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Biomedical subjects

S Castaigne

Publications and source records attributed to S Castaigne.

At least 109 records · Page 6Linked to original sources
PubMed1986

Interferon alpha in the treatment of hairy cell leukemia.

Fifty-four patients with hairy cell leukemia were treated for 7 months with three types of subcutaneously injected interferon: recombinant interferon alfa-2a from Hoffmann-La Roche (3 X 10(6) U daily); recombinant interferon alfa-2b from Schering (2 X 10(6) U/m2, three times per week); and partially purified human leukocyte interferon alpha from the Finnish Red Cross (3 X 10(6) U daily). After 4 months, in 27 patients hairy cells decreased dramatically (P less than 0.01) while platelets (P less than 0.05), monocytes (P less than 0.01), polymorphonuclear leukocytes (P less than 0.01) and hemoglobin (P less than 0.01) increased (in this order) as treatment progressed. Morphometric parameters were used to estimate the relative volume of hairy and myeloid cells present in bone marrow. Biopsies were performed at the beginning of the study and in the second, fourth, and seventh months thereafter. Bone marrow disorders were slower to improve as compared with blood. Six severe cases of hairy cell leukemia were responsive to treatment, but required special monitoring during the first 2 months. All three interferons studied are efficient. Interferon receptors, oncogene (mRNA levels) expression, and the relationship between PDGF and fibrosis in hairy cell leukemia are under investigation.

Adult↗
PubMed1986

Can peripheral T-cell lymphomas be morphologically subclassified? A morphometric approach to 21 cases.

Morphometric analysis of nuclear sizes and shapes was carried out on semithin sections of lymph node for 21 patients suffering from non-Hodgkin's peripheral T-cell malignant lymphoma (ML) (excluding mycosis and Sézary syndrome). Twenty cases of B-cell ML and three cases of Sézary syndrome with massive lymph node infiltration were also studied as references. Wright and Isaacson's recent proposals were applied to classify the peripheral T-cell MLs into monomorphic medium-cell ML (eight cases), pleomorphic ML (nine cases), and monomorphic large-cell ML (four cases). These three classes were readily distinguishable by morphometric analysis of nuclear sizes. Nuclear areas and their coefficients of variation were higher in pleomorphic MLs than in monomorphic medium-cell MLs (p less than 0.01). Large-cell monomorphic MLs were set apart by the histograms of their nuclear sizes. The mitoses were evaluated on histological sections and found to be more numerous in pleomorphic ML than in monomorphic medium-cell ML (p less than 0.05). Nuclear irregularity in the 21 cases of peripheral T-cell ML was lower than in Sézary cells. Morphometry clearly demonstrates the morphological distinctiveness of the subclasses of peripheral T-cell ML. Their biological significance has yet to be determined.

Adult↗
PubMed1986

Treatment of hairy cell leukemia with recombinant alpha interferon: II. In vivo down-regulation of alpha interferon receptors on tumor cells.

Interferons (IFNs) initiate their effects by interacting with specific high-affinity cell surface receptors, but little is known about the physiology of IFN receptor interaction in vivo. Treatment of patients suffering from hairy cell leukemia (HCL) with human recombinant alpha IFN results in significant tumor regression, with clinical improvement in a high percentage of cases. To investigate a possible relevance of binding parameters as response markers, IFN receptor interaction on tumor cells responsive to IFN in vivo was studied. Binding of human alpha 2 IFN to circulating hairy cells was analyzed before and during IFN therapy in ten patients selected on the basis of high numbers of peripheral hairy cells. Binding experiments were carried out on Ficoll-Paque fractionated peripheral cell samples containing a majority of hairy cells. All patients reacted to recombinant alpha IFN treatment with a striking decrease in binding capacity within 12 hours after the first injection. As demonstrated by using a monoclonal antibody able to recognize alpha 2 IFN bound to its receptor, this decreased binding capacity was not due to blocking by circulating IFN but rather to a decrease in receptor number. This receptor "down-regulation" was partially reversible after the first IFN injection. However, upon prolonged IFN therapy, all patients displayed a stable state of decreased receptor expression. Down-regulation of IFN receptors can be regarded as a response marker to IFN treatment. This response marker, however, was not correlated with the clinical response within the first months of IFN therapy.

Animals↗
PubMed1986

[Acute lymphoblastic leukemia in Burkitt cells: clinical, therapeutic and prognostic aspects].

This presentation reports on patients with 13 B - acute lymphoblastic leukemia (ALL), treated with intensive chemotherapy. To date 5 patients are alive, in complete remission (greater than 24 months), 4 of them had CNS disease at diagnosis; 7 patients relapsed, 2 to 4 months after complete remission, 6 of them having CNS relapse, isolated or with bone marrow involvement. The improvement in prognosis of B-ALL results from intensive chemotherapy, but the prognosis remains poor because of early relapses, especially CNS relapses (survival rate is less than 50%). The authors propose new therapeutic approaches.

Adolescent↗
PubMed1986

c-myc and c-fos expression during interferon-alpha therapy for hairy cell leukemia.

Low-dose interferon-alpha (IFN-alpha) therapy is consistently effective in the treatment of hairy cell leukemia (HCL). In two cases of resistance to IFN-alpha administration, we diagnosed variant HCL, a form of HCL with intermediate features between typical HCL and B cell prolymphocytic leukemia. We tried to distinguish variant and typical hairy cells (HCs) by Northern blot analysis of the oncogenes expressed in vivo. We report that variant HCs contain c-myc transcripts in contrast to typical HCs, whereas c-fos transcripts are detected in both cell types. We also report that the mRNA levels of c-myc are not modified in variant HCs by IFN-alpha treatment, whereas the level of c-fos mRNA is modulated in both types of HCs. Our findings suggest that the failure to modulate c-myc expression in vivo might indicate the limits of low-dose IFN-alpha therapy.

Cell Cycle↗
PubMed1986

Treatment of hairy cell leukemia with recombinant alpha interferon: I. Quantitative study of bone marrow changes during the first months of treatment.

Seventeen patients with hairy cell leukemia (HCL) were treated with low doses of recombinant alpha interferon (IFN) for over 4 months. Marked improvement was observed in peripheral blood and bone marrow in 15 of 17 patients. Comparison of pretreatment values and hemograms obtained after 4 months of treatment showed a marked decrease in circulating hairy cells (P less than .01), a decrease in the number of lymphocytes (P less than .01), a rise in the number of platelets (P less than .05), granulocytes (P less than .05), and monocytes (P less than .01), and a rise in the hemoglobin level (P less than .01). Transient reduction in the number of granulocytes was noted during the first month. Correction of thrombocytopenia often appeared within 2 months and usually preceded improvement of anemia, monocytopenia, and neutropenia. Bone marrow biopsy specimens were taken before treatment and 2, 4, and 7 months after its initiation. The volumes occupied by hairy cells, cells of the myeloid lines, and adipocytes were studied by stereological analysis of semithin sections. Decrease in the volume occupied by hairy cells was seen after 4 months of treatment (P less than .01), and the volume continued to decrease at the seventh month (P less than .05). Hairy cells were no longer detected on bone marrow biopsies of 4 of 17 patients by the fourth month and in 3 of 8 additional patients by the seventh month. A rise in the volume occupied by normal myeloid cells was visible by the second month of treatment (P less than .01). Nevertheless, the volume occupied by granulocytes remained lower than in the normal controls (P less than .01). After an initial increase during the first 2 months of treatment (P less than .01), the overall cellularity remained unchanged at 4 months and decreased significantly (P less than .05) at 7 months. Except for biopsies at 2 months, mean cellularity was below that of control biopsies (P less than .01).

Biopsy↗
PubMed1985

Low-dose cytosine arabinoside treatment for acute nonlymphocytic leukemia in elderly patients.

Thirty patients older than 65 years of age with acute nonlymphocytic leukemia were treated with low-dose cytosine arabinoside (10 mg/m2 subcutaneously every 12 hours for 15 to 21 days). Fifteen achieved complete remission and five had partial remission. Treatment was more effective when initial bone marrow cellularity was low (P = 0.007). Four of six patients with secondary leukemia entered complete or partial remission. Therapy was well tolerated with reduced myelosuppression and few number of early deaths. Sixteen patients followed the whole treatment as outpatients. Six of 12 patients who achieved complete remission showed no evidence of post-therapeutic bone marrow aplasia. These data are consistent with the view that low-dose cytosine arabinoside acts on leukemic cells as a differentiating agent.

Acute Disease↗
PubMed1985

[Treatment of acute myeloblastic leukemia in elderly patients with low-dose cytosine arabinoside].

Forty-eight patients, aged from 65 to 88 years, presenting with de novo acute myelogenous leukemia were treated with a low-dose cytarabine regimen (10 mg/sq.m subcutaneously 12-hourly for 15 to 28 days). Twenty-four complete remissions and 7 partial remissions were obtained. The complete remission rate correlated with low initial bone marrow cellularity (p less than 0.05). Bleeding occurred in 28 patients and fever was noted, also in 28 patients. Four patients died of infection during induction treatment. Fourteen patients were treated as out-patients, but regular medical supervision was necessary. The median duration of complete remission was 8 months. The median survival for all patients was 15 months. It is concluded that low-dose cytarabine is an alternative to intensive chemotherapy in elderly patients with acute myelogenous leukemia.

Aged↗
PubMed1985

[Treatment of malignant hemopathies with aracytine in low doses. Analysis of 159 cases].

Based on the in vitro experiments which showed the capacity of Aracytine (AraC) to induce differentiation of leukemic cells, low dose AraC treatment of patients with acute myeloid leukaemia (AML) or myelodysplastic syndromes (MDS) has been available since 1980. Many studies involving only small numbers of patients have demonstrated contradictory results regarding the efficacy or the mechanism of action of this regimen. A retrospective clinical study is presented, including 159 patients treated in 11 French institutions and 1 German institution (AML: 99 patients; MDS: 38 patients). The study confirms the efficacy of low dose AraC, especially in elderly patients with hypoplastic AML. Although, less severe than with high dose chemotherapy, toxicity needs regular monitoring. The mechanism of action cannot be ascertained by this clinical study, however half of the complete remissions were obtained with no bone marrow aplasia. Studies with low dose AraC and/or other in vitro differentiating agents need to be continued.

Aged↗
PubMed1985

Expression of vimentin intermediate filament cytoskeleton in acute nonlymphoblastic leukemias.

Since vimentin intermediate filament (IF) expression in hemopoietic cells varies with the cell lineage as well as the state of differentiation of the cells, we studied the vimentin cytoskeleton by direct immunofluorescence and electron microscopy in 50 cases of acute nonlymphocytic leukemias. We found that malignant cells tend to reproduce the vimentin organization characteristic of their normal cellular counterpart. Thus, in M2 and M3 leukemias (French-American-British classification), vimentin was often reduced to a juxtanuclear bundle of filaments contrasting with the rich filamentous network expressed by M4 or M5 leukemias. In erythroblastic leukemias (M6) and megakaryoblastic leukemias, both identified by the expression of lineage-specific antigens, the absence of vimentin IFs could be correlated with the level of differentiation reached by the blasts. M1 leukemias displayed an abnormal pattern of vimentin organization with aggregated filaments giving a ring-like structure. However, no abnormality of the vimentin polypeptide could be detected by two-dimensional electrophoresis. These results show that the expression of the vimentin IF cytoskeleton may be a useful marker of differentiation in the study of leukemic cells.

Acute Disease↗
PubMed1985

Intensive chemotherapy of hairy cell leukemia in patients with aggressive disease.

Seven patients with hairy cell leukemia were treated by intensive chemotherapy because they were considered to have a progressive disease and a poor short-term prognosis. The mean age was 47 years (range, 36 to 58). Six of seven patients had prior splenectomies with minor or transient hematologic responses. One patient had no spleen enlargement. The seven patients had never received any cytotoxic drugs and had prolonged granulocytopenia (less than 300/microL) with recurrent, severe infectious episodes. Chemotherapy included Rubidazone (zorubicine hydrochloride) 450 mg/m2 on day 1, arabinosyl cytosine 200 mg/m2/d from day 1 to day 5, and cyclophosphamide, 2,000 mg/m2 on day 5. Responses were assessed through examination of repeat bone marrow biopsy specimens and blood counts. A complete response was defined as normal blood counts associated with the disappearance of hairy cell infiltration and fibrosis on the bone marrow biopsy specimens. A partial response was defined as normal blood counts with persistence of leukemic cells in the bone marrow. Three patients achieved a complete response, and one patient had a partial response. Three patients died of infectious complications during induction chemotherapy. For the responding patients, the mean duration of aplasia was 37 +/- 5 days. Follow-up for the responding patients has been 44+, 24, 32+, and 23+ months. One patient with a complete response died while on maintenance therapy. We conclude that complete and prolonged histologic remission of hairy cell leukemia can be obtained with intensive chemotherapy. The toxicity of chemotherapy is such, however, that progressive disease after splenectomy needs to be more clearly defined.

Adult↗