Nonmyeloablative haploidentical stem-cell transplantation using anti-CD2 monoclonal antibody (MEDI-507)-based conditioning for refractory hematologic malignancies.
We initiated a clinical trial of nonmyeloablative haploidentical stem-cell transplantation (SCT) using MEDI-507, an immunoglobulin-G1 monoclonal anti-CD2 antibody. The trial was based on a preclinical major histocompatibility complex-mismatched bone marrow transplant model in which graft-versus-host disease (GVHD) was prevented and mixed chimerism as a platform for adoptive cellular immunotherapy was reliably induced. Twelve patients (three cohorts of four patients each) received cyclophosphamide, MEDI-507, and haploidentical unmanipulated bone marrow (n=8) or ex vivo T-cell-depleted peripheral blood stem cells (n=4) for chemorefractory hematologic malignancy. A two-dose regimen and schedule modifications of MEDI-507 were undertaken because of graft loss in the first cohort of four patients and GVHD in the second cohort. With ex vivo T-cell-depleted peripheral blood SCT, mixed chimerism occurred in all four patients without GVHD. Two patients, however, subsequently lost their grafts. Nonmyeloablative preparative therapy with MEDI-507 and haploidentical SCT have led to the reliable induction of at least transient mixed chimerism as a potential platform for adoptive cellular immunotherapy.
Spitzer
Thomas R
TR
Bone Marrow Transplantation Program/Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114-1126, USA.
McAfee
Steven L
SL
Dey
Bimalangshu R
BR
Colby
Christine
C
Hope
James
J
Grossberg
Howard
H
Preffer
Frederic
F
Shaffer
Juanita
J
Alexander
Stephen I
SI
Sachs
David H
DH
Sykes
Megan
M
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001853:Bone Marrow / Q000502:physiology; D016026:Bone Marrow Transplantation; D018801:CD2 Antigens / Q000276:immunology*; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000627:therapeutic use; D004334:Drug Administration Schedule; D006084:Graft Rejection / Q000453:epidemiology; D006238:Haploidy; D019337:Hematologic Neoplasms / Q000601:surgery*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D008875:Middle Aged; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*
D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide