Outcome of alloanergized haploidentical bone marrow transplantation after ex vivo costimulatory blockade: results of 2 phase 1 studies.
We report the outcomes of 24 patients with high-risk hematologic 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 costimulatory blockade. Ninety-five percent of evaluable patients engrafted and achieved full donor chimerism. Despite receiving a median T-cell dose of 29 x10(6)/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 posttransplantation period. Five patients reactivated cytomegalovirus (CMV), only one of whom required extended antiviral treatment. No deaths were attributable to CMV or other viral infections. Only 1 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.
Davies
Jeff K
JK
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Gribben
John G
JG
Brennan
Lisa L
LL
Yuk
Dongin
D
Nadler
Lee M
LM
Guinan
Eva C
EC
D000293:Adolescent; D000328:Adult; D001855:Bone Marrow Diseases / Q000150:complications / Q000628:therapy; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D017635:Clonal Anergy / Q000276:immunology*; D003586:Cytomegalovirus Infections; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D006801:Humans; D007223:Infant; D007519:Isoantigens; D017710:Lymphocyte Transfusion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*; D018183:Transplantation Chimera; D016896:Treatment Outcome
D007519:Isoantigens