Purpose: Therapeutic options for patients with high-risk myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) who relapse after allogeneic stem cell transplantation (SCT) are limited and prognosis is dismal. If applicable, transfusion of donor lymphocytes (DLI) with or without chemotherapy is the current standard therapy. But, in contrast to chronic myelogenous leukemia (CML), response rates after sole DLI in patients with relapsing MDS or AML after allogeneic SCT are poor. Addition of chemotherapy, usually low-dose cytarabine 100mg/m2 as continuous infusion for 7 days, can increase response rates only marginally. Also important, duration of response is short and long term survival even rare. The demethylating agent 5-aza-2′-deoxycytidine (5-Aza) has been shown to be effective in the treatment of MDS and AML. In addition to a direct cytotoxic effect, treatment with this demethylating drug also results in a rapid and stable transcription and cell surface expression of formerly unexpressed killer Ig-like receptors (KIRs) in natural killer cells (NK cells), thereby possibly enhancing the GvL effect of DLI.

Patients & treatment: In an intent-to-treat approach we treated 6 patients with high risk MDS or AML who relapsed after allogeneic SCT with 5-Aza plus DLI. Patients’ median age was 47.5 years (range 32–71 years). Before allogeneic SCT 4 patients had active disease, and 2 were in complete remission (CR). Two had family donors, 4 had unrelated donors. Median time for relapse after SCT was day +99 (range day +84 to day +300). Once relapse was diagnosed patients received 100mg/m2 5-Aza for five days via subcutaneous injection in two to four weeks intervals. If practical, patients received 1×106 CD3+ cells/kg bodyweight following the first course of 5-Aza, and in the absence of graft-versus host disease, this was followed by additional 5×106 CD3+ cells/kg bodyweight after 3 months.

Results: Five out of 6 patients responded to treatment with 5-Aza and DLI. Three patients achieved a complete remission (CR), two a partial remission (PR) and one patient died early due to progressive disease. Two patients developed extensive graft-versus host disease (GvHD), while, so far, four patients did not show any signs of GvHD. Side effects were manageable and limited to the hematopoietic system.

Of the three patients achieving CR, two patients relapsed again at extramedullary sites (heart and CNS). Two of these three patients achieving initial CR are alive, one in CR, one in PR, while one patient died due to CNS disease. One of the patients achieving a PR died due to progressive disease, and the other died after a second allogeneic SCT with progressive disease. Median survival of all patients was 125 days (range 39–397 days).

Conclusion: Overall, induction of CR after treatment with 5-Aza, and consolidation of CR via DLI followed the 5-Aza treatment is promising.

Disclosures: Novel therapeutic approach for patients with relapse MDS and AML after allogeneic SCT with the demethylating agent Vidaza plus DLI. Nothing to disclose.

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