Treosulfan - Fludarabine as Ablative Conditioning Regimen for Patients with High Risk Hematologic Malignancies.

Allogeneic stem cell transplant (allo HSCT) is a potentially curative approach for patients with hematologic malignancies but it is associated with high treatment related morbidity and mortality. Because transplant related mortality increases with age, advanced disease, and unrelated donors, patients older than 50–55 years may be excluded from this procedure. Reduced intensity conditioning regimens showed a low success rate in long-term follow-up, so new ablative reduced toxicity regimens are of striking interest. The aim of this study was to evaluate toxicity and efficacy of the combination consisting of Treosulfan (Busulphan derivative water soluble alkylating agent) and Fludarabine as a preparative regimen for patients receiving HSCs from matched siblings or unrelated donors for advanced heavily pretreated hematologic malignancies.

From July 2005 to June 2006, 21 consecutive patients (10 males, 11 females) were enrolled.

Mean age was 45 years (range 17–65). Underlying diseases were: acute leukemia (6 ALL, 5 AML), 1 CML, 3 MM, 5 MDS, 1 hystiocytic sarcoma). All patients were heavily pretreated; only 8 of them were in CR at transplant.

Conditioning consisted of Treosulfan (12–14 gr/m2 for 3 days) in combination with Fludarabine (30 mg/m2 for 5 days).

Cyclosporine plus short MTX and anti-thymocyte globulin (Thymoglobulin) were used as GVHD prophylaxis. Eleven (11) patients received HSCs from an HLA identical sibling and 10 from a matched unrelated donor. Source of stem cells was bone marrow in 4 patients, and peripheral blood in 17.

Twenty (20) patients engrafted; mean time to neutrophil recovery >500 × 109/L was 14 (range 10–24) days, to platelets >20,000 × 109/L was 14 (range 10–21) days. One patient receiving bone marrow did not engraft and died with active disease. Two (2) patients experienced GI toxicity (grade 2), 5 patients had grade 1 liver toxicity and 1 patient grade 1 renal toxicity. Four (4) pts presented acute GVHD (2 grade I, 2 grade II).

Eleven (11) patients (52%) are alive in complete remission with a follow-up ranging from 30 to 270 days; 4 died for recurrent disease; 5 patients are alive with active disease. This preliminary report shows that Treosulfan-Fludarabine-ATG conditioning regimen is well tolerated and characterized by reduced toxicity in a cohort of high risk patients with advanced age, who should otherwise be excluded from any other conventional transplant procedure.