In children with sickle cell anemia (SCA), high transcranial Doppler (TCD) velocities are associated with stroke risk, which is reduced by chronic transfusion. Whether matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) can reduce velocities in patients with SCA is unknown. OBJECTIVE To determine the association of MSD-HSCT with TCD velocities as a surrogate for the occurrence of ischemic stroke in children with SCA. DESIGN, SETTING, AND PARTICIPANTS Nonrandomized controlled intervention study conducted at 9 French centers. Patients with SCA were enrolled between December 2010 and June 2013, with 3-year follow-up ending in January 2017. Children with SCA were eligible if younger than 15 years, required chronic transfusions for persistently elevated TCD velocities, and had at least 1 sibling without SCA from the same 2 parents. Families agreed to HLA antigen typing and transplantation if a matched sibling donor was identified or to standard care in the absence of a matched sibling donor. EXPOSURES MSD-HSCT (n = 32), compared with standard care (n = 35) (transfusions for Ն1 year with potential switch to hydroxyurea thereafter), using propensity score matching. MAIN OUTCOMES AND MEASURES The primary outcome was the highest time-averaged mean of maximum velocities in 8 cerebral arteries, measured by TCD (TCD velocity) at 1 year. Twenty-five of 29 secondary outcomes were analyzed, including the highest TCD velocity at 3 years and normalization of velocities (<170 cm/s) and ferritin levels at 1 and 3 years. RESULTS Sixty-seven children with SCA (median age, 7.6 years; 35 girls [52%]) were enrolled (7 with stroke history). In the matched sample, highest TCD velocities at 1 year were significantly lower on average in the transplantation group (129.6 cm/s) vs the standard care group (170.4 cm/s; difference, −40.8 cm/s [95% CI, −62.9 to −18.6]; P < .001). Of the 25 analyzed secondary end points, 4 showed significant differences, including the highest TCD velocity at 3 years (112.4 cm/s in the transplantation group vs 156.7 cm/s in the standard care group; difference, −44.3 [95% CI, −71.9 to −21.1]; P = .001); normalization rate at 1 year (80.0% in the transplantation group vs 48.0% in the standard care group; difference, 32.0% [95% CI, 0.2% to 58.6%]; P = .045); and ferritin levels at 1 year (905 ng/mL in the transplantation group vs 2529 ng/mL in the standard care group; difference, −1624 [95% CI, −2370 to −879]; P < .001) and 3 years (382 ng/mL in the transplantation group vs 2170 ng/mL in the standard care group; difference, −1788 [95% CI, −2570 to −1006]; P < .001). CONCLUSIONS AND RELEVANCE Among children with SCA requiring chronic transfusion because of persistently elevated TCD velocities, MSD-HSCT was significantly associated with lower TCD velocities at 1 year compared with standard care. Further research is warranted to assess the effects of MSD-HSCT on clinical outcomes and over longer follow-up.
Intravenous ZDV remains an effective tool to reduce transmission in cases of virological failure, even in cART-treated women. However, for the vast majority of women with low viral loads at delivery, in the absence of obstetrical risk factors, systematic intravenous ZDV appears to be unnecessary.
No abstract
During the first successive waves of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants, adult patients with sickle cell disease (SCD), particularly older patients and those with the SC genotype, were reported to be at risk of severe coronavirus disease 2019 (COVID-19), whereas children seemed relatively spared. 1 Although the B.1.1.529 (Omicron) variant was considered to induce less severe forms than the Delta variant in adults, the last Omicron wave resulted in a surprising increase in hospitalised paediatric cases. 2 Nevertheless, little is known about the severity of the Omicron variant in patients with SCD, especially in children. In France, the COVID-19 vaccine has been recommended for adolescents with SCD aged >12 years since 28 May 2021, and for children with SCD aged 5-11 years since 30 November 2021. The objective of this study was to focus on severe outcomes in children with SCD infected by SARS-CoV-2 during the Omicron wave within the landscape of widespread COVID-19 vaccination.All paediatricians and adult-patient practitioners involved in SCD management in France were contacted by our national SCD consortia (see Ref. [1] for details) to report patients with SCD hospitalised with severe COVID-19 infection from 27 December 2021 to 30 April 2022, corresponding to the Omicron wave in France. SARS-CoV-2 infection was confirmed by reverse transcription polymerase chain reaction or rapid antigen-detection tests.Severe COVID-19 was defined as hospitalised patients with SCD with at least one of the following criteria: oxygen therapy >3 L/min, intensive care unit (ICU) admission, pulmonary embolism (PE), deep vein thrombosis (DVT), stroke, multisystem inflammatory syndrome in children (MIS-C), or a haemoglobin (Hb) level of <50 g/L.Anonymised data were collected by the investigators using standardised forms with a minimal dataset (Table 1). The only recorded biological value was the Hb level at admission. In line with the French legislation on retrospective studies of routine clinical practice, participants were not required to give their written informed consent. Patients or their parent/guardian were informed that their medical data could be used for research purposes, in accordance with General Data Protection Regulation 2016/679.During the 4-month Omicron wave, 29 patients with SCD with severe COVID-19 were reported by 13 French centres. In all, 17 (59%) were children (aged < 18 years), which is
Background: "Drepagreffe" is a French national prospective trial involving 67 sickle cell anemia (SCA)-children with a history of abnormal cerebral arterial velocities by TCD, and comparing for the first time the outcome of cerebral vasculopathy following transfusion program (TP) or transplantation (HSCT). Inclusion criteria at enrollment were children with SCA (SS/Sb0), younger than 15 years, with a history of abnormal cerebral arterial velocities (TAMMX ≥ 200 cm/sec) and placed on long-term TP, with at least one non-SCA sibling, and with parents accepting HLA-typing and HSCT if a genoidentical donor was available. The 2 arms (TP/HSCT) were defined by the random-availability of a genoidentical donor. Seven of the 67 patients had a history of stroke. Transplanted patients (n=32) received a conditioning regimen of Busilvex-CY 200 mg/kg and 20 mg/kg rabbit Thymoglobulin, with CSA and a short course of MTX or MMF for GvHD prophylaxis. In the TP arm (n=35), HbS% was maintained at < 30%, with an Hb at 9-11g/dL. At enrollment and 12 months post-enrollment, blood screening, Doppler, and cerebral MRI/MRA were performed along with cognitive performance testing, the latter being done in parallel in the non-SCA siblings. Preliminary findings on cerebral velocities as the primary endpoint were reported at the last ASH meeting (abstract 67237), and demonstrated that all patients were alive at one year and that the 32 transplanted patients had no chronic GVHD and the same hemoglobin profile as their donor. Velocities were significantly lower post-HSCT than under TP (p <0.001), and were normalized in a greater number of patients (p =0.003). Patients and Methods: We report here the cerebral imaging (MRI/MRA) and cognitive performance data performed at enrollment and after 12 months. The scoring applied for MRI was: 3 = territorial, 2 = borderzone (cortical and subcortical), 1 = white matter or basal ganglia infarcts, 0 to 3 = atrophia, and for MRA: 1 = mild stenosis (25-49%), 2 = moderate stenosis (50-74%), 3 = severe stenosis (75-99%), 4 = occlusion for each artery and 0 to 2 for Moya presence. Cognitive testing using the WPPSI-3 (3-6 yr), WISC-4 (7-16 yr) or WAIS-3 (>16 yr) scales, depending on the age, was performed in patients and in siblings when possible. Results: MRI/MRA data were available in 66/67 patients. At enrollment (M0), ischemic lesions and stenoses were present in 25 and 35/66 patients, respectively. Cognitive testing was obtained in 64 patients and 56 siblings. Paired analysis with siblings (Table 1) showed significant differences in Verbal Comprehension Index (VCI) with a mean difference of 7.6±14.5(p =0.0004), Processing Speed Index (PSI) 6.3±20.5 (p =0.04), and Full Scale IQ (FSIQ) 7.3±15.0 (p =0.01). After exclusion of the 7 patients with stroke history, significant differences were still observed in VCI (p =0.013) and FSIQ (p =0.019). Patient cognitive performance indexes were correlated negatively and significantly with the MRI and MRA scores (Table 2). At post-enrollment (M12),ischemic lesions and stenoses were present in 26/66 patients. The mean variation in MRI and MRA scores between M12 and M0 was not significantly different between the 2 arms (Table 3). The cognitive tests were performed at M12 in 60 patients (Table 4) and the performance indexes were improved in the TP compared to the HSCT arm, but only significantly for FSIQ. Conclusion This first prospective trial initially showed that HSCT reduces more significantly the cerebral velocities at M12 and in a higher proportion of patients than TP. Here, we show that patients with a history of abnormal cerebral velocities had significantly lower cognitive performances than their siblings, even in the absence of stroke history; however, there was no significant difference between the 2 arms for the outcomes of ischemic lesions and stenosis at M0 and M12. The fact that cognitive performances were improved in the TP compared to the HSCT arm might be explained by the stress of the HSCT procedure and the lack of schooling during this period. Despite the higher ability of HSCT to decrease velocities at M12 compared to TP, a longer follow-up will be required to demonstrate its effect on stenosis and cognitive performances; therefore, patients will be reassessed at 3 years post-HSCT. Disclosures Bernaudin: Novartis: Research Funding.
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