Activating mutations in RAS have been reported in about 10-15% of patients with AML; previous studies have not identified a prognostic significance. However, RAS mutations have emerged as a potential resistance mechanism to treatment with inhibitors of FLT3, IDH, and BCL2. We aimed to determine the characteristics and outcomes of patients with RAS-mutated (RAS-mut) AML across therapy subsets of 1410 patients newly diagnosed (ND AML). RAS-mut was observed in 273 (20%) patients. Overall, patients with RAS-mut AML had an estimated 3-year survival rate of 38% vs. 28% in those with RAS wild type (RAS-wt), p = .01. Among patients with RAS-mut, favorable karyotype and concomitant NPM1 mutations were associated with a higher CR/CRi rate, OR 23.2 (95% CI: 2.7-192.7; p < .001) and OR 2.8 (95% CI: 1.1-6.9; p = .02), respectively, while secondary and treated secondary (ts)-AML were associated with low response rates, OR 0.34 (95% CI: 0.1-0.9; p = .04) and OR 0.22 (95% CI: 0.09-0.5; p = .001), respectively. Intensive chemotherapy was associated with high response rates OR 5.9 (95% CI: 2.9-12.2; p < .001). Better median OS was observed among those with favorable karyotype, HR 0.28 (95% CI: 0.1-0.6; p = .002), and those treated with intensive chemotherapy, HR 0.42 (95% CI: 0.2-0.6 p < .001). Conversely, ts-AML and co-occurrence of mutations in TP53 were associated with poor median OS; HR 2.3 (95% CI: 1.4-3.9; p = .001) and HR 1.7 (95% CI: 0.9-3.1; p = .06), respectively. The addition of venetoclax was associated with a non-significant improvement in CR/CRi and OS. | INTRODUCTIONAcute Myeloid leukemia (AML), the most frequent acute leukemia in adults, is an aggressive hematologic malignancy presenting with an uncontrolled expansion of the myeloid blasts resulting in impaired hematopoiesis. Patient-related features such as age, performance status, prior malignancy, and exposure to cytotoxic therapies have been associated with an impact on outcomes. 1 Disease-related features such as conventional cytogenetics and mutational status of CEBPA, NPM1, and FLT3-ITD have been used in clinical practice to determine prognosis. More recently, with the advent of nextgeneration sequencing (NGS) technologies, additional recurrent

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Background Leukemic presentation of follicular lymphoma (FL) is uncommon, with most cases reported in older adults. Design This report describes an unusual case of a young adult diagnosed with leukemic phase of FL. We reviewed the existing literature on this rare presentation of the disease and its potential impact on patient outcomes. Results Leukemic phase of FL in young adults can be mistaken for other high‐grade hematologic malignancies. Morphology assessment and ancillary testing, such as flow cytometry and FISH analysis, can assist in achieving an accurate diagnosis of the leukemic phase of FL. Notably, our young patient responded well to therapy, which is different from what is typically observed in older patients who have a poorer prognosis. Further cases are needed to investigate the prognostic impact of the leukemic phase of FL in younger patients.

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e19029 Background: Hyperleukocytosis in AML is associated with inferior outcomes. Analyzing the factors associated with mortality in AML patients (pts) with a white blood cell count (WBC) ≥100 x 109/L can guide management and improve early mortality. Methods: We reviewed data from 129 pts with newly diagnosed AML presenting at our institution with WBC ≥100. Logistic regression models estimated odds ratios (OR) for 4-week mortality and Cox proportional hazard models estimated hazard ratios (HR) for overall survival (OS). Results: Median age was 65 years (range 23-86). 66% of pts had ECOG performance status (PS) <2. Median WBC was 146 (range 100-687) and 78 pts had clinical leukostasis (CL) including renal failure in 31 pts (24%), new onset hypoxia in 29 pts (23%), headache in 19 pts (15%), chest pain in 9 pts (7%) and neurological symptoms in 3 pts (2%). 29 pts (22%) had poor cytogenetics. FLT3 and RAS pathway mutations were found in 63% and 27% of pts, respectively. Compared with pts without evidence of CL, pts with CL were less likely to have good PS (ECOG PS <2, 58% vs 82%; P = 0.006), had higher 4-week (16% vs 2%; P = 0.015) and 8-week mortality (19% vs 6%; P = 0.038). Cytoreduction consisted of hydroxyurea in 124 pts (96%), cytarabine in 69 pts (54%) and leukapheresis in 31 pts (24%). Pts who underwent leukapheresis were less likely to receive cytarabine compared with pts who did not (35% vs 59%; P = 0.02); and tended to have more CL compared with pts who did not (74% vs 56%; P = 0.09). 30 pts had tumor lysis syndrome (TLS). TLS risk did not increase with WBC and was not associated with the cytoreductive modality used. 11 pts had intracranial hemorrhage (ICH): 9 pts (82%) with WBC ≥150 and 18% with WBC <150 (P = 0.048). No association was observed between the incidence of ICH and the cytoreductive therapy. 4-week and 8-week mortality rates were 10% and 14%, respectively. After a median follow-up of 49.4 months [mos] (95% CI 26.2-72.6), median OS was 14.3 mos (95% CI 7-21.6), with 2-year OS of 40%. Median OS was 12.3 mos (95% CI 7.4-17.2) compared with 29 mos (95% CI 2.1-55.6) in pts with or without CL, respectively (P = 0.007). Median OS was 9.9 mos (95% CI 7.5-12.2) and 21.3 mos (95% CI 10.7-31.8) among those who did or did not undergo leukapheresis, respectively (P=0.003). Median OS was 42 mos (95% CI 14.2-69.8) compared with 8 ms (95% CI 6-10) in pts < or ≥ 65 years. Conclusions: Older age, poor cytogenetics, TLS and DIC were associated with early mortality and inferior OS in pts with hyperleukocytosis. Careful monitoring of those pts with prompt cytoreduction and management of complications may help improve outcomes. [Table: see text]