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Biomedical subjects

D Hollard

Publications and source records attributed to D Hollard.

At least 19 recordsLinked to original sources
PubMed1996

A prospective randomized trial of idarubicin vs daunorubicin in combination chemotherapy for acute myelogenous leukemia of the age group 55 to 75.

A prospective randomized study was conducted comparing the efficacy and toxicity of two anthracyclines for the treatment of patients with acute myeloid leukemia (AML) between 55 and 75 years. A total of 220 patients were randomized to receive as induction chemotherapy cytosine arabinoside (Ara-C: 100 mg/m2/day; continuous infusion for 7 days) combined with either daunorubicin (DNR: 50 mg/m2/day, i.v. bolus for 3 days) (n=108) or idarubicin (IDA: 8 mg/m2/day, i.v. bolus for 5 days) (n=112). The complete remission (CR) rate was similar (P=0.296) after IDA (76/112; 68%) and DNR (66/108; 61%) (P=0.3). For patients aged 55-65, the CR rate was significantly higher after IDA (39/47; 83%) than after DNR (29/50; 58%) (P=0.007). Persistent leukemia was more frequent after DNR (26/108) than after IDA (13/112; P=0.015). Hematological and extra-hematological toxicities were similar. The CR patients were given a consolidation course of chemotherapy with Ara-C: 50 mg/m2/12 h, subcutaneously for 5 days, combined with either DNR:30 mg m2/day, i.v. bolus for 3 days or IDA:8 mg/m2/day i.v. bolus for 3 days according to the initial randomization, and then received a continuous maintenance treatment for 2 years. The survival and disease-free survival (DFS) were similar in both groups; there was no difference in the risk of relapse. However, there was a trend for a longer event-free survival (EFS) in the IDA group than for the DNR patients (P=0.07). Our results seem to indicate that IDA is probably more efficient than DNR for AML patients between 55 and 75 years, and confirm the data published in other studies comparing prospectively IDA and DNR in adults.

Aged↗
PubMed1996

Allogeneic vs autologous stem cell transplantation vs chemotherapy in patients with acute myeloid leukemia in first remission: the BGMT 87 study.

In 204 adult patients with de novo acute myeloid leukemia (AML), we prospectively compared allogeneic bone marrow transplantation (alloBMT), autologous stem cell transplantation (ASCT) and chemotherapy (Chemo). 162 patients (79.4%) achieved a complete remission (CR). Of the 135 patients who were still in CR after consolidation, 96 patients were less than 46 years of age: 36 patients had an HLA-identical sibling donor and were allocated for alloBMT (group I); they were compared to the 60 other patients who did not have an HLA-identical sibling donor and were treated with either ASCT or chemotherapy (group II). The 3-year disease-free survival was higher for group I patients (66.5 +/- 16%) than for the 60 group II patients (42.4 +/- 13%) (P < 0.05). The actuarial risk of relapse at 3 years was significantly lower for group I patients (24 +/- 15%) than for the other 60 group II patients (56 +/- 13%; P < 0.009). By multivariate analysis, the disease-free survival and risk of relapse were influenced by the initial WBC count (P < 0.02 and P < 0.006), the number of chemotherapy courses for CR (P < 0.001 and P < 0.01) and the type of post-induction treatment (alloBMT vs no alloBMT; P < 0.1 and P < 0.02). The 99 patients who did not fulfill the inclusion criteria for alloBMT were given intensive chemotherapy including high-dose aracytine. When they were still in CR (n = 77), these patients were then randomized for either ASCT (n = 39) or Chemo (n = 38). We were unable to detect any statistical difference between ASCT and Chemo for either disease-free survival, risk of relapse or survival. These results indicate that alloBMT seems to produce results which are at least superior to those of other therapeutic modalities. The results of either ASCT or Chemo look similar.

Acute Disease↗
PubMed1995

Therapy program for patients with advanced stages of chronic lymphocytic leukemia. Chlorambucil, splenectomy, and total lymph node irradiation.

BACKGROUND: The clinical course of chronic lymphocytic leukemia (CLL) is variable. Staging systems define high risk groups, such as patients with Rai's Stage III and IV and Binet's stage C disease, as having a poor overall median survival. Most combination therapy programs have resulted in similar results. Chlorambucil remains the most commonly used drug, and new drugs, such as fludarabine, are promising. METHODS: Fifty-three patients with poor prognosis CLL (Stage III and IV) underwent chlorambucil treatment at a high intermittent dose. When Stage 0 was obtained, patients were considered responders and kept under surveillance. When the patients stopped responding after one or several courses of chlorambucil, further therapy was performed, including splenectomy (29 patients) and total lymph node irradiation (9 of the 29 splenectomized patients). RESULTS: The overall median survival was 60 months. Thrombocytopenia and anemia were resolved in 55% and 82% of the patients, respectively, after chlorambucil therapy and in 85% and 100%, respectively, after splenectomy. Complications occurred in 34% of the splenectomized population. Total lymph node irradiation was poorly tolerated in 66% of the patients. When this analysis was performed, 24 patients were classified as having Stage 0 disease with no disease progression for a mean of 21 months. CONCLUSIONS: Therapy programs allowing the selection of responders by the successive use of high intermittent dose chlorambucil and splenectomy may be beneficial in treating patients with advanced stage CLL. Because of its toxicity, total lymph node irradiation has no significant therapeutic effect.

Adult↗
PubMed1994

A review of 76 patients with myelodysplastic syndromes treated with danazol.

BACKGROUND: Treatment of myelodysplastic syndromes (MDSs) remains unsatisfactory. A limited number of reports provide contradictory information on whether danazol, a synthetic androgen, may be useful in patients with MDS. METHODS: Between 1984 and 1992, 76 patients were treated with danazol (Danatrol, Winthrop) in an open nonrandomized study. Clinical status, blood counts, differential marrow cell counts, transfusion requirements, and liver enzymes were monitored at 3-month intervals during and 6 months after discontinuation of therapy. The authors present the retrospective analysis of this cohort of patients. RESULTS: This study shows a limited usefulness of danazol in patients with MDS. Blood counts were not significantly changed during danazol administration; neither were transfusion requirements. Overall survival and the rate of leukemic transformation were not affected when compared with 50 untreated patients or with data available in the literature. An increase in platelet numbers in four patients and in hemoglobin level in one patient was observed; these patients were unremarkable and were not transfused before initial danazol therapy; therefore, changes in blood counts were of limited clinical significance. The search for subgroups of patients likely to have a favorable response was unsuccessful. Side effects of danazol were limited. In addition, this study provides information on the frequency of antiplatelet antibodies and other autoantibodies in patients with MDS. CONCLUSIONS: This study does not support a positive effect of danazol in patients with MDS during long term follow-up. Anecdotal positive evolution in a few patients cannot be formally ascribed to danazol. These results should be interpreted by comparison with previous publications that report on small numbers of patients with limited follow-up. Based on these data, the authors cannot recommend the systematic use of danazol in MDS.

Adult↗
PubMed1994

A case of polycythemia vera occurring in a patient with acute non-lymphoblastic leukemia (ANLL) in long-term first complete remission.

Polycythemia vera (PV) is a chronic myeloproliferative syndrome which in a minority of patients evolves into acute leukemia. The association with other hematopoietic malignancies has also been reported. The relationship between PV, leukemia, and treatment used for PV remains unclear. We here report the unusual observation of a young patient who developed the complete clinical and biological picture of PV, 6 years after being successfully treated with conventional chemotherapy for acute non-lymphoblastic leukemia (ANLL).

Adult↗
PubMed1993

Constitutive expression of GM-CSF mRNA by CML blast cells is correlated with endogenous megakaryocytic colony formation.

Purified blast cells from peripheral blood of 12 patients, with chronic myelogenous leukemia (CML) in chronic phase, were analyzed for the constitutive expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) transcript. Seven out 12 patients exhibited the specific 1.0 kb GM-CSF mRNA. Six from these patients presented an increased level of spontaneous megakaryocytic colony formation. Using an immunocytochemical procedure, the presence of GM-CSF was detected in a large proportion (52% to 72%) of the blast cells of the three patients studied, who were selected for the high expression of GM-CSF mRNA transcripts. Because the role of GM-CSF in the regulation of human megakaryocytopoiesis is well documented, we investigated the inhibiting effect of anti-GM-CSF antibodies on the spontaneous megakaryocytic colony growth of three of the patients expressing the GM-CSF transcript. Addition of anti-GM-CSF had a high neutralizing effect ranging from 60% to 70% inhibition of endogenous megakaryocytic colony growth. As the GM-CSF synthesis by leukemic cells is often induced by interleukin-1 (IL-1), we also investigated the effect of anti-IL-1 antibody on the spontaneous megakaryocytic colony growth of the same three patients. No significant inhibiting effect was observed, showing that the role of GM-CSF in the spontaneous colony formation is not mediated by IL-1. In addition, patients who constitutively expressed the GM-CSF transcript and showed endogenous megakaryocytic colony growth were those having a significantly higher platelet count than the group of patients without GM-CSF transcript and with no endogenous megakaryocytic colonies. In conclusion, these results suggest that GM-CSF, but not IL-1, participates in the production of spontaneous megakaryocytic colony formation observed in some CML patients. The true autocrine or paracrine nature of this stimulation remains to be established.

Antibodies↗
PubMed1992

[Evaluation of three types of empirical antibiotherapy in patients with febrile neutropenia: imipenem-cilastatin versus ceftazidime-vancomycin versus ticarcillin-amikacin-vancomycin].

A three-arm prospective randomized trial was designed to compare the effectiveness of single drug therapy with imipenemcilastatin (IC), two-drug therapy with ceftazidime-vancomycin (CV), and three-drug therapy with ticarcillin-vancomycin-amikacin (TVA) for the empirical antimicrobial treatment of febrile neutropenia events. The objectives of the study were to determine whether IC monotherapy was as effective as combination drug therapy (CV or TVA) and to assess the value of adding vancomycin at initiation of treatment. One hundred eighty-three febrile neutropenia events were randomized and 125 were evaluable. Success rates were 73% with IC, 67% with CV, and 72% with TVA. There were no statistically significant differences between the three treatment groups, regardless of the duration and severity of neutropenia. Fifty-four bacterial isolates were recovered from 43 patients. Among recovered bacterial strains, 55% were Gram-negative and 45% were Gram-positive. Rates of bacteriologically documented failures (14/33) and superinfections (3/33) were similar in the three groups. Adverse events were rare but two patients given CV and three given TVA developed severe skin toxicity requiring modification of the antimicrobial regimen. IC alone showed similar effectiveness and less toxicity, as compared with CV or TVA. Vancomycin given initially increased toxicity but failed to improve the success rate. Vancomycin may be appropriate only in patients at high risk for infection with methicillin-resistant staphylococci.

Adolescent↗
PubMed1991

Allogeneic bone marrow transplantation in chronic lymphocytic leukemia: 17 cases. Report from the EBMTG.

Allogeneic bone marrow transplantation (BMT) was performed in 17 patients with chronic lymphocytic leukemia (CLL): 15 resistant and two untreated forms. There were 12 males and five females with a mean age of 40 years (32-49). The conditioning regimens and graft-versus-host disease (GVHD) prophylaxis varied. Successful engraftment was obtained in 15 evaluable cases. Lymphocytosis and clinical symptoms subsided in all but one case. All 15 evaluable patients developed acute GVHD. Among the 17 patients grafted, one early death was observed at the 15th day post-BMT, and one refractory patient died 2 months after BMT. Of the remaining 15 patients in complete remission (CR), four died from GVHD, hemorrhage and graft failure, and two relapsed at 7 and 54 months after BMT and died. Nine patients are alive in CR with a mean follow-up of 25.6 months (4-48). Chimerism was complete in eight patients and partial in the two T cell-depleted cases. In one case, an immunoglobulin gene rearrangement study showed no residual disease. These results suggest that allogenic BMT might be an alternative and possible curative therapy for refractory CLL in young patients when performed relatively early in the disease.

Adult↗
PubMed1990

Study of megakaryocytic progenitors (CFU-MK) in human long-term bone marrow cultures (LTBMC): adjuvant effect of plasma from aplastic patients.

Human long-term bone marrow cultures (LTBMC) provide a very interesting tool for studying the events that are involved in stem cell commitment. At the present time, megakaryocyte (MK) progenitor cells have never been demonstrated in this system. In an effort to detect this cell lineage, we modified the culture medium by substituting fetal calf serum (FCS) and horse serum (HS) mix with human plasma obtained from treated aplastic leukemic patients. This plasma was harvested between days 15 and 21 following induction chemotherapy or conditioning regimen for autograft or allogeneic bone marrow transplantation. Using LTBMC, 17 normal marrows were cultivated for 11 weeks in Iscove's modified Dulbecco's medium containing either 20% human aplastic plasma or control FCS/HS mixture. In this plasma medium we observed the development of an adherent layer morphologically comparable to that observed with standard medium. We demonstrated presence of MK cells at all stages of maturation for 10 weeks and MK colony-forming cells (CFU-MK) for 11 weeks in the culture supernatants. An increased production of nonadherent cells and granulocyte-macrophage progenitors (CFU-GM) was also observed. LTBMC in aplastic plasma medium provide a new method for studying megakaryocytopoiesis, especially in human hematological diseases.

Adolescent↗
PubMed1990

Clinical and hematological improvement in a patient receiving danazol therapy for myelofibrosis with myeloid metaplasia.

We report the positive effect of danazol on clinical and hematological data in a patient with myelofibrosis and myeloid metaplasia. Severe cytopenia was corrected within 2 months and was maintained for an additional 2-month period. Myeloid metaplasia (lymph nodes and skin lesions) was greatly reduced. The patient experienced no side effects. We propose further trials to confirm the utility of this agent in this disease.

Danazol↗
PubMed1989

Cryopreservation of human megakaryocytic progenitor cells (CFU-MK): influence of culture conditions.

The survival of human megakaryocytic progenitor cells (CFU-MK) after freezing using a two-step cooling technique was studied in a methylcellulose culture system, using different stimulating activities and their combinations. The best growth stimulating activity for CFU-MK was found in plasma from aplastic patients (PAP). PAP was roughly three times more potent than optimal doses of human recombinant interleukin 3 (IL3), itself two times more active than our batch of phytohemagglutinin stimulated leukocyte conditioned medium (PHA-LCM). The addition of erythropoietin (EPO) to PHA-LCM doubled the number of megakaryocytic colonies, but had no effect on the number of CFU-MK stimulated by IL3. Of the two batches of PAP used, one was optimal and the other was significantly improved by the addition of PHA-LCM. The percentage recovery of CFU-MK after freezing reached 70 to 80% in cultures stimulated by PHA-LCM and IL3 +/- EPO, and 58% in PAP-supplemented cultures. However, this last value was not significantly different from the previous ones. The percentage recovery of CFU-MK in each condition tested was similar to that obtained with the other myeloid progenitors, CFU-GM and BFU-E. However, the high CFU-MK stimulating activity of PAP is hindered by its high variability and shortage in supply. Thus it seems more appropriate to recommend the use of recombinant human IL3 because of its easily standardizable and consistent CFU-MK stimulating activity.

Cells, Cultured↗
PubMed1988

Immunophenotype of blast cells in chronic myeloid leukemia.

The immunophenotype of peripheral blood blast cells from 14 patients in the chronic phase of chronic myeloid leukemia (CML) was studied using a panel of monoclonal antibodies (McAb) directed against megakaryocytic, granulomonocytic, erythroid and lymphoid antigenic determinants. The blast cells were enriched by a simple bovine serum albumin (BSA) density-cut separation and cooled in liquid nitrogen. The study was done using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique on the thawed blast cells. A consistent pattern of reactivity with McAb was found in all patients, showing that blast cells were heterogeneous. A minor component of the blast cells react with platelet antibodies, most of them being labelled with anti-GPIIb-IIIa McAb. Anti-GPIb and Von Willebrand factor McAb detected 4 times fewer megakaryocytic blast cells, suggesting that these cells are located very early in the differentiation scheme. Two major blast cell compartments were labelled with early myelomonocytic (anti-CD13: MY7) and early erythroid (anti-CD36: FA6-152) McAb. The CD34 (My10) and DR antigens which are expressed by immature blast cells and myeloid progenitors of human bone marrow (BM) were present on more than 50% of the CML blast cells. Thus, the blast cells of chronic phase CML patients, showed the same cellular diversity as the increased progenitor cell compartment observed in this disease, and their differentiation stages seemed to be very closely related.

Antibodies, Monoclonal↗
PubMed1988

Allogeneic bone marrow transplantation in chronic lymphocytic leukemia: report from the European Cooperative Group for bone marrow transplantation (8 cases).

Allogenic bone marrow transplantation (BMT) was performed in 8 patients with B chronic lymphocytic leukemia (CLL): 6 males and 2 females with a median age of 41 years (37 to 46). Seven patients were resistant to previous therapy and were grafted in the evolutive phase. Only 1 patient was grafted without any previous treatment. At the time of BMT 5 patients were classified according to the Rai classification in stage IV, 1 in stage III and 2 in stage 1. The delay between diagnosis and BMT was 47 months (5 to 68). Graft versus host disease (GVHD) prophylaxis was methotrexate (1 patient), cyclosporine (2 patients), methotrexate + cyclosporine (3 patients), cyclosporine + physical removal of T cells (2 patients). The conditioning regimen was standard for 5 patients, reinforced for 3 patients with Chlorambucil (1 patient) and etoposide (2 patients). A successful engraftment was obtained in all cases. The lymphocytosis decreased slowly and disappeared from day 0 to day 28. All patients developed an acute GVHD 5 of which resolved. Three patients died: 2 of acute GVHD and 1 of intracerebral hemorrhage. Five patients are alive in persistent complete remission without clinical symptoms and with normal peripheral blood and normal bone marrow. The median follow-up is 27 months (13-53). This small series suggests that allogeneic BMT should be investigated in selected patients as possible curative treatment of CLL.

Acute Disease↗