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Biomedical subjects

P Ribaud

Publications and source records attributed to P Ribaud.

At least 55 records · Page 3Linked to original sources
PubMed1998

Influence of CD34 cell selection on the incidence of mixed chimaerism and minimal residual disease after allogeneic unrelated donor transplantation.

Marrow transplantation from unrelated donors has been linked with an increased risk of graft-versus-host disease (GVHD). In an attempt to lower the risk of acute GVHD we used CD34 marrow cell selection for T cell depletion. Since T cell depletion has been linked to an increased risk of relapse and an increased risk of marrow failure, we used PCR amplification of minisatellite sequences to investigate donor cell engraftment and RT-PCR amplification of recurrent chromosomal translocations to investigate the residual disease post-transplant. Twenty-three patients who underwent BMT after positive selection of the CD34-positive cell population were studied. Results were then compared with those of 37 patients who underwent transplantation with unmanipulated marrow graft. Among the 23 patients who received CD34+ selected cell grafts, seven (30%) had evidence of full donor engraftment, 14 had evidence of residual recipient cells (61%), one had a non-take, and one autologous bone marrow recovery. Analysis of the chimaerism status post-transplant in 36 patients who received unmanipulated marrow grafts showed that 31 patients (86%) had evidence of full donor engraftment. The difference in the incidence of mixed chimaerism profile between patients who received unmanipulated marrow graft and those receiving CD34+ selected cell grafts was statistically significant (P< 0.01). Nine patients who received CD34+ selected cell grafts could be analysed for the presence of minimal residual disease post-transplant (one with t(9;22) acute lymphoblastic leukaemia and eight with CML). In the patient transplanted for a Ph-positive acute leukaemia, and in two out of the eight patients with CML, the search fora fusion transcript was consistently negative after transplantation. Among the six patients with evidence of residual disease, three patients also had a mixed chimaerism profile and were given donor lymphocyte infusions. Minimal residual disease study was performed post-transplant in 16 patients who received unmanipulated marrow grafts. In 10 of 14 patients with CML, and in two patients with acute leukaemia the search for a fusion transcript was consistently negative after transplantation. The difference in the incidence of minimal residual disease between patients who received an unmanipulated marrow graft and those receiving CD34+ selected cell grafts was not statistically significantly significant, but numbers of patients included in this analysis are still few. In conclusion, our study highlights the strong influence of graft manipulation on the incidence of mixed chimaerism after transplantation from an unrelated donor.

Adolescent↗
PubMed1998

Unusual complications after bone marrow transplantation for dyskeratosis congenita.

Dyskeratosis congenita (DC) is a rare inherited disorder often associated with aplastic anaemia. We report the cases of five boys transplanted with an HLA-identical related donor for severe aplastic anaemia (SAA) associated to DC; in all cases successful engraftment was observed. Three patients died 2-8 years after bone marrow transplantation (BMT) with signs of endothelial cell damage syndrome (kidney microangiopathy and liver veno-occlusive disease). Another boy died 1 year after BMT from Evans syndrome and invasive aspergillosis. One boy currently presents anaemia, polyarthritis of unknown origin, pulmonary fibrosis and gut malabsorption 7.5 years after BMT. SAA associated with DC can be successfully treated by allogeneic BMT. However, these early and late complications observed are very unusual after BMT and probably reflect the association of transplanted-related factors, evolution of the underlying disease, and increased sensitivity of endothelial cells. Modified conditioning approaches, advances in supportive care and surveillance of these unusual complications offer the possibility of improved outcome for these patients.

Adolescent↗
PubMed1998

Transplantation for Fanconi's anaemia: long-term follow-up of fifty patients transplanted from a sibling donor after low-dose cyclophosphamide and thoraco-abdominal irradiation for conditioning.

We describe the long-term follow-up of 50 Fanconi's anaemia patients who were transplanted from a related donor with a median follow-up of >6 years. The survival estimate was 74.4% at 54 months and 58.5% at 100 months. All patients were conditioned with low-dose cyclophosphamide and thoraco-abdominal irradiation. Acute graft-versus-host disease (GvHD) of grade II or more developed in 26 patients and chronic GvHD developed in 30/43 (69.9%) patients. The survival of patients without chronic GvHD (n = 13) was 100%. In addition to chronic GvHD, 20 pre-transplant transfusions was shown to have an adverse impact on survival by multivariate analysis (relative risk = 7.08, P = 0.0003). Prospective follow-up of growth and endocrine function could be performed in 31 patients. Of 20 boys, six have already reached normal puberty within the expected time. Among the 11 girls, three were at the pubertal age at the time of analysis. Growth retardation was common, whereas late complications (e.g. peripheral hypothyroidism, cataract) were rare. However, the most important long-term complication was the occurrence of cancer in seven patients (8-year projected incidence 24%). Among the 32 survivors, 27 (84.5%) had a normal and four a moderately reduced performance status, and all achieved complete engraftment with donor cells. Therefore transplantation was able to cure these patients who remain at high risk for developing late complications. Clearly, a genetic predisposition and chronic GvHD could have led to the development of these cancers. However, we cannot completely rule out irradiation as a cofactor in the genesis of these cancers, and therefore no longer use irradiation for the conditioning of Fanconi's anaemia patients.

Adolescent↗
PubMed1998

Molecular typing of environmental and patient isolates of Aspergillus fumigatus from various hospital settings.

Fingerprinting of more than 700 clinical and environmental isolates of Aspergillus fumigatus from four differential hospital settings was undertaken with a dispersed repeated DNA sequence. The analysis of the environmental isolates showed that the airborne A. fumigatus population is extremely diverse, with 85% of the strains being represented as a single genotype isolated once. The remaining 15% of the strains were isolated several times and were able to persist for several months in the same hospital environment. No strains were found to be associated with a specific location inside the hospital, and identical strains were isolated from different buildings of the hospital and outdoors. Isolation of the same strain both from patients and from the environment of the same hospital is highly suggestive of a nosocomial infection. The characteristics of the environmental fungal population explains the two main results obtained from the typing of the clinical isolates: (i) the absence of a common strain responsible for an invasive aspergillosis outbreak results from the extreme diversity of the environmental population of A. fumigatus in contact with the patients, and (ii) patients hospitalized in different wards of the same hospital can be infected with the same strain since every patient might inhale the same spore population.

Air Microbiology↗
PubMed1997

Short- and long-term follow-up of thyroid dysfunction after allogeneic bone marrow transplantation without the use of preparative total body irradiation.

We studied the incidence and potential prognostic value of thyroid abnormalities after allogeneic bone marrow transplantation (BMT) without total body irradiation (TBI) conditioning. 77 consecutive patients who received a chemotherapy-alone-based conditioning regimen pretransplant were included. Free serum thyroxine (FT4), free serum triiodothyronine (FT3) and serum thyrotropin (TSH) levels were assayed before and 3 and 14 months after BMT. Patients were classified in three categories: normal thyroid profile if FT3 and FT4 were within the normal range and TSH was normal or low, peripheral thyroid insufficiency (PTI) if TSH was >4 mIU/l, or an 'euthyroid sick syndrome' (ETS) if FT3 and/or FT4 were low and TSH was normal or low. The incidence of thyroid dysfunction at 3 months was 57%, and 29% at 14 months. This was mostly due to the occurrence of ETS which was more frequent at 3 months (48%, 29/61) than at 14 months (19%, 9/48). Furthermore, at 3 months, survival was significantly lower in the ETS group (34.5%) than in the euthyroid group (96.2%), or in the PTI group (83.3%) (P < 0.0001). PTI was observed even in the absence of TBI in 11 patients (14%) and was equally distributed at 3 months (n = 6) and 14 months (n = 5). In conclusion, thyroid dysfunction is not a rare complication even without pretransplant TBI conditioning regimen. Hypothyroidism prevalence was 10%, and ETS, which was more frequently observed, displayed a dismal predictive value at 3 months.

Bone Marrow Transplantation↗
PubMed1997

Indications and timing of allogeneic bone marrow transplantation in myelodysplastic syndromes.

Allogeneic bone marrow transplantation is an effective treatment for myelodysplastic syndromes, providing a probable cure in about one-third of cases overall. It is generally reserved for patients under 50 years who have an HLA-compatible donor. Post-transplant disease-free survival rates vary according to several prognostic factors, which often overlap with those predicting the spontaneous outcome of the disease. Consequently, it is sometimes difficult to choose the indications and timing of bone marrow transplantation in this setting. Here we review the literature in an attempt to draw up relevant guidelines.

Antigenic Variation↗
PubMed1997

[Veno-occlusive disease after bone marrow transplantation: preventive effect of heparin].

Liver veno-occlusive disease is a severe toxic effect observed after bone marrow transplantation. Clinical manifestations are jaundice, painful liver enlargement, and fluid-sodium retention. Histologically there is non-thrombotic obliteration of the centro-lobular veins associated with centro-lobular necrosis. This severe complication of bone marrow transplantation occurs early and is caused by a toxic processing effect. Incidence is variable, 2 to 50% in reported series, depending on patients, type of marrow provessing and on diagnostic criteria (which hinders comparison between studies). According to most studies, veno-occlusive disease regresses spontaneously. Mortality, depending on the severity of the symptoms, varies from 20 to 50%. Pathogenesis remains under debate: the initial event would occur in the sinusoid endothelium creating a state of local hypercoagulability by release of tissue factors favoring deposit of coagulation factors, especially factor VIII, in the subendothelial region of the veinules. There is also a direct toxic effect on centro-lobular hepatocytes which is further aggravated by ischemia and venous stasis. use of heparin to prevent veno-occlusive disease was proposed by the Besançon group in 1985 after they observed a low incidence (1 case in 65) in patients who were given low doses of heparin to maintain patent central catheters. The same team confirmed in 1992 the low incidence in a large retrospective series of 444 patients given either an autograft (3 cases in 253 patients, i.e. 1.2%), or an allograft (5 cases in 191 patients, i.e. 2.6%). Two single-center studies, one in Seattle and the other at the Saint-Antoine hospital in Paris, published in 1990 and 1991, did not show any difference in patients given heparin or not. Inversely, a randomized study published by Attal in 1992 including 161 patients showed a significant difference in the incidence of veno-occlusive disease between patients given heparin (2.5%) and those who were not given heparin (13.7%; p < 0.01). All these studies show that with low doses (100-150 U/kg) the risk is very very low. The mechanism of action of heparin would appear to be related to its protective effect on the endothelium rather than its hemostasis effect. The vascular protective effect of prostaglandin E1 suggests it might also be useful in preventing veno-occlusive disease.

Anticoagulants↗
PubMed1996

Factors influencing outcome in de novo myelodysplastic syndromes treated by allogeneic bone marrow transplantation: a long-term study of 71 patients Société Française de Greffe de Moelle.

We report on 71 consecutive patients with de novo myelodysplastic syndromes referred to physicians belonging to the Société française de greffe de moelle from 1982 through 1991 and transplanted with marrow from HLA-identical siblings. There were 16 cases of refractory anemia, 27 of refractory anemia with excess of blast cells, and 28 of refractory anemia with excess of blast cells in transformation. Seventeen patients had received cytoreductive chemotherapy before the graft. The disease progressed in 17 patients between diagnosis and grafting. Twenty-three patients are alive with a median follow-up of 6 years, whereas 24 died from relapse and 24 from transplant-related complications. Kaplan-Meier estimates of event-free survival, relapse and transplant-related mortality at 7 years were 32%, 48%, and 39%, respectively. The log-rank test and Cox's model revealed better outcome among young patients, patients in an early stage of the French-American-British (FAB) classification or with a low percentage of marrow blasts before transplantation, patients who did not undergo cytoreductive chemotherapy before transplantation, and patients conditioned with total body irradiation and cyclophosphamide. The high rate of relapse in advanced FAB stages has led us to graft patients earlier in the course of the disease, and we are currently conducting a multicenter, randomized study to determine the value of intensive chemotherapy before grafting in patients with an excess of marrow blasts.

Adult↗
PubMed1996

Comparison of an enzyme immunoassay and latex agglutination test for detection of galactomannan in the diagnosis of invasive aspergillosis.

Aspergillus antigenemia was followed up in 215 consecutively observed bone marrow transplant (BMT) patients over a period of two years, using both a latex agglutination test and a sandwich immunocapture enzyme immunoassay (EIA) with a rat antigalactomannan monoclonal antibody as capture and detector antibody. For each patient, sequential sera (3 to 20) were obtained before and after BMT. No positivity was observed before BMT. After BMT, the EIA and latex agglutination test were positive in 19 and 4 patients respectively of 25 patients with confirmed aspergillosis and 14 and 7 of 15 patients with probable aspergillosis. In 19 of 25 patients with confirmed aspergillosis and 9 of 15 patients with probable aspergillosis, the EIA was more sensitive and detected infection earlier than the latex test. In all positive cases, antigenemia rapidly increased in sequential samples and remained strongly positive. In 31 of 169 (19%) BMT patients without clinical signs of aspergillosis, the EIA was occasionally positive in samples taken within the first month after BMT, giving a specificity of 81% in these patients. In non-BMT patients suffering from other diseases (n = 77), the specificity was 98.7%. The overall positive and negative predictive values for the EIA were 54% and 95% respectively. These results favour the use of EIA for early diagnosis and monitoring of aspergillosis in BMT patients, although the predictive value of transient positivity remains to be ascertained.

Animals↗
PubMed1995

Allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia in second remission: factors predictive of survival, relapse and graft-versus-host disease.

Between 1983 and 1993, 42 patients with acute lymphoblastic leukemia (ALL) in second complete remission (CR) underwent an allogeneic HLA-identical bone marrow transplant (BMT; there was one family mismatched graft). The conditioning regimens varied, consisting of cyclophosphamide (CY) and total body irradiation (TBI; n = 10); CY, TBI, Ara C, VP-16 (n = 11); TBI, Ara C, melphalan (n = 20) (TAM) or other (n = 1). Cyclosporine A (CsA) (n = 15) or CsA and methotrexate (MTX) (n = 24) were the main regimens for prophylaxis of graft-versus-host disease (GVHD). Nineteen of 42 patients are alive in CR ranging from 1 to 72 months after BMT with a median follow-up of 36 months. The 4-year actuarial survival rate was 53%. The actuarial relapse rate was 17%. Twenty three patients died: 4 patients of leukemic relapse, 9 of infection, 2 of acute GVHD, 2 of multiorgan failure after chronic GVHD, 2 of a secondary tumour and 4 patients died of other causes. Several pre- and post-transplant characteristics were analyzed to determine predictive factors for survival, relapse and GVHD. The relapse rate was significantly influenced by the type of conditioning regimen with no relapse in the TBI, Ara C, melphalan group. The analysis of long-term sequelae shows that there are no severe complications in this last group. Our results confirm that allogeneic BMT can lead to long-term survival for children with ALL in second CR and suggest an advantage of using the TAM conditioning regimen in the eradication of the leukemic disease.

Actuarial Analysis↗
PubMed1995

MR of cerebral aspergillosis in patients who have had bone marrow transplantation.

PURPOSE: To assess the CT and MR appearance of cerebral aspergillosis in patients who have undergone bone marrow transplantation. METHODS: The imaging and clinical data of five patients with cerebral aspergillosis were reviewed retrospectively and compared with autopsy findings. RESULTS: Lesions are often located in the basal ganglia and demonstrate an intermediate signal intensity within surrounding high-signal areas on long-repetition-time MR scans. The lesions were multiple in four of the five patients and more numerous on MR images than on CT scans. The lesions (which demonstrate no parenchymal enhancement) are consistent with acute infarcts as confirmed at autopsy. In the large lesions, there is early intravascular and meningeal enhancement, as expected in acute infarcts involving an appreciable portion of the territory of a cerebral artery. CONCLUSION: The diagnosis of early cerebral infarction in a patient considered at risk for invasive aspergillosis, even without overt pulmonary disease, is an indication to institute aggressive antifungal therapy.

Adult↗
PubMed1994

Avascular necrosis of bone after allogeneic bone marrow transplantation: clinical findings, incidence and risk factors.

In the present study we describe the incidence, clinical course, and management of avascular necrosis of bone following allogeneic bone marrow transplantation, and identify risk factors related to its development. All patients developing avascular necrosis of bone after allogeneic bone marrow transplantation between January 1974 and September 1992 were included in the analysis and were studied using the Hôpital Saint Louis Bone Marrow Transplant Database and hospital records. 27/727 allogeneic transplant recipients developed avascular necrosis leading to an 8.1% incidence at 5 years, by product limit estimate, ranging from 5% to 11.2%. Symptoms developed 119-1747 d (median 398 d) after transplantation. In these 27 patients a total of 52 joints were affected (mean 1.92 per patient, range 1-7). The hip joint was most often affected (69% of patients). All patients had joint pain that led to diagnosis by means of standard radiographs with or without the help of technetium-99 scans and/or magnetic resonance imaging. All but three patients received steroid therapy for acute graft-versus-host disease. Among 10 factors tested, three were shown to be significantly linked to an increased risk for developing avascular necrosis by multivariate analysis: male gender (relative risk (RR) 4.72, P = 0.002), age older than 16 (RR = 3.87, P = 0.004), and acute graft-versus-host disease requiring steroid therapy (RR = 6.30, P = 0.0002). 10 patients (37%) required joint replacement within 19 months (range 2-42) following diagnosis of avascular necrosis. In conclusion, avascular necrosis of bone is a frequent late complication of allogeneic bone marrow transplantation causing significant morbidity and requiring replacement surgery in one-third of affected patients. In this 18-year single-centre survey, older age, male gender and steroid therapy given for acute graft-versus-host disease were shown to independently increase the risk of avascular necrosis of bone.

Acute Disease↗
PubMed1994

Impact of liver disease and hepatitis infections on allogeneic bone marrow transplantation in Europe: a survey from the European Bone Marrow Transplantation (EBMT) Group--Infectious Diseases Working Party.

This survey investigated allogeneic bone marrow transplantation (BMT) policy in European BMT units by questionnaire, in relation to pre-transplant liver disease. It also assessed diagnostic standards for viral hepatitis infections and their prevalence in BMT candidates. Sixty-three EBMT centers from 22 countries participated in the survey. Median pre-transplant prevalences of HBsAg and anti-HCV positivity were 3.5% (range 0-15%) and 5% (range 0-45%), respectively. Forty-six (73%) centers adopt the policy of cancelling or postponing BMT in patients with ALT abnormalities but in four of these centers, BMT is not delayed when progressive disease or acute leukemia is present. In 17 institutions (27%) BMT was reported to be carried out irrespective of transaminase values. Data on fatal post-BMT liver disease were provided by 45 centers. The overall mortality rate for liver failure was 4.5% (258 of 5788) with no differences between centers performing or not performing BMT in cases of ALT elevation. These results indicate that there is strong concern in most European BMT units about performing BMT in the presence of ALT elevation and prospective studies on its real impact on fatal post-BMT liver disease should be conducted.

Alanine Transaminase↗
PubMed1994

[Invasive aspergillosis and bone marrow allograft].

Invasive aspergillosis is the most frequent cause of infectious death after allogeneic bone marrow transplantation. Risk factors include the patient's condition (granulocytopenia, immunosuppression) and his environment (air spores count). Pulmonary infections are prominent. Other infections usually occur in the setting of disseminated disease via hematogenous spread. Cerebral aspergillosis appears to be especially frequent and of very poor prognosis. Infections of the paranasal sinuses occur less often and are associated or not with pneumonitis. Mycologically confirmed diagnosis is difficult to obtain: treatment will often have to be instored on clinical findings alone or even on an empiric basis. However, the prognosis remains extremely poor explaining the actual physicians' concern in finding a better prophylaxis of this infection.

Amphotericin B↗
PubMed1994

Prophylaxis of toxoplasmosis infection with pyrimethamine/sulfadoxine (Fansidar) in bone marrow transplant recipients.

Prophylaxis against toxoplasmosis with weekly administration of pyrimethamine/sulfadoxine (Fansidar) was assessed for efficacy and toxicity in bone marrow transplant (BMT) recipients over a 21 month period. Sixty-nine of 90 consecutive seropositive patients were evaluable. Fansidar was administered from the time of established engraftment (median day 40, range days 13-100). Medication was scheduled to be continued until 6 months or longer in cases of continued immunosuppression (median 10 months, range day 72 to 22 months). No proven case of toxoplasmosis occurred in patients receiving prophylaxis. In addition, there were no cases of Pneumocystis carinii. Side-effects included BM suppression requiring cessation (n = 4) or interruption (n = 8) of therapy and rash (n = 1). To evaluate toxicity associated with prolonged therapy, 42 evaluable patients were assessed at 6 months following transplant (or at least 4 months of continuous treatment). Haematological toxicity was minimal and compounded in three patients showing moderate derangement by cytomegalovirus infection and graft-versus-host disease. Fansidar is an effective prophylactic agent against toxoplasmosis in BMT patients.

Adolescent↗
PubMed1994

Malignant diseases after allogeneic bone marrow transplantation: an updated overview.

Among late effects occurring after allogeneic bone marrow transplantation malignant diseases are of particular clinical concern as more patients survive the early phase after transplantation and remain free of their original disease. In this paper we briefly review data on the three malignant complications that have been described after allogeneic bone marrow transplantation: leukemias, lymphoma and solid tumours.

Anemia, Aplastic↗