Safety and efficacy of FLAG-Ida-based therapy combined with venetoclax for the treatment for newly diagnosed and relapsed/refractory patients with AML - A systematic review.

Venetoclax (VEN) in combination with intensive chemotherapy (IC) is increasingly used to treat patients with high-risk acute myeloid leukemia (AML). We conducted a systematic review to assess the safety and efficacy outcomes of FLAG-IDA in combination with VEN. The primary safety outcome was infection rate; the primary efficacy outcome was response to treatment (composite complete remission (CRc) and overall response rate (ORR). Risk of bias was assessed according to the ROBINS-I tool. Six studies including 221 patients with newly-diagnosed (ND AML (n = 120)) and R/R AML (n = 101) disease, were included in this systematic review. Pooling of results was not conducted due to major differences between studies. The reported rates of neutropenic fever, bacteremia, pneumonia and invasive fungal infections were at 44-55 %, 24-48 %, 12-30 % and 11-36 % of assessed patients, respectively. Time to ANC and platelet recovery ranged between 23 and 29 and 23-31 days, respectively. Early death rate was 8.7 % (14/160) patients: four patients at 30 days, additional ten in 60 days. CRc rates ranged between 53 % and 78 % for R/R AML. CRc for ND was reported by one study only (89 %). ORR were reported in 60-78 % of patients with R/R AML. Only one study reported an ORR for ND patients of 98 %. In our systematic review, FLAG-Ida plus VEN proved to be a potentially tolerable and effective regimen in ND and R/R AML patients. We suggest further evaluation and confirmation for the safety and efficacy of this new protocol in future RCTs.

Incidence, predictors and prognostic implications of dyspnea at admission among acute coronary syndrome patients without heart failure.

BACKGROUND: Among patients with stable coronary artery disease, effort-related dyspnea is associated with a larger ischemic territory and worse outcome. Whether dyspnea, not related to heart failure, is also associated with adverse outcome among patients with acute coronary syndromes (ACS) has not been fully elucidated. METHODS: We studied ACS patients enrolled in the biennial Acute Coronary Syndrome Israeli Surveys (ACSIS) during 2010-2013 who were classified as Killip 1. A retrospective comparative analysis was performed between patients with chest pain alone (n = 2017) and those with chest pain with dyspnea (n = 417). RESULTS: Patients with dyspnea were older (64.4 ±â€¯13 vs.61.8 ±â€¯12, p < 0.001), more frequently women (81% vs. 75% p < 0.001) and had higher rates of multiple comorbidities. Statistically significant predictors for dyspnea as a presenting symptom were female sex [HR 1.47 (1.11, 1.89)], chronic kidney disease [HR 1.81 (1.30, 2.52)], chronic obstructive pulmonary disease [HR 1.59 (1.045, 2.429)] and angina ≥24 h [HR 1.46 (1.147, 1.86)]. Patients presenting with dyspnea were less likely to undergo primary reperfusion (31% vs. 42%, p < 0.001) and overall coronary intervention (71% vs. 78%, p < 0.001) during their hospitalization. Mortality rates were significantly higher among patients presenting with dyspnea both at 30-day (3% vs. 2%, p = 0.017) and at 1-year follow-up (9% vs. 4%, p < 0.001). Dyspnea was as an independent predictor of 1-year mortality. CONCLUSION: The presence of dyspnea is frequent and associated with adverse outcome among patients with ACS without signs of heart failure. Early identification of this higher-risk cohort of patients may allow intensifying treatment and careful follow-up may be warranted.

Effects of natural and novel synthetic jasmonates in experimental metastatic melanoma.

BACKGROUND AND PURPOSE: No current treatment reliably affects the course of metastatic melanoma. Consequently, novel approaches to the control of metastasis are actively sought. The overall goal of the present study was to identify new anti-metastatic agents active against melanoma cells. EXPERIMENTAL APPROACH: Two directions were taken: 1. To determine whether the natural plant hormone methyl jasmonate, which kills cancer cells selectively, can suppress the characteristic metastatic behavior of B16-F10 melanoma cells; 2. To synthesize and identify novel jasmonate derivatives with better cytotoxic and anti-metastatic activities than methyl jasmonate. KEY RESULTS: We found that methyl jasmonate suppressed B16-F10 cell motility and inhibited the development of experimental lung metastases of these cells. Furthermore, methyl jasmonate suppressed the motility of a sub-clone of these cells over-expressing P-glycoprotein and exhibiting multidrug resistance. The synthetic derivative Compound I (5,7,9,10-tetrabromo derivative of methyl jasmonate, the most active derivative) had greater cytotoxic potency (IC(50), 0.04 mM) than methyl jasmonate (IC(50), 2.6mM). Compound I prevented B16-F10 cell adhesion efficiently and inhibited the development of lung metastases at a much lower dose than methyl jasmonate. CONCLUSIONS AND IMPLICATIONS: Natural and synthetic jasmonates have anti-metastatic actions. Further development of these agents for the suppression of metastasis in melanoma and other types of cancer is warranted.