History Of Vaso-occlusive Crisis Research Articles

Pulmonary function assessments and clinical correlates in children with sickle cell disease in Cape Town, South Africa

Objectives: Among children with sickle cell disease (SCD) in Africa, there are varied reports on pulmonary function assessments. Restrictive pulmonary function is common in children with SCD in Africa; however, reports from Africa are few. We aimed to describe pulmonary function and its clinical correlates in children with SCD in Cape Town, South Africa. Materials and Methods: A prospective cross-sectional study was carried out over seven months from October 2018 to April 2019 in children 6–16 years with SCD. Children with hemoglobin (Hb) genotypes, homozygous for the BS globin mutation, and sickle-beta0-thalassemia Hb were included in the study. Children were excluded if they had acute complications. Medical record review clinical, laboratory, and pulmonary function assessments were done. Data were entered into Excel and exported to Stata Version 16.0 statistical software for analysis. Results: A total of 25 participants were recruited, mean (standard deviation) age of 10 ± (3.0) years. Thirteen (53%) children were under ten years and 15 (60%) were male. The median/interquartile range age at diagnosis was 1.7 [0.8–3.0] years. SCD-related complications were common. A review of the medical records showed a third of the patients (32%) had at least one previous episode of acute chest syndrome, 20 (80%) had a history of vaso-occlusive crisis, and 15 (76%) had required at least one blood transfusion. Spirometry was performed on 19 (76%) of the participants 9 (47%) had abnormal lung function. The most common spirometry abnormality was a restrictive pattern (forced vital capacity (FVC) < lower limit of normal (LLN)). No participant had a positive bronchodilator response. Older age was associated with a decrease in forced expiratory volume in the first second (FEV1) Z-score (−0.16, 95% confidence interval [CI] −0.31, −0.01; P = 0.04). Children on hydroxyurea similarly had reduced FEV1 Z-score (−1.5, 95%CI −2.88, −0.12; P = 0.04) and reduced FVC Z-score (−2.21, 95%CI −3.64, −0.79; P < 0.001). Conclusion: Lung function abnormalities were common among children with SCD, with restrictive abnormality predominating. Asthma and obstructive airway abnormalities were uncommon in children with SCD in South Africa.

Association Between Dental Infection and Increased Incidence of Complications in Sickle Cell Disease Children: A Cross-sectional Study in Jeddah City

Aim: Children with sickle cell disease (SCD) are prone to many complications. However, little is known about oral infectious. This study aimed to assess the oral health status of pediatric patients with SCD and explore the associations between oral health conditions and clinical complications of SCD. Materials and Methods: A cross-sectional study was conducted in children with SCD admitted to the pediatric wards of two government hospitals in Jeddah city. The children were examined for dental caries, gingival diseases, oral lesions, and dental infections. Oral findings were compared between children who were hospitalized for vaso-occlusive crisis (VOC) or had a history of VOC in the last 6 or 12 months and those who were admitted for other reasons such as blood transfusion or other complications or had no history of VOC in the last 6 or 12 months. Results: A total of 107 children with SCD were included, with a mean age of 9.82 ± 3.82 years, of which 51 (47.7%) were females. Of the total, 58 (54.2%) were admitted because of VOC. There was a significant relationship between VOC and dental attrition ( P = 0.038), osteomyelitis, and dental abscesses ( P = 0.004). A significant association was found between the presence of dental abscesses and a history of osteomyelitis or avascular necrosis of long bones in the previous 12 months ( P = 0.001 and P = 0.041, respectively). Conclusion: Dental abscesses and non-carious lesions are likely to be associated with VOC; however, further prospective cohort studies are warranted to confirm this association and establish a causal relationship.

Syndrome thoracique aigu chez les patients drépanocytaires adultes

Sickle cell disease is a frequent genetic condition, due to a mutation of the β-globin gene, leading to the production of an abnormal S hemoglobin and characterized by multiple vaso-occlusive events. The acute chest syndrome is a severe complication associated with a significant disability and mortality. It is defined by the association of one or more clinical respiratory manifestations and a new infiltrate on lung imaging. Its pathophysiology is complex and implies vaso-occlusive phenomena (pulmonary vascular thrombosis, fat embolism), infection, and alveolar hypoventilation. S/S or S/β0-thalassemia genotype, a history of vaso-occlusive crisis or acute chest syndrome, a low F hemoglobin level (<5%), a high steady-state hemoglobin level (> 10 g/dL), or a high steady-state leukocytosis (>10 G/L) are the main risk factors. Febrile chest pain, dyspnea, sometimes cough with expectorations are its main clinical manifestations, and bi-basal crackles are found at auscultation. Inferior alveolar opacities with or without pleural effusions are identified on chest X-ray or CT-scan. Management of the acute chest syndrome should be prompt and implies, besides the recognition of severity signs, a multimodal analgesia, oxygen supplementation, sometimes a parenteral antibiotic treatment and the frequent use of blood transfusions especially in the most severe cases. Prevention is important and includes a regular monitoring of hospitalized patients and the use of incentive spirometry.

Resolution of Serious Vaso-Occlusive Pain Crises and Reduction in Patient-Reported Pain Intensity: Results from the Ongoing Phase 1/2 HGB-206 Group C Study of LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy

Resolution of Serious Vaso-Occlusive Pain Crises and Reduction in Patient-Reported Pain Intensity: Results from the Ongoing Phase 1/2 HGB-206 Group C Study of LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy

Hydroxyurea Exposure throughout Pregnancy in Patients with Sickle-Cell Disease : 4 Case Reports from European Non-Interventional, Multicentric, Prospective Escort-HU Study

Over the last decades, the number of sickle-cell disease (SCD) women reaching childbearing age and planning to become pregnant is increasing due to improvements in the management of the disease.[1] Physiological changes of pregnancy, such as increased metabolic demand, increased blood viscosity and hyper-coagulability, lead to an increased incidence of complications, such as vaso-occlusive crisis (VOC), acute chest syndrome (ACS), osteonecrosis, hepatic necrosis, leg ulcers, and thromboembolic events. [2] Vaso-occlusion may also involve the placenta, with villi fibrosis, necrosis, and infarction leading to impaired uteroplacental circulation, with consequent chronic fetal hypoxia and adverse fetal outcomes. Therefore, prenatal care is important to evaluate if intensification of treatment as blood transfusion or Hydroxyurea (HU) may be required. HU is approved in EU and USA for VOC including ACS in patients with SCD aged 2 years and over. HU is not recommended for use during pregnancy, primarily because animal studies have suggested potential teratogenic effects on the fetus. In some rare cases, discontinuation of HU treatment to avoid fetal exposure is not possible. A few cases of exposure to HU throughout the pregnancy are published in the literature,[3] but none in SCD patients. We hereby present four cases in which HU was taken during all pregnancy collected in the ESCORT-HU study (European Sickle Cell Disease COhoRT - HydroxyUrea), a multicentric, prospective, non-interventional European study which collected long-term safety information on HU when used in current practice. Patient #1 (GxP2, SS) had a history of VOC, osteonecrosis and leg ulcers and was started on HU at age 18. She had two previous pregnancies without HU exposure. No oral contraception was taken and she spontaneously conceived at age 37. HU was continued at the same dose. Patient #2 (G5P1, Sβ+) had a history of VOC, chronic anemia and heart disease, and was started on HU at age 19. At age 34, she started to receive treatment for fertility (gonadotropin and follitropin). HU which had been started 17 years earlier was continued. Patient #3 (G5P1, Sβ+) had a history of chronic severe anemia and was started on HU at age 37. She had a gynecological history of 1 spontaneous abortion, 2 elective abortions and 1 live birth (pregnancy complicated with preeclampsia). She had been on oral contraception before becoming spontaneously pregnant when aged 38. HU, which had been initiated 11 months earlier, was continued at same dose. Patient #4 (SS, G3P0) female with history of stroke with sequelae and VOC, initiated on HU at the age of 25 following post-transfusion alloimmunization. Gynecological history included one spontaneous abortion and one elective abortion when aged 21 and 23 years (before initiation of HU). Following removal of contraceptive device, she conceived spontaneously at age 27. These four women suffered from severe SCD symptoms which required special management during pregnancies. HU exposure during pregnancy is not recommended but these case reports highlight the difficulty for medical teams to deal with both strong desire to become pregnant and maternal and fetal morbidity and mortality in SCD. Similarly to literature data in non-SCD patients, all four pregnancies in SCD women with HU exposure throughout pregnancy had a favorable outcome and no malformation was reported among the neonates. Details of pregnancy course and outcome are provided in Table 1. Although it is highly recommended to avoid any fetal exposure to HU, it can be difficult in some SCD patients with severe symptoms and a wish to become pregnant, to stop the treatment during pregnancy. In these cases, a strict monitoring of the mother and fetus is necessary. [1] Silva F.A.C., Ferreira A.L.C.G., Hazin-Costa M.F., Dias M.L.G., Araújo A.S., Souza A.I., Adverse clinical and obstetric outcomes among pregnant women with different sickle cell disease genotypes, International Federation of Gynecology and Obstetrics, 2018 [2] Jain D., Atmapoojya P., Colah R., Lodha P. Sickle cell disease and pregnancy. Mediterr J Hematol Infect Dis 2019, 11(1): e2019040 [3] C Thauvin-Robinet, Exposure to hydroxyurea during pregnancy: a case series, Correspondence 2001 Disclosures No relevant conflicts of interest to declare.

Abnormal Cytokine Production By Mast Cell Cultures from Sickle Cell Anemia Patients in Response to Inflammatory Stimuli and to Co-Culture with Eosinophils

Mast cell function (MC) in pathologic states can be studied through their ability to secrete mediators in vitro depending on MC phenotype and the nature of the stimuli. Reports on MC mediators in sickle cell anemia (SCA) patients are scarce, but clinical signs of MC activation syndrome, such as increased plasma histamine in vaso‐occlusive crisis (VOC), and normal or slightly elevated serum tryptase have been reported. However, assessing the biological relevance of MC as a cytokine source is more challenging because it is unclear under which circumstances they secrete those products in vivo, or if the cytokines measured systemically stem from a different cell type. We aimed to investigate the profile of mediators involved in the inflammatory process produced by MC in SCA. Methods:The supernatant of 5-week old MC cultures (17 SCA, 8 HV) obtained from peripheral blood CD34+ cells from 29 SCA patients and 13 healthy volunteers (HV) was analyzed using a multiplex platform and colorimetric assays for endothelin-1 (ET-1) and substance P (SP) (10 SCA, 6 HV). A correlation matrix (Pearson correlations, R software, v. 3.6.1) was generated using laboratory and clinical data chosen based on their value as inflammatory or prognosis markers (hydroxyurea [HU] treatment, fetal hemoglobin [HbF], hemoglobin [Hb], vaso-occlusive crisis [VOC], percentage of peripheral blood neutrophils, eosinophils (Eos), basophils, erythroblasts, and reticulocytes), MC surface expression of CD117, CD48 and CD63, and the supernatant content of 11 cytokines. To investigate MC cytokine release, we tested the supernatants from Eos-MC co-cultures (3:1 ratio), and after stimulation with ET-1 (20 nM), SP (10 µM) and imatinib (20 µg/ml)(n=3 per treatment). Results: Out of 26 cytokines, we found elevated levels of the following in the supernatants of SCA-MC cultures (data represented as mean in pg/ml±SE): TNFα: SCA=88.7±18.4, HV=32.6±3.8; IFNγ: SCA=55.3±11.2, HV=15.7±1.8; MCP1: SCA=555.0±147.2, HV=145.3±35.2; RANTES: SCA=24.7±3.9, HV=10.7±1.8 (p&amp;lt;0.05). However, SCA-MC from patients treated with HU (n = 11) showed higher values of IL-1b, IL-4, IL-5, IL-9, IL-15, and FGF than HV (n=8) and HU-free patients (n=6) (p&amp;lt;0.05). Supernatants from SCA-MC had higher ET-1 production compared to HV-MC (SCA=16.3±1.2, HV=11.93±1.3, pg/ml, p=0.02) but SP production was similar (SCA=27.9±1.3; HV=31.49±0.7 pg/ml). ET-1 stimulation of MC cultures caused 2-fold increase in IL-1AR production on HV-MC, but failed to produce any effect on SCA-MC. Similarly, imatinib reduced FGF only in HV-MC samples (HV: 15.1±3.5, HV-HU: 4.0±1.6, pg/ml). No effect on cytokine production was observed with SP. Conversely, Eos-MC cocultures showed a 10- and 4-fold increase of IL-5 and IL-9, respectively, regardless of the origin of Eos (HV or SCA). SCA-MC/SCA-Eos co-cultures had elevated proinflammatory (IL-1b, IL-12, TNF-α) and angiogenic (FGF, VEGF) cytokines, RANTES, IL-7, IL-4, and IL1-RA compared with SCA-MC/HV-Eos and HV-MC/HV-Eos (p&amp;lt;0.05). Preliminary multiparametric analysis on data from SCA patients showed a strong negative correlation between HU therapy and VGEF production, and between HbF levels and CD63 expression (MC activation marker).We also found a positive correlation between history of VOC and eotaxin-1 produced by SCA-MC. Conclusions: We found that MC responses depend both on the origin of the cultured cell and the stimuli utilized. Despite differences between in vitro and in vivo MC populations, our data show that cultured SCA-MC have a sustained activated state and produce a repertoire of mediators that could contribute to a perivascular microenvironment in favor of leukocyte and endothelium activation. In terms of cytokine production, cultured SCA-MC were more sensitive to stimulation by SCA-Eos than by HV-Eos, which may be relevant to the pathophysiology of airway inflammation in SCA patients with asthma. Differences in cytokine production between SCA-MC cultures from patients treated or not with HU may reflect the variability in adherence to treatment, individual response to each compound, or epigenetic modifications during the MC differentiation process that affect the phenotype of the mature MC. These results support that mediators produced by MC can contribute to the chronic inflammatory state and may be implicated in exacerbated responses to eosinophil activation in SCA. Disclosures Fertrin: Agios Pharmaceuticals, Inc.: Research Funding.

Exploring the Drivers of Potential Clinical Benefit in Initial Patients Treated in the Hgb-206 Study of Lentiglobin for Sickle Cell Disease (SCD) Gene Therapy

Exploring the Drivers of Potential Clinical Benefit in Initial Patients Treated in the Hgb-206 Study of Lentiglobin for Sickle Cell Disease (SCD) Gene Therapy

Prophylaxis oral aspartame improves anaemia and decreases frequency and severity of vaso-occlusive painful crisis among sickle cell disease patients and noninferior to hydroxyurea

Background: Sickle cell disease (HbSS) causes much of the morbidity and mortality due to its chronic anaemia and vaso-occlusive painful crisis. Hydroxyurea is now using to treat HbSS. Aspartame appears to have antisickling properties. The objective of this study was to asses the effects of prophylaxis oral Aspartame among HbSS patients on anaemia and vaso-occlusive painful crisis.Methods: 208 cases of HbSS patients with history of vaso-occlusive crisis (VOC) and/or anaemia were selected for the study and divided into study group (n = 104) and control group (n = 104). 31 and 38 patients were on Hydroxyurea in study group and control group respectively. Baseline hemoglobin was estimated in all cases and oral Aspartame was given in a dose of 4 mg/kg/day in three divided doses. Monthly hemoglobin levels were measured in all cases for six months. Data were collected and compared with control data by using SPSS software version 25.Results: Mean baseline hemoglobin was 6.99 gm% and increased to 8.43 gm% (P &lt;0.05) after receiving Aspartame prophylaxis. Aspartame add on to Hydroxyurea also had increased in haemoglobin levels. Incidence of VOC was 7.26% in control group. In Hydroxyurea group 3.58% had VOC. In study group 1.2% and in add on to Hydroxyurea group had 1.125 of milder degree of VOC (P &lt;0.05).Conclusions: Aspartame appears to have antisickling properties and improves anaemia and decreases frequency and severity of VOC among HbSS patients and is non-inferior to Hydroxyurea.

Conjunctival microvascular hemodynamics following vaso-occlusive crisis in sickle cell disease.

Painful vaso-occlusive crisis (VOC) is the clinical hallmark of sickle cell disease (SCD). Microcirculatory hemodynamic changes following painful VOC may be indicative of future development of VOC events in subjects with SCD. The purpose of the present study was to determine alterations in conjunctival microvascular hemodynamics during non-crisis state in SCD subjects with a history of VOC. Conjunctival microcirculation imaging was performed to measure conjunctival diameter (D) and axial blood velocity (V) in 10 control and 30 SCD subjects. SCD subjects were categorized into two groups based on their history of VOC within a 2-year period before imaging (with or without VOC-H) and also based on whether there was progression in the rate of VOCs during a 2-year period following imaging as compared to before imaging (with or without VOC-P). Conjunctival V was significantly higher in SCD subjects with VOC-H than in both control subjects and SCD subjects without VOC-H (P≤0.03). Conjunctival V was also significantly higher in SCD subjects with VOC-P compared with control subjects and SCD subjects without VOC-P (P≤0.03). Assessment of the conjunctival microcirculation may be useful for understanding hemodynamic changes that lead to VOC events in SCD subjects.

Reduction of the Six-Minute Walk Distance in Children with Sickle Cell Disease Is Correlated with Silent Infarct: Results From a Cross-Sectional Evaluation in a Single Center in Belgium.

AbstractAbstract 2107▪▪This icon denotes a clinically relevant abstractThe 6-minute walk test (6MWT) evaluates the sub-maximal functional exercise capacity and can be used together with the tricuspid regurgitant jet velocity (TRV) and pro-BNP to screen pulmonary hypertension in adults with sickle cell disease (SCD). A reduced 6-minute walk distance (6MWD) is observed in adults with SCD with chronic pain, hip avascular necrosis and osteopenia. In children with SCD, baseline elevated TRV is associated with a decline in age-standardized 6MWD.The aim of our study is to explore the submaximal exercise capacity of children with SCD followed at the Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium and to analyze the factors affecting the 6MWT and the 6MWD.Since September 2011, all patients with SCD above 6 years of age were screened with the 6MWT as part of their follow-up in order to test if their functional capacity was altered. The age-standardized predicted value of the 6MWD was established as reported by Geiger. The 6MWT was considered as normal if the 6MWD was more than 80% of the age-standardized predicted value, moderately decreased between 60–80%, and severely altered less than 60%. Baseline hematological values, clinical events, cerebro-vascular disease, cardio-pulmonary parameters and disease-modifying treatment (DMT) were compared between those with normal and abnormal 6MWT and according to the 6MWD.Forty-six patients (20 boys and 26 girls) with a median age of 12 yrs were investigated. Forty-three were HbSS or HbSβ°, 2 HbSC and 1 HbSβ+. Thirty-two patients had a normal 6MWT and 14 an abnormal 6MWT. Only one patient had a severely altered test. These 2 groups were similar for age, sex, genotype and history of vaso-occlusive crisis or acute chest syndrome (ACS) as well as for the number of patients receiving DMT (either hydroxyurea (HU) or chronic transfusion). The proportion of patients with normal, conditional or abnormal transcranial doppler was also similar in both groups. Silent infarct (SI) on routine cerebral magnetic resonance imaging was found in 42.9% in the group with abnormal 6MWT versus only 19.4% in the group with normal 6MWT (p= 0.087). Pulmonary functional test, blood pressure, heart rate, systolic function and TRV were identical in both groups and only one patient had TRV >2.5m/sec. Baseline pulse oxymetry was slightly but significantly decreased in patients with abnormal 6MWT (98 versus 100%; p=0.022). Biological parameters were not statistically different between both groups. The 6MWD was not modified according to Hb, MCV, HbF, LDH and reticulocytes count or previous history of clinical event, except for the presence of SI (Table 1). Patients with or without SI were similar for age, sex, previous ACS or painful crisis as well as for hemolytic parameters (LDH: 945 versus 825 UI/l, p=0.832; reticulocytes: 273 versus 329 × 103/μl, p=0.548) and basal Hb (9.7 versus 8.8 g/dl, p=0.06). However patients without SI had significantly higher HbF and MCV values, and lower PMN count reflecting that most of them were treated with HU.In this cross-sectional study, the majority of children with SCD have a normal 6MWT. Abnormal 6MWT was not predicted by any clinical or biological features despite a trend to more SI in the group of children with abnormal test. In this series with only one high TRV patient, the sole factor which influences the 6MWD is the presence of SI. The lower exercise capacity of children with SCD with silent stroke may reflect some subclinical motor or sensitive impairment. Our data suggest also that HU might prevent SI which needs to be confirmed by larger prospective studies.Table 16-minute walk distance (6MWD) in 46 SCD children according to their biological values and clinical complicationsMean 6MWD in meters (SD)p valueMean Age in years (SD)p valueHemoglobin (g/dl)· ≥ 9 (N = 24)531.5 (95.4)0.17311.2 (2.8)<0.001· < 9 (N = 22)569.8 (92.2)14.5 (2.7)MCV (fL)· ≥ 90 (N = 24)536.1 (100.7)0.25112.6 (3.5)0.518· < 90 (N = 22)568.3 (86.8)13.2 (2.8)HbF (%)*· ≥ 10% (N = 30)544.0 (101.7)0.36013.2 (3.5)0.352· <10% (N = 15)570.1 (81.8)12.6 (2.4)LDH (UI/l)· ≥ 1000 (N = 14)526.8 (86.5)0.22911.8 (3.0)0.105· < 1000 (N = 32)562.3 (97.4)13.4 (3.1)Previous ACS*· Yes (N = 38)548.6 (98.3)0.62513.5 (3.1)0.453· No (N = 7)566.9 (85.5)12.5 (4.2)Silent Infarct· Yes (N = 12)502.5 (113.9)0.03512.1 (2.2)0.374· No (N = 34)568.9 (82.0)13.2 (3.4)*Missed information for 1 patient. Disclosures:No relevant conflicts of interest to declare.

Targeting Busulfan to Concentration Steady State of 600–700 ng/Ml Is Associated with Robust Engraftment and Decreased Toxicity in Patients with Sickle Cell Disease Receiving An HLA Identical Donor Transplant

Abstract 1966Sickle cell disease is a chronic illness with significant morbidity and mortality. The most frequent adverse events are painful vaso-occlusive crises (VOC) that often require hospitalization. VOC are recurrent and unpredictable and associated with higher mortality. Adults frequently suffer from the consequences of cumulative organ damage. The life expectancy of patients with sickle cell disease is still in the 40s by the most recent evaluation. The only curative therapy is allogeneic hematopoietic stem cell transplant. The major complication related to transplant includes transplant related mortality and graft rejection. We used the previously described regimen of busulfan, cyclophosphamide and ATG. Concentration steady state (CSS) of busulfan <600 ng/ml has been associated wth graft rejection and a CSS >900 ng/ml is associated with increased risk of regimen related toxicity. We targeted busulfan to a CSS of 600–700 ng/ml in an attempt to decrease regimen related toxicity and achieve donor engraftment.Between 2004 and 2011 14 patients underwent allogeneic bone marrow transplant from HLA identical siblings. Preparative regimen consisted of intravenous busulfan 0.8–1 mg/kg/dose for 16 doses, cyclophosphamide of 50 mg /kg daily for 4 doses, and equine ATG 30 mg/kg daily for 3 doses. Busulfan levels were measured after the first dose busulfan and subsequent doses were adjusted to provide a total exposure of concentration steady state of 600–700 ng/ml. Graft versus host disease prophylaxis was with cyclosporine starting on day −3 and short course methotrexate. Indications for transplantation included stoke or abnormal transcranial doppler (n=2), acute chest syndrome (n=1), renal disease (n=1), history of vaso-occlusive crisis in (n=10) and availability of HLA identical donor.The median age at time of transplant was 6.1 years (range 1.2–19 years). All patients received anti-seizure prophylaxis and antihypertensive therapy until all immune suppression was discontinued. All patients received a bone marrow graft from HLA identical siblings. The median busulfan steady state exposure was 648 ng/ml (range 607–670). Only 3 patients (21%) developed mucositis requiring parentral nutrition and none of the patients developed sinusoidal obstructive syndrome post transplant. All patient achieved neutrophil and platelet engraftment at a median of 18 and 22 days respectively. Grade II acute graft versus host disease developed in 2 patients (14%) and none of the 13 evaluable patients developed chronic GVHD (one patient is <100 days from transplant). Median donor engraftment is 100% (range 85–100) and all patients have achieved a hemoglobin profile identical to their donor’s. None of the patients experienced sickle cell related complications post transplant. With a median follow up of 600 days (range 70–2644), the event free and overall survival are both 100%. All patients who are beyond one year post transplant are off all immune suppression.We conclude that targeting of busulfan between 600 and 700 ng/ml in combination with cyclophosphamide and ATG can result in excellent and sustained engraftment with low risk of toxicity in young patients with sickle cell disease. Disclosures:No relevant conflicts of interest to declare.