Allogeneic Transplantation for Pediatric Acute Lymphoblastic Leukemia: The Emerging Role of Peritransplantation Minimal Residual Disease/Chimerism Monitoring and Novel Chemotherapeutic, Molecular, and Immune Approaches Aimed at Preventing Relapse

Michael A. Pulsipher, Peter Bader, Thomas Klingebiel, Laurence J.N. Cooper

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51 Citations (Scopus)

Abstract

Although improved donor sources and supportive care have decreased transplantation-related mortality over the past decade, relapse remains the principal cause of failure after allogeneic transplantation for high-risk pediatric acute lymphoblastic leukemia (ALL). Emerging tools of minimal residual disease (MRD) and chimerism monitoring before and after transplantation have defined those children at highest risk for relapse and provide the opportunity for intervention to prevent relapse. Specific methods aimed at decreasing relapse include the use of intensive treatment before transplantation to increase the percentage of patients undergoing the procedure with negative MRD, optimal transplantation preparative regimens, and posttransplantation interventions with targeted or immunologic therapy. Early data demonstrate decreased relapse with the use of sirolimus for all types of ALL and imatinib for ALL with the Philadelphia chromosome (Ph+ ALL) after transplantation. Patients with increasing chimerism or MRD have been shown to benefit from early withdrawal of immune suppression or donor lymphocyte infusion. Finally, various targeted immunologic therapies, including monoclonal antibodies, killer cell immunoglobulin-like receptor mismatching, natural killer cell therapy, and targeted T cell therapies, are emerging that also could have an affect on relapse and improve survival after transplantation for pediatric ALL.

Original languageEnglish (US)
Pages (from-to)62-71
Number of pages10
JournalBiology of Blood and Marrow Transplantation
Volume15
Issue number1 SUPPL.
DOIs
StatePublished - Jan 1 2009

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Chimerism
Homologous Transplantation
Residual Neoplasm
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Transplantation
Pediatrics
Recurrence
Cell- and Tissue-Based Therapy
Tissue Donors
KIR Receptors
Philadelphia Chromosome
Sirolimus
Natural Killer Cells
Therapeutics
Monoclonal Antibodies
Lymphocytes
T-Lymphocytes
Survival
Mortality

Keywords

  • Pediatric Allogeneic Transplantation, Acute Lymphoblastic Leukemia, Minimal Residual Disease, Immunotherapy

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

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abstract = "Although improved donor sources and supportive care have decreased transplantation-related mortality over the past decade, relapse remains the principal cause of failure after allogeneic transplantation for high-risk pediatric acute lymphoblastic leukemia (ALL). Emerging tools of minimal residual disease (MRD) and chimerism monitoring before and after transplantation have defined those children at highest risk for relapse and provide the opportunity for intervention to prevent relapse. Specific methods aimed at decreasing relapse include the use of intensive treatment before transplantation to increase the percentage of patients undergoing the procedure with negative MRD, optimal transplantation preparative regimens, and posttransplantation interventions with targeted or immunologic therapy. Early data demonstrate decreased relapse with the use of sirolimus for all types of ALL and imatinib for ALL with the Philadelphia chromosome (Ph+ ALL) after transplantation. Patients with increasing chimerism or MRD have been shown to benefit from early withdrawal of immune suppression or donor lymphocyte infusion. Finally, various targeted immunologic therapies, including monoclonal antibodies, killer cell immunoglobulin-like receptor mismatching, natural killer cell therapy, and targeted T cell therapies, are emerging that also could have an affect on relapse and improve survival after transplantation for pediatric ALL.",
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