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Biomedical subjects

L Douay

Publications and source records attributed to L Douay.

At least 109 records · Page 6Linked to original sources
PubMed1985

[Autograft of bone marrow treated by immunotoxin T 101 for the treatment of T-cell leukemia and lymphoma. Initial clinical cases].

In order to consolidate a complete or partial remission, 4 patients with T-cell malignancy received cyclophosphamide 120 mg/kg plus total body irradiation, followed by reinfusion of cryopreserved autologous bone marrow purged in vitro by the immunotoxin T 101 (SR 41322) composed of the murine monoclonal T 101 antibody coupled with the A chain of ricin. The immunotoxin was applied in doses of 10(-9) and 10(-8) M for periods of 4 and 20 hours at 37 degrees C. The recovery of CFUc and BFUe progenitors was total following incubation with IT 101, but reduced after cryopreservation (1-15 to 80% for CFUc,-33 to 47% for BFUe), haematopoietic recovery occurred within normal delays, demonstrating that autologous bone marrow pretreated with the immunotoxin can be successfully transplanted. However, the slow increase in lymphocytes and the occurrence of lethal infection in 2 cases indicate that an in-depth study of immunological reconstitution after in vitro treatment of bone marrow with ITT 101 is necessary.

Adolescent↗
PubMed1985

Regulation of human peripheral blood BFU-E growth in vitro by leukaemic B-lymphocytes.

We report a stimulating effect of leukaemic B-lymphocytes from anaemic and non-anaemic patients with CLL on the proliferation of normal peripheral blood BFU-E. Coculture of leukaemic B-cells at various concentrations (2.5 X 10(3)-10(6)) with 2.5 X 10(5) mononuclear cells from normal peripheral blood increased the number of BFU-E derived erythroid colonies. The same effect was observed when the number of target cells was varied in the presence of a fixed number of B-lymphocytes, with a clear linear relationship. B-cell conditioned medium gave a similar increase when added to the culture instead of B-cells. At high concentration of B-cells from anaemic patients, the size of the colonies was increased and a large number of macroscopic colonies was seen. The place of the B-cells in the regulation of erythroid progenitors in relation to monocytes and T-lymphocytes has still to be established.

Anemia↗
PubMed1985

Standardization and characterization of the procedure for in vitro treatment of human bone marrow with cyclophosphamide derivatives.

Thirty human bone marrow (BM) suspensions from patients with acute leukaemia patients in remission were processed with the Haemonetics 30 flow cell separator in order to separate buffy-coats and to treat them in vitro with a derivative of cyclophosphamide (ASTA Z 7557). After processing, the volumes of BM suspensions were reduced to 25%. Recoveries of leucocytes, CFUc and BFUe were respectively 62, 85 and 84%. In vitro treatment with doses of ASTA Z ranging from 50 to 140 micrograms/2 X 10(7) leucocytes (according to the CFUc sensitivity of each patient) destroyed 95 +/- 5% of initial CFUc. After freezing and thawing, recovery of CFUc from treated BM was poor (24%) in comparison to that obtained with untreated BM (79%).

Acute Disease↗
PubMed1985

Evidence for absence of toxicity of T101 immunotoxin on human hematopoietic progenitor cells prior to bone marrow transplantation.

T101-ricin A-chain immunotoxin is a hybrid molecule made up of the T101 monoclonal antibody bound to the A-chain of ricin. It specifically destroys cells expressing the cell surface T65 antigen. We have designed a preclinical study to evaluate its possible use for the in vitro treatment of T-cell hematological cancers prior to autologous bone marrow transplantation. The data presented here show that conditions previously defined to produce high tumor cell killing, i.e., a 20-hr incubation at 37 degrees in the presence of T101-ricin A-chain immunotoxin up to 10(-7) M in a 10 mM ammonium chloride solution, do not affect the in vitro proliferative capacity of human hematopoietic stem cells studied by means of semisolid medium cultures (granulocyte-macrophage progenitors, burst-forming units-erythrocyte) and continuous liquid cultures (pre-granulocyte-macrophage progenitors). Therefore, autologous bone marrow transplantation with T101-ricin A-chain immunotoxin-treated graft should be feasible.

Antibodies, Monoclonal↗
PubMed1985

Autologous bone marrow transplantation with marrow decontaminated by immunotoxin T 101 in the treatment of leukemia and lymphoma: first clinical observations.

Four patients with T-cell malignancies of poor prognosis (three with non-Hodgkin's lymphoma and one with acute lymphoblastic leukemia) received the following consolidation therapy for complete or partial remission: cyclophosphamide (120 mg/kg) plus total-body irradiation, followed by reinfusion of cryopreserved autologous marrow previously purged in vitro by immunotoxin T 101 (SR 41322). This immunotoxin is made of the murine monoclonal T 101 antibody coupled to chain A of ricin. The doses of immunotoxin used were 10(-9) and 10(-8) M, and the durations of incubation were 4 and 20 hours at 37 degrees C. Recovery of progenitors CFUc and BFUe was total following incubation with immunotoxin T 101, but diminished after cryopreservation (15%-80% for CFUc, 33%-47% for BFUe), suggesting an increased fragility of the incubated progenitors to freezing. In every case, hematopoietic recovery occurred within normal time periods, with a wbc count greater than 10(9)/L and a platelet count greater than 50 X 10(9)/L on Day 22 (range, 15-31) and Day 21 (range, 22-47), respectively, demonstrating the feasibility of autologous bone marrow transplantation with marrow pretreated by immunotoxin. However, the slow recovery of lymphocytes and the development of severe infections in two patients may indicate that an in-depth study of immunological reconstitution after in vitro treatment of the marrow with immunotoxin T 101 is necessary.

Adolescent↗
PubMed1985

[Experimental bases of the in vitro treatment of leukemic bone marrow by a derivative of cyclophosphamide: ASTA Z 7557].

The authors report their experience with the ASTA Z 7557, a derivative of cyclophosphamide, for the in vitro treatment of leukemic bone marrows. They determined the sensitivity of human leukemic progenitors (CFU-L, n = 9) and normal progenitors studied in semi-solid media cultures (CFU-GM, n = 37; BFU-e, n = 11) and in long term marrow culture (pré-CFU-GM n = 41). Data establish: The inhibition of the in vitro proliferation of CFU-L by ASTA Z 7557. The similar sensitivity of CFU-L and normal CFU-GM. The respect, at doses toxic on CFU-L and CFU-GM, of more primitive stem cells, capable of self-renewing and the existence of correlation between the intensiveness of treatment and the regeneration capacity of CFU-GM; therefore, they defined a maximum tolerable dose which spares 5 +/- 5% CFU-GM (DL 95) after treatment. The existence of a wide range susceptibility from patient to patient which requires the determination of the DL 95 for each individual patient.

Bone Marrow↗
PubMed1984

ASTA Z 7557 (INN mafosfamide) for the in vitro treatment of human leukemic bone marrows.

The in vitro treatment of leukemic bone marrows, collected during complete remission, aims at eliminating residual blast cells prior to freezing and preservation, while sparing normal hematopoietic stem cells. We report our experience on the activity of ASTA Z 7557 on human leukemic (CFU-L) and normal hematopoietic stem cells. The sensitivity of human leukemic and normal progenitor cells (CFU-c), detected in semi-solid media cultures, is similar. However, pre-CFUc progenitors detected in long term marrow cultures are much less sensitive to ASTA Z 7557. Therefore autologous bone marrow transplantation can successfully be done with pretreated marrows containing 5 +/- 5% residual CFUc. The wide range of stem cells sensitivity to ASTA Z 7557 justify the predetermination of the optimal dose of drug for incubation prior to marrow collection for each individual patient. Our preliminary clinical experience is exposed.

Bone Marrow Transplantation↗
PubMed1984

Autologous bone marrow transplantation in the treatment of poor prognosis non-Hodgkin's lymphomas.

Twelve patients with non-Hodgkin's lymphomas of poor prognosis were treated by TACC high-dose chemotherapy (cyclophosphamide 45 mg/kg/day X 4, cytosine arabinoside 200 mg/m2 i.v. q 12 hr X 7,6-thioguanin 100 mg/m2 p.o. X 7 and CCNU 200 or 250 mg/m2 p.o., single dose) followed by autologous bone marrow transplantation (ABMI) (infused dose: 853-20,000 CFU-c/kg). Patients were divided into 2 groups: those in primary therapy with high tumor load (group 1; 3 initial diagnoses, 3 relapses) and those in consolidation therapy for a low tumor load (group 2; 5 complete and 1 partial remissions). Results show that: (1) the aplasia following autologous bone marrow transplantation was short. Leukocyte (greater than 10(9)/1) and platelet (greater than 50 X 10(9)/1) recoveries were observed on day 12 (range, 9-19) and day 14 (range, 8-27). (2) In group 1 there were 3 complete remissions (8,21, 45+ months) and 3 failures, including 1 death to toxicity of TACC. The 3 remissions occurred in patients in primary therapy and overall survival of these patients from the time of initial diagnosis was 48+, 48+ and 60+ months. In group 2 there were 5 persisting complete remissions (12+ to 40+ months) and 1 failure. Overall survival of these patients was 23+, 24+, 27+, 42+ and 70+ months. In both groups failures were associated with contamination of the frozen marrow by tumor. The toxicity of the association TACC + ABMT was acceptable and dominated by the risk of pericardial effusion and infection. The latter was absent in group 2 and occurred in 5/6 cases in group 1. These preliminary results indicate that autologous bone marrow transplantation has a possible role in the aggressive treatment of non-Hodgkin's lymphomas of high-grade malignancy and that its use should preferentially be in the consolidation mode.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

[Non-Hodgkin's malignant lymphoma. Therapeutic value of autologous bone marrow transplantation].

Twelve patients with non-Hodgkin malignant lymphoma of poor prognosis were treated with heavy chemotherapy of the TACC type (cyclophosphamide 45 mg/kg/day i.v. X 4; cytosine arabinoside 200 mg/m2/12 hours i.v. X 7; 6-thioguanidine 100 mg/m2/12-hourly p.o X 7 and CCNU 200 or 250 mg/m2 p.o. single dose) followed by autologus bone marrow transplantation (853 to 20.000 CFUc/kg). The patients were divided into 2 groups depending on whether they received an induction treatment for large visible tumoral mass (group I: 3 initial presentations, 3 relapses) or a consolidation treatment for small residual tumour (group II: 6 complete and 1 partial remissions). The results show that autologous bone marrow transplantation shortens the duration of the therapeutic aplasia. White cell (greater than 10(9)/l) and platelet (greater than 50.10(9)/l) recovery was observed on days 12 (range 9-19) and 14 (range 8-27) respectively. In group I, 1 patient died of myocardial TACC toxity and acute renal failure on tumoral kidney; there were 2 failures and 3 complete remissions (8, 21, 45 + months). Remissions occurred in patients treated initially; the overall survival since diagnosis was 48+, 48+ and 60+ months. In group II patients there were 1 failure and 5 complete remissions persisting after a 2+ months to 30+ months follow-up; the overall survival was 23+, 24+, 27+, 42+ and 70+ months. The 3 failures in the series occurred in circumstances suggesting contamination of the cryopreserved bone marrow by tumoral cells. The toxicity, largely due to infection, of the TACC-bone marrow transplantation combination was tolerable. It was clearly lower in group II (6 patients, no septicaemia) than in group I (5/6 patients with septicaemia). These preliminary results confirm that there is room for autologous bone marrow transplantation in highly malignant non-Hodgkin lymphomas, particularly during complete remissions to facilitate the use of an aggressive consolidation chemotherapy.

Adult↗
PubMed1983

Delayed kinetics of recovery of haemopoiesis following autologous bone marrow transplantation. The role of excessively rapid marrow freezing rates after the release of fusion heat.

Thirty-five patients were treated by intensive chemotherapy and/or whole-body irradiation followed by reinjection of cryopreserved autologous bone marrow. In 8 patients the kinetics of recovery of haemopoiesis was delayed (recovery to 10(9) leucocytes/litre beyond day 27 and recovery to 50 X 10(9) platelets/litre beyond day 25). This delay was directly responsible for the death of 3 patients and contributed to a fatal outcome in 2 others (mortality rate 9-14%). Retrospective analysis of these 8 cases revealed that failure of autologous transplantation was associated with poor recovery of CFUc, which was in turn related to an excessively rapid freezing rate after the release of fusion heat. Recovery of CFUc to 50% or more was achieved in 100% of cases when the freezing rate was less than 5 degrees C/min, 45% for freezing rates between 5 and 10 degrees C/min and 22% when the freezing rate exceeded 10 degrees C/min (n = 71, P less than 0.001). There was an inverse linear or logarithmic relationship between CFUc recovery and freezing rate after the transition phase (r = -0.46, r = -0.43, P less than 0.001). The quantity of nitrogen introduced into the freezing chamber to annul the fusion heat must therefore be calibrated with accuracy so that the desired shortening of the transition phase will not be accompanied by an overly marked increase in the freezing rate, which would result in the destruction of stem cells. To ensure an adequate freezing rate, it is crucial to monitor the temperature continuously in each sample of bone marrow during the freezing process. This study also suggested that other factors may have interfered with the kinetics of recovery after autologous bone-marrow transplantation. These factors include myelofibrosis, the presence of an Australia antigen and administration of compounds that are toxic for the bone marrow after reinjection of cryopreserved marrow. However, the responsibility of these factors cannot be stated with certainty.

Adult↗
PubMed1983

The role of serum lipoproteins on the in vitro proliferative potential of human hematopoietic progenitors CFUC and CFUE.

The influence of various lipoprotein fractions on the proliferation of normal human hematopoietic progenitors, CFUC and CFUE, was studied in vitro. The lipoprotein fractions, very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (LDL), high density lipoproteins (HDL2 and HDL3), were isolated by sequential ultracentrifugation. The addition of each subfraction to lipoprotein deficient medium allowed us to distinguish two categories of lipoproteins: firstly, those with density d greater than 1.030, LDL, HDL2 and HDL3 which showed a marked inhibitory activity on CFUC and CFUE proliferation and, secondly, those with density d less than 1.030, VLDL and IDL which did not show any inhibitory activity. The regulatory role of lipoproteins on progenitor cell proliferation is discussed.

Cell Division↗
PubMed1982

[Bone marrow repopulation after heavy chemotherapy and autologous bone marrow transplantation. Monitoring with biopsies and marrow culture on agar (author's transl)].

Repopulation of the bone marrow after heavy chemotherapy and autologous transplantation was monitored by means of biopsies and bone marrow cultures on agar carried out simultaneously from the 2nd to the 33rd days after transplantation. A parallelism was observed between the reappearance of cell clusters on biopsy material and the growth of colonies in cultures, both being the centres from which the corresponding series proliferated. The clusters were almost invariably formed of one series. Repopulation began 3 to 5 days after transplantation and was complete between the 10th and 20th days. Oedematous dissociation persisted long after the clusters reappeared. Bone marrow repair was virtually always accompanied by plasmocytosis.

Adolescent↗
PubMed1982

[Critical role of rate previous freezing on the liberation of heat of fusion the preservation of hematopoietic cell lines].

71 bags of bone marrow cryopreserved and stored for periods up to 2 years, were thawed and CFUc recoveries were studied in relation to the rate of freezing following the heat of fusion. Excellent CFUc recoveries (greater than 50%) were obtained in all cases (11/11) for freezing rates smaller than 5 dgC/mn, whereas freezing rates greater than 10 dgC/mn produced poor recoveries in 78% of the cases (4/18). Intermediate freezing rates (5 less than 0 less than 10) resulted in intermediate yields of CFUc, with good recoveries in only 45% of the cases (19/42). These results indicate that CFUc recoveries and subsequently the kinetics of autologous engraftment following the infusion of cryopreserved marrow, which are already known to be related both to the freezing rate before the heat of fusion and the duration of the phase transition period, are also related to this new parameter, which should be carefully monitored during the freezing procedure.

Bone Marrow↗
PubMed1982

Study of granulocyte-macrophage progenitor (CFUc) preservation after slow freezing of bone marrow in the gas phase of liquid nitrogen.

Storage of human hematopoietic stem cells has been made possible through effective preservation of viability by freezing technique. We have studied the quantitative and qualitative aspects of granulocyte-macrophage precursor (CFUc) recovery from 29 bags of frozen bone marrow stored at - 160 degree C in the gas phase of liquid nitrogen for several months or years. it has been shown that with the freezing and preservation technique used, over 75% of the proliferative capacity of the cryopreserved CFUc was recovered. The influence of various factors on the quality of bone marrow preservation was studied and showed that dimethylsulfoxide (DMSO) appeared to cause substantial loss of CFUc at 4 degree C. Evaluation of CFUc in vitro is essential for determining the quality and richness of cryopreserved bone marrow with a view to using such marrow for autologous grafting intensive chemotherapy or total body irradiation in patients with hematological malignancies or solid tumors. No correlation was found between the number of nucleated bone marrow cells and CFUc content.

Adolescent↗
PubMedDate not supplied

Ex vivo expansion of mobilized peripheral blood stem cells.

The scarcity of donors for allogeneic bone marrow transplantation, the limited number of haematopoietic stem cell (HSC)/progenitors in cord blood samples and the sometimes insufficient number of mobilized peripheral blood cells collected from heavily treated cancer patients may benefit from ex vivo expansion of these cells for clinical transplantation. Depending on the clinical application, expansion of different haematopoietic cell subsets is required. HSC transplantation requires expansion of all cellular subsets including precursors, progenitors and HSCs for the short and long-term engraftment of patients. Quiescent HSCs may also be required for gene therapy by retrovirus. Finally, amplification of cells such as dendritic cells (DC) and different subsets of T and natural killer (NK) cells is required for immunotherapy. The different haematopoietic lineages are produced under different experimental conditions and the starting population is a critical parameter for the proposed clinical application. So it is essential to define the aims of haematopoietic cell expansion and to adapt the experimental conditions to obtain the required cell population. Mobilized peripheral blood cells are increasingly used as a source of haematopoietic cells. We review the biological characteristics of mobilized peripheral blood and the expansion of the different components according to the aims of their clinical use in the context of the progress currently achieved.

Animals↗