AML-387 Clinical Characteristics of Secondary Myeloid Neoplasms (MNs) in Patients With Inflammatory Bowel Disease (IBD)

Context: Patients with ulcerative colitis (UC) and Crohn's disease (CD) are at increased cancer risk. Very little data is available regarding the risk of secondary MN in patients with IBD. Objective: To describe the clinical characteristics of secondary MNs in patients with IBD. Methods: Retrospective study of patients with MNs previously treated for IBD. Results: Between 2012 and 2020, 43 patients were identified as having developed secondary MN during or after IBD treatment; 63% were women, and 81% were of white ethnicity. In 70% (30/43) of cases, secondary MNs arose after CD therapy, whereas 30% (13/43) arose after UC therapy. The median age at the time of MN diagnosis was 59 years (23–83 years), and latency from IBD diagnosis was 16 years (0–56 years). At the time of MN diagnosis, 25 patients were on active treatment for IBD (9 biological agent, 11 mesalamine, and 2 azathioprine), whereas 18 were in remission. Additionally, 8 patients (19%) had secondary cancer before the MN diagnosis (2 lymphoma, 2 skin cancer, ovarian cancer, uterine cancer, schwannoma, and adrenal tumor), and 3 patients received therapy. Acute myeloid leukemia (AML) was diagnosed in 74% of MN cases, 9 (21%) were myelodysplastic syndrome (MDS), and one each was MDS/myeloproliferative neoplasm (MPN) and chronic myelomonocytic leukemia (CMML). Cytogenetic abnormalities were detected in 70%: 13 patients (30%) with complex karyotype and 6 patients (14%) with core-binding factor (CBF) abnormalities (5 inv16 and 1 t [8;21]). Most common mutations were TP53 (23%), FLT3 (16%), RAS (19%), TET2 (16%), and DNMT3A (14%). Interestingly, all patients with CBF-AML had prior history of CD, including two treated with anti–TNF-α. The median overall survival (OS) was 2.17 yrs for the whole cohort, with no difference in OS between MNs arising from CD and UC (2.35 and 2.08 yrs for CD and UC, respectively). Seventeen patients underwent allogeneic stem cell transplantation (ASCT), which resulted in IBD remission in 13 patients (76%). Conclusions: Secondary MNs after IBD therapy included higher than expected prevalence of CBF-AML and were strongly associated with prior history of CD. ASCT led to remission of both MNs and IBD.