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Large pericardial effusion (LPE) and tamponade are purported manifestations associated with atypical chronic graft-versus-host disease (cGVHD); however, their temporal association with GVHD, management, and impact on overall outcome are not well established. We report a retrospective analysis of 38 patients who developed LPE from a cohort of 1265 (3.00%) patients age ≥18 years who underwent allogeneic hematopoietic cell transplantation (alloHCT) at Mayo Clinic between March 1993 and August 2020. The median patient age at the time of LPE was 54 years (interquartile range [IQR], 44 to 58 years), and 8 of the 38 patients (21%) had previous cardiomyopathy. The median time from alloHCT to detection of LPE was 197 days (IQR, 40 to 378 days). Overall, the incidence of grade II (15 of 38; 40%) and grade III-IV (9 of 38; 24%) acute GVHD (aGVHD) was higher in patients who developed LPE compared with those who did not develop LPE (P = .005). The incidence rates of moderate (10 of 38; 26%) and severe (15 of 38; 40%) cGVHD according to the 2014 National Institutes of Health cGVHD criteria were also higher in the LPE cohort (P = .03). Twenty-nine patients (76%) presented with cardiac tamponade, 32 patients (84%) underwent urgent pericardiocentesis for symptomatic LPE, and 2 patients had a pericardial window placement. Four patients were medically managed with colchicine, steroids, diuresis, and immunosuppressive therapy (IST). On multivariable analysis, HCT Comorbidity Index (HCT-CI) group (hazard ratio [HR] 3.57; [95% confidence interval (CI), 1.29 to 9.85; P = .014] for HCT-CI 1 to 2; 4.06 [95% CI, 1.50 to 10.99; P = .006] for HCT-CI ≥3) and aGVHD (HR, 2.38 [95% CI, 1.11 to 5.12; P = .026] for grade II and 2.82 [95% CI, 1.07 to 7.44; P = .038] for grade III-IV) were significant risk factors for developing LPE. At a median follow-up of 40 months post-alloHCT, median disease-free survival (DFS) was 34.2 months (95% CI, 25.3 to 45.7 months) in patients who did not develop LPE and 32.2 months (95% CI, 13.2 to undefined upper limit) in those who developed LPE (P = .41). The median overall survival (OS) post-alloHCT was 50.9 months (95% CI, 41.8 to 64.8 months) in patients who did not develop LPE and was 32.9 months (95% CI, 19.5 to undefined upper limit) in patients who developed LPE (P = .003). In summary, LPE and tamponade can present at various time points post-alloHCT, and management includes pericardiocentesis, steroids, and intensification/initiation of IST if associated with serositis. LPE does not appear to result in permanent cardiac damage but results in inferior OS., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Novel high-risk groups have recently been identified in adult acute lymphoblastic leukemia (ALL), including Philadelphia-like, therapy-related, and measurable residual disease after induction therapy. Furthermore, modern targeted therapies have recently been incorporated into ALL management; rituximab for CD20-positive and blinatumomab for measurable residual disease after induction therapy or relapsed or refractory disease. Allogeneic hematopoietic cell transplantation (allo-HCT) is recommended as consolidation therapy for high-risk ALL; however, its relative benefit for these high-risk groups and after novel therapies is unclear. We performed an analysis of posttransplantation outcomes in a cohort of 261 consecutive patients who underwent allo-HCT for ALL at the 3-site Mayo Clinic Cancer Center (January 1, 2008-December 31, 2018). With a median (range) follow-up of 22.4 months (0.5-135.0), the 100-day and 5-year cumulative incidences of nonrelapse mortality rates were 6.5% and 26.7%, respectively. The 5-year cumulative incidences of relapse and death were 22.6% and 46.2%, respectively. The 1-year estimate of the composite endpoint of graft-versus-host disease/relapse-free survival was 39.3%. We observed no associations of novel high-risk groups or modern targeted therapies with overall survival, nonrelapse mortality, or relapse in multivariable analysis. An increased risk of relapse was observed with T-ALL (hazard ratio, 2.16; 95% confidence interval, 1.14-4.09; P = .02) and hypodiploidy/near-triploidy (hazard ratio, 2.84; 95% confidence interval, 1.06-7.62; P = .04). Our analysis suggests that novel high-risk groups derive a similar benefit from allo-HCT as traditional high-risk adult ALL and that novel targeted therapies do not seem to independently predict for posttransplantation outcomes. It also calls for further exploration of maintenance strategies after Allo-HCT to prevent relapse in high-risk subgroups., (Copyright © 2020 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

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FLT3-internal tandem duplication occurs in 20-30% of acute myeloid leukemia and confers an adverse prognosis with its allelic ratio being a key risk stratifier. The US Food and Drug Administration recently approved FLT3 inhibitors midostaurin and gilteritinib in FLT3 mutation-positive acute myeloid leukemia. Historically, FLT3 was tested by fragment analysis, which has become the standard method endorsed by international guidelines. However, next generation sequencing is increasingly used at acute myeloid leukemia diagnosis given its ability to simultaneously evaluate multiple clinically informative markers. As FLT3-internal tandem duplication detection was known to be challenging by next generation sequencing and the results carry profound prognostic and therapeutic implications, it is important to thoroughly examine its performance in FLT3-internal tandem duplication detection and allelic ratio classification. In a comparative study with fragment analysis, we retrospectively reviewed our experience using a custom-designed, hybridization capture-based, targeted next generation sequencing panel. Among 7902 cases, FLT3-internal tandem duplication was detected in 335 with variable sizes (3-231 bp) and insertion sites. Fragment analysis was also performed in 402 cases, demonstrating 100% concordance in FLT3-internal tandem duplication detection. In 136 dual-tested, positive cases, 128/136 (94%) exhibited concordant high/low allelic ratio classifications. The remaining 6% showed borderline low allelic ratio by next generation sequencing. The two methods were concordant in FLT3-tyrosine kinase domain mutation detection at the hotspot D835/I836 targeted by fragment analysis. Furthermore, seven mutations which may benefit from FLT3 inhibitor therapy were detected by next generation sequencing, in regions not covered by fragment analysis. Our study demonstrates that using a hybridization capture-based chemistry and optimized bioinformatics pipeline, next generation sequencing can reliably detect FLT3-internal tandem duplication and classify its allelic ratio for acute myeloid leukemia risk stratification. Next generation sequencing also exhibits superior comprehensiveness in FLT3 mutation detection and may further improve personalized, targeted therapy in acute myeloid leukemia.