Introduction:Chronic myelomonocytic leukemia (CMML) is a genetically heterogeneous myeloid neoplasm characterized by the presence of both dysplastic and proliferative features and highly variable clinical outcome. A CMML specific prognostic system (CPSS) has been developed that stratifies patients in to low, intermediate and high risk groups based on WHO subtype, FAB subtype, transfusion dependent anemia, and karyotype. Somatic mutations and DNA methylation patterns can increase prognostic precision, but fail to explain a large part of the clinical variation, suggesting that additional variables, including comorbidities, may be major determinants of overall survival (OS) in CMML. Methods : We retrospectively identified CMML patients diagnosed between 1996 and 2017 at the Huntsman Cancer Hospital, University of Utah, using ICD codes, tumor registry data and electronic medical records. For all patients a diagnosis of CMML was confirmed based on 2008 WHO diagnostic criteria. Data on comorbidities at the time of diagnosis were obtained by search of electronic medical records using a customized rule based algorithm utilizing linguimatics text mining software (Natural language processing). The comorbidities were scored and categorized as per previously published reports: low, intermediate and high risk groups for MDS Comorbidity Index (MDS-CI) and low, mild, moderate/high (moderate and high included in the same group due to small number of patients) for the Charlson Comorbidity Index (CCI). Continuous variables were transformed into categorical variables, based on cutoffs used in previously published studies. Univariate analysis was performed using the Cox proportional hazards model for categories: MDS-CI (low, intermediate and high) and CCI (low, mild, moderate/high). Other variables analyzed included age (<70 or >70 years), sex (male or female), hemoglobin (<10 gm/dL or >10 gm/dL), platelet count (<100k/uL or >100k/uL), WHO subtype (CMML-0, CMML-1 and CMML-2), FAB subtype (CMML-MD or CMML-MP), karyotype (low, intermediate and high risk) and treatment with hypomethylating agents (yes or no). Kaplan-Meier methods were used for plotting OS. All analysis was performed using R statistical programming software version 3.2.1 (The R Foundation for Statistical Computing, Vienna, Austria). Results shown are censored at the time of allogeneic stem cell transplant. For OS the "Low" category is reference and the p-values are for comparison to this category using the Cox model. Results : We identified 94 patients with confirmed diagnosis of CMML. The median age was 76 (range 33-91 years) and 61 patients were men (65%). Fifty-five (58.5%), 34 (36.2%) and 5 (5.3%) patients were categorized as MDS-CI low, intermediate and high risk respectively. Sixty-two (66%), 26 (27.6%) and 6 (6.4%) were categorized as low, mild and moderate/high CCI risk. Hazard ratios (HR) for MDS-CI risk categories were: intermediate=1.26 (95% CI 0.71 to 2.23; p=0.425) and high risk=2.22 (95% CI 0.86-5.75); p=0.101). HR for CCI risk categories were: mild=1.01 (95% CI 0.56-1.82; p=0.964) moderate/high=4.18 (95% CI 1.57 to 11.10; p=0.004). HR for other variables are shown in Table 1. Kaplan-Meier curve representing the OS of the entire cohort categorized according to CCI and MDS-CI risk categoriesis shown in Figure 1. Estimated median survival for MDS-CI low, intermediate and high is 36, 36, and 23 months respectively. Median survival for CCI-CI low, mild, moderate/high risk categories was 36, 33, and 10 months respectively (Figure 1). Conclusions: High risk CCI and MDS-CI category patients are at markedly higher risk of death, suggesting that co-morbidities are major host-related determinant of OS in CMML. Given the association of clonal hematopoiesis of indeterminate potential (CHIP) with coronary heart disease (Jaiswal et al. N Engl J Med 2017; 377:111-121) and the fact that CHIP genes such as TET2are frequently mutated in CMML, it is conceivable that CMML causally contributes to comorbidities. Somatic mutation data are being collected for inclusion in a multivariate model that will be presented at the conference. Disclosures Shami: JSK Therapeutics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Lone Star Biotherapies: Equity Ownership; Pfizer: Consultancy; Baston Biologics Company: Membership on an entity's Board of Directors or advisory committees. Kovacsovics:Abbvie: Research Funding; Amgen: Honoraria, Research Funding. Deininger:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Blueprint: Consultancy.
Introduction: Follicular lymphomas (FL) of the gastrointestinal tract are rare. They are usually discovered incidentally, and the terminal ileum is the most prevalent location. We present a patient with a rare variant of FL involving the distal duodenum and proximal jejunum and its treatment with bendamustine-rituximab. Case Description/Methods: A 46-year-old female presented due to ongoing nausea, vomiting and diarrhea multiple times a day since many months. Her physical exam and laboratory data including stool studies were unremarkable. She underwent workup at an outside facility including an esophagogastroduodenoscopy (EGD) and colonoscopy, biopsies from which were unremarkable. Her computerized tomography (CT) scan of the abdomen showed mesenteric lymphadenopathy but was otherwise unremarkable. She reported that a capsule endoscopy was also done which showed ulcers in her small bowel. She was scheduled for an EGD with single balloon enteroscopy which showed nodular areas with white plaques in the distal duodenum and proximal jejunum. Her biopsies including immunohistochemistry and fluorescence in-situ hybridization (FISH) showed low-grade duodenal-type follicular lymphoma (DTFL) with translocation t(14;18) in the bcl-2 locus. Because of debilitating symptoms, she was treated with bendamustine-rituximab with resolution of her nausea and vomiting and significant improvement in her diarrhea. She was given loperamide and colestipol for mild persistent diarrhea. A repeat EGD with double balloon enteroscopy was performed after completing treatment which showed no gross abnormalities and biopsies did not demonstrate the presence of any lymphoproliferative disorder. (Figure ) Discussion: DTFL is a newly recognized entity in the WHO classification update. It is usually detected incidentally on endoscopy and diagnosed at a low grade and stage and stays localized to the duodenum in most cases. Due to the excellent prognosis, a wait and watch strategy is recommended. This case is unique because our patient presented with debilitating symptoms which are not classic of DTFL and hence treatment was initiated with chemotherapy resulting in significant improvement of her symptoms.[3480] Figure 1. A-Nodular areas with white plaques seen on balloon enteroscopy B-Histopathology demonstrating atypical lymphoid infiltration into lamina propria. The neoplastic cells are positive for CD20, CD10 and bcl-2 C-t(14;18)(q32;q21) (IGH/BCL2) translocation is detected by FISH. One green, one orange and two yellow fusion signals (x1000).
Introduction: Large cell neuroendocrine carcinomas (LCNECs) are characterized as large cells with areas of necrosis, neuroendocrine traits (palisading, trabeculae, etc.), ample cytoplasm and high mitotic rates. LCNECs are a rare, aggressive form of neuroendocrine tumor known to have high rates of metastasis. Our case highlights acute liver failure with rapid progression to death due to metastatic spread of LCNEC. Case Description/Methods: 71-year-old male with a history of prostate cancer requiring prostatectomy, hypertension, hyperlipidemia, and tobacco use, presented for shortness of breath and abdominal pain for 3 days. He was a poor historian and was unable to provide much history. Of note, the patient reported that he had imaging performed in spring 2021 to further evaluate his degenerative disc disease and was told there was concern for a cancerous process. Initial laboratory studies showed an elevated AST and ALT (over 300), and thrombocytopenia, but were otherwise unremarkable. Further imaging was performed, given the patient's history of reported malignancy. Initial chest X-ray was negative for acute findings and an abdominal ultrasound revealed a markedly abnormal appearance of the liver, suggestive of possible hepatic metastatic disease. Computed tomography scan of the chest/abdomen/pelvis showed a left hilar mass measuring 5.5 x 6cm with regional lymphadenopathy. The patient underwent a biopsy of the liver, and was later noted to have worsening liver enzymes, platelets, INR, and renal function, along with a lactic acid. He was transferred to the intensive care unit for further monitoring. Bowel ischemia and portal vein thrombosis were ruled out, and the patient became continually more acidotic, and had a pulseless electrical activity (PEA) arrest. He was revived and intubated, and placed on pressor support and continuous renal replacement therapy. His family decided to change his code status to "do not resuscitate" and the patient was made comfortable. Final results of the liver biopsy were obtained 2 days later, and showed findings consistent with high grade large cell neuroendocrine carcinoma. Immunohistochemical staining was positive for CD56, synaptophysin, CK7 and CK5/6. (Figure ) Discussion: Liver metastasis has been documented throughout the literature for other carcinomas, however very few in regards to LCNEC. Acute liver failure in such a short span of time, as in our case, highlights the mortality associated with LCNECs, and the difficulty in diagnosing the condition early in the disease course.[3338] Figure 1. CT abdomen/pelvis showing diffuse heterogeneity of the liver.
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