Haploidentical stem cell transplantation augmented by CD45RA negative lymphocytes provides rapid engraftment and excellent tolerability

Pediatr Blood Cancer. 2015 Apr;62(4):666-73. doi: 10.1002/pbc.25352. Epub 2015 Jan 5.

Abstract

Background: Haploidentical donors are being increasingly used for allogeneic hematopoietic cell transplantation (HCT). However, the requisite T-cell depletion results in a profound and often long-lasting immunocompromised state, and donor lymphocyte infusions bring a risk of graft-versus-host disease (GVHD). Naïve T-cells are believed to be among the most alloreactive T-cell subset and can be identified by CD45RA expression. Allogeneic HCT using CD45RA depletion has not been previously described for haploidentical donors.

Procedure: Eight children with relapsed or refractory solid tumors were transplanted following myeloablative conditioning. Each patient received two cell products, one created by CD3 depletion and the other through CD45RA depletion.

Results: Median CD34 recovery was 59.2% with CD45RA depletion, compared to 82.4% using CD3 depletion. Median CD3+ T-cell dose after CD45RA reduction was 99.2 × 10(6) cells/kg, yet depletion of CD3+ CD45RA+ cells exceeded 4.5 log. CD45RA depletion also resulted in substantial depletion of B-cells (median 2.45 log). All eight patients engrafted within 14 days and rapidly achieved 100% donor chimerism. No acute GVHD or secondary graft failure was observed.

Conclusions: CD45RA depletion is a novel approach to haploidentical HCT that offers rapid engraftment with minimal risk of GVHD.

Keywords: NK cells BMT; graft versus host disease; immunotherapy; stem cell transplantation.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Allografts
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Child
  • Child, Preschool
  • Graft Survival*
  • Graft vs Host Disease / metabolism
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Leukocyte Common Antigens*
  • Lymphocyte Depletion / methods*
  • Male
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • Unrelated Donors

Substances

  • Leukocyte Common Antigens