Haploidentical HCT using an αβ T-cell-depleted graft with targeted αβ(+) cells by add-back after a reduced intensity preparative regimen containing low-dose TBI

Bone Marrow Transplant. 2016 Sep;51(9):1217-22. doi: 10.1038/bmt.2016.114. Epub 2016 May 9.

Abstract

Between 2012 and 2015, 42 pediatric patients underwent haploidentical hematopoietic cell transplantation using an αβ(+) T-cell-depleted graft with targeted αβ cells at 1-5 × 10(5)/kg by add-back; 31 had hematologic malignancy (HM), 8 had non-malignant disease (NM) and 3 had solid tumors. All patients received uniform reduced-intensity conditioning with fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin and low-dose TBI. All 42 patients achieved neutrophil engraftment at a median of 10 days. The cumulative incidences (CIs) of ⩾grade II and ⩾grade III acute GvHD were 31±7.1% (SE) and 12±5.0%, respectively, and 1-year CI of chronic GvHD was 15±5.8%. One patient died of CMV pneumonia, leading to transplant-related mortality (TRM) of 2.6±2.5%. Sixteen patients relapsed and 11 died of disease. At a median follow-up of 19 months (range, 5-43 months), the estimated 2-year event-free survival for NM and HM were 88±11.7 and 50±10.1%, respectively. Our study demonstrated that haploidentical hematopoietic cell transplantation after ex vivo depletion of αβ(+) T cells with targeted dose noticeably reduced the graft failure rate and TRM in pediatric patients and could be applied to patients lacking a suitable related or unrelated donor.

MeSH terms

  • Adolescent
  • Antilymphocyte Serum / administration & dosage
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease / pathology
  • Hematologic Neoplasms / therapy*
  • Humans
  • Infant
  • Lymphocyte Depletion / methods*
  • Male
  • Neoplasms / therapy
  • Receptors, Antigen, T-Cell, alpha-beta
  • Survival Analysis
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation
  • Transplantation Conditioning / methods*
  • Transplantation, Haploidentical / adverse effects
  • Transplantation, Haploidentical / methods*
  • Transplantation, Haploidentical / mortality
  • Treatment Outcome
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives
  • Whole-Body Irradiation / methods
  • Young Adult

Substances

  • Antilymphocyte Serum
  • Receptors, Antigen, T-Cell, alpha-beta
  • Cyclophosphamide
  • Vidarabine
  • fludarabine