Clonal Architecture Of Mds Somatic Mutations Dynamically Changes During Azacitidine Therapy And Has Very Limited Potential To Predict Patient Outcome

Introduction: Myelodysplastic syndromes (MDS) are clonal disorders of myeloid hematopoietic stem cells. Recent studies has shown that nearly 90% of patients with MDS carry somatic mutations in bone marrow (BM). These findings triggered a number of studies to identify potential uses of these mutations for diagnostics and prognostics purposes. We focused on a group of 38 patients with advanced stages of the disease that were selected for Azacitidine (AZA) therapy. We then utilized a set of 98 BM samples from the patient cohort that were collected in different stages before, during, and after the period of 4-12 cycles of the therapy. Each patient provided 3 samples on average. This study excludes patients that died early on AZA. Median OS on AZA therapy was 31 Mo. Most prevalent MDS subtypes were RAEB-2 (55%), RAEB-1 (24%), and MDS/AML (13%). 20% of patients had complex karyotype or poor cytogenetics (MedOS=22Mo) and the rest had mostly normal karyotype or intermediate cytogenetics (MedOS=40Mo) prior to AZA. Progression to AML was observed in 55% of patients (PFS= 16 Mo). After 4 cycles, PR was achieved in 59% of patients, CR in 12%, while SD was maintained in 21%, and 9% of patients progressed (PD) to AML.