scholarly journals Genome-Wide Meta-Analysis of Systolic Blood Pressure in Children with Sickle Cell Disease

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e74193 ◽  
Author(s):  
Pallav Bhatnagar ◽  
Emily Barron-Casella ◽  
Christopher J. Bean ◽  
Jacqueline N. Milton ◽  
Clinton T. Baldwin ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sickle Cell Disease ◽  
Systolic Blood Pressure ◽  
Sickle Cell ◽  
Meta Analysis ◽  
Cell Disease ◽  
Genome Wide

Mechanisms of vascular instability in a transgenic mouse model of sickle cell disease

2000 ◽  
Vol 279 (6) ◽  
pp. R1949-R1955 ◽  
Author(s):  
K. A. Nath ◽  
V. Shah ◽  
J. J. Haggard ◽  
A. J. Croatt ◽  
L. A. Smith ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Lipid Peroxidation ◽  
Sickle Cell Disease ◽  
Mouse Model ◽  
Systolic Blood Pressure ◽  
Transgenic Mouse ◽  
Sickle Cell ◽  
Transgenic Mouse Model ◽  
Cell Disease

We investigated a transgenic mouse model of sickle cell disease, homozygous for deletion of mouse β-globin and containing transgenes for human βSand βS-antillesglobins linked to the transgene for human α-globin. In these mice, basal cGMP production in aortic rings is increased, whereas relaxation to an endothelium-dependent vasodilator, A-23187, is impaired. In contrast, aortic expression of endothelial nitric oxide synthase (NOS) is unaltered in sickle mice, whereas expression of inducible NOS is not detected in either group; plasma nitrate/nitrite concentrations and NOS activity are similar in both groups. Increased cGMP may reflect the stimulatory effect of peroxides (an activator of guanylate cyclase), because lipid peroxidation is increased in aortae and in plasma in sickle mice. Despite increased vascular cGMP levels in sickle mice, conscious systolic blood pressure is comparable to that of aged-matched controls; sickle mice, however, evince a greater rise in systolic blood pressure in response to nitro-l-arginine methyl ester, an inhibitor of NOS. Systemic concentrations of the vasoconstrictive oxidative product 8-isoprostane are increased in sickle mice. We conclude that vascular responses are altered in this transgenic sickle mouse and are accompanied by increased lipid peroxidation and production of cGMP; we suggest that oxidant-inducible vasoconstrictor systems such as isoprostanes may oppose nitric oxide-dependent and nitric oxide-independent mechanisms of vasodilatation in this transgenic sickle mouse. Destabilization of the vasoactive balance in the sickle vasculature by clinically relevant states may predispose to vasoocclusive disease.

Identification of Thrombospondin-1 and L-Selectin as Potential Plasma Biomarkers of Silent Cerebral Infarct In Children with Sickle Cell Disease Using a Proteomic-Based Approach

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 259-259
Author(s):  
Lisa M. Williams ◽  
Zongming Fu ◽  
Pratima Dulloor ◽  
Kun Yan ◽  
John J. Strouse ◽  
...  
Keyword(s):  
Blood Pressure ◽  
African American ◽  
Sickle Cell Disease ◽  
Systolic Blood Pressure ◽  
Sickle Cell ◽  
Vascular Endothelium ◽  
Validation Cohort ◽  
Plasma Samples ◽  
Cell Disease ◽  
Control Subjects

Abstract Abstract 259 Objectives: Silent cerebral infarction (SCI) occurs in approximately 27% of children with sickle cell disease (SCD) by age 6 years, and is associated with decreased neurocognitive function and a 14-fold increased risk of progression to overt stroke. While several clinical parameters, such as increased white blood cell (WBC) and platelet counts and decreased hemoglobin (Hb) or hematocrit, have been reported in the literature to be associated with SCI, to date no validated biomarkers exist to predict SCI in patients with SCD. Furthermore, recent unpublished data from the Silent Infarct Transfusion (SIT) Trial has identified systolic blood pressure and total hemoglobin as risk factors. The aim of this study was to identify candidate biomarker plasma proteins that correlate with SCI in patients with SCD. Methods: We used a proteomic discovery approach involving three sequential separation steps to compare the plasma proteomes of 15 children with SCD (7 with SCI and 8 without SCI), aged 5–15 years. Baseline steady-state plasma samples were obtained from the SIT Trial Biologic Repository and matched for age, Hb and WBC. Plasma samples were Hb depleted in the first dimension, separated using immunoaffinity depletion and reverse phase liquid chromatography fractionation, and then trypsin-digested for characterization using label-free quantification on a LTQ-Orbitrap (Thermo) mass spectrometer. The resulting MS/MS data were analyzed using PASS (Integrated Analysis, Bethesda, MD) with X! Tandem searches (www.thegpm.org; version 2008.12.01) of the International Protein Index peptide database (human, 3.19). We measured candidate proteins in a validation cohort of 116 children with SCD (n=65 SCI, 51 non-SCI) and 24 age-matched, healthy African American control subjects using enzyme-linked immunosorbent assays (thrombospondin 1 [TSP1], L-selectin, RandD Systems, Minneapolis, MN) and immunoassays (E- and P-selectin, Mesoscale Discovery, Maryland). All samples were run in duplicate according to the manufacturers' protocols. Statistical differences in biomarker plasma concentrations between groups were compared by the Mann-Whitney U test. Results: TSP1 (5 peptides) and L-selectin (3 peptides) were among 335 proteins that showed differential detection between the SCI and non-SCI groups based on the spectral counts. TSP1 is an extracellular matrix glycoprotein that is involved with platelet aggregation, inhibition of neovascularization and tumorigenesis and has been shown to promote the adherence of sickle erythrocytes to the vascular endothelium. L-selectin is an adhesion molecule that mediates leukocyte interaction with the vascular endothelium. In a validation cohort of 116 children with SCD (n=65 SCI, 51 non-SCI) and 24 age matched, healthy African American control subjects, TSP1 and L-selectin were both significantly increased in SCI vs. non-SCI groups (median 8.5 vs. 6.2 μ g/ml for TSP1, P =0.03; 1.5 vs. 1.4 μ g/ml for L-selectin, P =0.03). As expected, neither TSP nor L-selectin were elevated in the age-matched normal controls (median=4.6 μ g/ml for TSP1, P =0.10, 1.2 μ g/ml for L-selectin, P =0.10). The specificity of the L-selectin results was verified by demonstrating that E-selectin and P-selectin were not increased in the SCI group. TSP1 was correlated with baseline oxygen saturation in both the SCI and non-SCI groups (r=-0.51, and r=-0.35, P<0.001). L-selectin correlated with systolic blood pressure in the SCI group only (r=0.3, P<0.02). Conclusions: TSP1 and L-selectin may represent the first two plasma biomarkers of SCI in children with SCD. Although further studies are needed, these and other potential biomarkers may provide insight into the pathophysiology of SCI, and may fill an important clinical need in identifying children with SCD who are at risk for SCI. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A common molecular signature of patients with sickle cell disease revealed by microarray meta-analysis and a genome-wide association study

PLoS ONE ◽  
2018 ◽  
Vol 13 (7) ◽  
pp. e0199461 ◽  
Author(s):  
Cherif Ben Hamda ◽  
Raphael Sangeda ◽  
Liberata Mwita ◽  
Ayton Meintjes ◽  
Siana Nkya ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Association Study ◽  
Sickle Cell ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Molecular Signature ◽  
Cell Disease ◽  
Genome Wide ◽  
A Genome

scholarly journals GWAS Meta-Analysis of Glomerular Filtration Rate in Three Cohorts of Sickle Cell Disease Patients and In Vivo Functional Analysis Reveals Potential Nephropathy Candidate Genes

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 269-269
Author(s):  
Blair R. Anderson ◽  
Melanie E. Garrett ◽  
Karen L. Soldano ◽  
Eugene P. Orringer ◽  
James R. Eckman ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Glomerular Filtration ◽  
Sickle Cell ◽  
Genetic Risk ◽  
Filtration Rate ◽  
Meta Analysis ◽  
Zebrafish Embryos ◽  
Cell Disease ◽  
Genome Wide

Abstract BACKGROUND: Sickle cell disease nephropathy (SCDN) is a common complication of sickle cell disease (SCD) associated with risk for early mortality (Platt et al., 1994; Elmariah et al, 2014). To identify potential genetic risk factors for SCDN, we performed genome-wide association studies (GWAS) for glomerular filtration rate (GFR) in three well-characterized SCD cohorts and performed in vivo functional analysis of one of the candidate genes in zebrafish. METHODS: Three previously described SCD cohorts were utilized in this analysis: Outcome Modifying Genes in Sickle Cell Disease (OMG-SCD) (Elmariah et al, 2014), Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) (Machado et al, 2011) and Pulmonary Hypertension and the Hypoxic Response in Sickle Cell Disease (PUSH) (Minniti et al, 2009). Patients less than 16 years old were excluded from PUSH. GFR was estimated using the 'Modification of Diet in Renal Disease' (MDRD) study definition (Levey et al, 1999) and, in the OMG-SCD and Walk-PHaSST cohorts, dichotomized at the clinically relevant threshold of 90 ml/min/1.73m2. 1064 patients with complete data were included in the analysis (Table 1). Genotyping was performed using the Illumina Human610-Quad BeadChip (Illumina, San Diego, CA). Linear regression was utilized to test for association between each SNP and GFR, controlling for genome-wide principle components using PLINK (Purcell et al, 2008). Logistic regression was utilized for the analysis of GFR<90. A total of 479,389 SNPs in common across all three cohorts were tested in a meta-analysis using METAL (Willer et al, 2010). False discovery rate (FDR) p-values were generated using PROC MULTTEST in SAS (SAS Systems, Cary, NC). To target and functionally evaluate xylt1 in vivo, a morpholino (MO) was injected into zebrafish embryos at the 1-4 cell stage. A wild-type (WT) XYLT1 ORF clone (GenBank: BC156039) was transferred to the pCS2+ vector, and used as template to transcribe capped mRNA. XYLT1 mRNA was co-injected with xylt1-MO to rescue the phenotype and demonstrate assay specificity. Proteinuria was assessed in zebrafish models by quantification of GFP leakage as described (Zhou and Hildebrandt, 2012). Larva were scored at 5 days-post-fertilization (dpf) for cardiac or yolk-sac edema. RESULTS: For the meta-analysis of continuous GFR, the SNP with the most evidence for association was rs7553158 in the TNNI3K-FPGT locus (p= 7.1E-7). For the meta-analysis of GFR<90, the most significant association within a gene was rs7201659 in XYLT1 (p=1.7E-5). None of these findings met FDR significance. Nonetheless, knockdown of xylt1 in zebrafish embryos resulted in pericardial edema, a phenotype associated previously with glomerular filtration defects, which was confirmed by the detection of GFP leakage of an albumin equivalent protein in the surrounding media. Importantly, complementation of xylt1 morphants with WT human XYLT1 mRNA rescued significantly these filtration defects in developing embryos. DISCUSSION:The absence of mechanistic knowledge about SCDN has led to limited therapeutic options for patients. The present study seeks to identify genetic risk factors for SCDN and represents the largest GWAS of GFR in SCD patients to date. The GWAS was likely still underpowered, however, as none of the findings met FDR significance. Nonetheless, the most significant genes identified are excellent biologic candidates for kidney function. Fucose-1-Phosphate Guanylyltransferase (FPGT) converts GTP and β-l-fucose-1-phosphate to GDP-l-fucose, a process essential in the kidney to reutilize L-fucose from the turnover of glycolipids. It is also highly expressed in the porcine and human kidney (Pastuszak et al, 1998; GTEx, Broad Institute). Xylosyltransferase 1 (XYLT1, also known as XT-1) encodes the enzyme responsible for biosynthesis of heparin sulfate proteoglycans, which affect permeability of the glomerular basement membrane. Furthermore, the c.343G>T polymorphism in XYLT1 has been implicated in diabetic nephropathy (Schön et al, 2006). Here, we have identified putative novel nephropathy loci associated with kidney decline in the largest combined cohort of SCD patients to date. These results further our understanding of the underlying pathology of SCDN and have uncovered genetic markers that could be used for identification of at-risk SCD patients prior to the onset of kidney dysfunction. Disclosures No relevant conflicts of interest to declare.

Sickle Cell Disease Proteinuria Is Not Associated With Systolic Blood Pressure, CSSCD-Defined Hypertension, or Family History Of Hypertension In An International Cohort Of SCD Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 981-981
Author(s):  
Andrew Campbell ◽  
Biree Andemariam ◽  
Fredericka Sey ◽  
Connie M. Piccone ◽  
Baba PD Inusa ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cohort Study ◽  
Family History ◽  
Sickle Cell Disease ◽  
Renal Disease ◽  
Systolic Blood Pressure ◽  
Sickle Cell ◽  
Medical Center ◽  
Bivariate Analysis ◽  
Cell Disease

Abstract Background The prevalence of renal disease in sickle cell disease (SCD) is strikingly high and is associated with morbidity and mortality (Becker et al 2010, Powars et al 2005). In SCD children there is initially hyperfiltration with high GFRs followed by increasing proteinuria in the adolescent and adult SCD pts. (Becker at al 2010). Historically, hypertension (HTN) has been associated with Renal Disease in the general population and a few adult sickle cell nephropathy studies. HTN has been associated with Stroke in SCD. In an ongoing multicenter, international Renal SCD Cohort Study, we investigated the association Microalbuminuria and Macroalbuminuria to Patients Blood Pressure (SBP and DBP), Hypertension based on CSSCD Group Age Defined BP for SCD patients >90%tile (Pegelow et al 1997), and Family history (FH) of Hypertension and Renal Disease in a Crossectional (Peds and Adults), International, Multicenter group of SCD patients. Methods 272 pediatric and adult SCD (3-59 y/o) patients were recruited at baseline from 6 Centers (USA: Univ of Michigan, Case Medical Center/Rainbow Babies, Albert Einstein-Montefiore Medical Center, Univ of Connecticut; Italy: Univ. of Padova, Univ of Naples; Ghana: Korle-Bu Teaching Hospital). 88%(N=236) were severe SCD (SSorSBeta Zero) and 12%(N=31) were Mild Phenotype (SC or SBetaPlus). 58% were Children (<18y/o) and 42%(>18y/o) adults. FH of HTN and Renal Disease were obtained in 1st and 2nddegree relatives. Clinical history and laboratory studies including Pain crises patterns, SBP, DBP, BMI, CBC, Serum Crt, were collected. We obtained Urine Microalbumin/Crt(UMA) (mg/gm) obtained in 169 patients and categorized patients into 1) No Microalbuminuria(No UMA)<30mg/gm, 2) Microalbuminuria(MicroUMA) 30-299mg/gm and 3) Macroalbuminuria (MacroUMA) and obtained Urine protein/crt gm/gm(UProtCrt) in 101 SCD pts and were categorized 1) No proteinuria(NoUProt) <0.2 and 2) Macroproteinuria(MacroUProt)>0.2. Patient’s HTN was defined based on CSSCD SBP or DBP> 90%tile for each specifically defined age group( Pegelow et al 1997). Results In our SCD Renal Cohort Study, NoUMA in 71%(110/169), MicroUMA in 29%(48/169), MacroUMA in 2.2%(6/169) were observed. We also found NoUProt in 75%(N=75) and MacroUProt in 25%(n=25) within our cohort. Severe SCD pts represented 96%(n=46) of the MicroUMA pts, 100% or MacroUMA pts(N=6), and 92% MacroUProt pts(N=23). Proteinuria was disproportionately represented within the Adult SCD pts : 50% of Adults with MicroUMA(n=31) while only 16%(n=17) of Peds. UMA Mean Adult levels was 102(mean) vs. Peds UMA levels of 22(mean),(p=0.009); Also, Adult UProtCrt=0.21(mean)levels were >Peds=0.16, (p<0.001). HTN defined as SBP>90%tile or DBP >90%tile was present in 30%of the subjects(n=77).Thirty-One Percent(n=32) of Adults and 30%(n=45) of Peds pts had HTN. In a Bivariate Analysis(Pearson’s Correlation), HTN was not associated with UMA levels(p=0.919) or UPrtCrt levels(p=0.330). Further, mean UMA was lower in HTN SCD pts( m=24) vs NonHTN(SBP) pts(m=51). Mean UProt levels lower in the HTN group(0.15 ) vs NonHTN(0.20). SBP alone was not associated with UMA( p=0.083), UPrt( p=0.804) levels, MicroUMA(p=0.596). While FH of HTN was common in 75% of pts, FH HTN was not associated with UMA and UProtCrt levels, MicroUMA, MacroUMA, MacroUProt( p>0.05) patients. FH of Renal Disease was not associated with Proteinuria within our Cohort. However, Age( p<0.001: UProtCrt levels, UMA levels, MicroUMA, SBP) and hemoglobin(p=0.034: UProt Crt levels) was significantly associated with proteinuria within our cohort based on Bivariate Analysis. BMI was associated with SBP(p<0.001) and DBP(p<0.001) but not UProt or UMA levels. Further analysis revealed increasing proteinuria(UMA) within aging SCD pts:( 6-10 UMA= 15, 11-19 UMA =42, >20y/o UMA=114)(p=.035 One Way Anova) Conclusions Systolic Blood Pressure, HTN defined as SBP>90%tile or DBP >90%tile from the CSSCD Group, FH of HTN was not associated with Micro or Macroproteinuria based on UProtCrt and UMA levels in an international, cross-sectional cohort of SCD patients. Hemoglobin level and older age were strongly associated with proteinuria within our cohort of patients, consistent with previously well established studies. These findings are supportive of other factors outside of HTN including those intrinsic to SCD contributing to early onset SCD nephropathy. Disclosures: Perrotta: Novartis: Research Funding.

scholarly journals Antiphospholipid Antibodies in Sickle Cell Disease: A Systematic Review and Exploratory Meta-Analysis

2021 ◽  
Vol 27 ◽  
pp. 107602962110029
Author(s):  
Mira Merashli ◽  
Alessia Arcaro ◽  
Maria Graf ◽  
Matilde Caruso ◽  
Paul R. J. Ames ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Antiphospholipid Antibodies ◽  
Meta Analysis ◽  
Age Groups ◽  
Anticardiolipin Antibodies ◽  
Cell Disease ◽  
Pooled Prevalence ◽  
The Relationship

The relationship between antiphospholipid antibodies (aPL) and sickle cell disease (SCD) has never been systematically addressed. Our aim was to evaluate potential links between SCD and aPL in all age groups. EMBASE/PubMed was screened from inception to May 2020 and Peto odds ratios for rare events were calculated. The pooled prevalence (PP) of IgG anticardiolipin antibodies (aCL) was higher in individuals with SCD than in controls (27.9% vs 8.7%, P < 0.0001), that of IgM aCL was similar in the two groups (2.9% vs 2.7%); only individuals with SCD were positive for lupus anticoagulant (LA) (7.7% vs 0%, P < 0.0001). The PP of leg ulcers was similar between aPL positive and negative individuals (44% vs 53%) and between patients in acute crisis and stable patients (5.6% vs 7.3%). Reporting of aPL as a binary outcome and not as a titer precluded further interpretation. The results indicate that a prospective case-control study with serial measurements of a panel of aPL in SCD patients might be warranted, in order to understand further the possible pathogenic role of aPL in SCD.

scholarly journals Normal Non-HDL Cholesterol, Low Total Cholesterol, and HDL Cholesterol Levels in Sickle Cell Disease Patients in the Steady State: A Case-Control Study of Tema Metropolis

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Richard K. D. Ephraim ◽  
Patrick Adu ◽  
Edem Ake ◽  
Hope Agbodzakey ◽  
Prince Adoba ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Total Cholesterol ◽  
Sickle Cell ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Lipoprotein Cholesterol ◽  
Cell Disease ◽  
Cross Sectional

Background.Abnormal lipid homeostasis in sickle cell disease (SCD) is characterized by defects in plasma and erythrocyte lipids and may increase the risk of cardiovascular disease. This study assessed the lipid profile and non-HDL cholesterol level of SCD patients.Methods.A hospital-based cross-sectional study was conducted in 50 SCD patients, in the steady state, aged 8–28 years, attending the SCD clinic, and 50 healthy volunteers between the ages of 8–38 years. Serum lipids were determined by enzymatic methods and non-HDL cholesterol calculated by this formula: non-HDL-C = TC-HDL-C.Results.Total cholesterol (TC) (p=0.001) and high-density lipoprotein cholesterol (HDL-C) (p<0.0001) were significantly decreased in cases compared to controls. The levels of non-HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were similar among the participants. The levels of decrease in TC and HDL were associated with whether a patient was SCD-SS or SCD-SC. Systolic blood pressure and diastolic blood pressure were each significantly associated with increased VLDL [SBP,p=0.01, OR: 0.74 (CI: 0.6–0.93); DBP,p=0.023, OR: 1.45 (CI: 1.05–2.0)].Conclusion.Dyslipidemia is common among participants in this study. It was more pronounced in the SCD-SS than in SCD-SC. This dyslipidemia was associated with high VLDL as well as increased SBP and DBP.

scholarly journals Efficacy of Allogeneic Hematopoietic Cell Transplantation (HCT) in Sickle Cell Disease: Results of a Systematic Review/Meta-Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2106-2106
Author(s):  
Madiha Iqbal ◽  
Tea Reljic ◽  
Ernesto Ayala ◽  
Hemant S. Murthy ◽  
Ambuj Kumar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Sickle Cell Disease ◽  
Clinical Outcomes ◽  
Sickle Cell ◽  
Pediatric Patients ◽  
Medical Literature ◽  
Meta Analysis ◽  
Adult Patients ◽  
Cell Disease ◽  
Allogeneic Hct

Background: Sickle cell disease (SCD) is an inherited hemoglobinopathy which affects over 300,000 children born each year worldwide. In spite of improvement in supportive care in recent years, there is still a lack of effective treatment options. SCD leads to debilitating and cyclic episodes of erythrocyte sickling with progressive organ injury, contributing to lifetime morbidity and shortened life expectancy. Allogeneic HCT (allo-HCT) is a potentially curative therapy for SCD because engraftment is associated with resolution of the clinical phenotype of the disease and abrogation of its complications. Medical literature on allo-HCT for SCD is largely limited to children. Recent studies have evaluated the efficacy of allo-HCT in the adult population. Here, we conduct a systematic review/meta-analysis to assess the totality of evidence pertaining to the efficacy (or lack thereof) of allo-HCT in children and adults. Materials and methods: We performed a comprehensive search of the medical literature using PubMed/Medline, EMBASE and Cochrane library on July 3rd, 2019. We extracted data on clinical outcomes related to benefits (overall [OS] and disease free/event free survival [EFS/DFS]) and harms (non-relapse mortality [NRM] and graft failure [GF]), independently by two authors. Our search strategy identified 1001 references but only 30 studies (n= 1995 patients) were included in this systematic review/meta-analysis. We also performed a sub analysis on clinical outcomes for studies that included only pediatric patients (defined as <18 years) and those in patients ≥18 years of age. Results: Median age for patients enrolled in all the studies was at 10 years. Recurrent veno-occlusive crises represented the most common indication for allo-HCT followed by acute chest syndrome and stroke; nevertheless, most patients had more than one indication. Matched related donors (MRD) were the most common donor source (93%). Bone marrow was the most common source of hematopoietic stem cells (77%). Majority of patients underwent conditioning with myeloablative regimens (77%). Pooled OS rates (n=29 studies, 1681 patients) after allogeneic HCT was 95% (95%CI=93-96%) with low heterogeneity (I2=6.4%) among included studies (Figure 1). Pooled EFS/DFS rates (n=29 studies, 1894 patients) post-allografting was 90% (95%CI=87-93%) with moderate heterogeneity (I2=54%). Pooled NRM rates from 30 studies (1995 patients) was 4% (95%CI=2-6%) with low heterogeneity (I2=29.4%). Pooled GF rates from 28 studies (1851 patients) was 4% (95%CI=2-6%) with moderate heterogeneity (I2=55%). A subset analysis specifically for pediatric patients (n= 11 studies, 1009 patients, median age at 9.7 years) showed a pooled OS rate of 96% (95%CI=94-97%) with low heterogeneity (I2=0%); and for adult patients (n=3 studies, 51 patients, median age at 33.4 years) the pooled OS was 94% (95%CI=80-100%) with moderate heterogeneity (I2=52%). Pooled EFS/DFS for pediatric patients (n= 11 studies, 1009 patients) was at 89 %( 95%CI=84-93%) with moderate heterogeneity (I2=55.1%); and for adult patients (n=2 studies, 30 patients) was at 95% (95%CI=83-100%) with high heterogeneity (I2=96.5%). Pooled NRM from 10 studies with pediatric patients (281 patients) was at 6 % (95%CI=3-10%) with low heterogeneity (I2=0%); and from 3 studies with adult patients (51 patients) was at 1% (95%CI=0-7%) with low heterogeneity (I2=15.1%). Pooled GF from 10 studies with pediatric patients (281 patients) was at 3 % (95%CI=1-7%) with moderate heterogeneity (I2=40%); and from 2 studies with adult patients (30 patients) was at 5% (95%CI=0-17%) with high heterogeneity (I2=95.4%). Conclusions: The results of our systematic review/meta-analysis show excellent OS, EFS/DFS in children and adults undergoing allo-HCT with pooled OS rates exceeding 90%. The main limitation to offering an allo-HCT in SCD remains the availability of a suitable donor as 85% of patients meeting criteria do not have a MRD. We anticipate that with emergence of haploidentical transplantation the number of allo-HCT will increase in the future. GF remains a significant concern in this population and future studies should focus on novel immune suppression strategies to help reduce GF. Disclosures Kharfan-Dabaja: Pharmacyclics: Consultancy; Daiichi Sankyo: Consultancy.

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