La neutropénie auto-immune (NAI) est une cause fréquente de neutropénie chronique en particulier chez le nourrisson. So diagnostic repose actuellement sur la preuve immunologique du processus ...auto-immun. Ce travail a pour objectif de décrire cette affection et de définir la contribution du myélogramme dans son diagnostic.
Patients et méthodes.
— Cette étude porte sur dix enfants neutropéniques, six filles et quatre garcons, suivis entre 1990 et 1995, qui ont eu à la fois un myélogramme et une recherche d'anticorps antipolynucléaires (PN). Cinq enfants non neutropéniques dont le myélogramme était normal ont été pris comme témoins. Une méthode reproductible de quantification des images médullaires a été adoptée.
Résultats.
— Six patients sur dix ont présenté des signes de phagocytose élective de PN par les macrophages de la moelle, sans signe de dysgranulopoïèse et sans autre signe d'hémophagocytose. La recherche d'anticorps anti-PN était positive chez quatre de ces six enfants et chez les quatre enfants sans phagocytose médullaire des PN. Les deux patients sans autoanticorps présentaient une histoire clinique semblable aux autres avec présence de phagocytose élective de PN. Certains patients ont été traités temporairement pour des infections graves et traînantes par des immunoglobulines polyvalentes en intraveineuse et/ou du
granulocyte colony-stimulating factor (G-CSF). L'efficacité des immunoglobulines a été inconstante. Le G-CSF a été efficace à faible dose et il a permis de raccourcir la durée de l'infection.
Conclusion.
— Devant toute neutropénie durable de l'enfant, des images de phagocytose médullaire des PN par les macrophages peuvent représenter un signe indirect d'auto-immunité. Le G-CSF peut être utile en traitement court, en association avec une antibiothérapie adaptée en cas d'infections graves et traînantes.
Autoimmune neutropenia (AIN) is a frequent cause of chronic neutropenia especially in youngest children. Its diagnosis is established by immunological proof of the autoimmune mechanism. The aim of this study is to better describe this autoimmune process and to show the contribution of bone marrow smears to this diagnosis.
Patients and methods. — Ten children, six girls and four boys, were examined between 1990 and 1995. Eight of them had typical AIN, confirmed by the presence of antibodies against neutrophils. Two other patients were included on the basis of bone marrow pictures. Five non-neutropenic children with normal bone marrow smears were chosen as controls. Bone marrow analysis was always performed by the same cytologist according to a reproducible technique.
Results. — Six out of ten patients had important features of elective phagocytosis of neutrophils by marrow macrophages (unlike controls) without signs of dysgranulopoiesis or hemophagocytosis. Antibodies against neutrophils were detected in six patients with phagocytosis and in four patients without these cytological features. In two other children presenting the same bone marrow picture and clinical profile, an autoimmune process was probable, even in the absence of antibodies against neutrophils. Some patients had several infections and were given immunoglobulins and/or granulocyte colony-stimulating factor (G-CSF) therapy. The efficacy of Immunoglobulin was not constant, whereas G-CSF was effective at low doses and shortened the duration of infections.
Conclusion. — Prolonged neutropenia in childhood must lead to look for phagocytosis by marrow macrophages in bone marrow smears, as a possible sign of autoimmunity. Growth factors may temporarily be used associated with antibiotics therapy in severe and prolonged infections.
We have developed a strategy based on polymerase chain reaction (PCR) for detecting all possible gamma T-cell receptor (gamma TCR) rearrangements and the most common delta TCR rearrangements found in ...B- lineage and T-acute lymphoblastic leukemia (T-ALL). The segments amplified from blasts are then directly sequenced to derive clonospecific probes. From a series of 45 patients aged 1 to 15 years (42 B-lineage ALL, 3 T-ALL), 35 (83%) could be followed for minimal residual disease with at least one clonospecific probe. Detection of clonal markers using clonospecific probes routinely allowed the detection of 1 to 10 blasts out of 10(5) cells as determined by serial dilutions of the initial samples. Residual disease was quantitated by a competitive PCR assay based on the coamplification of an internal standard. Twenty children were prospectively followed for periods varying from 7 to 30 months. In most children, a progressive decrease of the tumor load was observed, and blasts became undetectable within 6 months after the initiation of treatment. A slower kinetics of decrease in tumor cells was found in three children. These three patients relapsed with blasts that continued to display the initial clonospecific markers. Three other children had a central nervous system relapse despite the absence of detectable medullary residual disease. The use of both delta and gamma TCR genes as clonal markers, as well as simplification in the methods to detect and quantify residual blasts reported here, will allow the study of the large number of patients required to determine the role of the detection of minimal residual disease by PCR in the follow-up of childhood ALL.
The marrows of patients with lysinuric protein intolerance (LPI) are generally considered as normal, even though autoerythrophagocytosis has been observed in some of them.
Lysinuric protein ...intolerance was recognized in two 12 and 15-year-old brothers who had been diagnosed following an immuno-hematological investigation. Clinical history had been characterized by a neonatal macrophage activation syndrome (hepatosplenomegaly, pancytopenia, hypofibrinogenemia and hypertriglyceridemia). A putative diagnosis of familial lymphohistiocytosis had been ruled out because of unusual clinical and immunological course. Both brothers had displayed chronic aversion to high-protein foods, failure to thrive, osteoporosis and developmental delay. Metabolic investigations had revealed chronic hyperammonemia while cationic aminoaciduria (lysine, arginine and ornithine) was only present during L-citrulline supplementation. Bone marrow examinations had been performed during the neonatal period and during later metabolic investigations. They both displayed a peculiar red cell and granulocytes phagocytosis by histiocytes and granulocytes precursors.
This aspect of bone marrow could be considered as a specific sign of LPI. This report suggests that appropriate metabolic investigations should be performed in any unexplained macrophage activation syndrome.
Les myélogrammes des enfants présentant une intolérance aux protéines dibasiques avec lysinurie sont habituellement normaux, même si des aspects d'autoérythrophagocytose ont été décrits chez certains ...d'entre eux.
Observation.
— Un diagnostic d'intolérance aux protéines dibasiques avec lysinurie a été porté chez deux frères âgés de 12 et 15 ans à la suite d'une investigation immunohématologique. La symptomatologie avait débuté en période néonatale par une association de signes compatibles avec un diagnostic de syndrome d'activation macrophagique. Il existait une hépatosplénomégalie, une pancytopénie, une hypofibrinogénémie, une hypertriglycéridémie. Ultérieurement, l'hypothèse d'une lymphohistiocytose familiale avait été récusée devant l'évolution inhabituellement favorable et le caractère intermittent du syndrome d'activation macrophagique. Durant les années qui ont suivi, outre les anomalies hématologiques, l'évolution s'était caractérisée par l'installation d'une anorexie élective pour les protéines, avec retard de croissance, ostéoporose et retard psychomoteur. Ce n'est qu'à 12 et 15 ans que l'investigation clinique et biologique de ces patients a permis de mettre en évidence une hyperammoniémie chronique. La supplémentation en L-citrulline, en faisant apparaître une hyperaminoacidurie spécifique (arginine, ornithine, lysine), a permis le diagnostic. L'analyse des médullogrammes, pratiqués en période néonatale et lors du diagnostic, a révélé une phagocytose particulière des érythroblastes et des polynucléaires neutrophiles simultanément par des macrophages et des progéniteurs granuleux.
Conclusions.
— Cet aspect du myélogramme pourrait être un des signes spécifiques de la maladie. Ces données suggèrent l'importance des investigations métaboliques devant tout syndrome d'activation macrophagique inexpliqué.
Background. — The marrows of patients with lysinuric protein intolerance (LPI) are generally considered as normal, even though autoerythrophagocytosis has been observed in some of them.
Case reports. — Lysinuric protein intolerance was recognized in two 12 and 15-year-old brothers who had been diagnosed following an immuno-hematological investigation. Clinical history had been characterized by a neonatal macrophage activation syndrome (hepatosplenomegaly, pancytopenia, hypofibrinogenemia and hypertriglyceridemia). A putative diagnosis of familial lymphohistiocytosis had been ruled out because of unusual clinical and immunological course. Both brothers had displayed chronic aversion to high-protein foods, failure to thrive, osteoporosis and developmental delay. Metabolic investigations had revealed chronic hyperammonemia while cationic aminoaciduria (lysine, arginine and ornithine) was only present during L-citrulline supplementation. Bone marrow examinations had been performed during the neonatal period and during later metabolic investigations. They both displayed a pecullar red cell and granulocytes phagocytosis by histiocytes and granulocytes precursors.
Conclusions. — This aspect of bone marrow could be considered as a specific sign of LPI. This report suggests that appropriate metabolic investigations should be performed in any unexplained macrophage activation syndrome.
Data about childhood acute lymphoblastic leukemia, the most common childhood malignancy in industrialized countries, are scarce in African publications. The purpose of this prospective, unicentric ...study were to assess the socio-demographic, clinic and laboratory characteristics of the children treated for lymphoblastic leukemia in our pediatric oncology unit in Gabriel Touré Teaching Hospital in Bamako, Mali.
This study includes all children between 1 and 15 years old treated for cytologically documented acute lymphoblastic leukemia from January 1, 2007 to September 30, 2009.
A total of 12 cases including 8 boys and 4 girls (sex ration, 2) were treated during the study period. Mean age was 92 months. Age was less than 4 years old in 2 cases. 5 (41,7%) were between 5 and 9 years in 5 (41.7%) and between 10 to 15 years in five. At the time of presentation, 9 patients (75%) were in a cachectic state; 10 had lymphadenopathies, splenomegaly and hepatomegaly; and 2 had neurological involvement. The delay for definitive diagnosis was 5 months in 4 cases (33,3 %) and less than 5 months in the remaining cases. Initial white blood cell count was more than 50 000/mm3 in 10 cases and less less than 50 000/mm3 in 2 cases. All patients were treated using the LAL GFAOP protocol including LAL1 in 6 cases, LAL2 in 5 and LAL3 in 1. Treatment complications were included 6 undocumented infections in 6 cases, hemorrhage in 2 and severe anemia in 4. Four patients died. At 5 years follow-up, overall survival rate was 66,7%.
A multicentric study including a greater number of children is needed to increase understanding of the characteristics of childhood acute lymphoblastic leukemia in sub-Saharan Africa.
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