C Curtillet

Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasburg, Alsace, France

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Publications (16)29.09 Total impact

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    ABSTRACT: This study aimed to describe kinetics of complete donor chimerism occurrence (cDC, >99·9% donor) after unrelated cord blood transplantation (UCBT), to identify its predictive factors and its impact on post-transplant outcome. Ninety-four children who received single UCBT after a myeloablative conditioning regimen had blood chimerism evaluation at predefined post-transplant dates, using a real-time polymerase chain reaction method with 0·1% sensitivity. Cumulative incidence of cDC at 1 year post-transplantation was 61·8%. Three predictive factors were identified in multivariate analysis: history of malignant disease (P = 0·03), older age (above 2·16 years, the first quartile of age, P = 0·0055) and higher level of cord/recipient human leucocyte antigen mismatch (4/6 vs. 5-6/6, P < 0·001) increased the probability of post-transplant cDC. Although graft cell dose had a strong impact on haematological recovery, it did not apparently influence cDC occurrence. Early cDC (i.e. more than 99·9% donor chimerism on days 15–30 post-transplant) appeared useful to predict engraftment (P = 0·003) as well as acute and chronic graft-versus-host disease (GvHD). Severe acute or chronic GvHD never occurred in patients with DC ≤99·9%, suggesting than even minimal residual host haematopoiesis is associated with a very low risk of GvHD after UCBT.
    British Journal of Haematology 04/2014; · 4.94 Impact Factor
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    02/2011;
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    ABSTRACT: We studied lymphocyte recovery in 88 children who consecutively underwent unrelated cord blood transplantation for malignant (n = 64) or nonmalignant (n = 24) diseases. All children but 3 received myeloablative conditioning regimens with pretransplant antithymocyte globulin. Median age was 5.6 years (0.1-18 years) and median follow-up was 40 months (10-136 months). The median dose of infused viable CD45(+) cells (vCD45) was 3.35 × 10(7)/kg with a ratio infused vCD45/collected total nucleated cell at 0.46. Immunologic endpoints were: time to achieve CD3(+) >500 and 1500/mm(3), CD4(+) >500/mm(3), CD8(+) >250/mm(3), CD19(+) >200/mm(3), natural killer >100/mm(3). These endpoints were analyzed through the use of cumulative curves for estimating incidence over time in the context of competing risks, and through Fine and Gray models to assess prognostic factors. The median time to reach these endpoints was 33, 97, 214, and 340 days for natural killer, B, CD8, and CD4 cells, respectively. In multivariate analysis, a high infused vCD45 cell dose improved CD3 (P = .014) and CD4 (P = .032) reconstitutions. A young recipient age also favored CD3 recovery (P = .013). With patients grouped according to vCD45 cell dose quartiles, the threshold for a better recovery was 3.35 × 10(7)/kg. Considering the ratio vCD45/TNC, this "immune recovery based" threshold corresponds to a higher cell dose than the minimum usually recommended dose for myelogenous engraftment. This may have important implication for UCB selection.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2011; 17(1):109-16. · 3.15 Impact Factor
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    ABSTRACT: We evaluate the prevalence and risk factors of the metabolic syndrome (MS) in young adults surviving childhood leukemia. During the years 2007 to 2008, assessment of MS was proposed to all adults included in the Leucémie de l'Enfant et de l'Adolescent program, a French prospective multicentric cohort of leukemia survivors. Among 220 eligible patients, 184 (83.6%) had complete evaluation. Median age at evaluation and follow-up duration were 21.2 and 15.4 years. Overall prevalence of MS was 9.2% (95% confidence interval, 5.5-14.4). There was no association of MS with sex, age at diagnosis, leukemia subtype, steroid therapy, and central nervous system irradiation. Patients were stratified according to 4 therapeutic modalities: chemotherapy alone (n = 97), chemotherapy and central nervous system irradiation (n = 27), hematopoietic stem cell transplantation (HSCT) without (n = 17) or with (n = 43) total body irradiation (TBI). MS occurred in 5.2%, 11.1%, 5.9%, and 18.6% of them, respectively. The higher risk observed in the HSCT-TBI group was significant in univariate and in multivariate analysis (odds ratio [OR] = 3.9, P = .03). HSCT with TBI was associated with a higher rate of hypertriglyceridemia (OR = 4.5, P = .004), low level of high-density lipoprotein cholesterol (OR = 2.5, P = .02), and elevated fasting glucose (OR = 6.1, P = .04) So, TBI is a major risk factor for MS. Further studies are warranted to explain this feature.
    Blood 01/2011; 117(17):4442-8. · 9.78 Impact Factor
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    ABSTRACT: We report results of RIC AHSCT in four adolescents with aggressive refractory HL. They all received three or four lines of therapy prior to RIC-AHSCT including autografts. At the time of RIC, they were in partial response except for one patient who had progressive chemoresistant disease. The conditioning regimen consisted of fludarabin, busulfan and ATG. They all had a matched related donor. The median follow-up was 12-16-month post-allograft. All patient transplants engrafted rapidly. The median time of hospitalization was 35 days. The median time to neutrophil recovery (>or=500/muL) was 19 days. All the patients were in complete donor chimerism at day 60. Four patients developed skin (grade <or= II) acute GvHD. All responded and all are alive. Two patients are in CR, one in PR and one relapsed six months after grafting after a PR. Each of the patients in PR received two DLI. These observations, together with the responses after DLI, suggest the presence of a graft vs. lymphoma effect in patients with advanced active HL. Prospective studies are needed to identify the patients likely to benefit most from this treatment approach.
    Pediatric Transplantation 03/2009; 14(1):109-14. · 1.50 Impact Factor
  • Archives De Pediatrie - ARCHIVES PEDIATRIE. 01/2008; 15(5):1015-1015.
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    ABSTRACT: We compared late side effects and quality of life (QoL) in 430 survivors of childhood acute leukaemia based on whether they had undergone haematopoietic cell transplantation (n=142) or not (n=288). Mean age was 18.2 years and mean follow-up duration was 11.9 years. Multivariate logistic regression analyses were performed to compare the risk of each type of late effect in the two groups. Based on age, VSP-A or SF36 questionnaires were used to assess QoL. For each QoL dimension, multiple linear regression was done to construct models of association with the treatment group. Transplanted patients experienced more side effects, including height growth failure, gonadal dysfunction, hypothyroidism and cataract. Children and adolescents in the two treatment groups reported similar QoL levels for almost all dimensions except a better perception of school work by young transplanted children and more difficulties in relating to the medical staff for transplanted adolescents. In adults, two differences in physical domain of QoL were detected but the calculated effect sizes were less than 0.2 in each case, suggesting an uncertain clinical significance. In spite of a higher risk of physical adverse events in the transplanted group, very few clinically significant differences in QoL are detectable.
    Bone Marrow Transplantation 12/2007; 40(9):897-904. · 3.54 Impact Factor
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    ABSTRACT: Cord blood (CB) units are increasingly used for allogeneic transplantation. Cell dose, a major factor for CB selection, is evaluated before freezing by each CB bank, using various techniques. This may introduce variability and affect the prediction of cell recovery after thawing, or haematopoietic reconstitution. Forty-two children were transplanted at the same institution with unrelated CB units. All units were thawed and evaluated at the same cell therapy facility, using standard procedures. We investigated: (i) factors that affect cell loss after thawing, and (ii) the importance of CD34(+) cell doses. Prefreeze and post-thaw CD34(+) cell doses were statistically correlated, thus suggesting that variability in numeration techniques used by different CB banks does not compromise the biological and clinical value of these figures. CD34(+) cell recovery appeared to be correlated with the absolute number of CD34(+) cells per frozen bag. Infused CD34(+) is the cell dose that better correlates with platelet reconstitution delay; in addition, when using a quartile comparison, haematopoietic recovery appeared to be related with prefreeze and post-thaw CD34(+) cell doses. We conclude that enumeration of CD34(+) cells in CB units is of biological significance, and may help select CB units and identify patients at risk of delayed recovery.
    Bone Marrow Transplantation 05/2007; 39(8):453-60. · 3.54 Impact Factor
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    ABSTRACT: Thrombotic thrombocytopenic purpura (TTP), when accompanied by regenerative anaemia with schizocytosis, thrombopenia and neurological manifestations, is a disease whose main characteristic is the absence of the von Willebrand factor (vWF) cleaving protease. The two types of TTP are distinguishable by the presence or absence of antiprotease inhibitors, which are, respectively, either acquired or constitutional. The acquired autoimmune form is most frequently observed in adults. OBSERVATION: An adolescent with a previous history of moderate, isolated thrombopenia first showed symptoms of TTP at the age of 14. Positive antiprotease inhibitors in combination with a degeneration of protease activity confirmed the diagnosis of acquired autoimmune TTP. A treatment consisting of daily plasma exchange led to rapid improvement; however, a failed attempt to space out plasma exchanges necessitated the introduction of 4 weekly injections of Rituximab beginning on day 40, which was successful. Indeed, since the second injection of Rituximab on day 51, the number of platelets stabilized at a normal level, thereby allowing for the complete cessation of plasma exchange. At this writing - day 89 - the patient remains in persistent remission. CONCLUSION: Given the different therapeutic and prognostic implications of the 2 types of TTP in child patients, it is mandatory to end at an accurate biological diagnosis: whereas the constitutional form is effectively treated with plasma injections, the acquired form, while initially requiring plasma exchange, often necessitates the use of immunosuppressors during acute or relapse phase. The present study concerns a paediatric case of acquired TTP treated successfully with Rituximab during an acute dependant phase.
    Archives de Pédiatrie 01/2007; 13(12):1521-4. · 0.36 Impact Factor
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    ABSTRACT: Thrombotic thrombocytopenic purpura (TTP), when accompanied by regenerative anaemia with schizocytosis, thrombopenia and neurological manifestations, is a disease whose main characteristic is the absence of the von Willebrand factor (vWF) cleaving protease. The two types of TTP are distinguishable by the presence or absence of antiprotease inhibitors, which are, respectively, either acquired or constitutional. The acquired autoimmune form is most frequently observed in adults.
    Archives De Pediatrie - ARCHIVES PEDIATRIE. 01/2006; 13(12):1521-1524.
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    ABSTRACT: To evaluate the percentage and risk factors of thyroid dysfunction in 79 children who underwent bone marrow transplantation in a single centre. The mean age of the cohort was 6.8 and mean follow-up 5.5 years. The 79 patients were divided in two groups according to the pretransplant conditioning regimen: fractionated total body irradiation (TBI)(N=54), chemotherapy with Busulphan (N=25). Thyroid function was evaluated by thyroid-stimulating hormone (TSH) and free thyroxine (fT4) tests. Overt hypothyroidism was defined by low fT4 blood levels and TSH > 4 mU/l, and compensated hypothyroidism by normal fT4 index and TSH >4 mU/L. The six-year probability of hypothyroidism was 36 +/-6% for the whole group of 79 patients, 49 +/-8% after TBI and 9 +/-6% in the Busulphan group (P <0.001). Neither gender, nor primary disease, nor presence of graft versus host disease were found to be statistically significant for occurrence of hypothyroidism in the TBI group. However, a younger age seemed to influence statistically the 6-year probability of hypothyroidism in the TBI group: 59 +/-9% if age <7.7 years versus 34 +/-13% if age >7.7 years (P =0.02). A careful follow-up of thyroid function is recommended even without TBI conditioning regimen. Young age as a potential risk factor of hypothyroidism has never been described and needs to be studied in a larger cohort.
    Archives de Pédiatrie 11/2004; 11(11):1326-32. · 0.36 Impact Factor
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    ABSTRACT: To evaluate the percentage and risk factors of thyroid dysfunction in 79 children who underwent bone marrow transplantation in a single centre.Patients and methods. – The mean age of the cohort was 6.8 and mean follow-up 5.5 years. The 79 patients were divided in two groups according to the pretransplant conditioning regimen: fractionated total body irradiation (TBI)(N =54), chemotherapy with Busulphan (N =25). Thyroid function was evaluated by thyroid-stimulating hormone (TSH) and free thyroxine (fT4) tests. Overt hypothyroidism was defined by low fT4 blood levels and TSH > 4mU/l, and compensated hypothyroidism by normal fT4 index and TSH >4mU/L.Results. – The six-year probability of hypothyroidism was 36 ±6% for the whole group of 79 patients, 49 ±8% after TBI and 9 ±6% in the Busulphan group (P <0.001). Neither gender, nor primary disease, nor presence of graft versus host disease were found to be statistically significant for occurrence of hypothyroidism in the TBI group. However, a younger age seemed to influence statistically the 6-year probability of hypothyroidism in the TBI group: 59 ±9% if age <7.7 years versus 34 ±13% if age >7.7 years (P =0.02).Conclusion. – A careful follow-up of thyroid function is recommended even without TBI conditioning regimen. Young age as a potential risk factor of hypothyroidism has never been described and needs to be studied in a larger cohort.
    Archives De Pediatrie - ARCHIVES PEDIATRIE. 01/2004; 11(11):1326-1332.
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    ABSTRACT: Fluorescence in situ hybridization (FISH) analysis in a case of infant acute monocytic leukemia M5 revealed a complex rearrangement between chromosomes 10 and 11, leading to the disruption of the MLL gene. Using two painting probes for chromosomes 10 and 11 and a specific probe for the MLL gene localized on 11q23, we observed a paracentric inversion of the 11q13-q23 fragment translocated to 10p12. Molecular analysis showed that AF10 localized on 10p12 was the fusion partner gene of MLL in this rearrangement (10;11). This report underlined the usefulness of FISH and molecular techniques in identifying complex rearrangements.
    Cancer Genetics and Cytogenetics 07/2002; 135(2):187-91. · 1.93 Impact Factor
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