ABSTRACT
In this retrospective study, we evaluated long-term survival and late effects in 137 patients affected by thalassemia major (TM) who received an allogeneic hematopoietic cell transplantation (HCT). Median age at HCT was 10.1 years. After a median follow-up of 30 years, 114 (83.2%) patients are living and 108 (78.8%) are cured. The cumulative incidence of nonrelapse mortality and thalassemia recurrence was 9.5% at 1 year and 10.2% at 39 years respectively. The 39-years cumulative incidence of overall survival and disease-free survival were 81.4% and 74.5%. One hundred twenty-three patients who survived more than 2 years after HCT were evaluated for late effects concerning hematological disorders, iron burden, growth, obesity, diabetes mellitus, thyroid and gonadal function, eye, heart, liver, lung, kidney, gastrointestinal, neurologic and psychiatric system, osteoarticular system, secondary solid cancer (SSC), performance status, and Covid-19 infection. Fertility was preserved in 21 males whose partners delivered 34 neonates and 25 females who delivered 26 neonates. Fifteen cases of SSC were diagnosed for a 39-year cumulative incidence of 16.4%. HCT represents a definitive cure for the majority of TM patients at the price, however, of a non-negligible early and late mortality which in the long run affects survival and disease-free survival.
Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Neoplasms, Second Primary , beta-Thalassemia , Male , Female , Infant, Newborn , Humans , Child , beta-Thalassemia/therapy , Retrospective Studies , Hematopoietic Stem Cell Transplantation/adverse effects , Disease-Free Survival , Neoplasms, Second Primary/etiology , Disease Progression , Transplantation Conditioning/adverse effectsABSTRACT
The stimulation of AT1R (Angiotensin II Receptor Type 1) by Angiotensin II has, in addition to the effects on the renin-angiotensin system, also pro-inflammatory effects through stimulation of ADAM17 and subsequent production of INF-gamma and Interleukin-6. This pro-inflammatory action stimulate the cytokine storm that characterizes the most severe forms of SARS-CoV-2 infection. We studied the effect of AT1Rab on the AT1R on 74 subjects with SARS-CoV-2 infection with respiratory symptoms requiring hospitalization. We divided the patients into 2 groups: 34 with moderate and 40 with severe symptoms that required ICU admission. Hospitalized subjects showed a 50% reduction in the frequency of AT1Rab compared to healthy reference population. Of the ICU patients, 33/40 (82.5%) were AT1Rab negative and 16/33 of them (48.5%) died. All 7 patients positive for AT1Rab survived. These preliminary data seem to indicate a protective role played by AT1R autoantibodies on inflammatory activation in SARS-CoV-2 infection pathology.