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Biomedical subjects

C Chabannon

Publications and source records attributed to C Chabannon.

79 records · Page 5Linked to original sources
PubMed1990

Study of megakaryocytic progenitors (CFU-MK) in human long-term bone marrow cultures (LTBMC): adjuvant effect of plasma from aplastic patients.

Human long-term bone marrow cultures (LTBMC) provide a very interesting tool for studying the events that are involved in stem cell commitment. At the present time, megakaryocyte (MK) progenitor cells have never been demonstrated in this system. In an effort to detect this cell lineage, we modified the culture medium by substituting fetal calf serum (FCS) and horse serum (HS) mix with human plasma obtained from treated aplastic leukemic patients. This plasma was harvested between days 15 and 21 following induction chemotherapy or conditioning regimen for autograft or allogeneic bone marrow transplantation. Using LTBMC, 17 normal marrows were cultivated for 11 weeks in Iscove's modified Dulbecco's medium containing either 20% human aplastic plasma or control FCS/HS mixture. In this plasma medium we observed the development of an adherent layer morphologically comparable to that observed with standard medium. We demonstrated presence of MK cells at all stages of maturation for 10 weeks and MK colony-forming cells (CFU-MK) for 11 weeks in the culture supernatants. An increased production of nonadherent cells and granulocyte-macrophage progenitors (CFU-GM) was also observed. LTBMC in aplastic plasma medium provide a new method for studying megakaryocytopoiesis, especially in human hematological diseases.

Adolescent↗
PubMed1990

Clinical and hematological improvement in a patient receiving danazol therapy for myelofibrosis with myeloid metaplasia.

We report the positive effect of danazol on clinical and hematological data in a patient with myelofibrosis and myeloid metaplasia. Severe cytopenia was corrected within 2 months and was maintained for an additional 2-month period. Myeloid metaplasia (lymph nodes and skin lesions) was greatly reduced. The patient experienced no side effects. We propose further trials to confirm the utility of this agent in this disease.

Danazol↗
PubMedDate not supplied

Survey of early disapearance of BCR/ABL fusion transcript after allogeneic or autologous stem cell transplantation for chronic myelogenous leukemia.

The detection of BCR-ABL specific RNA by RT-PCR has been shown to predict relapse when positive 6 months after allogeneic stem cell transplantation (SCT) for chronic myelogenous leukemia (CML). In the present study, the focus was on evaluation of residual disease during the first weeks following SCT. In this study, 177 blood or marrow samples were obtained from 33 patients who received allogeneic (20 patients) or autologous (13 patients) SCT on day 0, day 30 and every 3 months for 1 year. T-cell depletion (TCD) was performed in 4 cases. On day 0 (day of graft infusion), 10/30 evaluable patients had negative RT-PCR (33%) regardless of pretransplant characteristics. On day 30, 14/18 patients (77%) from the allogeneic group had negative RT-PCR versus 0% in the autologous group. 2/4 patients who received TCD allogeneic grafts had day 30-positive PCR. Five patients in the allogeneic group had at least one positive RT-PCR sample between day 30 and day 90: 3 of them subsequently relapsed suggesting possible correlation between early positivity and relapse. Our results show that disappearance of MRD can be achieved within 3 months after transplantation in the majority of patients treated with allogeneic but not after autologous SCT. This suggests that the GVL effect might be operational early during the first weeks following transplantation.

Adult↗
PubMedDate not supplied

Outpatient sequential high dose alkylation with stem cell support for patients with advanced breast cancer: a phase I-II study.

We evaluated the feasibility of administering, in an out-patient setting, a sequential high dose alkylating regimen with hematopoietic growth factor (HGF) and stem cell support to patients with advanced breast cancer. Peripheral blood stem cells (PBSC) were previously collected after chemotherapy and HGF. Two consecutive cycles of alkylating agents were planned: Thiotepa (T) then, 15 days later, BCNU (B). Three dose levels of each agent were administered in cohorts of consecutive patients: 400, 500 and 600 mg/m2 respectively. HGF and reinfusion of PBSC followed both cycles. Toxicity and response were evaluated according to the WHO recommendations. From April 1996 to August 1988, 30 women were enrolled: 8 in the first, 12 in the second and 10 in the third dose level. In all cases, B was administered after T with a median delay of 25 days because of grade 3/4 hematological toxicity. 4 patients did not receive B because of previous lung radiotherapy, persistent tricytopenia or insufficient PBSC collection. 19 patients with measurable lesions were considered for response. The objective response rate was 48% (11% CR, 37% PR). We recommended T and B at a dose of 600 mg/m2 to conduct a phase II study in metastatic breast cancer and even to administer B before T.

Antineoplastic Agents, Alkylating↗
PubMedDate not supplied

A defective retroviral vector encoding human interferon-alpha2 can transduce human leukemic cell lines.

Using the LXSN backbone, a defective retroviral vector (LISN) was constructed that encodes the human interferon (IFN)-alpha2 (hIFN-alpha2) gene and the neomycin resistance gene; the hIFN-alpha2 gene was cloned from human placental genomic DNA. High titers of the LISN retrovirus were produced by the amphotropic packaging cell line GP+envAM12. LISN is able to infect three human hematopoietic and leukemic cell lines: K562, LAMA-84, and TF-1. G418-resistant cells were detected in a similar proportion after infection with either the LISN retroviral vector or the LnLSN retroviral vector (encoding the nlsLacZ gene instead of hIFN-alpha2), suggesting that hIFN-alpha2 does not inhibit (or only partially inhibits) the production of retroviral particles by the packaging cell line and the infection of human cells. LISN-infected cells express and secrete hIFN-alpha2 as demonstrated by Northern blot analysis of poly(A)+ RNA, detection of the intracellular protein by fluorescence-activated cell sorter analysis, and detection of secreted hIFN-alpha in cell supernatants using an enzyme-linked immunosorbent assay. Retrovirally produced hIFN-alpha2 is biologically active, as demonstrated by the partial inhibition of the growth of K562 and TF-1, the modulation of the expression of cell surface antigens, the induction of the (2'-5') oligoadenylate synthetase, and, for LAMA-84, the down-modulation of the BCR-ABL protein. We conclude that the infection of human leukemic cell lines with a retroviral vector encoding hIFN-alpha2 is feasible and induces the expected biological effects. This experimental model will be useful in investigating the possibility of transducing normal and leukemic cells and hematopoietic progenitors and in determining the consequences of the autocrine production of hIFN-alpha2 on the behavior of these cells.

Animals↗