Submitted March 6, 2008
Accepted July 5, 2008
Outcome of alloanergized haploidentical bone marrow transplantation after ex vivo costimulatory blockade: results of two phase I studies
Jeff K Davies, John G. Gribben, Lisa L Brennan, Dongin Yuk, Lee M Nadler, and Eva C. Guinan*
Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States
Medical Oncolgy, St Bartholomew's Hospital, London, United Kingdom
Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States
Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
Hematology/Oncology, Children's Hospital, Boston, Massachusetts, United States
* Corresponding author; email: eva_guinan{at}dfci.harvard.edu.
We report the outcome of 24 patients with high-risk hematological malignancies or bone marrow failure (BMF) who received haploidentical bone marrow transplantation (BMT) after ex vivo induction of alloantigen-specific anergy in donor T cells by allostimulation in the presence of co-stimulatory blockade. 95% of evaluable patients engrafted and achieved full donor chimerism. Despite receiving a median T cell dose of 29 x 106/kg, only 5 of 21 evaluable patients developed Grade C (n=4) or D (n=1) acute graft-versus-host disease (GvHD), with only one attributable death. Twelve patients died from treatment-related mortality (TRM). Patients reconstituted T cell subsets and immunoglobulin levels rapidly with evidence of in vivo expansion of pathogen-specific T cells in the early post-transplant period. Five patients reactivated CMV, only one requiring extended antiviral treatment. No deaths were attributable to CMV or other viral infections. Only one of 12 evaluable patients developed chronic GvHD. Eight patients survive disease-free with normal performance scores (median follow-up 7 years). Thus, despite significant early TRM, ex vivo alloanergization can support administration of large numbers of haploidentical donor T cells, resulting in rapid immune reconstitution with very few viral infections. Surviving patients have excellent performance status and a low rate of chronic GVHD.
