STUDIES OF DECITABINE WITH ALLOGENEIC PROGENITOR-CELL TRANSPLANTATION

The aim was to determine the efficacy and safety of decitabine in the settings of relapse post-allogeneic progenitor cell transplantation or as part of the conditioning regimen. Three patients (two AML, one ALL ) received single agent decitabine 1000 mg/m(2) total dose) for treatm ent of relapse post-transplant (group 1). Median age was 32 years. Med ian time to relapse was 7 months. In another study four patients (thre e CML in an accelerated phase, one AMML) received decitabine 400 mg/m( 2), with busulfan 12 mg/kg and cyclophosphamide 100 mg/kg as condition ing for allogeneic stem cell transplantation (group 2). Median age was 42 years; median time to transplant was 5 months. All patients receiv ed at least 4 x 10(6) CD34(+) cells from their HLA compatible donors. All patients in group 1 achieved complete remissions after decitabine therapy. The median time to neutrophil and platelet recovery were 24 a nd 23 days, respectively. Two patients required reinfusion of donor ce lls because of delayed engraftment. One patient remains alive and in r emission 160 days post-decitabine therapy. Two patients in group 2 eng rafted on days 23 and 25. Two patients required reinfusion of stem cel ls because of lack of neutrophil recovery by day 21. Two patients achi eved complete cytogenetic and hematologic remission. Three patients ar e alive at 167, 129, and 109 days post-transplant, One patient died of progressive Pseudomonas cellulitis 54 days post-initial infusion. Dec itabine therapy is well tolerated in the setting of allogeneic stem ce ll transplantation, initial results in patients relapsing after transp lant are encouraging and warrant further studies. The causes of delaye d engraftment after single agent or combination therapy need to be bet ter explored, The existence of active metabolites of decitabine which may still be present in the blood at the time of stem cell infusions, and/or insufficient immunosuppression of the preparative regimen aree being explored as possible explanations for this phenomenon.