Therapy-related acute lymphoblastic leukemia is a distinct entity with adverse genetic features and clinical outcomes Journal Article


Authors: 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.
Article Title: Therapy-related acute lymphoblastic leukemia is a distinct entity with adverse genetic features and clinical outcomes
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 5 116), dn-ALL (n 5 100), and pm-ALL (n 5 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. © 2019 by The American Society of Hematology
Keywords: adult; cancer survival; controlled study; treatment response; aged; middle aged; gene mutation; human cell; major clinical study; overall survival; genetics; clinical feature; cytotoxic agent; doxorubicin; cancer patient; cancer radiotherapy; antineoplastic agent; gene; cohort analysis; cytogenetics; alkylating agent; cyclophosphamide; dexamethasone; vincristine; hematopoietic stem cell transplantation; retrospective study; acute lymphoblastic leukemia; risk assessment; myelodysplastic syndrome; gene rearrangement; cyclin dependent kinase inhibitor 2a; karyotype; t cell leukemia; genotoxicity; transcription factor runx1; gyrase inhibitor; dna methyltransferase 3a; asxl1 gene; clinical outcome; cdkn2a gene; cancer prognosis; long term survival; dnmt3a gene; human; male; female; priority journal; article; runx1 gene; ikzf1 gene; malignant neoplasm; kmt2a gene; adverse genetic feature
Journal Title: Blood Advances
Volume: 3
Issue: 24
ISSN: 2473-9529
Publisher: American Society of Hematology  
Date Published: 2019-12-23
Start Page: 4228
End Page: 4237
Language: English
DOI: 10.1182/bloodadvances.2019000925
PUBMED: 31869410
PROVIDER: scopus
PMCID: PMC6929388
DOI/URL:
Notes: Source: Scopus
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MSK Authors
  1. Martin Stuart Tallman
    494 Tallman
  2. Jae Hong Park
    178 Park
  3. Ross Levine
    540 Levine