Acute myeloid leukemia (AML) is frequently associated with hyperleukocytosis [white blood cell count (WBC) of >50 or >100 × 109/L at presentation] [1]. Hyperleukocytosis also predicts a higher risk...

The incidence of cardiac morbimortality in acute myeloid leukemia (AML) is not well known. We aim to estimate the cumulative incidence (CI) of cardiac events in AML patients and to identify risk factors for their occurrence. Among 571 newly diagnosed AML patients, 26 (4.6%) developed fatal cardiac events, and among 525 treated patients, 19 (3.6%) experienced fatal cardiac events (CI: 2% at 6 months; 6.7% at 9 years). Prior heart disease was associated with the development of fatal cardiac events (hazard ratio (HR) = 6.9). The CI of non-fatal cardiac events was 43.7% at 6 months and 56.9% at 9 years. Age ≥ 65 (HR = 2.2), relevant cardiac antecedents (HR = 1.4), and non-intensive chemotherapy (HR = 1.8) were associated with non-fatal cardiac events. The 9-year CI of grade 1–2 QTcF prolongation was 11.2%, grade 3 was 2.7%, and no patient had grade 4–5 events. The 9-year CI of grade 1–2 cardiac failure was 1.3%, grade 3–4 was 15%, and grade 5 was 2.1%; of grade 1–2, arrhythmia was 1.9%, grade 3–4 was 9.1%, and grade 5 was 1%. Among 285 intensive therapy patients, median overall survival decreased in those experiencing grade 3–4 cardiac events (p < 0.001). We observed a high incidence of cardiac toxicity associated with significant mortality in AML.

Introduction: Pts with AML often present with hyperleukocytosis, defined with a white blood cell count (WBC) of >50 or >100 × 10⁹/L. Hyperleukocytosis is associated with higher rates of complications and death especially when associated with clinical leukostasis. There are no clear guidelines outlining the best cytoreductive strategy and the use of leukapheresis is based on institutional practice. Limited data is available regarding characteristics of AML pts with hyperleukocytosis, treatment patterns, short and long-term clinical outcomes. Methods: Data were collected retrospectively from 12 centers in the United States and Europe. Eligible pts had newly diagnosed AML, WBC > 50 × 10⁹/L, and had received intensive chemotherapy (IC). Pts with hyperleukocytosis who did not receive IC are described in a separate Kaplan-Meier methods estimated overall survival (OS) from time of presentation till death or end of follow-up. Clinical evidence of leukostasis was defined as new onset hypoxia, chest pain, headache, focal neurological symptoms, priapism, intestinal ischemia and acute renal failure attributed to hyperleukocytosis by the primary provider of the pt. Results: Among 1050 pts with AML and hyperleukocytosis whose data were collected, 787 were reported to have received intensive chemotherapy and were included in this analysis. The median age was 55 years (range [R], 15-86), and 51% were male (Table 1). Median WBC at presentation was 109 × 10⁹/L (R, 47-561) and 57% had WBC > 100 × 10⁹/L. Median hemoglobin was 9.2 g/dL (R, 3.6-126) and median platelet count was 31 x 10⁹/L (R, 3-1268). A good, intermediate and poor risk karyotype were present in 31%, 51% and 18% of pts, respectively. Clinical leukostasis, tumor lysis syndrome (TLS) and disseminated intravascular coagulation (DIC) were present in 27%, 28% and 18% of pts at time of presentation, respectively (Table 1). Organs affected by leukostasis were the lung, CNS, retina, heart, kidney and GI tract in 44%, 36%, 6%, 6%, 5% and 4%, respectively. Leukapheresis was administered in 117 pts (15%) (Figure 1). Four centers did not use leukapheresis. 31% of pts with clinical leukostasis underwent leukapheresis and 10% of pts without clinical leukostasis received leukapheresis (p<0.001). Pts, who underwent leukapheresis, had statistically significant higher WBC and higher % of FLT3 mutations compared to pts, who did not undergo leukapheresis (Table 1). In pts who did not receive leukapheresis, hyperleukocytosis was managed either by immediate initiation of intensive chemotherapy (n=342, 53%) or by the administration of hydroxyurea followed by intensive chemotherapy (n=302, 47%). Pts managed with leukapheresis, received either immediate (within 24h) induction of intense chemotherapy (n=71, 61%) or delayed (after 24h) induction of intensive chemotherapy (n=42, 36%) after completion of leukapheresis. The 30-day mortality was 16.6% (95%CI, 13.9-19.3%); 20%, 11% and 14% of pts were admitted to the ICU, underwent hemodialysis, or required mechanical ventilation, respectively (Table 2). After initiation of chemotherapy, 51% (95%CI, 46.9%-54.1%) had a complete remission (CR), 14% (95%CI, 11.4%- 16.4%) had a complete remission with incomplete count recovery (CRi) and 4% (95%CI, 2.5%-5.4%) achieved a partial remission (PR) whereas 32% (95%CI, 28.7%-35.4%) had no response to therapy (Table 2). Response to chemotherapy lasted a median of 202 days (R,14-3575) and 43% of pts experienced a relapse of their disease; 31% of pts underwent a hematopoietic stem cell transplant (HSCT). Median OS for all pts was 12.6 months (95%CI, 11.5-14.9) (Figure 1A). Median OS was 14.1 months (95%CI, 12.3-18.7) for pts with a WBC 100 × 10⁹/L (p=0.11) (Figure 1B). Median OS was 15.2 months (95%CI, 13.4-17.5) for pts without clinical leukostasis, significantly longer than the median OS of 7.4 months (95%CI, 3.9-9.8) for pts with symptoms of leukostasis (p<0.0001) (Figure 1C). Conclusions: To our knowledge, this is largest reported cohort of pts with AML and hyperleukocytosis treated with intensive chemotherapy. Clinical leukostasis was present in about a quarter of pts and was associated with worse OS. Most pts were managed with chemotherapy alone, and leukapheresis was only used in a small subgroup of pts (15%). The impact of leukapheresis and other variables on outcomes are presented in a separate

Background/Objectives: Patients with relapsed/refractory (R/R) AML with FLT3 mutation (FLT3^mut) have a dismal prognosis. FLT3^mut offers a target for therapy in these patients. Gilteritinib (gilter) and quizartinib (quizar) have demonstrated efficacy as single agents in two phase 3 clinical trials. Methods: We retrospectively analyzed the characteristics, treatments, and outcomes of 50 patients with R/R FLT3^mut AML who received gilter or quizar as monotherapy in 27 Spanish centers before their commercial availability. Forty-four patients were treated with gilter and six with quizar. Results: The median age was 62.5 years, and 52% were women. Most patients presented with FLT3-ITD mutations (80%); 46% had refractory disease and 54% had relapsed disease at treatment initiation. First-line treatment was chemotherapy in 80% of patients, with 40% of these also receiving midostaurin. Twenty-five patients (50%) had previously received FLT3 inhibitor, and twenty-eight (56%) had received more than one line treatment before starting gilter/quizar. The rates of complete remission (CR), CR without hematological recovery (CRi), and partial remission were 22%, 18%, and 16%, respectively. The median overall survival (OS) and disease-free survival were 4.74 months and 2.99 months, respectively. We observed a significant improvement in OS in patients who had received only one prior line of therapy compared to those who had received two or more therapies (10.77 months vs. 4.24 months, p = 0.016). Multivariate analysis identified failure to achieve CR/CRi, receiving more than one prior line of therapy, age, and white blood cells count as independent prognostic factors for OS. The most common toxicities were febrile neutropenia, liver function abnormalities, and QT interval prolongation. Conclusions: Gilter/quizar monotherapy are effective and tolerable options for patients with R/R FLT3^mut AML in a real-world setting. Response and toxicity rates are similar to those reported in the phase 3 trials, despite the more heterogeneous nature of the study population.

• Dapolsertib (MEN1703) is a dual kinase inhibitor of proviral integration site for PIM and FLT3 kinases. • Dapolsertib has a manageable safety profile and activity in a phase 1/2 study in patients with AML.

Background: Information regarding the impact on healthcare systems of secondary acute myeloid leukemia (sAML) is scarce. Methods: A retrospective review of medical charts identified patients aged 60–75 years with sAML between 2010 and 2019. Patient information was collected from diagnosis to death or last follow-up. Outpatient resource use, reimbursement, frequency and duration of hospitalization, and transfusion burden were assessed. Forty-six patients with a median age of 64 years were included. Anthracycline plus cytarabine regimens were the most common induction treatment (39 patients, 85%). The ratio of the total days hospitalized between the total follow-up was 29%, with a sum of 204 hospitalizations (average four/patient; average duration 21 days). The total average reimbursement was EUR 90,008 per patient, with the majority (EUR 77,827) related to hospital admissions (EUR 17,403/hospitalization). Most hospitalizations (163, mean 22 days) occurred in the period before the first allogeneic hematopoietic stem cell transplant (alloHSCT), costing EUR 59,698 per patient and EUR 15,857 per hospitalization. The period after alloHSCT (in only 10 patients) had 41 hospitalizations (mean 21 days), and a mean reimbursement cost of EUR 99,542 per patient and EUR 24,278 per hospitalization. In conclusion, there is a high consumption of economic and healthcare resources in elderly patients with sAML receiving active treatments in Spain.