Preliminary report of a toxicity study of hydroxyurea in sickle cell disease. French Study Group on Sickle Cell Disease.

AIM: To evaluate the tolerance of hydroxyurea in children affected with sickle cell disease. DESIGN: Questionnaire study of French physicians likely to treat patients with sickle cell disease. Data were collected on 101 children with sickle cell disease, treated for a median of 22 months, 36 of whom were treated for more than three years. 13 children were younger than 5 years of age at inclusion. RESULTS: Hydroxyurea was stopped for medical reasons in 11 patients: 6 failures, 1 pregnancy, 1 cutaneous rash, 1 leg ulcer, 1 lupus. Acute lymphoblastic leukaemia occurred in a girl treated for 1.5 months with hydroxyurea, this short interval arguing against a causative association. One 17 year old boy had paraparesis after 8 years of treatment. CONCLUSIONS: No major short or medium term toxicity was related to hydroxyurea in this cohort of 101 children. However, the number of children treated for more than 3 years is too few to make firm conclusions on the long term tolerance of this drug.

Abdominal ultrasound findings in children with hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis, a variant of histiocytosis, is characterized by an uncontrolled activation of the cellular immune system, including hepatic mononuclear phagocytic cells. Abdominal ultrasound findings in children are evaluated in this disease. We present six pediatric cases, two with familial and four with sporadic hemophagocytic lymphohistiocytosis, examined by abdominal sonography. Three signs were frequently observed: thickening of the gallbladder wall (all cases), increased periportal echogenicity (four cases), and enlarged lymph nodes in the porta hepatis (four cases). Hepatomegaly, splenomegaly, and ascitic fluid may also be found. These imaging findings are not specific and may be seen in viral hepatitis. However, once hepatitis is excluded, they may suggest the diagnosis of hemophagocytic lymphohistiocytosis in a critically ill child. A bone smear must be done to establish the diagnosis.

Stable mixed chimerism without relapse after related allogeneic umbilical cord blood transplantation in a child with severe aplastic anemia.

Umbilical cord blood (UCB) cells from HLA-matched donors are used as an alternative to bone marrow for allogeneic transplantation and reports of successful UCB transplantation in patients with severe aplastic anemia (SAA) are scarce. SAA was discovered in a 4-year-old girl in February 1990. Transfusion support started in August 1990 and standard treatments were unsuccessful. The birth of an HLA-compatible brother in October 1993 permitted the cryopreservation of UCB. In December 1994 UCB transplantation was decided upon. No toxicity occurred. G-CSF was started at day 28. WBC and PMN reached 0.5 x 10(9)/l at days 33 and 37. RBC and platelet transfusion independence were reached at days 50 and 52. Mixed chimerism was demonstrated in blood cells at 1.5, 4 and 6 months after UCBT by molecular biology (VNTR). FISH studies yielded similar results at 15 and 18 months. Twenty months after UCBT, molecular biology showed full donor chimerism. Clinical follow-up (last follow-up: 32 months post transplant) is unremarkable. We suggest that CY and ATG may be a suitable regimen for related HLA-compatible UCBT in patients with SAA. Residual recipient cells can disappear even very late after UCBT, permitting the establishment of complete donor chimerism.

Philadelphia negative BCR-ABL positive chronic myeloid leukemia mimicking juvenile chronic myeloid leukemia in a 2-year-old child.

We present the case of a two-year-old child with an atypical presentation of chronic myeloid leukemia. At diagnosis, he showed clinical and biological features of juvenile chronic myeloid leukemia (CML). However, eosinophilia was observed in blood and bone marrow. The bone marrow karyotype did not demonstrate the Philadelphia chromosome but BCR-ABL rearrangement was shown to be present by reverse transcriptase polymerase chain reaction (RT-PCR) analysis and confirmed by fluorescent in situ hybridization (FISH) analysis. Discussion centres on the differentiation between juvenile CML and childhood chronic myelogenous Leukemia and the importance of carrying out RT PCR for all juvenile CML cases.

Digestive tract involvement in Langerhans cell histiocytosis. The French Langerhans Cell Histiocytosis Study Group.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease with a wide clinical spectrum. Although little is known of gastrointestinal involvement in LCH, it may be a major clinical problem. We investigated clinical, pathologic, and immunohistochemical features of digestive tract LCH involvement in children. PATIENTS: Selection criteria consisted of the presence of LCH with digestive symptoms, and histologic confirmation of gastrointestinal involvement. Seven children (2%) met the criteria among 348 cases of LCH in a French national retrospective survey from 1983 to 1993. Two children whose LCH was diagnosed in 1994 were also selected. RESULTS: Nine children with LCH and digestive tract involvement were studied. Clinical features at presentation included skin (9/9) and mucosal (4/9) involvement, failure to thrive (5/9), diarrhea (7/9), bloody stools (4/7), vomiting (4/9), and hypoalbuminemia (8/9). Five of the nine children died; factors associated with a poor prognosis included young age, organ dysfunction (stage 4), and need for parenteral nutrition. Unlike control biopsy specimens, LCH cells of children with digestive tract involvement disclosed expression of the mucosal homing receptor integrin alpha 4 beta 7 on frozen skin and digestive tract biopsy specimens. CONCLUSION: Cutaneous, mucosal, and digestive tract involvement in LCH is a clinicopathologic entity. The prognosis and treatment of LCH depend on the extent of the disease; therefore the treatment of these disseminated forms should not be delayed. Thus children with cutaneous LCH and digestive symptoms should undergo digestive tract biopsies. Studies of homing receptors may contribute to our understanding of the mechanisms of dissemination in LCH.

[Necrotizing enteritis during the therapeutic induction phase in leukemia. Value of surgical treatment]. / Entérite nécrosante à la phase d'induction thérapeutique d'une leucémie. Intérêt du traitement chirurgical.

A case of typhlitis in a 3,5 year old girl, during induction therapy for acute lymphoblastic leukemia is reported. This typhlitis, or necrotizing enterocolitis involving the coecum and right colon resulted in stercoral peritonitis during the neutropenic phase. After surgery, the patient had a favorable outcome with complete recovery. Knowledge about this uncommon but severe complication of hemopathies leads to follow clinical, microbiologic and radiologic rules of prophylaxis and screening. Typhlitis requires early treatment by supportive care and surgical cure if necessary.

[Possibilities for surgical excision of diffuse hepatoblastomas. Contribution and limitations of chemotherapy]. / Possibilités d'exérèse chirurgicale dans les hépatoblastomes diffus. Apport et limites de la chimiothérapie.

Four children with major hepatoblastoma were treated with extensive surgical excision and chemotherapy. Two right lobectomies and two left extended hepatectomies were performed. The first patient only received postoperative chemotherapy. The others three had preoperative chemotherapy for unresectable hepatoblastoma. All these children exhibited an initial response with marked reduction in size of their primary tumor. The only child who died during operation had disease involving both lobes of the liver, inferior vena cava and lungs metastasis. The follow up of the three other children is 26 to 32 months. Two of them are free of all disease. The third had lung isolated metastasis removed and is actually free of disease with follow up of 32 months. Authors discuss chemotherapy interest and limits in major hepatoblastoma.

[Echography and computed x-ray tomography in the diagnosis and surveillance of hepatoblastoma. Apropos of 5 cases]. / Apport de l'échographie et de la tomodensitométrie dans le diagnostic et la surveillance des hépatoblastomes. A propos de cinq observations.

Ultrasound imaging and CT scans were performed in a homogeneous group of five patients with hepatoblastoma. Effectiveness in determining characteristics of the tumor mass and its location and possible vascular extension were compared for the two exploratory methods. Findings suggest that these two examinations are useful and complementary for the diagnosis and follow up of hepatoblastoma.

[Acute positive Tdt leukemia with megakaryoblastic involvement. Apropos of an observation of an infant]. / Leucémie aiguë TdT positive avec participation mégacaryoblastique. A propos d'une observation faite chez le nourrisson.

After observation of a 10 month-old infant hospitalised for acute thrombopenia associated with signs of marked radiological hyperostosis, the initial medullograms showed a rich bone marrow free of blast cells. Subsequent complications of the thrombopenia were anemia, neutropenia and circulating blastosis. Marrow aspirations at various sites were unsuccessful. X-rays showed a worsening of the conditions and the child suffers attacks of intense pain. Ultrastructural cytochemistry and Tdt disclosed by immunofluorescence showed that the majority of blasts possessed Tdt and 2-3% were PPO positive. The presence of these 2 markers may correspond either to the presence of a promegakaryoblastic leukemia with aberrant Tdt, or to the coexistence of 2 types of blasts cells.

[Interest of ultrastructural study of skin and muscle biopsies in inborn storage diseases. A report of 18 cases (author's transl)]. / Intérêt de l'étude ultrastructurale des biopsies cutanée et musculaire dans les maladies de surcharge congénitales. A propos de 18 cas.

Skin and muscle biopsies were performed in 18 patients affected by various inborn storage disorders: mucopolysaccharidosis (MPS), sphingolipidosis, GM1 gangliosidosis, I-cell disease, ceroid-lipofuscinosis (CLF), adrenoleucodystrophy (ALD) and glycogenosis. In most cases, cutaneous and muscle biopsies demonstrate clearly the presence of storage inclusions in different cell types with great reproducibility and sometimes a specificity for a particular disease. Thus, electron microscopic examinations of skin and muscle, often complementary, can given valuable informations at two levels: - either a morphological confirmation depending on the type of the storage disease: e. g. clear, granular and fuzzy inclusions identified with mucopolysaccharidic material, lamellar and pseudomyelinic figures corresponding to lipidic structures are found in different cell types in MPS, gangliosidosis and sphingolipidosis; - or a diagnostic proof of some lysosomal diseases where there are very specific ultrastructural features such as the curvilinear bodies and fingerprint profiles in CLF or the spicular inclusions in ALD. These informations are the more important as the enzymatic defect is unknown in these inherited disorders. We conclude that the ultrastructural examination of a skin and muscle biopsy are an important tool for the diagnosis of a lysosomal storage disease which avoids any more difficult biopsies as brain, kidney, liver.

[Results of brain tomography in acute lymphoblastic leukemia in children]. / Résultats de la tomométrie encéphalique dans les leucemies aiguës lymphoblastiques de l'enfant.

Computerised axial tomography (CAT scan) was performed in 22 children with acute lymphoblastic leukaemia and in 13 the results were normal. In the other nine, various lesions were observed; namely intra-parenchymal lesions of density of (3 cases, one of which was calcified), intra-parenchymal lesions of decreased density (2 cases) and ventricular dilatation (7 cases). The role of the disease and of the treatment (intra-thecal methotrexate, cranial irradiation) in the development of these lesions is discussed. The CAT scan is an excellent method of monitoring the neurological problems in acute lymphoblastic leukaemia.

[Acute acalculous gallbladder disease in children: acute cholecystitis or acute gallbladder distension (author's transl)]. / Pathologie vésiculaire aiguë non lithiasique de l'enfant: cholécystite aiguë ou distension vésiculaire aiguë (à propos de 2 cas).

Acute acalculous gallbladder disease is rarely encountered in children. Two observations permit a review of its clinical, diagnostic, and therapeutic aspects. Acute acalculous cholecystitis and acute gallbladder distension present clinically in a similar fashion, although, in the latter the fever is usually absent and there is a history of episodic pain. The pathogenesis of these affections remains uncertain but generalized infection and anomalies of the cystic duct seem to be favoring circumstances. The diagnosis, rarely initially made, could be confirmed by oral cholecystography showing an non visualized gallbladder. Surgery is necessary in order to confirme or refute the diagnosis. The therapeutic approach can be either the simple drainage of the gallbladder or a cholecystectomy. Due to the risk of allowing a cervicocystic obstacle persist, it seems that a cholecystectomy, which is well tolerated by the child, would be preferable.