Azacitidine and Donor Lymphocyte Infusions As Treatment For Relapse After Allogeneic Stem Cell Transplantation - a Retrospective Multicenter Analysis In 115 Patients On Behalf Of The German Cooperative Transplant Study Group

Two prospective studies and small retrospective series have demonstrated feasibility and clinical efficacy of Azacitidine (Aza) as salvage therapy for relapse of AML or MDS after allo-HSCT. As a consequence, Aza has become a clinically relevant treatment alternative in this setting. Still, due to the heterogeneity and limited number of patients reported so far predictive factors for response and long-term survival are unknown.

We analyzed data of 115 pts (median age 50 years, range 21-72 years) with AML (n=90), MDS (n=23) or myeloproliferative syndrome (MPS n=2), who had experienced relapse (hematological n=101; molecular n=14) after a median of 181 days (range: 19-3349 days) after allo-HSCT. Patients were treated with Aza ± DLI at 11 German transplant centers and in 109 of them (95%) Aza was the first treatment of relapse. Patients received a median of 3 courses Aza (range 1-14) and 78 patients (68%) received DLI (median number of DLI = 2, range: 1-6). Thirty patients were treated within a prospective phase-II trial (NCT-00795548). Their results have been published previously but were updated for this analysis.

Following this treatment, 34 pts achieved CR (29%) and 8 patients achieved PR (7%) resulting in an overall response rate of 36%. Median time to CR was 84 days (range: 26-430 days) corresponding to 3 Aza cycles (range: 1-8 cycles). Of 6 patients with an extramedullary relapse, 3 patients achieved CR. The 2-year OS rate was 34%. With a median follow-up of 17 months (range 1-82) for survivors, 22 pts (65%) are in ongoing CR for a median of 16 months (range 2-48) without further treatment, while 12 pts relapsed again after a median of 11 months (range 2-48). Bone marrow blast count (< 20% vs. ≥20%, CR rate 47% vs. 12% p=0.0001) and type of relapse (molecular vs. hematological, CR rate 71% vs. 24%, p=0.0007) were identified as predictive factors for the achievement of CR. No correlation was found for any karyotype abnormalities, time interval from allo-HSCT to relapse, the presence of blasts in the peripheral blood and the diagnosis of MDS vs de-novo AML. Incidence and severity of acute GvHD (overall: 25%, grade I: 10%, grad II: 6%, grade III: 7%, grade IV: 2%) and chronic GvHD (overall 23%, limited 19%, extensive 4%) were low and mild.

This analysis shows that the combination Aza and DLI is a valuable treatment option in the challenging situation of relapse after allo-HSCT. The association of disease burden with the likelihood to respond emphasizes the need for stringent disease monitoring and early intervention.

Schroeder:Celgene: Financial travel support Other, Honoraria. Bug:Celgene: Honoraria, Travel grants Other. Platzbecker:Celgene: Honoraria. Kobbe:Celgene: Research Funding.