title: East Mediterranean region sickle cell disease mortality trial: retrospective multicenter cohort analysis of 735 patients.
abstract: Sickle cell disease (SCD), one of the most common genetic disorders worldwide, is characterized by hemolytic anemia and tissue damage from the rigid red blood cells. Although hydroxyurea and transfusion therapy are administered to treat the accompanying tissue injury, whether either one prolongs the lifespan of patients with SCD is unknown. SCD-related mortality data are available, but there are few studies on mortality-related factors based on evaluations of surviving patients. In addition, ethnic variability in patient registries has complicated detailed analyses. The aim of this study was to investigate mortality and mortality-related factors among an ethnically homogeneous population of patients with SCD. The 735 patients (102 children and 633 adults) included in this retrospective cohort study were of Eti-Turk origin and selected from 1367 patients seen at 5 regional hospitals. A central population management system was used to control for records of patient mortality. Data reliability was checked by a data supervision group. Mortality-related factors and predictors were identified in univariate and multivariate analyses using a Cox regression model with stepwise forward selection. The study group included patients with homozygous hemoglobin S (Hgb S) disease (67 %), Hb S-β(0) thalassemia (17 %), Hgb S-β(+) thalassemia (15 %), and Hb S-α thalassemia (1 %). They were followed for a median of 66 ± 44 (3-148) months. Overall mortality at 5 years was 6.1 %. Of the 45 patients who died, 44 (6 %) were adults and 1 (0.1 %) was a child. The mean age at death was 34.1 ± 10 (18-54) years for males, 40.1 ± 15 (17-64) years for females, and 36.6 ± 13 (17-64) years overall. Hydroxyurea was found to have a notable positive effect on mortality (p = 0.009). Mortality was also significantly related to hypertension and renal damage in a univariate analysis (p = 0.015 and p = 0.000, respectively). Acute chest syndrome, splenic sequestration, and prolonged painful-crisis-related multiorgan failure were the most common causes of mortality. In a multivariate analysis of laboratory values, only an elevated white blood cell count was related to mortality (p = 0.009). These data show that despite recent progress in the treatment of SCD, disease-related factors continue to result in mortality in young adult patients. Our results highlight the importance of evaluating curative treatment options for patients who have an appropriate stem cell donor in addition to improving patient care and patient education.
authors.affiliation: Department of Internal Medicine, Baskent University Faculty of Medicine, Ankara, Turkey.
authors.forename: Pelin Kardaş
authors.initials: PK
authors.lastname: Karacaoglu
authors.affiliation: Department of Internal Medicine, Family Medicine Division, Baskent University Faculty of Medicine, Ankara, Turkey.
authors.forename: Suheyl
authors.initials: S
authors.lastname: Asma
authors.affiliation: Department of Internal Medicine, Family Medicine Division, Baskent University Faculty of Medicine, Ankara, Turkey.
authors.forename: Aslı
authors.initials: A
authors.lastname: Korur
authors.affiliation: Department of Internal Medicine, Hematology Division, Baskent University Faculty of Medicine, Ankara, Turkey.
authors.forename: Soner
authors.initials: S
authors.lastname: Solmaz
authors.affiliation: Department of Internal Medicine, Hematology Division, Baskent University Faculty of Medicine, Ankara, Turkey.
authors.forename: Nurhilal Turgut
authors.initials: NT
authors.lastname: Buyukkurt
authors.affiliation: Department of Internal Medicine, Family Medicine Division, Baskent University Faculty of Medicine, Ankara, Turkey.
authors.forename: Cigdem
authors.initials: C
authors.lastname: Gereklioglu
authors.affiliation: Department of Internal Medicine, Hematology Division, Baskent University Faculty of Medicine, Ankara, Turkey.
authors.forename: Mutlu
authors.initials: M
authors.lastname: Kasar
authors.affiliation: Mersin State Hospital, Hematology Division, Mersin, Turkey.
authors.forename: Demircan
authors.initials: D
authors.lastname: Ozbalcı
authors.affiliation: Department of Internal Medicine, Pediatric Hematology Division, Mersin University Faculty of Medicine, Mersin, Turkey.
authors.forename: Selma
authors.initials: S
authors.lastname: Unal
authors.affiliation: Department of Internal Medicine, Hematology Division, Mustafa Kemal University Faculty of Medicine, Antakya, Turkey.
authors.forename: Hasan
authors.initials: H
authors.lastname: Kaya
authors.affiliation: Department of Internal Medicine, Hematology Division, Cukurova University Faculty of Medicine, Adana, Turkey.
authors.forename: Emel
authors.initials: E
authors.lastname: Gurkan
authors.affiliation: Department of Internal Medicine, Hematology Division, Baskent University Faculty of Medicine, Ankara, Turkey.
authors.forename: Mahmut
authors.initials: M
authors.lastname: Yeral
authors.affiliation: Medical statistics, Baskent University Faculty of Medicine, Adana, Turkey.
authors.forename: Çagla
authors.initials: Ç
authors.lastname: Sariturk
authors.affiliation: Department of Internal Medicine, Hematology Division, Baskent University Faculty of Medicine, Ankara, Turkey. drcanboga@hotmail.com.
authors.forename: Can
authors.initials: C
authors.lastname: Boga
authors.affiliation: Department of Internal Medicine, Hematology Division, Baskent University Faculty of Medicine, Ankara, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Ozdogu
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000175:diagnosis* / Q000401:mortality*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D019083:Mediterranean Region / Q000453:epidemiology; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D012189:Retrospective Studies; D014421:Turkey / Q000453:epidemiology; D055815:Young Adult
keywords: Acute chest syndrome; Hemoglobinopathy; Mortality; Painful crisis; Sickle cell disease