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D Maraninchi

Publications and source records attributed to D Maraninchi.

At least 145 records · Page 8Linked to original sources
PubMed1993

[Cytokines and malignant hemopathies: leukemias and bone marrow graft].

Cytokines are now part of the modern armentarium utilized against malignant blood diseases. The essentially lymphocytic haematopoietic growth factors (G-CSF, GM-CSF, IL-3) reduce the infectious morbidity associated with the deep and prolonged neuropoenia induced by the myelo-ablative conditioning for autologous or allogeneic bone marrow transplantations, and widening their indications is tempting. The reluctance expressed about their use in chemotherapy of acute myeloid leukaemia is abating now that controlled studies have shown that they preserve the complete response rate and shorten the duration of leucopoenia. Moreover, they modify the leukaemia biological response, which makes it possible to increase the cytotoxicity of certain drugs and constitutes a new approach to drug-resistant leukaemias. Immuno-modulating cytokines (interferon alpha, interferon gamma, interleukin-2) act through mechanisms that are still ill-defined: antitumoral activity, modification of biological responses, immunoactivation. Nevertheless, interferon alpha has revolutionized the treatment of hairy cell leukaemia and myeloid leukaemia, with a 70% remission rate. The scarcity of complete responses (10% of hairy cell leukaemias) or cytogenetic responses (20% of chronic myeloid leukaemias) justifies a combined treatment (chemotherapy+immunotherapy?) to improve these patients' cure rate. The anti-leukaemic activity of interleukin-2, observed in patients with refractory relapses, produces 33% of responses, including 10% of complete responses, and it is tempting to test the impact of this immunotherapy on the control of residual leukaemia as adjuvant of complete remission using randomized trials.

Antineoplastic Agents↗
PubMed1993

Autoimmune polyendocrine failure--type 1 (insulin-dependent) diabetes mellitus and hypothyroidism--after allogeneic bone marrow transplantation in a patient with lymphoblastic leukaemia.

In this report we describe a patient who, after allogeneic bone marrow transplantation from her HLA-identical sister, developed polyendocrine failure in the form of Type 1 (insulin-dependent) diabetes mellitus and hypothyroidism. This was the result of the transfer of donor lymphoid cells which were activated by allogeneic bone marrow transplantation. The full chimerism of the recipient was demonstrated by restriction fragment length polymorphism analysis from nucleated blood cells and fibroblast DNA. During the 9-year follow-up, the donor developed hypothyroidism and signs of pre-Type 1 diabetes. This clinical observation resembles the adoptive transfer of diabetes observed in non-obese-diabetic mice and BB rats and confirms the role of immune processes in the pathogenesis of this disease.

Adolescent↗
PubMed1993

High-dose chemotherapy with etoposide, cyclophosphamide and escalating dose of carboplatin followed by autologous bone marrow transplantation in cancer patients. A pilot study.

25 patients with poor-prognosis malignancies were treated with a combination of fixed-dose etoposide (1750 mg/m2), cyclophosphamide (6400 mg/m2) and escalating doses of carboplatin (from 800 to 1600 mg/m2) followed by autologous bone marrow transplantation (ABMT). The median duration of granulocytopenia (< 500/mm3) and thrombocytopenia (< 20,000/mm3) was 23 days and 20.5 days, respectively. The main non-haematological toxicity was gastro-intestinal, with moderate to severe diarrhoea in 15 patients. No significant renal toxicity was observed. 2 patients died early due to toxicity. The overall response rate was 58% including 42% having complete responses. 4 of the 25 patients are alive with no evidence of disease at 22, 27, 40 and 43 months after ABMT. The encouraging antitumoral activity of this regimen makes it a good candidate for intensified chemotherapy in patients with various malignancies. Toxicity is acceptable and may be reduced in the near future with the widespread use of haematopoietic growth factors.

Adolescent↗
PubMed1993

A tumour-associated antigen expression in human haematological malignancies.

Objective responses obtained with high-dose in vivo recombinant interleukin 2 (r-IL2) in some leukaemic patients suggest among other hypotheses that blasts might express tumour rejection antigens potentially recognized by cytolytic T lymphocytes. Such antigens have been described in human melanomas and the MAGE-1 gene, coding for a tumour rejection antigen was recently identified. This gene is expressed in various solid tumours, but not in normal cells. We have screened a panel of haematological malignancies by reverse transcription and PCR and we report that MAGE-1 is not expressed in the blasts from 48 patients whereas three cell lines derived from leukaemias express this gene.

Antigens, Neoplasm↗
PubMed1993

In vitro inhibition of interleukin-2-induced defective polymorphonuclear chemotaxis by TNF inhibitor.

Patients undergoing immunotherapy with interleukin-2 experience multiple side effects and are highly susceptible to bacteremia. In a previous study, we confirmed that a profound deficiency of neutrophil chemotaxis is induced by interleukin-2 therapy. Migration in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP), being normal before therapy, was markedly impaired after the first cycle and further decreased after the third cycle of treatment. A direct effect of interleukin-2 on neutrophil chemotaxis is controversial. However, peripheral blood cells exposed to interleukin-2 secrete secondary cytokines. In particular, the release of tumor necrosis factor after interleukin-2 injection has been proposed as an important regulatory mechanisms. When testing random migration and chemotaxis of neutrophils from normal subjects after incubation with the serum from treated patients, we found that this serum induced a defective chemotaxis similar to that of neutrophils from interleukin-2-treated patients. In order to assess the influence of tumor necrosis factor, we tested the effect of anti-tumor necrosis factor-alpha antibody on the chemotactic response of cells after incubation with the serum, and we observed a dose-dependent reduction of neutrophil chemotaxis deficiency. These data suggest that TNF is counteracting the neutrophil chemotactic deficiency observed during IL-2 treatment.

Adult↗
PubMed1993

Escalating high-dose carboplatin and autologous bone marrow transplantation in solid tumors.

Twenty-seven patients with poor-prognosis malignancies were treated with a combination (CARBOPEC) of fixed-dose etoposide (1,750 mg/m2), cyclophosphamide (6,400 mg/m2), and escalating doses of carboplatin (from 800 to 1,600 mg/m2) followed by autologous bone marrow transplantation (ABMT). All patients had previously received platinum derivatives. The diagnoses were as follows: germ cell tumors (GCTs; n = 15); ovarian carcinomas (n = 8); rhabdomyosarcomas (n = 3), and Hodgkin's disease (n = 1). All 27 patients were fully evaluated for toxicity. The median duration of granulocytopenia (leukocytes < 0.5 x 10(9)/l) and thrombocytopenia (platelets < 20 x 10(9)/l) was 23 and 20 days, respectively. Hematologic growth factors were used in 3 cases. The main nonhematologic toxicity was gastrointestinal, with moderate to severe diarrhea in 18 patients. No significant renal toxicity was observed. The overall response rate to this high-dose chemotherapy was 55%, with a complete response (CR) rate of 45% (9 patients). The median duration of CR was 9 months. Five of the 27 patients are alive with no evidence of disease (NED) at 5, 22, 27, 40, and 43 months after ABMT. Four of the 11 patients with refractory GCTs have NED at 5, 22, 27, and 40 months, together with 1 of the 3 responders (43 months). Our study shows the encouraging antitumor activity of this regimen. Similar chemotherapy schedules have also been used with high response rates in GCT, ovarian cancer, breast cancer, and soft tissue sarcoma in children. The CARBOPEC protocol seems to be a good candidate for therapy intensification in patients with various malignancies. A European trial for salvage therapy in GCT will be activated in the near future. Moreover, results should improve with the widespread use of hematopoietic growth factors and optimization of carboplatin administration that takes pharmacokinetic parameters into account.

Adolescent↗
PubMed1993

Incidence rate and risk factors for thyroid dysfunction during recombinant interleukin-2 therapy in advanced malignancies.

Immunotherapy using recombinant interleukin 2 (rIL-2) has been shown to induce thyroid dysfunction in some cancer patients. The purpose of the present study was to evaluate the incidence and risk factors of this adverse autoimmune response. Triiodothyronine, thyroxine and thyrotropin levels were measured serially in 146 consecutive patients treated with rIL-2 for refractory solid tumor (77 patients) or malign hemopathy (69 patients); rIL-2 was administered intravenously in 5-day cycles (18 x 10(6)-24 x 10(6) IU.m-2.day-1) either alone in 79 cases or in combination with autologous bone marrow transplantation in 26 cases, with interferon-gamma in 37 cases, with tumor necrosis factor-alpha in 13 and with cyclophosphamide in five cases. Some patients underwent more than one therapeutic protocol. Peripheral hypothyroidism was present upon entry in nine (6.2%) patients. Thyroid dysfunction appeared or worsened during rIL-2 therapy in 24 (16.4%) patients. Sixteen (10.9%) patients exhibited peripheral hypothyroidism, out of which four exhibited biphasic thyroiditis. Another five (3.4%) patients developed transient hyperthyroidism. Anomaly could not be classified in three patients. Thyroid dysfunction appeared early after one or two cycles. All surviving patients recovered. Only gender and presence of antithyroid antibody were correlated significantly with rIL-2-induced thyroid abnormalities. No correlation was found with any of the other risk factors studied, i.e. type of malignancy, rIL-2 treatment procedure, clinical efficacy, evolution of circulating lymphocyte subsets or other autoimmune antibodies. Antithyroid antibodies were detected in 60.9% of patients with this complication. Thyroid-stimulating antibodies were never detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

[High dose chemotherapy with autologous bone marrow transplantation in ovarian adenocarcinoma].

The present treatment of advanced ovarian adenocarcinoma patients is unsatisfactory, with 5-year survival rates of less than 15%. To obtain better results, one possibility is the use of therapeutic intensification with autologous bone marrow support. In effect, there is a known dose-response relationship in ovarian carcinoma, especially with alkylating agents. To date, a 69% response rate has been achieved with this kind of treatment in 39 patients refractory to standard therapy. However, responses are of short duration, with a median range of 6-7 months. Therapeutic intensification has been used in over 100 patients, as consolidation therapy, following first-line chemotherapy. For these patients, projected 3-year overall survival and disease-free survival rates are 30-50% and 20-40% respectively. These results compare favorably to those of standard therapy. Early deaths are more frequent in refractory patients (18%). Complete hematological recovery usually occurred within 3-4 weeks. Extra-hematological toxicity is related to previous treatment and to cytotoxic drugs used during intensification. These preliminary results, limited to a small series of patients, are sufficiently promising to continue and extend these trials.

Adenocarcinoma↗
PubMed1993

Pulmonary function changes 100 days and one year after bone marrow transplantation.

The pulmonary function of patients receiving autologous or allogeneic bone marrow transplantation (BMT) was studied before, 100 days after and 1 year after BMT. The 117 patients studied before transplantation showed a slight reduction in average total lung capacity (TLC) and transfer coefficient (KCO). These reductions were related to haematological disease, previous pulmonary disease or irradiation, or use of toxic lung chemotherapy. Studies 100 days after BMT showed TLC and KCO decreases of 5% and 8%, respectively. These decreases were related to different factors in autologous and allogeneic BMT. The results were influenced by previous pulmonary status in autologous BMT patients and the occurrence of GVHD in allogeneic BMT patients. Seventy patients underwent pulmonary function testing 1 year after BMT. The decrease in TLC values was greater in autologous BMT than in allogeneic BMT patients (107 +/- 3% to 100 +/- 3% versus 113 +/- 3% to 112 +/- 2%, respectively) although TLC remained normal in both groups. KCO values dropped significantly in both populations. Relapse of the initial disease was an important factor impairing lung function in the autologous group. TLC and KCO changes were strongly related to mortality in both groups. These results emphasise the need for frequent pulmonary function tests after BMT to detect and quantify lung function changes.

Adult↗
PubMed1993

The clinical consequences of haematological and non-haematological toxicity following bone marrow transplantation and the possible impact of haematopoietic growth factors.

Bone marrow transplantation (BMT) is a rescue therapy used in conjunction with high-dose chemotherapy, which is an effective treatment for overcoming resistant disease in selected malignancies. However, highly intensive preparative regimens produce severe life-threatening toxicity which may be haematological or non-haematological. Despite extensive supportive care including isolation, empiric antibiotic use and parenteral nutrition, toxicity is associated with a significant level of morbidity and mortality. A major cause of morbidity is infection resulting from the period of neutropenia caused by the ablation of the patient's marrow. The haematopoietic growth factors (HGFs) may provide effective therapy for improving haematopoietic reconstitution and therapy decrease the risk of infection, days of hospitalisation and subsequently reducing overall treatment cost. They may also be useful for enhancing neutrophil function, improving bone marrow yield and mobilising peripheral blood progenitor cells (PBPC). Recombinant G-CSF or GM-CSF may, therefore, improve the safety of the BMT procedure and increase its application to a greater number of patients.

Bone Marrow Transplantation↗
PubMed1993

HIV infection in autologous and allogeneic bone marrow transplant patients: a retrospective analysis of the Marseille bone marrow transplant population.

Twelve HIV-positive patients who either underwent or seroconverted after bone marrow transplantation (BMT) at the University of Marseille between 1981 and 1985 were reviewed in order to observe their rates of development of AIDS. Two patients were HIV positive prior to transplantation, while ten seroconverted after transplantation. Six patients underwent autologous BMT and six underwent allogeneic BMT; all of their respective donors were seronegative. Eleven patients developed AIDS (92%), with a mean AIDS-free time (AFT) of 1 year 8 months after BMT. Seven of those subjects died, with a mean survival over a 5-year follow-up period of 2.14 years after BMT. Five autologous recipients had a mean AFT of 2 years 3 months, with the sixth patient being AIDS free. The mean AFT for the allogeneic recipients was 1 year 2 months (p = NS), all of whom developed AIDS. These data suggest that the development of AIDS was rapid from the time when our patients seroconverted. However, this was not initially accompanied by poor survival. In summary, BMT may be indicated for HIV-positive patients who required myeloablation, despite an enhanced development of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Allogeneic bone marrow transplantation for acute myeloid leukemia in first remission: a randomized trial of a busulfan-Cytoxan versus Cytoxan-total body irradiation as preparative regimen: a report from the Group d'Etudes de la Greffe de Moelle Osseuse.

From October 1987 to December 1990, 101 patients with acute myeloid leukemia (AML) were randomized to be transplanted in first complete remission (CR1). Preparative regimen including Cytoxan (120 mg/kg) with total body irradiation (CYTBI) (N = 50) or busulfan (16 mg/kg) (BUSCY) (N = 51) was followed by allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling. Mean time between diagnosis and BMT was 119 days. The outcome for CYTBI at 2 years is better for probability of disease-free survival (DFS) (72% v 47%) (P less than .01), survival (75% v 51%) (P less than .02), relapse (14% v 34%) (P less than .04), and transplant mortality (8% v 27%) (P less than .06). In multivariable analysis, higher relapse and decreased survival and DFS were associated with BUSCY regimen, while chronic graft-versus-host disease also influenced independently the probability of relapse. This demonstrates the present limitation of busulfan use in this setting, possibly due to probable individual variations in biodisponibility. Furthermore, besides the anti-leukemic effect of preparative regimens, this trial points out the progress accomplished in BMT management (transplant mortality = 8% in CYTBI) over the last 20 years as well as the effectiveness of transplant in early first CR after CYTBI (DFS = 72% at 2 years).

Actuarial Analysis↗
PubMed1992

Pharmacokinetics of mitoxantrone in cancer patients treated by high-dose chemotherapy and autologous bone marrow transplantation.

We have studied the pharmacokinetics of mitoxantrone in cancer patients. Two regimens were used: eight women (10 kinetics) received a 10 min i.v. infusion of 12 mg m-2 of mitoxantrone; seven women (seven kinetics) received high-dose mitoxantrone associated to high-dose alkylating agents and underwent autologous bone marrow transplantation (BMT). High-dose mitoxantrone was administered according to two different protocols. The drug was quantified in plasma with an HPLC assay and pharmacokinetic analysis was performed with the APIS software. Mitoxantrone pharmacokinetics were best described by an open two- (six kinetics) or an open three compartment model (11 kinetics). A large interindivual variability was observed in pharmacokinetic parameters. In the first group of patients, mean +/- s.d. values of clearance, half-life and total distribution volume were 21.41 +/- 14.59 1 h-1, 19.83 +/- 23.95 h, 165.89 +/- 134.75 1 respectively. In the high-dose group, these values were 21.68 +/- 7.30 1 h-1, 50.26 +/- 20.62 h, 413.70 +/- 194.81 1 respectively. Results showed that identification through the open 2-compartment model is certainly related to the small number of late time-points. We therefore think that mitoxantrone pharmacokinetics is generally best described by an open 3-compartment model. Clearance values showed that there was no saturation in mitoxantrone elimination, even at the highest doses. Terminal elimination half-life was probably underestimated because of the lack of late time-points in some kinetics. The half-life is long for patients receiving high-dose mitoxantrone (mean value was 50 h) and it would be hazardous to perform BMT too early after mitoxantrone infusion. Mitoxantrone metabolites were detected in the plasma of five patients receiving high-dose mitoxantrone and in one with hepatic impairment.

Adolescent↗
PubMed1992

Pentoxifylline in vitro reverses neutrophil chemotactic deficiency induced by interleukin-2 treatment.

Patients undergoing immunotherapy with Interleukin-2 experience multiple side effects and are highly susceptible to bacteremia. In a previous study, we confirmed the profound neutrophil chemotactic deficiency induced by Interleukin-2 therapy. Peripheral blood cells exposed to Interleukin-2 in vitro secrete secondary cytokines. The release of tumor necrosis factor into the circulation after Interleukin-2 injection has been proposed as an important mechanism underlying cell function alterations. We tested chemotaxis of neutrophils from normal subjects after incubation with the serum from treated patients. Serums induced a defective chemotaxis of normal neutrophils similar to the one observed with neutrophils from Interleukin-2 treated patients. We have previously demonstrated a dose-dependent reversion of neutrophil chemotaxis after incubation with anti-Tumor Necrosis Factor-alpha antibody. Pentoxifylline is known for counteracting the inflammatory action of tumor necrosis factor. We tested its capability to reverse the chemotactic deficiency of neutrophils induced by treated patient serums. Pentoxifylline was added after incubation of normal cells with patient serum, and the directed chemotaxis was restored. Pentoxifylline may have a significant therapeutic potential for the prevention or treatment of complications related to inappropriately activated neutrophils.

Bacteremia↗
PubMed1992

Acute monocytic leukemia: prevalent cutaneous lesions. Two cases.

The authors report two cases of acute myeloid leukemia with prevalent cutaneous lesions. The positivity of granulo-monocytic antibodies and the exclusive cutaneous site of the lesions drove them previously to the diagnosis of histiocytic sarcoma. These cases stress the problem of the immunological identification of cutaneous lymphomas of "histiocytic" type.

Aged↗