Celikbradley9532

Acute myeloid leukemia (AML) is an aggressive malignancy of the bone marrow that has a poor prognosis with traditional cytotoxic chemotherapy, especially in elderly patients. In recent years, small molecule inhibitors targeting AML-associated IDH1, IDH2, and FLT3 mutations have been FDA approved. However, the majority of AML cases do not have a targetable mutation. A variety of novel agents targeting both previously untargetable mutations and general pathways in AML are currently being investigated. Herein, we review selected new targeted therapies currently in early-phase clinical investigation in AML.

The DOT1L inhibitor pinometostat in KMT2A-rearranged AML, the menin inhibitors KO-539 and SYNDX-5613 in KMT2Ar and NPM1-mutated AML, and the mutant TP53 inhibitor APR-246 are examples of novel agents targeting specific mutations in AML. In addition, BET inhibitors, polo-like kinase inhibitors, and MDM2 inhibitors are promising new drug classes for AML which do not depend on the presence of a particular mutngoing clinical trials. Additional studies will be necessary to determine how best to incorporate these novel agents into routine clinical treatment of AML.

The objective of this trial was to evaluate the safety and efficacy of melatonin oral gel mouthwashes in the prevention and treatment of oral mucositis (OM) in patients treated with concurrent radiation and systemic treatment for head and neck cancer.

Randomized, phase II, double-blind, placebo-controlled trial (11 ratio) of 3% melatonin oral gel mouthwashes vs. placebo, during IMRT (total dose ≥ 66Gy) plus concurrent Q3W cisplatin or cetuximab. Primary endpoint grade 3-4 OM or Severe Oral Mucositis (SOM) incidence by RTOG, NCI, and a composite RTOG-NCI scales. Secondary endpoints SOM duration and grade 2-4 OM or Ulcerative Oral Mucositis (UOM) incidence and duration.

Eighty-four patients were included in the study. Concurrent systemic treatments were cisplatin (n = 54; 64%) or cetuximab (n = 30; 36%). Compared with the placebo arm, RTOG-defined SOM incidence was numerically lower in the 3% melatonin oral gel arm (53 vs. 64%, P = 0.36). In patients treated with cisplatin, assessed by the RTOG-NCI composite scale, both SOM incidence (44 vs. 78%; P = 0.02) and median SOM duration (0 vs. 22days; P = 0.022) were significantly reduced in the melatonin arm. Median UOM duration assessed by the RTOG-NCI scale was also significantly shorter in the melatonin arm (49 vs. 73days; P = 0.014). Rate of adverse events and overall response rate were similar between the two arms.

Treatment with melatonin oral gel showed a consistent trend to lower incidence and shorter SOM duration and shorter duration of UOM. These results warrant further investigation in phase III clinical trial.

Treatment with melatonin oral gel showed a consistent trend to lower incidence and shorter SOM duration and shorter duration of UOM. These results warrant further investigation in phase III clinical trial.Studies investigating the safety of IgPro10 (Privigen®, CSL Behring, King of Prussia, PA, USA) in Japanese patients with primary immunodeficiency (PID) are lacking. This study evaluated safety and tolerability of IgPro10 in Japanese patients with PID. In this prospective, open-label, single-arm, registrational study for Japan, IgPro10 was administered intravenously at pre-study doses of 138-556 mg/kg body weight per 3-/4-weekly dosing cycle for up to 4 months. Frequency and intensity of adverse events (AEs), their relationship to IgPro10 and AE rate per infusion (AERI) were evaluated. Of 11 enrolled patients, 10 completed the study. The median (range) total duration of exposure was 16.14 (4.1-16.3) weeks. Eight patients reported 19 AEs, none severe (based on maximum severity), giving an AERI of 0.442. One AE was deemed related to IgPro10 treatment. Three patients experienced temporally associated AEs. No serious AEs or deaths were reported. Nine patients (90%) who completed the study tolerated flow rates of ≥ 8 mg/kg/min; 5 tolerated 12 mg/kg/min (7.2 mL/kg/h), translating into a threefold decrease in mean infusion time. IgPro10 was well tolerated at a flow rate of up to 12 mg/kg/min. Safety and tolerability findings were consistent with previously reported studies in non-Japanese patients with PID.The long-term effects of pegfilgrastim administered in the first cycle of chemotherapy in day-to-day practice remain unclear. We retrospectively identified 114 patients aged ≥ 70 years with diffuse large B-cell lymphoma who received a rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP) regimen in our institution. Twenty-six patients received pegfilgrastim (pegfilgrastim group); of the 88 patients scheduled to receive conventional granulocyte-colony stimulating factor (G-CSF) when their neutrophil count decreased (neut-adjusted-G group), conventional G-CSF was ultimately administered to 57. During the first cycle of R-CHOP, the incidence of febrile neutropenia was lower in the pegfilgrastim group than in the neut-adjusted-G group (0% vs. 18%, p = 0.020). Throughout all cycles, a higher proportion of patients exhibited sustained relative dose intensity (≥ 80%) in the pegfilgrastim group than in the neut-adjusted-G group (25% vs. 4.0%, p = 0.008). A lower proportion of patients received a reduced dose in the second cycle in the pegfilgrastim group than in the neut-adjusted-G group (0% vs. 10%, p = 0.116). Although the differences were not significant, the pegfilgrastim group showed higher progression-free survival and overall survival than the neut-adjusted-G group. Adequate prevention of febrile neutropenia using pegfilgrastim during the first cycle of R-CHOP may contribute to avoidance of dose intensity reduction in all cycles.

Intervention studies using New Zealand green-lipped or greenshell™ mussel (GSM) (Perna canaliculus) extract in osteoarthritis (OA) patients have shown effective pain relief. This systematic review summarises the efficacy of GSM extracts in the treatment of OA.

A literature search of the three databases EMBASE, MEDLINE, and Scopus was performed to identify relevant articles published up to March 2020. Inclusion criteria were clinical trials published in English measuring the effect of supplementation of whole or a lipid extract from GSM on pain and mobility outcomes in OA patients.

A total of nine clinical trials were included in systematic review, from which five studies were considered appropriate for inclusion in a forest plot. Pooled results showed that GSM extracts (lipid extract or whole powder) provide moderate and clinically significant treatment effects on a visual analogue scale (VAS) pain score (effect size -0.46; 95% CI -0.82 to -0.10; p = 0.01). click here The whole GSM extract improved gastrointestinal symptoms in OA patients taking anti-inflammatory medications.