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1.
J Assist Reprod Genet ; 41(4): 1027-1034, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38358434

RESUMEN

PURPOSE: To describe the experience of performing ovarian tissue cryopreservation (OTC) before hematopoietic stem cell transplantation (HSCT), among girls/women with severe sickle cell disease (SCD)(SS or S/ß0-thalassemia) who are, besides the usual surgical risk, at risk of SCD-related complications during the fertility preservation procedure for improving their counseling and management. METHODS: This retrospective study included 75 patients (girls/women) with SCD who have had OTC before myeloablative conditioning regimen (MAC) for HSCT. Characteristics of patients and data on OTC, ovarian status follow-up, and results of ovarian tissue transplantation (OTT) were collected in medical records. RESULTS: At OTC, the median (IQR 25-75; range) age of the patients was 9.6 (6.9-14.1; 3.6-28.3) years, 56/75 were prepubertal, and no SCD or surgery-related complications occurred. The median follow-up post-HSCT was > 9 years. At the last follow-up, among prepubertal patients at HSCT, 26/56 were ≥ 15 years old and presented with a premature ovarian insufficiency (POI), except 2, including the patient who had received an OTT to induce puberty. Eight were 13-15 years old and presented for POI. The remaining 22 patients were under 13. Among the 19 patients who were menarche at HSCT, 2 died 6 months post-HSCT and we do not have ovarian function follow-up for the other 2 patients. All the remaining patients (n = 15) had POI. Five patients had OTT. All had a return of ovarian function. One patient gave birth to a healthy baby. CONCLUSION: OTC is a safe fertility preservation technique and could be offered before MAC independent of the patient's age.


Asunto(s)
Anemia de Células Falciformes , Criopreservación , Preservación de la Fertilidad , Trasplante de Células Madre Hematopoyéticas , Ovario , Insuficiencia Ovárica Primaria , Humanos , Femenino , Preservación de la Fertilidad/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Criopreservación/métodos , Anemia de Células Falciformes/terapia , Ovario/trasplante , Niño , Adolescente , Adulto , Estudios de Seguimiento , Adulto Joven , Preescolar , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Acondicionamiento Pretrasplante/efectos adversos , Embarazo
2.
Haematologica ; 108(9): 2476-2486, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-36924235

RESUMEN

The burden of sickle cell disease (SCD) in France has been difficult to apprehend due to the paucity of reliable nationwide epidemiological data. We aimed to describe the epidemiology of SCD and evaluate its burden and costs. Patients with SCD and most severely affected patients were identified between 2012 and 2018 from the French National Health Data System database (SNDS, Système national des données de santé). Outcomes of interest included rates of acute and chronic complications, healthcare resource utilization and associated costs, and were compared in subpopulations of patients before and after hematopoietic stem cell transplantation, initiating hydroxyurea or a chronic transfusion program. Between 2012 and 2018, 22,619 patients with SCD were identified, among which 4,270 patients were defined as most severely affected. Rates of vaso-occlusion episodes and acute chest syndrome were 86.29 (95% confidence interval [CI]: 85.75-86.83] and 12.90 (95% CI: 12.69-13.11) per 100 person years in the study population and 166.9 (95% CI: 165.4- 168.4) and 22.71 (95% CI: 22.16-23.27) per 100 person years in most severely affected patients. Median (Q1-Q3) annualized total costs were €5,073.63 (range, €1,633.74-14,000.94) and €13,295.67 (range, €5,754.67-26,385.23) in the study population and most severely affected patients. Median annualized costs were ten times lower after treatment intensification for hematopoietic stem cell transplantation (€29,011.75 vs. €2,465.98; P<0.001), they slightly decreased after hydroxyurea initiation (€13,057.79 vs. €12,752.44; P=0.003) and were five times higher after chronic transfusion program initiation (€4,643.11 vs. €22,715.85; P<0.001). SCD still places a significant demand on health resources, even after therapeutic intensification.


Asunto(s)
Anemia de Células Falciformes , Trasplante de Células Madre Hematopoyéticas , Humanos , Hidroxiurea/uso terapéutico , Anemia de Células Falciformes/epidemiología , Anemia de Células Falciformes/terapia , Anemia de Células Falciformes/complicaciones , Francia/epidemiología , Bases de Datos Factuales
3.
Stroke ; 53(8): 2637-2646, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35387492

RESUMEN

BACKGROUND: Cerebral arteriopathy in patients with sickle cell anemia mainly affects the intracranial anterior circulation. However, the extracranial internal carotid artery (eICA) can also be stenosed and responsible for ischemic lesions. In children with sickle cell anemia, we perform routine annual Doppler ultrasound assessment of the eICA and magnetic resonance imaging with 3-dimensional time-of-flight magnetic resonance angiography of the Willis circle and neck arteries in those with abnormal velocity. Our aim was to report the evolution of eICA stenoses from 2011 to the present as a function of therapy in a retrospective case-series study. We hypothesized that chronic transfusion (CTT) would be more effective than hydroxyurea and simple observation on the evolution of eICA stenosis. METHODS: Eligibility criteria were a history of eICA velocity ≥160 cm/s with a minimum Doppler and magnetic resonance imaging follow-up of 1 year. eICAs were graded for stenosis according to NASCET (The North American Symptomatic Carotid Endarterectomy Trial). Magnetic resonance imaging was investigated for ischemic lesions. Treatment with hydroxyurea and CTT were obtained from the chart review. RESULTS: Fifty-four patients were included. Eight patients had a stroke history. The median (range) follow-up was 4.7 years (1.1-9.2 years). On the first neck magnetic resonance angiography, stenosis was present in 48/54 (89%) patients. Kinking was found in 39/54 (72%) patients. On the last neck magnetic resonance angiography, the proportion of patients with eICA stenosis decreased to 39/54 (72%). ICA occlusion occurred in 5 patients despite CTT. Three patients had carotid webs without intracranial stenosis. The proportion of patients with improvement in stenosis score was 8% with no treatment intensification, 20% with hydroxyurea, and 48% with CTT (P=0.016). The mean (SD) change per year in stenosis score was 0.40 (0.60) without intensification, 0.20 (0.53) with hydroxyurea, and -0.18 (0.55) with CTT (P=0.006). Ischemic lesions were present initially in 46% of patients, and the incidence of progressive ischemic lesions was 2.5 events/100 patient-years. Cox regression analysis showed that the initial score for eICA stenosis was a significant predictive factor for the risk of new silent cerebral infarct events. CONCLUSIONS: Our study reinforces the need to assess cervical arteries for better prevention of cerebral ischemia and encourage initiation of CTT in sickle cell anemia children with eICA stenosis.


Asunto(s)
Anemia de Células Falciformes , Enfermedades de las Arterias Carótidas , Estenosis Carotídea , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/diagnóstico por imagen , Anemia de Células Falciformes/epidemiología , Enfermedades de las Arterias Carótidas/complicaciones , Arteria Carótida Interna/diagnóstico por imagen , Estenosis Carotídea/complicaciones , Infarto Cerebral/etiología , Niño , Constricción Patológica/complicaciones , Humanos , Hidroxiurea/uso terapéutico , Estudios Retrospectivos
4.
Br J Haematol ; 193(1): 188-193, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33216975

RESUMEN

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.


Asunto(s)
Anemia de Células Falciformes/terapia , Transfusión Sanguínea/estadística & datos numéricos , Encéfalo/diagnóstico por imagen , Constricción Patológica/epidemiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adolescente , Anemia de Células Falciformes/patología , Donantes de Sangre/estadística & datos numéricos , Transfusión Sanguínea/normas , Encéfalo/irrigación sanguínea , Niño , Preescolar , Constricción Patológica/diagnóstico por imagen , Constricción Patológica/etiología , Estudios de Seguimiento , Humanos , Angiografía por Resonancia Magnética/métodos , Imagen por Resonancia Magnética , Evaluación de Resultado en la Atención de Salud , Estudios Prospectivos , Hermanos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & control , Ultrasonografía Doppler Transcraneal/estadística & datos numéricos
5.
Haematologica ; 105(5): 1240-1247, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31537695

RESUMEN

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.


Asunto(s)
Anemia de Células Falciformes , Trasplante de Células Madre Hematopoyéticas , Anemia de Células Falciformes/terapia , Quimerismo , Terapia Genética , Hematopoyesis , Humanos , Quimera por Trasplante , Trasplante Homólogo
6.
Haematologica ; 105(1): 91-101, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31097628

RESUMEN

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.


Asunto(s)
Anemia de Células Falciformes , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Anciano , Anemia de Células Falciformes/terapia , Quimerismo , Fertilidad , Francia/epidemiología , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Supervivencia sin Progresión , Hermanos , Acondicionamiento Pretrasplante
7.
Biol Blood Marrow Transplant ; 25(6): 1197-1209, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30500440

RESUMEN

Curative therapy for individuals with severe sickle cell disease (SCD) who lack an HLA-identical sibling donor has been frustratingly elusive. In with the goal of improving engraftment while minimizing transplantation-related morbidity, a multi-institutional learning collaborative was developed in the context of a Phase II clinical trial of nonmyeloablative, related HLA-haploidentical (haplo) bone marrow transplantation (BMT) with post-transplantation cyclophosphamide. All eligible participants had hemoglobin SS, and 89% (16 of 18) had an identifiable donor. The median patient age was 20.9 years (IQR, 12.1 to 26.0 years), and the most common indication for transplantation was overt stroke (in 69%; 11 of 16). In the first 3 patients, the conditioning regimen consisted of antithymocyte globulin, fludarabine, cyclophosphamide, and low-dose total body irradiation. Graft-versus-host disease (GVHD) prophylaxis included post-transplantation cyclophosphamide, mycophenolate mofetil, and sirolimus. Primary graft rejection occurred in 2 of the 3 patients (67%), which triggered the study-stopping rule. To reduce graft rejection risk, thiotepa was added to the conditioning regimen, and then 15 patients (including 2 with previous graft rejection) underwent haplo-BMT with this thiotepa-augmented conditioning regimen. At a median follow-up of 13.3 months (interquartile range [IQR], 3.8 to 23.1 months), 93% (14 of 15) had >95% stable donor engraftment at 6 months, with 100% overall survival. The median time to neutrophil engraftment (>500) was 22 days (IQR, 19 to 27 days), and that for platelet engraftment (>50 x 109/L) was 28 days (IQR, 27 days to not reached). Two patients had grade III-IV acute GVHD, 1 patient had mild chronic GVHD, and 86% of patients (6 of 7) were off immunosuppression therapy by 1-year post-transplantation. Our data suggest that haplo-BMT with post-transplantation cyclophosphamide and thiotepa improves donor engraftment without significantly increasing morbidity or mortality and could dramatically expand curative options for individuals with SCD.


Asunto(s)
Anemia de Células Falciformes/tratamiento farmacológico , Antineoplásicos Alquilantes/uso terapéutico , Trasplante de Médula Ósea/métodos , Ciclofosfamida/uso terapéutico , Inmunosupresores/uso terapéutico , Tiotepa/uso terapéutico , Adolescente , Adulto , Antineoplásicos Alquilantes/farmacología , Niño , Ciclofosfamida/farmacología , Femenino , Humanos , Inmunosupresores/farmacología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tiotepa/farmacología , Donantes de Tejidos , Adulto Joven
8.
Blood ; 129(11): 1548-1556, 2017 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-27965196

RESUMEN

Despite advances in supportive therapy to prevent complications of sickle cell disease (SCD), access to care is not universal. Hematopoietic cell transplantation is, to date, the only curative therapy for SCD, but its application is limited by availability of a suitable HLA-matched donor and lack of awareness of the benefits of transplant. Included in this study are 1000 recipients of HLA-identical sibling transplants performed between 1986 and 2013 and reported to the European Society for Blood and Marrow Transplantation, Eurocord, and the Center for International Blood and Marrow Transplant Research. The primary endpoint was event-free survival, defined as being alive without graft failure; risk factors were studied using a Cox regression models. The median age at transplantation was 9 years, and the median follow-up was longer than 5 years. Most patients received a myeloablative conditioning regimen (n = 873; 87%); the remainder received reduced-intensity conditioning regimens (n = 125; 13%). Bone marrow was the predominant stem cell source (n = 839; 84%); peripheral blood and cord blood progenitors were used in 73 (7%) and 88 (9%) patients, respectively. The 5-year event-free survival and overall survival were 91.4% (95% confidence interval, 89.6%-93.3%) and 92.9% (95% confidence interval, 91.1%-94.6%), respectively. Event-free survival was lower with increasing age at transplantation (hazard ratio [HR], 1.09; P < .001) and higher for transplantations performed after 2006 (HR, 0.95; P = .013). Twenty-three patients experienced graft failure, and 70 patients (7%) died, with the most common cause of death being infection. The excellent outcome of a cohort transplanted over the course of 3 decades confirms the role of HLA-identical sibling transplantation for children and adults with SCD.


Asunto(s)
Anemia de Células Falciformes/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Adolescente , Anemia de Células Falciformes/epidemiología , Anemia de Células Falciformes/mortalidad , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Supervivencia de Injerto , Antígenos HLA , Trasplante de Células Madre Hematopoyéticas/mortalidad , Histocompatibilidad , Humanos , Lactante , Masculino , Hermanos , Encuestas y Cuestionarios , Tasa de Supervivencia , Acondicionamiento Pretrasplante/métodos , Resultado del Tratamiento
9.
Pediatr Transplant ; 23(3): e13376, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30786109

RESUMEN

Genoidentical HSCT is currently the only curative treatment for SCA, preventing further vascular complications in high-risk children. Studies on the psychological implications of HSCT for recipient, sibling donor, and the rest of the family have been limited in SCA. This study enrolled ten families and used semi-structured interviews to explore the parents' experience at three time points: first before transplantation, then 3 months later, and 1 year later. Three themes emerged from the results: (a) the presence of anxiety, experienced throughout the process, and alleviated by coping strategies (positive thinking, family support, praying); (b) the ability to remain parents to recipient and other family members, despite apprehension and feelings of helplessness, reinforced by the mobilization of important resources at the individual/family levels; (c) the ability to acknowledge the opportunity for their child to be cured of the disease, despite feelings of guilt toward families without a donor, or their own families back home. Overall, the parental experience with HSCT is complex, involving intra-psychic, familial, cultural, religious, and existential factors. Thus, it is important for medical teams to be cognizant of these issues in order to provide the best support to families during the HSCT process.


Asunto(s)
Anemia de Células Falciformes/terapia , Ansiedad/etiología , Trasplante de Células Madre Hematopoyéticas , Donadores Vivos , Padres/psicología , Adaptación Psicológica , Adulto , Niño , Preescolar , Características Culturales , Familia/psicología , Salud de la Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Riesgo , Hermanos
10.
Acta Obstet Gynecol Scand ; 98(5): 630-637, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30919447

RESUMEN

INTRODUCTION: The preservation of fertility is an integral part of care of children requiring gonadotoxic treatments for cancer or non-malignant diseases. In France, the cryopreservation of ovarian tissue has been considered and has been offered as a clinical treatment since its inception. The aim of this study is to review 20 years of activity in fertility preservation by ovarian tissue cryopreservation (OTC) for children and the feasibility of oocyte isolation and cryopreservation from the ovarian tissue at a single center. MATERIAL AND METHODS: Retrospective study including patients aged 15 years or younger who underwent OTC, combined for some with oocyte cryopreservation of isolated oocytes, before a highly gonadotoxic treatment for malignant or non-malignant disease was initiated. We describe the evolution of activities in our program for fertility preservation and patient characteristics at the time of OTC and follow up. RESULTS: From April 1998 to December 2018, 418 girls and adolescents younger than 15 years of age underwent OTC, representing 40.5% of all females who have had ovarian tissue cryopreserved at our center. In all, 313 patients had malignant diseases and 105 had benign conditions. Between November 2009 and July 2013, oocytes were isolated and also cryopreserved in 50 cases. The mean age of patients was 6.9 years (range 0.3-15). The most frequent diagnoses in this cohort included neuroblastoma, acute leukemia and hemoglobinopathies; neuroblastoma being the most common diagnosis in very young patients. During follow up, three patients requested the use of their cryopreserved ovarian tissue. All had undergone ovarian tissue transplantation, one for puberty induction and the two others for restoring fertility. So far, no pregnancies have been achieved. Eighty-four patients who had OTC died. CONCLUSIONS: Ovarian tissue cryopreservation is the only available technique for preserving fertility of girls. To our knowledge this is the largest series of girls and adolescents younger than 15 years so far reported on procedures of OTC before highly gonadotoxic treatment in a single center.


Asunto(s)
Antineoplásicos , Criopreservación , Preservación de la Fertilidad , Neoplasias , Ovario , Adolescente , Antineoplásicos/uso terapéutico , Antineoplásicos/toxicidad , Niño , Preescolar , Criopreservación/métodos , Criopreservación/estadística & datos numéricos , Femenino , Preservación de la Fertilidad/métodos , Preservación de la Fertilidad/estadística & datos numéricos , Francia/epidemiología , Humanos , Lactante , Neoplasias/epidemiología , Neoplasias/terapia , Recuperación del Oocito , Evaluación de Procesos y Resultados en Atención de Salud , Utilización de Procedimientos y Técnicas/estadística & datos numéricos , Estudios Retrospectivos
11.
JAMA ; 321(3): 266-276, 2019 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-30667500

RESUMEN

Importance: 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 ≥1 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. Trial Registration: ClinicalTrials.gov Identifier: NCT01340404.


Asunto(s)
Anemia de Células Falciformes/terapia , Circulación Cerebrovascular/fisiología , Trasplante de Células Madre Hematopoyéticas , Hermanos , Ultrasonografía Doppler Transcraneal , Aloinjertos , Anemia de Células Falciformes/diagnóstico por imagen , Anemia de Células Falciformes/fisiopatología , Velocidad del Flujo Sanguíneo , Niño , Femenino , Ferritinas/sangre , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Puntaje de Propensión , Calidad de Vida , Acondicionamiento Pretrasplante
12.
J Infect Dis ; 217(3): 494-497, 2018 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-29087520

RESUMEN

As a live attenuated vaccine, yellow fever vaccine (YFV) is not routinely performed after allogeneic hematopoietic stem cell transplant (HSCT) despite it being the only efficient preventive therapy. We retrospectively identified 21 HSCT recipients immunized with YFV at a median of 39 months after HSCT and a median of 33 months after withdrawal of immunosuppression without any side effects. Eighteen evaluable patients had protective immunity after YFV. We also observed that a third of the recipients vaccinated with YFV before HSCT had persistent protective immunity after HSCT.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Huésped Inmunocomprometido , Trasplante Homólogo , Vacuna contra la Fiebre Amarilla/efectos adversos , Vacuna contra la Fiebre Amarilla/inmunología , Fiebre Amarilla/prevención & control , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/efectos adversos , Vacunas Atenuadas/inmunología , Vacuna contra la Fiebre Amarilla/administración & dosificación , Adulto Joven
13.
Blood ; 127(14): 1814-22, 2016 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-26851292

RESUMEN

Stroke risk in sickle cell anemia (SCA), predicted by high transcranial Doppler (TCD) velocities, is prevented by transfusions. We present the long-term follow-up of SCA children from the Créteil newborn cohort (1992-2012) detected at risk by TCD and placed on chronic transfusions. Patients with normalized velocities and no stenosis were treated with hydroxyurea, known to decrease anemia and hemolytic rate. Trimestrial Doppler was performed and transfusions restarted immediately in the case of reversion to abnormal velocities. Patients with a genoidentical donor underwent transplant. Abnormal time-averaged maximum mean velocities (TAMMV) ≥200 cm/s were detected in 92 SCA children at a mean age of 3.7 years (range, 1.3-8.3 years). No stroke occurred posttransfusion after a mean follow-up of 6.1 years. Normalization of velocities (TAMMV < 170 cm/s) was observed in 83.5% of patients. Stenosis, present in 27.5% of patients, was associated with the risk of non-normalization (P< .001). Switch from transfusions to hydroxyurea was prescribed for 45 patients, with a mean follow-up of 3.4 years. Reversion, predicted by baseline reticulocyte count ≥400 × 10(9)/L (P< .001), occurred in 28.9% (13/45) patients at the mean age of 7.1 years (range, 4.3-9.5 years). Transplant, performed in 24 patients, allowed transfusions to be safely stopped in all patients and velocities to be normalized in 4 patients who still had abnormal velocities on transfusions. This long-term cohort study shows that transfusions can be stopped not only in transplanted patients but also in a subset of patients switched to hydroxyurea, provided trimestrial Doppler follow-up and immediate restart of transfusions in the case of reversion.


Asunto(s)
Anemia de Células Falciformes , Transfusión Sanguínea , Circulación Cerebrovascular , Hidroxiurea/administración & dosificación , Accidente Cerebrovascular , Ultrasonografía Doppler Transcraneal , Anemia de Células Falciformes/diagnóstico por imagen , Anemia de Células Falciformes/fisiopatología , Anemia de Células Falciformes/terapia , Velocidad del Flujo Sanguíneo , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/prevención & control
15.
Haematologica ; 103(7): 1143-1149, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29599204

RESUMEN

In this retrospective study, we evaluate long-term complications in nearly all ß-thalassemia-major patients who successfully received allogeneic hematopoietic stem cell transplantation in France. Ninety-nine patients were analyzed with a median age of 5.9 years at transplantation. The median duration of clinical follow up was 12 years. All conditioning regimens were myeloablative, most were based on busulfan combined with cyclophosphamide, and more than 90% of patients underwent a transplant from a matched sibling donor. After transplantation, 11% of patients developed thyroid dysfunction, 5% diabetes, and 2% heart failure. Hypogonadism was present in 56% of females and 14% of males. Female patients who went on to normal puberty after transplant were significantly younger at transplantation than those who experienced delayed puberty (median age 2.5 vs 8.7 years). Fertility was preserved in 9 of 27 females aged 20 years or older and 2 other patients became pregnant following oocyte donation. In addition to patient's age and higher serum ferritin levels at transplantation, time elapsed since transplant was significantly associated with decreased height growth in multivariate analysis. Weight growth increased after transplantation particularly in females, 36% of adults being overweight at last evaluation. A comprehensive long-term monitoring, especially of endocrine late effects, is required after hematopoietic stem cell transplantation for thalassemia.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Talasemia beta/complicaciones , Talasemia beta/epidemiología , Adolescente , Adulto , Niño , Preescolar , Femenino , Francia/epidemiología , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Encuestas Epidemiológicas , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Periodo Posoperatorio , Pronóstico , Estudios Retrospectivos , Trasplante Homólogo/efectos adversos , Resultado del Tratamiento , Adulto Joven , Talasemia beta/terapia
17.
Am J Hematol ; 93(11): 1411-1419, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30132969

RESUMEN

In order to identify very early prognostic factors that can provide insights into subsequent clinical complications, we performed a comprehensive longitudinal multi-center cohort study on 57 infants with sickle cell anemia (55 SS; 2 Sß°) during the first 2 years of life (ClinicalTrials.gov: NCT01207037). Time to first occurrence of a severe clinical event-acute splenic sequestration (ASS), vaso-occlusive (VOC) event requiring hospitalization, transfusion requirement, conditional/ abnormal cerebral velocities, or death-was used as a composite endpoint. Infants were recruited at a mean age of 4.4 ±1 months. Median follow-up was 19.4 months. During the study period, 38.6% of infants experienced ≥1 severe event: 14% ASS, 22.8% ≥ 1 VOC (median age: 13.4 and 12.8 months, respectively) and 33.3% required transfusion. Of note, 77% of the cohort was hospitalized, with febrile illness being the leading cause for admission. Univariate analysis of various biomarkers measured at enrollment showed that fetal hemoglobin (HbF) was the strongest prognostic factor of subsequent severe outcome. Other biomarkers measured at enrolment including absolute neutrophil or reticulocyte counts, expression of erythroid adhesion markers, % of dense red cells, cellular deformability or ϒ-globin genetic variants, failed to be associated with severe clinical outcome. Multivariate analysis demonstrated that higher Hb concentration and HbF level are two independent protective factors (adjusted HRs (95% CI) 0.27 (0.11-0.73) and 0.16 (0.06-0.43), respectively). These findings imply that early measurement of HbF and Hb levels can identify infants at high risk for subsequent severe complications, who might maximally benefit from early disease modifying treatments.


Asunto(s)
Anemia de Células Falciformes/diagnóstico , Índice de Severidad de la Enfermedad , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/terapia , Biomarcadores/análisis , Transfusión Sanguínea , Estudios de Cohortes , Femenino , Hemoglobina Fetal/análisis , Hemoglobinas/análisis , Hospitalización , Humanos , Lactante , Estudios Longitudinales , Masculino , Pronóstico
18.
Blood ; 125(10): 1653-61, 2015 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-25533032

RESUMEN

Early transcranial Doppler (TCD) screening of the Créteil sickle cell anemia (SCA)-newborn cohort, and rapid initiation of transfusion programs, resulted in successful prevention of overt strokes, but a high cumulative risk of silent cerebral infarcts (SCI) remained, suggesting that TCD screening does not identify all patients with SCA at risk for SCI. We hypothesized that episodes of hypoperfusion/hypoxia, as observed during acute chest syndromes or acute anemic events (AAE), and extracranial internal carotid artery (eICA) stenoses, detectable via submandibular Doppler sonography and cervical magnetic resonance angiography (MRA), could also be risk factors for SCI. This study includes 189 stroke-free patients with SCA from the Créteil newborn cohort (1992-2010) followed longitudinally by magnetic resonance imaging/MRA, including cervical MRA at the last assessment. All patients with abnormal TCD and/or intracranial stenoses were placed on a transfusion program. Mean follow-up was 9.9 years (range, 2.2-19.9 years; 1844 patient-years). Annual rates of clinical events were calculated. The cumulative risk for SCI was 39.1% (95% confidence interval [CI], 23.5%-54.7%) by age 18 years, with no plateau. We confirm that baseline hemoglobin level lower than 7 g/dL before age 3 years is a highly significant predictive risk factor for SCI (hazard ratio, 2.97; 95% CI, 1.43-6.17; P = .004). Furthermore, we show that AAE rate (odds ratio, 2.64 per unit increase; 95% CI, 1.09-6.38; P = .031) and isolated eICA stenosis (odds ratio, 3.19; 95% CI, 1.18-8.70; P = .023) are significant and independent risk factors for SCI.


Asunto(s)
Anemia de Células Falciformes/complicaciones , Anemia/complicaciones , Estenosis Carotídea/complicaciones , Infarto Cerebral/etiología , Enfermedad Aguda , Adolescente , Anemia/sangre , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/genética , Velocidad del Flujo Sanguíneo , Arteria Carótida Interna , Estenosis Carotídea/diagnóstico , Estenosis Carotídea/fisiopatología , Infarto Cerebral/diagnóstico , Niño , Preescolar , Enfermedad Crónica , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Masculino , Factores de Riesgo , Adulto Joven
19.
Haematologica ; 102(6): 976-983, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28302713

RESUMEN

Efforts to implement family cord blood banking have been developed in the past decades for siblings requiring stem cell transplantation for conditions such as sickle cell disease. However, public banks are faced with challenging decisions about the units to be stored, discarded, or used for other endeavors. We report here 20 years of experience in family cord blood banking for sickle cell disease in two dedicated public banks. Participants were pregnant women who had a previous child diagnosed with homozygous sickle cell disease. Participation was voluntary and free of charge. All mothers underwent mandatory serological screening. Cord blood units were collected in different hospitals, but processed and stored in two public banks. A total of 338 units were stored for 302 families. Median recipient age was six years (11 months-15 years). Median collected volume and total nucleated cell count were 91 mL (range 23-230) and 8.6×108 (range 0.7-75×108), respectively. Microbial contamination was observed in 3.5% (n=12), positive hepatitis B serology in 25% (n=84), and homozygous sickle cell disease in 11% (n=37) of the collections. Forty-four units were HLA-identical to the intended recipient, and 28 units were released for transplantation either alone (n=23) or in combination with the bone marrow from the same donor (n=5), reflecting a utilization rate of 8%. Engraftment rate was 96% with 100% survival. Family cord blood banking yields good quality units for sibling transplantation. More comprehensive banking based on close collaboration among banks, clinical and transplant teams is recommended to optimize the use of these units.


Asunto(s)
Anemia de Células Falciformes/terapia , Almacenamiento de Sangre/métodos , Trasplante de Células Madre de Sangre del Cordón Umbilical/normas , Familia , Sangre Fetal/citología , Adolescente , Adulto , Bancos de Sangre/normas , Niño , Preescolar , Femenino , Supervivencia de Injerto , Histocompatibilidad , Humanos , Lactante , Masculino , Embarazo , Hermanos , Tasa de Supervivencia , Donantes de Tejidos , Adulto Joven
20.
Adv Exp Med Biol ; 1013: 89-122, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29127678

RESUMEN

Allogeneic hematopoietic stem cell transplantation (HSCT) can cure single gene disorders such as thalassemia and sickle cell anemia (SCA). These non-malignant diseases have in common severe hemolytic anemia and high proliferative bone marrow, requiring frequent transfusions. The risk of rejection is high and graft-vs-host disease is not desirable. Important progress has been made in the management of these diseases, including leukocyte depletion of blood products, and chelation therapy, for both diseases, and erythrocytapheresis and hydroxycarbamide for SCA. However, morbidity and quality of life are still of concern. Results have also significantly improved for HSCT, with the reduction of rejection by using anti-thymocyte globulin (ATG), which also decreases the risk of chronic graft-vs-host disease. Current data show a more than 90% chance of cure with myeloablative conditioning in children with hemoglobinopathy and a geno-identical donor. Results are similar whether the cell source is cord blood or bone marrow. Because of the risk of conditioning-related infertility, ovarian and/or testis cryopreservation should be discussed. Non-myeloablative conditioning regimens have also been successfully developed in adults with SCA and organ dysfunction, making cure possible. These encouraging results should incite to perform HLA typing early in families with hemoglobinopathies, and to systematically propose sibling cord blood cryopreservation for those without geno-identical donor.


Asunto(s)
Anemia de Células Falciformes/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Talasemia beta/terapia , Adulto , Suero Antilinfocítico/administración & dosificación , Niño , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Prueba de Histocompatibilidad , Humanos , Inmunosupresores/administración & dosificación , Calidad de Vida , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo , Resultado del Tratamiento
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