G Souillet

Shanghai Ruijin Hospital, Shanghai, Shanghai Shi, China

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Publications (190)637.45 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The present paper reports two new α-globin chain variants: Hb Boghé [α58(E7) His→Gln, α2] and Hb Charolles [α103(G10)His→Tyr,α1]. Hb Boghé was found in a 12-month-old girl who was treated for malignant histiocytosis at 9 months of age and received a bone marrow transplant from her sister. Hb Boghe was undetectable by isoelectrofocusing and high performance liquid chromatography of hemoglobins. It was only revealed by polyacrylamide gel electrophoresis of globin chains in the presence of urea-Triton X-100 and accounted for 10% of the total hemoglobin. Hb Charolles was detected in a 46-year-old patient who presented with microcytosis and hypochromia. It was easily detected by isoelectrofocusing and high performance liquid chromatography. Hb Charolles accounted for 11% of the total hemoglobin. Characterization of the two hemoglobin variants was achieved by DNA and restriction enzyme analyses. Oxygen equilibrium curves measured on whole blood with Hb Boghé were normal. DNA sequencing revealed the association of Hb Charolles with a common mutation of the α2 polyadenylation site: AATAAA→ AATAAG.
    07/2009; 23(4):345-352.
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    ABSTRACT: Despite progress in diagnosis and treatment, invasive aspergillosis (IA) remains a principal cause of mortality due to infection after allogeneic hematopoietic stem cell transplantation (AHSCT). In order to clarify the course of IA among children receiving an AHSCT before the advent of new drugs such as voriconazole or caspofungin, we retrospectively reviewed the medical records of all proven and probable IA between January 1986 and December 2000. 1) Ten children developed IA after AHSCT, mostly long after transplantation. Overall incidence was 2.7%. Seven of those children experienced 1 or more complications after AHSCT and before IA. Mortality was 90% with a median survival of 23 days (2-90). 2) Five children underwent AHSCT after a previous episode of IA. All patients were treated with systemic antifungal therapy combined with surgery. Median time between IA and AHSCT was 110 days (73-370). Two children were diagnosed with IA relapse after transplantation. One child was cured while the other died of IA and AHSCT complications. AHSCT could be considered even in the setting of previous IA, but established strategies implementing newer less toxic antifungal agents as treatment or prophylaxis in high-risk patients are needed.
    Transplant Infectious Disease 07/2008; 10(3):177-83. · 1.98 Impact Factor
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    ABSTRACT: Invasive aspergillosis (IA) is an increasingly common and often fatal fungal infection in children with haematological disorders. To describe the epidemiology, diagnosis, treatment and outcome of IA in children, retrospective review of the medical records of proven and probable IA between January 1986 and December 2000 was used. Twenty-four patients with IA were identified (10 proven and 14 probable) with a median age of 8.5 years. The incidence of IA was particularly high in acute myeloblastic leukaemia (5.35%) and leukaemia relapse (4%). Twenty-two patients presented with lung involvement. Broncho-alveolar lavage led to a diagnosis in 11 cases, but diagnosis was difficult and repeated invasive explorations were required. Antifungal therapy mainly consisted of amphotericin B. Eight patients underwent open-thorax surgery without any complication. Nine patients (37.5%) were cured of IA and three are still alive. The mortality was 87.5%. Three patients died of massive haemoptysis, including two before neutropenia recovery. Four patients presented with IA recurrence and three were cured again. Despite significant progress having been made in the treatment and diagnosis of IA, it is still a devastating complication in children with haematological disorders. New antifungal therapies and strategies are promising, but objective data are still lacking.
    Mycoses 04/2008; 51(2):109-16. · 1.28 Impact Factor
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    ABSTRACT: Hurler's syndrome (HS), the most severe form of mucopolysaccharidosis type-I, causes progressive deterioration of the central nervous system and death in childhood. Allogeneic stem cell transplantation (SCT) before the age of 2 years halts disease progression. Graft failure limits the success of SCT. We analyzed data on HS patients transplanted in Europe to identify the risk factors for graft failure. We compared outcomes in 146 HS patients transplanted with various conditioning regimens and grafts. Patients were transplanted between 1994 and 2004 and registered to the European Blood and Marrow Transplantation database. Risk factor analysis was performed using logistic regression. 'Survival' and 'alive and engrafted'-rate after first SCT was 85 and 56%, respectively. In multivariable analysis, T-cell depletion (odds ratio (OR) 0.18; 95% confidence interval (CI) 0.04-0.71; P=0.02) and reduced-intensity conditioning (OR 0.08; 95% CI 0.02-0.39; P=0.002) were the risk factors for graft failure. Busulfan targeting protected against graft failure (OR 5.76; 95% CI 1.20-27.54; P=0.028). No difference was noted between cell sources used (bone marrow, peripheral blood stem cells or cord blood (CB)); however, significantly more patients who received CB transplants had full-donor chimerism (OR 9.31; 95% CI 1.06-82.03; P=0.044). These outcomes may impact the safety/efficacy of SCT for 'inborn-errors of metabolism' at large. CB increased the likelihood of sustained engraftment associated with normal enzyme levels and could therefore be considered as a preferential cell source in SCT for 'inborn errors of metabolism'.
    Bone Marrow Transplantation 09/2007; · 3.54 Impact Factor
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    ABSTRACT: Busulfan is an alkylating agent used in a conditioning regimen prior to bone marrow transplantation. Busulfan has a narrow therapeutic index, giving rise to major liver toxicity (veno-occlusive disease), and a wide interpatient and intrapatient pharmacokinetic variability. This report presents the results of a population pharmacokinetic analysis leading to models based on underlying diseases requiring bone marrow transplantation. One hundred children received oral busulfan-based conditioning regimens between March 1998 and February 2006. Busulfan pharmacokinetic parameter estimates (Ka, first order absorption rate constant; Vs, volume of distribution related to the body weight; and Cl/F, apparent clearance) were estimated by using the nonparametric adaptative grid (NPAG) algorithm in patients divided into four groups according to initial diagnosis: metabolic diseases, hemoglobinopathies, hematological malignancies, and immune deficiencies. Ka and Vs did no differ significantly in the four subgroups. Cl/F and areas under the plasma concentration curve were significantly different in the four groups. Cl/F was significantly higher in the hemoglobinopathies group (P = 0.002), with a mean value of 7.78 L . h, whereas the immune deficiencies group was characterized by the lowest Cl/F (3.59 L . h). Interindividual variability was shown by high interindividual parameter percent coefficients of variation (CV%) but, nevertheless, with less diversity in the population parameter distributions for Vs in the three subgroups-metabolic diseases, hemoglobinopathies, and malignant diseases-and in Cl/F for patients with hemoglobinopathies. The fit was good for busulfan concentration predictions based on Bayesian individual posterior values, with little bias and good precision. In comparison with the overall population, the only model of subgroup presenting a greater precision was patients with hemoglobinopathies (P = 0.002). Use of these more specific models of a given disease may well result in more accurate individualization of busulfan dose regimens, especially in very sparse blood sampling situations.
    Therapeutic Drug Monitoring 05/2007; 29(2):177-84. · 2.23 Impact Factor
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    ABSTRACT: In vitro stimulation of human female T cells with male HLA-identical dendritic cells resulted in the generation of HLA-DQB1*0501/0502-restricted minor histocompatibility H-Y antigen-specific CD4(+) T cell clones. Two clones generated from different HLA-identical pairs were analyzed. Use of HLA-DQ5-expressing female Epstein-Barr virus transformed B lymphoblastoid cell lines transfected with various H-Y genes and loaded with overlapping peptides demonstrated that both T cell clones are specific for a peptide encoded by DDX3Y. Previously, an HLA-DQ5-restricted T cell clone specific for the same peptide was isolated from a patient with graft-versus-host disease. Thus, we compared the T cell receptor (TCR) rearrangements of the 2 in vitro generated T cell clones and the ex vivo isolated T cell clone. All 3 clones shared the same TCRBV5-4* gene segment and 2 of 3 clones also used similar TCR-Valpha segments. Our results suggest that T cells recognizing the HLA-DQ5/DDX3Y T cell epitope might be characterized by a relatively limited TCR-beta repertoire. The differences in the junctional TCR-beta region had no effect on the antigen specificity, but altered the capacity of the TCR to distinguish the HLA-DQ5/DDX3Y complex from its allelic counterpart. The results also demonstrate that in vitro stimulation of T cells with allogeneic HLA-identical dendritic cells may facilitate the characterization of in vivo, potentially relevant HLA class II-restricted minor H epitopes.
    Biology of Blood and Marrow Transplantation 12/2006; 12(11):1114-24. · 3.94 Impact Factor
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    ABSTRACT: In vitro stimulation of human female T cells with male HLA-identical dendritic cells resulted in the generation of HLA-DQB1*0501/0502-restricted minor histocompatibility H-Y antigen-specific CD4(+) T cell clones. Two clones generated from different HLA-identical pairs were analyzed. Use of HLA-DQ5-expressing female Epstein-Barr virus transformed B lymphoblastoid cell lines transfected with various H-Y genes and loaded with overlapping peptides demonstrated that both T cell clones are specific for a peptide encoded by DDX3Y. Previously, an HLA-DQ5-restricted T cell clone specific for the same peptide was isolated from a patient with graft-versus-host disease. Thus, we compared the T cell receptor (TCR) rearrangements of the 2 in vitro generated T cell clones and the ex vivo isolated T cell clone. All 3 clones shared the same TCRBV5-4* gene segment and 2 of 3 clones also used similar TCR-Valpha segments. Our results suggest that T cells recognizing the HLA-DQ5/DDX3Y T cell epitope might be characterized by a relatively limited TCR-beta repertoire. The differences in the junctional TCR-beta region had no effect on the antigen specificity, but altered the capacity of the TCR to distinguish the HLA-DQ5/DDX3Y complex from its allelic counterpart. The results also demonstrate that in vitro stimulation of T cells with allogeneic HLA-identical dendritic cells may facilitate the characterization of in vivo, potentially relevant HLA class II-restricted minor H epitopes.
    Biology of .Bloodand MarrowTransplantation. 01/2006; 12:1114-24..
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    ABSTRACT: Between September 1986 and June 1997, 24 children with high-risk ALL in CR1 were allografted after TAM (fractionated TBI, high-dose Ara-C, and melphalan; n = 10) or BAM protocol (busulfan, high-dose Ara-C, and melphalan; n = 14). The EFS for transplants from sibling donors was 33% with TAM and 62% with BAM (P = 0.148). The probability of acute GvHD was 70% with TAM and 15% with BAM (P = 0.003). Four of 17 evaluable patients relapsed: one after TAM and three after BAM. In all, 46 other children transplanted in CR beyond CR1 were studied for sequelae. Long-term side effects were more frequent in TAM vs BAM. In children with ALL, busulfan may be a good alternative to TBI to improve the quality of life.
    Bone Marrow Transplantation 11/2004; 34(8):667-73. · 3.54 Impact Factor
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    ABSTRACT: We retrospectively reviewed the results of serial pulmonary function tests (PFT) after allogeneic bone marrow transplantation (BMT) performed in 80 children at a single institution over a 16-year period. We looked for associations linking PFT results to graft-versus-host disease (GVHD), conditioning regimen (total body irradiation (TBI) vs busulphan), and cytomegalovirus immune status. The median follow-up after BMT was 4 years. At 2 years after BMT, significant declines were found in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), as compared to baseline. Both FEV1 and the FEV1/FVC ratio showed significantly greater reductions in the group conditioned with busulphan (n=22) than in the group conditioned with TBI (n=49) and were significantly lower in the patients with (n=16) than without (n=64) chronic GVHD. Busulphan may be associated with greater long-term lung toxicity than TBI. The relevance of this finding to selection of conditioning regimens for BMT should be examined in the light of the overall pattern of side effects. Chronic GVHD was associated with airway obstruction.
    Bone Marrow Transplantation 08/2004; 34(2):143-7. · 3.54 Impact Factor
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    ABSTRACT: Viral infections remain a major complication of allogeneic bone marrow transplantation. A population of children who underwent unrelated allogeneic bone marrow transplantation in a single centre has been followed-up for viral infections and diseases. We describe the detection of cytomegalovirus (CMV) and adenovirus among 75 children transplanted between 1989 and 2000. CMV was detected among 22 patients (29%) and adenovirus among 19 patients (25%); they were associated with clinical diseases in 10 and 8 patients, respectively. Four patients had adenovirus and CMV coinfection. The obvious risk factor for CMV infection is seropositivity of the recipient prior to transplantation. Adenovirus is detected significantly more frequently when conditioning regimen includes anti-thymocyte or anti-lymphocyte globulin. Diseases associated with adenovirus have been correlated with a significantly higher mortality rate, stressing the need for the implementation of a systematic virological survey for this virus and for the evaluation of therapeutic protocols including new molecules.
    Journal of Medical Virology 03/2004; 72(2):257-62. · 2.37 Impact Factor
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    ABSTRACT: The aim of this study was to identify the risk factors for acute graft-versus-host disease (aGVHD) in children transplanted from a matched-sibling donor (MSD) or an unrelated donor (UD). In all, 87 children consecutively underwent allogeneic bone marrow transplantation (BMT) from MSD (n=36), and UD (n=51). GVHD prophylaxis included CsA alone (n=33) or with MTX (n=51). ATG was added in UD-BMT and thalassemic recipients. CsA whole-blood concentrations were measured by EMIT and the dosing regimen was monitored by Bayesian pharmacokinetic modelling. Trough blood concentration (TBC) during the first 2 weeks post transplantation was lower in children who developed grade II-IV aGVHD than those developing no GVHD or only grade I (57+/-9 vs 94+/-8 ng/ml, P=0.007), whereas peak blood concentration and area under concentration curve vs time were similar in both groups. TBC <85 ng/ml and 'use of MTX' were associated with aGVHD in MSD-SCT (P=0.003 and 0.007, respectively) as well as in UD-SCT (P=0.006 and 0.003). Donor age >or=8 years was significant only in MSD-BMT. Our results have shown the significant decisive role of pharmacological factors such as CSA TBC or use of MTX in the occurrence of GVHD in MSD as well as in UD paediatric BMT.
    Bone Marrow Transplantation 11/2003; 32(9):881-7. · 3.54 Impact Factor
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    ABSTRACT: Bone marrow transplantation (BMT) from matched sibling donors has been useful for the treatment of acute lymphoblastic leukaemia in children with a poor prognosis but is not available to more than two-thirds of patients who do not have a matched allogeneic donor. This study was undertaken to assess one strategy of marrow graft rejection prevention when alternative marrow sources such as HLA-phenoidentical unrelated volunteers and HLA-partially incompatible relatives were used. Results have been compared with two matched groups of children with the same risks factors and disease status who underwent HLA-genoidentical or autologous BMT. The conditioning regimen was the same for the three groups of patients; in the study group anti-LFA-1 and anti-CD2 monoclonal antibodies combined with T-cell depletion of the marrow was added to prevent graft rejection and graft-versus-host disease. Nineteen patients were included and followed for a median of 25 months (14 months to 3 years). Bone marrow engraftment occurred in 83% of the evaluable patients. Post-transplantation infectious diseases were the most frequent causes of death in the study group, occurring in 31% of patients. No fatal infections occurred in the two control groups. Post-transplantation relapse of leukaemia occurred in 26% of study group's patients, in 58% of autologous BMT control group's patients and in 5% of HLA-genoidentical allogeneic group's patients. The event-free survival was 83% in the HLA-genoidentical control group, and 30% and 24% in the study group and in the autologous control group, respectively. In conclusion, a high rate of engraftment was achieved by the use of anti-LFA-1 and anti-CD2 antibodies. Occurrence of a long-lasting immunodeficiency, however, led to a high incidence of lethal infections and relapses. Combined approaches are therefore to be investigated accelerating immune reconstitution after transplantations of T-depleted HLA partially incompatible marrow.
    British Journal of Haematology 10/2003; 93(1):131 - 138. · 4.94 Impact Factor
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    ABSTRACT: In order to determine optimal CsA trough blood concentrations (TBC) in the early post transplantation period, we analysed relationships between TBC and acute graft-versus-host disease (aGVHD) in paediatric SCT. A total of 94 children consecutively underwent allogeneic stem cell transplantation (SCT) from: matched-sibling (MSD) (n=36), mismatched-related (MMRD) (n=3) and unrelated donors (UD) (n=55). GVHD prophylaxis usually included CsA alone or with methotrexate. Antithymocyte globulin was added in UD-SCT. TBC during the first weeks of post transplantation were estimated retrospectively by a Bayesian pharmacokinetic method and statistically associated with aGVHD. In MSD-SCT, the mean TBC during the first 2 weeks post transplantation were 42+/-10 and 90+/-7 ng/ml, respectively, in patients with grade II-IV and 0-I aGVHD (P=0.001). In SCT from UD and MMRD, TBC were 73+/-4 vs 95+/-8 ng/ml (P=0.284). For TBC >85 ng/ml, no patient developed grade II-IV aGVHD, 10 developed mild aGVHD and 30 had no aGVHD. For TBC <65 ng/ml, 7/11 patients receiving an MSD-SCT and 4/18 receiving an UD- or MMRD-SCT developed grade II-IV aGVHD. The mean TBC corresponding to each grade were: no GVHD: 101+/-10 ng/ml, mild: 77+/-11 ng/ml, moderate: 61+/-13 ng/ml, severe: 56+/-15 ng/ml (P <0.001). These results reveal a strong relationship between TBC during the early post transplantation period and the severity of aGVHD in paediatric SCT.
    Bone Marrow Transplantation 10/2003; 32(8):777-84. · 3.54 Impact Factor
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    ABSTRACT: Over the last 15 years, we have performed a total of 30 haematopoietic stem cell transplants on 27 children suffering from Hurler's syndrome. These children were of median age 11 months at the time of diagnosis and 25 months at the time of transplantation. The phenotype was severe in 21 cases (78%). The donor was familial in 13 cases: nine genotypically identical, one phenotypically identical father and three HLA-mismatched donors. Unrelated donors were selected in 17 cases: four phenotypically identical and 13 with 1-4 HLA mismatches. The conditioning regimen generally consisted of busulphan 600 mg/m(2) plus cyclophosphamide (Endoxan) 260 mg/kg and cyclosporin with methotrexate for GvHD prophylaxis. Rabbit anti-thymocyte globulin (Thymoglobuline) was given for all unrelated or familial mismatched transplantations. The median nucleated cell dose infused was 6.00 x 10(8) TNC/kg. No bone marrow (apart from one) was T cell depleted. For first transplants, engraftment was observed in 23/27 patients (pts) (85%). Primary graft failure was observed in 4/27 patients (16%), two were retransplanted from an unrelated donor, one with success. Four patients have died. The primary cause of death was infection in three cases (TRM : 11%) and disease progression in one case, after primary graft failure. Of the 23 living patients, two have disease progression after graft failure and 21 (78%) have functional grafts with a favourable long-term outcome after a median follow-up of 4.7 years, having either full or mixed chimaerism. Among surviving patients with functional grafts, 13 (62%) were transplanted from unrelated donors of whom 10 (77 %) had HLA disparities. There was a remarkably low incidence of GvHD. In our experience, haematopoietic stem cell transplantation using an HLA-matched familial donor or an HLA-matched or -mismatched unrelated donor without T cell depletion or irradiation can achieve a favourable outcome in Hurler's syndrome, with improved cognitive function, but with a limited effect on the corneas and skeleton.
    Bone Marrow Transplantation 07/2003; 31(12):1105-17. · 3.54 Impact Factor
  • Archives De Pediatrie - ARCHIVES PEDIATRIE. 01/2003; 10.
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    ABSTRACT: Hemoglobin Lyon-Bron was found in two members of a family of German ascent presenting with a moderate normocytic anemia. In this alpha 2 globin variant, the N-terminal valine of the chain was replaced by an alanine. Electrospray mass spectrometry of the alpha chain showed that, as normally, the initiator methionine was cleaved during globin processing but that the N alpha-terminal group was totally acetylated. This resulted in structural modifications of a region crucial for oxygen binding. As a consequence, hemoglobin Lyon-Bron displayed both a reduced chloride effect and a decreased oxygen affinity, this last point explaining the apparent anemia.
    American Journal of Hematology 04/2002; 69(3):214-8. · 4.00 Impact Factor
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    ABSTRACT: EBV viral load (EBV-VL) in PBMC was prospectively determined by semi-quantitative PCR in 85 stem cell transplants (40 genoidentical, 45 non-genoidentical) in order to characterize the kinetics of EBV-VL and to assess the ability of this measure to predict the development of EBV-induced lymphoproliferative disease (EBV-LPD). PCR was performed prior to and after transplantation. An EBV-VL >300 copies/microg DNA was chosen as the threshold for risk of developing an EBV-LPD. Two hundred and fifty-eight EBV-VL measures were evaluable. Five patients (5.9%) developed an EBV-LPD. All had an elevated EBV DNA peak level before EBV-LPD. Fifteen out of 80 recipients (18.7%) without EBV-LPD had EBV levels over 300 copies/microg DNA at least once during the follow-up. Overall, the manifestation of at least one EBV-VL over 300 copies/microg DNA during the entire follow-up demonstrated a sensitivity, specificity, positive and negative predictive value for the diagnosis of EBV-LPD of 100%, 81%, 25% and 100%, respectively. In patients without EBV-LPD, HLA incompatibility, grade > or = II acute GVHD and use of an unmanipulated graft were significantly associated with an EBV-VL >300 copies/microg DNA. This strategy appears sensitive for the diagnosis of EBV-LPD but its positive predictive value has to be improved in order to guide pre-emptive therapy.
    Bone Marrow Transplantation 02/2002; 29(1):21-8. · 3.54 Impact Factor
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    ABSTRACT: In order to control busulfan pharmacokinetic variability and toxicity, a specific monitoring protocol was instituted in our bone marrow transplant BMT paediatric patients including a test dose, daily Bayesian forecasting of busulfan plasma levels, and Bayesian individualization of busulfan dosage regimens. Twenty-nine children received BMT after a busulfan-based conditioning regimen. Individual pharmacokinetic parameters were obtained following a 0.5 mg*kg test dose and were used for daily individualization of dosage regimens during the subsequent 4-day course of treatment. Doses were adjusted to reach a target mean AUC per 6 h between 4 and 6 microg.h.ml(+1). Plasma busulfan assays were performed by liquid chromatography. Pharmacokinetic analysis used the USC*PACK software. The performance of the test dose to predict AUC during the busulfan regimen was evaluated. Incidence of toxicity, chimerism and relapse, overall Kaplan-Meier survival, and VOD-free survival were compared after matching our patients (group A) with patients conditioned by using standard doses of busulfan (group B). Busulfan doses were decreased in 69% of patients compared to conventional doses. Expected AUC was significantly correlated with observed AUC and predictability of the test dose was 101.9 +/- 17.9%. Incidence of VOD in group A was 3.4% vs 24.1% in group B, while the incidence of stomatitis was similar. Engraftment was successful in all patients in group A. The rate of full engraftment at 3 months post-BMT was higher in group A (P = 0.012). Long-term overall survival did not differ between the two groups, in contrast to the 90-day survival. VOD-free survival was higher in group A (P = 0.026). Pharmacokinetic monitoring and individualization of busulfan dosage regimen are useful in improving clinical outcome and reducing early mortality in paediatric bone marrow transplant recipients.
    Bone Marrow Transplantation 11/2001; 28(8):743-51. · 3.54 Impact Factor
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    ABSTRACT: There is now convincing evidence that minor histocompatibility antigens (mHag) may play a significant role in the pathogenesis of graft-versus-host disease after HLA-identical bone marrow transplantation. Indeed, in this clinical situation, T cells specific for mHag have been isolated. Here, we addressed whether one can generate mHag-specific T cells in vitro, without any in vivo immunization, among healthy blood donors. We used monocyte-derived dendritic cells (Mo-DCs) as antigen presenting cells to induce primary responses between healthy HLA-identical siblings, in mixed lymphocyte dendritic cell reactions (MLDCRs). We show that CD4+ T-cell clones, specific for the mHag H-Y, can be generated in vitro. These clones were derived from a gender-mismatched positive MLDCR pair of HLA-identical siblings and were restricted by the HLA DQB1*0502 molecule. In addition, these CD4+ T clones were also able to lyse allogeneic targets with the same pattern of restriction and specificity than helper function. Finally, acute myeloid leukemia (AML) blast cells were susceptible to lysis by these clones. Altogether, these results predict that Mo-DCs could help to generate class II-associated, mHag-specific, T-cell lines or clones in vitro, between healthy blood donors, without any need of transplantation-mediated immunization.
    Transplantation 06/2001; 71(10):1449-55. · 3.78 Impact Factor
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    ABSTRACT: In order to compare the outcomes of unrelated umbilical cord blood transplants (UCBTs) or bone marrow transplants, 541 children with acute leukemia (AL) transplanted with umbilical cord blood (n = 99), T-cell-depleted unrelated bone marrow transplants (T-UBMT) (n = 180), or nonmanipulated (UBMT) (n = 262), were analyzed in a retrospective multicenter study. Comparisons were performed after adjustment for patient, disease, and transplant variables. The major difference between the 3 groups was the higher number in the UCBT group of HLA mismatches (defined by serology for class I and molecular typing for DRB1). The donor was HLA mismatched in 92% of UCBTs, in 18% of UBMTs, and in 43% of T-UBMTs (P <.001). Other significant differences were observed in pretransplant disease characteristics, preparative regimens, graft-versus-host disease (GVHD) prophylaxis, and number of cells infused. Nonadjusted estimates of 2-year survival and event-free survival rates were 49% and 43%, respectively, in the UBMT group, 41% and 37% in the T-UBMT group, and 35% and 31% in the UCBT group. After adjustment, differences in outcomes appeared in the first 100 days after the transplantation. Compared with UBMT recipients, UCBT recipients had delayed hematopoietic recovery (Hazard ratio [HR] = 0.37; 95% confidence interval [95CI]: 0.27-0.52; P <.001), increased 100 day transplant-related mortality (HR = 2.13; 95CI: 1.20-3.76; P <.01) and decreased acute graft-versus-host disease (aGVHD) (HR = 0.50; 95CI: 0.34-0.73; P <.001). T-UBMT recipients had decreased aGVHD (HR = 0.25; 95CI: 0.17-0.36; P <.0001) and increased risk of relapse (HR = 1.96; 95CI: 1.11-3.45; P =.02). After day 100 posttransplant, the 3 groups achieved similar results in terms of relapse. Chronic GVHD was decreased after T-UBMT (HR = 0.21; 95CI: 0.11-0.37; P <.0001) and UCBT (HR = 0.24; 95CI: 0.01-0.66; P =.002), and overall mortality was higher in T-UBMT recipients (HR = 1.39; 95CI: 0.97-1.99; P <.07). In conclusion, the use of UCBT, as a source of hematopoietic stem cells, is a reasonable option for children with AL lacking an acceptably matched unrelated marrow donor.
    Blood 05/2001; 97(10):2962-71. · 9.78 Impact Factor

Publication Stats

3k Citations
637.45 Total Impact Points

Institutions

  • 2004
    • Shanghai Ruijin Hospital
      Shanghai, Shanghai Shi, China
  • 1983–2004
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
  • 1985–2002
    • CHU de Lyon - Institut d'hématologie et d'oncologie pédiatrique
      Lyons, Rhône-Alpes, France
  • 1999
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
    • University of Pavia
      Ticinum, Lombardy, Italy
  • 1998
    • Policlinico San Matteo Pavia Fondazione IRCCS
      Ticinum, Lombardy, Italy
  • 1996–1997
    • Centre Hospitalier Lyon Sud
      Lyons, Rhône-Alpes, France
  • 1995
    • French National Centre for Scientific Research
      • Centre de génétique moléculaire
      Paris, Ile-de-France, France
  • 1994
    • Hôpital Universitaire des Enfants Reine Fabiola
      • Department of Hemato-Oncology
      Brussels, BRU, Belgium
    • European Organisation for Research and Treatment of Cancer
      Bruxelles, Brussels Capital Region, Belgium
  • 1992
    • Institut National de la Transfusion Sanguine, Paris
      Lutetia Parisorum, Île-de-France, France
    • Claude Bernard University Lyon 1
      Villeurbanne, Rhône-Alpes, France