title: Challenges in the harmonization of immune monitoring studies and trial design for cell-based therapies in the context of hematopoietic cell transplantation for pediatric cancer patients.
abstract: Clinical trials aimed at improving results of hematopoietic cell transplantation (HCT) by adjuvant cell-based interventions in children have been limited by small numbers and pediatric-specific features. The need for a larger number of pediatric HCT centers to participate in trials has resulted in a demand for harmonization of disease-specific clinical trials and immune-monitoring. Thus far, most phase I/II trials select different end points evaluated at disparate time points, making inter-study comparisons difficult and, sometimes, impossible. In this review, we discuss the various aspects that are important to consider for harmonizing clinical trial design as well as the critical elements for standardized (immune)-monitoring protocols in cell-based intervention trials in the context of HCT. Comparison data from trials applying harmonized trial design will lead to optimized immunotherapeutic treatment protocols to maximize clinical efficacy while minimizing toxicity.
authors.affiliation: U-DAIR, Laboratory of Translational Immunology, UMC Utrecht, Utrecht, Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Nierkens
authors.affiliation: Division of Stem Cell Transplantation, Department of Pediatrics, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Arjan C
authors.initials: AC
authors.lastname: Lankester
authors.affiliation: Division of Haematology/Oncology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: R Maarten
authors.initials: RM
authors.lastname: Egeler
authors.affiliation: Department of Stem Cell Transplantation and Immunology, Hospital for Children and Adolescents, Frankfurt am Main, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.affiliation: Dipartimento di Oncoematologia Pediatrica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCSS), Ospedale Bambino Gesù, Roma, Italy; Università di Pavia, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Division of Hematology, Oncology and Blood & Marrow Transplantation, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pulsipher
authors.affiliation: Children's Research Institute, Children's National Health System, The George Washington University, Washington, DC, USA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bollard
authors.affiliation: Blood and Marrow Transplantation Program, Department of Pediatrics, UMC Utrecht, Utrecht, Netherlands; Laboratory of Translational Immunology, UMC Utrecht, Utrecht, Netherlands. Electronic address: J.J.Boelens@umcutrecht.nl.
authors.forename: Jaap-Jan
authors.initials: JJ
authors.lastname: Boelens
mesh_terms: D000293:Adolescent; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002648:Child; D002986:Clinical Trials as Topic / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015166:Monitoring, Immunologic; D009369:Neoplasms / Q000628:therapy*; D012107:Research Design
keywords: cell based therapy; clinical trial design; hematopoietic cell transplantation, immune monitoring; pediatric cancer