Azacitidine and donor lymphocyte infusions as first salvage therapy for relapse of AML or MDS after allogeneic stem cell transplantation

Abstract

The combination of azacitidine and donor lymphocyte infusions (DLI) as first salvage therapy for relapse after allogeneic transplantation (allo-HSCT) was studied in 30 patients with acute myeloid leukemia (AML; n=28) or myelodysplastic syndromes (MDS; n=2) within a prospective single-arm multicenter phase-II trial. Treatment schedule contained up to eight cycles azacitidine (100 mg/m(2)/day, days 1-5, every 28 days) followed by DLI (from 1-5 × 10(6) to 1-5 × 10(8) CD3(+)cells/kg) after every second azacitidine cycle. A median of three courses azacitidine (range 1-8) were administered, and 22 patients (73%) received DLI. Overall response rate was 30%, including seven complete remissions (CRs, 23%) and two partial remissions (7%). Five patients remain in CR for a median of 777 days (range 461-888). Patients with MDS or AML with myelodysplasia-related changes were more likely to respond (P=0.011), and a lower blast count (P=0.039) as well as high-risk cytogenetics (P=0.035) correlated with the likelihood to achieve CR. Incidence of acute and chronic graft-versus-host disease was 37% and 17%, respectively. Neutropenia and thrombocytopenia grade III/IV occurred during 65% and 63% of treatment cycles, while infections were the most common grade III/IV non-hematological toxicity. Azacitidine and DLI as salvage therapy is safe, induces long-term remissions and may become an alternative for patients with AML or MDS relapsing after allo-HSCT.

Azacitidine salvage therapy for relapse of myeloid malignancies following allogeneic hematopoietic SCT

“…In the current report, AZA was not used as first-line salvage therapy in 39% of patients. However, 38% of the patients responded, while only 15% achieved a CR, in line with the results from Schroeder et al 26 The OS rates at 1 and 2 years were, respectively, 25% and 5%. These modest results were achieved at the cost of a relatively high rate of toxicity with 56% of patients experiencing a grade 3 or 4 toxicity.…”

“…Retrospective analyses of AZA given at various doses and schedules for post-transplant relapse of AML and/or MDS have reported a response rate ranging from 55 to 72%, but with a poor survival ranging from 16 to 23% at 2 years. [22][23][24][25] Recently, Schroeder et al 26 conducted a prospective trial to evaluate the efficacy of AZA (100 mg/m 2 per day for 5 days) combined to DLI as first salvage therapy for relapse of AML or MDS after allo-HSCT. Seventy-three percent of the patients could receive DLI.…”

Second haematopoietic SCT using HLA-haploidentical donors in patients with relapse of acute leukaemia after a first allogeneic transplantation

“…1,2 Although no standard treatment has been defined, therapeutic options included (alone or in combination) conventional chemotherapy, demethylating agents, antibodies, targeted drugs, DLI and second allogeneic transplantation (HSCT2). [3][4][5][6] In HSCT2, most published studies have focussed on the effect of a second transplant from the original donor. 3,7 Nevertheless, change to another donor for HSCT2 is frequently considered to increase the efficacy of a putative GvL reaction.…”

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

“…Thus it is not surprising that rather extensive clinical experience exists with hypomethylating agents (HMAs) in the transplant setting. Others [4][5][6][7] as well as ourselves 8 have demonstrated a good tolerability and very encouraging activity of 5-azacytidine as treatment of AML/ MDS patients who relapsed after allograft. Intriguingly, even a lowdose, 3-day regimen of 5-azacytidine could result in durable CRs in some patients when combined with DLI.…”