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Arsenic trioxide (ATO)-based regimens are standard in acute promyelocytic leukemia (APL). ATO-related nephrotoxicity has not been reported. We reviewed APL patients treated with ATO to identify cases of acute kidney injury (AKI). Clinically significant cases were characterized. Multivariate analysis was performed to identify predictors of idiopathic, clinically significant AKI. One hundred and eight patients were included. ATO dose was 0.15 mg/kg/day using actual body weight with no dose cap. Thirty-one (28.7%) AKI cases were identified, 10 (32.3%) clinically significant. Six were idiopathic; five required dialysis. The proportion with significant, idiopathic AKI was 15.8% in patients receiving >15mg ATO versus 0% in those receiving ≤15mg (p = 0.001). On multivariate analysis, only ATO dose was a significant predictor of clinically significant AKI (odds ratio of 1.91, 95%CI, 1.19–3.07, p = 0.007). High-dose ATO may be associated with significant nephrotoxicity. We recommend that ATO dose be capped at 15 mg to minimize toxicity for this curable disease. [ABSTRACT FROM AUTHOR]

Background Mold-active primary antifungal prophylaxis (PAP) is routinely recommended in neutropenic patients with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) undergoing remission-induction chemotherapy (RIC). Isavuconazole (ISAV) is an extended spectrum mold-active triazole and has superior tolerability and fewer significant drug–drug interactions compared with other triazoles. Methods In our investigator-initiated, phase 2 trial, treatment-naive adult patients with AML or MDS starting RIC received ISAV per the dosing recommendations in the US label until neutrophil recovery (absolute neutrophil count [ANC] ≥ 0.5 × 109/L) and attainment of complete remission, occurrence of invasive fungal infection (IFI), or for a maximum of 12 weeks. The primary endpoint was the incidence of proven/probable IFI during ISAV PAP and up to 30 days after the last dose. Results Sixty-five of 75 enrolled patients received ISAV PAP (median age, 67 years, median ANC at enrollment, 0.72 × 109/L). Thirty-two patients (49%) received oral targeted leukemia treatments (venetoclax, FTL3 inhibitors). Including the 30-day follow-up period, probable/proven and possible IFIs were encountered in 4 (6%) and 8 patients (12%), respectively. ISAV trough serum concentrations were consistently > 1 µg/mL, showed low intraindividual variation, and were not significantly influenced by chemotherapy regimen. Tolerability of ISAV was excellent, with only 3 cases (5%) of mild to moderate elevations of liver function tests and no QTc prolongations. Conclusions ISAV is a safe and effective alternative for PAP in patients with newly diagnosed AML/MDS undergoing RIC in the era of recently approved or emerging small-molecule antileukemia therapies. Clinical Trials Registration NCT03019939. [ABSTRACT FROM AUTHOR]

Abstract A diet of energy-dense food, characterized mainly as a high-fat diet, leads to a persistent excessive consumption defined as overeating. According to the National Institute of Health, more than 2 in 3 adults in the United States are overweight or obese, straining our healthcare system with epidemic proportions. Diets that include abstaining from high-fat foods, ironically, result in an increase in motivation and craving for said high-fat foods, defined as an incubation effect because the behavior aids in developing overeating. Previously, we have shown that modulation of neuromedin U receptor 2 (NMUR2) in the paraventricular nucleus of the hypothalamus (PVN) results in increased food intake and motivation for energy-dense foods. Here, we continue our focus on NMUR2 in the PVN, but in relation to the incubation effect on craving for high-fat food. We employed a model for incubation of craving by having rats abstain from high-fat foods for 30 days before undergoing intake of fatty food on fixed ratio and progressive ratio schedules of reinforcement, and then assess their response to reactivity to cues. Using this model, we compared the feeding behaviors of rats that underwent an mRNA knockdown of the NMUR2 in the PVN to controls after both underwent a 30-day abstinence from high-fat foods. Our results show knockdown of NMUR2 in the PVN blocks the incubation of feeding behavior for food-related cues and high-fat foods. [ABSTRACT FROM AUTHOR]

AbstractWe report on the long-term efficacy and safety of a phase 2 trial of sequential cladribine and rituximab in hairy cell leukemia (HCL). One-hundred and thirty-nine patients were enrolled: 111 in the frontline setting, 18 in first relapse, and 10 with variant HCL (HCLv). A complete response (CR) was achieved in 133 of 137 evaluable participants (97%) with measurable residual disease (MRD) negativity in 102 (77%). MRD status was not associated with significant differences in event-free survival (EFS) or overall survival (OS). With a median follow-up of 7.8 years (range: 0.40–18.8), eight patients have experienced disease relapse (5.8%), 4/111 with newly diagnosed HCL (3·6%) and 4/10 with HCLv (40%) (p = 0.002). The 10-year EFS and OS rates were 86.7% and 91.1%, respectively. Grade 3 adverse events were observed in 28 participants (20·1%), mostly due to infections. Treatment of HCL with sequential cladribine followed by rituximab is associated with excellent efficacy and safety results both in the frontline and relapsed settings. [ABSTRACT FROM AUTHOR]

Acute promyelocytic leukemia (APL) is characterized by the chromosomal translocation t (15;17) and the resulting gene PML-RARA, used for measurable residual disease (MRD) monitoring. Despite highly effective therapy for APL, MRD monitoring practices are not fully established. We aimed to assess the value of MRD monitoring by RT-qPCR in patients with APL treated with ATRA and arsenic trioxide +/- GO. We reviewed 223 patients with APL treated with this regimen. RT-qPCR for PML-RARA was measured every 3 months, and at 12, 18, and 24 months after therapy. Seven patients relapsed. Time to relapse was 7.9-12.4 months in 6 patients, and one patient relapsed after 79.5 months. These data show that MRD monitoring may be important for the detection of relapse in patients treated with this regimen within one year after completing therapy, however, since late molecular relapse is rare, our data suggest a low value of MRD monitoring beyond that first year.