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

Biol Blood Marrow Transplant. 2016 Aug;22(8):1467-1472. doi: 10.1016/j.bbmt.2016.04.025. Epub 2016 May 6.

Abstract

Reduced-intensity conditioning (RIC) before hematopoietic stem cell transplantation (HCT) in children could result in fewer complications during follow-up compared with myeloablative regimens. Hence, many RIC regimens are under investigation, but long-term follow-up is essential. We describe late follow-up beyond 2 years post-HCT in 43 children with nonmalignant disorders who underwent related or unrelated donor (56%) HCT on a multicenter study using a RIC regimen (alemtuzumab, fludarabine, and melphalan) followed by bone marrow (n = 30), peripheral blood (n = 3), or umbilical cord blood (n = 10) HCT for immune dysfunction, bone marrow failure, metabolic disorders, or hemoglobinopathy. Recipients (median age, 7.5 years; range, 3 to 26) underwent HCT 2 to 8 years (median, 3.1 years) before this report. Full donor (67%) or stable mixed chimerism (33%) was noted without late graft rejection. Five patients (12%) required systemic immunosuppression therapy (IST) beyond 2 years post-HCT for graft-versus-host disease (GVHD); 2 patients died 38 and 79 months later, whereas the others improved, enabling an IST wean. Overall, 17 complications were documented in 10 patients (23%). Complications not related to GVHD included hypothyroidism (n = 2), low grade neoplasms (n = 2), and delayed puberty (n = 1). One patient with GVHD had ovarian failure; all other postpubertal females resumed normal ovarian function. Twenty-seven of 28 school-age recipients were functioning at grade level. RIC HCT recipients thus had few regimen-related toxicities during long-term follow-up. However, objective long-term follow-up is still necessary to identify complications so timely intervention may be planned.

Keywords: Childhood nonmalignant disorders; Late complications; Reduced-intensity conditioning; Stem cell transplantation.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alemtuzumab / therapeutic use*
  • Bone Marrow Transplantation / adverse effects
  • Bone Marrow Transplantation / methods*
  • Bone Marrow Transplantation / mortality
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Graft Survival
  • Hemoglobinopathies / mortality
  • Hemoglobinopathies / therapy
  • Humans
  • Male
  • Melphalan / administration & dosage
  • Myeloablative Agonists / therapeutic use*
  • Stem Cell Transplantation / adverse effects
  • Stem Cell Transplantation / methods*
  • Stem Cell Transplantation / mortality
  • Survival Analysis
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / methods*
  • Transplantation Conditioning / mortality
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives
  • Young Adult

Substances

  • Myeloablative Agonists
  • Alemtuzumab
  • Vidarabine
  • fludarabine
  • Melphalan