Mustafa, Reem A

Abstract We conducted this systematic review to evaluate outcomes of thrombolysis followed by anticoagulation vs anticoagulation alone in pediatric patients with venous thromboembolism (VTE). This systematic review addresses mortality, VTE resolution, recurrence, bleeding, and organ-specific outcomes in 5 PICO (population, intervention, comparison, outcomes) questions on thrombolysis across pulmonary embolism (PE), extremity deep vein thrombosis (DVT), right atrial thrombosis (RAT), cerebral sinus venous thrombosis (CSVT), and renal vein thrombosis (RVT). Meta-analysis reported risk ratios or differences (95% confidence intervals [CIs]), and absolute effects per 1000 patients. Certainty of evidence was assessed using GRADE (Grading of recommendation, assessment, Development, and Evaluation) guidelines. Thirteen nonrandomized studies were included and no randomized clinical trials addressed these questions. Thrombolysis might be associated with a higher risk of major bleeding, clinically relevant nonmajor bleeding, or unspecified bleeding with risk differences of 0.09 (95% CI, −0.06 to 0.23), 0.06 (95% CI, −0.11 to 0.22), and 0.09 (95% CI, −0.04 to 0.23), respectively. In PE with hemodynamic compromise, thrombolysis might be associated with a lower risk of mortality but conclusions on PE progression were uncertain in submassive PE. In DVT, thrombolysis may have little to no effect on mortality or thrombus resolution but might be associated with lower risk of postthrombotic syndrome. In RAT, thrombolysis might have little to no effect on thrombus resolution but a higher risk of major bleeding and mortality. For CSVT and RVT, the evidence was very limited. These findings were based on very-low-certainty evidence because of confounding and imprecision from small sample sizes. This systematic review highlights key challenges in developing recommendations for thrombolysis in children with VTE.

e18503 Background: Acute Myeloid Leukemia (AML) with FLT3-ITD mutations has poor prognosis and high relapse rates after allogeneic hematopoietic stem cell transplantation (allo-HCT). Post-transplant FLT3 inhibitor (FLT3i) maintenance therapy aims to prevent relapse and improve survival. However, randomized trials vary in FLT3i potency, its use during induction, maintenance duration, and measurable residual disease (MRD) assessment, which contribute to conflicting impacts on relapse-free survival (RFS) and overall survival (OS). This systematic review and meta-analysis assessed the efficacy and safety of FLT3i maintenance versus standard-of-care (SOC) in FLT3-ITD-positive AML post-allo-HCT. Methods: A systematic review was conducted following PRISMA guidelines, focusing on randomized controlled trials (RCTs) assessing FLT3i maintenance after allo-HCT. Comprehensive searches in PUBMED, EMBASE, CENTRAL, and ClinicalTrials.gov identified eligible studies. Statistical analyses were performed in R software (version 4.4.0) using the “meta” package. Results: Four RCTs involving 701 patients were included, with 351 patients in the intervention group and 350 in the control group. Patients’ ages ranged from 18 to 78 years, with 51.4% male and 48.6% female. Cytogenetic risk in the intervention group was 4.7% favorable, 74.4% intermediate, and 4.7% adverse; in the control group, these rates were 2.5%, 65.9%, and 4.7%, respectively. FLT3i maintenance significantly reduced pooled relapse risk (HR 0.50, 95% CI: 0.34–0.74) and pooled mortality (HR 0.63, 95% CI: 0.44–0.91) at a median follow up of 24 months from allo-HCT. Hematologic toxicity was higher in the FLT3i group (RR 2.12, 95% CI: 1.67–2.70), as was chronic GVHD (RR 1.18, 95% CI: 1.00–1.41). Acute GVHD (RR 1.05, 95% CI: 0.78–1.41) and hepatotoxicity (RR 1.09, 95% CI: 0.72–1.66) rates were similar, while skin toxicity was less frequent in the FLT3i group (RR 0.36, 95% CI: 0.16–0.84). Conclusions: Our analysis suggests that FLT3i maintenance post-allo-HCT improves RFS and OS in FLT3-ITD-mutated AML patients compared to SOC but is associated with increased hematologic toxicity and chronic GVHD. Future clinical trials should evaluate the benefit of FLT3i maintenance post alloHCT based on MRD status assessed by next generation sequencing (NGS) based assays. Outcomes reported by the included studies. Type of FLT3-i Relapse free survival at 24 months Overall Survival at 24 months HR (95% CI) P-value HR (95% CI) P-value Levis et al. Giltetrinib 0.679(0.459-1.005) 0.52 0.846(0.554-1.293) 0.44 Burchert et al. Sorafenib 0.39(0.18-0.85) 0.01 0.516(0.239-1.112) 0.85 Maziarz et al. Midostaurin 0.60(0.17-2.14) 0.42 0.58(0.19-1.79) 0.34 Xuan et al. Sorafenib 0.37(0.22-0.63) <0.0001 0.48(0.27-0.86) 0.01 Pooled Hazard Ratio (95% CI) 0.50 (0.34-0.74) 0.63 (0.44-0.91)

ObjectiveThe objective is to provide evidence‐based and expert guidance for the screening, treatment, and management of lupus nephritis.MethodsThe Core Team developed clinical questions for screening, treatment, and management of lupus nephritis using the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were completed for each PICO question, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the quality of evidence and to formulate recommendations. The Voting Panel achieved a consensus ≥70% on the direction (for or against) and strength (strong or conditional) of each recommendation.ResultsWe present 28 graded recommendations (7 strong, 21 conditional) and 13 ungraded, consensus‐based good practice statements for the screening and management of lupus nephritis. Our recommendations focus on the unifying principle that lupus nephritis therapy is continuous and ongoing, rather than consisting of discrete induction/initial and maintenance/subsequent therapies. Therapy should include pulse glucocorticoids followed by oral glucocorticoid taper and two additional immunosuppressive agents for 3–5 years for those achieving complete renal response.ConclusionThis guideline provides direction for clinicians regarding screening and treatment decisions for management of lupus nephritis. These recommendations should not be used to limit or deny access to therapies, as treatment decisions may vary due to the unique clinical situation and personal preferences of each individual patient.

Objective The objective is to provide evidence‐based and expert guidance for the screening, treatment, and management of lupus nephritis. Methods The Core Team developed clinical questions for screening, treatment, and management of lupus nephritis using the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were completed for each PICO question, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the quality of evidence and to formulate recommendations. The Voting Panel achieved a consensus ≥70% on the direction (for or against) and strength (strong or conditional) of each recommendation. Results We present 28 graded recommendations (7 strong, 21 conditional) and 13 ungraded, consensus‐based good practice statements for the screening and management of lupus nephritis. Our recommendations focus on the unifying principle that lupus nephritis therapy is continuous and ongoing, rather than consisting of discrete induction/initial and maintenance/subsequent therapies. Therapy should include pulse glucocorticoids followed by oral glucocorticoid taper and two additional immunosuppressive agents for 3–5 years for those achieving complete renal response. Conclusion This guideline provides direction for clinicians regarding screening and treatment decisions for management of lupus nephritis. These recommendations should not be used to limit or deny access to therapies, as treatment decisions may vary due to the unique clinical situation and personal preferences of each individual patient.