Claire Hoyoux

18F-FDG PET in children with lymphomas

PurposeThe aim of this study was to retrospectively evaluate the performance of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) in children with lymphomas, at various stages of their disease.MethodsTwenty-eight children (mean age 12.5 years, 14 girls, 14 boys) with Hodgkin’s disease (HD, n=17) or non-Hodgkin’s lymphoma (NHL, n=11) were evaluated. Patients were investigated at initial staging (n=19), early in the course of treatment (n=19), at the end of treatment (n=16) and during long-term follow-up (n=19). A total of 113 whole-body PET studies were performed on dedicated scanners. PET results were compared with the results of conventional methods (CMs) such as physical examination, laboratory studies, chest X-rays, computed tomography, magnetic resonance imaging, ultrasonography and bone scan when available.ResultsAt initial evaluation (group 1), PET changed the disease stage and treatment in 10.5% of the cases. In early evaluation of the response to treatment (group 2), PET failed to predict two relapses and one incomplete response to treatment. In this group, however, PET did not show any false positive results. There were only 4/75 false positive results for PET among patients studied at the end of treatment (group 3, specificity 94%) or during the systematic follow-up (group 4, specificity 95%), as compared with 27/75 for CMs (specificity 54% and 66%, respectively).Conclusion18F-FDG-PET is a useful tool for evaluating children with lymphomas. Large prospective studies are needed to appreciate its real impact on patient management.

Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report.

The first EORTC (European Organization of Research and Treatment of Cancer) acute myeloblastic leukemia (AML) pilot study (58872) was conducted between January 1988 and December 1991. Out of 108 patients, 78% achieved complete remission (CR), and event-free survival (EFS) and survival rates (s.e., %) at 7 years were 40 (5) and 51% (6%), respectively. It indicated that mitoxantrone could be substituted for conventional anthracyclines in the treatment of childhood AML without inducing cardiotoxicity. The aim of the next EORTC 58921 trial was to compare the efficacy and toxicity of idarubicin vs mitoxantrone in initial chemotherapy courses, further therapy consisting of allogeneic bone marrow transplantation (alloBMT) in patients with an HLA-compatible sibling donor or chemotherapy in patients without a donor. Out of 177 patients, recruited between October 1992 and December 2002, 81% reached CR. Overall 7-year EFS and survival rates were 49 (4) and 62% (4%), respectively. Out of 145 patients who received the first intensification, 39 had a sibling donor. In patients with or without a donor, the 7-year disease-free survival (DFS) rate was 63 (8) and 57% (5%) and the 7-year survival rate was 78 (7) and 65% (5%), respectively. Patients with favorable, intermediate and unfavorable cytogenetic features had a 5-year EFS rate of 57, 45 and 45% and a 5-year survival rate of 89, 67 and 53%, respectively.

Aberrant methylation of candidate tumor suppressor genes in neuroblastoma

CpG island hypermethylation has been recognized as an alternative mechanism for tumor suppressor gene inactivation. In this study, we performed methylation-specific PCR (MSP) to investigate the methylation status of 10 selected tumor suppressor genes in neuroblastoma. Seven of the investigated genes (CD44, RASSF1A, CASP8, PTEN, ZMYND10, CDH1, PRDM2) showed high frequencies (> or =30%) of methylation in 33 neuroblastoma cell lines. In 42 primary neuroblastoma tumors, the frequencies of methylation were 69%, CD44; 71%, RASSF1A; 56%, CASP8; 25%, PTEN; 15%, ZMYND10; 8%, CDH1; and 0%, PRDM2. Furthermore, CASP8 and CDH1 hypermethylation was significantly associated with poor event-free survival. Meta-analysis of 115 neuroblastoma tumors demonstrated a significant correlation between CASP8 methylation and MYCN amplification. In addition, there was a correlation between ZMYND10 methylation and MYCN amplification. The MSP data, together with optimized mRNA re-expression experiments (in terms of concentration and time of treatment and use of proper reference genes) further strengthen the notion that epigenetic alterations could play a significant role in NB oncogenesis. This study thus warrants the need for a global profiling of gene promoter hypermethylation to identify genome-wide aberrantly methylated genes in order to further understand neuroblastoma pathogenesis and to identify prognostic methylation markers.

Effects of methylprednisolone on the Fc-receptor function of human reticuloendothelial system in vivo.

Abstract. To determine whether the Fc‐receptor function of reticuloendothelial system (RES) is modified by corticosteroid administration, we studied the spleen to liver uptake ratios of autologous, 99Tc‐labelled heatdamaged or IgG‐coated erythrocytes, injected intravenously into 10 normal volunteers, 4 h after receiving a single dose of 32 mg of methylprednisolone by mouth.

Cord blood transplantation in a child with Pearson's disease

To the Editor: We report the first case of successful CBT in a molecular proved Pearson Disease (PD). The indication was hematologic but the interesting finding is the correction of non hematologic issues as metabolic acidosis and liver involvements. The patient presented neonatal hypoglycemia, metabolic acidosis, hyperlactacidemia and progressive pancytopenia treated by GCSF (5 mg/Kg three times a week) and transfusions. He never suffered from pancreatic insufficiency or neurologic disturbances (MRI normal). Diagnosis of PD [1–4] was established by bone marrow analysis (macrocytic sideroblastic anemia, ring sideroblasts and hematopoietic precursor vacuolization) (Fig. 1) and liver biopsy: mitochondrial respiratory enzymes measurements (spectrophotometry) revealed a combined deficiency of complexes I, III and IV (mitochondrial complexes) with an increase in complex II and in citrate synthetase (nuclear complexes). Mitochondrial DNA studies performed on blood sample (Southern Blot Analysis) detected deletion mutation (40% mutant mtDNA). Clinical symptoms from age 2 years onward worsened and blood products requirements increased; dysplasic features of red cells and platelet precursors were observed. Chromosome 7 deletion— del(7)(q22q32)—was detected in bone marrow until reaching 50% of hematopoietic cells. Because of these myelodysplasic finding, an unrelated cord blood transplantation (CBT) was performed at the age of nearly 3 years. The conditionning regimen included busulfan (37.5 mg/m days 8, 7, 6, 5), cyclophosphamide (60 mg/Kg days 4, 3) and Anti ThymoGlobulin (30 mg/Kg days 5, 4, 3). Hematopoietic recovery was normal and no major complications occurred. Three years after CBT the patient is doing well; hemogram is normal with complete engraftment of all donor cell lineages. Metabolic features of acidosis and lactacidemia as well as biological hepatic abnormalities resolved. A liver biopsy was performed showing resolution of morphological abnormalities; liver mitochondrial respiratory enzymes activities returned to normal range. Deletions of chromosome 7 in PD have not yet been reported, except after a double myeloablative therapy with reinfusion of PBSC [5]. Our patient had a successful hematopoietic transplant with correction of hematologic and non-hematologic features. These observations suggest possible interactions between hematopoietic tissue and mitochondrial abnormalities. Our clinical experience suggests hematopoietic transplantation is feasible in PD and could be useful in management of other severe mtDNA defect syndromes.

Osteopetrosis mimicking juvenile myelomonocytic leukemia.

A 5‐month‐old boy developed splenomegaly, anemia, thrombocytopenia with elevated white cells, monocytosis and immature granulocytes in the peripheral blood. Bone marrow showed dysplasia without blastosis. Increased colony‐forming unit‐granulocyte–macrophage was found in the peripheral blood, mimicking granulocyte–macrophage colony‐stimulating factor hypersensitivity. These findings fulfilled the diagnosis criteria for juvenile myelomonocytic leukemia (JMML), but no mutations in the CBL, NRAS, KRAS, or PTPN11 genes were detected. In addition to these findings severe hypogammaglobulinemia and elevated alkaline phosphatase were present. Bone X‐ray showed dense and radiopaque bones with a bone‐in‐bone appearance characteristic of infantile malignant osteopetrosis (IMO). Genetic mutation in T‐cell, immune regulator 1 (TCIRG1) was identified, confirming the diagnosis of IMO. Careful differential diagnosis including osteopetrosis, is therefore recommended in patients with clinical features and hematologic findings consistent with JMML.

Pediatric gastric lymphoma: a rare entity.

Primary gastric lymphoma is a rare event in childhood. We describe a 13-year-old boy with gastric Burkitt-like lymphoma localized in the fundus. Symptoms mimicking gastritis-epigastric pain, hypochromic anemia, anorexia, and weight loss had been present for a few months before diagnosis. No Helicobacter pylori infection was shown at diagnosis. Biopsies obtained by ultrasound gastroscopy proved the diagnosis; 18F-fluorodeoxyglucose-positron emission tomography detected an isolated large gastric hypermetabolic mass. According to the international FAB/LMB 96 trial, the patient was treated with chemotherapy alone and is in first complete remission 2½ years after diagnosis.

La pyknocytose infantile : une anemie neonatale mal connue a propos de 5cas.

UNLABELLED Infantile pyknocytosis (IP) is a rare hematological entity of newborns. It is a form of hemolytic anemia with unusual red cell morphology: the red blood cells are distorted, irregular, and small with many projections. Spontaneous resolution usually occurs by 4-6months of age. OBSERVATION We describe the clinical features and biological parameters of 5 cases of IP. The first symptoms were always early jaundice, which required phototherapy. Anemia was severe in all babies and red blood cell transfusion was needed. CONCLUSION IP is a rare cause of neonatal anemia whose diagnosis is based on a careful peripheral blood smear examination. In our study, anemia was severe and required red blood cell transfusion. Ethnic specificity and familial occurrence are reported in our experience.

Control of Nausea and Vomiting By Navoban(r) (tropisetron) in 131 Children Receiving Cytotoxic Chemotherapy

One hundred and thirty-one children with a median age of 5 years were administered Navoban (tropisetron), a selective antagonist of the serotonin receptor (5-HT3), dosed once daily at 0.2 mg/kg (with a maximum of 5 mg daily) in a study aimed at evaluating the prevention of nausea and vomiting induced by anti-cancer chemotherapy. The most common malignancy (in 49% of patients) was acute lymphocytic leukaemia. Patients received Navoban during one or more courses of emetogenic chemotherapy for a total of 455 courses administered intravenously or intravenously and intrathecally (IV + IT). Most patients (89%) had already received cytotoxic chemotherapy before enrollment for the trial. On Day 1, Navoban was administered slowly and intravenously as a single dose before the start of chemotherapy, or by mouth as a single daily dose on subsequent days (median treatment duration = 5 days). On the first 5 days of each course of chemotherapy, response to Navoban per 24-hour period was graded as: complete (absence of both nausea and vomiting), partial (1-4 vomits and/or less than 5 hours of nausea), or failure (more than 4 vomits and/or at least 5 hours of nausea). Ninety-six per cent of the intravenous chemotherapy group and 97% of the IV + IT chemotherapy group had a complete (70% and 55% respectively) or partial (26% and 42% respectively) response during the first 24-hour period of the first course in which Navoban was used. The second and subsequent courses yielded similar percentages. Delayed emesis was observed mainly during those courses employing the most emetogenic chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Nasal heterotopia versus pilocytic astrocytoma: A narrow border.

Failure of the anterior neuropore can lead to three main types of anomalies: nasal dermal sinus, encephalocele and nasal glioma or heterotopia. In this report, we describe a case of intracranial and extracranial glial heterotopia that probably resulted from a common failure of anterior neuropore development. We describe the prenatal radiological assessment based on ultrasound and MRI results, and consider their limitation for early fetal diagnosis. We also discuss the embryogenesis and the possible pathogenic mechanisms involved.