title: In stem cell transplantation, by limiting the morbidity of graft-versus-host disease tolerance to myeloablative conditioning is improved.
abstract: Myeloablative conditioning followed by T-cell depletion of grafts and reduced intensity conditioning (RIC) has both been shown to decrease treatment related mortality (TRM). However in RIC the incidence of graft vs. host disease (GvHD) is high and patients with aggressive diseases tend to relapse. Following myeloablative conditioning, patients with chemotherapy-responsive hematological malignancies underwent transplantation from HLA identical siblings. GvHD prophylaxis was by ex viva T-cell depletion with alemtuzumab. The outcome of these patients was analysed. At transplantation, the median age of 81 consecutive individuals was 45 years (range 15-60). GvHD was seen in 10% and was commonly associated with infections resulting in one and 3 year TRM of 15 and 20.5%. Fifteen patients relapsed, 10 who had myeloproliferative syndromes or lymphoma and two with myeloma responded to DLI. For the whole group, median follow up is 777 (range 7-2702) days and 73% remain disease free. Cox regression analysis for survival showed that only occurrence of GvHD was a significant adverse factor. Age order than median was not associated with worse outcome. By reducing the incidence and severity of GvHD, T-cell depletion of grafts leads to greater tolerance to myeloablative chemotherapy, resulting in acceptable TRM. This strategy should be compared with the RIC approaches.
authors.affiliation: Division of Haematology, University of Cape Town and Grotte Schuur Hospital, Cape Town, 7925 South Africa.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Novitzky
authors.forename: Valda
authors.initials: V
authors.lastname: Thomas
authors.forename: Cecile
authors.initials: C
authors.lastname: du Toit
authors.forename: Andrew
authors.initials: A
authors.lastname: Mcdonald
mesh_terms: D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D019072:Antibiotic Prophylaxis; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000494:pharmacology / Q000627:therapeutic use; D002066:Busulfan / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000601:surgery*; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D019653:Myeloablative Agonists / Q000009:adverse effects*; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000601:surgery; D009196:Myeloproliferative Disorders / Q000276:immunology / Q000601:surgery; D036102:Peripheral Blood Stem Cell Transplantation; D011446:Prospective Studies; D012306:Risk; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D019653:Myeloablative Agonists; D000074323:Alemtuzumab; D003520:Cyclophosphamide; D002066:Busulfan; D008558:Melphalan