Work

278: Treosulfan Plus Fludarabine for Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients with Acute Leukemia and Myelodysplastic Syndrome

Year: 2008

Type: article

Abstract: Myeloablative regimens followed by allogeneic HCT are effective in eradicating leukemia, but are associated with a moderately high risk for regimen-related toxicity (RRT) and transplant-related mortality (TRM). Nonmyeloablative and reduced intensity regimens, variably defined, have been used with resulting decreased RRT and NRM, but also higher rates of relapse compared to myeloablative regimens. Thus, there is a need to explore alternative regimens with sufficient intensity to mediate anti-leukemic activity without increasing RRT or TRM. The objective of this ongoing study was to determine the optimum dose of a new agent, treosulfan, in combination with fludarabine prior to allogeneic HCT in patients with acute myeloid (AML) or lymphoblastic leukemia (ALL) or myelodysplastic syndrome (MDS). “Optimal” dose was determined by safety and efficacy, as defined by incidence of severe/fatal RRT, graft failure and TRM. Thirty-six patients (8 children and 28 adults ≥ 18 years), with a median of 41 (5–58) years, and diagnosed with AML in first (n = 19), second remission (n = 7) or not in remission (n = 4), ALL in second remission (n = 2) or MDS (n = 4) have been treated. Patients were considered to be at high risk for TRM because of aggressive therapy for a prior malignancy, comorbid conditions or previous HCT. Patients received treosulfan at 12 (n = 5) or 14 g/m2/day (n = 31) on days -6 to -4, and fludarabine (30 mg/kg/day) on days -6 to -2. GVHD prophylaxis was with tacrolimus and methotrexate (n = 35) or cyclosporine and methotrexate (n = 1). Donors were HLA-matched siblings (n = 19) or unrelated volunteers (n = 17); source of stem cells were bone marrow (n = 7) or filgrastim-mobilized peripheral blood cells (n = 29). Neutrophil engraftment occurred at a median of 18 (11–30) days. Grade II-IV acute graft-versus-host disease (GVHD) was observed in 9 of 36 patients, and chronic GVHD in 8 of 23 evaluable patients surviving beyond post-transplant day 80. Dose-limiting RRT was observed in 1 of 36 patients (mucositis requiring intubation). With a median follow-up of 118 (20–575) days, estimated one-year overall and disease-free survival, relapse and TRM are 83%, 78%, 22% and 0%, respectively. Day-100 mortality is 6%. Treosulfan/fludarabine is a well-tolerated regimen with promising disease control and low rates of RRT and TRM in patients with acute leukemia and MDS. Further studies are warranted to evaluate the efficacy of this regimen.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2007.12.288