Anti-thymocyte globulin overcomes the negative impact of HLA mismatching in transplantation from unrelated donors

• Published in: Experimental hematology 2008-08, Vol.36 (8), p.1047-1054
• Main Authors: Ayuk, Francis, Diyachenko, Galina, Zabelina, Tatjana, Panse, Jens, Wolschke, Christine, Eiermann, Thomas, Binder, Thomas, Fehse, Boris, Erttmann, Rudolf, Kabisch, Hartmut, Bacher, Ulrike, Kröger, Nicolaus, Zander, Axel R
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Advanced Basic Science; Antilymphocyte Serum - therapeutic use; Child; Child, Preschool; Cyclosporine - therapeutic use; Disease-Free Survival; Female; Follow-Up Studies; Graft vs Host Disease - prevention & control; Hematology, Oncology and Palliative Medicine; Hematopoietic Stem Cell Transplantation - methods; Histocompatibility Testing; Humans; Immunosuppressive Agents - therapeutic use; Infant; Leukemia - therapy; Male; Methotrexate - therapeutic use; Middle Aged; Myelodysplastic Syndromes - therapy; Survival Rate; Transplantation Conditioning - methods
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2008.03.011

Objective About one third of patients requiring allogeneic hematopoetic stem cell transplantation (HSCT) would not find a matched sibling or alternative donor. Allogeneic HSCT from matched unrelated and mismatched donors carries an increased risk of graft-vs-host disease (GVHD) and transplant-related mortality (TRM). Materials and Methods We used anti-thymocyte globulin (ATG-Fresenius) at a median dose of 90 mg/kg body weight as part of a total body irradiation or busulfan-based conditioning regimen for prevention of serious GVHD. All patients received cyclosporine A and short-course methotrexate. We compared outcomes of 65 recipients of human leukocyte antigen (HLA)–mismatched unrelated grafts and 194 recipients of HLA-matched unrelated grafts. Mismatches involved one or two loci. Both groups were comparable in age, graft source, diagnosis, stage of disease, and conditioning regimen, and differed only in dose of ATG administered. Results For matched and mismatched transplants, respectively, there was no significant difference in graft failure (0.5% vs 3%; p = 0.16), in the cumulative incidence of grade II to IV acute GVHD (45% vs 35%; p = 0.14) and no difference in overall chronic GVHD (42% vs 40%; p = 0.68). Estimated overall survival (OS) and disease-free survival (DFS) at 5 years were 55% vs 50% ( p = 0.99) and 47% vs 47% ( p = 1.0), respectively. The cumulative incidence of relapse and TRM at 5 years were 24% vs 25% ( p = 0.63), and 29% vs 27% ( p = 0.59), respectively. Conclusion Inclusion of ATG-Fresenius in the conditioning regimen permits HSCT from mismatched unrelated donors without excess TRM and GVHD, resulting in identical OS and DFS of recipients of HLA-matched and HLA-mismatched grafts.