Molecular and cytogenetic characteristics of myeloid malignancies following luminal gastrointestinal cancer. (July 2019)

• Record Type: Journal Article
• Authors: Epstein-Peterson, Zachary D.; Devlin, Sean M.; Stein, Eytan M.; Klimek, Virginia M.; Saltz, Leonard B.; Tallman, Martin S.
• Is Part Of: Leukemia research. Volume 82(2019)
• Page Start: 19
• Page End: 23
• Publication Date: 2019-07
• Subjects: Treatment-related neoplasms -- Cytogenetics -- Molecular alterations -- Survivorship; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2019.05.010
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: With therapeutic advances, more patients achieve long-term disease control from gastrointestinal tract cancers. The disease patterns of myeloid neoplasms following treatment for gastrointestinal tract cancers have not been examined. This patient population frequently harbors adverse cytogenetic changes. DNTM3A was the most commonly-mutated gene in this population. Confirmatory studies are warranted to further explore this patient population and disease outcomes therein. Abstract: Purpose: Luminal gastrointestinal tract cancers (LGC) are common malignancies, and many patients can achieve long-term responses with surgery, cytotoxic and/or targeted therapies, and radiation. The long-term follow-up for patients with durable disease control has not been fully characterized, including subsequent malignancies. Such cases have not been comprehensively described. Patients and methods: We identified patients evaluated for myeloid malignancies (MyM) who had a prior LGC at our institution over a 35-year period. Patient, disease, and treatment information was collected for analysis. Cytogenetic risk profiles were designated according to the Revised International Prognostic Scoring System for MDS and the European LeukemiaNet Guidelines for AML. Results: 66 patients were included in our cohort with 71 prior LGC diagnoses, including three patients with multiple LGCs. 31 cases were treated with surgery alone, and 37 patients received chemotherapy. The median age at diagnosis of MyM was 71.8 years (range, 36.2–90.5), with median duration between initiation of treatment of LGC and diagnosis MyM of 7.9 years (range 0.005–38.8). Intermediate or adverse (AML)/poor-very poor (MDS) cytogenetic risk was common, occurring in 43% of MDS patients and 100% of AML patients; deletion 5q was the most common cytogenetic abnormality overall. DNMT3A mutations were the most common molecular alteration (6 patients with 7 mutations). Conclusions: Among patients with MyM following LGC, a high proportion harbored cytogenetic changes, many of which were adverse or poor-risk. Deletion 5q and mutated DNMT3A were the most common abnormalities identified.