Critical Care of the Pediatric Immunocompromised

Hematology/Oncology Patient An Evidence Based Guide

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Christine N. Duncan
Julie-An M. Talano • Jennifer A. McArthur
Editors

Critical Care of the Pediatric

Immunocompromised
Hematology/Oncology
Patient
An Evidence-Based Guide
Editors
Christine N. Duncan Julie-An M. Talano
Pediatric Hematology-Oncology Children’s Hospital of
Dana-Farber Cancer Institute Wisconsin-Milwaukee
Boston, MA Medical College of Wisconsin
USA Milwaukee, WI
USA
Jennifer A. McArthur
Department of Pediatric Medicine
St. Jude Children’s Research Hospital
Memphis, TN
USA

ISBN 978-3-030-01321-9    ISBN 978-3-030-01322-6 (eBook)

https://doi.org/10.1007/978-3-030-01322-6

Library of Congress Control Number: 2018965743

© Springer International Publishing 2019

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To families of children with cancer and
hematological disorders that we have cared
for in our ICUs
Contents

Part I Predisposing Diseases and Specific Considerations in

Critical Illness
1 The Changing Landscape of the Critical Care of Pediatric
Immunocompromised Hematology and Oncology Patients ������������������   3
Christine N. Duncan
2 Diagnosis and Treatment-Related Complications of
Acute Leukemia ����������������������������������������������������������������������������������������   9
Lauren Pommert, Steven Margossian, and Michael Burke
3 Neuro-oncologic Emergencies ������������������������������������������������������������������ 29
Jessica Clymer and Peter E. Manley
4 Solid Tumors Outside of the Central Nervous System �������������������������� 41
Hilary C. Schreiber and James S. Killinger
5 Primary Immunodeficiency Diseases ������������������������������������������������������ 55
Fayhan Alroqi, Abdulrahman Alsultan, and Mohammed Essa
6 Care of the Critically Ill Pediatric Sickle Cell Patient �������������������������� 71
Tolulope Rosanwo, Jennifer A. McArthur, and Natasha Archer
7 Bone Marrow Failure ������������������������������������������������������������������������������ 95
Sajad Khazal, Jorge Ricardo Galvez Silva, Monica Thakar, and
David Margolis
8 Hematopoietic Stem Cell Transplant and Cellular Therapy ���������������� 109
Priti Tewari, Rajinder Bajwa, Agne Taraseviciute, Jerelyn Moffet,
David McCall, and Kris M. Mahadeo
9 Diagnosis, Treatment, and Management of Hemophagocytic
Lymphohistiocytosis in the Critical Care Unit �������������������������������������� 159
Melissa Hines, Neel Bhatt, and Julie-An M. Talano

vii
viii Contents

Part II Critical Care Management

10 Early Recognition of Critical Illness ������������������������������������������������������ 185
Asya Agulnik
11 Acute Respiratory Failure and Management ���������������������������������������� 195
Prakadeshwari Rajapreyar, Whitney Kopp, and Adrienne Randolph
12 Cardiac Dysfunction in Hematology Oncology
and Hematopoietic Cell Transplant Patients ������������������������������������������ 211
Saad Ghafoor, Marshay James, Jason Goldberg,
and Jennifer A. McArthur
13 Acute Kidney Injury and Renal Replacement Therapy
in Immunocompromised Children ���������������������������������������������������������� 237
Joseph Angelo and Ayse A. Arikan
14 Critical Care Management: Sepsis and Disseminated
and Local Infections ���������������������������������������������������������������������������������� 253
Caitlin Hurley and Matt Zinter
15 ECMO Use in the Pediatric Immunocompromised
Hematology/Oncology Patient ���������������������������������������������������������������� 275
Robert A. Niebler and Leslie E. Lehmann
16 Pharmacy Implications ���������������������������������������������������������������������������� 291
Stacey Albuquerque
17 Psychosocial and Palliative Care ������������������������������������������������������������ 301
Sarah Tarquini, Candice Chow, and Christina Ullrich
18 Delirium ���������������������������������������������������������������������������������������������������� 325
Chani Traube
19 Nursing Considerations ���������������������������������������������������������������������������� 337
Brienne Leary, Barbara Cuccovia, and Colleen Nixon
Index ������������������������������������������������������������������������������������������������������������������ 409
Contributors

Asya Agulnik, MD, MPH Department of Global Pediatric Medicine, Division of

Critical Care, St. Jude Children’s Research Hospital, Memphis, TN, USA
Stacey Albuquerque Boston Children’s Pharmacy Department, Dana Farber/
Boston Children’s Cancer and Blood Disorders Center, Boston, MA, USA
Fayhan Alroqi Department of Pediatric, King Abdullah Specialized Children’s
Hospital, Riyadh, Saudi Arabia
King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
Abdulrahman Alsultan Department of Pediatric, King Abdullah Specialized
Children’s Hospital, Riyadh, Saudi Arabia
Department of Pediatric, College of Medicine, King Saud University, Riyadh, Saudi
Arabia
Joseph Angelo, MD Department of Pediatrics, Renal Section, Texas Children’s
Hospital/Baylor College of Medicine, Houston, TX, USA
Natasha Archer, MD, MPH Department of Pediatric Hematology and Oncology,
Dana-Farber Boston Children’s Cancer and Blood Disorders Center, Harvard
Medical School, Boston, MA, USA
Ayse A. Arikan, MD Renal Section, Critical Care Section, Texas Children’s
Hospital/Baylor College of Medicine, Houston, TX, USA
Rajinder Bajwa, MD Nationwide Children’s Hospital, Columbus, OH, USA
Neel Bhatt, MD Department of Pediatrics, Division of Pediatric Hematology/
Oncology, Medical College of Wisconsin, Children’s Hospital of Wisconsin,
Milwaukee, WI, USA

ix
x Contributors

Michael Burke, MD Division of Hematology/Oncology/Blood and Marrow

Transplant, Department of Pediatrics, Medical College of Wisconsin and Children’s
Hospital of Wisconsin, Milwaukee, WI, USA
Candice Chow, PhD Department of Psychosocial Oncology and Palliative Care,
Dana-Farber Boston Children’s Cancer and Blood Disorders Center, Harvard
Medical School, Boston, MA, USA
Jessica Clymer, MD Pediatric Neuro-oncology, Dana-Farber/Boston Children’s
Cancer and Blood Disorders Center, Boston, MA, USA
Barbara Cuccovia Pediatric Stem Cell Transplant Unit, Boston Children’s
Hospital, Boston, MA, USA
Christine N. Duncan, MD Pediatric Hematology-Oncology, Dana-Farber Cancer
Institute, Boston, MA, USA
Mohammed Essa Department of Pediatric, King Abdullah Specialized Children’s
Hospital, Riyadh, Saudi Arabia
King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
Jorge Ricardo Galvez Silva, MD Nicklaus Children’s Hospital, Miami Children’s
Health System, Miami, FL, USA
Saad Ghafoor, MD Department of Pediatrics, Division of Critical Care Medicine,
St. Jude Children’s Research Hospital, Memphis, TN, USA
Jason Goldberg, MD Pediatric Cardiomyopathy and Heart Transplantation,
University of Tennessee School of Health Sciences, Memphis, TN, USA
Department of Pediatrics, Division of Critical Care Medicine, St. Jude Children’s
Research Hospital, Memphis, TN, USA
Melissa Hines, MD Department of Pediatric Medicine, Division of Critical Care,
St. Jude Children’s Research Hospital, Memphis, TN, USA
Caitlin Hurley, MD Division of Critical Care Medicine and Department of Bone
Marrow Transplantation, St. Jude Children’s Research Hospital, Memphis, TN,
USA
Marshay James, DNP, MSNEd, CNE Department of Pediatrics, Division of
Critical Care Medicine, St. Jude Children’s Research Hospital, Memphis, TN, USA
Vanderbilt University School of Nursing, Nashville, TN, USA
Sajad Khazal, MD The University of Texas MD Anderson Cancer Center,
Houston, TX, USA
James S. Killinger, MD, F.C.C.M. Memorial Sloan Kettering Cancer Center,
New York, NY, USA
Contributors xi

Whitney Kopp, M.D. Division of Pediatric Critical Care Medicine, Medical

College of Wisconsin/Children’s Hospital of Wisconsin, Milwaukee, WI, USA
Brienne Leary Pediatric Medical-Surgical Intensive Care Unit, Boston Children’s
Hospital, Boston, MA, USA
Leslie E. Lehmann, MD Department of Pediatric Oncology, Dana-Farber Cancer
Institute/Boston Children’s Hospital, Boston, MA, USA
Kris M. Mahadeo, MD University of Texas MD Anderson Cancer Center,
Houston, TX, USA
Peter E. Manley, MD Pediatric Neuro-oncology, Dana-Farber/Boston Children’s
Cancer and Blood Disorders Center, Boston, MA, USA
David Margolis, MD Children’s Hospital of Wisconsin, Milwaukee, WI, USA
Steven Margossian, MD, PhD Harvard Medical School, Department of Pediatric
Oncology, Dana Farber Cancer Institute, Boston Children’s Hospital, Boston, MA,
USA
Jennifer A. McArthur, DO Department of Pediatrics, Division of Critical Care
Medicine, St. Jude Children’s Research Hospital, Memphis, TN, USA
Medical College of Wisconsin, Milwaukee, WI, USA
David McCall, MD University of Texas MD Anderson Cancer Center, Houston,
TX, USA
Jerelyn Moffet, PNP Duke Children’s Hospital, Durham, NC, USA
Robert A. Niebler, MD Department of Pediatrics, Section of Critical Care,
Medical College of Wisconsin, Milwaukee, WI, USA
Colleen Nixon Pediatric Hematology/Oncology Unit, Boston Children’s Hospital,
Boston, MA, USA
Lauren Pommert, MD Division of Hematology/Oncology/Blood and Marrow
Transplant, Department of Pediatrics, Medical College of Wisconsin and Children’s
Hospital of Wisconsin, Milwaukee, WI, USA
Prakadeshwari Rajapreyar, M.D. Division of Pediatric Critical Care Medicine,
Medical College of Wisconsin/Children’s Hospital of Wisconsin, Milwaukee, WI,
USA
Adrienne Randolph, M.D., M.Sc Division of Critical Care Medicine, Department
of Anesthesia, Critical Care and Pain Medicine, Boston Children’s Hospital, Boston,
MA, USA
Departments of Anesthesia and Pediatrics, Harvard Medical School, Boston, MA,
USA
xii Contributors

Tolulope Rosanwo Case Western Reserve University School of Medicine,

Cleveland, OH, USA
Hilary C. Schreiber, MD Memorial Sloan Kettering Cancer Center, New York,
NY, USA
Julie-An M. Talano, MD Department of Pediatrics, Division of Pediatric
Hematology/Oncology, Medical College of Wisconsin, Children’s Hospital of
Wisconsin, Milwaukee, WI, USA
Agne Taraseviciute, MD, PhD Children’s Hospital Los Angeles, University of
Southern California, Los Angeles, CA, USA
Sarah Tarquini, PhD Department of Psychosocial Oncology and Palliative Care,
Dana-Farber Boston Children’s Cancer and Blood Disorders Center, Harvard
Medical School, Boston, MA, USA
Priti Tewari, MD University of Texas MD Anderson Cancer Center, Houston, TX,
USA
Monica Thakar, MD Children’s Hospital of Wisconsin, Milwaukee, WI, USA
Chani Traube Department of Pediatrics, Division of Pediatric Critical Care
Medicine, Weill Cornell Medical College, New York, NY, USA
Christina Ullrich, MD, MPH Department of Pediatric Oncology; Department of
Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute and
Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
Matt Zinter, MD Department of Pediatrics, Division of Critical Care Medicine,
UCSF Benioff Children’s Hospitals, University of California, San Francisco, San
Francisco, CA, USA
 Part I
Predisposing Diseases and Specific
Considerations in Critical Illness
Chapter 1
The Changing Landscape of the Critical
Care of Pediatric Immunocompromised
Hematology and Oncology Patients

Christine N. Duncan

Immunocompromised children and adolescent patients who have hematologic or

oncologic diseases represent a small percentage of patients treated in pediatric
intensive care units (PICUs) but have a disproportionately high mortality rate. A
single-center study of 1278 patients admitted to a pediatric hematology-oncology
service over an 11-year period found an admission rate of 4.2% with an overall
PICU mortality rate of 38.9% [1]. Risk factors for PICU admission included
older age, diagnosis of nonmalignant disease, and treatment with HCT. A more
recent retrospective multicenter cohort analysis of almost 250,000 consecutive
PICU admissions using the Virtual PICU Systems database identified 10,365
patients diagnosed with a malignancy who were admitted to PICUs for reasons
other than perioperative admissions during the study period [2]. Children with
cancer accounted for 11.4% of all PICU deaths and had mortality of 6.8% (43%
in those who were mechanically ventilated) compared to 2.4% in patients without
malignancy.
Outcome data regarding patients admitted to PICUs who have nonmalignant
hematologic or immunologic diseases is limited, with the exception of those treated
with hematopoietic cell transplantation (HCT). Far more is known about patients
with oncologic diagnoses, and the literature is most robust regarding those treated
with HCT. The survival of children with hematologic and oncologic diseases has
improved in recent years despite remaining higher than those of other patients treated
in the PICU (Table 1.1). A meta-analysis of mortality trends of children treated in the
PICU after HCT over time showed a significant decrease in mortality associated
with the year of inclusion as did a large single-center study comparing outcomes
over time [3, 4]. However, interpreting comparisons of mortality across multiple

C. N. Duncan (*)
Pediatric Hematology-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
e-mail: [email protected]

© Springer International Publishing 2019 3

C. N. Duncan et al. (eds.), Critical Care of the Pediatric Immunocompromised
Hematology/Oncology Patient, https://doi.org/10.1007/978-3-030-01322-6_1
4 C. N. Duncan

Table 1.1 Published mortality of hematology, oncology, and HCT patients over time
Number of PICU PICU mortality
Reference Study period Population patients (%)
Hayes et al. [5] 1987–1997 HCT 39 73
Hallahan et al. [6] 1987–1996 Oncology and 150 27
HCT
Diaz De Heredia et al. 1991–1995 HCT 31 45
[7]
Lamas et al. [8] 1991–2000 HCT 44 70
Kache et al. [9] 1992–2004 HCT 81 82 (1992–1999)
41 (2000–2004)
Cheuk et al. [10] 1992–2002 HCT 19 84
Diaz et al. [11] 1993–2001 HCT 42 69
Jacobe et al. [12] 1994–1998 HCT 40 44
Heying et al. [13] 1995–1999 Oncology 48 25
(no HCT)
Tamburro et al. [4] 1996–2004 Oncology and 329 41
HCT
Tomaske et al. [14] 1998–2001 HCT 26 58
Gonzalez-Vincent et al. 1998–2002 HCT 36 53
[15]
Hassan et al. [16] 1998–2008 HCT 19 17
Faraci et al. [1] 1999–2010 Hematology/ 54 39
oncology
Asperberro et al. [17] 2000–2006 HCT 53 51
Bartram et al. [18] 2000–2008 Sickle cell 46 7
disease
Chima et al. [19] 2004–2010 HCT 155 37
Duncan et al. [20] 2005–2006 HCT 129 38
Zinter et al. [21] 2009–2012 HCT 1102 16.2
Zinter et al. [2] 2009–2012 Oncology 10,365 6.8
Rowan et al. [22] 2009–2014 HCT 222 60
HCT hematopoietic cell transplantation

studies must be done with caution. The published literature is comprised almost
exclusively of retrospective studies, and the inclusion criteria are not ­consistent
across studies. Some studies include only those felt to be at highest risk for worst
outcome, specifically HCT patients supported with mechanical ventilation, whereas
others include patients with all oncology diagnoses and admitted to the PICU for all
indications. There are multiple reasons for the improved outcomes including scien-
tific advances in critical care, hematology, oncology, and HCT. Equally important
have been advances in supportive care and infectious disease management.
The severity of illness of immunocompromised hematology and oncology
patients admitted to PICUs is broad including planned postoperative admissions,
semi-urgent admissions of patients with worsening illness, and the emergent trans-
fer of rapidly decompensating children. Equally broad are the reasons for critical
1 The Changing Landscape of the Critical Care of Pediatric Immunocompromised… 5

illness in this diverse population including infection, organ compromise, and com-
plications of the primary disease. The management of critically ill immunocompro-
mised children and adolescents must be guided by the primary disease and patient’s
treatment. General principles of the initial management and stabilization of criti-
cally ill hematology and oncology patients, in most cases, can follow practices
applied to other children. Thereafter, the management is strongly influenced not
only by the reason for the need for critical care, but by the unique features of the
underlying disease as well. For example, the early care of a child with sickle cell
anemia experiencing acute respiratory dysfunction may mirror that of a patient with
acute lymphoblastic leukemia or one with severe combined immune deficiency.
After the primary stabilization of the patient, an understanding of the underlying
disease is key to the next steps of diagnosis and management. In the example, one
may consider acute chest syndrome as the cause of the respiratory distress in the
patient with sickle cell anemia. Clearly this would not be on the list of potential
etiologies in a child with leukemia in whom infection may be a chief concern. The
therapy that the child receives to treat the primary disease is important as the critical
illness may be a direct result or influenced heavily by the treatment. A clear example
is that of children undergoing HCT who may have organ compromise, bleeding,
infection, graft-versus-host disease, and other toxicities related to the recent and
past therapy in addition to underlying comorbidities.
A goal of this textbook is to provide an understanding of the specific aspects of
different diagnoses and therapies that impact the critical care of immunocompro-
mised hematology and oncology patients. It is unrealistic to expect PICU providers
to have a comprehensive understanding of all the diseases and therapies used in this
population and for hematologists-oncologists to fully understand advances in ICU
care. This is particularly true given the rapidly changing landscape of pediatric hema-
tologic and oncologic care. Recent years have seen the development and expanded
use of molecularly targeted medications, chimeric antigen receptor T-cell (CAR-T)
therapy, and gene therapy. Each of these and other emerging therapies carry unique
risks. Because of the complexity of diagnoses and treatment, a collaborative relation-
ship between the PICU and the disease-specific teams is important to the care of
these patients. Different models for cooperative care are addressed later in this text.
Multiple research consortia including the Pediatric Acute Lung Injury and Sepsis
Investigators and Pediatric Blood and Marrow Transplant Consortium have focused
on the care of immunocompromised h­ ematology and oncology patients. The work
of these and other groups is important as the community works to improve the sur-
vival of these vulnerable patients.

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