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Biomedical subjects

C Belanger

Publications and source records attributed to C Belanger.

At least 37 records · Page 2Linked to original sources

Use of an anti-interleukin-2 receptor monoclonal antibody for GVHD prophylaxis in unrelated donor BMT.

Severe acute GVHD remains the main complication in unrelated donor BMT (UD-BMT). The previous encouraging reports on the use of anti-IL-2 receptor monoclonal Ab (33B31) for GVHD prophylaxis in genoidentical BMT led us to add this Ab to the standard GVHD prophylaxis regimen (MTX plus CsA). Sixty-four consecutive patients received 33B31, 20 mg on days 1 and 2, then 10 mg per day from day 3 to day 28 in association with CsA and MTX. They were compared with a historical control group of 89 patients who received conventional GVHD prophylaxis. The 33B31 was well tolerated. We did not find any statistical difference in terms of incidence and time of onset of severe GVHD, occurrence of chronic GVHD, engraftment, relapse or survival among the two groups. Immunization occurred but did not influence serum levels of 33B31. No correlation was found between the severity of GVHD and serum Ab levels. We conclude that other approaches for reducing acute GVHD should be developed to improve UD-BMT results.

Actuarial Analysis↗

High-dose recombinant human erythropoietin administered intravenously for the treatment of anaemia in myelodysplastic syndromes.

As the importance of recombinant human erythropoietin (r-HuEPO) therapy has been clearly demonstrated in anaemic patients with chronic renal failure (CRF), we carried out an open, non-randomized, non-placebo-controlled trial of high-dose intravenous (i.v.) r-HuEPO (100,000 U twice weekly) therapy in 14 anaemic, transfusion-dependent patients. Clinical response was defined by a rise in haemoglobin concentration to 9-11 g/dl and/or a reduction in the transfusion requirement during the treatment period compared with the 12 weeks before treatment. Eight patients completed the 12-week treatment and 4 were still under treatment, 1 at 10 weeks, 2 at 8 weeks and 1 at 4 weeks. Only those patients completing treatment were included in the efficacy evaluation. After treatment there was no significant change in haemoglobin concentrations, reticulocyte counts, or transfusion requirements. However, the number of patients included is too low to allow any definitive conclusion to be made.

Adult↗

Peripheral blood stem cell collection and autografting in high risk lymphomas.

Peripheral blood stem cells (PBSC) were collected from 29 patients with high risk Hodgkin's disease (n = 3) or non-Hodgkin's lymphoma (n = 26) in partial remission or first sensitive relapse. Patients had either bone marrow involvement or hypoplastic bone marrow. The conditioning regimen prior PBSC collection included amsacrine and cytosine arabinoside (Ara-C) or Ara-C alone. PBSC collection was performed after leukocyte counts reached 1 x 10(9)/1. A good yield was obtained in 23 patients, whereas sufficient numbers of CFU-GM were not obtained in six cases. Twenty-one patients have been transplanted. All patients except one achieved bone marrow engraftment. Eight patients are in complete remission (mean duration 15 months). The estimated 2 years survival rate is 46.4% (CI 25-68%). This procedure would seems a good alternative in poor prognosis lymphomas.

Adult↗

Allogeneic bone marrow transplantation in multiple myeloma. European Group for Bone Marrow Transplantation.

BACKGROUND AND METHODS: In contrast to autologous bone marrow transplants for hematologic cancers, allogeneic transplants contain no tumor cells that might cause a relapse. We report the results of such allogeneic bone marrow transplantation using HLA-compatible sibling donors in 90 patients with multiple myeloma performed in 26 European centers between 1983 and 1989. RESULTS: At the time of the most recent follow-up, 79 months after the start of the study, 47 patients were alive and 43 were dead. The rate of complete remission after bone marrow transplantation was 43 percent for all patients and 58 percent for the patients who had engraftment. The actuarial survival at 76 months was 40 percent. The median duration of relapse-free survival among patients who were in complete remission after bone marrow transplantation was 48 months. The stage of the disease at diagnosis and the number of treatment regimens tried before bone marrow transplantation were predictive of the likelihood of complete remission after engraftment. There were trends toward longer survival among patients who were responsive to treatment before bone marrow transplantation, patients with Stage I disease at diagnosis, and patients who had received only first-line treatment before transplantation, as compared with those who were not responsive, those with Stage II or III disease at diagnosis, and those who had received three or more lines of treatment, but the differences in these factors were not statistically significant. Two post-transplantation factors predicted better long-term survival: complete remission after engraftment and grade I graft-versus-host disease, rather than grade II, III, or IV. CONCLUSIONS: Allogeneic bone marrow transplantation with the use of HLA-matched sibling donors appears to be a promising method of treatment for some patients with multiple myeloma.

Adult↗

Correlation between the biological and therapeutic effects of interferon-alpha in low-grade nodular non-Hodgkin's lymphoma: lack of in vivo down-regulation and reduced affinity of IFN-alpha receptors in unresponsive patients.

We investigated the correlations between the biological effects of interferon-alpha (IFN-alpha) and clinical responsiveness in low-grade non-Hodgkin's lymphomas (NHL). In this disease, 40-50% of cases respond to IFN-alpha therapy. Patients with nodular NHL were selected for a phase II trial in which they were treated daily with 9 x 10(6) U of IFN-alpha 2a. Binding experiments with [125I]IFN-alpha 2a showed the presence of IFN-alpha receptors on tumor B-cells isolated from lymph nodes before therapy in 9 out of 10 patients. Receptor levels were not related to the subsequent clinical responses. However, no specific binding was detected in one patient who turned out to be unresponsive to IFN-alpha treatment. Single injections of IFN-alpha 2a before beginning the therapeutic protocol resulted in down-regulation of IFN-alpha receptors without change in their affinity in peripheral blood leukocytes from only patients who subsequently responded to therapy (4/10). In 4/5 non-responders and one patient displaying a minor response, receptor numbers did not decrease but Kd values rose markedly in all six cases. These results indicate that lack of in vivo IFN-alpha receptor down-regulation and reduced receptor affinity, as detected before therapy, may be correlated with failure of IFN-alpha therapy in nodular NHL.

2',5'-Oligoadenylate Synthetase↗

LEF-1, a gene encoding a lymphoid-specific protein with an HMG domain, regulates T-cell receptor alpha enhancer function [corrected].

Lymphoid-specific cDNA clones were isolated that encode a nuclear protein with homology to the chromosomal nonhistone protein HMG-1 and to putative regulators of cell specialization, including the mammalian testis-determining factor SRY and fungal mating-type proteins. The gene represented by the isolated cDNA clones, termed LEF-1 (lymphoid enhancer-binding factor 1), is developmentally regulated and expressed in pre-B and T lymphocytes but not in later-stage B cells or nonlymphoid tissues. Both endogenous and recombinant LEF-1 were shown to bind to a functionally important site in the T-cell antigen receptor (TCR) alpha enhancer. Maximal TCR alpha enhancer activity was found to parallel the cell type-specific expression pattern of LEF-1. Moreover, forced expression of recombinant LEF-1 in late stage B cells increases TCR alpha enhancer function. Taken together, these data suggest that LEF-1 is a regulatory participant in lymphocyte gene expression and differentiation.

Amino Acid Sequence↗

Matched unrelated bone marrow transplants. Results from the French group (GEGMO).

From a bank of 50,000 HLA typed French bone marrow donors, 125 transplants have been performed since 1986, with HLA AB and DR--identical MLC--negative donors. The median age was 25 years and the diagnosis was CGL in 59 cases, ALL in 22 cases, AML in 17 cases, SAA in 7 cases, inborn errors in 7 cases and others in 13 cases. Most of the patients received a standard conditioning regimen according to their diagnosis. The prophylaxis of GVHD was methotrexate and cyclosporine A in 77 cases; in addition to this combination 44 patients received an anti-IL2 receptor monoclonal antibody from day +1 to day +28. There was no difference between the two groups as regards the incidence and severity of GVH or survival. The actuarial survival was 36% with a median follow up of 300 days. Unlike matched sibling grafts, the usual prognostic factors such as stage of disease or age were not found to significantly modify the incidence of GVHD, which was 75%. The results of matched unrelated donor transplants are reasonably good, but must be improved by a better selection of donors and better prevention of GVHD.

Actuarial Analysis↗

Allogeneic bone marrow transplantation in patients with multiple myeloma.

50 patients with a median age of 41 years (range 29-54) underwent allogenic bone marrow transplantation for multiple myeloma. 35 patients were on second-line treatment, and 15 on first-line treatment. 24 patients were considered refractory to previous treatment. 45 patients received marrow from HLA-matched sibling donors (3 of these from twin donors), and 5 from unrelated or related non-sibling donors. 21 patients entered complete remission, while 15 had persistent disease following repopulation of the marrow. 14 patients were not evaluable for remission status because of early transplantation-related death. The overall median survival from bone marrow transplantation was 27 months, with a projected long-term survival of 34%. Patients who were 40 yr of age or older had a survival that was not different from that of patients between 29 and 40 yr of age. The median disease-free survival of patients who entered complete remissions was 41 months. These patients tended to have a longer survival than patients with persistent disease following repopulation of the marrow. Allogeneic bone marrow transplantation appears to be a promising method for treatment of certain patients with multiple myeloma.

Adult↗

Failure of amphotericin B spray to prevent aspergillosis in granulocytopenic patients.

We tested the efficiency of a nasal spray of Amphotericin B (AmB) in leukemic patients, in an attempt to prevent pulmonary Aspergillosis. From January to July, 8 cases of invasive Aspergillosis (IA) in 19 new leukemic patients were identified. Between July and September 15 patients were treated by prophylactic nasal spray of AmB (daily dose 5 mg). Compliance was excellent, but nevertheless typical IA developed in 5 patients. We conclude that at the dosage used prophylactic administration of nasal spray of (AmB) does not prevent IA.

Administration, Intranasal↗

A case-control study of risk indicators among women with premenopausal and early postmenopausal breast cancer.

Among 714 premenopausal and 130 postmenopausal breast cancer cases matched with 8440 controls for age in years and menopausal status, risk indicators for breast cancer were similar, although most associations were stronger in the premenopausal women. Compared with nulliparous women, the relative risk (RR) for those with first birth before age 25 years was 0.7 (95% confidence limits [CL] from 0.5 to 0.9) among premenopausal women, and 0.7 (0.4-1.4) for postmenopausal women. In the premenopausal cases, a history of breast cancer in a sister gave a RR of 3.0 (2.1-4.1) and in a mother 1.9 (1.4-2.5), whereas for the postmenopausal women the RRs were 1.4 (0.6-3.1) and 1.3 (0.6-2.6), respectively. Fibrocystic breast disease was also a significant predictor of subsequent breast cancer in the premenopausal and postmenopausal women. In relation to women having a single birth, premenopausal women with six or more births had a risk of breast cancer of 0.6 (0.4-1.0), which was present even after adjustment for age at first birth.

Age Factors↗

A case-control study of oral contraceptive use and breast cancer.

Among 989 cases of breast cancer and 9,890 controls selected from a cohort of married, female registered nurses aged 30-55 years, the relative risk (RR) of breast cancer for women who had ever used oral contraceptives (OC) compared with those who had never used them was 1.0, with 95% confidence limits 0.9-1.2. Among OC users, there was no consistent pattern of excess risk with increasing duration; in fact, the few women who had used OC longest (greater than 10 yr) had a slightly lower risk than never-users. Moreover, there was no association between OC use and breast cancer among women with a positive history of breast cancer in the mother or sister or with OC use before their first pregnancy. The only subgroup of women among whom any adverse effect was apparent was current OC users aged 50-55 years (two onsets expected vs. seven observed). This finding is consistent with earlier reports of an increased risk of breast cancer among older OC users; however, it is also likely to reflect, at least to some extent, the play of chance, since at ages 45-49 and in each younger age group fewer cases than expected were observed among current OC users.

Adult↗

Oral contraceptive use and malignant melanoma.

There was no overall relationship between a prior history of oral contraceptive (OC) use and the development of melanoma among 141 cases of nonfatal malignant melanoma and 2,820 age-matched controls drawn from respondents to a large postal survey of registered U.S. nurses; crude relative risk (RR) was 0.93 and 95% confidence limits (CL) were between 0.64 and 1.36. Adjustment for a number of additional variables did not alter this estimate materially. Duration of OC use and interval since first use were similarly unrelated to the occurrence of melanoma. For women diagnosed before age 40, there was a crude positive association of "ever" use of OC and melanoma (RR = 1.78; 95% CL, 1.11-2.86). However, adjustment for geography and other variables diminished this association and rendered it statistically not significant (RR = 1.43, 95% CL, 0.83-2.46). These data do not support the hypothesis that OC use is an independent risk factor for melanoma.

Adult↗

Early menopause and the risk of myocardial infarction.

We evaluated the relation between age at menopause and the risk of nonfatal myocardial infarction (MI) among 121,964 nurses who responded to a mail questionnaire. Of 279 women who reported having been hospitalized for MI, 123 (44%) were postmenopausal (i.e., no longer menstruating) at the time of hospitalization, compared with 1,859 (33%) of 5,580 age-matched control subjects. Among women who became menopausal because of bilateral oophorectomy, the estimated relative risk of MI increased with decreasing age at menopause, and women who underwent bilateral oophorectomy before age 35 were estimated to have a risk of hospitalization for MI approximately 7.2 times (95% confidence interval, 4.5 to 11.4) that of premenopausal women. Hysterectomy without the removal of both ovaries was only weakly associated with an increased risk. The data support the hypothesis that premature cessation of ovarian function increases the risk of nonfatal MI.

Adult↗