Comparison of Allogeneic Stem Cell Transplantation for Transformed Acute Myeloid Leukemia Derived from MDS, CMML or MPN. a Report of the Chronic Malignancies Working Party of EBMT

Introduction

Myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) and chronic myelomonocytic leukemia (CMML) can progress to acute myeloid leukemia (transformed AML). The aim of this EBMT registry study was to compare 3 year outcome in patients with transformed AMLwho received allogeneic stem cell transplantation according to the primary disease.

Patients and Methods

Within the European Society of Blood and Marrow Transplantation (EBMT) registry, we found 4214 patients (female: 39%, male: 61%) with transformed acute myeloid leukemia, who received allogeneic stem cell transplantation between 2000 and 2014. The primary disease was MDS (n=3541), CMML (n=251) or MPN (n=422). The median age at transplantation was 58 years (range, 18-79) and 59% received a reduced intensity (RIC) conditioning regimen. The majority of the patients received stem cells from an unrelated donor (62%) and 50% were in complete remission at time of transplantation. Within the different groups of primary diseases, MDS patients were more often in CR (53%) than patients with CMML (47%) or MPN (43%). RIC was also more frequently used in MDS patients (65%), than in CMML (64%) and MPN patients (58%).

Results

After a median follow up of 46.5 months , the estimated 3 year relapse-free (RFS) and overall survival (OS) for the entire group was 36% (95%CI: 34-38%) and 40% (95% CI: 33-42%), respectively.The cumulative incidence of relapse and non-relapse mortality (NRM) was 37% (95% CI: 35-39%) and 27% (95% CI: 26-29%), respectively.

In a univariate analysis, patients with primary disease MDS had a significant better 3 year OS and RFS (41% and 37%) than patients with CMML (36% and 30) and MPN (32% and 25%) (p<0.001), due to a significant lower incidence of relapse at 3 years (35% vs 43% vs 50%, p<0.001). Other risk factors for worse OS were higher patient's age (>60 years), unrelated donor, not being in complete remission and low Karnofsky index (< 80%), while T-cell depletion, intensity of the conditioning regimen and TBI as conditioning regimen did not influence survival significantly.

In a multivariate analysis for OS beside age >60 years (HR 1.31; 95% CI: 1.13-1.52, p<0.001), unrelated donor (HR 1.12; 95% CI: 1.04-1.23, p=0.005), CMV +/- constellation (HR 1.13; 95%CI: 0.99-1.28, p=0.05), Karnofsky index > 80 (HR 0.66; 95% CI: 0.58-0.74, p< 0.001), non CR (HR 1.50; 95% CI: 1.38-1.63, p<0.001) PBSC as stem cell source (HR 0.86; 95% CI:0.75-0.97, p=0.02) and transformed AML from MPN (HR 1.24; 95% CI: 1.085-1.41, p=0.002) remained a significant factor in comparison to transformed AML from MDS, while outcome of transformed AML from CMML did not reach statistical significance in comparison to MDS (HR 1.10; 95% CI: 0.933-1.30, p=0.25)

Conclusion

This large EBMT registry study demonstrates that the primary underlying disease influence outcome of transformed acute myeloid leukemia in addition to other risk factors.