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3.
Br J Haematol ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33216975

RESUMO

We report here the 3-year stenosis outcome in 60 stroke-free children with sickle cell anaemia (SCA) and an abnormal transcranial Doppler history, enrolled in the DREPAGREFFE trial, which compared stem cell transplantation (SCT) with standard-care (chronic transfusion for 1-year minimum). Twenty-eight patients with matched sibling donors were transplanted, while 32 remained on standard-care. Stenosis scores were calculated after performing cerebral/cervical 3D time-of-flight magnetic resonance angiography. Fourteen patients had stenosis at enrollment, but only five SCT versus 10 standard-care patients still had stenosis at 3 years. Stenosis scores remained stable on standard-care, but significantly improved after SCT (P = 0·006). No patient developed stenosis after SCT, while two on standard-care did, indicating better stenosis prevention and improved outcome after SCT.

6.
Blood ; 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32976551

RESUMO

Sperm parameters are known to be impaired in men with sickle cell disease (SCD). Although treatment with hydroxyurea (HU) impacts sperm quality, sperm preservation is impossible before puberty. The present study's primary objective was to analyze and compare sperm parameters in male SCD patients exposed (or not) to HU before puberty. Twenty-six sperm samples from 15 patients (median (range) age: 17 (16-23)) treated with HU during childhood were compared with 46 samples from 23 HU-naïve patients (median (range) age: 20 (16-24)). The median (range) age at HU initiation was 6 years (1-14), the median duration of HU treatment was 4 years (0.5-10) and the mean ± standard deviation dose of HU was 22.4 ± 3.7 mg/kg/day. Although we observed substantial quantitative and qualitative semen abnormalities in all patients, there were no significant differences in semen volume, sperm concentration, total sperm count, and spermatozoa motility, morphology and vitality between the HU-exposed and HU-naïve groups. At the time of the semen analysis, respectively 100% and 52% of the patients in the HU-exposed and HU-naïve groups were on transfusion therapy. Hydroxyurea's specific effect on spermatogenesis in very young infants and the putative value of transfusion for reversing HU's toxicity warrant further investigation.

7.
Bull Cancer ; 107(9): 925-933, 2020 Sep.
Artigo em Francês | MEDLINE | ID: mdl-32921398

RESUMO

Sickle cell disease is associated with severe complications and early mortality in adults. In children, hematopoietic stem cell transplant from HLA-identical sibling can stop the progression of the disease and leads to more than 95% long-term free survival without sickle cell disease. The aim of this workshop was to define indications and modalities of allogeneic hematopoietic stem cell transplant in children and adults with sickle cell disease. Patient and sibling HLA typing should be proposed, early in the course of the disease, when intensification therapies are required. Indications of transplant from HLA-identical sibling in children and adults are, cerebral vasculopathy, occurrence of vaso-occlusive events despite hydroxycarbamide, renal and hepatic diseases related to SCD, chronic anemia<7g/dL despite hydroxycarbamide, need to maintain transfusion programs longer than six months, and major transfusion difficulties related to red blood cell alloimmunization. In children with an HLA-identical sibling donor, we recommend a myeloablative conditioning regimen associating high dose busulfan, cyclophosphamide and ATG, considering the excellent results of this approach In patients over 15 years of age, we recommend the NIH approach consisting of a reduced intensity conditioning regimen by alemtuzumab, and 3Gy total body irradiation, followed by peripheral hematopoietic stem cells and post-transplant immunosuppression by sirolimus In the absence of HLA-identical sibling donor, there is no definitive data for preferring transplant from unrelated versus haplo-identical donors but we recommend to evaluate these approaches in prospective trials.


Assuntos
Anemia Falciforme/cirurgia , Transplante de Células-Tronco Hematopoéticas , Adulto , Criança , Humanos , Transplante Homólogo
8.
Soins Pediatr Pueric ; 41(314): 35-41, 2020.
Artigo em Francês | MEDLINE | ID: mdl-32771206

RESUMO

The effect of a standardized musical intervention for adolescents with sickle cell disease was studied. Two groups were evaluated using the visual analog scale of pain and the anxiety-state inventory before and after a standardized musical intervention or breathing intervention. A significant decrease in scores was observed, most notably for the group benefiting from the standardized musical intervention. This intervention could be integrated into the overall management of adolescents with sickle cell disease.


Assuntos
Anemia Falciforme/terapia , Ansiedade/prevenção & controle , Musicoterapia , Manejo da Dor/métodos , Dor/prevenção & controle , Adolescente , Anemia Falciforme/complicações , Anemia Falciforme/psicologia , Ansiedade/etiologia , Humanos , Dor/etiologia , Resultado do Tratamento
9.
Clin Chem Lab Med ; 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32813673

RESUMO

Objectives Newborn screening (NBS) for ß-thalassemia is based on measuring the expression of the hemoglobin A (HbA) fraction. An absence or very low level of HbA at birth may indicate ß-thalassemia. The difficulty is that the HbA fraction at birth is correlated with gestational age (GA) and highly variable between individuals. We used HbA expressed in multiples of the normal (MoM) to evaluate relevant thresholds for NBS of ß-thalassemia. Methods The chosen threshold (HbA≤0.25 MoM) was prospectively applied for 32 months in our regional NBS program for sickle cell disease, for all tests performed, to identify patients at risk of ß-thalassemia. Reliability of this threshold was evaluated at the end of the study. Results In all, 343,036 newborns were tested, and 84 suspected cases of ß-thalassemia were detected by applying the threshold of HbA≤0.25 MoM. Among the n=64 cases with confirmatory tests, 14 were confirmed using molecular analysis as ß-thalassemia diseases, 37 were confirmed as ß-thalassemia trait and 13 were false-positive. Determination of the optimum threshold for ß-thalassemia screening showed that HbA≤0.16 MoM had a sensitivity of 100% and a specificity of 95.3%, whatever the GA. Conclusions NBS for ß-thalassemia diseases is effective, regardless of the birth term, using the single robust threshold of HbA≤0.16 MoM. A higher threshold would also allow screening for carriers, which could be interesting when ß-thalassemia constitutes a public health problem.

10.
Eur J Contracept Reprod Health Care ; 25(4): 293-298, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32496830

RESUMO

PURPOSE: Focussing on sickle cell disease (SCD), the objective of this study was to assess adolescents' sexual heath experience in the context of their chronic illness. MATERIALS AND METHODS: We included teenagers from 14 to 19 years old followed for SCD in a hospital located in Créteil (France) from March 2017 to February 2018. Their sexual health experience was assessed by a self-questionnaire with three key themes: contraceptive experience, awareness of sexuality with chronic disease and level of information on the genetic transmission of the disease. RESULTS: 99 questionnaires were analysed. Only six SCD adolescents (one girl and five boys) reported being sexually active. Despite a very regular follow-up of their illness, only 13% of the boys and girls had received information on contraception at the hospital. Most adolescents (85% of boys and 81% of girls) did not think that the disease would interfere with sexual intercourse. The genetic pattern was well known (85% of boys and 87% of girls). CONCLUSION: Young people with SCD need more information on contraception. Clinicians caring for them should be aware of the need for sexual health information in order to propose prevention actions adapted to these young people with chronic disease.

11.
Ann Rheum Dis ; 79(8): 999-1006, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32527868

RESUMO

BACKGROUND: Current data suggest that COVID-19 is less frequent in children, with a milder course. However, over the past weeks, an increase in the number of children presenting to hospitals in the greater Paris region with a phenotype resembling Kawasaki disease (KD) has led to an alert by the French national health authorities. METHODS: Multicentre compilation of patients with KD in Paris region since April 2020, associated with the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ('Kawa-COVID-19'). A historical cohort of 'classical' KD served as a comparator. RESULTS: Sixteen patients were included (sex ratio=1, median age 10 years IQR (4·7 to 12.5)). SARS-CoV-2 was detected in 12 cases (69%), while a further three cases had documented recent contact with a quantitative PCR-positive individual (19%). Cardiac involvement included myocarditis in 44% (n=7). Factors prognostic for the development of severe disease (ie, requiring intensive care, n=7) were age over 5 years and ferritinaemia >1400 µg/L. Only five patients (31%) were successfully treated with a single intravenous immunoglobulin (IVIg) infusion, while 10 patients (62%) required a second line of treatment. The Kawa-COVID-19 cohort differed from a comparator group of 'classical' KD by older age at onset 10 vs 2 years (p<0.0001), lower platelet count (188 vs 383 G/L (p<0.0001)), a higher rate of myocarditis 7/16 vs 3/220 (p=0.0001) and resistance to first IVIg treatment 10/16 vs 45/220 (p=0.004). CONCLUSION: Kawa-COVID-19 likely represents a new systemic inflammatory syndrome temporally associated with SARS-CoV-2 infection in children. Further prospective international studies are necessary to confirm these findings and better understand the pathophysiology of Kawa-COVID-19. Trial registration number NCT02377245.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Pneumonia Viral/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Síndrome de Linfonodos Mucocutâneos/virologia , Pandemias , Paris/epidemiologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/virologia
13.
J Clin Med ; 9(1)2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31947773

RESUMO

Perceived exertion is an important self-limiting factor influencing functional capacity in patients with sickle cell anemia (SCA). Exercise-related hemoglobin desaturation (EHD) may occur during a six-minute walking test (6MWT) and could influence the perceived rate of exertion. The aims of this study were (1) to compare the 6MWT responses (heart rate, perceived rate of exertion, and distance covered) between SCA children with and without EHD, and (2) to test the associations between EHD and several biological/physiological parameters. Nine of 51 SCA children (18%) at steady state (mean age 11.9 ± 3.8 years) exhibited EHD at the end of the 6MWT. The rate of perceived exertion increased with exercise in the two groups, but reached higher values in the EHD group. Heart rate and performance during the 6MWT did not differ between the two groups. The magnitude of change in SpO2 during the 6MWT was independently associated with the red blood cell (RBC) deformability and RBC aggregates strength. This study demonstrates that SCA children with EHD during a 6MWT have a higher rate of perceived exertion than non-EHD children despite a similar physiological demand, and that abnormal RBC rheology determinants appear to be significant contributors.

14.
Haematologica ; 105(5): 1240-1247, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31537695

RESUMO

Although studies of mixed chimerism following hematopoietic stem cell transplantation in patients with sickle cell disease (SCD) may provide insights into the engraftment needed to correct the disease and into immunological reconstitution, an extensive multilineage analysis is lacking. We analyzed chimerism simultaneously in peripheral erythroid and granulomonocytic precursors/progenitors, highly purified B and T lymphocytes, monocytes, granulocytes and red blood cells (RBC). Thirty-four patients with mixed chimerism and ≥12 months of follow-up were included. A selective advantage of donor RBC and their progenitors/precursors led to full chimerism in mature RBC (despite partial engraftment of other lineages), and resulted in the clinical control of the disease. Six patients with donor chimerism <50% had hemolysis (reticulocytosis) and higher HbS than their donor. Four of them had donor chimerism <30%, including a patient with AA donor (hemoglobin >10 g/dL) and three with AS donors (hemoglobin <10 g/dL). However, only one vaso-occlusive crisis occurred with 68.7% HbS. Except in the patients with the lowest chimerism, the donor engraftment was lower for T cells than for the other lineages. In a context of mixed chimerism after hematopoietic stem cell transplantation for SCD, myeloid (rather than T cell) engraftment was the key efficacy criterion. Results show that myeloid chimerism as low as 30% was sufficient to prevent a vaso-occlusive crisis in transplants from an AA donor but not constantly from an AS donor. However, the correction of hemolysis requires higher donor chimerism levels (i.e ≥50%) in both AA and AS recipients. In the future, this group of patients may need a different therapeutic approach.

15.
Haematologica ; 105(1): 91-101, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31097628

RESUMO

Allogeneic stem cell transplantation remains the only curative treatment for sickle cell anemia (SCA), but the place of myeloablative conditioning in the procedure remains to be defined. The aim of the present study was to analyze long-term outcomes, including chimerism, SCA-related events and biological data (hemoglobin, reticulocytes, HbS%), and fertility in a French series of 234 SCA patients under 30 years of age who, from 1988 to 2012, received a matched-sibling-donor stem cell transplantation following standardized myeloablative conditioning [busulfan, cyclophosphamide and rabbit antithymocyte globulin (ATG)]. Since the first report of the series (1988-2004), 151 new consecutive patients with SCA have been similarly transplanted. Considering death, non-engraftment or rejection (donor cells <5%) as events, the 5-year event-free survival was 97.9% (95% confidence interval: 95.5-100%), confirming, since the year 2000, an at least 95% chance of cure. In the overall cohort (n=234, median follow up 7.9 years), event-free survival was not associated with age, but chronic-graft-versus-host disease (cGvHD) was independently associated with recipient's age >15 years (hazard ratio=4.37; P=0.002) and lower (5-15 vs 20 mg/kg) ATG dose (hazard ratio=4.55; P=0.001). At one year, 44% of patients had mixed chimerism (5-95% donor cells), but those prepared with ATG had no graft rejection. No events related to SCA occurred in patients with mixed chimerism, even those with 15-20% donor cells, but hemolytic anemia stigmata were observed with donor cells <50%. Myeloablative transplantation with matched-sibling donor currently has a higher event-free survival (98%) in patients under 30 years of age than that reported for non-myeloablative conditioning (88%). Nevertheless, the risk of cGvHD in older patients and the need to preserve fertility might be indications for a non-myeloablative conditioning.

16.
J Clin Med ; 8(11)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683997

RESUMO

This prospective observational study sought to ascertain clinical and laboratory parameters associated with the development of acute chest syndrome (ACS) during vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD). It was performed at the pediatric department of the university Intercommunal Créteil hospital. All children with SCD (all sickle genotypes) consecutively admitted from November 2013 to December 2016 for painful VOEs and no evidence of ACS were included. Clinical and laboratory parameters collected at admission and within 48 h after admission were compared for children in whom ACS developed or not. Variables that were statistically significant on univariate analysis or considered to be clinically relevant were included in a multivariable model to ascertain the risk factors associated with the development of ACS during a VOE. The variables retained in the multivariate model were used to construct a predictive score for ACS. For each included child and during the study period, only data from the first VOE and/or the first ACS were analyzed. Among 191 hospitalizations for painful VOEs, for 176 children with SCD, ACS developed in 35 during hospitalization. Mean hospital stay was longer for children with ACS versus VOEs alone (7.6 (±2.3) vs. 3.3 (±1.8) days, p < 0.0001), and all children with ACS versus 28/156 (17.9%) with VOEs alone received red blood cell transfusion (p < 0.0001). The multivariate model retained pain score (≥9/10), pain localization (abdominal or spinal pain or involving more than two limbs), and high reticulocyte (≥260 × 109/L) and neutrophil (>10 × 109/L) counts, at admission, as independently associated with ACS development. The area under the receiver operating characteristic curve for the ACS predictive score was 0.82 (95% CI: 0.74-0.89), and the negative predictive value was 97.7%. The evolution profiles during the first 48 h differed between children with ACS and VOEs alone, with a more rapid decline of pain score and leucocytosis in children with VOEs. Clinical and laboratory measurements at admission may be simple parameters to identify children with increased risk of ACS development during VOEs and to facilitate early diagnosis of this respiratory complication. Also, the persistent elevation of leukocyte count on day 2 may be considered a sign of evolving ACS.

17.
J Clin Med ; 8(10)2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31618899

RESUMO

Over the past 3 decades, the pediatric department of the university Intercommunal Créteil hospital, a referral center for sickle cell disease (SCD), has prospectively evaluated immunoglobulin (Ig) levels in a cohort of 888 children with SCD, including 731 with severe sickle genotypes (HbSS and HbSß0 thalassemia) and 157 with milder genotypes (HbSC and HbSß+ thalassemia). We found consistent sickle genotype differences in levels of IgG and IgA, with increased levels of IgA and IgG in the severe versus milder genotype, from early childhood to late adolescence. Additionally, our results revealed a low serum IgM level, irrespective of sickle genotype. Finally, we found that IgA and IgG levels were significantly increased after therapeutic intensification with hydroxyurea but were stabilized in children receiving a transfusion program. The mechanisms contributing to these changes in Ig levels are unclear as is their clinical significance. We believe they should be further investigated.

18.
J Clin Med ; 8(10)2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31581727

RESUMO

This study's objective was to assess, on a national scale, residual risks of death, major disease-related events, and quality of care during the first five years in children diagnosed at birth with sickle cell disease (SCD). Data were retrospectively collected from medical files of all children with SCD born between 2006-2010 in France. Out of 1792 eligible subjects, 1620 patients (71.8% SS or S/beta°-thalassemia -SB°-) had available follow-up data, across 69 centers. Overall probability of survival by five years was 98.9%, with 12/18 deaths related to SCD. Probability of overt stroke by five years in SS/SB° patients was 1.1%, while transcranial Doppler (TCD) was performed in 81% before three years of age. A total of 26 patients had meningitis/septicemia (pneumococcal in eight cases). Prophylactic penicillin was started at a median age of 2.2 months and 87% of children had received appropriate conjugate pneumococcal vaccination at one year. By five years, the probability of survival without SCD-related events was 10.7% for SS/SB° patients. In contrast, hydroxyurea was prescribed in 13.7% and bone marrow transplant performed in nine patients only. In this study, residual risks of severe complications were low, probably resulting from a good national TCD, vaccination, and healthcare system coverage. Nonetheless, burden of disease remained high, stressing the need for disease-modifying or curative therapy.

19.
Blood ; 134(1): 9-21, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-30940614

RESUMO

Evans syndrome (ES) is a rare severe autoimmune disorder characterized by the combination of autoimmune hemolytic anemia and immune thrombocytopenia. In most cases, the underlying cause is unknown. We sought to identify genetic defects in pediatric ES (pES), based on a hypothesis of strong genetic determinism. In a national, prospective cohort of 203 patients with early-onset ES (median [range] age at last follow-up: 16.3 years ([1.2-41.0 years]) initiated in 2004, 80 nonselected consecutive individuals underwent genetic testing. The clinical data were analyzed as a function of the genetic findings. Fifty-two patients (65%) received a genetic diagnosis (the M+ group): 49 carried germline mutations and 3 carried somatic variants. Thirty-two (40%) had pathogenic mutations in 1 of 9 genes known to be involved in primary immunodeficiencies (TNFRSF6, CTLA4, STAT3, PIK3CD, CBL, ADAR1, LRBA, RAG1, and KRAS), whereas 20 patients (25%) carried probable pathogenic variants in 16 genes that had not previously been reported in the context of autoimmune disease. Lastly, no genetic abnormalities were found in the remaining 28 patients (35%, the M- group). The M+ group displayed more severe disease than the M- group, with a greater frequency of additional immunopathologic manifestations and a greater median number of lines of treatment. Six patients (all from the M+ group) died during the study. In conclusion, pES was potentially genetically determined in at least 65% of cases. Systematic, wide-ranging genetic screening should be offered in pES; the genetic findings have prognostic significance and may guide the choice of a targeted treatment.


Assuntos
Anemia Hemolítica Autoimune/genética , Anemia Hemolítica Autoimune/imunologia , Trombocitopenia/genética , Trombocitopenia/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Mutação , Adulto Jovem
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