Cellular Therapy and Stem Cell Transplantation
Carrie L. Kitko, MD1*, Catherine M Bollard,
MBChB2,3,4, Mitchell S. Cairo, MD5,
Joseph Chewning, MD6, Terry J. Fry,
MD7,8, Michael A. Pulsipher, MD9,
Shalini Shenoy, MBBS10, Donna A. Wall,
MD11, John E. Levine, MD, MS12
1 Pediatric Stem Cell Transplant Program, Vanderbilt
University Medical Center, Nashville, TN
2 Center for Cancer and Immunology Research,
Children’s National Hospital, Washington, DC
3 GW Cancer Center, George Washington University,
Washington, DC
4 Division of Blood and Marrow Transplantation,
Children’s National Hospital, Washington, DC
5 Division of Pediatric Hematology, Oncology and Stem
Cell Transplantation, Maria Fareri Children’s Hospital, Westchester
Medical Center, New York Medical College, Valhalla, New York, NY
6 Division of Hematology and Oncology, University of
Alabama at Birmingham, Birmingham, AL
7 Department of Pediatrics, University of Colorado
Anschutz Medical Campus, Aurora, CO
8 Center for Cancer and Blood Disorders, Children’s
Hospital Colorado, Aurora, CO
9 Division of Hematology and Oncology, Intermountain
Primary Children’s Hospital, Huntsman Cancer Institute, Spencer Fox
Eccles School of Medicine, Salt Lake City, UT
10 Division of Pediatric Hematology and Oncology,
Department of Pediatrics, Washington University, St Louis, MO
11 Division of Haematology/Oncology, Hospital for Sick
Children, Toronto, Canada
12 Tisch Cancer Institute, Icahn School of Medicine at
Mount Sinai, New York, NY
*Corresponding Author : Carrie L. Kitko, MD, Division of
Pediatric Hematology/Oncology, Department of Pediatrics, Vanderbilt
University Medical Center, Nashville, TN. Email: carrie.l.kitko@vumc.org
Word count:
Abstract: 160
Manuscript: 3499
Figures: 2
Tables: 4
Funding support: Grant support from the National Institute of
Health, U10CA180886, U10CA180899, U10CA098543, U10CA098413.
Abstract : Since the publication of the last Cellular Therapy
and Stem Cell Transplant blueprint in 2013, Children’s Oncology Group
cellular therapy-based trials for advanced the field and created new
standards of care across a wide spectrum of pediatric cancer diagnoses.
Key findings include that tandem autologous transplant improved survival
for patients with neuroblastoma and atypical teratoid/rhabdoid brain
tumors, one umbilical cord blood (UCB) donor was safer than two UCB
donors, killer immunoglobulin receptor (KIR) mismatched donors did not
improve survival for pediatric acute myeloid leukemia when in
vivo T cell depletion is used and the depth of remission as measured by
next-generation sequencing based minimal residual disease assessment
pre-transplant was the best predictor of relapse for acute lymphoblastic
leukemia. Plans for the next decade include optimizing donor selection
for transplants for acute leukemia/myelodysplastic syndrome, using novel
engineered cellular therapies to target a wide array of malignancies,
and developing better treatments for cellular therapy toxicities such as
viral infections and graft-vs-host disease.
Introduction : The Cellular Therapy and Stem Cell
Transplantation (CT) committee is a domain within the Children’s
Oncology Group (COG) and as such develops its own trials in addition to
collaborating with other diseases committees, domains, and disciplines
as well as external groups such as the Pediatric Transplant and Cellular
Therapy Consortium (PTCTC) and the Blood and Marrow Transplant Clinical
Trials Network (BMT CTN; Figure 1) in areas related to transplant and
cellular therapy for pediatric cancer. For some COG studies, the primary
research question concerns cellular therapy practice such as the best
donor source, e.g., ASCT2031, haploidentical vs unrelated donor),
preparative regimen intensity for juvenile myelomonocytic leukemia
(JMML) (ASCT1221), or whether the inclusion of sirolimus in
graft-vs-host disease (GVHD) prophylaxis can improve outcomes for
patients with minimal residual disease (MRD) prior to transplant
(ASCT0431). Such studies are best run by the CT committee directly; in
other cases, the cellular therapy component may be one block of a larger
treatment plan for specific diseases, such as ACNS0333 and ANBL0532
(tandem autologous transplant as consolidation following induction
chemotherapy for brain tumors and neuroblastoma respectively). Studies
focused on supportive care may be more appropriate for the Cancer
Control and Supportive Care domain portfolio, such as ACCL0934 or
ACCL1131, testing different infection prophylaxis strategies early
post-HCT.
The hematopoietic cell transplantation (HCT) field has seen major
advancements over the past decade such as immune effector cell therapy
(e.g., CD19-directed chimeric antigen receptor T cells [CAR T-cells]
for B-cell malignancies) and hematopoietic stem cell gene therapy for
hemoglobinopathies.1-3 As a result, many transplant
programs, national organizations, and journals changed their names to be
more inclusive of these emerging treatments. The former COG Stem Cell
Transplant Committee was renamed the Cellular Therapy (CT) Committee to
reflect this evolution in the field. Looking to the future, COG’s strong
record of accomplishment in studying rare diseases is ideally suited to
test emerging immune based cellular therapies for multiple hematologic
and solid cancers in children and to treat post-HCT complications such
as GVHD and refractory viral infections among others.
Most pediatric transplant and cellular therapy programs and smaller
consortia treat small numbers of patients. International cooperative
groups such as COG are necessary to conduct pivotal trials that require
larger numbers of patients to move the field forward. The CT Committee’s
three overarching goals are: 1) to improve the efficacy of CT
(allogeneic, autologous and immune effector cells) in childhood cancer;
2) to improve the safety of CT; and 3) to optimize design, collaborate
in the development, and assure timely completion of CT-related treatment
and research protocols developed through COG disease and domain
committees.