Busulfan, fludarabine, and melphalan are effective conditioning for pediatric and young adult patients with myeloid malignancies underdoing matched sibling or alternative donor transplantation

alexandrossfakianakis shared this article with you from Inoreader Busulfan, fludarabine, and melphalan are effective conditioning for pediatric and young adult patients with myeloid malignancies underdoing matched sibling or alternative donor transplantation via Pediatric Blood & Cancer Abstract Background Allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative option for patients with high-risk myeloid malignancies. Procedure We present our 10-year experience (October 2012 to October 2021) of consecutive allo-HCT in patients with myeloid malignancies treated on the pediatric HCT service and conditioned with myeloablative targeted dose—busulfan (BU), fludarabine (FLU), and melphalan (MEL). Twenty-three children, adolescents, and young adult patients (CAYA) (median age 15.4 years) with acute myeloid leukemia (AML, n = 17), myelodysplastic syndrome (MDS, n = 4), or chronic myeloid leukemia (CML, n = 2) underwent allo-HCT post-BU-FLU-MEL. Four patients had treatment-related AML/MDS. Donor/stem cell source was matched sibling donor (MSD) PBSC (n = 7), matched unrelated donor (MUD) PBSC (n = 2), umbilical cord blood (UCB) (n = 3), or haploidentical-BMT (n = 11). Risk stratification was low (n = 2), intermediate (n = 15), high (n = 3), and very high risk (n = 1). The two patients with CML had failed tyrosine kinase inhibitor t herapies. Results With a median follow-up of 41.6 months, the relapse rate is only 4.5% with an overall survival (OS) 100%, progression-free survival (PFS) 95.5%, and graft-versus-host-free-relapse-free survival (GRFS) 67.8%. The donor source and the acute graft-versus-host disease (GvHD) prophylaxis regimen significantly impacted grade II–IV aGvHD 66.7% versus 19.2% (p = .039) and chronic graft-versus-host-disease (cGvHD) 66.7% versus 0% (p = .002) in the patients receiving MSD or MUD PBSC compared to haplo-BMT, respectively, resulting in improved GRFS in haplo-BMT, 83.3% compared to 40% matched donor peripheral blood stem cell transplant (PBSCT) (p = .025). Conclusions Our results demonstrate that BU-FLU-MEL is efficacious conditioning for disease control in young patients with myeloid malignancies undergoing MSD or alternative donor allo-HCT, but in the setting of PBSC grafts with cyclosporine A-methotrexate (CSA-MTX) GvHD prophylaxis, it results in an unacceptably high incidence of GvHD. View on Web

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Cardiovascular toxicities with pediatric tyrosine kinase inhibitor therapy: An analysis of adverse events reported to the Food and Drug Administration

alexandrossfakianakis shared this article with you from Inoreader Cardiovascular toxicities with pediatric tyrosine kinase inhibitor therapy: An analysis of adverse events reported to the Food and Drug Administration via Pediatric Blood & Cancer Abstract We sought to examine cardiovascular toxicities associated with tyrosine kinase inhibitors in pediatrics. We examined 1624 pediatric adverse events with imatinib, dasatinib, sorafenib, pazopanib, crizotinib, and ruxolitinib reported to the Food and Drug Administration between January 1, 2015, and August 14, 2020. There were 102 cardiovascular event reports. Hypertension was the most commonly reported cardiovascular event and was most frequently associated with sorafenib and pazopanib. The presence of infection increased the reporting odds of cardiovascular events overall and specifically cardiac arrest, heart failure, and hypertension. These data provide early insight into cardiovascular toxicities with tyrosine kinase inhibitor use in pediatrics. View on Web

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The Effect of Hyperosmolar Water-Soluble Contrast for the Management of Adhesive Small Bowel Obstruction: A Systematic Review and Meta-Analysis

alexandrossfakianakis shared this article with you from Inoreader The Effect of Hyperosmolar Water-Soluble Contrast for the Management of Adhesive Small Bowel Obstruction: A Systematic Review and Meta-Analysis via Annals of Surgery - Most Popular Articles Objective: To better understand the efficacy of water-soluble contrast (WSC) in the treatment of adhesive small bowel obstruction (SBO). Background: Guidelines recommend using WSC to treat adhesive SBO nonoperatively by acting as a cathartic agent. The evidence supporting this practice is mixed. Methods: A systematic review and meta-analysis of published articles describing the effect of WSC compared with control treatments was performed for the period of January 1, 1990 to November 1, 2021. Study quality was assessed using the Cochrane risk-of-bias and the Newcastle-Ottawa tools. The therapeutic effect of WSC was assessed by operative rates and hospital length of stay (HLOS) in nonsurgical patients. Results: The initial search yielded 4879 articles, of which, 28 were selected for full text review. We identified 11 eligible randomized controlled trials (RCTs) which included 817 patients and 9 observational studies of 3944 patients. HLOS in nonsurgical patients decreased by 1.95 days (95% confidence interval: 0.56–3.3) in the RCTs and could not be assessed in the observational studies. WSC did not significantly affect operative rates in the RCTs (19.8% vs. 21.4%) but did reduce rates in the observational studies (11% vs. 16%, risk ratio: 0.56, 95% confidence interval: 0.39–0.82). Conclusion: WSC studies may reduce HLOS for patients who have SBO and do not require surgery. However, the current literature is heterogenous with considerable design limitations. High-quality RCTs are needed using standardized protocols to determine the full benefit of WSC for the management of SBO. View on Web

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