Decitabine with allogeneic peripheral blood stem cell transplantation in the therapy of leukemia relapse following a prior transplant: results of a phase I study

Relapse after allogeneic progenitor cell transplant is associated with a po or prognosis for patients with advanced leukemia, with few curative options available. Use of novel chemotherapeutic agents with limited toxicity is w arranted. We investigated the role of decitabine, a pyrimidine analogue wit h significant anti-leukemic effect and limited toxicity, in this setting. F ourteen patients with advanced acute leukemia or transformed chronic myelog enous leukemia (CML) who had failed previous allogeneic transplant were tre ated. Decitabine at doses of 100 mg/m(2) to 150 mg/m(2) given every 12 h fo r 5 days was followed hy infusion of stem cells from the original donor 2 t o 5 days after the completion of chemotherapy, Dose of decitabine was escal ated in cohorts of three patients based on the modified Fibonacci scheme. T he primary study end-point was assessment of the toxicity of the regimen wi th secondary endpoints of response and survival. Eight patients responded w ith either a complete remission or partial hematological remission (absence of blasts in peripheral blood and bone marrow but with platelet count <100 x 10(9)/l), Toxicity was limited with no grade 3 or 4 toxicity directly at tributable to the treatment. The median survival for all patients was 190 d ays (range 11o 1215+ days). Decitabine at doses of 100 mg/m(2) to 150 mg/m( 2) given every 12 h for 5 days, followed by stem cell infusion from the ori ginal donor was well tolerated, and was associated with acceptable myelosup pression, Current response data should encourage further study of this drug , either alone or in combination with other agents, for treatment of relaps ed acute leukemia after an allogeneic transplant.