over-treating
2. Hematologists may feel guilt/responsibility to provide EOL care to patients they’ve known for years, esp if complications/early death. So may refer to PC late.
3. Misconceptions - HM specialists may think of PC as only for EOL care OR they feel “PC” has negative connotation for patients/families –> so late referrals to PC
4. Deficiencies in collaborative culture

HM specialist often sole clinician providing active treatment (minimal surgery/rads in HM), so “mistrust/suspicion” of outsiders

5. Distrust and negative experiences

HM specialists express past negative experiences (i.e uninformed PC physicians makes patient DNR during treatable complication of therapy) as barrier to referring

6. Exaggerated self sufficiency

HM specialists believe they already do PC, but don’t understand that it’s not just EOL care

HM - dz (prognosis unknown)
HM - pt (neg connotation)
HM - self reliance
HM - pall service = EOL only
HM - pall MD = stop tx, distrust

Question 29

List 2 “system based barriers” to hospice care in HM.

Answer 29

1. Hospice services conditional on discontinuation of therapy
2. Blood product support not available/feasible in hospice

(i.e. patients needing frequent transfusions to prevent bleeding or for subsistence will die in hospital as they wish to continue transfusion support)

• transfusion dependent patients also tend to have shorter length of stay in hospice

Question 30

What does emerging evidence show about patient outcomes when palliative care consultation integrated into hospital admissions for stem cell transplant?

Answer 30

RCT shows patients receiving specialist PC had significant benefit in symptom scores, QOL, anxiety, depression.

There was sustained response in depressed mood, posttraumatic stress at 6 months post SCT

• demonstrates value of IPC in supporting patients/caregivers through physically/emotionally traumatic experience of SCT.