PF737 SURVIVAL RATES AND CAUSES OF DEATH IN ELDERLY PATIENTS WITH SICKLE CELL DISEASE
Authors: V.M. Pinto, G. Graziadei, V. Voi, A. Quota, P. Rigano, V. Spadola, C. Fidone, B. Gianesin, L. De Franceschi, G.L. Forni
Journal: HemaSphere (2019)

Background: Sickle cell disease (SCD) is endemic in the native Italian population, mainly localized in Southern regions with prevalent βthal/HbS genotype. In the last decade, the number of affected SCD subjects has increased globally throughout Italy, partly due to the migratory phenomena from North and Central Africa, the Balkans, Central and South American countries, and the Far East, leading to a change in the national distribution of SCD. Aims: The main aim of the study was to define survival and causes of death in elderly SCD patients with ß+/ßS, ß°/ßS, and ßS/ßS genotype. Methods: This is an observational longitudinal systemic multicenter study (registered at: https://clinicaltrials.gov/ct2/show/NCT03397017). Data were collected from 2015 to 2018 through a standard web-based application (available at: www.SITE-italia.org) encrypted by the Central Server. The study was approved by the Ethics Committee of the Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy. Results: Six hundred and ninety-seven patients from six Italian hemoglobinopathy comprehensive care centers were evaluated: 203 ß+/ßS, 206 ß°/ßS, 288 ßS/ßS, equally distributed by gender. Median age was 41 years [interquartile range (IQR): 30–52 years] for Caucasians and 17 years (IQR: 8–31 years) for Africans (p < 0.001). Ninety percent of African patients presented ßS/ßS genotype. Distribution of genotypes in Caucasians was: 189 ß+/ßS (38%), 197 ß°/ßS (40%), 111 ßS/ßS (22%), with no significant differences in age among the three subgroups. Fifty-eight patients died during the study: 19 ß+/ßS, 23 ß°/ßS, 16 ßS/ßS (Caucasians accounted for 100%, 96% and 81%, respectively). Causes of death were: 20 acute chest syndrome (ACS), 18 liver failure, 7 stroke, 4 solid cancer, 2 kidney failure, 1 sepsis, 1 pulmonary hypertension, 5 other causes. As shown in Fig. 1A, no difference in the causes of death was observed among genotypes. One hundred and eighty-nine patients were splenectomized: 62 ß+/ßS, 103 ß°/ßS, 24 ßS/ßS (Caucasians accounted for 100%, 100% and 80%, respectively). There was a significant difference in age at splenectomy in ß+/ßS compared to ß°/ßS and ßS/ßS (p < 0.001). ßS/ßS Africans were younger than Caucasians; therefore, to avoid age-related bias, survival analysis was limited to the Caucasian population. No differences were found in survival according to different genotypes (p = 0.7, Figure 1B) or splenectomy (p = 0.5). Figure 1. Caucasian sickle cell disease (SCD) patients. (A) Causes of death (n = 54 patients). Acute Chest Syndrome (ACS). (B) Survival curves by genotypeSummary/Conclusion: The Italian SCD population is characterized by a cohort of elderly Caucasians with a long-term follow up (median follow up 37 years; 95%CI: 36–39 years, calculated by the “reverse Kaplan-Meier” technique) and a younger cohort of patients of African descent. The major finding of our study is that genotype or splenectomy does not affect the overall survival of SCD patients. ACS was the first cause of death; unexpectedly, liver failure was the second cause of death in elderly SCD patients, most likely due to chronic sickle cell-related liver damage. The analysis of others factors triggering chronic hepatopathy is under evaluation in this large population of elderly SCD subjects.