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Biomedical subjects

D Guyotat

Publications and source records attributed to D Guyotat.

At least 109 records · Page 6Linked to original sources

Expression of CD 19 antigen on acute monoblastic leukemia cells at diagnosis and after TPA-induced differentiation.

We have previously shown that CD 19, a B-lymphoid differentiation antigen, is expressed on acute myeloid leukemia cells. In this study, the expression of CD 19 and CD 14 (a monocytic antigen) was investigated in 18 cases of acute monoblastic leukemia. The staining by anti-CD 19 antibody (SB4) ranged between 26 and 81% of the cells, and was significantly correlated with the staining by anti-CD 14. Double stainings confirmed that the antigens were expressed on the same cells. After a 48-hr culture in the presence of TPA, most cells became adherent and lost CD 19 antigen, whereas CD 14 was still expressed with only minimal changes. It is concluded that CD 19 antigen is expressed on more immature stages of monoblastic leukemias. The hypothesis that CD 19 could be an early monocytic differentiation antigen is discussed.

Antigens, CD19↗

Evaluation of a Candida antigen detection test (Cand-Tec) in the diagnosis of deep candidiasis in neutropenic patients.

The diagnostic efficiency of a serum Candida antigen detection test Cand-Tec test) was prospectively investigated in 104 leukemic patients treated by intensive chemotherapy or allogeneic bone marrow transplantation. Candida antigen titers were determined on admission and then weekly as long as patients remained neutropenic. Nine patients had a proven disseminated yeast infection (diagnosed only at autopsy in five cases). The highest Candida antigen titers were 1:2 in two patients and 1:4 or more in seven patients (sensitivity: 76% for this last titer). This highest titer was observed 12 days before to 3 days after the diagnosis. Seven out of the 97 patients without proven deep candidiasis had a maximum titer of 1:4 (specificity: 93%). The positive predictive value was 50% for a titer of 1:4 and 24% for a titer of 1:2, whereas the negative predictive value was 100% for a titer of 1:4 and 97% for a titer of 1:2. Patients with elevated titers were mostly treated by chemotherapy, were older and had a worse prognosis than those with negative titers, although the duration of neutropenia was similar. It is concluded that Candida antigen detection is a reliable method of diagnosis of deep candidiasis in neutropenic patients. The clinical interest in this test, with special regard to empiric antifungal therapy, is discussed.

Agranulocytosis↗

Acute leukaemia with t(4;11) in patients previously exposed to carcinogens.

We report three cases of acute leukaemia with t(4;11) (q21;q23), one of them of undifferentiated and the other two of lymphoid phenotype, occurring after adjuvant radiochemotherapy for breast cancer (two cases) or occupational exposure to radiation (one case). Although the myeloid phenotype and characteristic chromosomal anomalies usually observed in secondary leukaemia were lacking, our observations raise the possibility of causal relationship between exposure to carcinogens and the occurrence of a leukaemia with t(4;11).

Acute Disease↗

Acute leukaemia following high-dose chemoradiotherapy with bone marrow rescue for ovarian teratoma.

A case of acute leukaemia following intensive chemo- and radiotherapy for solid tumour is reported. A 15-year-old girl received four courses of chemotherapy with adriamycin, cyclophosphamide and cisplatinum after the surgical diagnosis of ovarian immature teratoma. An intensification treatment was performed with cyclophosphamide and total body irradiation, followed by marrow rescue. The diagnosis of myelomonocytic acute leukaemia was performed 8 months later. The patient died after a transient improvement following a treatment by hydroxyurea. The roles of the primary tumour, of the chemotherapy and of the marrow transplantation in the occurrence of leukaemia are discussed.

Acute Disease↗

Initial clonal acute lymphoblastic transformation of chronic lymphocytic leukemia with (11;14) and (8;12) chromosome translocations and acquired homozygosity.

A 69-year-old woman presented with chronic lymphocytic leukemia (CLL) diagnosed after bone marrow recovery following intensive chemotherapy for acute lymphoblastic leukemia. The retrospective diagnosis of initial blastic transformation of CLL was made. The patient eventually died, 5 months after initial blastic phase, from a blastic relapse of her CLL. Immunologic and karyotypic studies of the lymphoid cells at different times during the evolution of the disease provided evidence that both the small lymphocytes and the large blastic cells originated from the same clone since they carried the same surface markers and the same (11;14) (q13;q32) translocation. A subpopulation of cells carried in addition a t(8;12) (q24;q22) together with the loss of the normal chromosome 8 and homozygosity for the abnormal der(8). The possibility that this second population might correspond to the blast cells and that the occurrence of the t(8;12) with homozygosity might be linked to blastic transformation of the CLL is discussed.

Aged↗

Allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia in first complete remission.

Twenty-seven patients ranging in age from 15 to 36 years participated in a pilot study, and underwent allogeneic bone marrow transplantation (BMT) for acute lymphoblastic leukemia (ALL) in first complete remission (CR) in four French centers. All patients were grafted from human leukocyte antigen/mixed leukocyte culture (HLA/MLC) identical sibling after conditioning regimen consisting of cyclophosphamide and total body irradiation (TBI). Sixteen patients are alive in persistent first remission, with a median follow-up of 56 months (range, 41 to 82 months). The 6-year Kaplan-Meier probability of disease-free survival (DFS) is 59%. Only three patients relapsed (5, 7, and 7 months after transplantation). These interesting results have led us to propose, in accord with a French multicentric protocol, allogeneic BMT for adults under 40 years of age during the first CR of ALL.

Adolescent↗

[Early bacterial infections after allogenic bone marrow grafts].

The bacterial infections occurring during the period of neutropenia have been reviewed in a series of 100 allogeneic bone marrow transplant patients. Forty episodes of septicaemia were observed, in 37 patients, with a large majority of Gram positive organisms (thirty cases). Only one case of major local infection occurred (Gram negative meningitis). A non-bacterial infection was seen in 10 patients, and 36 patients presented with fever of unknown origin. Three patients who failed to engraft died of bacterial infection. Surveillance cultures showed that upper respiratory tract was a frequent site of invasion, not only for Gram positive, but also for Gram negative organisms (Pseudomonas aeruginosa).

Adolescent↗

Culture of putative Langerhans cell bone marrow precursors: characterization of their phenotype.

We searched for the presence of human CD1-positive cells in bone marrow populations in order to characterize putative Langerhans cell precursors. Bone marrow progenitors were cultured in 0.8% methylcellulose supplemented with 10% granulocyte-macrophage (GM) colony-stimulating factor(s) GCT and HTB9. We compared the kinetics of these two factors and found that GCT was the more appropriate for our study. After 8 days of culture, colony-forming units of granulocyte-macrophages (CFU-GM) were tested for the presence of CD1-positive cells using the immunofluorescence technique. Positive cells were counted by cytofluorometric analysis: 9.4% CD1a (BL6), 13.4% CD1c (L161), 4.3% CD1b (NuT2), 4.6% CD2 (T11), and 25.5% CD33 (My9). Ultrastructural features and phenotype were then specified by the immunogold labeling technique using electron microscopy. A subpopulation of CD1-positive cells showed the ultrastructural morphology of bone marrow pro-monocyte/monocyte cells. By using well-characterized monoclonal antibodies, it was demonstrated that these cells expressed the following phenotype: CD14+, CD33+, CD4+, HLA-DR+, HLA-DP+, HLA-DQ-, OKT10-, CD2-. These data indicate that these bone marrow promonocyte/monocyte progenitors express a phenotype similar to that of epidermal Langerhans cells but the density of each antigen is much lower than that observed on mature skin dendritic cells.

Antibodies, Monoclonal↗

Impact of T-cell depletion on outcome of allogeneic bone-marrow transplantation for standard-risk leukaemias.

71 leukaemic patients having HLA-matched bone-marrow transplants (BMT) were randomised to receive whole marrow (group A) or marrow depleted of T cells by treatment with monoclonal antibodies (anti CD4-CD5-CD8, group B; anti CD2-CD5-CD7, group C) plus complement. All patients received cyclophosphamide and total body irradiation before transplantation and cyclosporin after BMT. Marrow treatment removed 97% of T cells (median) in group B and 99% in group C. Although both serious and mild graft-versus-host disease (GVHD) were reduced in T-cell depleted patients, graft failure and relapse were increased. Graft failure was caused by GVHD and transplant complications in the controls and by rejection and relapse in the T-cell depleted groups; relapse-free survival did not differ between the groups. Without better control of host immunity and of the residual leukaemia T-cell depletion of the marrow, BMT should not be pursued in standard-risk patients.

Adolescent↗

Incidence and prognosis of cytomegalovirus infections following allogenic bone marrow transplantation.

The incidence and the outcome of cytomegalovirus (CMV) infections were evaluated in 83 adult recipients of allogenic bone marrow transplantation. Virological and serological surveillance was performed weekly for 3 months posttransplant, and then every other week or every month until 1 year. CMV infection occurred in 45 patients, with a cumulative risk of 62% at 1 year and 66% at 2 years. In multivariate analysis, two factors significantly influenced the incidence of CMV infection: patients with pretransplant positive anti-CMV titres had a risk of infection of 72% at 1 year versus 33% for patients with negative titres. Patients with acute myeloid leukemia were also infected more frequently (85% at 1 year) than patients with acute lymphoblastic leukemia (56%), chronic granulocytic leukemia (45%), or aplastic anemia (47%). In both univariate and multivariate analysis, CMV infection was not associated with a worse prognosis. However, 5 (out of 10) cases of lethal interstitial pneumonitis were associated with CMV, and two patients died of possible CMV encephalitis. All these patients had been suffering from severe acute or chronic graft versus host disease.

Adult↗

Surface markers in acute non-lymphoid leukemia: analysis with a panel of 36 monoclonal antibodies.

The reactivity of a panel of monoclonal antibodies was studied in fifty-four cases of acute myeloid (AML) or undifferentiated (AUL) leukemias. Thirty-six antibodies from the Myeloid section of the Second Workshop on Human Leukocyte Differentiation Antigens were used in an indirect immunofluorescence assay. The antibodies could be classified into three groups recognizing respectively granulocytic, monocytic or granulomonocytic leukemias. Most antibodies stained erythroblastic and megakaryoblastic leukemias. In each group, it was possible to define antibodies staining either the less differentiated forms (FAB M 1 and M 5 a) or the more differentiated forms (M 2, M 3, M 4 and M 5 b). Six out of eight AUL were stained by some of the antibodies (mainly from the monocytic group). However, a heterogeneity of stainings in a same blast population was observed.

Acute Disease↗

Day 4 bone marrow aspirate for prediction of resistance to induction chemotherapy in acute myeloid leukemia.

Bone marrow aspirate was performed on day 4 of a 7-day induction chemotherapy regimen using daunorubicin, cytosine arabinoside and thioguanine in 42 patients with acute myeloid leukemia (AML). The mean percentage of remaining abnormal cells in day 4 bone marrow was significantly higher in patients having resistant disease (RD) than in patients entering complete remission (CR). Except for patients with FAB M3 AML, most patients who had more than 40% abnormal cells in their day 4 bone marrow had RD. In addition, patients entering CR despite having more than 40% abnormal cells remaining in their day 4 bone marrow seemed to have short CR.

Adolescent↗

Adult acute lymphoblastic leukaemia: is cell proliferation related to other clinical and biological features?

Flow cytometry with propidium iodide and fluorescein isothiocyanate was used to study 46 cases of adult acute lymphoid leukaemia (ALL) before any form of chemotherapy. Cell proliferation was related to the other clinical and biological characteristics and its prognostic significance was evaluated. The following cell-cycle variables were determined: S, G2 + M, and the Low Protein Content fraction of G1 (LPC fraction). The L3 group, corresponding to B-ALL, had significantly higher proliferation than L1 and L2 (P less than 0.01). The proliferation rate was not significantly higher for T-ALL than for the other phenotypes. Complete remission was successfully induced significantly more often in cases with the LPC fraction under 50% (P less than 0.05). Failure was mainly related to resistance to chemotherapy. Of the four patients who died during aplasia, three had an LPC fraction below 25%. Duration of complete remission and survival were significantly shorter for L3 which is the most proliferative ALL (P less than 0.01). Survival was also found to be longer (P less than 0.05) when G2 + M was between 3.8% and 5.1%. This finding and the negative correlation between S and G2 + M (P less than 0.01) are discussed.

Adolescent↗