Prophylactic use of carvedilol to prevent ventricular dysfunction in patients with cancer treated with doxorubicin

Objective: Deterioration in ventricular function is often observed in patients treated with anthracyclines for cancer. There is a paucity of evidence on interventions that might provide cardio-protection. We investigated whether prophylactic use of carvedilol can prevent doxorubicin-induced cardiotoxicity and whether any observed effect is dose related. Methods: A prospective, randomized, double-blind study in patients treated with doxorubicin, comparing placebo (n = 38) with different doses of carvedilol [6.25 mg/day (n = 41), 12.5 mg/day (n = 38) or 25 mg/day (n = 37)]. The primary endpoint was the measured change in left ventricular ejection fraction (LVEF) from baseline to 6 months. Results: LVEF decreased from 62 ± 5% at baseline to 58 ± 7% at 6-months (p = 0.002) in patients assigned to placebo but no statistically significant changes were observed in any of the 3 carvedilol groups. At 6 months, only one of 116 patients (1%) assigned to carvedilol had an LVEF < 50% compared to four of the 38 assigned to placebo (11%), (p = 0.013). No significant differences were noted between carvedilol and placebo in terms of the development of diastolic dysfunction, clinically overt heart failure or death. Conclusions: Carvedilol might prevent deterioration in LVEF in cancer patients treated with doxorubicin. This effect may not be dose related within the studied range

Is the outcome of childhood acute myeloid leukemia with t(8;21) inferior in Saudi Arabia? A multicenter SAPHOS leukemia group study

Background: Despite the confirmed favorable prognosis of childhood t(8;21) acute myeloid leukemia (AML), recent reports suggest heterogeneity in survival outcomes in this subtype of AML may be influenced by ethnicity. Therefore, we aimed to assess the outcome of childhood t(8;21) AML in an Arab population to evaluate if survival outcomes were inferior and determine the predictive relevance of additional cytogenetic abnormalities. Methods: This multicenter retrospective study analyzed 175 de novo AML children of 14 years of age or younger consecutively diagnosed between January 2005 and December 2012. Survival outcomes were analyzed and patients with t(8;21) were stratified on the basis of karyotype into sole and additional cytogenetic groups. Results: A total of 33 (18.9%) patients had t(8;21) AML. Complete remission (CR) was achieved in 31 (93.9%) patients. The 5-year overall survival, event-free survival, cumulative incidence of relapse (CIR), and remission death rates were 59.9 ± 9.2, 45.6 ± 9.1, 36.4, and 9.1%, respectively. Despite the administration of hematopoietic stem-cell-transplant salvage therapy in first relapse, five out of 11 (45.5%) relapsed patients died of disease. Subanalysis of sole vs. additional cytogenetic abnormalities revealed no significant difference in outcome. Conclusion: In the present study, childhood t(8;21) AML was associated with inferior survival and resistance to salvage therapy compared to reports from international groups. The inferior outcomes were unrelated to additional cytogenetic abnormalities. Further detailed genetic studies are warranted to unmask the biological and clinical differences between racial/ethnic groups. Given the high CR rate of childhood t(8;21) AML, further modification of postremission therapy to improve the CIR rate is needed