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

Abstract

Patients with hematopoietic malignancies relapsing after allogeneic hematopoietic SCT (allo-HSCT) have a poor prognosis. We retrospectively analyzed the patients who received azacitidine in our center in the course of treatment of their post-transplant relapse. We identified 31 patients. Relapse occurred at a median of 3.7 (1.7-37.6) months following allo-HSCT. Patients received a median number of three cycles (1-12) of azacitidine (7 days, 75 mg/m 2 daily). Thirty-nine percent of patients had either a monosomal karyotype or a complex karyotype. Eleven patients (35%) received at least one DLI. Eleven patients responded to azacitidine, with four patients achieving a CR (13%). Median time to best response was 92 (35-247) days, with a median duration of 209 (64-751) days. One-year estimated survival rate was 14%. In conclusion, azacitidine may reinduce durable remissions in very few patients with AML or myelodysplastic syndrome. The toxicity related to azacitidine was high, although it may be difficult to distinguish between treatment-related side effects, namely due to cytopenia and toxicity due to the relapse or disease progression itself. Early administration of azacitidine after transplant followed by DLI should be considered as a pre-emptive therapy for potential relapse in patients with minimal residual disease or high-risk myeloid malignancies.

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

“…The CR rate of 9.7% in this analysis was lower than that in other studies with this approach, for example, Tessoulin et al 23 (CR 14%, overall response rate (ORR) 29%), Schroeder et al 6 (CR 23%, ORR 30%) and Czibere et al 5 (CR 23%, ORR 72%). One possible reason for this is the lower dosage (2, 3 or 4 days) of 5-azacytidine 100 mg per day, which 75% of our patients received as a starting dose.…”

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.…”

Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia

“…8,9 A number of small series have reported that AZA can induce remissions in patients who relapse after an allogeneic transplant, raising the possibility that this agent represents a potential new treatment strategy in this challenging patient population. [10][11][12] Furthermore, it has been suggested in single arm studies that AZA may augment the anti-tumor activity of DLI in patients who relapse after an allograft. 13 However, importantly, so far there has been no systematic analysis of the clinical activity of AZA in patients who have relapsed after an allograft for AML or MDS, or of whether its activity is increased by the concurrent administration of DLI.…”

“…Prospective studies to confirm optimal treatment options in this challenging patient population are required. relapse after allogeneic stem cell transplantation for acute myeloid leukemia Charles Craddock, 1 Myriam Labopin, 2 Marie Robin, 3 Juergen Finke, 4 Patrice Chevallier, 5 Ibrahim Yakoub-Agha, 6 Jean Henri Bourhis, 7 Henrik Sengelov, 8 Didier Blaise, 9 Thomas Luft, 10 Michael Hallek, 11 Nicolaus Kröger, 12 Arnon Nagler, *13 and Mohamad Mohty developing effective treatment options for patients with recurrent disease after allogeneic SCT, and the great majority remain destined to die of resistant disease. 3 Although a small number of patients with disease recurrence can survive long term after a second transplant or donor lymphocyte infusion (DLI), the success of both these treatment modalities is contingent on the prior acquisition of morphological remission with salvage therapy.…”