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.

Conditioning regimens in allo-SCT for thalassemia major

“…29 However, the median age in the BU group was 7 years versus 9.6 years in the treosulfan group and the treosulfan group had 75% Class III patient of whom 52.4% were Class III HR as defined previously. In the BU arm 58% were Class III and the number that fulfilled the criteria of Class III HR is not available.…”

Hemopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000–2010

“…For example, patients' clinical conditions and transplantation events, such as causes of transplant-related mortality, were not detailed. Several experiences, such as those of North America and the FarEast, [14][15][16][17][18][19] were also not reported to the EBMT registry. However, the EBMT ProMISe regulations and the large number of cases reported guarantee the accuracy of the data presented.…”

Treosulfan-based conditioning regimens for allogeneic haematopoietic stem cell transplantation in children with non-malignant diseases

“…5,6,9,14,20,21 In this retrospective EBMT study, we evaluated the toxicity profile and outcome of 316 patients with non-malignant diseases undergoing HSCT, following treosulfan-based conditioning. To our knowledge, this is the largest such study to date.…”