European Journal of Haematology最新文献

Prior to the national shortage of iron dextran in early 2023, it was the most commonly administered intravenous iron infusion at our institution. After the shortage impacted the health system, alternatives such as iron sucrose and sodium ferric gluconate/sucrose were required that utilized lower doses given at more frequent patient visits. Coinciding with their more prevalent use, an increase in iron infusion reactions was observed. Our study analyzed 880 patients who received iron infusions in three Henry Ford Hospital clinics in metropolitan Detroit, Michigan, from July 2022–June 2023. The 74 reactions that occurred were most commonly associated with iron sucrose at the 500 mg dose (41/74, 55.41%, p < 0.0001). Most reactions observed across all iron formulations and doses were mild, with 83.7% being Grade 0 or 1 as defined by the United States Drug Allergy Registry (USDAR) grading scale for immediate reactions. Patients who experienced an infusion reaction were less likely to complete their infusion plans (OR 0.004 for iron dextran, OR 0.128 for iron sucrose, p < 0.0001), with infusions most commonly being completely discontinued thereafter, with a minority pursuing alternative options. More patients with lower number of doses scheduled for iron dextran completed their infusion schedules than those with more doses, but the opposite was seen for iron sucrose. We assessed the impact of the national shortage of iron dextran examining infusion reactions with various iron infusions and doses.

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder, and recent research suggests that gut microbiota and inflammatory cytokines may play a significant role in its pathogenesis. However, the specific effects of these factors on ITP and their relationships remain unclear. We conducted a two-step, two-sample Mendelian randomization study using an inverse variance-weighted approach to investigate the causal role of the gut microbiota in ITP and the mediating effect of inflammatory cytokines on their association. The results showed that among the 473 gut microbiota species, 11 were positively associated and 12 were negatively associated with the risk of ITP. Among the 91 screened inflammatory cytokines, five (CXCL10, CXCL5, IL-12RA, TRAIL, and VEGF-A) were found to have a causal relationship with ITP. Mediation analysis revealed that the gut microbiota UBA1066 promoted the occurrence of ITP through CXCL10 mediation, with a mediation effect of 0.118932 (95% CI: 0.049471–0.188393) accounting for 9.95% of the total effect. Gut microbiota Treponema promoted ITP through VEGF-A mediation, with a mediation effect of 0.045873 (95% CI: 0.01456–0.07718) accounting for 4.28% of the total effect. Gut microbiota Haloplasma promoted the occurrence of ITP via CXCL5. The mediating effect of CXCL5 was 0.038409 (95% CI = 0.00107718–0.07575082), with a mediating ratio of 16.79%. This study revealed a causal relationship between gut microbiota composition and ITP risk, highlighting three inflammatory cytokines as potential causal mediators of this relationship. These findings provide potential targets and biomarkers for the prevention and treatment of ITP with significant clinical implications.

Clonal evolution (CE) is a driving force behind the development and progression of acute myeloid leukemia (AML). Advances in molecular and cytogenetic assays have improved the depth and breadth of detection of CE in AML, which is defined here as a detected change in cytogenetic or molecular profile at relapsed or refractory (RR) disease. In this study, we demonstrate the clinical impact of CE in a cohort of patients with RR AML treated between 2013 and 2023. We discovered CE is significantly more frequent in relapsed disease (58.2%, [46.6%, 69.2%]) than in refractory disease (21.1%, [14.4%, 29.2%], p < 0.001). CE negatively impacts prognosis when detected by conventional karyotyping in refractory disease (4.2 vs. 13.9 months, p < 0.011). In contrast with prior literature, CE had no impact on overall survival if detected in relapsed disease. Surprisingly, those who achieved negative measurable residual disease (MRD) were no more likely to eliminate their original clone than those who did not (p = 1). We found several cytogenetic and molecular signatures which may predispose to CE: aberrations of chromosome 17, trisomy 8, TP53, KRAS, and FLT3-TKD. Finally, physicians were less likely to retreat those with CE with IC after receiving IC as first-line therapy (35.0% vs. 70.9%, p = 0.004). This study illustrates the role of CE in chemotherapy-resistant AML; we identify unique cytogenetic and molecular signatures that define a subset of patients associated with a dismal prognosis. As next-generation sequencing panels expand and new methods to characterize cytogenetic abnormalities emerge, our findings establish a basis for future studies investigating the prognostic and therapeutic impact of CE.