Hematopoietic stem cell transplantation for adult sickle cell disease in the era of universal donor availibility.

Current projections estimate that the number of newborns with sickle cell disease (SCD) globally will exceed 400,000 by 2050. Over the last three decades, increased newborn screening, supportive care, and use of hydroxyurea therapy, have decreased early childhood mortality among individuals affected with SCD. Despite hematopoietic cell transplantation (HCT) being curative in SCD, its impact on disease free survival remains unknown, especially in adults, partly due to previous limitations in donor options and perceived mortality in adults using myeloablative conditioning. Novel non-myeloablative or reduced intensity conditioning regimens have made HCT safer and applicable to adults with SCD who were previously excluded. Other reasons for limited use of HCT in SCD includes referral bias, provider preference, poor education of patient/families, perceived procedure risks, costs and limited logistic resources in both low income, middle income, and high income countries. Current data from landmark studies indicate that both the long-term disease-free survival and overall survival exceed 90% after matched sibling donor HCT in children. Improving transplant outcomes and expanding donor pool will increase the use of transplant for SCD, especially in affected adults. On-going investigations using matched umbilical cord units, unrelated matched donor, and related haploidentical donors, promises to make HCT a viable option for nearly all eligible patients with SCD. This systematic review focuses on the recent data for HCT for patients with adult SCD with particular emphasis on donor sources and availability as illustrated by a case presentation exhibiting real world issues.

Epidemiological aspects of Budd-Chiari in Egyptian patients: a single-center study.

AIM: To describe the socio-demographic features, etiology, and risk factors for Budd-Chiari syndrome (BCS) in Egyptian patients. METHODS: Ninety-four Egyptian patients with confirmed primary Budd-Chiari syndrome were presented to the Budd-Chiari Study Group (BCSG) and admitted to the Tropical Medicine Department of Ain Shams University Hospital (Cairo, Egypt). Complete clinical evaluation and laboratory investigations, including a thrombophilia workup and full radiological assessment, were performed to determine underlying disease etiologies. RESULTS: BCS was chronic in 79.8% of patients, acute or subacute in 19.1%, and fulminant in 1.1%. Factor V Leiden mutation (FVLM) was the most common etiological cause of disease (53.1%), followed by mutation of the gene encoding methylene tetrahydrofolate reductase (MTHFR) (51.6%). Current or recent hormonal treatment was documented in 15.5% of females, and BCS associated with pregnancy was present in 17.2% of females. Etiology could not be determined in 8.5% of patients. Males had significantly higher rates of MTHFR gene mutation and Behçet's disease, and females had significantly higher rates of secondary antiphospholipid antibody syndrome. A highly significant positive relationship was evident between the presence of Behçet's disease and inferior vena caval occlusion, either alone or combined with occlusion of the hepatic veins (P < 0.0001). CONCLUSION: FVLM is the most common disease etiology and MTHFR the second most common in Egyptian BCS patients. BCS etiology tends to vary with geographic region.

Factor V G1691A (Leiden) is a major etiological factor in Egyptian Budd-Chiari syndrome patients.

OBJECTIVE: Budd-Chiari syndrome is a multifactorial disease in which several prothrombotic disorders may predispose patients to the development of thrombosis at this uncommon location (hepatic veins). The aim of this study was to determine the prevalence and characteristics of inherited thrombophilia in Egyptian Budd-Chiari syndrome patients. METHODS: The study included 47 Budd-Chiari syndrome patients (20 children and 27 adults). Genotyping of Factor V G1691A (Leiden), prothrombin G20210A (PT), and methylenetetrahydrofolate reductase C677T were performed using real-time PCR and fluorescence melting curve detection analysis. RESULTS: Factor V Leiden was observed in 29 patients (61.7%). It is the only factor that caused Budd-Chiari syndrome in 18 of the patients and in 5 of the patients with inferior vena cava involvement. Myeloproliferative disease was noted in 12 (25.5%) patients, antiphospholipid syndrome in 5 (10.6%), and Behcet's disease in 3 (6.4%). Interestingly, 3 of the children with Budd-Chiari syndrome had lipid storage disease. CONCLUSION: Factor V Leiden was a major etiological factor in Egyptian Budd-Chiari syndrome patients, which may have been related to the high frequency of this mutation in the study region. Factor V Leiden was also a strong thrombophilic factor and the leading cause of inferior vena cava thrombosis in these patients. Lipid storage disease should be included as a risk factor for Budd-Chiari syndrome.