5-Azacytidine and DLI can induce long-term remissions in AML patients relapsed after allograft

Abstract

DNA-hypomethylating agents are a viable treatment option for AML/myelodysplastic syndrome (MDS) relapse after allograft by upregulating Ags on blasts before DLI. Seventy-two patients with relapsed AML (n = 62), MDS (n = 8) and other myeloid neoplasms (n = 2) after allograft were treated with low-dose 5-azacytidine and, if feasible, DLI. Patient characteristics: median age 62 years (range 20-75), 42% with adverse cytogenetics, 82% not in remission at transplant and 83% received fludarabine-based reducedtoxicity conditioning. Median duration from transplant to 5-azacytidine was 289 days (range 59-2133). Response criteria: CR, temporary disease control or treatment failure. A median of 2.7 courses (range 1-10) were administered; 65 out of 72 patients also received DLI (41 already before 5-azacytidine). Ten patients developed acute GVHD and two succumbed to treatment-related sepsis. CR rate was 9.7% (in two patients lasting 45 years), 44% had temporary disease control (median duration 71 days, range 31-380). Median survival from 5-azacytidine was 108 days, 21 patients proceeded to subsequent transplant. In multivariate analysis, peripheral blood blasts o 1% were predictive of longer OS (P = 0.03). Taken together, long-term remissions can be induced by this well-tolerated outpatient treatment, particularly in patients without peripheral blood blasts.

Long-term follow-up of therapy-related myelodysplasia and AML patients treated with allogeneic hematopoietic cell transplantation

“…Newer relapse concepts implement hypomethylating agents such as 5-azacytidine before DLI infusion, resulting in promising long-term remission rates in a subset of patients. 17 However, preventing the occurrence of relapse should be the primary goal of future concepts. In this regard, several groups are investigating the role of 5-azacytidine as part of a maintenance treatment after allogeneic hematopoietic cell transplantation in high-risk AML patients as demethylating agents have been shown to increase the GvL effect while reducing GvHD.…”

Hypomethylating agents for treatment and prevention of relapse after allogeneic blood stem cell transplantation

“…Table 1 summarizes the publications regarding the use of Aza as salvage treatment for relapse after allo-SCT: until now a total of 601 patients with AML, MDS and other related myeloid malignancies have been published with varying schedules and dosages of Aza. These included 3 prospective, non-randomized trials and the majority of patients reported retrospectively [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. Furthermore, Aza was the first treatment of relapse and combined with DLI in some of these patients, while other patients had previously received other salvage therapies or did not receive DLI.…”

Prophylactic donor lymphocyte infusion in patients with high-risk acute myeloid leukemia: ready for prime time?

“…8 Donor lymphocyte infusion (DLI) can result in prolonged CR but only in a minority of patients with low-disease burden. 9 Similarly, an association of DLI and azacitidine induces only a few persistent CR, 10 whereas a second allo-HCT (in a group of highly selected patients) results in a 2-year OS rate of 20%. 11,12 Given the poor prognosis of patients who experience relapse after allo-HCT, several groups of investigators have assessed various post-transplant approaches aimed at preventing disease relapse in high-risk AML patients (Table 1).…”