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D Fière

Publications and source records attributed to D Fière.

At least 37 records · Page 2Linked to original sources

Prognostic value of early response to chemotherapy assessed by the day 15 bone marrow aspiration in adult acute lymphoblastic leukemia: a prospective analysis of 437 cases and its application for designing induction chemotherapy trials.

The early response to induction chemotherapy assessed by the percentage of residual blast cells in the D15 bone marrow aspiration was prospectively evaluated in 437 patients included in the same multicentric trial of newly diagnosed adult acute lymphoblastic leukemia (LALA87). Among them, 286 patients (65.4%) had < or = 5% residual blasts and their complete remission (CR) rate at D28 was 91% while the CR rate at D28 was only 34% for the 151 patients (34.6%) with more than 5% blasts at D15 of the induction chemotherapy. The persistence of more than 5% of blasts was associated with a significantly worse overall survival (P < 0.0001) and worse disease-free survival (P = 0.02). These data are used as a support for simulating different strategies in order to improve CR rates in future clinical trials. Results are consistent with the fact that D15 marrow evaluation might be a relevant test allowing an early intensification of a subgroup of patients predicted to fail with conventional induction chemotherapy.

Adolescent↗

[Occupational exposure and malignant hemopathies: a case-control study in Lyon (France)].

A hospital based case-control study was carried out in Lyon with the aim of assessing the association between haematologic malignancies and occupational exposures to 320 compounds. Job histories were obtained by questionnaire for 118 cases (52 non Hodgkin lymphomas, 48 acute myeloid leukemia, 18 others leukaemias), and 118 controls with diseases other than cancer from the same general hospital; controls were matched for sex, age and nationality. Systematic coding of exposures based on a blind analysis of job histories, was done by a team of experts in chemistry and occupational health. Mantel-Haenszel analysis was performed. Significantly elevated odds-ratio were observed for non Hodgkin lymphomas and exposure to mineral oils (14.86; 2.76-80.0), excavation dusts (3.91; 0.94-15.95), alkali compounds (2.90; 1.09-7.68), inks (2.47; 1.09-5.17). For inks, a dose-response relation was observed. Elevated odds-ratios appeared for acute myeloid leukaemias and arsenic compounds (3.02; 0.90-10.13) and lead compounds (3.70; 1.09-13.44). When regarding industrial activities, two of them are more frequently found: food industries (14 cases/5 controls), public works (12 cases/0 control). When regarding jobs, winding (6 cases/0 control), glass workers (8 cases/1 control) and warehousemen (10 cases and 4 controls) are more often seen among cases.

Adult↗

Fusarium infections in immunocompromised patients: case reports and literature review.

Five cases are reported of Fusarium infection in patients with aplasia following chemotherapy of leukemia. The clinical signs, diagnosis and course of the infection during treatment are outlined and discussed in conjunction with the characteristics of other cases already reported in the literature. Sixty-three cases of Fusarium infection have been reported in immunocompromised patients, 44 cases since 1985. These included patients with hematological malignancies (58 cases), especially acute leukemia (43 cases). The main sites of infection were the skin (46 cases), blood (28 cases) and lungs (13 cases). The infection was mostly diagnosed by means of skin biopsy but also by means of positive blood cultures. Forty-three strains were identified, 19 of which were Fusarium solani. Amphotericin B treatment was given in 55 cases, often combined with other antifungal agents, leukocyte transfusions or granulocyte-macrophage-colony stimulating factor. The outcome was fatal in 36 of the 63 cases reported, often due to resistance of the strain to antifungal agents, particularly amphotericin B (20 of 33 strains tested). The most important risk factor seems to be profound and prolonged aplasia. Deep mycoses due to Fusarium species thus pose an important problem and are occurring in increasing numbers in immunocompromised patients. Treatment of these infections is difficult and the prognosis is poor.

Adult↗

Adult acute lymphoblastic leukemia: a multicentric randomized trial testing bone marrow transplantation as postremission therapy. The French Group on Therapy for Adult Acute Lymphoblastic Leukemia.

PURPOSE: In a prospective multicenter study, we analyzed the benefits of allogeneic bone marrow transplantation (BMT) in a nonselected group of adult patients with acute lymphoblastic leukemia (ALL) and, by a randomized trial, evaluated the effectiveness of autologous BMT over chemotherapy as postremission therapy in patients younger than 50 years who were not candidates for allogeneic BMT. PATIENTS AND METHODS: After induction therapy that randomized patients to receive one of two anthracycline-containing regimens, either daunorubicin (DNR) or zorubicin (ZRB), patients were assigned to postremission treatment according to age and results of HLA typing. Patients younger than 40 years with an HLA-identical sibling (group 1) were scheduled to receive cyclophosphamide 60 mg/kg on days 1 and 2, total-body irradiation (TBI), and allogeneic BMT. Patients older than 50 years (group 2) received the chemotherapy arm composed of three monthly consolidation courses (DNR or ZRB, cytarabine, and asparaginase) followed by maintenance chemotherapy (modified L10 regimen). The remaining population (group 3) was randomly assigned to receive, after the three 1-month consolidation courses, either the chemotherapy arm or autologous BMT following a conditioning regimen similar to that of group 1. RESULTS: Of the 572 assessable patients, 436 achieved complete remission (78% +/- 2% for DNR v 74% +/- 3% for ZRB; P = .3). The estimated 3-year disease-free survival (DFS) rate for the 116 patients included in group 1 was 43% +/- 5%. Both autologous BMT (95 patients) and chemotherapy (96 patients) produced comparable 3-year DFS rates (39% +/- 5% v 32% +/- 5%) and survival durations (49% +/- 5% v 42% +/- 5%). However, late relapses after 36 months were mainly observed in the chemotherapy arm. CONCLUSION: This first interim analysis did not demonstrate a benefit of this autologous BMT procedure over classical maintenance chemotherapy in patients with ALL who received consolidation chemotherapy.

Adolescent↗

[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↗

Response of hematopoietic precursor cells to hematopoietic growth factors in the myelodysplastic syndromes.

The in vitro effects of 4 recombinant hematopoietic growth factors on myelodysplastic syndrome cells from 22 patients were assessed by colony assays (CFU-GM, BFU-E). DNA synthesis, cytological and cell phenotypic studies. Growth factors seemed to be potent stimulators on cell proliferation, but showed only limited effects on cell differentiation. Combinations of factors were more efficient than factors used alone. Nevertheless, culture growth patterns remained abnormal. Cell proliferation was major in the cases with excess of blasts with, in 2 cases, stimulation of leukemic cells.

Cell Differentiation↗

[Intensive induction and early consolidation of acute lymphoid leukemia in the adult. A pilot study of feasibility and long-term development].

Between April and December, 1982, a multicentre pilot study was conducted in 45 patients aged from 16 to 73 years suffering from acute lymphoblastic leukaemia to test the feasibility of an intensive and short induction phase followed by an early consolidation phase. All patients received a 5-day course of induction chemotherapy with prednisone, vincristine, AraC and rubidazone, then a "triple A regimen" for consolidation, consisting of adriamycin, AraC and asparaginase. The complete remission rate was 73 per cent. Toxicity during induction was characterized by frequent infections, but the consolidation treatment was well tolerated. Thus, the sequence intensive induction-early consolidation proved feasible and acceptable. In terms of survival, 8 out of the 33 patients in remission are still alive and well after more than 4 1/2 years.

Adolescent↗

Alternating v repeated postremission treatment in adult acute myelogenous leukemia: a randomized phase III study (AML6) of the EORTC Leukemia Cooperative Group.

The value of a postremission treatment in acute myelogenous leukemia (AML), with alternating combinations of non-cross-resistant drugs, has been prospectively assessed. Of 515 evaluable patients, 347 (67.4%) entered into complete remission (CR), following induction treatment with daunorubicin (DNR), vincristine (VCR), and cytosine arabinoside (ara-C). After one consolidation course, 248 patients were randomized for six courses of intensive maintenance: either repeated treatment with DNR-VCR-ara-C, or alternating treatment where amsacrine (AMSA) was combined with high dose ara-C on cycle 1,3, and 5 and with 5-azacytidine on cycle 2, 4, and 6. Ninety-nine patients were not randomized: 57 were introduced in a bone marrow transplantation (BMT) program, and 42 went off study, mainly for treatment toxicity or refusal. The main prognostic factors for achievement of CR were performance status, cytogenetics, and age, and for the disease-free survival (DFS): age and number of courses to CR. The rate of second remission was fairly high (64%) for patients relapsing off therapy. The DFS appeared identical (median, 53 weeks), in the two randomized arms, the alternating treatment not showing superiority to the repeated one, in spite of an increased toxicity. The median overall survival for patients achieving a CR was 90 weeks. The reason for the failure of alternating maintenance treatment to improve the DFS is probably related to an insufficient dose intensity: five patients who relapsed during maintenance arm B achieved a second CR with a more intensive combination of high-dose ara-C and AMSA. In addition, 60 patients underwent a BMT (43 allogeneic and 17 autologous). The DFS of patients treated with allogeneic BMT tended to be superior to the one obtained with the chemotherapy program. However the overall survival, as well as the event-free survival, seemed equivalent, including patients who relapsed before the planned BMT. Comparisons between allogeneic BMT, autologous BMT, and intensive consolidation during first CR deserve further prospective studies in AML.

Adolescent↗

Treatment of adult acute lymphoblastic leukemia. Preliminary results of a trial from the French Group.

We present here the results of a cooperative trial in 244 adult patients with acute lymphoblastic leukemia. Induction therapy with vincristine, cytoxan, and prednisone (VCP) gave the same complete remission rate after one course as more aggressive induction with vincristine, rubidazone, araC, and prednisone (VRAP) due to increased toxic death in the aggressive arm. Because of high efficacy of salvage therapy with VRAP regimen in patients failing to achieve CR with VCP regimen, patients initially randomized to receive VCP had a significantly higher CR rate than patients initially receiving VRAP (87% vs. 73%, p = 0.01). Patients randomized to receive postremission consolidation using adriamycin, araC, and asparaginase (AAA) prior to maintenance had a significantly longer remission than patients not receiving consolidation (p less than 0.005). At the time of analysis allogeneic bone marrow transplantation does not significantly increase disease-free survival when compared with intensive consolidation chemotherapy.

Adult↗

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↗

Acute leukemia with t(4;11) following treatment for breast cancer.

We report the case of a 51-year-old woman presenting t(4;11) acute undifferentiated leukemia 19 months after initiation of adjuvant radio-chemotherapy for a breast cancer. Morphology of the blasts was FAB L2 and cytochemical and immunological studies were in favor of an undifferentiated leukemia. A possible relationship between t(4;11) leukemia and exposure to carcinogens is discussed.

Acute Disease↗

Intensive timed chemotherapy protocol for 37 resistant or relapsing acute myeloid leukemias.

Thirty-seven patients with acute myeloid leukemia in relapse or at initial diagnosis but resistant to conventional induction regimen have been treated by single-cycle timed sequential chemotherapy, including continuous infusion of cytarabine over 72 hours on Days 1-3 and 8-10 and short injections of daunorubicin on Days 1-3. There were 21 complete remissions (56%), 11 failures, and five early deaths. For responders, median durations of complete remission and survival were 7 and 12 months, respectively.

Adult↗

[Histological transformation of low malignancy lymphoproliferative syndromes. Clinical and developmental study of 32 cases].

Fourteen out of 283 patients with chronic lymphoid leukaemia, 2 out of 47 with Waldenström's disease and 16 out of 136 with low malignancy lymphoma (follicular with predominant small cleaved cells, mixed follicular with small and large cells, or diffuse lymphocytic) underwent histological transformation of their disease into a highly malignant lymphoma (immunoblastic in 14 of the 32 cases). There are no clinical or biological signs that predict these changes which seem to occur haphazardly in time. Seven patients died within one month of the diagnosis. The classical treatments failed. Complete remission was obtained in 5 cases with the intensive and sequential chemotherapy used for initially aggressive lymphomas.

Antineoplastic Combined Chemotherapy Protocols↗

[Severe quantitative bone marrow insufficiency: results of treatment with high-dose antilymphocyte serum].

Nineteen patients with severe aplastic anaemia were treated with 21 courses of horse antithymocyte globulins (ATG). Changes in haematological parameters were correlated with ATG dosage. One of the 11 patients who received less than 100 mg/kg is still alive after more than 12 months. One of the 10 patients who received more than 100 mg/kg died of infection; in the remaining 9 patients, treatment resulted in increase or even return to normal of haemoglobin, polymorphonuclear and platelet levels. None of these 9 patients relapsed during a median follow-up of 16 months (range: 7 to 35 months). Immediate drug tolerance and serum sickness were unrelated to ATG dosage. These results confirm the therapeutic effectiveness of antithymocytic globulins in severe aplastic anaemia; they also suggest that 150 mg/kg doses are required to obtain satisfactory and long-lasting results.

Adolescent↗

Cellular pharmacokinetics of daunorubicin: uptake by leukaemic cells in vivo and fate.

In 6 patients with acute myeloblastic leukaemia, daunorubicin was assayed in leukaemic cells from peripheral blood or bone marrow. The cells were separated from red blood cells and granulocytes by centrifugation on a Ficoll-Isopac gradient. The assay was performed by high performance liquid chromatography. Daunorubicin concentrations in peripheral leukaemic cells, 2 hours after the end of the infusion, were much higher than in plasma, the cell/plasma concentration ratio reaching about 350 and rising to almost 700 at 24 h. At that time, drug concentrations were even higher in the bone marrow leukaemic cells. The value of the assay of daunorubicin in cells as method for monitoring therapy is discussed.

Adult↗