title: Treosulfan-thiotepa-fludarabine-based conditioning regimen for allogeneic transplantation in patients with thalassemia major: a single-center experience from north India.
abstract: Hematopoietic stem cell transplantation (HSCT) is the definite treatment for patients with thalassemia major. A busulfan (Bu) and cyclophosphamide (Cy)-based regimen has been the standard myeloablative chemotherapy, but it is associated with higher treatment-related toxicity, particularly in patients classified as high risk by the Pesaro criteria. Treosulfan-based conditioning regimens have been found to be equally effective and less toxic. Consequently, we analyzed the safety and efficacy of treosulfan/thiotepa/fludarabine (treo/thio/flu)-based conditioning regimens for allogeneic HSCT in patients with thalassemia major between February 2010 and September 2012. We compared those results retrospectively with results in patients who underwent previous HSCT with a Bu/Cy/antithymocyte globulin (ATG)-based conditioning regimen. A treo/thio/flu-based conditioning regimen was used in 28 consecutive patients with thalassemia major. The median patient age was 9.7 years (range, 2-18 years), and the mean CD34(+) stem cell dose was 6.18 × 10(6)/kg. Neutrophil and platelet engraftment occurred at a median of 15 days (range, 12-23 days) and 21 days (range, 14-34 days), respectively. Three patients developed veno-occlusive disease, 4 patients developed acute graft-versus-host disease (GVHD), and 2 patients had chronic GVHD. Treatment-related mortality (TRM) was 21.4%. Two patients experienced secondary graft rejection. We compared these results with results in patients who underwent previous HSCT using a Bu/Cy/ATG-based conditioning regimen. Twelve patients were treated with this protocol, at a median age of 7.2 years (range, 2-11 years). One patient had moderate veno-occlusive disease, 2 patients developed acute GVHD, 2 patients had chronic GVHD, and 2 patients experienced graft rejection. There was no TRM in this group. We found no significant differences between the 2 groups (treo/thio/flu vs Bu/Cy/ATG) in terms of the incidence of acute GVHD, chronic GVHD, TRM, and graft failure, although a trend toward higher TRM was seen with the treo/thio/flu regimen.
authors.affiliation: Department of Hemato-Oncology and Bone Marrow Transplantation, Bone Marrow Transplant Centre, BLK Superspeciality Hospital, New Delhi, India. drdharma@hotmail.com
authors.forename: Dharma
authors.initials: D
authors.lastname: Choudhary
authors.forename: Sanjeev Kumar
authors.initials: SK
authors.lastname: Sharma
authors.forename: Nitin
authors.initials: N
authors.lastname: Gupta
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kharya
authors.forename: Punita
authors.initials: P
authors.lastname: Pavecha
authors.forename: Anil
authors.initials: A
authors.lastname: Handoo
authors.forename: Rasika
authors.initials: R
authors.lastname: Setia
authors.forename: Satyendra
authors.initials: S
authors.lastname: Katewa
mesh_terms: D000293:Adolescent; D002066:Busulfan / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007194:India; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D012189:Retrospective Studies; D016019:Survival Analysis; D013852:Thiotepa / Q000627:therapeutic use*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017086:beta-Thalassemia / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*
chemical_list: D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D016572:Cyclosporine; D013852:Thiotepa; C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine