Cytogenetic Risk Groups and Minimal Residual Disease Are Strong Prognostic Factors for Post-Transplant Outcome in Patients with Acute Myeloid Leukaemia and Myelodysplastic Syndrome

Abstract 4482

Allogeneic stem cell transplantation (alloSCT) is a curative treatment option for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Relapse after alloSCT is still a major cause for the treatment failure. Molecular genetic (FLT3, NPM1 mutations) and cytogenetic risk-categories have an important impact on the prognosis of patients undergoing alloSCT. However, it has been shown that there is a closely relationship between the level of minimal residual disease (MRD) and relapse after alloSCT in leukemia patients.

We analyzed 140 AML/MDS patients transplanted at our institution. We examined the contribution of cytogenetic aberrations and molecular genetic markers detected prior alloSCT to survival, relapse, and mortality after transplantation. Furthermore, we analyzed MRD status after consolidation therapy and in post-transplant period. We classified molecular genetic/cytogenetic status before alloSCT into 2 groups: low-risk: good and intermediate-risk karyotype, FLT3-wt, NPM1-mutated cases and high-risk: adverse-risk cytogenetic, FLT3-ITD mutated cases. A good risk karyotype was present in 8 patients; an intermediate risk in 56 patients, whereas 76 patients had a poor cytogenetic risk. 51 patients were treated with standard myeloablative conditioning regiments prior to alloSCT, 73 patients received reduced intensity conditioning and 16 non-myeloablative conditioning. 40 patients had a matched-related donor and 100 patients had a matched-unrelated donor. Overall survival (OS) in the group of patients with low cytogenetic risk was 839 days as compared with 613 days in high-risk group. The low risk cohort also showed a lower relapse (33% vs. 51%, p<0,03) and mortality rate (20% vs. 71%, p<0,003). We analyzed MRD status in all patients after consolidation therapy. MRD negative patients are characterized by favorable prognosis as compared with MRD positive patients, OS 87% vs. 53%, p<0,001. We conclude that risk-stratification combining molecular genetics and cytogenetics aberrations at the time of diagnosis with post-consolidation MRD status improve identification of high-risk category of patients. New treatment strategies are needed to overcome poor outcome of high risk AML patients, for instance, immunotherapy options like prophylactic DLI, shorter and modified immunosuppression, specific reduced intensity conditioning or new drugs like tyrosine kinase inhibitors.