Outcomes of patients with AML and MDS who relapse or progress after reduced intensity allogeneic hematopoietic cell transplantation

Abstract

We describe treatment, outcomes and prognostic factors for patients who relapse following transplantation with a reduced intensity conditioning regimen. Seventy consecutive patients with high-risk myeloid malignancies underwent transplant and 25 (36%) relapsed, a median of 120 days later. The median percentage of bone marrow blasts at relapse was 24, the median donor chimerism was 73% and new karyotypic abnormalities occurred in 8 out of 20 (40%) evaluable patients. Twenty-one patients (84%) received aggressive treatment for relapse, including chemotherapy (60%), second hematopoietic cell transplantation (HCT; 52%) and/or donor lymphocyte infusion (DLI; 12%). Thirteen achieved a complete response (CR) and four remain in CR. Median overall survival (OS) after relapse was 6 months (95% confidence interval ¼ 2.7-9.9 months), and actuarial 1 year OS was 24%. Most deaths were due to disease progression (17/20, 85%). We did not observe an advantage for cellular therapy (DLI or second transplant) compared to chemotherapy. Salvage therapy for relapse after reduced intensity HCT is feasible, associated with low treatment-related mortality, and may result in prolonged survival in select patients. Studies exploring the optimal treatment for relapse following reduced intensity HCT are warranted.

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

“…AZA administration and toxicity AZA was administered for a median of three cycles (range, [1][2][3][4][5][6][7][8][9][10][11][12], at a dose of 75 mg/m 2 per day for 7 days every 4 weeks for the majority of the patients (92%). AZA dose was reduced to 60 mg/m 2 per day (two patients) for 7 days according to the attending physician because of fear of toxicity.…”

“…1,2 Reductions of immunosuppressive therapy, chemotherapy with or without infusion of DLI or second allo-HSCT are regularly proposed, but results remain disappointing. [3][4][5] Azacitidine (AZA), a DNA-hypomethylating agent with a relatively low toxicity profile, emerged in the recent years as an attractive treatment modality in patients with myeloid malignancies who are not eligible to intensive chemotherapy.…”

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

“…[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. However, the impact of donor change on outcome is unclear, and available data are limited.…”

Azacytidine treatment after discontinuation of immunosuppressants in patients with myelodysplastic syndrome and relapse after allo-SCT at a single center

“…However, the therapeutic options for patients who relapse after transplantation are limited. 1 Attempts to maximize the GVL effects by donor lymphocyte infusion have been generally unsuccessful for restoration of a CR. 2 Trials of donor lymphocyte infusion in combination with chemotherapy have shown increased response rates, but the long-term survival of relapsed patients is low.…”