Combined therapy in children and adolescents with classical Hodgkin's lymphoma: A report from the SFCE on MDH-03 national guidelines.

Hodgkin's lymphoma (HL) in children and adolescents is highly curable, but children are at risk of long-term toxicity. The MDH-03 guidelines were established in order to decrease the burden of treatment in good-responder patients, and this report should be considered a step toward further optimization of treatment within large collaborative trials. We report the therapy and long-term outcomes of 417 children and adolescents treated according to the national guidelines, which were applied between 2003 and 2007 in France. The patients were stratified into three groups according to disease extension. Chemotherapy consisted of four cycles of VBVP (vinblastine, bleomycin, VP16, prednisone) in localized stages (G1/95 pts/23%), four cycles of COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone, adriamycin, bleomycin, vinblastine) cycles in intermediate stages (G2/184 pts/44%) and three cycles of OPPA (vincristine, procarbazine, prednisone, adriamycin) plus three cycles of COPP in advanced stages (G3/138 pts/33%). Radiation therapy of the involved field was given to 97% of the patients, with the dose limited to 20 Gy in good responders (88%). With a median follow-up of 6.6 years, the 5-year event-free survival (EFS) and overall survival (OS) were 86.7% (83.1-89.7%) and 97% (94.5-98.1%), respectively. EFS and OS for G1, G2, and G3 were 98% and 100%, 81% and 97%, and 87% and 95%, respectively. Low-risk patients treated without alkylating agents and anthracycline had excellent outcomes and a low expected incidence of late effects. Intensification with a third OPPA cycle in high-risk group patients, including stage IV patients, allowed for very good outcomes, without increased toxicity.

CNS-3 status remains an independent adverse prognosis factor in children with acute lymphoblastic leukemia (ALL) treated without cranial irradiation: Results of EORTC Children Leukemia Group study 58951.

AIM: To evaluate the prognostic significance of initial central nervous system (CNS) involvement of children with acute lymphoblastic leukemia (ALL) enrolled in the EORTC 58951 trial. PATIENTS AND METHODS: From 1998 to 2008, 1930 ALL patients were included in the randomized EORTC 58951 trial. Overall treatment intensity was adjusted according to known prognostic factors including the level of minimal residual disease after induction treatment. CNS-directed therapy comprised four to 11 courses of i.v. methotrexate (5g/m2), and 10 to 19 intrathecal chemotherapy injections, depending on risk group and CNS status. Cranial irradiation was omitted for all patients. RESULTS: The overall 8-year event-free survival (EFS) and overall survival (OS) rates were 81.3% and 88.1%, respectively. In the CNS-1, TPL+, CNS-2, and CNS-3 groups, the 8-year EFS rates were 82.1%, 77.1%, 78.3%, and 57.4%, respectively. Multivariable analysis indicated that initial CNS-3 status, but not CNS-2 or TLP+, was an independent adverse predictor of outcome. The 8-year incidence of isolated CNS relapse was 1.7% and of isolated or combined CNS relapse it was 3.7%. NCI high-risk group, male sex, CNS-2 and CNS-3 status were independent predictors for a higher incidence of any CNS relapse. CONCLUSIONS: CNS-3 status remains associated with poor prognosis and requires intensification of both systemic and CNS-directed therapy. This trial was registered at https://clinicaltrials.gov/under/NCT00003728.

[Fortuitously discovered neutropenia in children: diagnosis and follow-up]. / Neutropénies de découverte fortuite chez l'enfant : diagnostic et suivi.

Neutropenia seems to be quite frequent in current pediatric practice and can confuse the clinician since it may result from a severe cause. The aim of this study was to provide a prospective description of episodes of neutropenia in children to assess its clinical relevance in a general pediatric cohort consulting and/or hospitalized in a French university hospital. In this prospective observational and monocentric study conducted from April 2012 to April 2013, we included all the patients under 18 years of age who presented neutropenia (defined as an absolute neutrophil count [ANC] below 1×10(9)/L before 1 year of age and below 1.5×10(9)/L beyond) on a whole blood count (WBC) performed in our hospital. Patients treated with chemotherapy were not included. Medical records were regularly checked for at least 1 year after inclusion, and clinical and biological data were collected prospectively to compare transient episodes of neutropenia (<3 months) with persistent episodes of neutropenia (>3months). Of 55,018 consultations and 13,967 hospitalizations (chemotherapy excluded), 8966 blood counts were performed and 250 episodes of neutropenia were found in 238 patients. Data concerning clinical progression were available in 195 cases of which 136 had at least one subsequent WBC. Two hundred thirty-one episodes corresponded to new episodes, while neutropenia preexisted before inclusion in the others. The median follow-up was 12.8 months. Most episodes of neutropenia occurred in children <2 years of age (52%), with a median age of 22.2 months. Mean ANC was 0.943×10(9)/L (±0.340) and a few episodes of neutropenia were below 0.5×10(9)/L (9.2%). Neutropenia persisted more than 3 months in only 13.2% of cases. When neutropenia was below 0.5×10(9)/L, it significantly persisted (RR=3.08; 95% CI [1.31-7.22]). Other factors associated with persistent neutropenia were thrombocytopenia, monocytopenia, a CRP more than 70mg/L, significant abnormality on the clinical exam, and age over 24 months. However, multivariate analysis showed that only an ANC below 0.5×10(9)/L was significantly associated with persistence. While etiology could not be determined in 32% of cases, neutropenia resulted mostly from infectious causes (37.8%), with other causes being more anecdotal. The majority of infectious episodes of neutropenia were viral (90.3%). Like other studies, this investigation suggests that most episodes of neutropenia concern young children, are transient, are benign and often due to infectious diseases. Although it may not reflect the medullar stock or the real capacity of neutrophils to fight bacterial infections, it seems that neutropenia below 0.5×10(9)/L is more likely to persist and be complicated, as previous studies also suggest. To conclude, neutropenia is not exceptional in children and, even if it often results from viral infections and mostly evolves favorably, the clinician should closely monitor these patients, especially when neutrophils are below 0.5×10(9)/L.

[Angiomatoid fibrous histiocytoma: a rare pathologic entity]. / Histiocytome fibreux angiomatoïde: une entité rare.

Angiomatoid fibrous histiocytoma is an unusual tumor, affecting primarily young adults who develop local disease with favorable prognosis. This contrasts with the aggressive natural history of malignant fibrohistiocytoma. We report case of a 9-year-old girl who presented with a tumor mass of soft tissues with an unusual deep location, thereby with non distinctive clinical features. Surgical treatment was performed.

[Mandibular chloroma]. / Chlorome mandibulaire.

CASE REPORT: A 23 year-old girl was admitted for a facial tumefaction, fixed to the mandible. The X-rays showed a fuzzy osteolytic lesion of the mandibular angle. The CT-scan confirmed the rupture of the cortical bone and the extension to the soft tissue. Biopsy provided the diagnosis of granulocytic monoblastic sarcoma (chloroma). Chemotherapy was efficient. DISCUSSION: Mandibular localizations of chloroma are rare. Granulocytic monoblastic sarcoma is a localized tumor made of extramedullar immature granulocytes, in general associated (or more rarely preceded by) with leukemia. Early diagnosis is important because high dose chemotherapy induction may completely cure leukemia.

[Histiocytic proliferative diseases. Discussion of a case report]. / Proliférations histiocytaires. Discussion à propos d'un cas.

The case of a ten month old female with initial clinical and histological findings suggestive of inappropriate macrophage activation syndrome is reported. Subsequently, clinical and pathological changes refuted this diagnosis and demonstrated that the patient had Langherans cell histiocytosis. Clinical, laboratory and pathological findings characteristic of each type of histiocytosis are reviewed. Histological and immunohistochemical studies allow to establish the diagnosis of Langherans cell histiocytosis. The finding of erythrophagocytosis in our patient suggests that two types of histiocyte proliferation can coexist in the same individual.

[Hemophilic arthropathies. Apropos of 51 cases]. / Arthropathies hémophiliques. A propos de cinquante et un cas.

After defining the clinical, roentgenological and anatomic features of the various kinds of hemophilia-related joint disease (acute hemarthrosis, subacute arthritis, and chronic joint disease), we present a study of outcomes in fifty-one hemophiliac children aged 0 to 15 years and followed-up from January 1968 through December 1987 at the Angers Regional University Hospital. Four hundred and sixty-four cases of hemarthrosis were seen. Risk factors for hemarthrosis were severe hemophilia and age between 5 and 15 years, and the joints most often involved were the ankles, knees, and elbows. Sequelae of hemarthrosis were extremely prevalent in this study population: 100% of patients with severe hemophilia and 90% of patients with a factor activity of 3% or less exhibited chronic joint disease by the age of fifteen, with varying degrees of functional impairment. Because a first episode of hemarthrosis is often followed by recurrences in the same joint, we underline the need for prevention and careful treatment of acute episodes, which are the only means for decreasing articular sequelae.

[Malaria and pregnancy. Report of a case of congenital Plasmodium falciparum malaria]. / Paludisme et grossesse. A propos d'une observation de paludisme congénital à Plasmodium falciparum.

We report a case of congenital malaria due to a chloroquine-resistant strain of Plasmodium falciparum acquired in Mali. Ours is the first report of chloroquine-resistant congenital malaria in this part of Africa. We recall the various pathophysiologic, diagnostic and therapeutic features of this disease that should be considered in every neonate born to a mother who may have malaria. Although such cases are infrequent, we also discuss the very serious problems, mainly therapeutic, that they raise in several countries where they are endemic (South-East Asia and Africa particularly).

Interaction of von Willebrand factor with platelets activated by thrombin or a synthetic 7-amino acid peptide derived from the cleaved thrombin receptor.

Thrombin and the 7-mer agonist peptide from its receptor (SFLLRNP) were compared for their ability to promote the binding of vWF to platelets. Identical Ca(2+)-dependence and kinetics of activation were observed. Studies of inhibition of the binding by a series of monoclonal antibodies to GPIb, GPIIb/IIIa and vWF and experiments performed using platelets from patients with Glanzmann thrombasthenia or Bernard-Soulier syndrome enabled to identify GPIIb/IIIa as the receptor of vWF. Binding isotherms of vWF in the presence of an excess of either agonist yielded a similar number of binding sites but an apparent dissociation constant slightly but consistently higher with the 7-mer peptide than with thrombin. The latter point was confirmed by studying the binding of limiting amounts of vWF to platelets as a function of the agonist concentration. The lower affinity in the presence of 7-mer peptide was not corrected by adding increasing amounts of FPR-thrombin, a derivative with irreversibly blocked active site but retaining the binding properties of the active enzyme. Conversely, the higher affinity observed with thrombin was decreased when platelets were treated with Serratia protease which selectively cleaved GPIb but did not affect the function of the thrombin receptor and GPIIb/IIa. Our data thus suggest that both the 7-mer peptide and thrombin are able to induce the assembly of functional GPIIb/IIIa.(ABSTRACT TRUNCATED AT 250 WORDS)