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Biomedical subjects

D Maraninchi

Publications and source records attributed to D Maraninchi.

At least 235 records · Page 13Linked to original sources

[Allogeneic bone marrow transplantation in the treatment of acute leukemias of children. Study of 26 patients].

Twenty-six children with acute leukemia were treated with allogeneic marrow transplantation from HLA identical siblings after a conditioning regimen with Cyclophosphamide-total body irradiation (19 patients), Melphalan-total body irradiation (6 patients) or Busulfan-cyclophosphamide (1 patient). Eighteen were transplanted in complete remission (4 with acute non lymphoblastic leukemia in first remission, 14 with acute lymphoblastic leukemia: 6 in first, 6 in second and 2 in subsequent remission): 2 died of cytomegalovirus pneumoniae, 1 relapsed and 15 survive in continuous complete remission from 5 to 42 months after transplantation (median = 22 months). Eight were transplanted in relapse, 7 achieve complete remission, 5 of them relapsed, 1 died of G.V.H. and 1 survives in continuous complete remission 46 months after transplantation. Actuarial analysis shows a disease free survival rate at 3 years of 82% for patients transplanted in remission and 12% for patients transplanted in relapse (p less than 0.01).

Acute Disease↗

Clinical pharmacokinetics of ciclosporin A in bone marrow transplantation patients.

Ciclosporin A (CsA) plasma concentrations were monitored by radioimmunoassay after administration IV and PO to 15 patients before allogeneic bone marrow transplantation. The clearance (10.4 +/- 5.41 1/h), half-life (26.4 +/- 14.6 h), and bioavailability (16% +/- 10%) calculated directly from experimental data showed wide interindividual variations. The kinetics after IV infusion, monitored over 2-5 days, appeared to be triphasic. A three-compartment open mamillary model was thus used to simulate the distribution and elimination kinetics of CsA. The distributive delay between administration PO and absorption in the plasma was approximated using a series of six additional compartments connected with a single transfer rate constant. Then, for each patient, the experimental data corresponding to both IV and PO administration were fitted using a single set of rate constants. Clearance and bioavailability calculated from model parameters correlated well with direct estimations obtained from the areas under the concentration time curves. Drug monitoring and linear modeling will be used in an attempt to achieve stable predetermined plasma concentrations of CsA in bone marrow transplantation patients receiving the drug either IV or PO.

Administration, Oral↗

Phase-I-II study of high-dose melphalan and autologous marrow transplantation in adult patients with poor-risk non-Hodgkin's lymphomas.

Eleven adult patients with poor-risk non-Hodgkin's lymphoma were treated with high-dose melphalan (140 mg/m2) or high-dose combination chemotherapy (BCNU, Ara-C, vindesine and melphalan) followed by autologous bone marrow transplantation. Six of the eight patients evaluable for response achieved complete remission and one achieved partial remission. Response duration ranged from 1.5 to 12 months (median 2 months). Prompt hematological recovery occurred in all patients. The duration of aplasia and the extrahematological toxicity were similar in both groups. High-dose melphalan alone or associated with other drugs followed by marrow infusion appears to produce a high response rate and demonstrates the potential for salvaging patients with refractory lymphoma.

Adult↗

Methotrexate-vindesine association in leukemia: pharmacokinetic study.

Methotrexate (MTX) and vindesine (VDS) have both been found effective in the treatment of acute leukemia. With regard to their pharmacological effects at the cellular level they can reportedly interact. Administration of MTX at high dose levels has been suggested as both a curative and preventive treatment of blastic meningitis. The purpose of this work was to determine whether an injection of VDS leads to any change in MTX clearance and uptake in the cerebrospinal fluid (CSF). The plasma pharmacokinetic and CSF influx of MTX and VDS were assayed after high dose systemic MTX with an intravenous bolus of VDS administered in the treatment of acute lymphoblastic leukemia. The MTX concentration was determined by enzymatic assay and VDS by radio immunoassay. No interrelation between these drugs was found. MTX levels in the CSF were sufficient for therapeutic effectiveness but were not affected by intravenous VDS. Detectable amounts of VDS were observed in the CSF but were not altered by MTX.

Adult↗

Massive chemotherapy with autologous bone marrow transplantation in 50 cases of bad prognosis non-Hodgkin's lymphoma.

50 cases of advanced, intermediate (18) and high grade (32) non-Hodgkin's lymphoma (NHL) including 16 with Burkitt lymphoma have been treated with very high dose chemotherapy and autologous bone marrow transplantation (ABMT). These cases represent a retrospective analysis of the combined experience of a recently established collaborative group. 31 patients were treated with a protocol used in Lyon, 12 with that used in Marseille and seven with that used in London. Although the details of drug administration differed, each protocol was based on high dose alkylating agent (cyclophosphamide or melphalan), BCNU and cytosine arabinoside. 16 patients had drug resistant progressive NHL. Of these 11 responded to high dose treatment (nine CR, two PR). The duration of CR in this group was short (median 104d) and only one patient was in CR at 1 year. 19 patients had relapsed on previous therapy but were still responding to conventional rescue therapy. Following high dose therapy 47% of these patients are in continuous CR with a median time of observation of 300 d (73-962 d). Seven patients were partial responders to conventional induction therapy. Of these, six had a CR with high dose treatment and are still in CR (range 39-1230 d, median 200 d). Eight patients received high dose therapy as intensification after a long delay to CR with conventional treatment. Of these, four are alive and in remission 124-763 d after treatment. The high dose protocols produced significant morbidity with 25 patients (50%) having major or minor treatment-related complications, and there were seven treatment related deaths (14%). However, these results indicate that durable responses can be obtained with high dose chemotherapy in patients who have been heavily treated and indicate a role for this type of treatment at an earlier stage in advanced non-Hodgkin's lymphoma.

Adolescent↗

Increased prostaglandin E production in malignant lymphomas.

Prostaglandin E (PGE) production was evaluated in 18 normal subjects and 29 patients with Hodgkin's and non-Hodgkin's lymphomas. Plasma PGE levels of patients were found to be highly increased. Increased PGE synthesis was demonstrated in conditioned media from peripheral blood and bone marrow mononuclear cells, arising from the adherent cell fraction enriched in monocytes. No relationship with clinical or pathological findings was observed.

Adolescent↗

T-lymphocyte subpopulations identified by monoclonal antibodies after human bone-marrow transplantation.

Peripheral T-lymphocyte reconstitution after bone-marrow transplantation, 12 allogeneic and 13 autologous, was studied by indirect immunofluorescence assay using mouse monoclonal antibodies. Abnormal counts were detected in the two major sub-populations of T-cells i.e. helper and T cytotoxic-suppressor lymphocytes, defined by monoclonal antibodies (alpha Leu 3a and B 9.2), and in DR antigen-positive T-cells. The pattern of T-lymphocytes replenishment was identical for both types of transplant, and was not affected by Graft Versus Host disease (GVHD).

Antibodies, Monoclonal↗

High-dose melphalan with autologous bone marrow rescue for the treatment of advanced adult solid tumors.

High-dose melphalan followed by "rescue" with autologous marrow stored for 12-24 hours at room temperature was used in the treatment of 14 patients with advanced tumors refractory to conventional treatment. Twelve patients were evaluable, with three complete responses (25%), five partial responses (42%), and two minimal responses (16%). Response durations ranged from 4 to 38 weeks (median, 7). There were two treatment-related deaths and one patient developed acute nonlymphocytic leukemia 3 months after a second course of high-dose melphalan.

Adult↗

High-dose melphalan and autologous bone marrow transplant for relapsed acute leukaemia.

Seven patients with relapsed acute leukaemia were treated with high-dose melphalan (HDM) followed by the infusion of autologous cryopreserved remission marrow. Toxicity was minimal and all seven patients had a complete response. Four patients are still in unmaintained remission at 14, 13, 10, and 3 months, the first two having received a second course of HDM to consolidate the result. The role of HDM as a form of intensification therapy for patients with acute myeloid leukaemia in first remission should be investigated.

Adult↗

[Granulocytic progenitors in bone marrow autografts].

Granulocytic progenitor cells (CFC) are a better reflection of stem cell pools than precursors. Their total number can be estimated during hematologic steady-state (N = 70 +/- 29 x 10(5) CFC/kg); the amount of marrow necessary to perform a bone marrow transplantation is only 1% of the total pool. CFC are useful but have a mainly qualitative value in evaluating the viability of marrow stored for 24 h at room temperature (92%) or marrow thawed after DMSO cryopreservation (62%). Sequential study of CFC in patients receiving autologous marrow transplantation enables differentiation of engraftment from autologous recovery. In 11 recipients of autologous marrow transplantation, no statistical relation was observed between number of infused CFC and severity of granulocytopenia. Further studies will be necessary to evaluate a better marker of real hematopoietic stem cells.

Adolescent↗