Association of the social disorganization index with time to first septic shock event in children with acute myeloid leukemia.

BACKGROUND: Pediatric acute myeloid leukemia (AML) chemotherapy increases the risk of life-threatening complications, including septic shock (SS). An area-based measure of social determinants of health, the social disorganization index (SDI), was hypothesized to be associated with SS and SS-associated death (SS-death). METHODS: Children treated for de novo AML on two Children's Oncology Group trials at institutions contributing to the Pediatric Health Information System (PHIS) database were included. The SDI was calculated via residential zip code data from the US Census Bureau. SS was identified via PHIS resource utilization codes. SS-death was defined as death within 2 weeks of an antecedent SS event. Patients were followed from 7 days after the start of chemotherapy until the first of end of front-line therapy, death, relapse, or removal from study. Multivariable-adjusted Cox regressions estimated hazard ratios (HRs) comparing time to first SS by SDI group. RESULTS: The assembled cohort included 700 patients, with 207 (29.6%) sustaining at least one SS event. There were 233 (33%) in the SDI-5 group (highest disorganization). Adjusted time to incident SS did not statistically significantly differ by SDI (reference, SDI-1; SDI-2: HR, 0.84 [95% confidence interval (CI), 0.51-1.41]; SDI-3: HR, 0.70 [95% CI, 0.42-1.16]; SDI-4: HR, 0.97 [95% CI, 0.61-1.53]; SDI-5: HR, 0.72 [95% CI, 0.45-1.14]). Nine patients (4.4%) with SS experienced SS-death; seven of these patients (78%) were in SDI-4 or SDI-5. CONCLUSIONS: In a large, nationally representative cohort of trial-enrolled pediatric patients with AML, there was no significant association between the SDI and time to SS.

Comprehensive molecular and clinical characterization of NUP98 fusions in pediatric acute myeloid leukemia.

NUP98 fusions comprise a family of rare recurrent alterations in AML, associated with adverse outcomes. In order to define the underlying biology and clinical implications of this family of fusions, we performed comprehensive transcriptome, epigenome, and immunophenotypic profiling of 2,235 children and young adults with AML and identified 160 NUP98 rearrangements (7.2%), including 108 NUP98-NSD1 (4.8%), 32 NUP98-KDM5A (1.4%) and 20 NUP98-X cases (0.9%) with 13 different fusion partners. Fusion partners defined disease characteristics and biology; patients with NUP98-NSD1 or NUP98-KDM5A had distinct immunophenotypic, transcriptomic, and epigenomic profiles. Unlike the two most prevalent NUP98 fusions, NUP98-X variants are typically not cryptic. Furthermore, NUP98-X cases are associated with WT1 mutations, and have epigenomic profiles that resemble either NUP98-NSD1 or NUP98-KDM5A. Cooperating FLT3-ITD and WT1 mutations define NUP98-NSD1, and chromosome 13 aberrations are highly enriched in NUP98-KDM5A. Importantly, we demonstrate that NUP98 fusions portend dismal overall survival, with the noteworthy exception of patients bearing abnormal chromosome 13 (clinicaltrials gov. Identifiers: NCT00002798, NCT00070174, NCT00372593, NCT01371981).