[Towards cure for all children with acute lymphoblastic leukemia?].

Childhood acute lymphoblastic leukemia is a model in oncology. The outcome was dismal 40 years ago but is now generally excellent, owing to the recent advent of new drugs. These advances were made possible by the creation of specialized units, better supportive care (transfusions, antibiotics and pain control) and intense biological and clinical research coordinated by national and international cooperative groups, allowing the use of available drugs to be optimized.

[A brief history of treatments for childhood acute lymphoblastic leukaemia].

Acute lymphoblastic leukaemia is the most frequent childhood malignancy. The first effective drugs, which provided only short-lived complete remission, started to be used in the 1950s. All the effective drugs currently in use were discovered in the 1960s, when the first multidrug chemotherapy regimens were shown to confer prolonged complete remission, raising the possibility of a cure.

Testicular anti-mullerian hormone secretion is stimulated by recombinant human FSH in patients with congenital hypogonadotropic hypogonadism.

Serum anti-Mullerian hormone (AMH), a prepubertal Sertoli cell marker, declines during puberty as an early sign of testicular testosterone (T) production. When T synthesis or action is impaired, serum AMH is abnormally high in the first months after birth and at puberty but normal between these two periods. We postulated that FSH might be responsible for AMH up-regulation in the absence of androgen inhibition.

Hypogonadotropic hypogonadism as a model of post-natal testicular anti-Müllerian hormone secretion in humans.

The pituitary gonadotropins are the main regulators of testicular hormonal secretion in humans. Hypogonadotropic hypogonadism (HH), characterized by the absence of secretion of endogenous gonadotropins is therefore a convenient model to asses the respective effects of luteinizing hormone (LH) (or human chorionic gonadotropin (hCG)), exogenous testosterone (T) and FSH on gonadal function. In order to investigate the hormonal control of AMH secretion in man, serum AMH levels were measured in adult patients with congenital HH (CHH) and with post-pubertal acquired HH (AHH) either untreated, during hCG or T therapy.

[Pilot study and preliminary validation of the French version of a quality-of-life questionnaire specific for subjects with growth hormone deficiency].

This study forms part of a research project seeking to develop a standardized questionnaire by which clinicians can assess the impact of growth hormone (GH) deficiency and its treatment on the "perceived health" or health-related quality of life of adults. The specific aim of this study was to translate and adapt for French patients the AGHDA (Adult Growth Hormone Deficiency Assessment) a standardized health-related quality of life measure for use with GH-deficient adults, initially developed in the United Kingdom, and to collect data which could be used to assess the main psychometric characteristics of its French version the ISPA-HC (Indicateur de Santé Perceptuelle Adulte-Hormone de Croissance). The main properties analyzed are: 1/ The scale's acceptability, as determined by means of face-to-face interviews with a small number of subjects, then by an ad hoc questionnaire administered during a test-retest study; 2/ The scale's reliability, as determined by a test-retest study (with a 15-days interval between tests); 3/ The scale's concurrent validity, as expressed by comparison with scores obtained by means of a generic quality of life scale, the ISPN (the French version of the Nottingham Health Profile).

[French results of enzyme replacement therapy in Gaucher's disease].

Gaucher disease is an inborn recessive autosomal disease due to a partial deficiency of the lysosomal enzyme beta glucocerebrosidase. The deficient activity leads to accumulation of the lipid glucocerebroside in the liver, the spleen and bone marrow with concomitant anemia and thrombocytopenia. Patients with Gaucher disease have been classified in three types: type I is the more common, neurological manifestations occur in types II and III.

Response of Diamond-Blackfan anemia to metoclopramide: evidence for a role for prolactin in erythropoiesis.

A 47-year-old woman with severe macrocytic anemia markedly improved during the second and third trimesters of 3 pregnancies and when breast-feeding her 2 children. Because the serum prolactin level is elevated at these times, we later treated her with metoclopramide (10 mg orally 3 times daily), a medication known to induce prolactin release. Her serum prolactin levels increased from 7 to 133 ng/mL (normal < 20 ng/mL) and hematocrit from 17% to 22% to 35%.

Impact of addition of maintenance therapy to intensive induction and consolidation chemotherapy for childhood acute myeloblastic leukemia: results of a prospective randomized trial, LAME 89/91. Leucámie Aiqüe Myéloïde Enfant.

Purpose: To determine whether the use of maintenance therapy (MT) delivered after intensive induction and consolidation therapy confers any advantage in childhood acute myeloid leukemia (AML).

Patients And Methods: A total of 268 children with AML were registered in the Leucámie Aiquë Myéloïde Enfant (LAME) 89/91 protocol. This regimen included an intensive induction phase (mitoxantrone plus cytarabine) and, for patients without allograft, two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase, and amsacrine.

Day-care, early common infections and childhood acute leukaemia: a multicentre French case-control study.

We conducted a case-control study to investigate the role of early infections in the aetiology of childhood acute leukaemias. The study included 280 incident cases (240 acute lymphoblastic leukaemia and 40 acute non-lymphoblastic leukaemia) and 288 hospital controls, frequency matched by age, gender, hospital, catchment area of the hospital and ethnic origin. Data were obtained from standardised face-to-face interviews of the mothers.

Family cancer history and risk of childhood acute leukemia (France).

Objective: A case-control study was carried out to investigate the role of a family history of solid tumor or hematologic neoplasm in the etiology of childhood acute leukemia.

Methods: Family cancer history in first- and second-degree relatives was compared in 279 incident cases (242 cases of acute lymphocytic leukemia and 37 of acute myeloid leukemia) and 285 controls. Recruitment was stratified by age, gender, hospital, area of residence, and ethnic origin.

The postmenopausal ovary is not a major androgen-producing gland.

It is currently believed that the postmenopausal ovary remains a gonadotropin-driven, androgen-producing gland. However, the adrenal contribution to circulating androgen levels may explain some conflicting results previously reported. In addition, the steroidogenic potential and gonadotropin responsiveness of the postmenopausal ovary have not been recently reassessed.

[Prognosis of acute lymphoblastic leukemia in children. Results of the French protocol FRALLE 93].

1,120 children were included in protocol FRALLE 93 from june 1993 to september 1998. Disease Free Survival for the all protocol is 78% +/- 3 and overall survival 83% +/- 3. Various clinical and laboratory features at the time of diagnosis have been correlated with prognosis.

Normal pituitary hypertrophy as a frequent cause of pituitary incidentaloma: a follow-up study.

Enlargement of the pituitary gland is a frequent cause of incidentaloma and of referrals to endocrinologists for hormonal evaluation and therapeutic advice. In neuroradiological series, 25-50% of healthy women who are 18-35 yr old have a convex superior pituitary contour, but pituitary height exceeds 9 mm in less than 0.5% of cases.

Efficacy of amphotericin B lipid complex in the treatment of invasive fungal infections in immunosuppressed paediatric patients.

The safety and efficacy of amphotericin B lipid complex (ABLC) were evaluated in a retrospective study of 46 paediatric patients with invasive infections. The study included a large proportion of patients who were refractory to or intolerant of conventional antifungal therapy. The mean age of the children was 9.

Teicoplanin in the treatment of serious infection.

The merits and dosing regimens for teicoplanin in the treatment of endocarditis, bacteremia, bone and joint infections, pediatric use, non in-patient use and in the ICU are discussed. Teicoplanin has several advantages over vancomycin in the treatment of serious infections: long half-life, lower nephrotoxicity, and lack of requirement for serum assays. The recommended regimen for teicoplanin is three loading doses of 6 mg/kg (400 mg) q12h, then 6 mg/kg (400 mg) q24h.

Prognostic study of continuous variables (white blood cell count, peripheral blast cell count, haemoglobin level, platelet count and age) in childhood acute lymphoblastic leukaemia. Analysis Of a population of 1545 children treated by the French Acute Lymphoblastic Leukaemia Group (FRALLE).

Many cutpoints have been proposed to categorize continuous variables in childhood acute lymphoblastic leukaemia (white blood cell count, peripheral blast cell count, haemoglobin level, platelet count and age), and have been used to define therapeutic subgroups. This variation in the choice of cutpoints leads to a bias called the 'Will Rogers phenomenon'. The aim of this study was to analyse variations in the relative risk of relapse or death as a function of continuous prognostic variables in childhood ALL and to discuss the choice of cutpoints.

Efficacy and tolerability of the long-acting somatostatin analog lanreotide in acromegaly. A 12-month multicenter study of 58 acromegalic patients. French Multicenter Study Group on Lanreotide in Acromegaly.

Objective: To determine the effects of the new somatostatin analogue, lanreotide, in its prolonged released form (PR), in patients with acromegaly.

Design: Prospective open multicenter non comparative study.

Setting: Thirty-three university-affiliated medical centers.

Vascular reactivity in acromegalic patients: preliminary evidence for regional endothelial dysfunction and increased sympathetic vasoconstriction.

Background And Objectives: Hypertension is found in one-third of acromegalic patients. An heterogenous distribution of cardiac output has been recently demonstrated in acromegalic patients with an increased blood flow at the level of the upper limb, suggesting that acromegalic patients may have some degree of endothelial dysfunction. Elsewhere, studies involving hypopituitary GH-deficient adults have shown that GH and/or IGF-I may have direct effect on endothelial function.

Effects of human recombinant luteinizing hormone and follicle-stimulating hormone in patients with acquired hypogonadotropic hypogonadism: study of Sertoli and Leydig cell secretions and interactions.

Unlabelled: Experimental data suggest that FSH-stimulated Sertoli cells can enhance LH-induced Leydig cell testosterone (T) production. The function of Leydig and Sertoli cells can be selectively studied by using recombinant human LH (rhLH) and recombinant human FSH (rhFSH) in patients with complete gonadotropin deficiency. The aim of the present study was to assess the secretion of testicular T, estradiol (E2), and inhibin B and the physiological relevance of the Sertoli-Leydig cell interaction in man.

Measurement of plasma free luteinizing hormone beta-subunit in women.

Little is known about the physiological secretion of the free beta-subunit of LH (LHbeta). The aim of this study was to compare in women the secretion of LHbeta, using sensitive and specific two-site immunoassays, with dimeric LH and the free common alpha-subunit (FAS). The LHbeta assay does not recognize the dimeric LH and cross-reacts only with free hCG beta-subunit (CGbeta).

Use of recombinant human granulocyte colony-stimulating factor to increase chemotherapy dose-intensity: a randomized trial in very high-risk childhood acute lymphoblastic leukemia.

Purpose: To determine whether the use of a recombinant human granulocyte colony-stimulating factor ([G-CSF] lenogastrim) can increase the chemotherapy dose-intensity (CDI) delivered during consolidation chemotherapy of childhood acute lymphoblastic leukemia (ALL).

Patients And Methods: Sixty-seven children with very high-risk ALL were randomized (slow early response to therapy, 55 patients; translocation t(9;22) or t(4;11), 12 patients). Consolidation consisted of six courses of chemotherapy; the first, third, and fifth courses were a combination of high-dose cytarabine, etoposide, and dexamethasone (R3), whereas the second, fourth, and sixth courses included vincristine, prednisone, cyclophosphamide, doxorubicin, and methotrexate (COPADM).

Localized childhood Hodgkin's disease: response-adapted chemotherapy with etoposide, bleomycin, vinblastine, and prednisone before low-dose radiation therapy-results of the French Society of Pediatric Oncology Study MDH90.

Purpose: The French Society of Pediatric Oncology MDH82 study demonstrated the effectiveness of 20 Gy irradiation of involved fields after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, vincristine, procarbazine, and prednisone/ABVD chemotherapy in children with localized Hodgkin's disease (HD). The response to primary chemotherapy was the only predictor of survival. To reduce long-term treatment complications without compromising efficacy, the MDH90 study was based on a new chemotherapy regimen devoid of both alkylating agents and anthracycline, followed by 20 Gy of radiotherapy (RT) for good responders.