Malika Benkerrou

• Hôpital Universitaire Robert Debré

BACKGROUND HU (Hydroxycarbamide or Hydroxyurea) is a myelosuppressive drug marketed since 1968 for the treatment of hematological malignancies, and approved since 2007 in the European Union (EU) and 2017 in the Unites States of America (USA) for preventing vaso-occlusive crises (VOC) including acute chest syndromes (ACS) in adults, adolescents and...

Hydroxyurea (HU) is approved in EU and USA for preventing vaso-occlusive crises (VOC) including acute chest syndromes (ACS) in adults, adolescents and children ≥2 years with sickle-cell disease (SCD). Further to the double blinded, randomized controlled Multicenter Study of Hydroxyurea administration (MSH) which provided the first data on clinical...

Conclusion: despite the low number of patients included in our study, SCA does not seem to be a risk factor for severe TB. What is Known: • Tuberculosis (TB) remains a global health problem particularly in developing countries, and Sickle cell anaemia (SCA) is currently one of the most common genetic diseases in the world that mainly affects Afric...

Although the primary origin of sickle cell disease is a hemoglobin disorder, several cell types contribute considerably to the physiopathology of the disease. The adhesion of neutrophils to activated endothelium is critical in sickle cell disease pathophysiology and the targeting of neutrophils and their interactions with endothelium represent impo...

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...

Children with sickle cell anemia (SCA) may be at risk of cerebral vasculopathy and strokes, which can be prevented by chronic transfusion programs. Repeated transfusions of packed red blood cells (PRBCs) is currently the simplest and most used technique for chronic transfusion programs. However, iron overload is one of the major side effects of thi...

Table of contents: PHYSICIANS ABSTRACTSO1 Impact of tracheal cuff shape on microaspiration of gastric contents in intubated critically ill patients: a multicenter randomized controlled study (BEST CUFF)Emmanuelle Jaillette, Christophe Girault, Guillaume Brunin, Farid Zerimech, Arnaud Chiche, Céline Broucqsault-Dedrie, Cyril Fayolle, Franck Minacor...

We conducted a retrospective study on newborns with sickle-cell disease (SCD), born 1995-2009, followed in a multicentre hospital-based network. We assessed patient outcomes, medical care and compliance with the national guidelines published in December 2005. Data from 1033 patients (742 SS/Sβ°-thalassaemia) with 6776 patient-years of follow-up wer...

Neonatal screening for sickle cell disease (SCD), the most common of recessive autosomic hemoglobin disorders, allows detection of affected babies (homozygous sickle cell disease, compound heterozygote SC, and S b-thalassemia) in a target population. A dry blood sample is obtained by heel stick and analyzed by high-performance liquid chromatography...

Background: Chronic exchange transfusion is effective for primary and secondary prevention of stroke in children with sickle cell anemia (SCA). Erythrocytapheresis is recognized to be the most efficient approach; however, it is not widely implemented and is not suitable for all patients. The aim of our study was to compare automated exchange trans...

Résumé La drépanocytose, maladie génétique la plus répandue au monde, se manifeste principalement par des douleurs intenses et imprévisibles. Ces crises de douleurs nécessitent parfois une prise en charge hospitalière médicale et psychique. Au cours des crises douloureuses, l’enfant est plongé dans un état de détresse qui le confronte à des angoiss...

Children with sickle cell disease (SCD) have a significant vascular morbidity, especially cerebral macrovasculopathy (CV), detectable by transcranial Doppler. This study aimed to identify risk factors for CV using longitudinal biological and clinical data in a SCD newborn cohort followed at the Robert Debre Reference centre (n = 375 SS/Sβ(0) ). Med...

Pain is the main symptom in sickle cell disease and is a major issue in its management. Its complexity often makes assessment difficult for both patients and caregivers. This study looks for a link between anxiety in children with sickle cell disease at the beginning of their hospital stay and the difficulties experienced by caregivers to assess th...

Children with sickle cell disease have a significant vascular morbidity, specifically cerebral vasculopathy (CV) that can be detected by transcranial Doppler. The aim of this study was to identify CV risk factors using longitudinal biological and clinical data including upper and lower respiratory tract evaluation in the newborn cohort of Robert De...

Background: Cerebral vasculopathy is a serious complication of sickle cell anemia. Overt strokes are largely due to intracranial arteriopathy, detected by routine transcranial Doppler and largely prevented through chronic transfusions. As extracranial internal carotid artery arteriopathy was considered rare, it has not been routinely assessed in s...

Children with sickle cell disease (SCD) have a significant vascular morbidity responsible of pain and stroke. They are at high risk of cerebral vasculopathy (CV) that can be detected in these children by transcranial Doppler. The aim of this study was to identify risk factors for CV using longitudinal data in the 375 newborn cohort of Robert Debre...

In patients with sickle cell anaemia (SCA), concomitant glucose-6-phosphate dehydrogenase (G6PD) deficiency is usually described as having no effect and only occasionally as increasing severity. We analysed sequential clinical and biological data for the first 42 months of life in SCA patients diagnosed by neonatal screening, including 27 G6PD-defi...

Rationale Allogeneic hematopoietic stem-cell transplantation (HSCT) is the only curative treatment for sickle cell disease (SCD). Cerebral vasculopathy was the principal indication for transplantation. These children could present impaired neuropsychological development related to different causes, hence the value of exploring their intellectual ca...

Hematogenous osteoarticular infections of the hand and the wrist in children with sickle cell anemia are rare and no specific studies for this location have been published. This retrospective and comparative study reviewed 34 children who carry the diagnosis of osteoarticular infections of the wrist and the hand at our institution during a 10-year...

RATIONALE: Allogeneic hematopoietic stem-cell transplantation (HSCT) is the only curative treatment for sickle cell disease (SCD). Cerebral vasculopathy was the principal indication for transplantation. These children could present impaired neuropsychological development related to different causes, hence the value of exploring their intellectual c...

Objective To examine morbidity among children with sickle-cell disease (SCD) during and after travel to a tropical area. Design Observational study. Setting Tertiary care children; Robert Debré Hospital, Paris, France. Population Children with SCD younger than 18 years old and managed in the SCD referral centre at the Robert Debré Hospital who trav...

Background. Microparticles are cell membrane-derived microvesicles released during cell apoptosis and activation processes. They have been described as bio-markers in various vascular diseases, including sickle cell anaemia, and associated with an increased risk of thrombosis. We investigated the effects of foetal haemoglobin level, a factor known...

Acute splenic sequestration crisis (ASSC) is an unpredictable life-threatening complication of sickle cell disease (SCD) in infants. Here, our objective was to update available clinical information on ASSC. We retrospectively studied the 190 patients who were diagnosed at birth with SS or Sbeta(0) in the Paris conurbation between 2000 and 2009 and...

Les syndromes drépanocytaires majeurs sont, en général, la conséquence de la mutation drépanocytaire à l’état homozygote ou associé en trans à un autre variant de l’hémoglobine ou à un trait β-thalassémique. Nous rapportons deux cas de syndromes drépanocytaires atypiques identifiés parmi les enfants dépistés et suivis à l’hôpital pédiatrique Robert...

Emerging metabolomic tools can now be used to establish metabolic signatures of specialized circulating hematopoietic cells in physiologic or pathologic conditions and in human hematologic diseases. To determine metabolomes of normal and sickle cell erythrocytes, we used an extraction method of erythrocytes metabolites coupled with a liquid chromat...

Major histocompatibility complex (MHC) class II deficiency is a rare primary immunodeficiency disorder characterized by defects in human leukocyte antigen class II expression, inconsistent expression of human leukocyte class I molecules, and a lack of cellular and humoral immune responses to foreign antigens. Clinical onset occurs early in life wit...

522 Rationale Allogeneic hematopoietic stem-cell transplantation (HSCT) is the only curative treatment for sickle cell disease (SCD). Cerebral vasculopathy with or w/o stroke or ischemic lesion was the principal indication for transplantation. All the patients received grafts from a sibling donor after a myeloablative conditioning regimen (Bu 16mg...

Sickle cell anemia (SCA) is a single-gene mutation genetic disease characterized by a highly variable clinical presentation. Genetic modifiers of the general outcome have been reported, some of them linked to the aand b-globin gene clusters. In addition, polymorphisms linked to various genes have been associated with specific complications of the d...

This retrospective study assessed the long-term effect of transfusional exchange therapy on MRA/MRI abnormalities in 24 homozygous sickle-cell anemia (HbSS) children presenting with abnormal brain MRA. The median time elapsed from baseline to last available MRA was 29 months. Follow-up MRAs showed improvement, stabilization or worsening of cerebrov...

Chédiak-Higashi syndrome (CHS) is a rare immunodeficient disorder. Patients with CHS are prone to severe periodontitis. To date, limited improvement following periodontal therapy has been reported. Thus, successful clinical outcomes in patients with CHS are of interest. A 12-year-old girl was referred to the Department of Pediatric Dentistry, Hôtel...

Sickle cell anaemia, the most prevalent genetic disease in the black population, is characterised by the polymerisation of the abnormal haemoglobin S, which leads to vascular occlusion and severe painful crisis. Hydroxyurea is the fi rst drug that has been shown to reduce the clinical severity of sickle cell anaemia in adults. Several trials have b...

We investigated adhesion receptor levels on red blood cells, reticulocytes and erythroid progenitors from children with sickle cell disease treated or not with hydroxyurea. Four groups of patients were investigated: (i) children receiving hydroxyurea for severe vaso-occlusive events (n=26); (ii) untreated children with a history of vaso-occlusive e...

To evaluate safety and immunogenicity of the pneumococcal 7-valent conjugate vaccine (PCV7) when administered to infants with sickle cell disease (SCD) at 2, 3, and 4 months of age with a booster dose of a 23-valent pneumococcal polysaccharide vaccine (PS-23) at 15 to 18 months of age. This open-label multicenter study in France enrolled 2-month-ol...

Immunoglobulin class switch recombination (CSR) deficiencies are rare primary immunodeficiencies, characterized by a lack of switched isotype (IgG, IgA, or IgE) production, variably associated with abnormal somatic hypermutation (SHM). Deficiencies in CD40 ligand, CD40, activation-induced cytidine deaminase, and uracil-N-glycosylase may account for...

Given the controversy concerning the effects of steroids in patients with sickle cell disease (SCD), we evaluated the tolerability of long-term steroid treatment in 16 children with SCD and autoimmune and/or systemic diseases. The steroid treatment was poorly tolerated.

Hamartomas of the spleen or splenomas are uncommon benign lesions that predominantly occur in adults. We report a case of an 11-year-old girl with sickle cell anemia who had a single splenic 1.8 cm nodule incidentally found during splenectomy and histologically characterized by disorganized red pulp tissue without interspersed white pulp leading to...

L’hamartome de la rate ou splénome est une lésion bénigne rare, principalement observée chez l’adulte. Nous rapportons l’observation d’une fillette de 11 ans, atteinte d’une drépanocytose homozygote chez laquelle est découvert fortuitement sur la pièce de splénectomie un nodule unique de 1,8 cm, histologiquement constitué de pulpe rouge désorganisé...

Les syndromes drépanocytaires majeurs sont, en général, la conséquence de la muta- tion drépanocytaire à l’état homozygote ou associé en trans à un autre variant de l’hémoglobine ou à un trait 􏰀-thalassémique. Nous rapportons un cas de syndrome drépanocytaire atypique identifié parmi les enfants dépistés et suivis à l’hôpital pédiatrique Robert-Deb...

Hematopoietic cell transplantation (HCT) is the only potentially curative treatment for sickle cell disease (SCD). The probability of event-free survival is currently between 85 and 90% after matched sibling-donor HCT. This intensive treatment conducts to a major change for patients and families. The purpose of the present study was to determine th...

Preoperative endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy (ES) are an effective strategy for choledocholithiasis, but complications such as pancreatitis and outcome in children are unknown. The laparoscopic cholecystectomy became the new gold standard in children for cholelithiasis. For the choledocholithiasis in chi...

Plasma endothelin-1 (ET-1) is elevated in patients with sickle cell disease (SCD). Hydroxyurea (HU) is the only drug with demonstrated clinical efficacy in SCD. Here we show that treatment with HU results in a decreased concentration of circulating ET-1 which is not correlated with the HU-induced increase in HbF level. Blunting of the ET-1 vasocons...

Splenectomy is frequently performed in children for various hematologic and autoimmune disorders. We reviewed our indication for splenectomy, our technique of laparoscopic, splenectomy, and our results. The aim of this study was to show if an anterior approach with elective vessel endoligature in a patient in decubitus position was a better and saf...

Bone marrow transplantation (BMT) from matched sibling donors has been useful for the treatment of acute lymphoblastic leukaemia in children with a poor prognosis but is not available to more than two-thirds of patients who do not have a matched allogeneic donor. This study was undertaken to assess one strategy of marrow graft rejection prevention...

Impaired polymorphonuclear neutrophil (PMN) functions during sickle cell anemia (SCA) may have a pathogenic role in the onset of vasoocclusive events. We used flow cytometry to study, in whole blood, the adhesion molecule expression and respiratory burst of PMNs from children with SCA. Three different clinical groups were studied: (1) patients with...

Impaired polymorphonuclear neutrophil (PMN) functions during sickle cell anemia (SCA) may have a pathogenic role in the onset of vasoocclusive events. We used flow cytometry to study, in whole blood, the adhesion molecule expression and respiratory burst of PMNs from children with SCA. Three different clinical groups were studied: (1) patients with...

Background and Purpose: Splenectomy is frequently performed in children for various hematologic and autoimmune diseases. We review our indications for splenectomy, our technique of laparoscopic splenectomy using an anterior approach, and our results. Patient and Methods: Between January 1996 and May 2000, 35 children aged 1 to 14 years (mean 7 year...

A subset of 299 patients with homozygous sickle cell anaemia, enrolled in the cohort of the French Study Group on sickle cell disease (SCD), was investigated in this study. The majority of patients were children (mean age 10.1±5.8 yr) of first generation immigrants from Western and Central Africa, the others originated from the French West Indies (...

Pediatric laparoscopic splenectomy is a relatively new surgical procedure. Advances in instrumentation and technique now make this procedure possible. Splenectomy is frequently performed in children for various hematologic and autoimmune diseases. This article reviews the indication for splenectomy, the technique of laparoscopic splenectomy and our...

We report a five-year experience of targeted neonatal screening for sickle cell disease in the northern part of the Paris area as well as the follow-up procedure of screened patients. This geographic area in France is characterized by a high frequency of populations at risk for sickle cell disease. Among 115,480 tested newborns, 250 patients were d...

Pediatric laparoscopic splenectomy is a relatively new surgical procedure. Advances in instrumentation and technique now make this procedure possible. Splenectomy is frequently performed in children for various hematologic and autoimmune diseases.Patients and methods. – This article reviews the indication for splenectomy, the technique of laparosco...

We report a five-year experience of targeted neonatal screening for sickle cell disease in the northern part of the Paris area as well as the follow-up procedure of screened patients.Population. – This geographic area in France is characterized by a high frequency of populations at risk for sickle cell disease.Results. – Among 115,480 tested newbor...

Gallbladder stones are very common in patients with sickle cell disease and are the cause of recurrent abdominal pain. Their management has been highly controversial, especially for children. Nonoperated patients and those treated on an emergency basis have a very high rate of morbidity (>50%). We performed a retrospective review of a series of 29...

Background: Gallbladder stones are very common in patients with sickle cell disease and are the cause of recurrent abdominal pain. Their management has been highly controversial, especially for children. Nonoperated patients and those treated on an emergency basis have a very high rate of morbidity (>50%). Methods: We performed a retrospective revi...

The French national programme for the neonatal screening of sickle cell disease (SCD) was set up in 1995. This screening is targeted at newborn infants at risk. Over 5 years, 115,480 newborn infants were tested from 80 maternity departments from the northern part of the Paris area. 250 Patients with SCD were identified--that is, one in 462 newborn...

Pediatric laparoscopic splenectomy is a relatively new surgical procedure. Advances in instrumentation and technique now make this procedure possible. Splenectomy is frequently performed in children for various hematologic and autoimmune diseases.Patients and methods. – This article reviews the indication for splenectomy, the technique of laparosco...

Résumé (in English below) Nous rapportons l’expérience de cinq années de dépistage néonatal ciblé de la drépanocytose dans le nord-francilien, ainsi que la procédure de prise en charge des enfants atteints. Population. – Ce secteur géographique est caractérisé par une forte fréquence des populations à risque pour la drépanocytose. Résultats. – Sur...

Abdominal pain is frequent in drepanocytosis carrying children and vaso-occlusive in origin. It may be isolated or projected, reveal diverse clinical situations including pneumopathies, angiocholitis, bone necrosis and osteomyelitis and consequently imposes a thorough, well-directed clinical examination as well as the administration of major antalg...

A subset of 299 patients with homozygous sickle cell anaemia, enrolled in the cohort of the French Study Group on sickle cell disease (SCD), was investigated in this study. The majority of patients were children (mean age 10.1 +/- 5.8 yr) of first generation immigrants from Western and Central Africa, the others originated from the French West Indi...

In recent years, physicians at the Robert-Debré pediatric hospital in Paris perceived an increase in activity linked to sickle cell disease care. Our study had two objectives: first, to describe the evolution of care for children with sickle cell disease in the hospital, then, if a heavier intensity of care was shown, to try to investigate its caus...

After obtaining familial informed consent, between January 1996 and July 1997, 173 children (5 to 15 years old) with sickle cell disease were enrolled in a prospective multicenter study using blood screening, transcranial Doppler ultrasonography (n = 143), cerebral magnetic resonance imaging (n = 144), and neuropsychologic performance evaluation (n...

Aim In recent years, physicians at the Robert-Debré pédiatric hospital in Paris perceived an increase in activity linked to sickle cell disease care. Our study had two objectives: first, to describe the evolution of care for children with sickle cell disease in the hospital, then, if a heavier intensity of care was shown, to try to investigate its...

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder in which an immune deficiency occurs in association with pigmentation abnormalities. Most patients who do not undergo bone marrow transplantation die of a lymphoproliferative syndrome, though some patients with CHS have a relatively milder clinical course of the disease. The larg...

Sickle cell disease is an autosomal recessive hemoglobinopathy that is so serious and common (1/1750 births in continental France) as to cause a significant public health burden. Genetic counseling of high-risk individuals is complex because of the considerable variability of phenotypes within a given genotype and of the absence of an early predict...

Chronic hemolytic anemia is a consistent and early manifestation of sickle cell anemia that arises as a direct consequence of the hemoglobin abnormality. Genotype is the main determinant of steady-state hemoglobin levels and of the occurrence of acute anemic events, although considerable interindividual variability exists for a given genotype. Anem...

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4, also known as CD152) has been shown to play a major role in the regulation of T cell activation. Its membrane expression is highly regulated by endocytosis and trafficking through the secretory lysosome pathway. Chediak-Higashi syndrome (CHS) is an inherited disorder caused by mutations in the ly...

Although blood transfusion (BT) therapy remains a key component of the weaponry used to treat acute and chronic sickle cell disease complications, its indications and modalities are currently the focus of a critical reappraisal prompted by the introduction of hydroxyurea, recent improvements in allogeneic bone marrow transplantation, and increasing...

B-lymphoproliferative disorder (BLPD) is a rare but severe complication of organ and bone marrow transplantation (BMT). Profound cytotoxic T-cell deficiency is thought to allow the outgrowth of Epstein-Barr virus-transformed B cells. When possible, reduction of immunosuppressive treatment or surgery for localized disease may cure BLPD. Therapeutic...

B-lymphoproliferative disorder (BLPD) is a rare but severe complication of organ and bone marrow transplantation (BMT). Profound cytotoxic T-cell deficiency is thought to allow the outgrowth of Epstein-Barr virus–transformed B cells. When possible, reduction of immunosuppressive treatment or surgery for localized disease may cure BLPD. Therapeutic...

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare genetic disorder associated with the onset early in life of overwhelming activation of T lymphocytes and macrophages invariably leading to death. Allogeneic bone marrow transplantation (BMT) from an HLA-identical related donor is the treatment of choice in patients with this disease. Howev...

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare genetic disorder associated with the onset early in life of overwhelming activation of T lymphocytes and macrophages invariably leading to death. Allogeneic bone marrow transplantation (BMT) from an HLA-identical related donor is the treatment of choice in patients with this disease. Howev...

Recently, an inherited syndrome characterized by nonmalignant lymphoprolif-eration with autoimmune manifestations, caused by mutations of the Fas (CD95) receptor gene has been described. Because of disease severity, i.e. unremitting lymphoproliferation in a child with complete Fas deficiency, a haploidentical bone marrow transplantation (BMT) was p...

We describe two children with a severe combined immune deficiency (SCID) with B cells. Following a T-cell-depleted haploidentical bone marrow transplantation (BMT), they both developed a chronic graft-versus-host disease (GVHD) of the skin and a severe persisting hyperbilirubinaemia and elevated liver enzymes. The diagnosis of a vanishing bile duct...

The surface molecule named Fas/CD95, which is expressed on activated lymphocytes, can trigger cell death following interaction with its ligand (Fas L). This Fas-Fas-L interaction is thought to be a major regulatory mechanism for controlling the life span of peripheral lymphocytes, and therefore autoimmunity. We assessed clinical, immunological and...

We retrospectively analyzed the outcome of bone marrow transplantation (BMT) performed in 26 patients with Wiskott-Aldrich syndrome (WAS) in one center. Twenty-eight transplantation procedures were performed. Ten unselected patients received unmanipulated marrow from a donor with genetically identical human leukocyte antigen (HLA). Eight patients w...

Bone marrow transplantation (BMT) from matched sibling donors has been useful for the treatment of acute lymphoblastic leukaemia in children with a poor prognosis but is not available to more than two-thirds of patients who do not have a matched allogeneic donor. This study was undertaken to assess one strategy of marrow graft rejection prevention...

We have retrospectively analyzed the outcome of bone marrow transplantation (BMT) in 14 patients with leukocyte adhesion deficiency (LAD) performed in two centers between 1981 and 1993. Five patients received BMT from HLA-identical donors. Nine received T-depleted marrow from two HLA antigen- or haplotype-incompatible parents. Conditioning regimen...

; the CD40 ligand transcripts in that patient's T cells had a deletion of 10 base pairs (bp) in the extracellular domain of the CD40 ligand (nu- cleotides 447 to 456). The intragenic CD40 ligand microsatellite probe revealed a polymorphism in the family. A 164-bp allele (allele 2) was identified in affected Subjects III-1 and III-3 (Fig. 3). 21 Sub...