Treosulfan/Fludarabine - a Low Toxicity but Myeloablative Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation in Chronic Myeloid Leukemia.

Although allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only treatment of proved long-term efficacy in chronic myeloid leukemia (CML), high procedure-related toxicity observed after oral busulfan- or TBI-based conditioning limits its applicability and deteriorates outcome.

In a series of 13 CML patients (age 35, range 16–52 years) we introduced a novel myeloablative conditioning regimen consisting of Treosulfan (alkylyting agent, soluble Busulfan-derivative) 14 g/m2/d. on days −6, −5, −4, Fludarabine 30 mg/m2/d on days −5, −4, −3, −2, −1, and, in case of unrelated donor transplants (URD-HSCT), anti-thymocyte globulin (Thymoglobulin) at a total dose of 6 mg/kg. Twelve patients were in the 1^st chronic phase, one - in 2^nd chronic phase. Median disease prior to alloHSCT equaled 10 (6–90) months. 8 patients were given transplant from an unrelated donor, 5 - from HLA identical sibling. GVHD prophylaxis consisted of cyclosporin A and short-course Methotrexate.

All patients engrafted after a period of absolute agranulocytosis. Median time to neutrophil recovery >0.5 G/L was 24 (13–42) days, and to PLT >50 G/L - 21 (13–38) days. 1/13 patient experienced grade 3 mucositis; no severe neutropenic infection nor hepatic toxicity was observed. None of the patients developed grade III–IV acute GVHD, 1/13 patient experienced grade II acute GVHD. One patient died of EBV-related lymphoproliferative disease; the cumulative incidence of transplant-related mortality at 1 year equaled 8% (1/13).

11/13 patients achieved complete molecular remission and complete donor chimerism within 100 days after alloHSCT. The remaining two patients required immunosuppression taper and additional interferone treatment. The probability of current disease-free survival at one year equaled 92%. We conclude that Treosulfan/Fludarabine +/− ATG myeloablative conditioning is characterized by reduced toxicity and low incidence of acute GVHD. This together with high anti-leukemic efficacy makes the regimen feasible in CML patients.