Long-Term Outcome of Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia Beyond First Complete Remission – a Single Center Experience

Aims: Allogeneic stem cell transplantation (alloSCT) in first complete remission (CR1) has become a standard of care for many patients (pts) with intermediate or high risk acute myeloid leukemia (AML). Furthermore, pts with relapsed AML may be salvaged by re-induction and subsequent alloSCT. Here, we analyzed the outcome of pts with AML transplanted beyond CR1 at our center between 1996 and 2013.

Pts and Methods: 120 pts (50 female, 70 male) with a median age of 49 (19-72) years were retrospectively analyzed as of June 30^th, 2013. 92 pts had de novo AML and 28 pts had secondary or therapy-related AML. 63 pts were in CR2 whereas 57 pts were refractory to re-induction therapy and had active disease at the time of alloSCT. The SWOG/ECOG cytogenetic risk profile was favorable in 16 pts, intermediate in 53 pts, and unfavorable in 34 pts (unknown: 11 pts, undetermined: 6 pts). Conditioning consisted of a 12 Gy TBI-based myeloablative regimen (MAC) in 51 pts. 61 pts received reduced intensity conditioning (RIC: FLU/BU/ATG) and 9 pts were conditioned using the FlamsaRIC protocol. A matched related donor was available in 33 pts. 62 pts had a matched-unrelated donor and 25 pts had a mismatched unrelated donor.

Results: After a median follow-up of 39 (3-185) months, 44 pts are alive and in CR. Causes of death were relapse in 37 pts or non-relapse mortality (NRM) in 36 pts. At 1, 3, and 5 years after alloSCT projected overall survival (OS) or disease-free survival (DFS) of the entire cohort was 50% (41-60%), 40% (30-50%), and 39% (29-49%) or 48% (39-58%), 39% (30-49%), or 38% (28-47%). At the same time points the cumulative incidence of relapse (CIR) or NRM (CINRM) was 25% (19-35%), 31% (23-41%), and 32% (24-42%) or 25% (21-38%), 28% (21-38%), or 30% (22-40%). In univariate analysis pts refractory to re-induction therapy had a significantly lower 3-year DFS (26%) as compared to pts transplanted in CR2 (54%) (HR 1.8 (95%CI: 1.1-2.8), p=0.01), due to an increased relapse rate (40% vs 24%, p=0.003). Similarly, an interval of ≤12 months from diagnosis to alloSCT was predictive for a lower 3-year DFS as compared to an interval of >12 months (21% vs 52%) (HR 2.0 (95%CI: 1.2-3.3), p=0.002), due to an increased relapse incidence (47% vs 23%, p<0.001). All other factors examined, i.e. gender, cytogenetic risk, AML subtype, age group, type of conditioning, donor, or year of alloSCT, were not predictive for OS, DFS, CIR, or CINRM. In multivariate analysis, remission status and time from diagnosis to transplantation were identified as independent prognosticators for OS, DFS, and CIR.

Conclusions: In sum, our data indicate that pts with AML beyond CR1 may be successfully salvaged by alloSCT. In particular, pts transplanted in CR2 benefit the most. Pts refractory to re-induction may be candidates for alloSCT as well. However, these pts have a poorer outcome due to a high relapse rate irrespective of the cytogenetic risk profile and the conditioning regimen used.