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Biomedical subjects

D Guyotat

Publications and source records attributed to D Guyotat.

At least 73 records · Page 4Linked to original sources
PubMed1992

Plasma itraconazole concentrations in neutropenic patients after repeated high-dose treatment.

Two different treatments with repeated oral high doses of itraconazole were tested for 10 days in 20 neutropenic patients, 10 receiving 400 mg per day and 10 receiving 600 mg per day. In each group 5 patients were treated for acute leukaemia and 5 patients were recipients of autologous bone-marrow transplantation (ABMT). Itraconazole plasma concentrations were assayed by high-performance liquid chromatography. Statistical analysis disclosed a significant interaction between the dispensed dose and the patient types. The difference between the two doses of itraconazole was greater in the ABMT than in the leukaemia patients. After 10 days at 600 mg per day all the ABMT patients had an itraconazole plasma concentration higher than 250 micrograms/l. Therefore, 600 mg per day seems more efficient to obtain a therapeutic level of itraconazole in ABMT patients but this needs to be confirmed for all the neutropenic patients.

Acute Disease↗
PubMed1992

Specific binding of anti-N-acetyllactosamine monoclonal antibody 1B2 to acute myeloid leukaemia cells.

1B2 is an IgM monoclonal antibody binding to glycoconjugates bearing the terminal N-acetyllactosamine structure. It agglutinates human erythrocytes. Various cell lines, peripheral blood leucocytes, normal marrow and blast cells from 179 acute myeloid leukaemia (AML) and 11 acute lymphoblastic leukaemia (ALL) patients were tested for reactivity with 1B2. Myelomonocytic (CFU-GM), erythroid (BFU-E), mixed (CFU-GEMM) and leukaemic (CFU-L) progenitor cells were tested in clonogenic assays. Granulocytes, monocytes, myeloid cell lines and 152 out of 179 AML were positive. All FAB subtypes were equally recognised. Lymphocytes, T-cell and Burkitt's cell lines, and 10 of 11 ALL samples were negative. 1B2 inhibited partially day 7 CFU-GM, whereas it was not toxic for BFU-E, CFU-GEMM and day 14 CFU-GM. Leukaemic clonogenic cells were killed in 33 out of 36 AML (more than 40% growth inhibition). 1B2 identifies the more mature steps of myeloid differentiation. It may be useful in the diagnosis of AML, and is a candidate for remission marrow purging before autologous transplantation.

Amino Sugars↗
PubMed1992

CD1-reactive leukemic cells in bone marrow: presence of Langerhans cell marker on leukemic monocytic cells.

Langerhans cells originate in bone marrow and probably belong to the monocyte-macrophage lineage. CD1 is a specific marker of Langerhans cells. By immunofluorescence and immunoelectron microscopy, CD1a antigen and myeloid markers (CD11, CD13, CD14, CD15, CD33, HLA-DR) were studied in 53 cases of acute myeloid leukemias (AML) and 3 acute lymphoblastic leukemias (ALL). The 11 ANLL without monocytic component were CD1a negative. 2/5 of acute myelomonocytic leukemias (AML4) and 9/37 of acute monocytic leukemias (AML5) were positive. All 3 ALL were negative. No correlation was found between CD1a and myeloid markers. CD1a+ AML did not differ from CD1a- AML with regard to cytogenetics or response to therapy. The CD1a positive cells may originate from an abnormal proliferation of CD1a positive cells which are present in bone marrow and which may differentiate into Langerhans cell precursors.

Antigens, CD↗
PubMed1992

Correlation of MDR1/P-170 expression with daunorubicin uptake and sensitivity of leukemic progenitors in acute myeloid leukemia.

Prior studies have shown that multidrug resistance gene products may be detected in acute myeloid leukemia (AML) cells, and are associated with poor response to therapy. We studied whether P-170 expression was associated with in vitro daunorubicin (DNR) accumulation and sensitivity of leukemic clonogenic cells (CFU-L) to DNR in 16 newly diagnosed AML samples. P-170 expression was assessed by indirect immunofluorescence using the monoclonal antibody MRK16. DNR cellular content was measured by flow cytometry after short incubation with increasing concentrations of DNR, and was not correlated with P-170 expression, although there was a trend for higher values in P-170-negative samples. The sensitivity of CFU-L was studied in a semisolid culture assay by calculating the dose of DNR inhibiting the growth of 90% of CFU-L (D90). The D90 was significantly higher in P-170-positive than in P-170-negative samples (mean = 1.68 +/- 0.42 microgram/ml versus 0.97 +/- 0.35 micrograms/ml respectively, p less than 0.005). Eight of 9 cases achieving complete remission (CR) after intensive chemotherapy were P-170-negative, whereas 7 of 7 nonresponders were P-170-positive (p less than 10(-5)). D90 was significantly lower for patients achieving CR than for those who did not achieve CR (1.12 +/- 0.55 micrograms/ml versus 1.59 +/- 0.37 micrograms/ml, p = 0.04). It is concluded that P-170 expression is correlated with in vitro resistance of clonogenic cells to DNR and may be one mechanism of resistance to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Chromosome studies in stimulated lymphocytes of 50 patients with B-cell chronic lymphocytic leukemia.

The chromosome constitutions of stimulated lymphocytes from 50 B-cell chronic lymphocytic leukemia patients were studied using different stimulation systems, i.e., TPA alone or associated with different cytokines. Adequate metaphases were obtained in 44 subjects (88%). Among 20 patients with abnormal karyotypes (45.5%), 7 had trisomy 12. The most frequent structural abnormality was a 14q+ resulting from translocations including one t(11;14) and two t(14;17), while deletions on the long arms of chromosomes 6 and 13 constituted a second common alteration. The most important finding in this series was the recurrence of a t(18;22) observed in two cases.

Adult↗
PubMed1992

Streptococcal bacteremia in neutropenic adult patients.

In order to define the circumstances of occurrence, clinical presentation and prognostic factors of streptococcal bacteremia in neutropenic patients, we retrospectively reviewed 60 cases of streptococcal bacteremia following intensive chemotherapy for acute myeloblastic leukemia (AML), acute lymphoblastic leukemia (ALL) or allogeneic bone marrow transplantation. Causative streptococcal species included streptococcus viridans (42 cases), streptococcus faecalis (12), streptococcus pneumoniae (4) and other streptococci (2). All patients were febrile and 32% presented diffuse pneumopathy with frequent isolation of streptococci from bronchoalveolar washing fluids. There were no statistical differences in presentation between the bacteremia caused by different streptococcal species. Death occurred in 22% of the patients and factors favoring poor prognosis included pneumopathy (p less than 0.001), more than 2 positive blood cultures (p less than 0.01) and initial chemotherapy for AML (p less than 0.01). Pneumopathy occurred more frequently after chemotherapy for AML. It is concluded that streptococcal bacteremia is to be prevented in patients undergoing intensive chemotherapy, particularly if cytarabine is used.

Adolescent↗
PubMed1992

Autologous bone marrow transplantation vs intensive chemotherapy in first complete remission: interim results of GOELAM study in AML.

In November 1987, the French group GOELAM initiated a randomized study comparing allogeneic bone marrow transplantation (BMT), autologous bone marrow transplantation (ABMT) and intensive consolidation chemotherapy (ICC). The induction treatment was randomized between Idarubicin plus Cytarabine and Zorubicine plus Cytarabine: 223 patients with de novo AML and aged 15-50 years are currently evaluable and 178 of them (80%) have achieved complete remission (CR) with no significant difference between both arms. Forty four patients under 40 years of age and having a HLA identical sibling were assigned to BMT and 38 were actually transplanted. Thirty of the 134 other patients did not receive the planned first course of ICC, 4 patients died during this course, and 21 were excluded before randomisation. Thus, only 64 patients have currently been randomized between the 2nd course of ICC (34 patients) and ABMT (30 patients). ABMT was prepared by the Baltimore regimen and the marrow was unpurged. With a median follow-up time of 29 months, the actuarial risk of relapse at 3 years is 29% for BMT, 38% for ABMT and 53% for ICC. The 3 year disease free survival (DFS) is 51% for BMT, 62% for ABMT and 47% for ICC. These differences are not statistically significant. When intention to treat is considered, there is no difference in the actuarial DFS between the BMT and the non BMT groups. Longer follow-up time and larger number of patients are warranted to demonstrate any significant advantage of one of these approaches.

Acute Disease↗
PubMed1991

In vitro effects of recombinant hemopoietic growth factors on progenitor cells from patients with myelodysplastic syndromes.

The effects of four recombinant hemopoietic growth factors (HGF) and of the impure factor HTB9 on proliferation and maturation of marrow myeloid (CFU-GM) and erythroid (BFU-E) progenitor cells were studied in 22 cases of myelodysplastic syndromes (MDS). In most cases, IL-3, GM-CSF and G-CSF increased significantly the number of myeloid colonies, the best combination being IL-3 + GM-CSF. A significant increase in the myeloid colony/cluster ratio was also noted, but cytological examination of colony cells showed little maturation. The analysis of myeloid colony surface markers with four monoclonal antibodies (to CD13, CD15, CD33 and CD34) showed minor modifications with an increase of CD13 and CD15 in about one third of cases when compared to control without HGF. Erythroid colonies were obtained in one case with erythropoietin alone, and in 19 cases with the addition of GM-CSF and/or IL-3. In short-term liquid cultures, IL-3, GM-CSF and G-CSF increased 3H-thymidine incorporation. We conclude that progenitor cells of most MDS are able to proliferate in the presence of HGF, with wide case-to-case variations. However, the pattern of growth remains abnormal when compared to normal marrow. Although the combination of IL-3 and GM-CSF is the most efficient, there is a large overlap in the stimulating effects of all factors studied.

Antigens, CD↗
PubMed1991

Pefloxacin and vancomycin vs. gentamicin, colistin sulphate and vancomycin for prevention of infections in granulocytopenic patients: a randomised double-blind study.

To test the value of pefloxacin for the prevention of infections in patients with chemotherapy-induced neutropenia, oral pefloxacin plus vancomycin (PV) (n = 76) or gentamicin, colistin sulphate and vancomycin (GCV) (n = 74) were administered in a randomised double-blind study. Infections were significantly less severe in the PV than in the GCV group. Patients receiving PV had significantly fewer episodes of bacteraemia and central venous line infections than patients treated with GCV. Gram-positive and gram-negative infections were significantly less frequent in patients receiving PV, because of fewer infections with Staphylococcus species and enterobacteriaceae. Stool culture detected significantly more gram-positive organisms in the PV group and more gram-negative organisms in the GCV group. Thus, PV was more efficacious than GCV for the prevention of gram-positive and gram-negative infections in the neutropenic patients, despite lower efficacy in eradicating gram-positive organisms from the lower intestinal tract.

Adult↗
PubMed1991

Influence of the fractionation of total body irradiation on complications and relapse rate for chronic myelogenous leukemia. The Groupe d'Etude des greffes de moelle osseuse (GEGMO).

One hundred eighty patients with chronic myelogenous leukemia, who received an unmanipulated marrow graft from an Human Leucocyte Antigen identical sibling donor, were reported to our group (G.E.G.M.O.) by 21 transplant teams. All were grafted after a total body irradiation-cytoxan conditioning regimen. Of these 180 patients, 126 were non-randomly assigned to single dose total body irradiation (STBI group) and, 54 to fractionated total body irradiation (FTBI group). With a median follow-up of 40 months, there is no statistically significant difference in the 5-year survival rate between the two groups (51% for the whole population). In a first step we demonstrate by multivariate analysis that total body irradiation fractionation can dramatically decrease the incidence of interstitial pneumonitis. However, a multivariate analysis of potent risk factors for relapse post-transplant strongly suggests that TBI fractionation is also linked to an increased relapse rate. So, a sparing effect of fractionation for lung tissue could be offset by a less effective leukemic stem cell kill. Those results from a retrospective, non-randomized, multi-institutional study clearly need additional clinical data, ideally from a randomized study.

Bone Marrow Transplantation↗
PubMed1991

[Bronchiolitis obliterans with severe obstructive ventilation disorder after a bone marrow transplant. Study of 7 cases].

In 40 to 60% of bone marrow grafts there are pulmonary complications of which the most frequent is the occurrence of an interstitial pneumonia. We report 7 cases here of a more rare complication, that of bronchiolitis obliterans (BO). Between December 1979 and November 1989, 7 patients (3.4% of our cases of GMO) have developed over several months a chronic obstructive respiratory failure (a mean VEMS of 43% of the theoretical value) in the year following the transplantation (mean delay 190 days). 6 patients presented with cutaneous, digestive or hepatic signs of chronic graft v host illness (GVH) whereas the prevalence of this complication in the population studied was 17%. Treatment combining bronchodilators and immunosuppressants was only successful in 2 cases and the outcome was fatal in the 5 other cases as a result of respiratory failure (mean delay 208 days between the appearance of respiratory symptoms and death). The pathogenesis of BO after GMO remains poorly understood. It may rest on an immune process during the course of which the BO would be the result of a chronic pulmonary GVH. Another hypothesis is that the state of the immunosuppression in these patients would favour the appearance of a bronchiolitis of an infectious origin, particularly viral. The prognosis of BO after GMO is very poor and in the absence of specific effective treatment the therapeutic strategy remains essentially that of prevention by the early detection of respiratory anomalies.

Adolescent↗
PubMed1991

[Modification of in vitro hematopoiesis induced by addition of GM-CSF in long term normal human bone marrow cultures].

We have studied the effects of GM-CSF on cell growth in Dexter's type normal human long-term bone marrow cultures. Non adherent and adherent cells were weekly harvested and studied all over the time of culture up to 10 weeks: number, cytology, hematopoietic granulocyte-macrophage progenitors content (CFU-GM). Control consisted of cultures without growth factor. GM-CSF (100 ng/ml) induced a significant increase in the number of non adherent and adherent cells, mainly increasing the number of cells of the granulocytic lineage. GM-CSF also induced a transient increase in the number of CFU-GM in the non adherent fraction, but as from week 6 of culture, there were no more CFU-GM. At last GM-CSF inhibited completely or partially the adipocyte growth in the adherent stromal cell layers. In conclusion, at this concentration, GM-CSF might be responsible for the accelerated aging, maybe linked to the hematopoietic stem cells exhaustion and to the almost exclusive presence of monocyte-macrophage cell types in the culture supernatant.

Analysis of Variance↗
PubMed1990

Myelodysplastic syndromes: a study of surface markers and in vitro growth patterns.

A study of surface markers and in vitro growth in semi-solid and liquid medium was performed in 35 patients with newly diagnosed myelodysplastic syndrome (MDS). Surface markers were studied by CD34, CD13, CD14, CD15, and CD33 monoclonal antibodies. There was no strict correlation with the FAB typing, but CD34 was expressed only in refractory anemia with excess of blasts (RAEB) or RAEB in transformation (RAEB-t). CD14 was markedly positive in the 4 cases of chronic myelomonocytic leukemia. Colony-forming cells were assessed by culture in semi-solid medium in the presence of HTB9 as growth factor. Four growth patterns were identified: a) normal growth (6 cases); b) no growth or low plating efficiency (10 cases); c) low colony and high cluster number (15 cases); and d) normal or high colony number with high number of clusters (4 cases). Expression of CD34 was associated with low colony and high cluster number. Finally we studied the proliferation and differentiation capacities in liquid culture without stimulating factor. Fifteen patients had a spontaneous proliferation. This was not correlated with any surface marker. Differentiation assessed by the loss of CD34 and/or the increase of CD15 by more than 20% at day 7 was observed in 21 cases. None of the surface markers or growth patterns was associated with a specific chromosomal abnormality, except the lack of growth in liquid culture observed in all 5q deletion cases. In univariate analysis, RAEB and RAEB-t FAB subtypes, percentage of blasts higher than 5%, staining by CD33 and CD34, and lack of differentiation in liquid culture were significantly associated with progression to leukemia and shorter survival. In multivariate analysis, only CD34 expression (P = .002) and percentage of blasts (P = .05) remained independent significant variables. CD34 was the only significant variable for prediction of survival (P = .05). It is concluded that surface marker analysis at diagnosis and after liquid culture may be a useful tool for the initial evaluation of MDS.

Antigens, CD↗