Allogeneic Stem Cell Transplantation for Therapy-Related Myelodysplastic Syndrome (t-MDS) and Acute Myeloid Leukemia. A Report from the MDS Subcommittee of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

Background: With the prolonged survival and increasing cure rate for some malignancies there appears to be an increasing incidence of therapy related MDS or AML.

Methods: Between 1981 and 2006, 486 patients (pts) with t-MDS or t-AML underwent allogeneic stem cell transplantation (SCT) and were reported to the EBMT registry. The median age of the pts was 40 years (r., 3–69) and primary disease were solid tumor (n=167), malignant lymphoma (n=141), myeloproliferative syndrome (n=12), acute leukaemia (n=32), aplastic anemia (n=16) and autoimmune disease (n=1). The median time from primary diagnosis to t-MDS/t-AML was 54 months (r., 1–416). Diagnosis were: RA/RARS (n=28), RAEB (n=49), RAEB-T (n=44) and t-AML (n=308). At time of transplantation, 268 pts were in complete and 186 pts not in complete remission (CR). Cytogenetic abnormalities were found in 262 pts.

Results: For the entire study population the cumulative incidence of non-relapse mortality (NRM) and relapse at 3 years was 37% and 34%. In a multivariate analysis significant factors for higher incidence of relapse were “non CR” at SCT (HR:2.20; 95% CI: 1.44–3.36, p<0.001) and abnormal cytogenetic (HR: 1.78; 95% CI: 1.03–3.07; p=0.04), while higher NRM was noted for higher pts age: 40–50 years (HR: 2.25; 95%CI: 1.46–3.46, p<0.001) and older than 50 years (HR: 2.67; 95% CI: 1.68–4.25, p<0.001). Furthermore, there was a marked reduction in NRM per calendar year during the study period (HR: 0.93; 95% CI: 0.90–0.96, p<0.001). The 3 year event-free (EFS) and overall survival (OS) was 31% and 34%. In a multivariate analysis EFS was negatively influenced by higher age: 40–50 years (HR: 1.91; 95% CI: 1.39–2.61, p<0.001) and age > 50 years (HR: 1.95; 95% CI: 1.36–2.78, p<0.001), abnormal cytogenetic (HR: 1.41; 95% CI: 1.01–1.99; p=0.05), “non CR” at SCT (HR: 1.78; 95% CI 1.34–2.36; p<0.001) and disease status RAEB-T (HR:2.23; 95% CI: 1.20–4.13; p=0.01) and t-AML (HR: 2.00; 95% CI; 1.13–3.52, p=0.02). A significant higher EFS and OS was seen per calendar year (HR: 0.96:; 95% CI: 0.94–0.98, p=0.004) and (HR: 0.95:; 95% CI: 0.93–0.98, p=0.001). OS was further influenced by higher age: 40–50 years (HR: 1.93; 95%CI: 1.61–2.68, p<0.001) and age > 50 years (HR: 2.13; 95% CI: 1.47–3.08, p<0.001), “non CR” at SCT (HR: 1.57; 95% CI 1.18–2.09; p<0.001) and disease status RAEB-T (HR:2.44; 95% CI: 1.27–4.66; p=0.007) and t-AML (HR: 2.26; 95% CI; 1.19–3.92, p=0.02).

Conclusion: Allogeneic SCT can cure pts with therapy related MDS or AML. During study period a better EFS and OS could be seen per calendar year due to a marked reduction in non-relapse mortality. Advanced disease-status, abnormal cytogenetics and higher age of the pts are the most significant factors for survival.