Blast transformation in chronic myelomonocytic leukemia: Risk factors, genetic features, survival, and treatment outcome

Among 274 patients with chronic myelomonocytic leukemia (CMML) and followed for a median of 17.1 months, blast transformation (BT) occurred in 36 (13%). On multivariable analysis, risk factors for BT were presence of circulating blasts (HR 5.7; 95% CI 2.8-11.9) and female gender (HR 2.6; 95% CI 1.3-5.1); the results remained unchanged when analysis was restricted to CMML-1. ASXL1/SRSF2/SF3B1/U2AF1/SETBP1 mutational frequencies were not significantly different between time of CMML diagnosis and BT. Median survival post-BT was 4.7 months (5-year survival 6%) and better with allogeneic stem cell transplant (SCT) (14.3 months vs. 4.3 months for chemotherapy vs. 0.9 months for supportive care; P=0.03). Neither karyotype nor mutational status was independently associated with risk of BT or post-BT survival. We conclude that female patients with CMML and those with circulating blasts are at a higher risk of BT. Post-BT survival is dismal and our observations suggest consideration of allogeneic SCT prior to BT.