Treosulfan-Based Myeloablative Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation Is Associated with Reduced Toxicity without Increased Risk of Relapse.

The goal of this study was to evaluate toxicity and efficacy of allogeneic hematopoietic cell transplantation (alloHCT) with Treosulfan (alkylyting agent, soluble Busulfan-derivative)-based conditioning as a preparative regimen. The outcome of 27 patients (CML-15, AML-9, ALL-1, SAA-2) given Treosulfan 3x14 g/m² + Fludarabine 5x30 mg/m² (n=15) or cyclofosfamide (CTX) 120 mg/kg (n=12) was compared with that of 146 patients treated with Busulfan 16 mg/kg + CTX 120 mg/kg between 2000–2004. In case of unrelated donor (URD)-HCT patients were additionally given anti-thymocyte globulin. GVHD prophylaxis consisted of cyclosporin A and short-course Methotrexate. The indications for alloHSCT were comparable for both subgroups. The patients age was 35(14–56)y and 30(14–55)y, the proportion of URD-HCT was 55% and 45%, peripheral blood was used as a source of stem cells in 33% and 11% of cases, and the proportion of patients with advanced disease (AML and ALL >CR1; CML > CP1) equaled 26% and 19%, respectively.

The cumulative incidence of non-relapse mortality at one year was 8% for the Treosulfan (EBV-LPD n=1, cerebral hemorrhage n=1) and 32% for the Busulfan group (p=0.11). Grade II-IV neutropenic infections occurred in 5% and 13% (p=NS) and grade II-IV mucositis in 9% and 61% of patients (p<0.001), respectively. Other serious adverse events were infrequent. Both subgroups did not differ in terms of time to neutrophil and platelet recovery, as well as for need of RBC and platelet transfusions. Median hospital stay since the date of alloHCT was shorter after Treosulfan- compared to Busulfan-based conditioning (31 (21–55) d. vs. 40.5 (21–153) d., p<0.001).

The overall survival and disease-free survival at one year equaled 92% vs. 67% (p=0.11), and 92% vs. 66% (p=0.09) for the Treosulfan group and the Busulfan group, respectively. None of the patients experienced hematologic relapse among Treosulfan- compared to 3% among Busulfan-treated alloHCT recipients. However, in two CML patients given Treosulfan-based regimen, the immunosuppression taper and interferon or imatinib therapy was neccessary to establish complete chimera. We conclude that Treosulfan + Fludarabine (or CTX) +/− ATG conditioning regimen is characterized by reduced toxicity resulting in shorter hospital stay and low transplat-related mortality. The pattern of hematopoietic recovery is similar to that of Busulfan + CTX indicating myeloablative character of the Treosulfan-based regimen. The risk of relapse is low and comparable for both kinds of treatment.