Nonmyeloablative haploidentical stem-cell transplantation using anti-CD2 monoclonal antibody (MEDI-507)-based conditioning for refractory hematologic malignancies
| Autor: | Juanita Shaffer, Megan Sykes, David H. Sachs, Steven L. McAfee, Howard Grossberg, Bimalangshu R. Dey, Thomas R. Spitzer, Stephen I. Alexander, J Hope, Christine Colby, Frederic I. Preffer |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
Graft Rejection Transplantation Conditioning Cyclophosphamide medicine.medical_treatment CD2 Antigens Transplantation Chimera Haploidy Drug Administration Schedule Cohort Studies Bone Marrow medicine Humans Bone Marrow Transplantation Transplantation business.industry Incidence Stem Cells Antibodies Monoclonal Immunotherapy Middle Aged surgical procedures operative medicine.anatomical_structure Hematologic Neoplasms Immunology Monoclonal Bone marrow Stem cell business Immunosuppressive Agents Ex vivo Stem Cell Transplantation medicine.drug |
| Zdroj: | Transplantation. 75:1748-1751 |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/01.tp.0000064211.23536.ad |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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