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J J Viala

Publications and source records attributed to J J Viala.

At least 19 recordsLinked to original sources

Determination of plasma cell labelling index with bromodeoxyuridine using a double immunoenzymatic technique.

Myeloma plasma cells were double stained using peroxidase and alkaline phosphatase labelled monoclonal anti-BrdU and anti-intracytoplasmic immunoglobulins. Samples were methanol fixed; DNA was denatured with formamide. The results allowed easy identification of plasma cells, their cytological examination and the calculation of percentage of plasma cells in S phase. Good correlation was found with the labelling index obtained with tritiated thymidine.

Bromodeoxyuridine

Aggregation to thrombin and collagen of platelets from a Glanzmann thrombasthenic patient lacking glycoproteins IIb and IIIa.

The aim of this study was to investigate the platelets of a Glanzmann thrombasthenic patient, which in citrated PRP failed to respond to various agonists, but aggregated and secreted to high concentrations of thrombin (0.36, 0.72 and 1 U/ml) and collagen (4, 10 and 20 micrograms/ml) when washed and resuspended in a Tyrode-albumin solution (containing 2 mM Ca2+). Aggregation of the patient platelets was not affected by anti-IIb/IIIa monoclonal antibody (P18) which strongly inhibits thrombin or collagen induced aggregation of normal platelets. Washed platelets of this patient did not aggregate to ADP (10-100 microM) in the presence of added fibrinogen (2 mg/ml) nor bind 125I-labelled fibrinogen (40 to 320 micrograms/ml) when thrombin-stimulated. Different anti-IIb/IIIa monoclonal antibodies (P2, P18) when used in binding or crossed immunoelectrophoretic studies showed a complete absence of the IIb-IIIa glycoprotein complex on the patient platelets. Moreover, glycoproteins IIb or IIIa were absent on silver-stained two-dimensional (non-reduced/reduced) polyacrylamide gel separations of the patient platelets and were not detected by Western blots used in combination with anti-PLA1 (antigen present on IIIa), anti-Leka (antigen present on IIb). This study shows that platelets lacking glycoproteins IIb or IIIa can aggregate in response to high concentrations of collagen or thrombin when resuspended in the presence of physiological concentrations of calcium. Results obtained in this study could indicate the existence of other mechanisms (other than the IIb-IIIa glycoprotein complex) involving glycolipids, heparans, proteoglycans, and/or unknown membrane glycoproteins to mediate platelet aggregation of stimulated thrombasthenic platelets.

Adult

Influence of cigarette smoking on the presentation and course of chronic myelogenous leukemia.

It is known that cigarette smoking induces leukocytosis and increased genetic instability in normal individuals. Therefore, a retrospective review was conducted of 173 patients with chronic myelogenous leukemia to detect a possible influence of cigarette smoking on initial characteristics at the time of presentation and on the course of this disease. Thirty-nine patients (23%) were smoking 5 cigarettes/d or more at time of diagnosis. Cigarette smoking was significantly related to male sex (P = 0.0005) and younger age at diagnosis (P = 0.02) and smokers tended to have lower leukocyte counts (P = 0.07) than nonsmokers. Cigarette smoking was significantly associated with early blast crisis (P less than 0.0001) and short survival (P less than 0.0001). Other characteristics associated with a poor prognosis included hepatomegaly, anemia, and a high percentage of peripheral blast cells at time of diagnosis. When studied in a multivariate analysis, cigarette smoking remained the strongest prognostic factor for both occurrence of blast crisis (P = 0.0003) and overall survival (P = 0.0001). Other poor prognosis factors found in the multivariate analysis included a high percentage of blasts in the peripheral blood at time of diagnosis and high platelet count. It is possible that cigarette smoke may act as a promoter or cocarcinogen in the transformation of chronic myelogenous leukemia.

Blast Crisis

Phase II trial of plicamycin and hydroxyurea in acute myelogenous leukemia.

A total of 23 patients with high-risk acute myelogenous leukemia (AML) at diagnosis (2 patients), relapsing AML (14) or resistant AML (6) were treated with 25 micrograms/kg i.v. plicamycin every other day for 3 weeks and 500-4,000 mg hydroxyurea per day p. o. according to the WBC count. Aplasia was observed in only two patients. Severe extrahematologic toxicity included sepsis (four cases), vomiting (four patients), toxic hepatitis (three cases), and fibrinopenia (one patient). No partial or complete responses were observed. The 95% confidence interval limit of the overall response rate (CR + PR) was 0-14%.

Bone Marrow

Increased in vivo biosynthesis of prostacyclin and thromboxane A2 in chronic idiopathic thrombocytopenic purpura.

The production of thromboxane A2 (TxA2) and prostacyclin (PGI2) was studied in patients with chronic idiopathic thrombocytopenic purpura (10 patients) compared to central thrombocytopenia (five patients) and healthy subjects (10 subjects). This production was monitored by the assay of urinary 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha as respective breakdown products of TxA2 and PGI2 by stable isotope dilution assays employing negative ion-chemical gas-chromatography-mass-spectrometry. Evidence is presented for the existence of an enhanced PGI2 and TxA2 urinary excretion in the group of idiopathic thrombocytopenic purpura (ITP) patients. Moreover, production of serum TxB2 per platelet was decreased in ITP group. These results provide arguments for an in vivo platelet cyclooxygenase hyperactivity during chronic ITP.

6-Ketoprostaglandin F1 alpha

The syndrome of abnormal chromatin clumping in leucocytes: a myelodysplastic disorder with proliferative features?

Five patients presenting extremely exaggerated chromatin clumping in leucocytes, associated with a loss of segmentation, are described. Peripheral cytopenia, a high percentage of circulating immature granulocytes (chiefly myelocytes) with variable leucocytosis, marrow hypercellularity with granulocytic hyperplasia and moderate dysplastic changes in erythroblastic and megakaryocytic lines, constitute, together with the granulocytic nuclear anomaly, the characteristic features of the studied cases. Cytogenetic analysis showed a clonal 12p anomaly in one of the three cases available for study. Survival was poor with a median of 15 months, bleeding and infections being responsible for the majority of deaths. All these findings point to abnormal chromatin clumping in leucocytes as the marker of a true entity with both myelodysplastic and myeloproliferative features. We propose that it take its place among myelodysplastic syndromes (MDS) beside chronic myelomonocytic leukaemia (CMML), with which it shares many similarities in clinical and biological behaviour.

Aged

Prognostic factors in angioimmunoblastic lymphadenopathy.

In order to identify prognostic factors in angioimmunoblastic lymphadenopathy (AIL), 30 directly diagnosed patients were prospectively followed for more than 42 months. Age and sex distribution, clinical and laboratory findings and evolution were not different from previously reported series. Median duration of survival was 24 months. Parameters associated with a longer survival in our series were localized adenopathies (P = 0.01) and the achievement of a remission (P less than 0.0001). Features associated with a shorter survival included drug exposure in relation to the onset of the disease (P = 0.02), rash (P less than 0.0001), lymph node eosinophilia (P = 0.03) and elevated serum lactic dehydrogenase (P = 0.03). Drug exposure and rash were, however, significantly dependent (P = 0.02). In addition, lymphopenia, the presence of circulating immune complexes, and the absence of polyclonal hypergammaglobulinemia may indicate a poor prognosis, although the significance level is not achieved in this short series. None of the parameters tested was significantly related to the lymphomatous transformation of AIL, which occurred in four cases. It is concluded that multicentric prospective studies of AIL are necessary in order to better define this disorder, to find prognostic factors, and to optimize therapy.

Adult

Angioimmunoblastic lymphadenopathy with malignant transformation during long-term remission of ocular melanoma.

A 52-year-old woman presented with angioimmunoblastic lymphadenopathy five years after undergoing enucleation for ocular melanoma. She was first treated by corticotherapy and azathioprine and had two successive remissions over an 18-month period. Lymph node biopsy performed when lymphadenopathy relapsed for the second time showed focal malignant transformation of angioimmunoblastic lymphadenopathy. Intensive polychemotherapy induced a complete remission. Three months after completion of chemotherapy, the patient presented with hepatic metastases from her melanoma and died shortly thereafter. This is believed to be the first documented association between angioimmunoblastic lymphadenopathy and melanoma. Issues regarding the relationship between angioimmunoblastic lymphadenopathy and nonlymphoid malignancies are raised.

Biopsy

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

Philadelphia chromosome-positive acute lymphoblastic leukaemia following radiotherapy for carcinoma of the cervix.

We report the case of a 70-year-old woman in whom Philadelphia chromosome-positive acute leukaemia occurred 12 years after radiation therapy for a carcinoma of the cervix. Morphology of the blasts was undifferentiated and immunological studies were in favour of a CALLA-positive acute lymphoblastic leukaemia. A possible relationship between the onset of leukaemia and the former radiation therapy is suggested.

Aged

Intensive chemotherapy in aggressive lymphomas: updated results of LNH-80 protocol and prognostic factors affecting response and survival.

One hundred patients with aggressive malignant lymphomas treated with the LNH-80 regimen were evaluated for long-term survival and pretreatment characteristics predictive of response and survival. LNH-80 consists of three intensive courses of adriamycin cyclophosphamide vindesine bleomycin (ACVB) followed by sequential consolidation and final intensification. Eighty-four patients went into complete remission (CR), eight had a partial response (PR), three failed to respond, and five died during induction. Twenty-three patients (27%) relapsed, in two of whom a prolonged second remission was obtained. Sixty-three patients are currently alive, two of them with disease. Four patients died in CR. Median survival and median freedom from relapse survival were not reached with a median follow-up of 4 1/2 years. Characteristics negatively associated with response in multivariate analysis were: poor performance status, bone marrow involvement, and two or more extranodal sites of disease. Duration of CR was associated with splenic involvement. Three characteristics were negatively associated with survival in multivariate analysis: age, high grade subtypes, and bone marrow involvement.

Antineoplastic Combined Chemotherapy Protocols

[Totally implantable venous-access systems: apropos of experiences of 30 patients].

Thirty-one totally implantable venous access system were investigated in patients who required intravenous administration of chemotherapy, drugs, nutrients solutions, blood products and blood sampling. Mean duration of venous access was 179 days (ranged from 9 to 429 days). Eight complications were observed, five benign without consequence on port system use, three severe (infections) requiring its removal. No death occurred during implantation and port system use. Patient acceptance was better than with other methods for repeated vascular access. In patients requiring prolonged chemotherapy, totally implantable venous access systems represent a new technique of long term venous access, with easy implantation and lack of restriction of daily activities. Review of literature show that complications are most frequently local and easy to manage. Four types of complications may have severe consequences for patient and/or port system use: catheter occlusion, venous thrombosis, local and/or general infection, and skin necrosis subsequent or not to extravasation. They represent the major cause of port system removal, but this is seldom necessary. Acquired experience allow to justify an earlier implantation of totally implantable venous access systems before chemotherapy and destruction of available surface vessels.

Adult

Influence of daunorubicin and cytarabine sequencing on the outcome of therapy in acute myelogenous leukemia: a randomized trial.

Ninety-seven patients less than or equal to 70 years of age with previously untreated primary acute myeloblastic leukemia were randomly treated with either the DAT or TAD regimen: daunorubicin (70 mg/m2/day) administered on Days 1-3 (DAT) or 5-7 (TAD) of a 7-day sequence consisting of cytarabine (200 mg/m2/day) and 6-thioguanine (200 mg/m2/day). Complete responders received consolidation, maintenance, and final intensification over 14 months using mostly the same drugs as during induction and administered in the same sequence. The regimens did not significantly differ from each other with regard to toxicity or efficacy. Complete remission rate was 80% in the two groups, and median duration of complete remission was 549 days with DAT and 518 days with TAD.

Adult

Cell-cycle prognostic value in adult acute myeloid leukemia. The choice of the best variables.

Flow cytometry with simultaneous analysis of DNA and protein content allows a most exhaustive study of cell-cycle for the prognostic evaluation of acute myeloid leukemia (AML). Sixty-seven cases of AML were studied before any form of chemotherapy had been undertaken. We determined the following cell-cycle variables: S, S + G2 + M, low protein content fraction (LPC-fraction) and high protein content fraction of G1 (HPC-G1). Patients were stratified according to age: S and S + G2 + M phases were higher for patients over 50 who did not achieve a complete remission. LPC-fraction was significantly lower for patients older than 50 who did not achieve a complete remission not only compared to the complete remission group of patients over 50, but also compared to the younger non responder group. The duration of survival was significantly longer when LPC-fraction was higher than 26% and HPC-G1 lower than 70%. Length of survival was also better when S + G2 + M was longer than 5.75%. Analysis of the therapy failure showed that S + G2 + M and LPC-fraction were significantly different between the complete remission group and the group of patients dying in aplasia. Overall, patients older than 50 with a proliferative leukemia had a worse prognosis.

Adolescent