RESUMO
Asthma, a prevalent chronic respiratory condition characterized by inflammation of the airways and bronchoconstriction, has demonstrated a potential association with hemoglobinopathies such as thalassemia and sickle cell disease (SCD). Numerous studies have highlighted a higher prevalence of asthma among thalassemia patients compared to the general population, with rates ranging around 30%. Similarly, asthma frequently coexists with SCD, affecting approximately 20-48% of patients. Children with SCD often experience heightened lower airway obstruction and airway hyper-reactivity. Notably, the presence of asthma in SCD exacerbates respiratory symptoms and increases the risk of severe complications like acute chest syndrome, stroke, vaso-occlusive episodes, and early mortality. Several studies have noted a decrease in various cytokines such as IFN-γ and IL-10, along with higher levels of both IL-6 and IL-8, suggesting an overactivation of pro-inflammatory mechanisms in patients with hemoglobinopathies, which could trigger inflammatory conditions such as asthma. The exact mechanisms driving this association are better elucidated but may involve factors such as chronic inflammation, oxidative stress, and immune dysregulation associated with thalassemia-related complications like chronic hemolytic anemia and iron overload. This review aims to comprehensively analyze the relationship between asthma and hemoglobinopathies, with a focus on thalassemia and SCD. It emphasizes the importance of interdisciplinary collaboration among pulmonologists, hematologists, and other healthcare professionals to effectively manage this complex interplay. Understanding this link is crucial for improving care and outcomes in affected individuals.
RESUMO
BACKGROUND: Gemtuzumab-ozogamycin (GO) is approved in combination with high-dose chemotherapy for treatment-naïve low- and intermediate-risk acute myeloid leukemia (AML). AIMS: In this retrospective real-life multicenter study, we reported efficacy and safety of GO plus high-dose chemotherapy in newly diagnosed AML patients. METHODS AND RESULTS: A total of 31 fit low- and intermediate-risk AML patients treated with GO-based regimens were retrospectively included in this real-life multicenter study, and results were compared with a control cohort treated with 3 + 7 alone. Complete remission (CR) rate after induction was 77%, and most responders (45%) underwent two GO-based consolidation, and minimal residual disease (MRD) negativity was observed in 17 cases (55%) after the end of consolidation. Low genetic risk was associated with increased CR rate compared with intermediate-risk AML (88% vs. 33%; p < .001), as well as prolonged overall survival (OS; hazard ratio, 0.16; 95% confidential interval, 0.02-0.89; p < .001). GO addition resulted in a survival benefit for low-risk AML (median OS not reached vs. 25 months; p = .19) while not for intermediate-risk subjects (10 vs. 13 months; p = .92), compared with the control group. Moreover, GO-treated patients experienced fever of unknown origin or sepsis in 42% or 36% of cases, respectively, with one death during induction due to septic shock, with similar rates compared with the control group (p = .3480 and p = .5297, respectively). No cases of veno-occlusive disease after allogeneic transplantation were observed. CONCLUSIONS: Our real-life multicenter study confirmed GO-based treatment efficacy with high MRD negativity rates in fit newly diagnosed AML patients, especially in those with low genetic risk and core binding factor, while limited benefits were observed in intermediate-risk AML. However, further validation on larger prospective cohorts is required.