Impact of Donor Type on Outcome after Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia Patients: Analysis of the German-Austrian Acute Myeloid Leukemia Study Group (AMLSG)

Abstract

Background:Despite recent advances in identifying novel molecular targets in AML patients, intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT) still remains a cornerstone of AML therapy. However, outcome of HSCT depends on the availability of a donor and the donor type. Prior studies comparing HSCT from HLA-matched related donors (MRD) with matched unrelated donors (MUD), demonstrated conflicting results with regards to outcome. These conflicting results might be attributed to the genetic heterogeneity of AML.Aims:To analyze outcome with respect to donor type of 952 AML patients who received HSCT in first complete remission (CR) and were treated within prospective AMLSG trials.Methods:Within the AMLSG trials conducted between 1993 and 2013, of a total of 4991 patients (excluding acute promyelocytic leukemia), 3408 (2744 younger (<61 years old), 664 older (≥61 years old)) patients achieved a first CR after intensive double induction therapy. Of these, 867 (31%) younger and 85 (13%) older patients received HSCT in first CR. Distributions of donor types were 511 matched related donors (MRD), 435 matched unrelated donors (MUD) and 6 haplo-identical donors. The latter were grouped together with MUD.Results:Distributions of donor type over time are illustrated in table 1 indicating two clear trends with increasing numbers of MUD transplants and increasing median age in MUD- and MRD-transplants in recent years. There was no significant difference in overall survival, cumulative incidence of relapse (CIR) and death (CID) all estimated at 4 years according to the three time periods for MRD (p=0.56, p=0.15, p=0.10, respectively) and MUD (p=0.27, p=0.20, p=0.88, respectively).Table 1Time period1993-20022003-20072008-2013Total no.103611021270MRDNo.186 (18%)182 (17%)143 (11%)Median age42.7yrs46.0yrs51yrs4-yr-OS (95%-CI)59% (53-67)66% (59-73)61% (53-72)4-yr-CIR (SE)21% (3%)25% (3%)29% (4%)4-yr-CID (SE)25% (3%)15% (3%)18% (3%)MUDNo.42 (4%)131 (12%)268 (21%)Median age41.1yrs47.9yrs50.6yrs4-yr-OS (95%-CI)52% (39-70)46% (38-58)54% (47-61)4-yr-CIR (SE)21% (3%)25% (3%)29% (4%)4-yr-CID (SE)25% (3%)15% (3%)18% (3%)Table 2ELN risk categorylowinter-1inter-2highTotal no.867711433318MRDNo.78 (9%)122 (17%)66 (15%)57 (18%)4-yr-OS (95%-CI)84% (76-93)50% (51-69)53% (41-67)57% (44-72)4-yr-CIR (SE)7% (3%)24% (4%)35% (6%)49% (7%)4-yr-CID (SE)13% (4%)23% (4%)23% (6%)12% (4%)MUDNo.21 (2%)139 (20%)76 (18%)109 (36%)4-yr-OS (95%-CI)69% (52-93)58 (49-68)52% (41 67)35% (26-46)4-yr-CIR (SE)0%28% (4%)32% (6%)44% (5%)4-yr-CID (SE)31% (11%)20% (4%)17% (5%)28% (4%)There were no differences in stratified survival analyses for time period between MRD and MUD-transplants in the low, intermediate-1 and intermediate-2 risk groups with respect to OS (p=0.12, p=0.86, p=0.98), CIR (p=0.28, p=0.54, p=0.94) and CID (p=0.09, p=0.57, p=0.39). In the high risk group, OS was significantly superior after MRD-transplant compared to MUD-transplant (p=0.02), but without significant differences in CIR (p=0.74) and CID (p=0.08). Equivalent efficacy could also be shown in a subgroup analyses focusing on all FLT3-ITD positive patients (MRD, n=103, MRD, n=147) for OS (p=0.71), CIR (p=0.53) and CID (p=0.69).Conclusions: Our results based on prospective interventional studies support the perception that MUD-transplants are equal to MRD-transplants in patients with AML in first CR. Only within the ELN high risk group, patients with MRD-transplants showed superior OS but without differences in CIR and CID as compared to MUD-transplants. DisclosuresKobbe:Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Medac: Other; Astellas: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Neovii: Other. Götze:Celgene Corp, Novartis Pharma: Honoraria. Fiedler:TEVA: Travel reimbursement for meeting attendance Other. Petzer:Celgene: Honoraria, unrestricted grant Other. Lübbert:Cephalon / TEVA: Travel support Other. Greil:Bristol-Myers-Squibb: Consultancy, Honoraria; Cephalon: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Amgen: Honoraria, Research Funding; Eisai: Honoraria; Mundipharma: Honoraria, Research Funding; Merck: Honoraria; Janssen-Cilag: Honoraria; Genentech: Honoraria, Research Funding; Novartis: Honoraria; Astra-Zeneca: Honoraria; Boehringer-Ingelheim: Honoraria; Pfizer: Honoraria, Research Funding; Roche: Honoraria; Sanofi Aventis: Honoraria; GSK: Research Funding; Ratiopharm: Research Funding. Döhner:Novartis: Research Funding. Döhner:TEVA: Research Funding.