Management of refractory/relapsed acute leukemia with heart limitation by anthracycline-free chemotherapy regimens in pediatric patients: New hypothesis and new approach

Background: Anthracycline therapy for acute leukemia may be associated with significant morbidity and mortality in children or elderly patients that have a degree of heart failure. Patients with prior anthracycline exposure, those with pre-existing heart disease, or who have received the total anthracycline dose present an increased risk for cardiotoxicity. Therefore, new chemotherapy regimens in these situations would be life saving for leukemia patients. We have conducted a systematic review of possible strategies for rescue regimens without anthracycline in refractory acute leukemia patients. Methods: We gathered the data from 5 creation databases and relevant website until August 2016. We selected randomized clinical trials or other studies that used anthracycline-free chemotherapy regimens to treat acute refractory leukemia in children and adults. The quality of the studies was evaluated according to the Cochrane risk of the polarization tool. All stages of the review were independently conducted by two authors. We obtained data from 75 main clinical trials. Results: There were 75 trials included from which 4 were considered to be at low risk for bias. Most trials showed that the improvement did not reach statistical significance. Conclusion: Evidence existed to support the use of the combination of fludarabine, cytarabine, and filgrastim, ICE-rituximab chemotherapy regimens, or monoclonal antibodies such as tyrosine kinase inhibitors (Sorafenib) useful for acute refractory/relapsed leukemia.These drugs are used as first salvage regimens or clofarabine and cladribine for acute myeloid leukemia in patients for whom combined anthracycline chemotherapy is inappropriate. © 2018, Shiraz University of Medical Sciences. All rights reserved

Management of refractory/relapsed acute leukemia with heart limitation by anthracycline-free chemotherapy regimens in pediatric patients: New hypothesis and new approach

Background: Anthracycline therapy for acute leukemia may be associated with significant morbidity and mortality in children or elderly patients that have a degree of heart failure. Patients with prior anthracycline exposure, those with pre-existing heart disease, or who have received the total anthracycline dose present an increased risk for cardiotoxicity. Therefore, new chemotherapy regimens in these situations would be life saving for leukemia patients. We have conducted a systematic review of possible strategies for rescue regimens without anthracycline in refractory acute leukemia patients. Methods: We gathered the data from 5 creation databases and relevant website until August 2016. We selected randomized clinical trials or other studies that used anthracycline-free chemotherapy regimens to treat acute refractory leukemia in children and adults. The quality of the studies was evaluated according to the Cochrane risk of the polarization tool. All stages of the review were independently conducted by two authors. We obtained data from 75 main clinical trials. Results: There were 75 trials included from which 4 were considered to be at low risk for bias. Most trials showed that the improvement did not reach statistical significance. Conclusion: Evidence existed to support the use of the combination of fludarabine, cytarabine, and filgrastim, ICE-rituximab chemotherapy regimens, or monoclonal antibodies such as tyrosine kinase inhibitors (Sorafenib) useful for acute refractory/relapsed leukemia.These drugs are used as first salvage regimens or clofarabine and cladribine for acute myeloid leukemia in patients for whom combined anthracycline chemotherapy is inappropriate. © 2018, Shiraz University of Medical Sciences. All rights reserved

Radiation-induced non-targeted effect and carcinogenesis; implications in clinical radiotherapy

Bystander or non-targeted effect is known to be an interesting phenomenon in radio-biology. The genetic consequences of bystander effect on non-irradiated cells have shown that this phenomenon can be considered as one of the most important factors involved in secondary cancer after exposure to ionizing radiation. Every year, millions of people around the world undergo radiotherapy in order to cure different types of cancers. The most crucial aim of radiotherapy is to improve treatment efficiency by reducing early and late effects of exposure to clinical doses of radiation. Secondary cancer induction resulted from exposure to high doses of radiation during treatment can reduce the effectiveness of this modality for cancer treatment. The perception of carcinogenesis risk of bystander effects and factors involved in this phenomenon might help reduce secondary cancer incidence years after radiotherapy. Different mo-dalities such as radiation LET, dose and dose rate, fractionation, types of tissue, gender of patients, etc. may be involved in carcinogenesis risk of bystander effects. Therefore, selecting an appropriate treatment modality may improve cost-effectiveness of radiation therapy as well as the quality of life in survived patients. In this review, we first focus on the carcinogenesis evidence of non-targeted effects in radiotherapy and then review physical and biological factors that may influence the risk of secondary cancer induced by this phenomenon. © 2018, Shiraz University of Medical Sciences. All rights reserved

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo