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Long-Term Follow-Up after Reduced-Intensity Conditioning and Stem Cell Transplantation for Childhood Nonmalignant

Lisa M Madden1, Robert J Hayashi1, Ka Wah Chan2

  • 1Division of Pediatric Hematology Oncology, Washington University School of Medicine, St. Louis, Missouri.

Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation
|May 11, 2016
PubMed
Summary

Reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HCT) in children shows few long-term complications. This study highlights the safety and efficacy of RIC HCT for nonmalignant disorders beyond two years post-transplant.

Keywords:
Childhood nonmalignant disordersLate complicationsReduced-intensity conditioningStem cell transplantation

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Area of Science:

  • Pediatric Hematology
  • Immunology
  • Transplantation Science

Background:

  • Reduced-intensity conditioning (RIC) regimens for hematopoietic stem cell transplantation (HCT) are investigated for children due to potentially fewer complications than myeloablative regimens.
  • Long-term follow-up data for RIC regimens in pediatric nonmalignant disorders are essential to fully assess safety and efficacy.

Purpose of the Study:

  • To evaluate late complications and outcomes beyond two years post-HCT in children with nonmalignant disorders who received a specific RIC regimen.
  • To assess the long-term graft function and regimen-related toxicities associated with alemtuzumab, fludarabine, and melphalan-based RIC HCT.

Main Methods:

  • A multicenter study involving 43 children with nonmalignant disorders undergoing related or unrelated donor HCT using a RIC regimen (alemtuzumab, fludarabine, melphalan).
  • Analysis of late follow-up data (beyond 2 years) including chimerism, graft-versus-host disease (GVHD), complications, and functional outcomes (ovarian function, school performance).

Main Results:

  • Full donor chimerism or stable mixed chimerism was achieved in all patients without late graft rejection.
  • Graft-versus-host disease (GVHD) required systemic immunosuppression therapy (IST) in 12% of patients, with two late deaths. Overall, 23% experienced complications, including hypothyroidism, low-grade neoplasms, and delayed puberty.
  • Most postpubertal females resumed normal ovarian function, and 96% of school-age recipients functioned at grade level.

Conclusions:

  • Reduced-intensity conditioning (RIC) HCT using alemtuzumab, fludarabine, and melphalan demonstrates a favorable long-term safety profile with few regimen-related toxicities in children with nonmalignant disorders.
  • While generally safe, ongoing long-term surveillance is crucial for early identification and management of potential late complications, including those related to GVHD and endocrine dysfunction.