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Biomedical subjects

G Cornu

Publications and source records attributed to G Cornu.

At least 37 records · Page 2Linked to original sources
PubMed1998

Haematopoietic stem cell transplantation for sickle cell anaemia: the first 50 patients transplanted in Belgium.

Fifty patients affected by sickle cell anaemia underwent transplantation of HLA-identical haematopoietic stem cells (bone marrow, 48; cord blood, 2). Two groups of patients were considered for transplantation. Group 1 included 36 permanent residents of a European country who, retrospectively, met the inclusion criteria accepted at a consensus conference held in Seattle in 1990, wherein children were selected because they already had evidence of a morbid course. Group 2 included 14 patients who were transplanted earlier, had not received more than three blood transfusions and were transplanted because they had decided to return to their country of origin. Kaplan-Meier estimates of overall survival, event-free survival and disease-free survival at 11 years of the whole grafted population are 93, 82 and 85%, respectively. In group 1, overall survival, EFS and DFS were 88, 76 and 80% and in group 2, 100, 93 and 93%, respectively. Clinical manifestations of the disease, as well as disease associated haemolytic anaemia, disappeared in all successfully treated patients. Recovery of spleen function was present in seven out of 10 evaluated patients. Adverse events (death, absence of engraftment, mixed chimerism and relapse) occurred more frequently in group 1 than in group 2 (25% vs 7%, P< 0.001). Acute graft-versus-host disease (GVHD) was present in 20 patients (grade I or II, 19; grade III, 1), chronic GVHD in 10 (limited, 7; extensive, 3). One patient developed an acute myeloid leukaemia. Gonadal dysfunction was present in all patients (six boys and eight girls) transplanted close to or after puberty, although transient in one adolescent girl.

Adolescent↗
PubMed1998

Critical study of prognostic factors in childhood acute lymphoblastic leukaemia: differences in outcome are poorly explained by the most significant prognostic variables. Fralle group. French Acute Lymphoblastic Leukaemia study group.

We determined the proportion of survival variability explained by the usual prognostic factors in childhood acute lymphoblastic leukaemia (ALL) during a prognostic study of 1552 patients enrolled in three consecutive Fralle group protocols (Fralle 83, Fralle 87 and Fralle 89). The event-free survival rates at 5 years were 54.8% (SD 1.9), 43.1%) (SD 2.7) and 55.6% (SD 2.2), respectively. In the univariate analysis the following variables were predictive of poor outcome: male gender, elevated leucocytosis (> 50 x 10(9)/l), circulating blastosis. haemoglobin >12 g/dl, platelet count <100 x 10(9)/l, age under 1 year or over 9 years, enlarged mediastinum, nodes, spleen and liver, T phenotype, absence of CD10+ cells; testicular and meningeal involvement, poor response to induction therapy (CCSG M3), and LDH >400 U/l. Among the cytogenetic features, hyperdiploidy had a protective effect, whereas hypodiploidy, translocation and other structural abnormalities had a negative influence, particularly in cases of t(9;22) or t(4;11). Multivariate analysis summarized the prognostic information in terms of four variables: age, gender, leucocytosis and cytogenetic features. Missing data had little influence on the results. However, despite their significance in the multivariate analysis, these four variables each had very low predictive power (1.1% for gender, 2.0% for age, 3.5% for leucocytosis, and 1.6% for cytogenetic features). Thus, the most significant prognostic factors in childhood ALL each explain no more than 4% of the variability in prognosis. This may explain the disappointing practical value of these factors and underlines the need for prognostic tools in childhood ALL.

Age Factors↗
PubMed1998

Total body irradiation-high-dose cytosine arabinoside and melphalan followed by allogeneic bone marrow transplantation from HLA-identical siblings in the treatment of children with acute lymphoblastic leukaemia after relapse while receiving chemotherapy: a Société Française de Greffe de Moelle study.

We investigated the use of a new conditioning regimen followed by allogeneic bone marrow transplantation (BMT) for treating children with acute lymphoblastic leukaemia (ALL) after relapse within 6 months of the completion of therapy. One hundred and sixteen children with acute lymphoblastic leukaemia in second or subsequent complete remission (CR) underwent allogeneic bone marrow transplantation from HLA-identical siblings after a preparative regimen comprising total body irradiation (TBI), high-dose cytosine arabinoside and melphalan (TAM regimen). The Kaplan-Meier product-limit estimate (mean +/- SE) of disease-free survival (DFS) at 7 years was 59.5 +/- 9% (95% confidence interval). The estimated chance of relapse was 22.5 +/- 15% with a median follow-up of 88.5 months (range 51-132). 26 patients (22.4%) died with no evidence of recurrent leukaemia, mainly from interstitial pneumonitis, veno-occlusive disease or acute graft-versus-host disease (GVHD). Three factors significantly affected DFS: acute GVHD. site of relapse and, for children in second remission after a marrow relapse, the disease status at the time of transplantation. The DFS were 59.02 +/- 12.6%, 37.5 +/- 19.8% and 774 +/- 15% among patients in CR2 after a marrow relapse, in CR3 or in untreated partial marrow relapse, and in CR2 after an isolated CNS relapse, respectively. The lowest DFS was seen in children with acute GVHD grades 3-4. Two significant factors were associated with relapse: the marrow status at the time of transplantation and chronic GVHD. The relapse rate was lower among children in CR2 or with chronic GVHD. We conclude that transplantation after the TAM regimen is an effective therapy for this population with acceptable toxicity, particularly for children in second remission after a very early marrow relapse, or those with early isolated CNS involvement.

Adolescent↗
PubMed1998

Repeated-dose pharmacokinetics of an oral solution of itraconazole in infants and children.

The safety, tolerability, and pharmacokinetics of an oral solution of itraconazole and its active metabolite hydroxyitraconazole were investigated in an open multicenter study of 26 infants and children aged 6 months to 12 years with documented mucosal fungal infections or at risk for the development of invasive fungal disease. The most frequent underlying illness was acute lymphoblastic leukemia, except in the patients aged 6 months to 2 years, of whom six were liver transplant recipients. The patients were treated with itraconazole at a dosage of 5 mg/kg of body weight once daily for 2 weeks. Blood samples were taken after the first dose, during treatment, and up to 8 days after the last itraconazole dose. On day 1, the mean peak concentrations in plasma after the first and last doses (Cmax) and areas under the concentration-time curve from 0 to 24 h (AUC0-24) for itraconazole and hydroxyitraconazole were lower in the children aged 6 months to 2 years than in children aged 2 to 12 years but were comparable on day 14. The mean AUC0-24-based accumulation factors of itraconazole and hydroxyitraconazole from day 1 to 14 ranged from 3.3 to 8.6 and 2.3 to 11.4, respectively. After 14 days of treatment, Cmax, AUC0-24, and the half-life, respectively, were (mean +/- standard deviation) 571+/-416 ng/ml, 6,930+/-5,830 ng.h/ml, and 47+/-55 h in the children aged 6 months to 2 years; 534+/-431 ng/ml, 7,330+/-5,420 ng.h/ml, and 30.6+/-25.3 h in the children aged 2 to 5 years; and 631+/-358 ng/ml, 8,770+/-5,050 ng.h/ml, and 28.3+/-9.6 h in the children aged 5 to 12 years. There was a tendency to have more frequent low minimum concentrations of the drugs in plasma for both itraconazole and hydroxyitraconazole for the children aged 6 months to 2 years. The oral bioavailability of the solubilizer hydroxypropyl-beta-cyclodextrin was less than 1% in the majority of the patients. In conclusion, an itraconazole oral solution given at 5 mg/kg/day provides potentially therapeutic concentrations in plasma, which are, however, substantially lower than those attained in adult cancer patients, and is well tolerated and safe in infants and children.

Administration, Oral↗
PubMed1998

Related cord blood transplants: the Eurocord experience from 78 transplants. Eurocord Transplant group.

Eurocord Transplant has established a registry for studying results of cord blood transplant. We have analyzed 78 patients who have received a related CBT between October 1988 and December 1996. The median follow-up time was 29 months (1-99). The median age was 5 years (0.2-20), median weight 19 kg (5-50). Forty-six patients had a malignant disease: 32 acute leukemia (AL), six chronic myeloid leukemia (CML), four myelodysplastic syndrome, two neuroblastoma and two non-Hodgkin lymphoma. Thirty-two patients were transplanted for non-malignant diseases including 17 bone marrow failure syndromes (BMFS), three sickle cell anemia, five thalassemia and seven inborn errors. The donor was an HLA-identical sibling in 60 cases and an HLA-mismatched donor in 18 cases. As conditioning, 36 patients received irradiation and 40 patients received associated busulfan-containing regimens. GVHD prophylaxis consisted of CsA alone in 36 cases, CsA associated with prednisone in eight cases, CsA, methotrexate (Mtx) with or without prednisone in 28 cases and CsA with monoclonal antibody or ATG in four cases. The median number of nucleated cells (NC) infused/kg was 3.9 x 10(7) (0.7-15). One-year survival was 63 +/- 6%. Age, weight, HLA identity and negative cytomegalovirus (CMV) serology in the recipient were significant favorable prognostic factors. Among these 78 patients, the incidence of grade > or = II GVHD was 9% in HLA-matched CBT and 50% in mismatched CBT (P < 0.001). Neutrophil engraftment was associated with age <6 years (P = 0.02) and weight <20 kg (P = 0.02). It was 73% in patients receiving <3.7 x 10(7) nucleated cells (NC) infused/kg and 85% in patients receiving more (P = 0.06). Favorable factors for platelets engraftment were age <6 years (P = 0.03), weight <20 kg (P = 0.002) and HLA identity (P < 0.0001). Related cord blood transplantation offers a good alternative to BMT. Theses results are in favor of freezing cord blood in families in whom a transplant might be indicated.

Adolescent↗
PubMed1997

Disseminated Mycobacterium avium infection in a child with decreased tumour necrosis factor production.

UNLABELLED: Disseminated atypical mycobacterium infection is essentially reported in cellular immunodeficient children. Cell-mediated immunity including cytokines like tumour necrosis factor alpha (TNF) and gamma interferon (IFN) is the most important factor allowing control of the dissemination of Mycobacterium. We report a child with disseminated Mycobacterium avium infection without classical immunodeficiency or HIV infection. Immunological studies revealed a defect of TNF production when the monocytes of the patient were primed with endotoxin (Escherichia coli). CONCLUSION: This patient represents a further case of possible macrophage defect explaining the susceptibility to intracellular pathogens.

Child, Preschool↗
PubMed1997

A prospective study of minimal residual disease in childhood B-lineage acute lymphoblastic leukaemia: MRD level at the end of induction is a strong predictive factor of relapse.

We prospectively investigated minimal residual disease (MRD) in 51 children with B-lineage acute lymphoblastic leukaemia (ALL) treated according to the Fralle 93 protocol. PCR follow-up was performed in children in morphological and cytogenetic complete remission, provided an immunoglobulin (IgH) gene rearrangement could be detected using FR 3/J(H) amplimers. MRD was studied according to our previously described methodology, with a few modifications including the use of a consensus J(H) probe to control for PCR efficiency variations. Out of the initial 51 patients, 34 were assessable for MRD at the end of induction at the time of analysis. MRD levels were as follows: > 1/10(3) in 26%, 1/10(3) to 1/10(4) in 50% and < 1/10(4) or not detectable in 24%. With a median follow-up of 20 months there were five relapses, all of which occurred in the group of patients with MRD > 1/10(3). To date, none of the patients with MRD < or = 1/10(3) (good molecular responder) has relapsed. Classification according to molecular response at the end of induction did not correlate with the conventional risks groups: there were no statistically significant differences between good and bad molecular responders. Of particular interest is the absence of correlation between WBC at diagnosis and MRD level at the end of induction. We conclude that classification of patients into good and bad molecular responders using PCR seems to be a better prognostic indicator than conventional risk factors in childhood B-lineage ALL. Patients with MRD level > 1/10(3) have a particularly poor outcome and should always be considered for alternative therapeutic strategies in the future, whereas in good molecular responders belonging to poor or intermediate risk categories, treatment de-escalation might be contemplated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Hematopoietic stem cell transplantation for sickle cell anemia.

Hematopoietic stem cell transplantation is the only therapy able to cure sickle cell anemia at the present time. So far, transplantations have been undertaken in approximatively 140 sickle cell patients all over the world, with good results. The selection of patients for transplantation remains a subject of dilemma because of the unpredictable course of the disease and the lack of valuable prognostic markers. The selection criteria accepted so far concern young patients under the age of 16, with a morbid course of the disease and having a HLA-compatible sibling. In Belgium, patients going back to their country of origin were also considered for transplantation. For 100 patients who underwent transplantation in Europe, the current Kaplan-Meier estimates of overall survival, event-free survival, and disease-free survival rates are 90%, 79%, and 81%, respectively. Benefits and side effects are analyzed.

Adolescent↗
PubMed1996

Hydroxyurea for treatment of severe sickle cell anemia: a pediatric clinical trial.

Hydroxyurea (HU) enhances the synthesis of fetal hemoglobin (HbF) and can improve the clinical course of some adult patients with sickle cell anemia (SCA). In a randomized trial, we studied the biologic effects and the clinical benefit of HU in children and young adults with severe SCA. Twenty-five patients (median age, 9 years) were randomized to receive either HU (at the initial dosage of 20 mg/kg/d) or a placebo for 6 months and were then switched to the other arm for the next 6 months. Among the 22 evaluable patients (median age, 8 years), significant increases in HbF and mean corpuscular volume occurred during the HU treatment period. The white blood cell and reticulocytes counts decreased significantly, but these changes were not clinically relevant. Sixteen of 22 patients (73%) experienced a complete disappearance of events requiring hospitalization. The number of days of hospitalization as well as the number of hospitalizations for patients on HU, as compared with those for the patients receiving placebo, were significantly reduced. We conclude that treatment with HU in children and young adults is feasible, well-tolerated, and improves the clinical course of SCA. The long-term effects of HU require further investigation.

Adolescent↗
PubMed1996

Acetylcholinesterase from Bungarus venom: a monomeric species.

The venom of Bungarus fasciatus, an Elapidae snake, contains a high level of AChE activity. Partial peptide sequences show that it is closely homologous to other AChEs. Bungarus venom AChE is a non-amphiphilic monomeric species, a molecular form of AChE which has not been previously found in significant levels in other tissues. The composition of carbohydrates suggests the presence of N-glycans of the 'complex' and 'hybrid' types. Ion exchange chromatography, isoelectric focusing and electrophoresis in non-denaturing and denaturing conditions reveal a complex microheterogeneity of this enzyme, which is partly related to its glycosylation.

Acetylcholinesterase↗
PubMed1996

Radiographic skeletal survey and radionuclide bone scan in Langerhans cell histiocytosis of bone.

BACKGROUND: The lack of a consensus in the literature on the imaging strategy in Langerhans cell histiocytosis (LCH) bone lesions in childhood. OBJECTIVE: To evaluate the relative value of radionuclide bone scan (RBS) and radiographic skeletal survey (RSS) in the detection of LCH bone lesions, both in the initial work-up of the disease and during the follow-up period. MATERIALS AND METHODS: Ten children with bone lesions evaluated by means of RSS and RBS in a retrospective study (1984-1993). RESULTS: Fifty radiologically and/or scintigraphically abnormal foci were detected: 27 anomalies in the initial work-up (12 by both RSS and RBS, 8 by RSS only and 7 by RBS only) and 23 additional anomalies during follow-up (10 by both RSS and RBS, 10 by RSS only and 3 by RBS only). RSS+/RBS- lesions (n = 18) are more frequently encountered in the skull (P = 0.038), and more frequently lack radiologic signs of osteoblastic activity (P = 0.020), than RSS+/RBS+ lesions (n = 22). RSS-/ RBS+ abnormalities (n = 10) were most frequently insignificant. CONCLUSION: In the initial work-up both RSS and RBS should be carried out, while in the follow-up only RSS should be performed.

Adolescent↗
PubMed1996

Persistence of fetal hemoglobin production after successful transplantation of cord blood stem cells in a patient with sickle cell anemia.

A girl with sickle cell anemia was treated with cord blood transplantation combined with hematopoietic growth factor. Cord blood cells were collected from a sister with an identical human leukocyte antigen complex who was a carrier of the sickle cell trait (hemoglobin AS). The patient had complete engraftment and no graft-versus-host disease. The persistence of a high level of fetal hemoglobin 6 months after engraftment was noted.

Anemia, Sickle Cell↗
PubMed1996

Laparoscopic splenectomy in adults and children: experience with 31 patients.

BACKGROUND: Open surgery is the standard approach for splenectomy in hematologic disorders, but a few cases of successful laparoscopic splenectomy have been reported. METHODS: Thirty-one patients (18 adults, group 1; and 13 children, group 2) underwent laparoscopic splenectomy. Indications for surgery included idiopathic thrombocytopenic purpura (25 patients), congenital spherocytosis (4 patients), and hemolytic anemia (2 patients). In 97% of the patients the diameter of the spleen was less than 15 cm. RESULTS: Laparoscopic splenectomy was successful in 94% of the patients; conversion to open surgery was mainly related to hemorrhage. Accessory spleen was found in 39% in group 1 and 8% in group 2. Two adults received intraoperative autotransfusion. Postoperative morbidity was minimal. The median postoperative stay was 3 days (range, 2 to 12 days) in group 1 and 2 days (range, 2 to 5 days) in group 2. CONCLUSIONS: Laparoscopic splenectomy is safe in both adults and children. Adequate selection of patients (small-size spleen, splenic destruction on preoperative scanning of platelets), appropriate preparation in patients with idiopathic thrombocytopenic purpura (immunoglobulin G), and meticulous surgical technique (with routine opening of the gastrocolic ligament to search for accessory spleen) are key factors in obtaining the same long-term results as with open surgery.

Adolescent↗
PubMed1996

Bone marrow transplantation for sickle cell anemia.

The use of bone marrow transplantation for hemoglobinopathies was first proposed in thalassemia major and is now the therapy of choice for young patients affected by this disorder and having a suitable donor. Even though bone marrow transplantation is very effective in treating sickle cell anemia, enthusiasm for it is restrained by the unpredictable course of the disease. Selection criteria are difficult to establish and vary among medical teams and their patients' characteristics. Some of the factors playing a role in the decision are summarized in this article. They include genetic and environmental factors, features of the patient such as age or the presence of organ damage, and the possibility of using new alternative therapeutic approaches.

Anemia, Sickle Cell↗
PubMed1995

Allogeneic bone marrow transplantation for lysosomal storage diseases. The European Group for Bone Marrow Transplantation.

Patients with lysosomal storage disorders have visceral, skeletal, and neurological abnormalities and a limited life expectancy. Bone marrow transplantation has been used to correct the metabolic defects and leads to metabolic improvements in most patients. However, the long-term effect of such therapy is uncertain. We analysed the data from 63 patients transplanted for lysosomal storage diseases. The transplant-related mortality was 10% if an HLA-identical sibling marrow donor was available (n = 40) and 20-25% if mismatched tissue was used. Data on the effect of bone marrow transplantation on biochemical and clinical disease variables were available in 29 of the 63. 28 had a follow-up duration of 1.0-10.2 years; 1 patient died of disease progression in the first year after stable engraftment. 13 patients who had severe neurological symptoms at the time of transplantation showed disease progression. Engraftment of bone marrow in 5 patients with non-neuronopathic Gaucher's disease led to complete disappearance of symptoms. 11 patients had skeletal symptoms because of various mucopolysaccharidoses (MPSs). There was stabilisation of the skeletal lesions during the observation period of 1.4-6.4 years, but none of the patients showed significant regression of the skeletal symptoms. The visceral features (hepatosplenomegaly, cardiac hypertrophy, and upper airway obstruction) in these patients abated after transplantation. We could not evaluate the biochemical and clinical variables in 34 patients because of graft rejection, transplant-related mortality, or follow-up of less than 1 year. There were significant beneficial effects of bone marrow transplantation in patients with non-neuronopathic Gaucher's disease. Stabilisation of disease was observed in patients with MPS-I and MPS-II; this potential benefit needs to be confirmed by longer follow-up. Bone marrow transplantation was not effective if severe neurological symptoms were already present at the time of transplantation.

Adolescent↗
PubMed1995

Glycosylation of a novel member of the immunoglobulin gene superfamily expressed in rat carcinoma cell lines.

MAb E4 recognizes a 66-kDa glycoprotein, pE4, which is a member of the immunoglobulin gene superfamily. This protein is expressed at the cell surface in rat colon and mammary carcinomas, but only in trace amounts in normal adult rat tissues. Since expression of aberrant carbohydrate structures is often associated with malignant transformation, glycosylation of pE4 was analyzed. Reactivity of lectins with pE4 suggested the absence of N-acetylneuraminic acid, terminal galactose and O-linked glycan, and the presence of N-linked glycans. Tunicamycin treatment reduced the binding of MAb E4 to cancer cells suggesting that the E4 epitope is at least partially glycosylated. Digestions with neuraminidases, O-glycosidase and peptide-N-glycosidase F confirmed these results. Pronase treatment abolished the binding of MAb E4, indicating that E4 epitope involves not only a carbohydrate determinant but also a peptide moiety. Mild periodate oxidation abolished the binding of MAb E4, indicating that non-reducing terminus carbohydrates are part of the E4 epitope. Neutral sugar analysis revealed the absence of galactose and the presence of fucose. Since fucose is sensitive to periodate oxidation, this sugar could be the carbohydrate part of the determinant recognized by MAb E4. Reactivity of lectins specific for fucose indicated the presence of alpha(1-6)-fucose on pE4.

Adenocarcinoma↗
PubMed1995

[Primary tumor calcification in a case of Burkitt's lymphoma].

A case of abdominal Burkitt lymphoma in a 8-year-old boy is reported. The authors discuss a very unusual feature of this untreated lesion, intratumoral calcification remaining unchanged after 4 years of follow-up.

Antineoplastic Combined Chemotherapy Protocols↗