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
Authors: Schroeder Thomas , Rachlis Elena , Bug Gesine , Stelljes Matthias , Klein Stefan A. , Wolf Dominik , Ringhoffer Mark , Czibere Akos G. , Nachtkamp Kathrin , Dienst Ariane , Kondakci Mustafa , Stadler Michael , Platzbecker Uwe , Uharek Lutz , Luft Thomas , Fenk Roland , Germing Ulrich , Bornhäuser Martin , Kröger Nicolaus , Haas Rainer , Kobbe Guido 
Published: October 2019

Background

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.

Patients and Methods

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.

Results

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.

Conclusion

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.

Disclosures:

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