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C Cordonnier

Publications and source records attributed to C Cordonnier.

At least 163 records · Page 9Linked to original sources

[Clinical, diagnostic and physiopathological aspects of cytomegalovirus pneumonia after bone marrow transplantation].

Cytomegalovirus (CMV) is the most common cause of interstitial pneumonia following bone marrow transplantation. CMV pneumonia (CMV Pn) is particularly worrying after allografts since its incidence and severity are closely linked to graft-versus-host disease (GVHD). In similarly conditioned patients, the risk of CMV Pn is the same after autografts and allografts without GVHD; it is inexistant in bone marrow transplantations between twins. These findings, together with numerous experimental data, make CMV Pn a model of viral pneumonia in which the severity of the pneumonia seems to correlate mainly with an immunological reaction that is toxic for pulmonary cells, and CMV acts as a triggering agent rather than as a direct pathogen. As regards treatment, the ganciclovir-immunoglobulins combination has been very encouraging in the first patients treated, but as its mode of action is uncertain our enthusiasm must be tempered, especially since the results recently obtained in a greater number of patients seems to be less favourable than the initial results. The effectiveness of this costly drug combination, which in practice should be reserved for patients who received allografts or autografts plus pulmonary radiotherapy, deserves a more precise re-evaluation.

Bone Marrow Transplantation↗

Frequent detection of minimal residual disease by use of the polymerase chain reaction in long-term survivors after bone marrow transplantation for chronic myeloid leukemia.

The polymerase chain reaction (PCR) allows the detection of minimal amounts of nucleic sequences and has been successfully used to test for the chronic myeloid leukemia-specific bcr/abl transcripts. We studied blood samples from 17 patients who had undergone allogeneic bone marrow transplantation for CML, using a modified polymerase chain reaction-based assay for the detection of leukemic mRNA. This nested PCR technique was found to be highly sensitive, detecting the chimeric bcr/abl transcript in 16 of 17 patients including several long-term survivors. Cytogenetic techniques failed to detect Ph mitoses. The clinical significance of the persisting bcr/abl transcript for long periods following BMT is poorly understood and remains to be elucidated by further studies.

Bone Marrow Transplantation↗

Central nervous system relapses after bone marrow transplantation for acute lymphoblastic leukemia in remission.

This study defines the risk of central nervous system (CNS) relapse in patients undergoing bone marrow transplantation (BMT) for acute lymphoblastic leukemia (ALL) in remission, with no posttransplant prophylactic CNS therapy. Ninety-two consecutive patients in complete remission received BMT for ALL (n = 82) or high-grade non-Hodgkin's lymphoma with poor prognostic factors at diagnosis (n = 10). Sixty-six patients received allogeneic BMT (Allo-BMT) and 26 patients, without an identical sibling, underwent autologous BMT (Auto-BMT). Fifteen patients had CNS involvement at diagnosis and underwent BMT in first remission. Eight patients experienced CNS relapse after BMT, corresponding to a probability of 11% at 3 years. Apart from a history of prior CNS involvement, no patient characteristic evaluated statistically influenced CNS relapse after BMT. The probability of CNS relapse was 5.5% for the 70 patients without history of CNS involvement and 27.5% for the 22 patients with prior CNS involvement. However, subgroup analysis showed that the increased risk of CNS relapse is mainly observed in Auto-BMT patients with history of prior CNS involvement, particularly in patients undergoing BMT in first remission (three of five Auto-BMT versus one of ten Allo-BMT). Taking into account the multiple factors which influence the occurrence and the treatment of CNS leukemia, the results on this retrospective study suggests that (1) for patients without CNS involvement at diagnosis and for whom BMT is performed in first remission, cranial irradiation before BMT and posttransplant prophylactic CNS therapy can be omitted because of the low probability of CNS relapse after BMT (3.4%), when total-body irradiation (TBI) is included in the conditioning regimen; and (2) the difference observed between Allo-BMT and Auto-BMT patients with previous CNS involvement and undergoing BMT in first remission could indicate that graft-versus-host leukemia acts even in the CNS in Allo-BMT patients.

Adolescent↗

[Nosocomial infections in neutropenic patients].

Neutropenia is the most important predisposing factor for bacterial infection in immunocompromised hosts. It is mostly associated with mucosal damage as a consequence of chemotherapy. Nearly 50 p. 100 of infections occurring in neutropenic patients are acquired in the hospital. Colonization precedes infection in 80 p. 100 of the cases. The sources of colonization are ubiquitous and include water, air, food and medical personnel while gut colonization is more often responsible for infection than in normal patients. Fungal infection also emerges as an increasing problem in haematology. The use of gut sterilization and of sophisticated protected environments has decreased the frequency and mortality of infection in high risk patients.

Agranulocytosis↗

[Mixed lympho-epidermal cell cultures: value in bone marrow grafts].

Graft-versus-host disease (GVHD) is the major complication of allogeneic HLA-identical bone marrow transplantation. GVHD is induced by the activation of mature T cells in the graft which react against minor antigens of the recipient. Mixed epidermal cell-lymphocyte cultures (MELC), which constitute an in vitro model of epidermal cell-lymphocyte interactions, make it possible to study the presentation of antigens to the lymphoid cells by epidermal Langerhans cells. We performed MELC in 66 patients who had received an HLA-identical bone marrow transplant for malignant blood disease. The bone marrow received by 29 recipients had been depleted of mature T cells, whereas 37 recipients had received a non-depleted bone marrow. A complete, uni- and multivariate statistical analysis was carried out on recipients of non-depleted bone marrow to evaluate the risk factors for acute and chronic GVHD. This study showed that MELC between donor and recipient was the most predictive parameter for the occurrence of GVHD. Other factors were a history of previous pregnancies in female donors and a diagnosis of chronic myelogenous leukaemia. These results may be of value in the selection of donors and for a better determination of the need for bone marrow depletion.

Animals↗

Cost of allogeneic bone marrow transplantation in four diseases.

The cost of bone-marrow transplantation is compared in 4 diseases: acute myelogenous leukaemia, severe combined immunodeficiency, severe aplastic anaemia and chronic granulocytic leukaemia. Hospital cost components directly related to the clinical protocols applied are valorized. Results confirm the well-known fact that bone-marrow transplantation is a costly technique. The unit cost of a transplantation can vary from 1 to 2 between departments for the sole reason that patients treated are not suffering from the same illness. For one disease, the unit cost may vary from 1 to 2.7 when post-graft complications arise. Furthermore, in the health-care sector, as well as in every other economic sector, costs do not remain stable: they vary in time most especially when treatment protocols evolve. This type of cost information is the basis for management control systems without which physicians, hospital managers and health-care authorities cannot communicate effectively. In countries where health care is largely financed by the community, what is at stake is the future of advanced technologies in medicine.

Acquired Immunodeficiency Syndrome↗

Acral erythema and systemic toxicity related to CHA induction therapy in acute myeloid leukemia.

Seventy-two adult patients with previously untreated acute myeloid leukemia received the CHA regimen as induction chemotherapy: CCNU 80 mg/m2 on day 1, Adriamycin 35 mg/m2 i.v. on days 1, 2 and 3, and continuous infusion of cytarabine 100 mg/m2/24 h from day 1 to 10. Forty-nine patients (68%) presented at least one of the following symptoms: acral erythema with dysesthesias in the palms and/or soles (39%); cholestatic hepatitis (39%); profuse sterile diarrhea associated with abdominal distention (33%); acute cerebellar dysfunction (32%) and non-cardiogenic pulmonary edema (21%). Most of these toxic symptoms appeared 8-20 days after the first dose. As these clinical features were absent or exceptional in patients treated with another regimen within a controlled trial, they are reported as toxic-side-effects of the chemotherapy regimen. Acral erythema was found to be predictive of complete remission (P less than 0.01, odds ratio: 6.33); neurotoxicity was prognostic for death in aplasia (P less than 0.05); the absence of any of the five symptoms was associated with failure of the induction regimen (P less than 0.02).

Adolescent↗

Failure of a CD18/anti-LFA1 monoclonal antibody infusion to prevent graft rejection in leukemic patients receiving T-depleted allogeneic bone marrow transplantation.

CD18 antibodies react with the common beta chain of the human leukocyte function antigen (LFA1)* and thus block the functions mediated by the three identified molecules in humans. A murine CD18 monoclonal antibody was infused in 8 leukemic patients receiving allogeneic T-depleted bone marrow transplantation in order to prevent graft rejection. This was part of the conditioning, including total-body irradiation and high-dose chemotherapy, given to all patients. To prevent graft-versus-host disease the donor bone marrow T cells were depleted using complement-mediated cytolysis or a ricin A conjugate immunotoxin, and cyclosporine or methotrexate were given posttransplant. A persistent level of free circulating anti-LFA1 antibody was detected in 5/8 patients. Despite this, 5 graft failures occurred, with 2 patients experiencing late rejection (days 60 and 97) following HLA-identical transplantation and 3 patients having no engraftment following haplo-mismatched transplant. One other patient died of early sepsis. Only 2 patients (who differed at 1 HLA locus from their donor) are alive with long-term complete chimerism (300 and 315 days). Transient inhibition of recipients' leukocyte functions with an anti-LFA1 antibody did not appear to facilitate engraftment of allogeneic T-depleted marrow transplantation for leukemias.

Adolescent↗

IgG subclass deficiency in acute myeloid leukemia.

Serum IgG subclass levels were measured using a competitive indirect immunoenzymatic assay with monoclonal antibodies in 22 acute myeloid leukemia patients at presentation and prior to specific therapy. Three patients had moderate IgG1 deficiency and 1 moderate IgG3 deficiency. Two of the three IgG1 deficient patients (and only one other) failed to respond to induction chemotherapy and the third died of bone marrow aplasia during induction.

Adolescent↗

Venocclusive disease of the liver after allogeneic bone marrow transplantation in man.

One hundred and fifty-one consecutive patients underwent allogeneic bone marrow transplantation (B.M.T.) following high-dose chemotherapy and single dose total body irradiation (T.B.I.) for hematologic malignancies between September 1980 and December 1985. All patients included in this study were treated using a 60 Co beam to deliver a prescribed dose of 10 Gy to the mid-plane of the abdomen. Total body irradiation was performed the day before B.M.T. The mean instantaneous dose-rate was 3.5 cGy/min (range: 2.6 to 4.7). The real dose received was measured using thermoluminescent dosimeters (lithium borate). The difference between the doses delivered to the liver and to the mid-plane of the abdomen did not exceed 5%. The mean real dose delivered to the reference point was 10 Gy (range 8.3 to 11.7). Ninety five per cent of the patients received a dose ranging from 9.1 Gy to 10.9 Gy. High-dose cyclophosphamide was given to 126 patients with a "standard-risk" of relapse (60 mg/kg on day 5 and 4 before B.M.T.). Chemotherapy was intensified by the addition of other drugs in 25 patients with "higher-risk" of relapse. We analyzed the effect of the following pretransplant characteristics on the subsequent posttransplant development of V.O.D.: age, sex, ASAT and/or ALAT before conditioning regimen, diagnosis and status of malignant disease, history of liver disease, interval between diagnosis of hematologic malignancy and B.M.T., conditioning regimen (i.e., classical or intensified) and dose delivered to the liver during T.B.I. Seventeen patients were classified as having clinical V.O.D. giving a prevalence of 11.2%. In the first 2 months following B.M.T., death occurred respectively in 9 of 17 (53%) and 23 of 134 (17%) patients with and without clinical V.O.D. Univariate analysis showed that four characteristics were significantly related to an increased prevalence of V.O.D.: sex (11/62 females vs 6/89 males; p less than 0.05); history of liver disease (7/28 vs 10/117 patients without antecedent; p less than 0.01); ASAT and/or ALAT levels greater than 1.5 upper normal limit (11/49 vs 6/102 patients with levels less than 1.5; p less than 0.01) and intensified conditioning regimen (6/25 vs 11/126 patients with classical regimen; p less than 0.05). The conditioning regimen and history of liver disease were highly correlated to transaminases levels. Only two factors, transaminases levels and female sex, remained significantly associated with V.O.D. after multivariate analysis.

Adolescent↗

The mixed epidermal cell lymphocyte-reaction is the most predictive factor of acute graft-versus-host disease in bone marrow graft recipients.

Risk factors for acute graft-versus-host disease (GvHD) remain controversial. We performed uni- and multivariate statistical analyses on a series of 37 patients receiving a non-depleted allogeneic bone marrow transplant from an HLA-identical sibling donor for a haematological malignancy, in order to identify risk factors for GvHD. Three factors were associated with development of moderate to severe GvHD: a positive mixed epidermal cell-lymphocyte reaction (MECLR) between donor and recipient, previous pregnancies in female donors and chronic myeloid leukaemia diagnosis. The MECLR was the most important predictive factor, selected in first rank by the stepwise linear discriminant analysis. Combining these three prognostic factors in the jackknifed procedure, we could correctly classify 33/37 patients in two groups: grade O-I versus grade II-IV acute GvHD. These results should apply to donor selection and to predict donor/recipient pairs at high risk of GvHD who might benefit of bone marrow T-cell depletion and those at low risk for whom depletion could be avoided.

Adolescent↗

Allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia in first complete remission.

Twenty-seven patients ranging in age from 15 to 36 years participated in a pilot study, and underwent allogeneic bone marrow transplantation (BMT) for acute lymphoblastic leukemia (ALL) in first complete remission (CR) in four French centers. All patients were grafted from human leukocyte antigen/mixed leukocyte culture (HLA/MLC) identical sibling after conditioning regimen consisting of cyclophosphamide and total body irradiation (TBI). Sixteen patients are alive in persistent first remission, with a median follow-up of 56 months (range, 41 to 82 months). The 6-year Kaplan-Meier probability of disease-free survival (DFS) is 59%. Only three patients relapsed (5, 7, and 7 months after transplantation). These interesting results have led us to propose, in accord with a French multicentric protocol, allogeneic BMT for adults under 40 years of age during the first CR of ALL.

Adolescent↗

[Value of a fraction of low molecular weight heparin, enoxaparine, in patients at high risk of hemorrhage and thrombosis].

Treatment of patients with both thromboembolic manifestations and acute bleeding episodes is poorly defined. The use of low molecular weight heparin fractions has been shown to provide prophylactic antithrombotic activity in humans, with the possibility of fewer hemorrhagic complications because of their low anticoagulant activity and weaker action on platelets. An open trial was carried out in 50 patients. 47 of whom had a recent history of thromboembolic accident (34 venous thrombosis, including 13 with pulmonary embolism, 9 systemic arterial episodes, 4 cardiac emboli) and 3 who required prophylaxis. Conventional heparin therapy was contraindicated in all patients: 30 because of major digestive or muscle hemorrhage and 20 with high hemorrhagic risk (neurosurgery, deep thrombocytopenia). Enoxaparine (Laboratoire Pharmuka, Gennevilliers) was administered as 1 mg/kg/24 hours as 2 divided injections with adjustment to maintain an anti-Xa activity of 0.1 to 0.4 IU/ml. Antithrombotic efficacy as function of type of pathology was rated excellent in all patients, while tolerance, evaluated similarly by tests chosen as a function of type of hemorrhage, was good: one patient had moderate bleeding after accidental overdose and 4 patients minor bleeding. Enoxaparine by subcutaneous injection could represent a new therapeutic approach by improving the efficacy/risk ratio in this type of patients.

Blood Coagulation Tests↗

[Transfusion strategy for patients in therapeutic aplasia. Experience of the Henri Mondor Hospital apropos of 2 successive protocols].

Retrospective analysis of two transfusion protocols applied in our institution to the bone marrow transplanted patients was conducted. Granulocyte transfusions should be only proposed as a therapeutic treatment to patients with severe well documented bacterial infection resistant to an adapted antibiotherapy. Leukocyte-depleted blood products reduce the incidence of HLA-immunization but do not influence the frequency of CMV infections. Random single donor platelet concentrates (obtained by cytapheresis) could decrease the incidence of polyspecific HLA-antibodies in comparison with the use of random standard platelet concentrates. The best transfusion protocol should associate leukocyte-depleted blood products with transfusion of prophylactic single donor platelet concentrates. In our institution, this protocol is less expensive than the protocol with prophylactic white blood cell transfusions and has the same cost than other protocols using standard blood products.

Agranulocytosis↗

Evaluation of three assays on alveolar lavage fluid in the diagnosis of cytomegalovirus pneumonitis after bone marrow transplantation.

Cytologic examination, immunofluorescence assays, and cultures for virus were compared prospectively in the detection of cytomegalovirus (CMV) in cells obtained by 41 bronchoalveolar lavages (BALs) from 30 bone marrow transplant recipients with pneumonia. No evidence of CMV was found in 21 BALs. Viral inclusions, positive immunologic assays, and positive cultures were found in 14, 15, and 18 BALs, respectively. Cytological and immunologic results were closely related except in one BAL. In five BALs, a positive culture for virus was the sole criterion noted for diagnosis of CMV. The patients with both cytologically and immunologically positive results were more likely to die with or from respiratory failure (P less than .05), diffuse interstitial patterns (P less than .01), and severe acute graft-vs.-host disease (P less than .02) than were the patients without any criterion for diagnosis of CMV. The discrepancies with the previously reported data, the interpretation of the three diagnostic procedures, and the ability of BAL to diagnose CMV pneumonia are discussed.

Adolescent↗