Yvan Samson
Laval University
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Lancet Oncology | 2010
Steven E. Lipshultz; Rebecca E. Scully; Stuart R. Lipsitz; Stephen E. Sallan; Lewis B. Silverman; Tracie L. Miller; Elly Barry; Barbara L. Asselin; Uma H. Athale; Luis A. Clavell; Eric Larsen; Albert Moghrabi; Yvan Samson; Bruno Michon; Marshall A. Schorin; Harvey J. Cohen; Donna Neuberg; E. John Orav; Steven D. Colan
BACKGROUND Doxorubicin chemotherapy is associated with cardiomyopathy. Dexrazoxane reduces cardiac damage during treatment with doxorubicin in children with acute lymphoblastic leukaemia (ALL). We aimed to establish the long-term effect of dexrazoxane on the subclinical state of cardiac health in survivors of childhood high-risk ALL 5 years after completion of doxorubicin treatment. METHODS Between January, 1996, and September, 2000, children with high-risk ALL were enrolled from nine centres in the USA, Canada, and Puerto Rico. Patients were assigned by block randomisation to receive ten doses of 30 mg/m² doxorubicin alone or the same dose of doxorubicin preceded by 300 mg/m² dexrazoxane. Treatment assignment was obtained through a telephone call to a centralised registrar to conceal allocation. Investigators were masked to treatment assignment but treating physicians and patients were not; however, investigators, physicians, and patients were masked to study serum cardiac troponin-T concentrations and echocardiographic measurements. The primary endpoints were late left ventricular structure and function abnormalities as assessed by echocardiography; analyses were done including all patients with data available after treatment completion. This trial has been completed and is registered with ClinicalTrials.gov, number NCT00165087. FINDINGS 100 children were assigned to doxorubicin (66 analysed) and 105 to doxorubicin plus dexrazoxane (68 analysed). 5 years after the completion of doxorubicin chemotherapy, mean left ventricular fractional shortening and end-systolic dimension Z scores were significantly worse than normal for children who received doxorubicin alone (left ventricular fractional shortening: -0·82, 95% CI -1·31 to -0·33; end-systolic dimension: 0·57, 0·21-0·93) but not for those who also received dexrazoxane (-0·41, -0·88 to 0·06; 0·15, -0·20 to 0·51). The protective effect of dexrazoxane, relative to doxorubicin alone, on left ventricular wall thickness (difference between groups: 0·47, 0·46-0·48) and thickness-to-dimension ratio (0·66, 0·64-0·68) were the only statistically significant characteristics at 5 years. Subgroup analysis showed dexrazoxane protection (p=0·04) for left ventricular fractional shortening at 5 years in girls (1·17, 0·24-2·11), but not in boys (-0·10, -0·87 to 0·68). Similarly, subgroup analysis showed dexrazoxane protection (p=0·046) for the left ventricular thickness-to-dimension ratio at 5 years in girls (1·15, 0·44-1·85), but not in boys (0·19, -0·42 to 0·81). With a median follow-up for recurrence and death of 8·7 years (range 1·3-12·1), event-free survival was 77% (95% CI 67-84) for children in the doxorubicin-alone group, and 76% (67-84) for children in the doxorubicin plus dexrazoxane group (p=0·99). INTERPRETATION Dexrazoxane provides long-term cardioprotection without compromising oncological efficacy in doxorubicin-treated children with high-risk ALL. Dexrazoxane exerts greater long-term cardioprotective effects in girls than in boys. FUNDING US National Institutes of Health, Childrens Cardiomyopathy Foundation, University of Miami Womens Cancer Association, Lance Armstrong Foundation, Roche Diagnostics, Pfizer, and Novartis.
Journal of Clinical Oncology | 2002
Steven E. Lipshultz; Amy L. Giantris; Stuart R. Lipsitz; Virginia Dalton; Barbara L. Asselin; Ronald Barr; Luis A. Clavell; Craig A. Hurwitz; Albert Moghrabi; Yvan Samson; Marshall A. Schorin; Richard D. Gelber; Stephen E. Sallan; Steven D. Colan
PURPOSE Acute doxorubicin-induced cardiotoxicity can be prevented in adults by continuous infusion of the drug, but mechanisms of cardiotoxicity are different in children. We compared cardiac outcomes in children receiving bolus or continuous infusion of doxorubicin. PATIENTS AND METHODS In a randomized study, children with high-risk acute lymphoblastic leukemia received doxorubicin 360 mg/m(2) in 30-mg/m(2) doses every 3 weeks either by bolus (within 1 hour, n = 57) or by continuous infusion (over 48 hours, n = 64). Echocardiograms obtained before doxorubicin and at longest follow-up times were centrally remeasured, and z scores of cardiac measurements were calculated based on a healthy population. RESULTS The groups were similar in age, sex distribution, doxorubicin dose, and duration of follow-up. Before treatment, measures of left ventricular (LV) structure and function did not reveal dilated cardiomyopathy and were not statistically different between bolus and continuous-infusion groups. The follow-up echocardiograms demonstrated no significant difference between the two groups for any cardiac characteristic, but both groups showed significant abnormalities of LV structure and function compared with normal and with baseline. For example, the mean LV fractional shortening fell by approximately two SD in both groups between the two echocardiograms. LV contractility was depressed in both groups (for bolus patients, median z score = -0.70 SD, P =.006; for continuous-infusion patients, median z score = -0.765, P =.005). Dilated cardiomyopathy and inadequate LV hypertrophy were noted in both groups. Clinical cardiac manifestations and event-free survival did not differ. CONCLUSION Continuous doxorubicin infusion over 48 hours for childhood leukemia did not offer a cardioprotective advantage over bolus infusion. Both regimens were associated with progressive subclinical cardiotoxicity. Other cardioprotective strategies should be explored.
Leukemia | 2000
Lewis B. Silverman; Lieven Declerck; R. D. Gelber; VKimball Dalton; Barbara L. Asselin; Ronald D. Barr; Luis A. Clavell; Craig A. Hurwitz; Albert Moghrabi; Yvan Samson; Marshall A. Schorin; Jeffrey M. Lipton; Harvey J. Cohen; Stephen E. Sallan
The Dana-Farber Cancer Institute (DFCI) ALL consortium has been conducting clinical trials in childhood acute lymphoblastic leukemia (ALL) since 1981. The treatment backbone has included intensive, multi-agent remission induction, early intensification with weekly, high-dose asparaginase, cranial radiation for the majority of patients, frequent vincristine/ corticosteroid pulses during post-remission therapy, and for high-risk patients, doxorubicin during intensification. Between 1981 and 1995, 1255 children with newly diagnosed ALL were evaluated on four consecutive protocols: 81-01 (1981–1985), 85-01 (1985–1987), 87-01 (1987–1991) and 91-01 (1991–1995). The 5-year event-free survival (EFS) rates (± standard error) for all patients by protocol were as follows: 74 ± 3% (81-01), 78 ± 3% (85-01), 77 ± 2% (87-01) and 83 ± 2% (91-01). The 5-year EFS rates ranged from 78 to 85% for patients with B-progenitor phenotype retrospectively classified as NCI standard-risk, 63–82% for NCI high-risk B-progenitor patients, and 70–79% for patients with T cell phenotype. Results of randomized studies revealed that neither high-dose methotrexate during induction (protocol 87-01) nor high-dose 6-mercaptopurine during intensification (protocol 91-01) were associated with improvement in EFS compared with standard doses. Current studies continue to focus on improving efficacy while minimizing acute and late toxicities.
Journal of Clinical Oncology | 2007
Elly Barry; Daniel J. DeAngelo; Donna Neuberg; Kristen E. Stevenson; Mignon L. Loh; Barbara L. Asselin; Ronald D. Barr; Luis A. Clavell; Craig A. Hurwitz; Albert Moghrabi; Yvan Samson; Marshall A. Schorin; Harvey J. Cohen; Stephen E. Sallan; Lewis B. Silverman
PURPOSE Historically, adolescents with acute lymphoblastic leukemia (ALL) have had inferior outcomes when compared with younger children. We report the outcome of adolescents treated on Dana-Farber Cancer Institute (DFCI; Boston, MA) ALL Consortium Protocols conducted between 1991 and 2000. PATIENTS AND METHODS A total of 844 patients aged 1 to 18 years, with newly diagnosed ALL were enrolled onto two consecutive DFCI-ALL Consortium Protocols. We compared outcomes in three age groups: children aged 1 to 10 years (n = 685), young adolescents aged 10 to 15 years (n = 108), and older adolescents aged 15 to 18 years (n = 51). RESULTS With a median follow-up of 6.5 years, the 5-year event-free survival (EFS) for those aged 1 to 10 years was 85% (SE, 1%), compared with 77% (SE, 4%) for those aged 10 to 15 years, and 78% (SE, 6%) for those aged 15 to 18 years (P = .09). Adolescents were more likely to present with T-cell phenotype (P < .001) and less likely to have the TEL-AML1 fusion (P = .05). The incidence of pancreatitis and thromboembolic complications, but not asparaginase allergy, was higher in patients 10 years of age compared with those younger than 10 years. However, there was no difference in the rate of treatment-related complications between the 10- to 15-year and 15- to 18-year age groups. CONCLUSION Adolescents were more likely to present at diagnosis with biologically higher risk disease (T-cell phenotype and absence of the TEL-AML1 fusion) and more likely to experience treatment-related complications than younger children. However, the 5-year EFS for older adolescents was 78% +/- 6%, which is superior to published outcomes for similarly aged patients treated with other pediatric and adult ALL regimens. Based on this experience, we currently are piloting our regimen in patients aged 18 to 50 years.
Journal of Clinical Oncology | 2008
Elly Barry; Lynda M. Vrooman; Suzanne E. Dahlberg; Donna Neuberg; Barbara L. Asselin; Uma H. Athale; Luis A. Clavell; Eric Larsen; Albert Moghrabi; Yvan Samson; Marshall A. Schorin; Harvey J. Cohen; Steven E. Lipshultz; Stephen E. Sallan; Lewis B. Silverman
PURPOSE Dexrazoxane is a drug used to prevent anthracycline-induced cardiotoxicity. A recent report found an association between the use of dexrazoxane and the risk of developing secondary malignant neoplasms (SMNs) in children with Hodgkins disease. We report the absence of an association of SMNs in children with acute lymphoblastic leukemia (ALL) treated on Dana-Farber Cancer Institute ALL Consortium Protocol 95-01. PATIENTS AND METHODS Two hundred five children with high-risk (HR) ALL were randomly assigned to receive doxorubicin alone (n = 100) or doxorubicin with dexrazoxane (n = 105) during the induction and intensification phases of multiagent chemotherapy. We compared incidence of SMNs in these two groups. RESULTS With a median follow-up of 6.2 years, no differences in the incidence of SMNs were noted between the group that received dexrazoxane and the group that did not (P = .66). One SMN (a melanoma located outside of the cranial radiation field) occurred in a patient who was randomly assigned to doxorubicin alone. No SMNs were observed in patients randomly assigned to receive dexrazoxane. CONCLUSION Dexrazoxane was not associated with an increased risk of SMNs in children treated for HR ALL. Given the potential importance of dexrazoxane as a cardioprotectant, we recommend that dexrazoxane continue to be used and studied in doxorubicin-containing pediatric regimens.
Journal of Clinical Oncology | 2003
Virginia Dalton; Montse Rue; Lewis B. Silverman; Richard D. Gelber; Barbara L. Asselin; Ronald D. Barr; Luis A. Clavell; Craig A. Hurwitz; Albert Moghrabi; Yvan Samson; Marshall A. Schorin; Nancy J. Tarbell; Stephen E. Sallan; Laurie E. Cohen
PURPOSE We evaluated the long-term effects of treatment on height and weight in children with acute lymphoblastic leukemia (ALL) treated with one of the following three different CNS therapies: intrathecal therapy alone, intrathecal therapy with conventional cranial radiation, or intrathecal therapy with twice-daily radiation. PATIENTS AND METHODS Between 1987 and 1995, 618 children treated on two consecutive Dana-Farber Cancer Institute Consortium protocols for ALL were measured for height and weight at diagnosis, and approximately every 6 months thereafter. Patient height, weight, and body mass index (BMI) were converted to z scores for age and sex using the 2000 Centers for Disease Control and Prevention growth charts for the United States. RESULTS Children younger than 13 years at diagnosis had a statistically significant decrease in their height z scores and an increase in their BMI z scores, regardless of whether they had received cranial radiation. Young age at diagnosis and increased chemotherapy intensity were major risk factors. Unexpectedly, there was no significant difference in long-term height between children who received radiation and those who did not. CONCLUSION Final height is compromised in survivors of ALL. The detrimental effects on height occur during therapy without the ability for long-term catch-up growth. Although patients became overweight for height, this seemed to be a result of relative height loss with normal weight gain rather than accelerated weight gain. The type of CNS treatment received did not affect changes in height, weight, or BMI.
Pediatrics | 2008
Juliana T. Teo; Robert J. Klaassen; Conrad V. Fernandez; Rochelle Yanofsky; John Wu; Josette Champagne; Mariana Silva; Jeffrey H. Lipton; Jossee Brossard; Yvan Samson; Sharon Abish; MacGregor Steele; Kaiser Ali; Uma H. Athale; Lawrence Jardine; John P. Hand; Elena Tsangaris; Isaac Odame; Joseph Beyene; Yigal Dror
OBJECTIVE. Unclassified inherited bone marrow failure syndromes are a heterogeneous group of genetic disorders that represent either new syndromes or atypical clinical courses of known inherited bone marrow failure syndromes. The relative prevalence of the unclassified inherited bone marrow failure syndromes and their characteristics and the clinical and economic challenges that they create have never been studied. METHODS. We analyzed cases of inherited bone marrow failure syndrome in the Canadian Inherited Marrow Failure Registry that were deemed unclassifiable at study entry. RESULTS. From October 2001 to March 2006, 39 of the 162 patients enrolled in the Canadian Inherited Marrow Failure Registry were registered as having unclassified inherited bone marrow failure syndromes. These patients presented at a significantly older age (median: 9 months) than the patients with classified inherited bone marrow failure syndrome (median: 1 month) and had substantial variation in the clinical presentations. The hematologic phenotype, however, was similar to the classified inherited bone marrow failure syndromes and included single- or multiple-lineage cytopenia, severe aplastic anemia, myelodysplasia, and malignancy. Grouping patients according to the affected blood cell lineage(s) and to the presence of associated physical malformations was not always sufficient to characterize a condition, because affected members from several families fit into different phenotypic groups. Compared with the classified inherited bone marrow failure syndromes, the patients with unclassified inherited bone marrow failure syndromes had 3.2 more specific diagnostic tests at 4.5 times higher cost per evaluated patient to attempt to categorize their syndrome. At last follow-up, only 20% of the unclassified inherited bone marrow failure syndromes were ultimately diagnosed with a specific syndrome on the basis of the development of new clinical findings or positive genetic tests. CONCLUSIONS. Unclassified inherited bone marrow failure syndromes are relatively common among the inherited bone marrow failure syndromes and present a major diagnostic and therapeutic dilemma.
Journal of Clinical Oncology | 2006
Stéphane Barrette; Mark Bernstein; Jean-Marie Leclerc; Martin A. Champagne; Yvan Samson; Josee Brossard; William G. Woods
PURPOSE The Québec Neuroblastoma Screening Program was put in place to investigate the possibility of decreasing mortality from high-risk neuroblastoma through early screening. We assess treatment complications in the patients diagnosed during this screening program. PATIENTS AND METHODS A total of 476,603 patients born during the screening period were eligible. Parents of 425,838 children (89%) agreed to participate in the 3-week screening, and 73% agreed to participate in the 6-month screening. Forty-five patients had neuroblastoma. We reviewed the medical and research charts for all patients diagnosed by screening. Follow-up was available from 8 to 13 years after screening. RESULTS Forty-five patients were diagnosed by screening. All patients were treated according to the Pediatric Oncology Group recommendations of the time. All patients had surgery, and 29 patients received chemotherapy. No patient died from neuroblastoma. Eleven patients suffered complications from treatment. Two patients had life-threatening complications. CONCLUSION In view of the lack of impact of screening programs on neuroblastoma mortality, evidence that many of the tumors detected through screening can be observed without treatment and the serious complications that may arise from therapy, we do not support neuroblastoma screening programs for children.
Pediatric Blood & Cancer | 2014
Daniel A. Morgenstern; Monia Marzouki; Ute Bartels; Meredith S. Irwin; Giselle Sholler; Janet Gammon; Rosanna Yankanah; Bing Wu; Yvan Samson; Sylvain Baruchel
The combination of vinblastine and mammalian target of rapamycin (mTOR) inhibitor sirolimus inhibits the growth of neuroblastoma xenografts through pro‐apoptotic and anti‐angiogenic mechanisms. This phase I study aimed to explore the safety and toxicity of this combination in pediatric patients with advanced solid tumors.
Pediatric Blood & Cancer | 2006
J.M. Steele; Lillian Sung; Robert J. Klaassen; Conrad V. Fernandez; Rochelle Yanofsky; John Wu; Isaac Odame; Mariana Silva; J. Champagne; K. Ali; J. Brossard; Yvan Samson; S. Abish; D. Le; L. Jardine; J.P. Hand; Jeffrey H. Lipton; K. Charpentier; D. Stephens; M. Freedman; Yigal Dror
Inherited bone marrow failure syndromes (IMFSs) are genetic disorders characterized by defective single‐lineage or multi‐lineage hematopoiesis. IMFS patients are at risk for severe cytopenias, development of marrow cytogenetic abnormalities (MCA), myelodysplasia (MDS), and malignancy. The rate of disease progression and proportion of patients at risk for these complications is currently unclear. We examined recently diagnosed IMFS patients to determine distribution of diagnoses, disease progression and development of significant outcomes.