Molecular and cytogenetic characteristics of myeloid malignancies following luminal gastrointestinal cancer.

Abstract

PURPOSE\nLuminal 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.\n\n\nPATIENTS AND METHODS\nWe 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.\n\n\nRESULTS\n66 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).\n\n\nCONCLUSIONS\nAmong 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.