Mar 9, 2017 - with sickle cell disease living in England: a neonatal cohort in East. London. ..... Patients ful- filled WHO classification criteria for BL or HGBCL.3.
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MEKONTSO DESSAP ET AL.
Correspondence Samir K. Ballas, MD, FACP, Cardeza Foundation for Hematologic Research, 1020 Locust Street, Suite 394, Philadelphia PA 19107, USA. E-mail: samir.ballas@jefferson.edu
biomarker of aging.1 Telomere attrition and the resulting cellular senescence could play a role in pathologic states associated with chronic inflammation or oxidative stress, as seen during sickle cell disease (SCD).2,3 SCD associates hemolytic and viscosity-related complications,
Present address Nina Anderson, Tova Healthcare, 601 New Castle Avenue, Wilmington, Delaware 19801
leading to decreased life expectancy.4 The single gene mutation responsible for abnormal sickle hemoglobin (HbS) contrasts with the phenotypic heterogeneity observed among SCD patients. The objectives of this study were to evaluate whether telomere attrition is asso-
REFERENCES [1] Quinn CT, Rogers ZR, McCavit TL, et al. Improved survival of children and adolescents with sickle cell disease. Blood. 2010;115:3447–3452. [2] Telfer P, Coen P, Chakravorty S, et al. Clinical outcomes in children with sickle cell disease living in England: a neonatal cohort in East London. Haematologica. 2007;92:905–912. [3] Lobo CL, Ballas SK, Domingos AC, et al. Newborn screening program for hemoglobinopathies in Rio de Janeiro, Brazil. Pediatr Blood Cancer. 2014;61:34–39. [4] Quinn CT, Rogers ZR, Buchanan GR. Survival of children with sickle cell disease. Blood. 2004;103:4023–4027. [5] Quinn CT. Do not leave for tomorrow what you can do today. Pediatr Blood Cancer. 2015;62:1879–1880. [6] Hamideh D, Alvarez O. Sickle cell disease related mortality in the United States (1999-2009). Pediatr Blood Cancer. 2013;60:1482–1486. [7] Paulukonis ST, Eckman JR, Snyder AB, et al. Defining sickle cell disease mortality using a population-based surveillance system, 2004 through 2008. Public Health Rep. 2016;131:367–375. [8] Hemker BG, Brousseau DC, Yan K, et al. When children with sicklecell disease become adults: lack of outpatient care leads to increased use of the emergency department. Am J Hematol. 2011;86:863–865. [9] Stollon NB, Paine CW, Lucas MS, et al. Transitioning adolescents and young adults with sickle cell disease from pediatric to adult health care: provider perspectives. J Pediatr Hematol Oncol. 2015;37:577–583. [10] Ballas SK, Dampier C. Outcome of transitioning pediatric patients with sickle cell disease to adult programs. Blood (ASH Annual Meeting Abstracts). 2004;104:Abstract 3743. [11] Aduloju S, Palmer S, Eckman JR. Mortality in sickle cell patient transitioning from pediatric to adult program: 10 years grady comprehensive sickle cell center experience. Blood (ASH Annual Meeting Abstracts). 2008;112:1426. [12] Ballas SK, Bauserman RL, McCarthy WF, et al. Utilization of analgesics in the multicenter study of hydroxyurea in sickle cell anemia: effect of sex, age, and geographical location. Am J Hematol. 2010;85:613–616. [13] Yusuf S, Wittes J. Interpreting geographic variations in results of randomized, controlled trials. N Engl J Med. 2016;375:2263–2271.
ciated with SCD, its phenotypic presentations, and outcomes. Between 2003 and 2013, consecutive homozygous SCD patients over 15 years of age were enrolled with one or more of their family member with an AA genotype (controls). The study was approved by institutional review board and all patients signed written informed consent. Clinical and laboratory data were measured during a routine visit at steady state, ie >2 months from a painful crisis, and >3 months from transfusion or hydroxyurea intake. Follow-up information for survival (up to 10 years) was obtained by medical chart review and interview of the family and referring physician. All SCD patients and control subjects underwent blood sampling for genotype determination and biological assessment—blood cell count, hemoglobin electrophoresis, and red blood cell (RBC) density, assessed by measuring the percentage of dense RBCs (density >1.120) and the median density of RBCs. The telomere length was measured in white blood cells by using quantitative PCR.5 The telomere repeat copy number to single-gene copy number (T/S) ratio was determined with a 7900HT thermocycler (Applied Biosystems, Foster City, CA) in a 384-well format, using the comparative Ct method (T/S 5 2–DDCt). Continuous data were expressed as mean 6 standard deviation and were compared using the Student T-test or Mann–Whitney test. Categorical variables, expressed as percentages, were evaluated using the chi-square test or Fisher exact test. To evaluate the association between telomere length and age, we used the Pearson r correlation coefficient. SCD patients were further separated into two groups with longer or shorter telomere length, based on the mean value of the T/S ratio in this group. Survival curves were generated using the Kaplan–Meier method and compared using the logrank test. Mortality over the follow-up period was also analyzed using multivariable Cox model including factors yielding a P-value
