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Biomedical subjects

C Cordonnier

Publications and source records attributed to C Cordonnier.

At least 145 records · Page 8Linked to original sources

Allogeneic bone marrow transplantation for adult acute lymphoblastic leukemia in first complete remission: factors predictive of transplant-related mortality and influence of total body irradiation modalities.

In a retrospective multicentre study, we analyzed 184 consecutive patients who underwent bone marrow transplantation (BMT) from identical siblings for adult acute lymphoblastic leukemia in first complete remission between March 1980 and May 1989. The main causes of transplant-related mortality were GVHD and interstitial pneumonitis. Univariate and multivariate analyses identified the mode of total body irradiation (TBI) as the only independent predictive factor of transplant-related mortality. Ninety-one patients received single-dose TBI and 93 received fractionated-dose TBI as part of the conditioning regimen prior to BMT. Transplant-related mortality was more frequent in the single dose group (p = 0.017). The incidence of interstitial pneumonitis, acute and chronic GVHD and veno-occlusive disease of the liver was not statistically different between the two irradiation groups. However, fatal interstitial pneumonitis was significantly more frequent in the single dose irradiation group (p = 0.031). These results show that transplant-related mortality is closely associated with the mode of TBI administration. The increased relapse rate in the fractionated group explains why there was no difference between the two groups in terms of overall leukemia-free survival.

Adolescent↗

Practices for cytomegalovirus diagnosis, prophylaxis and treatment in allogeneic bone marrow transplant recipients: a report from the Working Party for Infectious Diseases of the EBMT.

During the past few years major progress has been made in the diagnosis and therapy of CMV infection after allogeneic BMT. The aim of this survey was to investigate the use of diagnostic techniques, use of prophylaxis and the therapeutic strategies among members of the EBMT. Seventy centers from 20 countries responded to the survey. Sixty-seven centers (96%) routinely tried to diagnose CMV from the blood. Fifty-seven centers used standard or rapid isolation techniques. Thirty-seven centers used one of the newly developed techniques, antigenemia detection in leukocytes or PCR together with isolation, while 10 centers used one of these two techniques without standard isolation. Fifty-five centers regularly performed bronchoscopy and bronchoalveolar lavage on the suspicion of CMV pneumonia but only 12 centers required detection of CMV in specimens from the lavage or lungs as the indication to start therapy; 31 centers started therapy on symptoms of pneumonia combined with CMV detection from any site. Prophylaxis was used in 54 centers (84%). The most commonly used regimen was high-dose acyclovir which was used by 42 centers, while seven centers used ganciclovir. The strategy of early therapy was used by 53 centers (76%) and was most frequently based on detection of viremia or CMV antigen in the blood. CMV pneumonia was treated by a combination of ganciclovir and i.v. immunoglobulin by 64 centers, by foscarnet and immunoglobulin in 5 centers and by ganciclovir alone in 5 centers. CMV gastrointestinal disease was treated by antiviral therapy alone in 18 centers and by a combination of antiviral therapy and iv immunoglobulin in 46 centers.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗

Granulocyte-macrophage colony-stimulating factor in association to timed-sequential chemotherapy with mitoxantrone, etoposide, and cytarabine for refractory acute myelogenous leukemia.

Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), given intravenously 5 micrograms/kg per day, was administered on days 4-8 of timed-sequential chemotherapy (TSC) with mitoxantrone, 12 mg/m2 per day on days 1-3, etoposide, 200 mg/m2 per day on days 8-10 and cytarabine, 500 mg/m2 per day on days 1-3 and 8-10, in 22 patients aged < 60 years with refractory acute myelogenous leukemia in an attempt to increase recruitment of leukemic cells in S phase before the second sequence of TSC. Thirty-eight patients treated with TSC without GM-CSF in a previous trial served as historical controls. In GM-CSF-treated patients, median duration of neutropenia < 0.5 x 10(9)/1 was 33 days and of platelet transfusion requirement 30 days, without any increase by comparison with controls. WHO grade 3 or more extra-hematologic toxicity included sepsis in 60% of patients, vomiting in 30%, diarrhea in 15%, hyper-bilirubinemia in 15%, and mucositis in 10%, without any difference with controls. Among 20 evaluable patients six individuals (30%), with a 95% confidence interval (CI) ranging from 12-54% achieved complete remission, 11 (55%, CI 31-77%) did not respond to therapy and three (15%, CI 3-38%) died from infection. There was no demonstrable in vivo proliferation of leukemic cells during the 5 days of administration of GM-CSF. The average percentage of bone marrow cells in S phase in five patients was 4.0 +/- 2.8 on day 4 and 7.0 +/- 7.2 on day 8 (p = NS). In this cohort of patients refractory to cytarabine, addition of GM-CSF did not increase efficacy of TSC by comparison with historical controls.

Adolescent↗

Sclerodermatous chronic graft-versus-host disease. Analysis of seven cases.

BACKGROUND: Sclerodermatous chronic graft-versus-host disease is a disabling complication after allogeneic bone marrow transplantation from HLA-identical sibling donors. Only a few series of patients have been reported and the dermatologic features have never been extensively described. OBJECTIVE: The purpose of the study was to describe clinical and biologic features of chronic sclerodermatous graft-versus-host disease and to compare them with scleroderma. METHODS: We reviewed 196 patients grafted between April 1973 and July 1987 with survival times sufficient to be at risk of chronic graft-versus-host disease. Seven had the sclerodermatous form. RESULTS: Most patients had disseminated sclerosis of the trunk and the proximal portions of the limbs. In two cases, atrophy of the skin was predominant, corresponding with a severe clinical evolution. Periorbital pigmentation was observed as an initial manifestation in three cases. Visceral manifestations resembled those observed in scleroderma but histologic and immunologic studies demonstrated clear differences. Response to therapy was variable. CONCLUSION: Chronic sclerodermatous graft-versus-host disease may realize two different patterns. Major atrophy is associated with a more severe progression.

Adolescent↗

Treatment of interstitial pneumonitis due to cytomegalovirus with ganciclovir and intravenous immune globulin: experience of European Bone Marrow Transplant Group.

Data on 49 allogeneic bone marrow transplant (BMT) recipients who developed interstitial pneumonia due to cytomegalovirus (CMV) were collected retrospectively. All patients were treated with ganciclovir and high doses of intravenous immune globulin, although types of immune globulins and schedules of treatment varied. Seventeen (35%) of 49 patients responded to treatment. Thirty days after the diagnosis of interstitial pneumonia, the survival rate among patients was 31%. CMV was detected in 81% of patients on whom autopsies were performed. The survival rate among patients who received total body irradiation (TBI) was significantly lower (11 [27%] of 41) than that among patients who did not receive TBI (six [75%] of eight; odds ratio = 12.3; P = .009). No other factor, including age, grade of graft-versus-host disease, types and dose of immune globulin used, or dose of ganciclovir, was correlated to survival. These results show that although survival of allogeneic BMT recipients with CMV interstitial pneumonia has improved, more than one-half of the patients still died of pneumonia. Thus, both prophylaxis for and treatment of CMV infection must be improved.

Adolescent↗

Immunogenicity of Haemophilus influenzae type b conjugate vaccine in allogeneic bone marrow recipients.

A randomized study was conducted in 40 allogeneic marrow recipients to compare the immunogenicity of two Haemophilus influenzae type b (Hib) vaccines (either the Hib capsular polysaccharide [Hib-CPS] or tetanus toxoid-conjugated Hib-CPS [Hib-CPS-T]). A second injection consisted of Hib-CPS-T. Before immunization, 3 patients had serum antibody levels > 1 microgram/mL. After the first injection, the response was better after Hib-CPS-T than after Hib-CPS but lower than in normal subjects; a number of patients lacked any IgG antibody response, especially after Hib-CPS. Of patients who received two injections of Hib-CPS-T, 85% achieved an antibody concentration > or = 1 microgram/mL. Hib-CPS-T induced a response in IgG2-deficient patients whereas Hib-CPS alone did not. IgG antibodies predominantly belonged to the IgG1 subclass. The antibody response was better in patients immunized late after graft. This study shows that Hib-CPS-T is more immunogenic than Hib-CPS in marrow recipients.

Adult↗

Bronchoalveolar lavage in immunocompromised patients. Clinical and functional consequences.

Fiberoptic bronchoscopy and bronchoalveolar lavage are major tools in the diagnosis of acute pneumonia in immunocompromised patients. We conducted a prospective study to assess the morbidity associated with this procedure in 14 patients with AIDS and 16 patients with drug-induced immunosuppression. No patient had a PaO2 lower than 70 mm Hg with additional oxygen. Clinical data, chest roentgenogram, pulmonary function test, forced vital capacity, forced expiratory volume in one second, and arterial blood gases were recorded before and after bronchoscopy. Arterial oxygen saturation was monitored during the procedure, and initial, lowest, and final saturation values were noted. The patients were separated into three groups on the basis of chest roentgenographic findings. No procedure-induced pneumonia or need for tracheal intubation occurred. Minor clinical symptoms induced by the lavage in seven patients resolved spontaneously. By contrast, mean SaO2 decreased markedly during the procedure from 94 +/- 3 to 87 +/- 5 percent (p less than 0.0001) and returned to only 89 +/- 5 percent at the end of the procedure. Lowest SaO2 during the procedure and final SaO2 correlated poorly with initial SaO2 but correlated well with initial FVC and FEV1 (p less than 0.01). The PFT values were lower following bronchoscopy. O2 desaturation was more pronounced in patients with severe roentgenographic abnormalities. No significant differences were found between the three groups of patients, or between the AIDS and DII patients in terms of changes in PFT values. We conclude that in immunocompromised patients, bronchoscopy with BAL induces severe arterial oxygen desaturation which is correlated with initial PFT and chest roentgenographic findings, and most of these abnormalities are transient and do not lead to major complications.

Acquired Immunodeficiency Syndrome↗

[BCG osteoarthritis on knee prosthesis after intra-vesical BCG therapy].

A case of Calmette-Guérin bacillus (BCG) infection of a knee implant during intravesical BCG-therapy is reported. The course was favorable after replacement of the implant and administration of antituberculous agents. This case of septic osteoarthritis due to the BCG is different from cases of reactive polyarthritis reported after intravesical instillations of BCG. It probably resulted from diffusion of the BCG via the bloodstream.

Administration, Intravesical↗

Intensive sequential chemotherapy with mitoxantrone and continuous infusion etoposide and cytarabine for previously treated acute myelogenous leukemia.

Intensive sequential chemotherapy with mitoxantrone, 12 mg/m2/d on days 1 through 3, etoposide, 200 mg/m2/d as a continuous infusion on days 8 through 10, and cytarabine, 500 mg/m2/d as a continuous infusion on days 1 through 3 and 8 through 10 was administered to 72 patients aged less than 60 years with previously treated acute myelogenous leukemia (AML). Forty patients had refractory AML (nonresponse to prior therapy, early first relapse, or multiple relapse) and 32 had late first relapse. Sixty-one percent of patients, with a 95% confidence interval (CI) ranging from 49% to 72%, achieved complete remission (CR), including 45% (CI: 30% to 62%) of refractory patients and 81% (CI: 64% to 93%) of late first relapse patients. Twenty-nine percent of patients (CI: 19% to 41%) did not respond to therapy and 10% (CI: 4% to 19%) died from therapy-related toxicity. Median duration of aplasia was 30 days. Nonhematologic WHO grade 3 or more toxicity included sepsis (57% of patients), vomiting (10%), mucositis (35%), diarrhea (7%), skin rash (6%), and hyperbilirubinemia (11%). Postinduction therapy was attempted in 36 of 44 CR patients: 16 of them received a second course of the same regimen, 7 received maintenance chemotherapy, 4 underwent autologous bone marrow transplantation (BMT), and 9 allogeneic BMT. At a median follow-up of 20 months, 23 of the 44 complete remitters have relapsed, 1 to 14 months after achievement of CR, including 19 of 31 patients not undergoing BMT. Median survival is 7 months with 16% (CI: 4% to 28%) projected survival at 47 months. Median disease-free survival is 6 months with 21% (CI: 3% to 39%) of CR patients projected to remain disease-free at 46 months. Twenty-six percent (CI: 13% to 43%) of the evaluable patients who did not receive transplantation had inversion of CR duration. Among patients younger than 50 years, there was no significant difference in disease-free survival between patients receiving postinduction chemotherapy and those receiving BMT. We conclude that this chemotherapy regimen is highly efficient and could be used as first-line therapy in young patients with AML.

Antineoplastic Combined Chemotherapy Protocols↗

Effects of calcium-free solution, calcium antagonists, and the calcium agonist BAY K 8644 on mechanical responses of skeletal muscle from patients susceptible to malignant hyperthermia.

The purpose of this investigation was to determine if alteration in the function of the dihydropyridine receptor may in turn modify halothane-induced contractures in muscle bundles from patients susceptible to malignant hyperthermia (MH). The effects of Ca(2+)-free Krebs Ringer (KR) solution, 5 microM verapamil, 5 microM nifedipine, and 10 microM of the Ca2+ agonist BAY K 8644 on halothane-induced contracture were therefore investigated. The halothane-induced contracture was prevented in the absence of extracellular Ca2+ and significantly reduced in the presence of verapamil or nifedipine. BAY K 8644 significantly enhanced the 0.5-, 1.0-, and 1.5-vol % halothane-induced contracture in MH-susceptible muscle bundles. When BAY K 8644 was dissolved in Ca(2+)-free KR solution, no contracture was observed in MH-susceptible muscle bundles. These results on cut MH-susceptible human muscle bundles support the hypothesis that halothane-induced contracture in MH can be modified by the binding of Ca2+ agonists or antagonists to the dihydropyridine receptor. The role of Ca2+ entry phenomena remains unclear, but the results suggest that extracellular Ca2+ is required to reprime or to bind to some sites of the dihydropyridine receptors.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Toxic epidermal necrolysis after bone marrow transplantation: study of nine cases.

Acute graft-versus-host reaction after allogeneic bone marrow transplantation has been reported to induce toxic epidermal necrolysis. To assess the respective role of acute graft-versus-host disease and of drug reaction in this setting, we retrospectively reviewed nine cases of toxic epidermal necrolysis that occurred in a series of 152 allogenic bone marrow recipients. In five cases visceral involvement was suggestive of acute graft-versus-host disease without any drug more than "doubtfully" suspected. In four cases extracutaneous symptoms were absent or mild and suspect drugs (mainly sulfonamides) had been administered with a timing suggestive of "possible" causality. All nine patients died, mainly from infection possibly aggravated by high doses of corticosteroids. We conclude that toxic epidermal necrolysis may be more frequent than generally thought after bone marrow transplantation and has a poor prognosis. It seems to be related to a drug reaction to sulfonamides as often as to acute graft-versus-host disease.

Acute Disease↗

Use of the calcium agonist BAY K 8644 for in vitro diagnosis of susceptibility to malignant hyperthermia.

We have studied the effects of the calcium agonist BAY K 8644 on the in vitro halothane test in 10 malignant hyperthermia-susceptible (MHS), 12 MH "equivocal" to halothane (MHEh), 30 MH non-susceptible (MHN) and 10 control patients. BAY K 8644 potentiated the halothane-induced contracture in muscle strips from both MHS and MHEh patients. The drug produced a more obvious difference in contracture responses between the MHEh group compared with the MHN and control groups.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Allogeneic bone marrow transplantation in adults with Burkitt's lymphoma or acute lymphoblastic leukemia in first complete remission.

The prognosis of adults with Burkitt's lymphoma is very poor and depends on initial CNS and/or bone marrow involvement. We report results in nine adult patients with CNS (n = 9) and/or bone marrow involvement (n = 7) treated in first complete remission (CR) with allogeneic bone marrow transplantation (BMT). CNS treatment before the conditioning regimen consisted of cranial irradiation at 15 Gy (n = 8) and intrathecal chemotherapy (n = 9). The conditioning regimen included cyclophosphamide and total body irradiation (TBI) in a single dose. No postgraft CNS prophylaxis was administered. At the present time, seven patients are alive and disease-free at 18, 23, 44, 47, 54, 54, and 59 months. Two patients died at 14 and 7 months from transfusion-related acquired immune deficiency syndrome and bacterial septicemia and were disease-free at the time of their death. These preliminary results should encourage the use of BMT. A prospective randomized trial is warranted to further specify and investigate the advantages of allogeneic BMT versus conventional chemotherapy.

Adolescent↗