Selective depletion of bone marrow T lymphocytes with anti-CD5 monoclonal antibodies: effective prophylaxis for graft-versus-host disease in patients with hematologic malignancies
| Autor: | J H, Antin, B E, Bierer, B R, Smith, J, Ferrara, E C, Guinan, C, Sieff, D E, Golan, R M, Macklis, N J, Tarbell, E, Lynch |
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| Rok vydání: | 1991 |
| Předmět: |
Adult
Male Leukemia Adolescent T-Lymphocytes Bone Marrow Purging Graft Survival Immunology Antibodies Monoclonal Graft vs Host Disease Bone Marrow Cells chemical and pharmacologic phenomena Cell Biology Hematology Middle Aged CD5 Antigens Biochemistry Lymphocyte Depletion Lymphoproliferative Disorders Antigens CD Humans Female Aged |
| Zdroj: | Blood. 78:2139-2149 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v78.8.2139.bloodjournal7882139 |
| Popis: | Seventy-one patients with hematologic malignancies received bone marrow from a histocompatible sibling (n = 48) or a partially matched relative (n = 23) that had been depleted of CD5+ T cells with either an anti-CD5 mooclonal antibody (MoAb) plus complement (anti-Leu1 + C) or an anti- CD5 MoAb conjugated to ricin A chain (ST1 immunotoxin [ST1-IT]). These patients received intensive chemoradiotherapy consisting of cytosine arabinoside, cyclophosphamide, and fractionated total body irradiation. Both anti-Leu1 + C and ST1-IT ex vivo treatments effectively depleted bone marrow of T cells (97% and 95%, respectively). Overall, primary and late graft failure each occurred in 4% of evaluable patients. The diagnosis of myelodysplasia was a significant risk factor for graft failure (P less than .001), and if myelodysplastic patients were excluded, there were no graft failures in major histocompatibility complex (MHC)-matched patients and 2 of 23 (8.7%) in MHC-mismatched patients. The actuarial risk of grade 2 to 4 acute graft-versus-host disease (GVHD) was 23% in MHC-matched patients and 50% in MHC- mismatched patients. In MHC-matched patients, acute GVHD tended to be mild and treatable with corticosteroids. Chronic GVHD was observed in 6 of 36 (17%) MHC-matched patients and none of 11 MHC-mismatched patients. There were no deaths attributable to GVHD in the MHC-matched group. Epstein-Barr virus-associated lymphoproliferative disorders were observed in 3 of 23 MHC-mismatched patients. The actuarial event-free survival was 38% in the MHC-matched patients versus 21% in the MHC- mismatched patients. However, if outcome is analyzed by risk of relapse, low-risk patients had a 62% actuarial survival compared with 11% in high-risk patients. These data indicate that the use of anti-CD5 MoAbs can effectively control GVHD in histocompatible patients, and that additional strategies are required in MHC-mismatched and high-risk patients. |
| Databáze: | OpenAIRE |
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