Biomedical subjects
Publications and source records attributed to D Frappaz.
The authors report on a pediatric case of transient neutropenia with erythroblastopenia secondary to human parvovirus infection occurring in a child without underlying hemolytic disease. The heterogeneity of hematologic manifestations in such infections is discussed.
Treatment modalities of childhood brain tumors are associated with adverse neuropsychologic sequelae that may be manifested years after therapy. Based on recent published studies, the authors review the etiological factors, the symptoms and the evolutive features of these disorders and their management.
Glioblastomas and medulloblastomas are models for studying the implication of growth factors and oncogenes in tumor development. Amplification and/or hyperexpression of oncogenes result in products that may mimic growth factors and/or their receptors; cells may demonstrate autocrine and/or paracrine activity. Prognostic implications of such findings are suggested.
The authors review the literature concerning chromosomal abnormalities in childhood brain tumors: medulloblastomas, ependymomas, and gliomas of low and high grade. Though these technics require further development, they highlight the role of cytogenetic modification in oncogenesis of brain tumors.
Medulloblastoma is a frequent brain tumor in childhood. Recent advances in histogenesis, management of early and late side-effects, and prognosis are discussed in this review.
Despite great histological polymorphism, clinical features of supratentorial brain tumors are mainly limited to neurological deficit, and focal epilepsy and/or symptoms secondary to raised intracranial pressure. The treatment relies on surgery and radiotherapy; chemotherapy has not yet demonstrated its efficacy. Failures are explained by the limitation of neurosurgery, and by the toxicity of the radiotherapy that precludes the use of high dosages. Some good vital results are hampered by neuropsychic sequellae.
Based on the experience acquired in post-natal liver transplantation since 1974, we recently initiated pre-natal, in utero stem cell transplantation from the human fetal liver. The first two fetuses that we treated had immunodeficiencies, the third one had thalassemia major. Donors and recipients were not matched. The fetal cells were infused in the umbilical vein of the first two patients and injected intraperitoneally into the third one, under ultrasonic visualization. The first patient, born in 1988, has both engraftment of donor cells and reconstitution of cell-mediated immunity. This child, who had bare lymphocyte syndrome, has no clinical manifestation of the disease and he lives normally at home. The second child, born in 1989, has not yet developed a significant reconstitution of immunity although donor cell engraftment has been proven (Y chromosome in this female patient). The third patient has also evidence of donor cell take (Y chromosome in a female patient) but the effect on thalassemia has not yet been fully analyzed (donor hemoglobin present in small quantity). In all 3 cases, no side-effect of any kind developed in the mother nor in the fetus. Several advantages appear to be associated with in utero FLT: increased probability of graft take, ideal isolation of patient (in the uterus), optimal environment for fetal cell development (in the fetal host).
Explore the source record for details and available documents.
Explore the source record for details and available documents.
From August 1985 to April 1988, 17 patients have been allografted in France for TM. Fourteen (82%) are alive, 10 (58%) are cured and 4 in autologous reconstitution. Three died, 2 of whom after a second transplantation, and 2 due to CMV interstitial pneumonia. Ten of 17 were conditioned by cyclophosphamide (Cy: 200 mg/kg) and busulfan (Bu: 14 mg/kg): 10 are alive, 6 cured and 4 in autologous reconstitution. Five received Cy (200 mg/kg) Bu (16 mg/kg) +/- total lymphoid irradiation (TLI) (3 patients): 2 patients are cured (one after hepatic veno-occlusive disease), and 3 died. For 2 patients, conditioning included total body irradiation: both are cured. Graft versus host (GVH) reaction prevention included: 4 T cell depletion (with additional prevention in 3; 2 are cured, one is in autologous reconstitution, 1 died); 5 cyclosporine alone (2 cured, 2 autologous reconstitution, 1 dead) and 8 cyclosporine + methotrexate (6 cured, 1 autologous reconstitution, 1 dead). Four of 12 evaluable patients presented a less than or equal to 2 grade acute GVHd. None had received a T cell depleted marrow. Bone marrow transplantation is the only curative treatment currently available for TM patients with HLA identical donors. It should be proposed to any young patient before iron overload is established. Optimal conditioning includes Cy (200 mg/kg) + Bu (14 mg/kg). The best protocol for GVHd prevention remains to be defined.
Thirty-one patients, 13 adults and 18 children, were included in a phase II study of combined treatment with CDDP 40 mg/m2 and VP16 100 or 200 mg/m2 for 5 days. Fourteen patients were primary refractory to front-line treatment and 17 were treated at relapse (9 on therapy, 8 off therapy). Four were low-grade follicular lymphomas, 7 intermediate grade lymphomas, and 20 high grade lymphomas. One of the 14 primary refractory cases responded (CR) whereas 3 PR and 10 CR were observed among the 17 relapses. Toxicity was acceptable. 9 patients are still alive after bone marrow transplantation (median survival, 16 months). This combination is an effective salvage regime before autologous bone marrow transplantation for relapsed NHL, but cannot be recommended for progression on front-line therapy.
The effect of epidermal growth factor (EGF) on the in vitro growth of human malignant tumors was compared in serum-supplemented (n = 54) and serum-free (N = 41) media at clonal density to determine the true EGF dependency of tumors. In the complete absence of serum at a 1,000 cells/cm2 seeding inoculation (approximately 100-200 adherent cells), EGF increased growth by greater than 50% in 27 of 41 specimens (66%), and growth increased by 100% or more in 18 of these EGF-sensitive tumors. In 12 serum-free cultures (29%), in vitro growth failed to occur without EGF. With 10% serum supplementation and a lower cell density (250 cells/cm2), EGF increased growth by greater than 50% in 34 of 54 specimens (63%), of which 25 had more than a 100% increase. The maximum growth induced by EGF in serum was usually seen in those tumors already capable of moderate in vitro growth. No difference in response to EGF was detected between specimens from primary tumors (n = 24) and those from metastases (n = 30). Under the stringent culture conditions of complete absence of serum and with tumors seeded at a low cell number, EGF stimulated most primary or metastatic human tumors to establish and sustain short-term in vitro growth successfully.
Explore the source record for details and available documents.
The authors (pediatricians and psychiatrists) report on a three-year-experience of joint interviews with parents of children with malignant diseases. These meetings, held at diagnosis and a few months afterwards, throw a light on the familial environment and help parents in expressing their feelings towards their traumatic situation.
Acute methotrexate intoxication occurred in 4 patients despite adequate alkaline hyperhydration and classical folinic acid rescue. Three of these patients had no previous risk factor. Charcoal haemoperfusion with haemodialysis was promptly instituted and the methotrexate blood levels rapidly decreased, avoiding further renal damage and multisystemic involvement. Chemotherapy could subsequently be performed in 3 of the 4 patients without delay and toxicity. Charcoal haemofiltration appears to be an excellent treatment of methotrexate intoxication.
Using the adhesive tumor cell culture system, we studied the effect of epidermal growth factor (EGF) on 16 primary and 7 metastatic fresh human tumors of the nervous system cultured in serum-free and serum-supplemented media at low cell density. In serum-free conditions, EGF significantly enhanced the growth of glial tumor cells. This positive effect was less pronounced for metastases to the brain. No significant enhancement was observed for the other tumor types (primitive neuroectodermal tumors and various tumors of neuroepithelial/mesenchymal origin). The addition of serum obscured this effect of EGF, even at the lowest cell densities. In 7 tumors, the simultaneous addition of platelet-derived growth factor did not enhance the EGF response. Subtypes of brain tumors respond to EGF in vitro under serum-free conditions.
Eleven autologous bone marrow transplantations (ABMT) were performed in 10 patients with T lymphoblastic lymphoma. All patients were grafted because of a very bad prognosis: 2 cases of progressive disease (1 primary failure, 1 resistant relapse): 0/2 alive, 2 late complete remissions: 1/2 alive, 7 sensitive relapses (2/7 alive). Finally, 3 out of 10 patients are survived. This salvage therapy for a failure of a front line strategy with 78% disease-free survival without ABMT seems of interest. ABMT is still indicated as salvage therapy for 20% of these patients.
Autologous bone marrow transplantation is now a major tool in the treatment of human leukemias and lymphomas. Evaluation of residual disease by standard cytological methods is difficult. Cytogenetics provide clonal markers which are specific features of leukemic cells. Detection of minimal disease by chromosomal methods is possible in acute leukemias, it requires karyotyping of a few hundred metaphases from a short term culture. A preselection of the material to be examined will improve the degree of sensitivity of the method.