Therapy-related acute lymphoblastic leukemia is a distinct entity with adverse genetic features and clinical outcomes. Blood advances Saygin, C., Kishtagari, A., Cassaday, R. D., Reizine, N., Yurkiewicz, I., Liedtke, M., Stock, W., Larson, R. A., Levine, R. L., Tallman, M. S., Park, J. H., Kerr, C., Przychodzen, B., Sekeres, M. A., Kalaycio, M. E., Carraway, H. E., Hamilton, B. K., Sobecks, R., Gerds, A., Mukherjee, S., Nazha, A., Maciejewski, J. P., Advani, A. S. 2019; 3 (24): 4228–37

Abstract

Patients with therapy-related acute lymphoblastic leukemia (t-ALL) represent a small subset of acute lymphoblastic leukemia (ALL) patients who received genotoxic therapy (ie, chemotherapy or radiation) for a prior malignancy. These patients should be distinguished from patients with de novo ALL (dn-ALL) and ALL patients who have a history of prior malignancy but have not received cytotoxic therapies in the past (acute lymphoblastic leukemia with prior malignancy [pm-ALL]). We report a retrospective multi-institutional study of patients with t-ALL (n = 116), dn-ALL (n = 100), and pm-ALL (n = 20) to investigate the impact of prior cytotoxic therapies on clinical outcomes. Compared with patients with pm-ALL, t-ALL patients had a significantly shorter interval between the first malignancy and ALL diagnosis and a higher frequency of poor-risk cytogenetic features, including KMT2A rearrangements and myelodysplastic syndrome-like abnormalities (eg, monosomal karyotype). We observed a variety of mutations among t-ALL patients, with the majority of patients exhibiting mutations that were more common with myeloid malignancies (eg, DNMT3A, RUNX1, ASXL1), whereas others had ALL-type mutations (eg, CDKN2A, IKZF1). Median overall survival was significantly shorter in the t-ALL cohort compared with patients with dn-ALL or pm-ALL. Patients who were eligible for hematopoietic cell transplantation had improved long-term survival. Collectively, our results support t-ALL as a distinct entity based on its biologic and clinical features.

View details for DOI 10.1182/bloodadvances.2019000925

View details for PubMedID 31869410