23 results on '"Huguet F"'
Search Results
2. Improved outcome of acute promyelocytic leukemia with high WBC counts over the last 15 years: the European APL Group experience.
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Kelaidi C, Chevret S, De Botton S, Raffoux E, Guerci A, Thomas X, Pigneux A, Lamy T, Rigal-Huguet F, Meyer-Monard S, Chevallier P, Maloisel F, Deconinck E, Ferrant A, Fegueux N, Ifrah N, Sanz M, Dombret H, Fenaux P, and Adès L
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- 2009
- Full Text
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3. Chemoradiotherapy in the management of locally advanced pancreatic carcinoma: a qualitative systematic review.
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Huguet F, Girard N, Guerche CS, Hennequin C, Mornex F, and Azria D
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- 2009
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4. Pediatric-Inspired Therapy in Adults With Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia: The GRAALL-2003 Study.
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Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, and Dombret H
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- 2009
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5. HIV-specific differences in outcome of squamous cell carcinoma of the anal canal: a multicentric cohort study of HIV-positive patients receiving highly active antiretroviral therapy.
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Oehler-Jänne C, Huguet F, Provencher S, Seifert B, Negretti L, Riener M, Bonet M, Allal AS, and Ciernik IF
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- 2008
6. Concomitant administration of weekly oxaliplatin, fluorouracil continuous infusion, and radiotherapy after 2 months of gemcitabine and oxaliplatin induction in patients with locally advanced pancreatic cancer: a Groupe Coordinateur Multidisciplinaire...
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Moureau-Zabotto L, Phélip JM, Afchain P, Mineur L, André T, Vendrely V, Lledo G, Dupuis O, Huguet F, Touboul E, Balosso J, and Louvet C
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- 2008
7. Significance of Measurable Residual Disease in Adult Philadelphia Chromosome-Positive ALL: A GRAAPH-2014 Study.
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Kim R, Chalandon Y, Rousselot P, Cayuela JM, Huguet F, Balsat M, Passet M, Chevallier P, Hicheri Y, Raffoux E, Leguay T, Chantepie S, Maury S, Hayette S, Solly F, Braun T, De Prijck B, Cacheux V, Salanoubat C, Farnault L, Guibaud I, Lamarque M, Gastaud L, Lemasle E, Brissot E, Tavernier E, Bilger K, Villate A, Soulier J, Graux C, Lhéritier V, Dombret H, Boissel N, and Clappier E
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- Humans, Adult, Male, Female, Middle Aged, Pyrimidines therapeutic use, Young Adult, Fusion Proteins, bcr-abl genetics, Aged, Prognosis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Adolescent, Proto-Oncogene Proteins c-abl genetics, Neoplasm, Residual, Hematopoietic Stem Cell Transplantation, Philadelphia Chromosome, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology
- Abstract
Purpose: BCR::ABL1 quantification is widely regarded as the standard for monitoring measurable residual disease (MRD) in Philadelphia chromosome-positive (Ph+) ALL. However, recent evidence of BCR::ABL1 multilineage involvement questions the significance of BCR::ABL1 MRD. We aimed to define the prognostic role of MRD as assessed by BCR::ABL1 or lymphoid-specific immunoglobulin/T-cell receptor ( IG/TR ) gene markers., Patients and Methods: We conducted BCR::ABL1 and IG/TR quantification after each treatment cycle in 264 patients treated in the GRAAPH-2014 trial, which used four cycles of reduced-intensity chemotherapy with nilotinib, followed by hematopoietic stem-cell transplantation (HSCT)., Results: Comparing BCR::ABL1 and IG/TR MRD revealed residual BCR::ABL1 -positive non-ALL cells in 98 (43%) of 228 patients, defining multilineage Ph+ ALL. Despite poorer BCR::ABL1 responses, patients with multilineage Ph+ ALL had similar disease-free survival (DFS; hazard ratio [HR], 0.83 [95% CI, 0.49 to 1.41]; P = .50). Although BCR::ABL1 response failed to predict outcomes, IG/TR positivity (≥0.01%) was strongly associated with lower DFS (after cycle 2, HR, 2.49 [95% CI, 1.40 to 4.40]; P = .002; after cycle 4, HR, 4.13 [95% CI, 1.82 to 9.38]; P = .001). In multivariable analysis, both IG/TR positivity after cycle 2 and initial WBC count ≥30 × 10
9 /L predicted poorer DFS, enabling to define a high-risk group having a 4-year DFS of 56.5% compared with 87.6% (HR, 3.72 [95% CI, 1.93 to 7.15]; P < .001). Moreover, allogeneic HSCT significantly improved DFS in the high-risk group (HR, 0.33 [95% CI, 0.18 to 0.60]; P < .001), whereas the standard-risk group had favorable outcomes regardless of allogeneic HSCT., Conclusion: Our findings challenge the significance of BCR::ABL1 monitoring in adult Ph+ ALL and demonstrate the prognostic role of IG/TR MRD. This study provides a framework for using MRD to guide treatment strategies in adults with Ph+ ALL.- Published
- 2024
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8. Cross-Modality Comparisons Between Radiofrequency Ablation and Stereotactic Body Radiotherapy for Treatment of Hepatocellular Carcinoma: Limitations of the National Cancer Database.
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Olsen JR, Murphy JD, Hallemeier CL, Apisarnthanarax S, Huguet F, and Jabbour SK
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- Humans, Radiofrequency Ablation, Carcinoma, Hepatocellular surgery, Catheter Ablation, Liver Neoplasms surgery, Radiosurgery
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- 2018
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9. Intensified Therapy of Acute Lymphoblastic Leukemia in Adults: Report of the Randomized GRAALL-2005 Clinical Trial.
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Huguet F, Chevret S, Leguay T, Thomas X, Boissel N, Escoffre-Barbe M, Chevallier P, Hunault M, Vey N, Bonmati C, Lepretre S, Marolleau JP, Pabst T, Rousselot P, Buzyn A, Cahn JY, Lhéritier V, Béné MC, Asnafi V, Delabesse E, Macintyre E, Chalandon Y, Ifrah N, and Dombret H
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- Aged, Disease-Free Survival, Female, Humans, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Antineoplastic Agents, Alkylating administration & dosage, Cyclophosphamide administration & dosage, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Purpose To evaluate randomly the role of hyperfractionated cyclophosphamide (hyper-C) dose intensification in adults with newly diagnosed Philadelphia chromosome-negative acute lymphoblastic leukemia treated with a pediatric-inspired protocol and to determine the upper age limit for treatment tolerability in this context. Patients and Methods A total of 787 evaluable patients (B/T lineage, 525 and 262, respectively; median age, 36.1 years) were randomly assigned to receive a standard dose of cyclophosphamide or hyper-C during first induction and late intensification. Compliance with chemotherapy was assessed by median doses actually received during each treatment phase by patients potentially exposed to the full planned doses. Results Overall complete remission (CR) rate was 91.9%. With a median follow-up of 5.2 years, the 5-year rate of event-free survival (EFS) and overall survival (OS) was 52.2% (95% CI, 48.5% to 55.7%) and 58.5% (95% CI, 54.8% to 61.9%), respectively. Randomization to the hyper-C arm did not increase the CR rate or prolong EFS or OS. As a result of worse treatment tolerance, advanced age continuously affected CR rate, EFS, and OS, with 55 years as the best age cutoff. At 5 years, EFS was 55.7% (95% CI, 51.8% to 59.4%) for patients younger than 55 years of age versus 25.8% (95% CI, 19.9% to 35.6%) in older patients (hazard ratio, 2.16; P < .001). Patients ≥ 55 years of age, in whom a lower compliance to the whole planned chemotherapy was observed, benefited significantly from hyper-C, whereas younger patients did not. Conclusion No significant benefit was associated with the introduction of a hyper-C sequence into a frontline pediatric-like adult acute lymphoblastic leukemia therapy. Overall, tolerability of an intensive pediatric-derived treatment was poor in patients ≥ 55 years of age.
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- 2018
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10. Early Response-Based Therapy Stratification Improves Survival in Adult Early Thymic Precursor Acute Lymphoblastic Leukemia: A Group for Research on Adult Acute Lymphoblastic Leukemia Study.
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Bond J, Graux C, Lhermitte L, Lara D, Cluzeau T, Leguay T, Cieslak A, Trinquand A, Pastoret C, Belhocine M, Spicuglia S, Lheritier V, Leprêtre S, Thomas X, Huguet F, Ifrah N, Dombret H, Macintyre E, Boissel N, and Asnafi V
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- Adult, Cyclophosphamide administration & dosage, DNA Methylation genetics, DNA Mutational Analysis, Drug Resistance, Neoplasm, Female, Genotype, Hematopoiesis genetics, Histones chemistry, Humans, Immunophenotyping, Male, Prognosis, Receptors, Cytokine genetics, Signal Transduction genetics, Survival Rate, Transplantation, Homologous, ras Proteins genetics, ras Proteins metabolism, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Hematopoietic Stem Cell Transplantation, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma therapy, Thymus Neoplasms genetics, Thymus Neoplasms therapy
- Abstract
Purpose Early thymic precursor (ETP) acute lymphoblastic leukemia (ALL) is an immunophenotypically defined subgroup of T-cell ALL (T-ALL) associated with high rates of intrinsic treatment resistance. Studies in children have shown that the negative prognostic impact of chemotherapy resistance is abrogated by the implementation of early response-based intensification strategies. Comparable data in adults are lacking. Patients and Methods We performed comprehensive clinicobiologic, genetic, and survival analyses of a large cohort of 213 adult patients with T-ALL, including 47 patients with ETP-ALL, treated in the GRAALL (Group for Research on Adult Acute Lymphoblastic Leukemia) -2003 and -2005 studies. Results Targeted next-generation sequencing revealed that the genotype of immunophenotypically defined adult T-ALL is similar to the pediatric equivalent, with high rates of mutations in factors involved in cytokine receptor and RAS signaling (62.2%), hematopoietic development (29.7%), and chemical modification of histones (48.6%). In contrast to pediatric cases, mutations in DNA methylation factor genes were also common (32.4%). We found that despite expected high levels of early bone marrow chemotherapy resistance (87%), the overall prognosis for adults with ETP-ALL treated using the GRAALL protocols was not inferior to that of the non-ETP-ALL group (5-year overall survival: ETP, 59.6%; 95% CI, 44.2% to 72.0% v non-ETP, 66.5%; 95% CI, 58.7% to 73.2%; P = 0.33) and that allogeneic stem-cell transplantation had a beneficial effect in a large proportion of patients with ETP-ALL. Conclusion Our results suggest that the use of response-based risk stratification and therapy intensification abrogates the poor prognosis of adult ETP-ALL.
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- 2017
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11. Long-Term Follow-Up of the French Stop Imatinib (STIM1) Study in Patients With Chronic Myeloid Leukemia.
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Etienne G, Guilhot J, Rea D, Rigal-Huguet F, Nicolini F, Charbonnier A, Guerci-Bresler A, Legros L, Varet B, Gardembas M, Dubruille V, Tulliez M, Noel MP, Ianotto JC, Villemagne B, Carré M, Guilhot F, Rousselot P, and Mahon FX
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- Adult, Aged, Aged, 80 and over, Antineoplastic Agents adverse effects, Biomarkers, Tumor genetics, Disease Progression, Disease-Free Survival, Drug Administration Schedule, Female, Follow-Up Studies, France, Fusion Proteins, bcr-abl genetics, Humans, Imatinib Mesylate adverse effects, Kaplan-Meier Estimate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive enzymology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Male, Middle Aged, Molecular Diagnostic Techniques, Neoplasm, Residual, Patient Selection, Predictive Value of Tests, Prospective Studies, Protein Kinase Inhibitors adverse effects, Recurrence, Risk Factors, Time Factors, Treatment Outcome, Antineoplastic Agents administration & dosage, Imatinib Mesylate administration & dosage, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Protein Kinase Inhibitors administration & dosage
- Abstract
Purpose Imatinib (IM) can safely be discontinued in patients with chronic myeloid leukemia (CML) who have had undetectable minimal residual disease (UMRD) for at least 2 years. We report the final results of the Stop Imatinib (STIM1) study with a long follow-up. Patients and Methods IM was prospectively discontinued in 100 patients with CML with UMRD sustained for at least 2 years. Molecular recurrence (MR) was defined as positivity of BCR-ABL transcript in a quantitative reverse transcriptase polymerase chain reaction assay confirmed by a second analysis point that indicated an increase of one log in relation to the first analysis point at two successive assessments or loss of major molecular response at one point. Results The median molecular follow-up after treatment discontinuation was 77 months (range, 9 to 95 months). Sixty-one patients lost UMRD after a median of 2.5 months (range, 1 to 22 months), and one patient died with UMRD at 10 months. Molecular recurrence-free survival was 43% (95% CI, 33% to 52%) at 6 months and 38% (95% CI, 29% to 47%) at 60 months. Treatment was restarted in 57 of 61 patients with MR, and 55 patients achieved a second UMRD with a median time of 4 months (range, 1 to 16 months). None of the patients experienced a CML progression. Analyses of the characteristics of the study population identified that the Sokal risk score and duration of IM treatment were significantly associated with the probability of MR. Conclusion With a median follow-up of more than 6 years after treatment discontinuation, the STIM1 study demonstrates that IM can safely be discontinued in patients with a sustained deep molecular response with no late MR.
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- 2017
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12. Pediatric-Like Acute Lymphoblastic Leukemia Therapy in Adults With Lymphoblastic Lymphoma: The GRAALL-LYSA LL03 Study.
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Lepretre S, Touzart A, Vermeulin T, Picquenot JM, Tanguy-Schmidt A, Salles G, Lamy T, Béné MC, Raffoux E, Huguet F, Chevallier P, Bologna S, Bouabdallah R, Benichou J, Brière J, Moreau A, Tallon-Simon V, Seris S, Graux C, Asnafi V, Ifrah N, Macintyre E, and Dombret H
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- Adolescent, Adult, Cell Cycle Proteins genetics, Central Nervous System Diseases etiology, Consolidation Chemotherapy methods, Disease-Free Survival, F-Box Proteins genetics, F-Box-WD Repeat-Containing Protein 7, Female, Hematopoietic Stem Cell Transplantation, Humans, Induction Chemotherapy methods, L-Lactate Dehydrogenase blood, Maintenance Chemotherapy methods, Male, Middle Aged, PTEN Phosphohydrolase genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma therapy, Prospective Studies, Receptor, Notch1 genetics, Recurrence, Survival Rate, Treatment Outcome, Ubiquitin-Protein Ligases genetics, Young Adult, ras Proteins genetics, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Purpose: This study evaluated the efficacy of pediatric-like acute lymphoblastic leukemia (ALL) therapy in adults with lymphoblastic lymphoma (LL)., Patients and Methods: This was a prospective phase II study in adults 18 to 59 years old with previously untreated LL. Patients were treated with an adapted pediatric-like ALL protocol, which included a corticosteroid prephase, a five-drug induction reinforced by sequential cyclophosphamide administration, dose-dense consolidation, late intensification, CNS prophylaxis, and a 2-year maintenance phase. Treatment response was assessed by computed tomography and optional positron emission tomography. Allogeneic hematopoietic stem cell transplant was offered to selected patients in first complete remission (CR) or unconfirmed CR., Results: The study enrolled 148 patients (131 with T-lineage LL [T-LL] and 17 with B-lineage LL [B-LL]). A total of 119 patients with T-LL (90.8%) and 13 with B-LL (76.5%) reached CR/unconfirmed CR, including 26 with T-LL and two with B-LL who needed a second induction salvage course. Relapse occurred in 34 patients with T-LL and four with B-LL. In patients with T-LL, 3-year event-free survival was 63.3% (95% CI, 54.2% to 71.0%), disease-free survival was 72.4% (95% CI, 63.0% to 79.7%), and overall survival was 69.2% (95% CI, 60.0% to 76.7%). Multivariate analysis identified serum lactate dehydrogenase level and the NOTCH1/FBXW7/RAS/PTEN oncogene (a four-gene oncogenetic classifier) status but not positron emission tomography or hematopoietic stem cell transplant as independent prognostic factors for outcome in T-LL., Conclusion: In adults with LL, an intensive pediatric-like ALL treatment protocol was associated with a good response rate and outcome. In patients with T-LL, the four-gene oncogenetic classifier and lactate dehydrogenase level were independent prognostic indicators., (© 2015 by American Society of Clinical Oncology.)
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- 2016
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13. Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study.
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Trinquand A, Tanguy-Schmidt A, Ben Abdelali R, Lambert J, Beldjord K, Lengliné E, De Gunzburg N, Payet-Bornet D, Lhermitte L, Mossafa H, Lhéritier V, Bond J, Huguet F, Buzyn A, Leguay T, Cahn JY, Thomas X, Chalandon Y, Delannoy A, Bonmati C, Maury S, Nadel B, Macintyre E, Ifrah N, Dombret H, and Asnafi V
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- Adult, Disease-Free Survival, F-Box-WD Repeat-Containing Protein 7, Female, Genetic Predisposition to Disease, Humans, Kaplan-Meier Estimate, Male, Multivariate Analysis, Phenotype, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma classification, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma therapy, Predictive Value of Tests, Proportional Hazards Models, Proto-Oncogene Proteins p21(ras), Risk Factors, Time Factors, Young Adult, Cell Cycle Proteins genetics, DNA Mutational Analysis, F-Box Proteins genetics, GTP Phosphohydrolases genetics, Gene Deletion, Membrane Proteins genetics, Mutation, PTEN Phosphohydrolase genetics, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma genetics, Proto-Oncogene Proteins genetics, Receptor, Notch1 genetics, Ubiquitin-Protein Ligases genetics, ras Proteins genetics
- Abstract
Purpose: The Group for Research in Adult Acute Lymphoblastic Leukemia (GRAALL) recently reported a significantly better outcome in T-cell acute lymphoblastic leukemia (T-ALL) harboring NOTCH1 and/or FBXW7 (N/F) mutations compared with unmutated T-ALL. Despite this, one third of patients with N/F-mutated T-ALL experienced relapse., Patients and Methods: In a series of 212 adult T-ALLs included in the multicenter randomized GRAALL-2003 and -2005 trials, we searched for additional N/K-RAS mutations and PTEN defects (mutations and gene deletion)., Results: N/F mutations were identified in 143 (67%) of 212 patients, and lack of N/F mutation was confirmed to be associated with a poor prognosis. K-RAS, N-RAS, and PTEN mutations/deletions were identified in three (1.6%) of 191, 17 (8.9%) of 191, and 21 (12%) of 175 patients, respectively. The favorable prognostic significance of N/F mutations was restricted to patients without RAS/PTEN abnormalities. These observations led us to propose a new T-ALL oncogenetic classifier defining low-risk patients as those with N/F mutation but no RAS/PTEN mutation (97 of 189 patients; 51%) and all other patients (49%; including 13% with N/F and RAS/PTEN mutations) as high-risk patients. In multivariable analysis, this oncogenetic classifier remained the only significant prognostic covariate (event-free survival: hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.15; P < .001; and overall survival: HR, 3.2; 95% CI, 1.9 to 5.6; P < .001)., Conclusion: These data demonstrate that the presence of N/F mutations in the absence of RAS or PTEN abnormalities predicts good outcome in almost 50% of adult T-ALL. Conversely, the absence of N/F or presence of RAS/PTEN alterations identifies the remaining cohort of patients with poor prognosis.
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- 2013
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14. Nomogram to predict subsequent brain metastasis in patients with metastatic breast cancer.
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Graesslin O, Abdulkarim BS, Coutant C, Huguet F, Gabos Z, Hsu L, Marpeau O, Uzan S, Pusztai L, Strom EA, Hortobagyi GN, Rouzier R, and Ibrahim NK
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- Adult, Aged, Aged, 80 and over, Brain Neoplasms mortality, Brain Neoplasms therapy, Breast Neoplasms mortality, Breast Neoplasms therapy, Canada epidemiology, Disease-Free Survival, Female, Humans, Logistic Models, Middle Aged, Neoplasm Staging, Odds Ratio, Predictive Value of Tests, ROC Curve, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, Brain Neoplasms secondary, Breast Neoplasms pathology, Nomograms
- Abstract
PURPOSE Brain metastasis is usually a fatal event in patients with stage IV breast cancer. We hypothesized that its occurrence can be predicted if a clinical nomogram can be developed, thus allowing for selection of enriched patient populations for prevention trials. PATIENTS AND METHODS Electronic medical records of patients with metastatic breast cancer were retrospectively reviewed for the period between January 2000 and February 2007 under a study approved by the institutional review board. A multivariate logistic regression analysis of selected prognostic features was done. A nomogram to predict brain metastasis was constructed and validated in a cohort of 128 patients with brain metastasis treated at the Cross Cancer Institute (Edmonton, Alberta, Canada). Results Of 2,136 patients with breast cancer, 362 developed subsequent brain metastasis. Age, grade, negative status of estrogen receptor and human epidermal growth factor receptor 2, number of metastatic sites (one v > one), and short disease-free survival were significantly and independently associated with subsequent brain metastasis. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.68 (95% CI, 0.66 to 0.69) in the training set. The validation set showed a good discrimination with an AUC of 0.74 (95% CI, 0.70 to 0.79). The nomogram was well calibrated, with no significant difference between the predicted and the observed probabilities. CONCLUSION We have developed a robust tool that is able to predict subsequent brain metastasis in patients with breast cancer with nonbrain metastatic disease. Selection of an enriched patient population at high risk for brain metastasis will facilitate the design of trials aiming at its prevention.
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- 2010
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15. Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II and III studies.
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Huguet F, André T, Hammel P, Artru P, Balosso J, Selle F, Deniaud-Alexandre E, Ruszniewski P, Touboul E, Labianca R, de Gramont A, and Louvet C
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- Adenocarcinoma pathology, Adult, Aged, Aged, 80 and over, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, Combined Modality Therapy, Disease Progression, Female, Humans, Male, Middle Aged, Multicenter Studies as Topic, Pancreatic Neoplasms pathology, Retrospective Studies, Survival Analysis, Adenocarcinoma drug therapy, Adenocarcinoma radiotherapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms radiotherapy
- Abstract
Purpose: The management of locally advanced (LA) pancreatic cancer patients remains controversial. To select patients who could benefit from chemoradiotherapy (CRT), the therapeutic strategy used by the Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR) consisted of initial chemotherapy (CT) for at least 3 months. The decision to administer CRT or continue CT in nonprogressive patients was the investigator's choice., Patients and Methods: Retrospective analysis of outcome in 181 patients with LA pancreatic cancer (76 women and 105 men; mean age, 61 years; range, 37 to 85 years) enrolled onto prospective phase II and III GERCOR studies was performed to compare the survival of patients who received CRT with that of patients who continued CT alone., Results: Median progression-free survival (PFS) and overall survival (OS) times for the 181 patients were 6.3 and 11.4 months, respectively. Fifty-three patients (29.3%) had metastatic disease after 3 months of CT and were not eligible for CRT. Among the 128 remaining patients (70.3%) who had no disease progression and who were, therefore, eligible for CRT, 72 (56%) received CRT (group A), whereas 56 (44%) continued with CT (group B). The two groups were balanced for initial characteristics (performance status, sex, age, and type of CT), as well as for induction CT results. In groups A and B, the median PFS times were 10.8 and 7.4 months, respectively (P = .005), and the median OS times were 15.0 and 11.7 months, respectively (P = .0009)., Conclusion: These results suggest that, after control of disease by initial CT, CRT could significantly improve survival in patients with LA pancreatic cancer compared with CT alone. A prospective phase III study is ongoing to evaluate this strategy.
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- 2007
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16. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group.
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Adès L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, Stoppa AM, Lamy T, Rigal-Huguet F, Vekhoff A, Meyer-Monard S, Maloisel F, Deconinck E, Ferrant A, Thomas X, Fegueux N, Chomienne C, Dombret H, Degos L, and Fenaux P
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- Adult, Daunorubicin administration & dosage, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Remission Induction, Survival Analysis, Tretinoin administration & dosage, Antimetabolites, Antineoplastic therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cytarabine therapeutic use, Leukemia, Promyelocytic, Acute drug therapy
- Abstract
Purpose: Several phase II studies have suggested that cytarabine (AraC) was not required in the treatment of newly diagnosed acute promyelocytic leukemia (APL) patients receiving all-trans-retinoic acid (ATRA), an anthracycline, and maintenance therapy, and we aimed at confirming this finding in a randomized trial., Patients and Methods: Newly diagnosed APL patients younger than age 60 years with a WBC count of less than 10,000/microL were randomly assigned to receive either ATRA combined with and followed by three daunorubicin (DNR) plus AraC courses and a 2-year maintenance regimen (AraC group) or the same treatment but without AraC (no AraC group). Patients older than age 60 years and patients with initial WBC count of more than 10,000/microL were not randomly assigned but received risk-adapted treatment, with higher dose of AraC and CNS prophylaxis in patients with WBC counts more than 10,000/microL., Results: Overall, 328 (96.5%) of 340 patients achieved complete remission (CR). In the AraC and the no AraC groups, the CR rates were 99% and 94% (P = .12), the 2-year cumulative incidence of relapse (CIR) rates were 4.7% and 15.9% (P = .011), the event-free survival (EFS) rates were 93.3% and 77.2% (P = .0021), and survival rates were 97.9% and 89.6% (P = .0066), respectively. In patients younger than age 60 years with WBC counts more than 10,000/microL, the CR, 2-year CIR, EFS, and survival rates were 97.3%, 2.9%, 89%, and 91.9%, respectively., Conclusion: These results support a role for AraC in addition to ATRA and anthracyclines in the treatment of newly diagnosed APL, at least using DNR at the cumulative dose we used and with the consolidation and maintenance regimens we used.
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- 2006
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17. Early allogeneic stem-cell transplantation for young adults with acute myeloblastic leukemia in first complete remission: an intent-to-treat long-term analysis of the BGMT experience.
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Jourdan E, Boiron JM, Dastugue N, Vey N, Marit G, Rigal-Huguet F, Molina L, Fegueux N, Pigneux A, Recher C, Rossi JF, Attal M, Sotto JJ, Maraninchi D, Reiffers J, Bardou VJ, Esterni B, and Blaise D
- Subjects
- Acute Disease, Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Combined Modality Therapy, Disease-Free Survival, Female, Humans, Male, Middle Aged, Prospective Studies, Remission Induction, Time Factors, Tissue and Organ Procurement, Transplantation, Autologous, Transplantation, Homologous, Treatment Outcome, Leukemia, Myeloid therapy, Stem Cell Transplantation methods
- Abstract
Purpose: We analyzed the impact of allogeneic stem-cell transplantation (alloSCT) as an early consolidation for young patients with acute myeloblastic leukemia in first complete remission (CR1) through four successive protocols., Patients and Methods: Of the 472 patients who achieved CR1, 182 (38%) had an HLA-identical sibling (donor group), and alloSCT was performed in 171 patients (94%). Of the 290 patients without donor (no-donor group), 62% received an autologous SCT., Results: In an intent-to-treat analysis based on donor availability, the overall 10-year survival probability was 51% v 43% (P = .11) for the donor and no-donor groups, respectively. A Cox analysis determined that four factors had independent prognostic significance for survival (initial WBC count, French-American-British subtypes, cytogenetic risk, and number of induction courses). This permitted constitution of a simple index that reclassified 21% of the patients compared with usual cytogenetic classification and identified three subpopulations with different outcome and different impact of alloSCT., Conclusion: AlloSCT was associated with a survival advantage for an intermediate-risk group. In other groups, numbers are limited for definitive conclusion. However, early performed alloSCT does not seem to be the optimal treatment of high-risk patients or offer any advantage over intensive chemotherapy in low-risk patients.
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- 2005
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18. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial.
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Thomas X, Boiron JM, Huguet F, Dombret H, Bradstock K, Vey N, Kovacsovics T, Delannoy A, Fegueux N, Fenaux P, Stamatoullas A, Vernant JP, Tournilhac O, Buzyn A, Reman O, Charrin C, Boucheix C, Gabert J, Lhéritier V, and Fiere D
- Subjects
- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Combined Modality Therapy, Disease-Free Survival, Female, Humans, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Remission Induction, Risk Factors, Stem Cell Transplantation, Survival Analysis, Transplantation, Autologous, Treatment Outcome, Whole-Body Irradiation, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Purpose: We analyzed the benefits of a risk-adapted postremission strategy in adult lymphoblastic leukemia (ALL), and re-evaluated stem-cell transplantation (SCT) for high-risk ALL., Patients and Methods: A total of 922 adult patients entered onto the trial according to risk groups: standard-risk ALL (group 1), high-risk ALL (group 2), Philadelphia chromosome-positive ALL (group 3), and CNS-positive ALL (group 4). All received a standard four-drug/4-week induction course. Patients from group 1 who achieved a complete remission (CR) after one course of induction therapy were randomly assigned between intensive and less intensive postremission chemotherapy, whereas those who achieved CR after salvage therapy were then included in group 2. Patients in groups 2, 3, and 4 with an HLA-identical sibling were assigned to allogeneic SCT. In groups 3 and 4, autologous SCT was offered to all other patients, whereas in group 2 they were randomly assigned between chemotherapy and autologous SCT., Results: Overall, 771 patients achieved CR (84%). Median disease-free survival (DFS) was 17.5 months, with 3-year DFS at 37%. In group 1, the 3-year DFS rate was 41%, with no difference between arms of postremission randomization. In groups 2 and 4, the 3-year DFS rates were 38% and 44%, respectively. In group 2, autologous SCT and chemotherapy resulted in comparable median DFS. Patients with an HLA-matched sibling (groups 2 and 4) had improved DFS. Three-year DFS was 24% in group 3., Conclusion: Allogeneic SCT improved DFS in high-risk ALL in the first CR. Autologous SCT did not confer a significant benefit over chemotherapy for high-risk ALL.
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- 2004
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- View/download PDF
19. Therapy-related acute promyelocytic leukemia.
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Beaumont M, Sanz M, Carli PM, Maloisel F, Thomas X, Detourmignies L, Guerci A, Gratecos N, Rayon C, San Miguel J, Odriozola J, Cahn JY, Huguet F, Vekhof A, Stamatoulas A, Dombret H, Capote F, Esteve J, Stoppa AM, and Fenaux P
- Subjects
- Adult, Aged, Aged, 80 and over, Antibiotics, Antineoplastic administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Belgium epidemiology, Breast Neoplasms drug therapy, Breast Neoplasms radiotherapy, Child, DNA Topoisomerases, Type II, Female, France epidemiology, Humans, Leukemia, Promyelocytic, Acute drug therapy, Leukemia, Promyelocytic, Acute epidemiology, Leukemia, Promyelocytic, Acute genetics, Lymphoma drug therapy, Lymphoma radiotherapy, Male, Middle Aged, Retrospective Studies, Spain epidemiology, Treatment Outcome, Tretinoin administration & dosage, Antineoplastic Agents adverse effects, Leukemia, Promyelocytic, Acute etiology, Leukemia, Radiation-Induced drug therapy, Leukemia, Radiation-Induced epidemiology, Leukemia, Radiation-Induced genetics
- Abstract
Purpose: To analyze patient cases of therapy-related acute promyelocytic leukemia (tAPL), occurring after chemotherapy (CT), radiotherapy (RT) or both for a prior disorder, diagnosed during the last 20 years in three European countries., Patients and Methods: The primary disorder and its treatment, interval from primary disorder to tAPL, characteristics of tAPL, and its outcome were analyzed in 106 patients., Results: Eighty of the 106 cases of tAPL were diagnosed during the last 10 years, indicating an increasing incidence of tAPL. Primary disorders were predominantly breast carcinoma (60 patients), non-Hodgkin's lymphoma (15 patients), and other solid tumors (25 patients). Thirty patients had received CT alone, 27 patients had received RT alone, and 49 patients had received both. CT included at least one alkylating agent in 68 patients and at least one topoisomerase II inhibitor in 61 patients, including anthracyclines (30 patients), mitoxantrone (28 patients), and epipodophyllotoxins (19 patients). Median interval from primary disorder to tAPL diagnosis was 25 months (range, 4 to 276 months). Characteristics of tAPL were generally similar to those of de novo APL. With treatment using anthracycline-cytarabine-based CT or all-trans-retinoic acid combined with CT, actuarial survival was 59% at 8 years., Conclusion: tAPL is not exceptional, and develops usually less than 3 years after a primary neoplasm (especially breast carcinoma) treated in particular with topoisomerase II-targeted drugs (anthracyclines or mitoxantrone and less often etoposide). Characteristics and outcome of tAPL seem similar to those of de novo APL.
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- 2003
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20. Escalating dose of mitoxantrone with high-dose cyclophosphamide, carmustine, and etoposide in patients with refractory lymphoma undergoing autologous bone marrow transplantation.
- Author
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Attal M, Canal P, Schlaifer D, Chatelut E, Dezeuze A, Huguet F, Payen C, Pris J, and Laurent G
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- Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols pharmacokinetics, Bone Marrow Diseases chemically induced, Carmustine administration & dosage, Cyclophosphamide administration & dosage, Etoposide administration & dosage, Female, Humans, Male, Middle Aged, Mitoxantrone adverse effects, Mitoxantrone pharmacokinetics, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Diseases prevention & control, Bone Marrow Transplantation, Lymphoma drug therapy, Mitoxantrone administration & dosage
- Abstract
Purpose: We conducted a dose-finding study of mitoxantrone (MITO) in combination with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (CBV) in refractory lymphoma undergoing autologous bone marrow transplantation (ABMT). The objective were to determine the following: (1) the maximum-tolerated dose of MITO, (2) the extramedullary toxicity of this regimen, (3) its antitumor activity, and (4) the pharmacokinetic characteristics of MITO at each dose level., Patients and Methods: Escalating doses of MITO (15 to 90 mg/m2, single bolus infusion on day -8) followed by CBV were administered to 20 patients (mean age, 38.5 years) with refractory lymphoma. MITO concentrations were determined by high-performance liquid chromatography (HPLC)., Results: No toxic death occurred. The maximum-tolerated dose appears to be 75 mg/m2. Two of five patients treated with 90 mg/m2 developed severe organ toxicity, versus zero of 15 treated with doses up to 75 mg/m2. Duration of neutropenia was longer for patients treated with 90 mg/m2 (31.7 days) than for patients treated with doses up to 75 mg/m2 (22.1 days) (P < .05). A linear relationship was observed between administered dose of MITO and (1) plasma peak value, (2) area under the curve (AUC), and (3) plasma concentration on the day of marrow infusion (day 0). Hematologic toxicity was related to the terminal half-life (T1/2) of MITO, and day-0 plasma concentration. A high complete response (CR) rate was observed (60%), and eight of 11 (73%) patients treated with MITO > or = 60 mg/m2 achieved a CR., Conclusion: MITO (up to 75 mg/m2) and CBV can be administered with acceptable toxicity and a promising CR rate in this poor-risk population, justifying further phase II studies.
- Published
- 1994
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21. Adult acute lymphoblastic leukemia: a multicentric randomized trial testing bone marrow transplantation as postremission therapy. The French Group on Therapy for Adult Acute Lymphoblastic Leukemia.
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Fière D, Lepage E, Sebban C, Boucheix C, Gisselbrecht C, Vernant JP, Varet B, Broustet A, Cahn JY, and Rigal-Huguet F
- Subjects
- Adolescent, Adult, Antineoplastic Agents adverse effects, Antineoplastic Agents therapeutic use, Combined Modality Therapy, Female, Humans, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma immunology, Prospective Studies, Remission Induction, Survival Analysis, Treatment Outcome, Bone Marrow Transplantation, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Purpose: In a prospective multicenter study, we analyzed the benefits of allogeneic bone marrow transplantation (BMT) in a nonselected group of adult patients with acute lymphoblastic leukemia (ALL) and, by a randomized trial, evaluated the effectiveness of autologous BMT over chemotherapy as postremission therapy in patients younger than 50 years who were not candidates for allogeneic BMT., Patients and Methods: After induction therapy that randomized patients to receive one of two anthracycline-containing regimens, either daunorubicin (DNR) or zorubicin (ZRB), patients were assigned to postremission treatment according to age and results of HLA typing. Patients younger than 40 years with an HLA-identical sibling (group 1) were scheduled to receive cyclophosphamide 60 mg/kg on days 1 and 2, total-body irradiation (TBI), and allogeneic BMT. Patients older than 50 years (group 2) received the chemotherapy arm composed of three monthly consolidation courses (DNR or ZRB, cytarabine, and asparaginase) followed by maintenance chemotherapy (modified L10 regimen). The remaining population (group 3) was randomly assigned to receive, after the three 1-month consolidation courses, either the chemotherapy arm or autologous BMT following a conditioning regimen similar to that of group 1., Results: Of the 572 assessable patients, 436 achieved complete remission (78% +/- 2% for DNR v 74% +/- 3% for ZRB; P = .3). The estimated 3-year disease-free survival (DFS) rate for the 116 patients included in group 1 was 43% +/- 5%. Both autologous BMT (95 patients) and chemotherapy (96 patients) produced comparable 3-year DFS rates (39% +/- 5% v 32% +/- 5%) and survival durations (49% +/- 5% v 42% +/- 5%). However, late relapses after 36 months were mainly observed in the chemotherapy arm., Conclusion: This first interim analysis did not demonstrate a benefit of this autologous BMT procedure over classical maintenance chemotherapy in patients with ALL who received consolidation chemotherapy.
- Published
- 1993
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22. Prevention of gram-positive infections after bone marrow transplantation by systemic vancomycin: a prospective, randomized trial.
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Attal M, Schlaifer D, Rubie H, Huguet F, Charlet JP, Bloom E, Lemozy J, Massip P, Pris J, and Laurent G
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Female, Fever drug therapy, Humans, Infant, Male, Middle Aged, Prospective Studies, Bacterial Infections prevention & control, Bone Marrow Transplantation, Gram-Positive Bacteria, Neutropenia complications, Postoperative Complications prevention & control, Vancomycin therapeutic use
- Abstract
Gram-positive bacteria are the most commonly isolated organisms after bone marrow transplantation (BMT) and severe streptococcus septicemia has been reported. In order to evaluate the benefit of a gram-positive prophylaxis after BMT, we conducted a prospective, randomized trial of systemic vancomycin among 60 patients undergoing BMT for hematologic malignancies. Patients were randomized to receive (n = 30) or not receive (n = 30) prophylactic vancomycin 15 mg/kg every 12 hours from day -2 until resolution of neutropenia or until the first episode of fever. All patients were treated in laminar air-flow rooms, received sterile diet, total gut decontamination, and had central venous catheters placed surgically. Vancomycin was found to be highly effective in preventing gram-positive infections that occurred in 11 of 30 patients in the control group versus zero of 30 in the vancomycin group (P less than .002). All gram-positive infections occurring in the control group were symptomatic (nine septicemia and two local infections), and one patient with Streptococcus septicemia died with pneumonia. Thus, gram-positive prophylaxis was found to decrease infection morbidity after BMT. Moreover, the number of days with fever (P less than .001), and empiric antibiotic therapy (P less than .01) was reduced without added toxicity or cost. This study confirmed the high prevalence of gram-positive infections after BMT and emphasized the clinical benefits of an adapted prophylaxis.
- Published
- 1991
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23. Treatment of relapsed acute myeloid leukemia with idarubicin and intermediate-dose cytarabine.
- Author
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Harousseau JL, Reiffers J, Hurteloup P, Milpied N, Guy H, Rigal-Huguet F, Facon T, Dufour P, and Ifrah N
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Clinical Trials as Topic, Cytarabine administration & dosage, Cytarabine adverse effects, Female, Humans, Idarubicin administration & dosage, Idarubicin adverse effects, Male, Middle Aged, Recurrence, Remission Induction, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Myeloid, Acute drug therapy
- Abstract
High-dose cytarabine (HDARA-C) is an effective but toxic treatment for acute myeloid leukemia (AML). In order to reduce the incidence of severe complications noted with HDARA-C-containing regimens, we used a combination of intravenous (IV) idarubicin (IDARUB) at optimal dosage and cytarabine (ARA-C) at intermediate dosage. Thirty-five patients aged 23 to 78 years (median, 56) with AML in first relapse received IDARUB, 8 mg/m2/d for five days, and ARA-C, 1 g/m2 every 12 hours for six doses. Of the 35 patients, 21 achieved a complete remission (CR), four had a partial remission (PR), four died in aplasia, and six were nonresponders. The only factor influencing the CR rate was the duration of the first CR (35% for patients relapsing before 16 months v 83% for patients relapsing after 16 months, P = .003). Mucositis was the most significant extrahematologic side effect. Diarrhea, skin toxicity, and hepatic disturbances were rare and mild. There was no cerebellar toxicity, even in 25 patients greater than 50 years of age. This regimen is effective and well tolerated even in elderly patients, and could be used either as induction or consolidation therapy for the treatment of AML.
- Published
- 1989
- Full Text
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