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Biomedical subjects

N Philippe

Publications and source records attributed to N Philippe.

At least 109 records · Page 6Linked to original sources
PubMed1987

Sequential cisplatin/VM-26 and vincristine/cyclophosphamide/doxorubicin in metastatic neuroblastoma: an effective alternating non-cross-resistant regimen?

We report the results of a French multicentric pilot study of remission induction therapy in metastatic neuroblastoma. Thirty-five successive unselected patients entered the study over 1 year and were treated by alternating sequences of cisplatin/VM-26 (PE) and vincristine/cyclophosphamide/doxorubicin (CADO). Three courses of each sequence were delivered. Disease reevaluation was extensive, with special focus on bone marrow status. Using strict criteria, 24 patients (68%) achieved a good partial response (GPR), which comprised normalization of bone marrow, and ten (28%) achieved a partial response (PR), and one progressed. The overall response rate was 96%. Thirty-two patients underwent surgery, and complete macroscopic removal of the primary was achieved in 21 (65%). After completion of induction and surgery, six patients (17%) were in complete remission (CRm), without evidence of any residual disease; nine (26%) were in very good partial remission (VGPRm; same as CRm except persistence of nonpathologically evaluable improved bone scan), and 19 (51%) were in partial remission (PRm). Toxicity was acceptable, and no treatment-related deaths occurred. These results show no substantial improvement compared with those previously reported with similar but nonalternating regimens. We advocate a two-category concept (response, remission) to describe initial therapy results in metastatic neuroblastoma and emphasize the need to assess bone marrow by an extensive evaluation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

High-dose chemoradiotherapy with bone marrow transplantation as consolidation treatment in neuroblastoma: an unselected group of stage IV patients over 1 year of age.

Since January 1983, 56 consecutive children over 1 year of age with stage IV neuroblastoma entered an aggressive protocol, including chemotherapy, radiation therapy, and bone marrow transplantation. The induction protocol included platinum and epipodophyllotoxin (VM-26), alternating with cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, OH), and vincristine (PE/CADO). Surgery was performed after 2 to 4 months, and consolidation with intensive chemoradiotherapy and bone marrow transplantation (BMT) was performed within 12 months of diagnosis. The combination of vincristine, melphalan and total body irradiation (TBI) was used before BMT, and no further treatment was administered before progression. With the exception of two allografts, autologous BMT (ABMT) was given in all cases and was purged using an immunomagnetic procedure (Kemshead technique) in 32 of 35 cases, and a chemical procedure in three of 35. Of the 56 patients, 45 were evaluable. Of those, 23 were grafted in partial remission (PR), and 14 were grafted in either complete remission (CR) or very good partial remission (VGPR). The acute toxic death rate was 19%, the relapse rate was 32%, and the progressive disease rate was 19%. The progression-free survival in the CR/VGPR group (ie, 44% at 32 months post-diagnosis) and in the PR group (13% at 32 months) was not significantly different (P greater than .05). At 24 months, the overall survival of the 56 unselected patients was 39% compared with 12% for comparable patients previously treated by our group (P less than .005).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Prevention of graft-versus-host disease in HLA-matched bone marrow transplantation for malignant diseases: a multicentric study of 62 patients using 3-pan-T monoclonal antibodies and rabbit complement.

In order to evaluate the effectiveness and reproducibility of T cell depletion in human leukocyte antigen (HLA)-matched bone marrow graft to prevent graft-v-host disease (GVHD), our multicentric study (nine different centers) investigated 62 consecutive patients with poor prognosis leukemia or hematosarcoma from June 1984 to November 1985. The data were updated October 1, 1986, and the mean follow-up was 18 +/- 4.3 months. T cells were depleted with a combination of 3-pan-T cell monoclonal antibodies (CD2 "D66"; CD5 "A50"; CD7 "I21") with a single incubation of rabbit complement (C'). The average number of T cells infused was 0.66 X 10(6) +/- 0.56/kg body weight. Twenty-six patients received chemoprophylaxis for GVHD, 16 received methotrexate, and ten received cyclosporin A. Only a single case of severe (greater than grade II) GVHD was observed, yet the incidence of graft failure was 19%. Factors that might have influenced the occurrence of graft failure appear to be the lack of radiotherapy in the conditioning regimen; the conditioning regimen itself (fractionated total body irradiation [TBI], 12 Gy, v single dose is better than TBI, 10 Gy, but still not statistically significant); and the age of the patients (high-risk after 30 years of age). In contrast, neither the number of nucleated cells reinfused nor the level of T cell depletion (provided the T cells were below critical numbers) seemed to have an influence, nor did chemoprophylaxis for GVHD or splenectomy in chronic granulocytic leukemia (CGL) patients. The survival of graft failure patients was very poor (one of 11; survival at 15 months of the initial graft). Thus, our study demonstrates the reproducibility and high effectiveness in preventing GVHD by immunodepletion of T cells in a large-scale multicentric assay, in which compliance with the protocol of immunodepletion was reasonably good. This study thus provides interesting clues to overcoming graft rejection.

Adolescent↗
PubMed1986

Sp alpha I/65 hereditary elliptocytosis in North Africa.

The Sp alpha I/65 variant of the spectrin has been recently described in black people with hereditary elliptocytosis (HE). The present study reports on a similar Sp alpha I/65 variant in nine North African persons belonging to four unrelated families. The abnormality was associated with a variable degree of elliptocytosis. In one case, red cell morphology was normal. In the nine carriers of the biochemical abnormality, the spectrin dimer self-association was defective. The association constant was reduced: 0.65 to 1.7 X 10(5) M-1 (controls: 4.6 +/- 0.5 X 10(5) mM-1 (n = 21)); in six cases, there was a higher level of spectrin dimer in the low ionic strength extract at 4 degrees C: 13.0 to 19.7% (controls: 6.4 +/- 2.1% (n = 7)). Limited tryptic digests of spectrin from the nine persons revealed a decrease of the 80,000-dalton alpha-1 domain, and the concomitant appearance of a peptide with a molecular weight of 65,000 daltons and an isoelectric point ranging from 5.0 to 5.1. There was a correlation between the proportion of the 65,000-dalton fragments, the defect of spectrin self-association, and the extent of morphological alteration. This is the first large series concerning a spectrin abnormality in non-black persons. In North Africa, cases of HE that are not due to a protein 4.1 defect have turned out so far to be associated with the Sp alpha I/65 variant.

Algeria↗
PubMed1986

[Acute parvovirus B 19-induced erythroblastopenia and hereditary spherocytosis. Apropos of 1 pediatric case and review of the literature].

Authors report a new case of acute erythroblastopenia linked to a parvovirus B 19 infection by a 10 years old boy suffering from an hereditary spherocytosis. Aurillac antigen or parvovirus B 19 is one of the smallest virus to be known. It has been well demonstrated in vitro that the virus inhibits especially erythropoiesis but mechanism remains unclear. Systematic vaccination of all children at risk with congenital or acquired chronic haemolytic anaemia should be in the near future the best prophylaxis of parvovirus B 19 infections.

Acute Disease↗
PubMed1986

[Seriousness of severe acquired aplastic anemia in children. Apropos of 32 cases].

Thirty-two cases of severe aplastic anemia in children less than 16 years of age, observed between 1967 and 1985 in the Rhône-Alpes area were studied retrospectively. A toxic cause was suspected in 7 cases, an hepatitis in 5 cases. Patients presented with 2 of the 3 following cytopenias during the 3 weeks following diagnosis: hemoglobin level below 100 g/l, reticulocyte count lower than 20 G/l, neutrophil polymorphonuclear leukocyte count below 0.5 G/l, platelet count lower than 20 G/l. Whatever the treatment, prognosis was poor: 6 surviving patients (18.7%). Nineteen patients did not undergo bone marrow transplantation: only 2 are surviving after 4 years, one after low dose corticosteroid therapy, the other after antilymphocyte globulins and androgen therapy; 10 of 17 deaths occurred in the first 4 months. Thirteen bone marrow transplantations from sibling donors, of which 10 HLA A, B DR identical and 3 haploidentical allowed for 8 prolonged takes but only 4 survivors of whom 2 lasted for more than 2 years.

Anemia, Aplastic↗
PubMed1986

[Allogeneic bone marrow transplantation in acute lymphoblastic leukemia of children. Analysis of prognostic factors. GEGMO (Bone Marrow Study Group) study].

Sixty-five children with acute lymphoblastic leukemia (ALL) underwent allogenic bone marrow transplantation (BMT) from an HLA identical donor, following cytoreduction with cyclophosphamide and total body irradiation (TBI): 15 were transplanted in 1st remission, 43 in 2nd and 7 in 3rd or in 4th. The Kaplan Meier estimate of surviving disease free at 4 years post BMT was 49.9% and the probability of continued remission at 4 years was 63.3%. Fourteen patients relapsed between 90 and 690 days (mean: 240 +/- 88) post BMT. The other causes of BMP failure included: graft versus host disease, veno-occlusive disease and sepsis. No interstitial pneumonitis has been reported. Patients who had a relapse while on chemotherapy had a higher probability of relapse than those who had a relapse while off therapy (p less than 0.01). We conclude that allogeneic BMT is the treatment of choice for children with ALL in second hematologic remission, the interval between diagnosis and first relapse being the most significant prognostic factor. Patients with poor prognosis might benefit from a more intensive chemotherapy/total body irradiation schedule or a BMT earlier in the course of their disease.

Adolescent↗
PubMed1985

Intravenous plasmin-treated gammaglobulin therapy in idiopathic thrombocytopenic purpura. Results in 40 patients.

A study of the effects of high-dose IV plasmin-treated IgG was undertaken in 40 patients (30 children and 10 adults) with idiopathic thrombocytopenic purpura (ITP). After a first course of treatment, a success therapy (platelet counts greater than 100 X 10(9)/l) was observed in 21 patients. The results after additional courses of pH 4 treated IgG in 7 patients tended to indicate that the 2 kinds of concentrates might induce similar platelet responses. No significant side-effects were observed. Platelet associated (PA), IgG, IgM and C3 levels were determined before therapy and on the 7th day after the first infusion (day 8) in 27 patients (36 courses). In spite of great variability, overall results showed a significant decrease in PA IgG (P less than 0.05), PA IgM (P less than 0.01) and PA C3 (P less than 0.001) at day 8. A significant inverse relationship was found between either PA IgG, or PA IgM or PA C3 levels, and platelets counts (respectively, r = -0.57, -0.55, -0.66, P less than 0.001). Our results also showed that pretreatment platelet counts were higher in patients with success therapy (25.8 +/- 16.9 X 10(9)/l) than in others (11.3 +/- 12.1 X 10(9)/l, P less than 0.001). This suggested that pretreatment platelet counts could help predicting the platelet response.

Adolescent↗
PubMed1985

Massive therapy and autologous bone marrow transplantation in very bad prognosis Burkitt's lymphoma.

During 1980-1983, two major advances were made in the treatment of Burkitt's lymphoma (BL): conventional but aggressive chemotherapy raised the overall survival rate from 42% with the SFOP1 protocol, COPAD, to 80% with SFOP protocols LMB 01 and 02; and massive chemotherapy followed by autologous bone-marrow transplantation (ABMT) enabled 40% of relapses to be cured. Ten patients included in the COPAD protocol were treated with massive therapy: seven because of relapse, one because of partial remission after two months' induction therapy and two because of long delay before first complete remission (CR). The therapy used was bischloroethyl nitrosourea, cytosine arabinoside, cyclophosphamide (CPM) and 6-thioguanine (BACT) in nine cases and CPM in one. The response rate was 100%, and disease-free survival was reached in five of ten cases, including four with no evidence of disease for over two years. In nine of ten patients who received ABMT, the bone marrow (BM) was not decontaminated, and BM involvement was found at death prior to day 86 from ABMT in four of five failures. Clinical and cytological analyses led to no firm conclusion about the role, if any, of reinjected BM in this outcome: a liquid-culture monitoring system used in six cases showed BM malignant cells present in the graft in one early relapse and absent in two relapses in which BACT failed; in three long-term survivors, no malignant cell was found in the graft. This first group of ten showed the efficiency of BACT and the necessity of purging BM in at least some cases before ABMT. Of the second group, selected from 43 patients given LMB 01 and 02 protocols, eight were treated by massive therapy and ABMT: one with localized stages I and II disease, four with stage III and three with stage IV. These patients received massive therapy either because of early relapse, progressive disease, partial remission after induction therapy or long delay before CR, or as a consolidation of CR in cases of central nervous system or cerebrospinal fluid involvement. In this group, four of eight are disease-free; three of them had normal BM by in-vitro liquid-culture monitoring; their BM was not decontaminated and they had no BM relapses. In the other five cases, BM was decontaminated by Asta Z in one and by y-29/55 antibody in four.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1983

Massive BACT chemotherapy with autologous bone marrow transplantation in 17 cases of non-Hodgkin's malignant lymphoma with a very bad prognosis.

A group of 12 children and 5 adults, all with diffuse non-Hodgkin's malignant lymphoma (NHML), received massive chemotherapy regimens. The stages of the disease were as follows: 7 patients were in second complete remission; 6 in a progressive phase of the disease; and 4 in first complete remission which occurred late in the course of the disease. All patients received BACT (BCNU+aracytine+cyclophosphamide+thioguanine) or TACC (idem with CCNU) at different dose levels: 6/17 received 10 Gy total-body irradiation (TBI) after BACT treatment; 16/17 received autologous bone marrow transplantation (ABMT) previously stored in liquid nitrogen to combat the medullary effects of chemotherapy. Direct therapy-related deaths occurred in 4/17 patients (1 Aspergillus endocarditis; 1 Moskowitz syndrome; 1 veno-occlusive disease of the liver; and 1 Escherichia coli pneumopathy) and 6/17 patients relapsed between days 25 and 70 of treatment. Seven out of these 17 patients are still alive NED 102-900 days (mean, 475 days) after the beginning of therapy without receiving maintenance treatment. Massive chemotherapy could thus be the best treatment for NHML in relapse, but the high percentage of early therapy-related deaths is a strong limiting factor for patients before relapse.

Adolescent↗
PubMed1983

[Varicella-zoster virus infections in the immunosuppressed child. Treatment with Acyclovir and controls].

Sixty minutes intravenous infusions of Acyclovir were given at 5 to 10 mg/kg 3 times daily for 6 to 11 days in 20 immunodeficient children with varicella (9 cases) and herpes zoster (11 cases) in a controlled open study. Twelve patients had a life-threatening illness. All patients who received therapy before the first 4 days had a more rapid cessation of new vesicles formation and more rapid scarring. Fourteen controlled children had accelerated clearance of viral antigens from vesicles. In 19 cases, virus was no longer isolated after the 3rd day. Eighteen patients recovered within 6 to 10 days. No relapse of varicella zoster virus infections had been observed 1 to 18 months after the end of treatment. Two children with varicellous interstitial pneumonia died 8 and 32 days after the end of treatment. In 3 cases, zoster pains reappeared 8 days after Acyclovir therapy was stopped. The drug was well-tolerated, but control of renal functions is necessary.

Acyclovir↗