A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing.

Dolores Grosso, Thomas Jefferson University
Matthew Carabasi, Thomas Jefferson University
Joanne Filicko-O'Hara, Thomas Jefferson University
Margaret Kasner, Thomas Jefferson University
John L Wagner, Thomas Jefferson University
Beth Colombe, Thomas Jefferson University
Patricia Cornett Farley, Thomas Jefferson University
William O'Hara, Thomas Jefferson University
Phyllis Flomenberg, Thomas Jefferson University
Maria Werner-Wasik, Thomas Jefferson University
Janet Brunner, Center for International Blood and Marrow Transplant Research (CIBMTR), Milwaukee, WI
Bijoyesh Mookerjee, Thomas Jefferson University
Terry Hyslop, Thomas Jefferson University
Mark Weiss, Thomas Jefferson University
Neal Flomenberg, Thomas Jefferson University

Document Type Article

This article has been peer reviewed. It is the authors' final version prior to publication in Blood.

Volume 118, Issue 7, October 2011, Pages 4732-4739.

The published version is available at DOI: 10.1182/blood-2011-07-365338. Copyright © American Society of Hematology


Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have identified threshold doses of T cells below which severe 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 × 10(8)/kg of T cells resulted in consistent engraftment, immune reconstitution, and acceptable rates of GVHD. Cumulative incidences of grade III-IV GVHD, nonrelapse mortality (NRM), and relapse-related mortality were 7.4%, 22.2%, and 29.6%, respectively. With a follow-up of 28-56 months, the 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 www.clinicaltrials.gov as NCT00429143.