Abstract
Decitabine is approved for the treatment of patients with intermediate- and high-risk myelodysplastic syndrome (MDS). In vitro studies have demonstrated an increased expression of MHC class I molecules, HLA-DR and beta-2-microglobulin on the surface of MDS cells after decitabine therapy, potentially increasing their susceptibility to immune surveillance mechanisms and a graft-versus-leukemia effect. We analyzed the outcome of 12 patients with MDS with a median age of 58.5 years (range, 37 – 66) who underwent an allogeneic stem cell transplant (5 sibling, 5 unrelated, 2 cord blood) after prior therapy with decitabine. At diagnosis, 2 patients had intermediate-1, 7 intermediate-2 and 3 high risk MDS by the international prognostic scoring system. Nine had a non-myeloablative and 3 an ablative regimen. The source of stem cells was marrow in 2, peripheral blood in 8 and cord blood in 2. The patients had received decitabine for a median of 5.5 cycles (range, 1 – 20) and a median duration of treatment of 7.1 months (range, 1 – 27). Decitabine was well tolerated with reversible gastrointestinal toxicity and neutropenic infections as the main toxicity. Best response to decitabine was CR in 4 patients, PR in 6, and hematological improvement in 2. Eight had disease progression on decitabine. Five patients received additional chemotherapy and achieved a CR before transplant. The median time between completion of decitabine and transplant was 3.4 months (range, 0.2 – 11.7). At the time of transplant, 8 patients were in CR and 4 in PR. The median CD34+ cell number was 4.17 x 106 cells/kg (range, 0.58 – 10.1 x 106 cells/kg). Eleven patients engrafted and one had secondary engraftment failure. Median times to neutrophil and platelet engraftment were 13.7 days (range, 7 – 27) and 17.3 days (range, 7 – 28), respectively. No unusual toxicity was encountered. Nine patients (75%) developed acute GVHD, and 6 chronic GVHD (55% of those alive beyond 100 days). Ten patients were in CR and 1 in PR at day 100 post transplant. With a median follow 11.5 months (range, 3 – 26), 9 patients are alive (8 in CR and 1 with progressive disease) and 3 have died (2 after relapse and 1 from GVHD and sepsis). We conclude that prior therapy with hypomethylating agents may potentially improve the outcome of allogeneic transplant in MDS through enhancement of graft versus leukemia effect and should be examined prospectively.
Generation of multi-leukemia antigen-specific T cells to enhance the graft-versus-leukemia effect after allogeneic stem cell transplant
