NPM1mut acute myeloid leukemia (AML) has been identified as a distinct entity of myeloid neoplasms according to the 2017 European LeukemiaNet (ELN) guidelines. It confers a favorable prognosis regardless of cytogenetic abnormalities. We evaluated 418 newly diagnosed AML patients to test the validity of this hypothesis. Seventy-four patients with NPM1mut AML showed a good response to induction and a relatively favorable prognosis. Abnormal karyotypes were observed in 15 patients. Chromosomal abnormalities were significantly associated with a worse prognosis in NPM1mut AML patients (5-year overall survival (OS): 38.9 ± 12.9%, p = .037; event-free survival (EFS): 33.3 ± 12.2%, p = .043, respectively). Four patients with abnormal karyotypes who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) during CR1 had longer survival than those who received chemotherapy only. Multivariable analysis revealed abnormal karyotypes independently predicted OS and EFS among NPM1mut AML patients. In summary, cytogenetic abnormalities are strong prognostic indicators in NPM1mut AML. Therefore, they should be classified accordingly, and alloHSCT should be performed on selected patients during CR1.

The therapeutic landscape for acute myeloid leukemia (AML) has changed dramatically with the approval of targeted agents, including venetoclax, midostaurin, gilteritinib, ivosidenib, and enasidenib, among others. However, older patients with AML continue to experience poorer outcomes and are in ongoing need of more effective and less toxic regimens. This review examines the efficacy of novel therapeutics and promising combination approaches to further improve outcomes in the treatment of patients with AML.

Midostaurin is a multitargeted tyrosine kinase inhibitor approved by the Food and Drug Administration for FMS-related tyrosine kinase 3-positive acute myeloid leukemia in combination with standard daunorubicin and cytarabine induction and high-dose cytarabine consolidation. The pharmacokinetics of midostaurin in the setting of severe renal impairment (creatinine clearance [CrCl] 15-29 mL/min utilizing Cockcroft-Gault method) and end-stage renal disease are unknown. Midostaurin is primarily metabolized by the liver through the CYP3A4 enzyme with fecal excretion accounting for 95% of the dose (4% recovered as unchanged drug). Only 5% of the parent drug is found in the urine. This is the first case report documenting the administration of midostaurin in two patients with end-stage renal disease on HD. Given the limited excretion of both active and inactive metabolites of midostaurin in the urine, one does not expect an increase in toxicity related to impaired drug excretion. Although this report describes the likely successful utilization of midostaurin, caution should be exercised when administering in patient populations with end organ disease. Medical history, concomitant comorbidities, and goals of therapy should be taken into account.

Complement is undeniably quintessential for innate immunity by detecting and eliminating infectious microorganisms. Recent work, however, highlights an equally profound impact of complement on the induction and regulation of a wide range of immune cells. In particular, the complement regulator CD46 emerges as a key sensor of immune activation and a vital modulator of adaptive immunity. In this review, we summarize the current knowledge of CD46-mediated signalling events and their functional consequences on immune-competent cells with a specific focus on those in CD4(+) T cells. We will also discuss the promises and challenges that potential therapeutic modulation of CD46 may hold and pose.

About 50% of acute myeloid leukemia (AML) patients show the occurrence of non-random chromosome rearrangements. Most of the recurrent karyotypic rearrangements in AML have been defined as distinct disease entities in the 2008 World Health Organization (WHO) classification. In this paper we report an AML case showing a novel t(4;16)(q25;q23.1) rearrangement causing the activation of epidermal growth factor (EGF) and elongation of long-chain fatty acids family member 6 (ELOVL6) genes, rather than the generation of a novel fusion gene.