Use of a T cell-specific monoclonal antibody, T10B9, in a novel allogeneic stem cell transplantation protocol for hematologic malignancy high-risk patients
| Autor: | Suzanne Humphries, Stephen A. Brown, Claire Pomeroy, D. E. Reece, Gordon L. Phillips, Dianna S. Howard, Richard J. Kryscio, Gary vanZant, John S. Thompson, Rita Kramer |
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| Jazyk: | angličtina |
| Předmět: |
Adult
Male Melphalan medicine.medical_specialty T-Lymphocytes medicine.medical_treatment Graft vs Host Disease Gastroenterology Internal medicine Regimen-related toxicity medicine Humans Transplantation Homologous Treatment Failure Aged Chemotherapy Transplantation IL-6 Leukemia Anti-T cell monoclonal antibody MEDI-500 (T10B9) Acute graft-versus-host disease Cumulative dose business.industry Lymphoma Non-Hodgkin Stem cell transplantation Antibodies Monoclonal Hematology Middle Aged Survival Analysis Surgery Leukocyte Transfusion Treatment Outcome surgical procedures operative TNF-α Toxicity Female Stem cell business Immunosuppressive Agents Busulfan CD8 medicine.drug |
| Zdroj: | Biology of Blood and Marrow Transplantation. (12):858-866 |
| ISSN: | 1083-8791 |
| DOI: | 10.1016/j.bbmt.2004.09.006 |
| Popis: | To reduce the toxicity of traditional conditioning regimens for allogeneic stem cell transplantation (allo-SCT), we used single-agent chemotherapy conditioning with either busulfan (total cumulative dose, 16 mg/kg) or melphalan (200 to 240 mg/m2), followed by the anti-T cell-specific monoclonal antibody T10B9 (MEDI-500) daily for 3 days. T cell-replete SCT was performed from HLA-identical sibling donors. Acute graft-versus-host disease (aGVHD) prophylaxis consisted of 7 additional days of T10B9 and delayed onset of cyclosporine (ie, on day +4 or +5). Twenty-six high-risk hematologic malignancy patients were entered onto this study. All 24 patients who survived longer than 8 days engrafted, although 1 patient experienced late graft failure. Deaths occurred in 21 of 26 patients because of infection (n = 7), progression/recurrence of primary disease (n = 6), aGVHD (n = 4), regimen-related toxicity (n = 1), and other causes (n = 3). Five of these patients are enjoying disease-free survival with a median survival of 1193 days after allo-SCT. The conditioning regimen induced modulation of surface expression of CD3 (but not CD4 or CD8) and was associated with decreasing tumor necrosis factor-α (but not interleukin-6) serum levels. In conclusion, single-agent chemotherapy conditioning with T10B9 produced durable engraftment and long-term survival in some patients who would not have qualified for a traditional allo-SCT. |
| Databáze: | OpenAIRE |
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