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Nathalie Dhedin

Publications and source records attributed to Nathalie Dhedin.

9 recordsLinked to original sources
PubMed2006

Acute eosinophilic pneumonia after allogeneic hematopoietic stem cell transplantation.

A 55-year old woman with multiple myeloma was treated with hematopoietic stem cell transplantation (HSCT). She developed cutaneous and hepatic graft-vs-host disease (GVHD). Sixty-five days after HSCT, acute respiratory failure occurred. A thoracic computed tomography scan showed bilateral patchy infiltrates. Bronchoalveolar lavage revealed 40% eosinophils on differential cell count with no infectious pathogens. These findings were in favor of acute eosinophilic pneumonia. High-dose steroid treatment was started, which had a rapid and lasting favorable course. After HSCT, clinicians should be aware that acute eosinophilic pneumonia mimics infectious pneumonitis and can be associated with GVHD.

Acute Disease↗
PubMed2005

NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells and inhibitory effect of NKG2A override GvL effect.

Natural killer (NK) cell alloreactivity is reported to mediate strong GvL (graft versus leukemia) effect in patients after haploidentical stem-cell transplantation (SCT) for acute myeloid leukemia (AML). Because subsequent immune reconstitution remains a major concern, we studied NK-cell recovery in 10 patients with AML who received haplomismatched SC transplants, among whom no GvL effect was observed, despite the mismatched immunoglobulin-like receptor (KIR) ligand in the GvH direction for 8 of 10 patients. NK cells generated after SCT exhibited an immature phenotype: the cytotoxic CD3- CD56(dim) subset was small, expression of KIRs and NKp30 was reduced, while CD94/NKG2A expression was increased. This phenotype was associated to in vitro lower levels of cytotoxicity against a K562 cell line and against primary mismatched AML blasts than donor samples. This impaired lysis was correlated with CD94/NKG2A expression in NK cells. Blockading CD94/NKG2A restored lysis against the AML blasts, which all expressed HLA-E, the ligand for CD94/NKG2A. Our present study allows a better understanding of the NK-cell differentiation after SCT. These results revealed that the NK cells generated after haplomismatched SCT are blocked at an immature state characterized by specific phenotypic features and impaired functioning, having potential impact for immune responsiveness and transplantation outcome.

Adolescent↗
PubMed2005

Plasmacytoid dendritic cell reconstitution following bone marrow transplantation: subnormal recovery and functional deficit of IFN-alpha/beta production in response to herpes simplex virus.

Infections with herpesviruses were frequent after bone marrow transplantation (BMT) before the preventive use of antiviral drugs, suggesting a deficit of innate immunity. A retrospective phenotypical and functional study was carried out on 25 patients 1-36 months after allogeneic BMT. Leukocyte counts followed a normal reconstitution, including natural killer (NK) cells and monocytes. Plasmacytoid dendritic cell (PDC) counts increased steadily, although they remained below normal values after 2 years. Most patients produced less interferon- alpha/beta (IFN-alphabeta) in vitro than healthy controls after infection with herpes simplex virus type 1 (HSV-1), whereas they responded normally to Sendai virus (SV). In addition, 6 patients had biologic signs of infection with herpesviruses, confirming a specific immunologic deficit against these viruses. IFN production was not correlated to PDC counts or to the occurrence of graft-versus-host disease (GVHD). Because all patients were under immunosuppressive treatment, we investigated the effect of drugs on IFN production by mononuclear cells. Glucocorticoids and cyclosporine A inhibited IFN production by infected leukocytes, with a predominant action on HSV-1-infected PDC. The inability of transplanted patients to mount an efficient immune response to herpesviruses may be partly related to drug toxicity toward cells of the innate immune system.

Adult↗
PubMed2004

Predicting the costs of allogeneic sibling stem-cell transplantation: results from a prospective, multicenter, French study.

BACKGROUND: Allogeneic hematopoietic stem-cell transplantation is a widely used, cost-intensive procedure. Our purpose was to estimate costs and determine cost predictors. METHODS: We used data from a prospective French study comparing four doses of immunoglobulins. Resource use of hematopoietic stem-cell transplant recipients during the first 6 months posttransplant, both inpatient and ambulatory costs, in 85 patients from five centers were collected prospectively and costed. Baseline data and clinical events were retrieved. Protocol-driven costs were excluded. Multivariable analysis evaluated the association between costs and patient's pretransplant status and transplant-related complications. Because of the absence of differences in outcome among the four randomization groups, cost data for all patients were pooled. RESULTS: Total costs per patient were the following: mean 76,237 Euros; standard deviation 32,565 Euros; median 69,516 Euros; range 183,758 to 14,761Euros. The major cost driver was hospital days. No association was found between costs and baseline status. The "predictors" of higher costs (adding an average 20,000 Euros/patient) were the occurrence of transplant-related complications: graft-versus-host disease and repeated infections that were unpredictable before transplant in this homogeneous group of patients. CONCLUSION: Our data highlight the discrepancy between the Diagnosis Related Group prospective payment system and actual costs. The actual cost of geno-identical stem-cell transplantation results from posttransplant complications that cannot be predicted prospectively and require ex post cost adjustment.

Acute Disease↗
PubMed2003

Successsful voriconazole treatment of disseminated fusarium infection in an immunocompromised patient.

Fusarium infection is known to cause major morbidity and mortality in immunocompromised hosts. We report the successful treatment of disseminated Fusarium infection with skin manifestations in a severely neutropenic, immunocompromised host with voriconazole, a new second-generation triazole. Voriconazole might be an alternative therapy for patients with neutropenia who have fusariosis that is refractory or unresponsive to amphotericin B or its liposomal formulation.

Aged↗
PubMed2002

Development of a real-time polymerase chain reaction assay for the diagnosis of human herpesvirus-6 infection and application to bone marrow transplant patients.

A quantitative real-time PCR assay was developed for human herpesvirus-6 (HHV-6) genome based on TaqMan technology. After choosing a region of interest into the U65-U66 genes of HHV-6 genome, its nucleotide sequence was determined among four HHV-6 strains (one variant A and three variants B) to exclude a variability of sensitivity due to interstrain sequence differences. A plasmid containing HHV-6 target sequences identical to those of reference type viruses was constructed with the aim of standardisation. This HHV-6 genomic quantitation assay has a threshold sensitivity of ten copy equivalents (EqCop) per reaction. In order to test the feasibility of this assay directly on human samples, the technique was applied to the quantitation of HHV-6 genome in 30 blood samples from healthy subjects as well as 31 blood samples and three samples of cerebrospinal fluid (CSF) from 21 bone marrow transplant (BMT) recipients and four patients with a haematological disease but not treated by bone marrow transplantation. HHV-6 load ranged between 0.00015 and 0.0008 equivalent DNA copy number (EqCop) per 100 peripheral blood mononuclear cells (PBMCs) in healthy subjects whereas it ranged from <10 to 7500 EqCop per 100 PBMCs, and from <10 to 415,820 EqCop per 100 microl of whole CSF in patients. The efficacy of treatment with antiherpetic drug was associated with a decrease of the viral load in the CSF of one patient. This method leads to relevant results in term of range of quantitation, sensitivity, and safety against contamination by amplicons, and might constitute a useful tool for the follow-up of BMT recipients particularly in the presence of antiherpetic therapy.

Adult↗
PubMed2002

All trans retinoic acid in combination with intermediate-dose cytarabine and idarubicin in patients with relapsed or refractory non promyelocytic acute myeloid leukemia: a phase II randomized trial.

INTRODUCTION: All trans retinoic acid has shown a remarkable effectiveness in acute promyelocytic leukemia. These results have encouraged studies of treatment with ATRA in other acute myeloid leukemia subtypes. PATIENTS AND METHODS: In order to evaluate toxicity and antileukemic efficacy of all ATRA in patients with relapsed or refractory non promyelocytic AML, 95 patients (median age, 58 years; range, 20 to 80 years), with unclassified AML according to the FAB classification or secondary AML at diagnosis, or refractory or relapsing AML, received induction therapy with Idarubicin, 10 mg/m(2)/day, for 3 days and cytarabine, 1000 mg/m(2)/12 h, for 6 days, alone or combined, on a randomized basis, with ATRA, 45 mg/m(2)/day, from day 1 to complete remission. Patients in CR received maintenance therapy with 6 monthly courses combining Ida, 10 mg/m(2)/day, intravenously, on day 1 with Ara-C100 mg/m(2)/day, subcutaneously, from day 1 to day 5. RESULTS: Results were evaluated after one induction course. Overall 54 patients (57%, 26 with ATRA and 28 without ATRA) achieved CR including five patients treated at time of initial diagnosis, seven previously resistant, 38 in first relapse and four in further relapse. Thirty patients (31%) had resistant disease and 11 (12%) died from toxicity. Median time for neutrophil recovery to 0.5 x 10(9)/l and platelets to 20 x 10(9)/l was 31 and 21 days respectively. Severe toxicity (WHO grade >or=3) included infections (37%), diarrhea (9%), bleeding (3%), vomiting (16%), hyperbilirubinemia (5%), mucositis (6%) and hypercreatininemia (2%). No ATRA syndrome was noted in the ATRA arm. Median overall survival for the entire cohort was 6.3 months and median disease-free survival was 4.7 months. There were no statistical differences in terms of CR, DFS, and OS between the two arms. CONCLUSION: We conclude that ATRA in combination with Ida and Ara-C can be administered safely to high-risk AML patients. However, in this setting, ATRA did not offer any advantage when compared to chemotherapy alone.

Acute Disease↗