Decitabine in Combination with Donor Lymphocyte Infusion as Salvage Therapy for Relapsed AML Post-Allogeneic Stem Cell Transplantation

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Prognosis is extremely poor for AML patients who relapse after allogeneic stem cell transplantation. Donor Lymphocyte infusions (DLI) can be used to salvage these patients with complete response rates reported to be 10-15% with an associated 40-60% chance of developing clinically significant GVHD. The mechanism by which DLI results in clinical responses is thought to be a T-cell mediated process. Data suggest that DLI normalizes the T-cell receptor repertoire and expands the anti-leukemic cell population. Hypomethylating agents, which appear to foster the graft versus leukemia phenomenon, were combined with DLI in attempt to enhance the graft versus leukemia effect. We report ten AML patients who received Decitabine +/- Etoposide with incremental DLI as salvage after relapse from allogeneic stem cell transplantation during the years 2007-2010. These patients were between the ages of 26- 73 years. Six patients had de novo AML. Three patients were transformed from MDS, and one from essential thrombocythemia. Eight patients had reduced intensity conditioning regimens. Two patients received a fully ablative preparative regimen. Average time to progression post transplant was 17 months. Patients received Decitabine at 20mg/m2 for 5 - 10 days, some in combination with Etoposide for 3-5days for disease control. Patients received 1-4 courses of treatment approximately every 28 days with DLI between days 14-21. Two patients who progressed while receiving Decitabine/Etoposide received Clofarabine at 20-52mg/m2 for 5 days, with subsequent DLI. Cell dose ranged from 1.27 to 31.7 CD3+ cells / kg. Two patients received a mobilized DLI. Six out of ten patients regained full chimerism. One patient who relapsed with extra medullary disease never lost his graft. Seven out of ten patients achieved a complete remission. Only one patient developed Grade 2 GVHD of the skin. Overall survival in these patients after relapse from allogeneic transplantation was 10.8 months. The combination of Decitabine and DLI is a well tolerated outpatient therapeutic option for patients with relapsed AML post allogeneic stem cell transplantation. The majority of patients regained full chimerism and achieved complete remission with little or no GVHD.