Psychosomatics 2019:60:331 342 © 2019 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.

Review Article

Psychological Considerations in Hematopoietic

Stem Cell Transplantation

Hermioni L. Amonoo, M.D., MPP, Christina N. Massey, Ph.D., Melanie E. Freedman, B.S.,
Areej El-Jawahri, M.D., Halyna L. Vitagliano, M.D., M.Sci., William F. Pirl, M.D., M.P.H.,
Jeff C. Huffman, M.D.

Background: In recent decades, advances in transplanta- vulnerability factors, as well as practical interventions for
tion medicine, and improved posttransplant care have managing these challenges. Results: We outline the
reduced morbidity and mortality from hematopoietic phases of the HSCT hospitalization and discuss common
stem cell transplantations (HSCTs). However, patients psychological challenges, such as depression, delirium,
undergoing HSCT report a high prevalence of psycholog- and post-traumatic stress reactions that accompany
ical distress, which can negatively impact recovery, func- HSCT. We suggest an approach to psychiatric consults
tion, and health outcomes, including mortality and higher during the HSCT hospitalization and discuss practical
risk of graft vs. host disease. Appropriate assessment and interventions for managing psychological challenges in
management of these psychological symptoms lead to this population. Conclusions: Though pharmacological
better engagement with treatment and a variety of supe- and behavioral interventions have been successfully used
rior health outcomes. Objective: We provide a narrative to treat psychosocial challenges in HSCT, further
review of the psychological challenges that accompany research is needed to understand the optimal psychiatric
HSCT and suggest management approaches to equip assessment tools, treatment strategies, and the long-term
psychiatric consultants involved in the care of this patient psychiatric care needed to address psychiatric comorbid-
population. Methods: We reviewed published work in ities in this growing patient population.
PubMed, PsycInfo, and Scopus electronic databases on (Psychosomatics 2019; 60:331 342)
the common psychological challenges in HSCT, their

Key words: Psychiatric consult, Hematopoietic stem cell transplant, Depression, Anxiety, Delirium, Posttraumatic stress.

Received January 9, 2019; revised February 7, 2019; accepted Febru-

ary 8, 2019. From the Dana Farber Cancer Institute (H.L.A., H.L.V.,
INTRODUCTION W.F.P.), Department of Psychosocial Oncology, Brookline, MA;
Brigham and Women’s Hospital (H.L.A.), Boston, MA; Department
of Psychiatry (H.L.A., H.L.V., W.F.P., J.C.H.), Harvard Medical
A growing number of patients have undergone hemato- School, Boston, MA; Massachusetts General Hospital (C.N.M.,
poietic stem cell transplantion (HSCT) in recent decades M.E.F., J.C.H.), Department of Psychiatry, Boston, MA; Massachu-
setts General Hospital (A.E.-J.), Department of Hematology/Oncol-
with more than 50,000 HSCTs performed worldwide
ogy, Boston, MA. Send correspondence and reprint requests to
each year.1 HSCT is usually reserved for patients with Hermioni L. Amonoo, MD, MPP, Brigham & Women’s Hospital, 60
life-threatening diseases to provide life-prolonging or Fenwood Road, Fourth Floor, Boston, MA 02115; e-mail:
Hermioni_lokko@dfci.harard.edu
curative treatment.2 Advances in transplantation medi- © 2019 Academy of Consultation-Liaison Psychiatry. Published by
cine, including improvement in supportive care and Elsevier Inc. All rights reserved.

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Psychological Considerations in Hematopoietic Stem Cell Transplantation

infection management, use of peripheral blood stem stem cells can be from the patient (autologous) or a
cells from unrelated or alternative donors, and donor (allogeneic) derived from bone marrow,
improved posttransplant care, have resulted in reduced peripheral blood, or umbilical cord blood. The type of
morbidity and mortality from HSCT.3,4 hematologic malignancies (including leukemias,
Although most patients who undergo HSCT do not lymphomas, myelodysplastic syndromes, and myelo-
have psychiatric comorbidity, a high prevalence of psy- mas) or benign hematologic conditions (e.g., aplastic
chological distress (including depression symptoms anemia and bone marrow failure syndromes) deter-
[approx. 35%],5 delirium [approx. 35%],6 and posttrau- mine the type of stem cells used in HSCT. In most
matic stress disorder [PTSD] symptoms [approx. 20%]7) HSCT centers, patients are required to undergo a psy-
is reported by these patients and observed by their clin- chiatric evaluation as part of the pretransplant process.
icians.8 10 Psychological distress in HSCT patients is The pretransplant psychiatric evaluation can serve as a
associated with worse health outcomes, including baseline for the patient’s mental health and prepare
increased mortality11 and a higher risk of graft vs. host patients for HSCT.15 There is no standard mental
disease (GVHD).12 Psychological stress-related factors health evaluation for this process and depending on an
potentially modulate cell engraftment and recovery fol- institution’s resources, the pretransplant mental health
lowing transplantation via the hypothalamic pituitary evaluation can be completed by psychiatrists, social
adrenal and sympathetic nervous system axes.12 Hence, workers, or psychologists.
the implications of biobehavioral/psychological pro- A detailed review of oncologic, medical, psychiatric
cesses in the recovery following HSCT necessitates that and family psychiatric history provides insights into
psychological distress is assessed and addressed ade- patients’ risk for psychiatric disorders either in relation
quately during the HSCT process. to or irrespective of HSCT status. Information from
Historically, clinicians have perceived physical oncologists and primary care providers informs the
and psychological burden associated with HSCT as medical and medication history. Some pertinent risk
expected and unmodifiable.13 However, a high level factors to assess include substance abuse history,
of emotional distress over a sustained periods in neuropsychiatric limitations (e.g., memory problems)
HSCT patients may result in anxiety, depression, or that could interfere with the required follow-up after
both.14 Adequate assessment and treatment of psy- HSCT and overall treatment compliance, including
chological symptoms during recovery from HSCT, medications. HSCT centers are not widespread and
positively impact a patient’s ability to engage and most patients travel a long distance from their support-
adhere fully with treatment, to better cope with the ive communities for an extended period to undergo
peaks and valleys of recovery, and to have a better treatment. Hence, a comprehensive evaluation of
quality of life. We seek to review the common psycho- patients’ expectations and social supports is imperative
logical challenges associated with HSCT (from the to understanding potential psychosocial barriers to
preparation for the transplant to recovery) and to good coping.
offer concrete recommendations and practical man- Psychological risk factors rarely contribute to
agement strategies for consultation-liaison (C-L) psy- decisions regarding HSCT eligibility and most HSCT
chiatrists involved in the care of this growing patient centers transplant the majority of eligible patients.
population. The HSCT process consists of different However, all HSCT candidates should be screened for
stages with somewhat distinct medical and psycholog- common psychiatric symptoms (e.g., depressive symp-
ical challenges. Hence, we describe the stages of trans- toms, anxiety symptoms, PTSD symptoms, and sleep
plantation. problems) because of the negative impact of psychiatric
disorders on recovery. In addition to identifying and
PRETRANSPLANTATION PSYCHOLOGICAL communicating identified psychological risk factors to
CONSIDERATIONS the primary HSCT team, it is especially important to
proactively include recommendations for mitigating
Most patients are considered for HSCT after an exten- and managing these risk factors during the HSCT and
sive oncologic evaluation (that includes failed treat- recovery. For example, in the population at risk for
ment modalities) by an oncologist. The transplanted worsening psychological distress during the HSCT use

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 Amonoo et al.

of antidepressants, supportive psychotherapy, or social Posttransplant

work evaluations before transplant could help attenuate
the negative impact of depression during HSCT and The posttransplant period can be divided into two
recovery. Effective treatment of psychological chal- phases (the acute posttransplant phase [the first 100
lenges in the HSCT population results in improved days], and the chronic posttransplant phase [>100 days
outcomes.16 and up to several years]) and psychological distress
associated with these phases could differ. The HSCT
admission usually ends around day 14 20 and routine
PHASES OF HSCT HOSPITALIZATION follow-up care post HSCT lasts until day 100, with
twice-weekly outpatient visits for several weeks. The
The HSCT hospitalization consists of the conditioning continued isolation (where patients are restricted from
regimen, the transplantation itself, the engraftment contact with large numbers of people or crowds includ-
phase, and the posttransplant phase. Below is a brief ing restaurants) for the recovery continues into the first
description of these transplantation phases. 100 days of the recovery.
For patients who usually maintain an active lifestyle
Conditioning (Minus Days) at baseline, a significant amount of emotional distress dur-
HSCT begins with a conditioning regimen that con- ing this phase of the recovery is common as they cannot
sists of chemotherapy and at times total body radia- engage in vigorous or outdoor activities that were previ-
tion. The conditioning regimen destroys patients’ ously considered meaningful or contributed positively to
lymphocytes in preparation for the subsequent trans- quality of life.19 Patients (especially allogeneic recipients)
plant that aims to restore immune function.17 Barring who also have a high burden of physical complications
outpatient transplants,18 the conditioning regimen including severe GVHD or readmissions to the hospital
commences the inpatient admission for the HSCT, and also report a higher level of emotional distress compared
the total duration is about 6 to 8 days depending on with patients (especially autologous recipients) who have
the type of regimen (autologous vs. allogeneic). The uneventful recoveries.12
conditioning days are sometimes referred to as the
“minus days.” COMMON PSYCHIATRIC MANIFESTATIONS
IN HSCT
Transplantation (Day 0)
A variety of psychological challenges are observed in
The second phase of the HSCT hospitalization is the HSCT patients at different stages of the transplantation
stem cell infusion (commonly referred to as Day 0). process. In this section, we discuss the common psycho-
Depending on response to the conditioning regimen, a logical challenges that accompany the HSCT and delin-
small proportion of patients will go into the transplant eate where normal psychological reactions transition to
with significant physical symptoms that impacts their psychiatric disorders.
level of psychological distress.
Anxiety
Engraftment (Plus Days)
Although HSCT patients have multiple reasons to be
The engraftment days, also referred to as the “plus anxious, anxiety is known to be heightened in the minus
days,” follow the transplant. Transplanted stem cells days as patients eagerly anticipate the transplantation
start making new blood cells approximately 8 18 days itself.20 Some patients worry about their response to the
or longer after the stem cell infusion depending on transplant, their quality of life in recovery while in isola-
whether the transplanted cells are autologous vs. alloge- tion, and their ability to manage potential complica-
neic. The combination of increased physical symptoms tions in recovery, especially if they are far from home
(e.g., nausea, anorexia, pain, diarrhea, fever, hair loss) and social support. Specific examples of anxiety that are
and other medical illnesses can result in significant psy- prevalent in HSCT patients include: (1) “my donor was
chological distress. not a perfect (10/10) match so my leukemia would

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Psychological Considerations in Hematopoietic Stem Cell Transplantation

relapse” or (2) “my toddler is going to forget who I am El-Jawahri et al. found that 28.4% of patients met crite-
because I am going to be in the hospital for 30 or more ria for PTSD and depression at 6 months post-HSCT.8
days.” Potential responses to these thought distortions In addition, the study also found that a decline in qual-
would be: (1) validate patient’s concern, and then work ity of life and an increase in depressive symptoms dur-
with the HSCT clinician to educate the patient about ing the HSCT hospitalization were important
outcomes with donors who are not perfect matches, and predictors of PTSD symptoms.
(2) explore with the patient how to stay engaged with
children using technology, such as Facetime during Sleep Disruption
potentially long HSCT hospitalizations. The Lym-
phoma and Leukemia Society21 provides patients and Sleep disturbances are common among HSCT
caregivers with general information about the HSCT patients with more than 50% reporting sleep disruption
process in preparation for transplant. However, we are before the transplant, up to 82% experiencing moder-
aware of no evidence-based patient materials about the ate-to-severe sleep disruption during the transplant hos-
HSCT that aims to reduce anticipatory anxiety for the pitalization and 43% posttransplant.27 Different
transplant hospitalization. There is increasing evidence chemotherapy regimens as well as glucocorticoid treat-
to support the positive impact of communication skills ment have also been associated with sleep disruption.28
training for oncologists. However, we are not aware of Specifically, among HSCT patients, conditioning che-
any oncology communication skills programs that spe- motherapeutic and alkylating antineoplastic agents,
cifically address the impact of HSCT clinicians’ commu- such as busulfan and cyclophosphamide increase the
nication on patients’ anticipatory anxiety.22,23 Anxiety risk of insomnia.29 Although obstructive sleep apnea is
may not meet criteria for anxiety disorder. However, in a common sleep disorder among HSCT patients, most
a subset of patients, nervousness, apprehension, and have not been officially diagnosed with the disease or
worry is so excessive that it jeopardizes their ability to received adequate management.27
engage with treatment and subsequent follow-up care.12
For most patients, the potential etiologies of anxiety Depression
include premorbid generalized anxiety disorder, specific
phobia, panic disorder, adjustment disorder with anxi- Depression is relatively prevalent (35%) at all stages
ety, delirium, and existential distress. of the transplantation process and can interfere with
recovery.5,30 In a prospective study of patients who
Posttraumatic Stress Reactions received either autogeneic or allogeneic transplants at
the Brigham and Women’s Hospital or Dana-Farber
Historically, medical events and treatments have not Cancer Institute, 35% met criteria for depression, and
been considered as traumatic events that precipitate depressed patients had a 3-fold greater risk of dying
PTSD. However, life-threatening medical conditions than nondepressed patients between 6 and 23 months
and their treatment, especially in the cancer population after HSCT when other prognostic factors were
have been identified as stressors that can precipitate adjusted for.5 As in most medical populations, depres-
PTSD.24 The prevalence rate of PTSD in the HSCT sion in HSCT patients can be difficult to assess due to
population is 20%.25 In addition to the fear of cancer the potential increased burden of physical symptoms,
recurrence as in most cancer patients, the HSCT hospi- such as insomnia and poor appetite that may accom-
talization and acute recovery, which is unlike other can- pany the HSCT recovery. Additionally, anhedonia can
cer treatments has been considered a traumatic and can be difficult to assess in HSCT patients, because the
result in PTSD.8 HSCT patients can relive cancer and HSCT hospitalization and acute recovery restrictions
treatment experience with nightmares, flashbacks, or preclude patients from participating in activities they
continuous thoughts about the HSCT process. These may typically enjoy. Depression observed in HSCT
PTSD symptoms are not age-dependent and can be sim- may also develop years after the transplant with the
ilar to that of patients who do not have cancer.26 In a prevalence increasing until 5 years posttransplant.20
prospective study that sought to understand the predic- The predictive factors for depression include a history
tors of worsening quality of life and PTSD symptoms, of depression and medical comorbidities associated

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 Amonoo et al.

with the cancer and HSCT.31,32 The differential diagno- on the type of transplant and its associated complica-
sis for depressive symptoms includes major depressive tions in the acute recovery period.
disorder, adjustment disorder with depressed mood,
persistent depressive disorder (dysthymia), demoraliza- Neurocognitive Dysfunction Other than Delirium
tion, bipolar disorder, and delirium. The evidence for
depression screening or depression diagnostic tools spe- Neurocognitive dysfunction in HSCT survivors is a
cifically for the HSCT patient population are lacking, major cause of morbidity and mortality, and its preva-
although routine depression screening tools such as the lence is up to 60% 22 82 months post-HSCT.40 Cogni-
Patient Health Questionnaire (PHQ-9) has been clini- tive deficits in the HSCT population span several
cally useful.33 cognitive domains, including attention, memory, men-
tal processing speed, coordination, and executive func-
Delirium tioning.41,42 HSCT patients who report cognitive
problems are more likely to report difficulties with emo-
With the incidence range of 18% 85%, delirium is tional and physical functioning as well as difficulty
the most common neuropsychiatric disorder in cancer managing HSCT-related symptoms.43 Risk factors for
patients.34 The prevalence of delirium in HSCT is neurocognitive dysfunction include conditioning che-
about 35% with the highest frequency, 2 weeks fol- motherapeutic regimens that cross the blood brain bar-
lowing the HSCT in the engraftment and recovery rier (e.g., busulfan, cytarabine arabinoside, and
days.7,26,35 As in most cancer patients, delirium is fludarabine) and total body radiation, immunosuppres-
often unrecognized and undertreated in the HSCT sive therapy (e.g., steroids, tacrolimus) for GVHD, cen-
population.26 Pretransplant risk factors for delirium tral nervous system infections, and primary CNS
in the HSCT population include lower cognitive func- disorders.40 Neurocognitive dysfunction not only
tion, renal dysfunction, decreased oxygen saturation impacts function and quality of life, but also psycholog-
level, lower functioning, decreased white blood cell ical and social well-being of patients.44 Although studies
count (and its associated increased risk for rare infec- on preventative measures of neurocognitive dysfunc-
tions), decreased hemoglobin, decreased platelet tion, other than delirium in the HSCT population is lim-
count, and higher magnesium.36,37 Interestingly, ited, addressing sleep difficulties, depressive symptoms,
unlike other cancer patients, disease severity, func- and fatigue may assist with improving cognitive
tional status, and age have not been reliable predic- functioning.45
tors of delirium in the HSCT population due to an
overall healthy baseline for the majority of patients Adjustment Reactions
who undergo HSCT.26 For a given patient, the etiol-
ogy of delirium is complex. Common causes of delir- The isolation and adjustment to a variety of restric-
ium in HSCT patients include medications (e.g., tions (including a neutropenic transplant diet, social iso-
steroids, analgesics, and chemotherapy), infections, lation or avoidance of large crowds) adds to the
metabolic derangements, neutropenia, pancytopenia, emotional challenge of the engraftment days. It is diffi-
and long hospitalizations. Delirium can often be cult to define what a “normal adjustment” to the HSCT
accompanied by various psychiatric symptoms, is as this varies significantly among patients and can be
including depression, anxiety, and psychosis. Addi- dependent on many factors, such as a person’s coping
tionally, patients with delirium during an allogeneic style and associated defense mechanisms. Coping mech-
HSCT are significantly more likely to have persistent anisms can be both helpful and/or maladaptive to
anxiety, fatigue, and distress 80 days posttransplanta- patients and can impact how they manage their illness
tion with some psychological symptoms persisting for or the HSCT.46 Planning, acceptance, humor, and posi-
up to one year post HSCT.38,39 Critical to managing tive framing are active forms of coping, which can alter
the neuropsychiatric symptoms of delirium is treating how one perceives stress. Avoidance, behavioral dis-
the underlying medical condition that is usually driv- engagement, or venting are less active ways of coping.
ing the symptoms in HSCT patients, the underlying Evidence suggests that an avoidant coping style, or
medical condition could vary significantly depending methods of coping in which individuals do not actively

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Psychological Considerations in Hematopoietic Stem Cell Transplantation

try to gain mastery or control over potentially distress- VULNERABILITY FACTORS FOR
ing or stressful events, is more likely to lead to increased PSYCHOLOGICAL CHALLENGES
emotional distress in HSCT patients.47,48 Difficulty cop-
ing can result in an adjustment disorder. A psychiatric Patient, disease, and medication factors make an HSCT
assessment during the engraftment days may provide patient vulnerable to psychiatric comorbidities during
useful insights in delineating between a normal emo- the transplant.
tional response to the stressors associated with trans-
plant vs. nascent psychiatric disorders that will benefit Patient Factors
from aggressive treatment and management.
Older patients are predisposed to certain psychiatric
conditions, such as delirium, compared to younger
Demoralization
patients.54 Historically, women have a greater predispo-
Although demoralization can be observed in HSCT sition to certain mood disorders, such as depression and
patients at any stage of the treatment, engraftment anxiety.55 A history of mental health problems results
days predispose people to demoralization due to the in a greater risk of developing psychiatric comorbid-
length of isolation and hospitalization, as well as the ities.35 Poorer pretransplantation executive functioning
increased prevalence of medical comorbidity.49 is associated with higher delirium severity and neuro-
Demoralized patients feel disempowered and help- cognitive dysfunction.56 Social support plays a signifi-
less. However, demoralization differs from depres- cant role in various health outcomes, such as quality of
sion in that it lacks the persistent low mood seen in life and functioning for HSCT patients.11 Financial
depression; normal fluctuations in mood are still pre- problems, lower educational levels, and overall lower
served and the resolution of the adverse situations socioeconomic status results in a greater predisposition
rapidly restores the capacity to feel enjoyment and to emotional problems.35
hope.50 For cancer patients with a long course of
treatment and recovery, such as in HSCT, demorali- Disease Factors
zation can be persistent at any stage of the HSCT pro-
cess and be difficult to distinguish from other mood A more aggressive cancer diagnosis (based on biolog-
disorders.51 ical and genetic markers) and lack of responsivity to
treatment yields a higher risk for psychological distress
PSYCHIATRIC CONSULT DURING THE HSCT (especially anxiety) and psychiatric comorbidities.57
ADMISSION A higher burden of medical comorbidities bears a
higher level of emotional distress.31,58 Rehospitalization
The primary goal of new psychiatric consultations dur- after the transplant increases the risk of psychological
ing the HSCT hospitalization is to determine whether issues as well.32
the observed or reported psychiatric symptoms repre-
sent normal reactions to a life-threatening illness, a new Medication and Treatment Factors
or recurrent psychiatric disorders, or a manifestation or
side effects of the treatment.52 Assessing psychiatric HSCT chemotherapeutic regimens cause a variety of
symptoms and disorders in HSCT patients, like most side effects, which contribute to the burden of physical
medical populations, can be challenging and compli- symptoms. Hence, both directly (as in the case of alky-
cated as the physical symptoms that manifest in various lating agents such as cyclophosphamide) and indirectly,
psychiatric disorders (e.g., fatigue and poor appetite in chemotherapeutic agents can impact the level of psy-
major depressive disorder) may result from HSCT or chological distress and comorbidities in patients.59
the complications that ensue from the HSCT. Hence, Whole brain radiation as part of the conditioning regi-
familiarity and expertise with both psychiatric disease men, also predisposes to a variety of neurocognitive
management and the HSCT process is essential. Table 1 and behavioral issues.44 Medications, such as steroids,
outlines our suggested considerations for an inpatient can also cause a wide variety of psychiatric syndromes
psychiatric consultation for HSCT patients. including mood, anxiety, psychotic disorders as well as

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 Amonoo et al.

TABLE 1. Approach to an Inpatient Psychiatric Consult for a HSCT Patient

Step Explanation
Preparation  Obtain detailed medical history, stage in transplantation, hospital course, and complications from the primary
HSCT team
 Review the electronic medical records, including both pertinent inpatient and outpatient medical records
 Review social work records
 Review any psychiatric records (including for prior psychiatric history and psychiatric medications) if available
 Review chemotherapeutic regimens used in the conditioning stage and/or radiation
 Review inpatient medications
 Inquire about behavioral issues and deficits in engagement with care from inpatient nursing team
 Review laboratory results
 Review brain imaging results
Patient interview  Obtain a comprehensive history of both physical and psychiatric symptoms
 Inquire about pain symptoms
 Determine psychiatric history including prior psychiatric treatment and medications
 Conduct a safety assessment
 Gather social history including the nature of social supports, religion and spirituality factors
 Conduct a mental status exam including a cognitive screening instrument, e.g., MoCA53
Differential diagnoses  Consider common medical etiologies of neuropsychiatric symptoms, e.g., rare infections [including from viruses
(Herpes viruses, such as Human Herpes Virus 6, Epstein Barr viruses), parasites (toxoplasmosis), fungus (mucor-
mycosis)], thyroid disease, and nutritional deficiencies in addition to psychiatric diagnoses
 Explore potential symptoms related to existential distress
 Elicit difficulty coping and adjustment issues that do not necessarily qualify for an adjustment disorder
Treatment/interventions  Pharmacological interventions including psychiatric medications
 Non-pharmacological interventions, e.g., cognitive behavioral therapy
 Spiritual care services
 Social work support
Considerations for  Awareness of the complex nature of the inpatient care team including medical house staff who may rotate quite
liaison with care team often over the course of a transplant admission
 Familiarity with primary HSCT team who would likely follow patient over the course of the transplant for
continuity
 Familiarity with inpatient social workers who follow patients closely

delirium.35 Notably, the type of transplant (allogeneic and research has trailed behind the clinical practice.
vs. autologous) matters and impacts the risk of psycho- Several classes of psychopharmacologic agents (includ-
logical distress and psychiatric morbidity in HSCT ing antidepressants, antipsychotics, and anxiolytics)
patients. Specifically, the recovery and risk of psychiat- have been used with good efficacy.34 A thoughtful con-
ric comorbidity following an autologous and allogeneic sideration of drug-drug reactions, somatic symptom,
transplant, especially during the survivorship phase, are and adverse effect profiles (especially those pertaining
very different as allogeneic recipients are at much higher to the bone marrow environment), and medical comor-
risk for long-term psychological distress. bidities is necessary for the selection of pharmacological
agent.35 A comprehensive discussion of all the drug-
PRACTICAL INTERVENTIONS FOR drug interactions between psychopharmacological
MANAGING PSYCHIATRIC DISORDERS IN agents and a broad range of medications (e.g., antibiot-
HSCT ics, immunosuppressants, and chemotherapeutic regi-
mens) used by HSCT patients is important but beyond
Both pharmacological and nonpharmacological inter- the scope of this review.
ventions can be used to manage psychiatric disorders Antidepressants from various classes, such as selective
comorbid with the HSCT process. serotonin reuptake inhibitors (SSRIs), or selective norepi-
nephrine reuptake inhibitors (SNRIs) can effectively man-
Psychopharmacological Interventions age depression and anxiety symptoms. However, SSRIs
and SNRIs can reduce platelet serotonin resulting in plate-
Pharmacotherapy is commonly used to treat psychi- let dysfunction and an increased risk of bruising and
atric symptoms in HSCT patients although evidence bleeding, especially for HSCT patients.60 Fluoxetine,

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Psychological Considerations in Hematopoietic Stem Cell Transplantation

paroxetine, and sertraline should be used cautiously as recovery.68 Forms of CBT are thought to be among the
they have the highest degree of serotonin reuptake inhibi- most efficacious psychotherapeutic treatments for a
tion and are more frequently associated with bleeding variety of psychiatric syndromes.69 Various subtypes
problems.61 Mirtazapine, an atypical antidepressant used (e.g., a telephone administered CBT therapy to reduce
primarily for the treatment of depression can be especially treatment-related PTSD symptoms)70 of CBT that have
useful in managing mood and anxiety symptoms in been used with HSCT patients include the coping skills
HSCT because of its additional anxiolytic, sedative, anti- interventions targeted primarily at learning more effec-
emetic, and appetite stimulation properties. However, on tive ways to cope with emotional distress. Stress man-
rare occasions, mirtazapine can cause neutropenia and agement with relaxation, a 2-pronged program that is
agranulocytosis.62,63 Although antidepressants are the geared toward increasing awareness of triggers for stress
gold standard for managing anxiety symptoms, benzodia- while also teaching behavioral relaxation methods that
zepines can be used to manage acute or intermittent anxi- help to slow heart rate, breathing rate, and decrease
ety that may arise at different stages of the transplant muscle tension have also been used. Relaxation and
process. Benzodiazepines rarely cause agranulocytosis but mindfulness-based71 interventions can also be used as a
clonazepam and diazepam have been reported to cause stand-alone treatment and is also sometimes combined
thrombocytopenia, anemia, and leukopenia.64 with psychoeducation and other general lifestyle inter-
Antipsychotic medications effectively manage the ventions (e.g., exercise programs).
neuropsychiatric and behavioral issues that accom- Psychological interventions that provide the platform
pany delirium. Antipsychotics also have anxiolytic for patients to share their HSCT experience and stories
(e.g., quetiapine, olanzapine, and haloperidol), anti- can also reduce emotional and psychological distress.68
emetic (e.g., olanzapine), appetite stimulation (e.g., For example, Rini et al.72 found that in 30 HSCT survi-
olanzapine), and sedative properties in medical popu- vors who participated in a psychological intervention
lations. However, several antipsychotic medications where patients shared their experiences of the HSCT with
including olanzapine, clozapine, chlorpromazine, and their peers, patient stories made peers feel more prepared
haloperidol are associated with agranulocytosis and for the treatment and decision making, reduced fear and
neutropenia.64 66 uncertainty, and fostered hope. Importantly, such inter-
Mood stabilizers and antiepileptics (e.g., valproic ventions are not practical during the HSCT hospitaliza-
acid and carbamazepine) used for patients with comor- tion as patients are isolated from other patients.
bid psychiatric disorders, such as bipolar disorder, can Palliative care interventions benefit HSCT patients
result in thrombocytopenia and neutropenia. Lithium, in myriad ways, beyond the management of physical
a standard mood stabilizer for bipolar depression, indu- symptoms. Palliative care interventions facilitate the
ces leukocytosis and thrombocytopenia. Valproic acid discussion of end-of-life care, preferences of patients
is also commonly used to manage agitation in patients with overarching goal of maintaining the wellbeing of
with delirium whose medical problems prohibit the use patients, irrespective of goals of care or intended out-
of antipsychotic medications.67 comes.73 Recent studies of palliative care interventions
on psychological challenges in HSCT have been very
Nonpharmacological Interventions promising. For example, El-Jawahri et al.8 studied the
impact of inpatient palliative care interventions on
Behavioral interventions can successfully address patient’s quality of life and outcomes, and found that
psychological distress in HSCT patients although there integrated palliative care service with the HSCT admis-
are limited to no randomized controlled trials testing sion resulted in improvements in depression and PTSD
the efficacy of these interventions in this population. symptoms at 6-months posttransplant.
Cognitive-behavioral therapy (CBT) methods entail Spirituality is a multidimensional construct that
psychoeducation regarding how maladaptive thoughts, embodies both existential and religious faith practices
emotions, and behaviors can serve to maintain distress, via individuals’ expression of meaning and connected-
approaches to identifying and changing the distorted ness to self, others or sacred things.74 Spirituality has
thinking, and learning more effective coping skills to been associated with improved adjustment and func-
manage stressors associated with treatment and tioning in a variety of cancer patients.75 Specifically for

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 Amonoo et al.

HSCT, Wingard et al.76 found that in long-term survi- are uniquely positioned to work with both oncological
vors of HSCT, greater spiritual well-being was associ- and HSCT clinicians in the management of psychiatric
ated with better mental health. Harris et al.77 also comorbidities in the HSCT population. A comprehen-
found that in HSCT patients with chronic GVHD, sive diagnostic approach that uncovers both physical
patients who reported the lowest spiritual well-being and psychological symptoms with a nuanced under-
reported worse physical, emotional, social, and func- standing of how hematologic malignancies and the
tional well-being. Some HSCT centers, such as the HSCT naturally impact these symptoms is essential to
Dana-Farber Cancer Institute, have spiritual care inform psychiatric diagnosis and treatment strategies.
resources for patients to have their stem cells Early identification of patient vulnerabilities to psychi-
“blessed” at the time of stem cell infusion. At the atric comorbidities can also facilitate timely diagnostic
Dana-Farber Cancer Institute, more than half of the assessment and treatment. Both pharmacological and
allogenic and autogeneic transplant patients agree to behavioral interventions have been successfully used to
stem cell blessings-anecdotally, patients have treat psychosocial challenges in HSCT, although
reported this to reduce anxiety and promote hope research and evidence has trailed behind clinical prac-
and comfort during the transplantation.78 Despite tice. Considering the complex nature of HSCT and the
the mixed and limited evidence on the impact of reli- intensive prolonged recovery, further research is needed
gion and spirituality on psychological well-being of to understand the optimal psychiatric assessment tools,
patients, spiritual care services, when available to and treatment strategies needed to address psychiatric
some HSCT patients may be beneficial in managing comorbidities in this growing and important popula-
psychological distress. tion.

CONCLUSION Funding: Time for development and completion of

this review was funded by the Harvard Medical School
Although in recent years, HSCT has become a life-sav- Dupont-Warren Research Fellowship Award (to HA),
ing treatment for some patients with hematologic malig- Harvard Medical School Livingston Research Award (to
nancies, there is a high prevalence of psychological HA) and grant 1-17-ICTS-099 from the American Dia-
distress and psychiatric comorbidities which impact betes Association and NIDDK R21DK109313 from the
quality of life, function, and recovery. A diverse range National Institutes of Health (to JH).
of psychological challenges have been observed at dif- Declarations of Interest: None.
ferent stages of the transplant process. C-L psychiatrists

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