A two-step approach to myeloablative haploidentical stem cell transplantation: a phase I/II trial performed with optimized T-cell dosing

Dolores Grosso, Matthew Carabasi, Joanne Filicko-O'Hara, Margaret Kasner, John L. Wagner, Beth Colombe, Patricia Cornett Farley, William O'Hara, Phyllis Flomenberg, Maria Werner-Wasik, Janet Brunner, Bijoyesh Mookerjee, Terry Hyslop, Mark Weiss and Neal Flomenberg


Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have identified threshold doses of T cells below which severe graft-versus-host (GVHD) is usually absent. However, little is known regarding optimal T cell dosing as it relates to engraftment, immune reconstitution, and relapse. To begin to address this question, we developed a 2 step myeloablative approach to haploidentical HSCT in which 27 patients conditioned with total body irradiation (TBI) were given a fixed dose of donor T cells (HSCT step 1), followed by cyclophosphamide (CY) for T cell tolerization. A CD34 selected HSC product (HSCT step 2) was infused after CY. A dose of 2 x108/kg T cells resulted in consistent engraftment, immune reconstitution, and acceptable rates of GVHD. Cumulative incidences of grade III-IV GVHD, non-relapse mortality and relapse-related mortality were 7.4%, 22.2%, and 29.6% respectively. With a follow-up of 28-56 months, 3 year probability of overall survival for the whole cohort is 48% and 75% in patients without disease at HSCT. In the context of CY tolerization, a high, fixed dose of haploidentical T cells was associated with encouraging outcomes especially in good risk patients, and can serve as the basis for further exploration and optimization of this 2 step approach. This study is registered at as NCT00429143.

  • Submitted July 7, 2011.
  • Accepted August 17, 2011.