33 results on '"B. Desablens"'
Search Results
2. Results of a Prospective Study of High-Dose or Conventional Anthracycline-Cyclophosphamide Regimen Plus Radiotherapy for Localized Adult Non-Hodgkin's Primary Bone Lymphoma
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Jean-Pierre Marolleau, T. Lamy, S Lissandre, B Desablens, Ghandi Damaj, JF Abgrall, Roch Houot, Marie-Pierre Moles-Moreau, Philippe Casassus, Reda Garidi, Aline Schmidt-Tanguy, P Rodon, Jonchère, Laurent, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier de Blois (CHB), Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, Service clinique des Maladies du Sang, Hôpital Saint-Quentin, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
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Oncology ,Pathology ,medicine.medical_specialty ,Article Subject ,Anthracycline ,Performance status ,Cyclophosphamide ,business.industry ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Retrospective cohort study ,Hematology ,3. Good health ,Primary Bone Lymphoma ,Radiation therapy ,[SDV] Life Sciences [q-bio] ,Regimen ,Internal medicine ,medicine ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Prospective cohort study ,business ,medicine.drug ,Research Article - Abstract
Background. Primary bone lymphoma (PBL) is a rare entity that has only been reviewed in one prospective and small retrospective studies, from which it is difficult to establish treatment guidelines. We prospectively evaluated high-dose or conventional anthracycline-cyclophosphamide dose and radiotherapy for PBL.Patients and Methods. The GOELAMS prospective multicenter study (1986–1998) enrolled adults with localized high-grade PBL according to age and performance status (PS). Patients Results. Among the 26 patients included (VCAP: 19; VCEP-bleomycin: 7), 39% had poor PS ≥2. With a median follow-up of 8 years, overall survival, event-free survival, and relapse-free survival were 64%, 62%, and 65%, respectively, with no significant difference between treatment groups. Poor PS was significantly associated with shorter OS and EFS.Conclusions. Our results confirm the efficacy of our age-based therapeutic strategy. High-doses anthracycline-cyclophosphamide did not improve the outcome. VCEP-bleomycin is effective and well tolerated for old patients. The intensification must be considered for patients with PS ≥2, a poor prognostic factor.
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- 2014
3. Primary lymphoma of the central nervous system. An unresolved therapeutic problem
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Brigitte Gindrey-Vie, Gérard Socié, C. Piprot-Chauffat, F. Pene, D. Legars, Josette Brière, Alain Laugier, N. Ifran, Michel Schlienger, B. Desablens, J. L. Marin, C. Thurel, and J. Mikol
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Cancer Research ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Central nervous system ,Primary central nervous system lymphoma ,Treatment results ,medicine.disease ,Gastroenterology ,Surgery ,Radiation therapy ,medicine.anatomical_structure ,Oncology ,Internal medicine ,Primary lymphoma ,medicine ,Risk factor ,business ,Median survival - Abstract
From January 1979 to December 1987, 35 cases of primary central nervous system lymphoma (CNS-L) were treated. We recently reviewed these cases focusing on treatment results, treatment modalities, and radiotherapy (RT) or chemotherapy-radiotherapy (CT-RT). Variables such as age, risk factors, presenting symptoms, and histologic condition (all were high-grade or intermediate-grade non-Hodgkin's lymphomas [NHL]) and radiologic data were similar to those of series reported previously. The median survival time was 36 months (+/- 0.2 months) and the disease-free survival (DFS) time was 16 months (+/- 0.12 months). Twelve of 32 patients evaluable for treatment results experienced a recurrence (all but one occurred in the CNS). The DFS rate was 70% for the CT-RT group and 50% for the RT group (median follow-up time, 24 months). Therapeutic results in CNS-L are discussed with special emphasis on a putative role of CT in the management of this rare type of tumor.
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- 1990
4. Primary Sjogren's syndrome associated agranulocytosis: a benign disorder?
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B. Desablens, Jean Sibilia, B. Tribout, A.-L. Voyer, Valérie Gouilleux-Gruart, Paul Coppo, F. Maloisel, M.-H. Schlageter, K. Lassoued, Joëlle Goetz, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Physiopathologie des arthrites, Université Louis Pasteur - Strasbourg I, service hématologie Strasbourg, and CHU Strasbourg
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Adult ,Neutropenia ,Concise Report ,health care facilities, manpower, and services ,[SDV]Life Sciences [q-bio] ,Immunology ,education ,Arthritis ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Pregnancy ,Immunopathology ,Granulocyte Colony-Stimulating Factor ,medicine ,Immunology and Allergy ,Humans ,030212 general & internal medicine ,health care economics and organizations ,Aged ,030203 arthritis & rheumatology ,Leukopenia ,medicine.diagnostic_test ,business.industry ,Bone Marrow Examination ,Middle Aged ,medicine.disease ,3. Good health ,Granulocyte colony-stimulating factor ,Bone marrow examination ,medicine.anatomical_structure ,Methotrexate ,Sjogren's Syndrome ,Treatment Outcome ,Antibodies, Antinuclear ,Antirheumatic Agents ,Female ,Steroids ,Bone marrow ,medicine.symptom ,business ,medicine.drug ,Agranulocytosis - Abstract
To report on an uncommon association of agranulocytosis in primary Sjögren's syndrome (SS).The clinical, haematological, and immunological features of seven patients with primary SS associated with a chronic (6 months) agranulocytosis, and the outcome of the patients, were analysed.Patients were white women with an unexplained agranulocytosis. They all had non-erosive arthritis and three had a thrombocytopenia or Evan's syndrome. In three patients, transient or durable expansion of T lymphocytes was present in the peripheral blood or in the bone marrow, but evolved independently from neutrophil counts. There was no paroxysmal nocturnal haemoglobinuria clone or antibodies to neutrophil surface antigens. In vitro bone marrow culture was normal (four patients) or showed a decrease in colony forming unit-granulocyte monocyte (CFU-GM) and colony forming unit-erythroblast (CFU-E) (one patient). Serum levels of soluble Fas ligand (sFasL) were normal, and granulocyte-colony stimulating factor (G-CSF) concentrations were either normal or raised. One patient was treated with steroids associated with intravenous immunoglobulins and achieved a lasting response. Two other patients were treated with steroids and methotrexate, with poor efficacy. Short courses of subcutaneous G-CSF produced a transient and mild response in all three patients. Complete recovery of the neutrophils occurred temporarily during pregnancy in two patients. After a mean follow up of 34.8 months (range 6-139) all patients were alive and none developed serious infections.A subset of patients with primary SS and non-destructive arthritis may develop a chronic but well tolerated agranulocytosis that is usually poorly responsive to steroids and oral methotrexate.
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- 2003
5. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group
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P, Fenaux, C, Chastang, S, Chevret, M, Sanz, H, Dombret, E, Archimbaud, M, Fey, C, Rayon, F, Huguet, J J, Sotto, C, Gardin, P C, Makhoul, P, Travade, E, Solary, N, Fegueux, D, Bordessoule, J S, Miguel, H, Link, B, Desablens, A, Stamatoullas, E, Deconinck, F, Maloisel, S, Castaigne, C, Preudhomme, and L, Degos
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Adult ,Male ,Adolescent ,Mercaptopurine ,Remission Induction ,Infant ,Tretinoin ,Middle Aged ,Drug Administration Schedule ,Methotrexate ,Treatment Outcome ,Leukemia, Promyelocytic, Acute ,Child, Preschool ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Female ,Child ,Aged - Abstract
All transretinoic acid (ATRA) followed by daunorubicin (DNR)-AraC chemotherapy (CT) has improved the outcome of acute promyelocytic leukemia (APL) by comparison to CT alone. In a randomized trial, (1) we compared 2 induction schedules (ATRA followed by CT [ATRA--CT] and ATRA plus CT [ATRA+CT, with CT added on day 3 of ATRA treatment]) and (2) we assessed the role of maintenance treatment. Four hundred thirteen patients/=75 years of age and with newly diagnosed APL were included. Induction treatment was stratified on white blood cell (WBC) count and age: patients/=65 years of age and with an initial WBC count of/=5,000/microL (n = 208) were randomized between ATRA--CT and ATRA+CT (initially randomized patients); patients with a WBC count greater than (high WBC count group, n = 163) and patients 66 to 75 years of age with a WBC count greater than 5,000/microL (elderly group, n = 42) were not initially randomized and received ATRA+CT from day 1 and ATRA --CT, respectively. All patients achieving CR received 2 additional DNR-AraC courses (only 1 in patients 66 to 75 years of age) and were then randomized for maintenance between no treatment, intermittent ATRA (15 days every 3 months) for 2 years, continuous low-dose CT (6 mercaptopurine + methotrexate) for 2 years, or both, using a 2-by-2 factorial design. Overall, 381 (92%) of the patients achieved complete remission (CR), 31 (7%) suffered an early death, and only 1 patient had leukemic resistance. ATRA syndrome occurred in 64 patients (15%) and was fatal in 5 cases. The CR rate was similar in all induction treatment groups. Event-free survival (EFS) was significantly lower in the high WBC group (P =.0002) and close to significance in the elderly group (P =.086) as compared with initially randomized patients. Relapse at 2 years was estimated at 6% in the ATRA+CT group, versus 16% in the ATRA--CT group (P =.04, relative risk [RR] =.41). EFS at 2 years was estimated at 84% in the ATRA+CT group, versus 77% in the ATRA--CT group (P =.1, RR =.62). Two hundred eighty-nine patients were randomized for maintenance. The 2-year relapse rate was 11% in patients randomized to continuous maintenance CT and 27% in patients randomized to no CT (P =.0002) and 13% in patients randomized to intermittent ATRA and 25% in patients randomized to no ATRA (P =.02). An additive effect of continuous maintenance CT and intermittent ATRA was seen, and only 6 of the 74 patients who received both maintenance treatments had relapsed. Overall survival was improved in patients who received maintenance CT (P =.01), and there was a trend for better survival in patients who received maintenance ATRA (P =.22). Our findings strongly suggest that early addition of chemotherapy to ATRA and maintenance therapy combining continuous CT and intermittent ATRA can reduce the incidence of relapse in APL. This effect already translates into significantly better survival for maintenance treatment with continuous CT.
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- 1999
6. A placebo-controlled study of recombinant human granulocyte-macrophage colony-stimulating factor administered during and after induction treatment for de novo acute myelogenous leukemia in elderly patients. Groupe Ouest Est Leucémies Aiguës Myéloblastiques (GOELAM)
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F, Witz, A, Sadoun, M C, Perrin, C, Berthou, J, Brière, J Y, Cahn, B, Lioure, B, Witz, S, François, B, Desablens, B, Pignon, P Y, Le Prisé, B, Audhuy, D, Caillot, P, Casassus, M, Delain, B, Christian, Z, Tellier, V, Polin, P, Hurteloup, and J L, Harousseau
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Leukemia, Myeloid, Acute ,Antineoplastic Combined Chemotherapy Protocols ,Remission Induction ,Age Factors ,Granulocyte-Macrophage Colony-Stimulating Factor ,Humans ,Middle Aged ,Infusions, Intravenous ,Survival Analysis ,Recombinant Proteins ,Aged - Abstract
The complete remission (CR) rate after intensive chemotherapy for acute myelogenous leukemia (AML) remains low in elderly patients, mainly because of a higher infectious mortality rate related to neutropenia and an increased incidence of adverse prognostic factors. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to potentially recruit leukemic blasts into cell cycle and improve cytotoxic effects when given during chemotherapy, and to shorten the duration of neutropenia when administered after chemotherapy. Two hundred forty patients aged 55 to 75 years who had newly diagnosed AML were randomly assigned to receive placebo or Escherichia coli-derived GM-CSF (5 micrograms/kg/d by 6-hour intravenous infusion) starting during induction chemotherapy on day 1 and continued through and after chemotherapy until recovery of neutrophils, or evidence of regrowth of leukemia, or up to day 28. Induction chemotherapy consisted of idarubicin (8 mg/m2/d on days 1 to 5) and cytarabine (100 mg/m2/d on days 1 to 7). The study drug was not administered subsequent to the induction course. Patients who achieved a CR received continuous maintenance therapy for 1 year with four quarterly reinduction courses; in the 55- to 64-year age subgroup, patients were randomly assigned to receive or not a consolidation course before maintenance therapy. The CR rate was similar in the GM-CSF and placebo groups (63% and 60.5%, respectively; P = .79). The mortality, rate of resistant disease, and rate of regrowth of leukemia were also similar in both groups. The time to neutrophil recovery was shorter in patients who received GM-CSF (24 v 29 days; P = .0001), but the incidence and characteristics of infectious events were not different. The 2-year disease-free survival (DFS) rate was significantly improved in the GM-CSF group (48% v 21% in the placebo group; P = .003). This effect was highly significant in the cohort of patients aged 55 to 64, but only marginal in patients/=65 years of age. There was a trend toward a longer overall survival (OS) in the GM-CSF group (P = .082). In summary, the administration of GM-CSF, concomitantly with chemotherapy and thereafter during induction course in AML, shortened the time to neutrophil recovery, but did not improve the CR rate in patients aged 55 to 75. Nonetheless, DFS and OS were significantly prolonged in patients aged 55 to 64 treated with GM-CSF. These results are promising and further evaluation of myeloid growth factors in AML is warranted.
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- 1998
7. Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. The Groupe Ouest Est Leucémies Aiguës Myéloblastiques (GOELAM)
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J L, Harousseau, J Y, Cahn, B, Pignon, F, Witz, N, Milpied, M, Delain, B, Lioure, T, Lamy, B, Desablens, F, Guilhot, D, Caillot, J F, Abgrall, S, Francois, J, Briere, D, Guyotat, P, Casassus, B, Audhuy, Z, Tellier, P, Hurteloup, and P, Herve
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Adult ,Antimetabolites, Antineoplastic ,Antibiotics, Antineoplastic ,Adolescent ,Daunorubicin ,Remission Induction ,Cytarabine ,Middle Aged ,Prognosis ,Leukemia, Myeloid ,Acute Disease ,Antineoplastic Combined Chemotherapy Protocols ,Multivariate Analysis ,Outcome Assessment, Health Care ,Humans ,Idarubicin ,Bone Marrow Transplantation - Abstract
Three intensive consolidation strategies are currently proposed to younger adults with acute myeloid leukemia (AML) in first complete remission (CR): allogeneic or autologous bone marrow transplantation (BMT) and intensive consolidation chemotherapy (ICC). Patients aged 15 to 50 years with de novo AML received an induction treatment with 7 days of cytarabine and either idarubicin or rubidazone. After achievement of a CR, patients up to the age of 40 and having an HLA-identical sibling were assigned to undergo an allogeneic BMT. All the other patients received a first course of ICC with high-dose cytarabine and the same anthracycline as for induction. They were then randomly assigned to either receive a second course of ICC with amsacrine and etoposide or a combination of busulfan and cyclosphosphamide followed by an unpurged autologous BMT. Of 517 eligible patients, 367 had a CR, but only 219 (59.5%) actually received the planned intensive postremission treatment (73 allogeneic BMT, 75 autologous BMT, and 71 ICC). With a median follow-up of 62 months, the 4-year disease-free survival (DFS) of the 367 patients in CR was 39.5%. The 4-year overall survival (OS) of the 517 eligible patients was 40.5%. In multivariate analysis, DFS and OS were influenced only by the initial white blood cell count and by the French-American-British classification. The type of postremission therapy had no significant impact on the outcome. There was no difference in the 4-year DFS and OS between 88 patients for whom an allogeneic BMT was scheduled (respectively, 44% and 53%) and 134 patients of the same age category and without an HLA-identical sibling (respectively, 38% and 53%). Similarly, there was no difference in the outcome between autologous BMT and ICC. The 4-year DFS was 44% for the 86 patients randomly assigned to autologous BMT and 40% for the 78 patients assigned to ICC (P = .41). The 4-year OS was similar in the two groups (50% v 54.5%, P = .72). The median duration of hospitalization and thrombocytopenia were longer after autologous BMT (39 v 32 days, P = .006, and 109.5 v 18.5 days, P = .0001, respectively). After a first course of ICC, a second course of chemotherapy is less myelotoxic than an unpurged autologous BMT but yields comparable DFS and OS rates.
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- 1997
8. Is the International Prognostic Index for aggressive lymphomas useful for low-grade lymphoma patients? Applicability to stage III-IV patients. The GOELAMS Group, France
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C, Foussard, B, Desablens, L, Sensebe, S, François, N, Milpied, E, Deconinck, V, Delwail, J, Dugay, T, Lamy, C, Ghandour, A, Le Mevel, H, Maisonneuve, P, Casassus, and P, Colombat
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Treatment Outcome ,L-Lactate Dehydrogenase ,Predictive Value of Tests ,Lymphoma, Non-Hodgkin ,Humans ,Prospective Studies ,Middle Aged ,Prognosis ,Severity of Illness Index ,Survival Analysis ,Neoplasm Staging - Abstract
The International Prognostic Index (IPI) is widely used to predict outcome of patients with aggressive lymphomas. Our goal was to assess the prognostic value of this index for low-grade lymphoma.One hundred eighty-two patients with disseminated (stage III or IV) low-grade lymphoma were enrolled in a prospective multicenter trial. According to the initial features, treatment either was started immediately or was deferred until indicated by disease progression. Patients received the same polychemotherapy regimen, given monthly for six cycles. They were assigned to one of four risk groups according to the number of presenting risk factors: low-risk (0 or 1), low-intermediate-risk (2), high-intermediate-risk (3), high-risk groups (4).Survival curves (Kaplan-Meier method) demonstrated a high significant difference for the four groups (log-rank: P0.0001). Median survival for the low-risk group has yet to be reached, while that for the three other groups are, respectively, 65, 34, and 12 months.In this study, the IPI has been found to be an important prognostic tool in low-grade lymphoma and may be used in the selection of appropriate therapeutic approaches for individual patients.
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- 1997
9. Hodgkin's disease during HIV1 infection: the French registry experience. French Registry of HIV-associated Tumors
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J M, Andrieu, S, Roithmann, J M, Tourani, R, Levy, B, Desablens, C, le Maignan, J A, Gastaut, P, Brice, M, Raphael, and B, Taillan
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Adult ,Male ,Adolescent ,HIV Infections ,Middle Aged ,Prognosis ,Hodgkin Disease ,Survival Rate ,HIV-1 ,Humans ,Female ,France ,Registries ,Aged ,Lymphoma, AIDS-Related - Abstract
The first cases of Hodgkin's disease (HD) associated with HIV infection were reported in 1984. Since then, short series of seropositive patients suffering from HD have been published. In order to identify the characteristics, treatment response and outcome of HIV-associated Hodgkin's disease (HIV-HD), the data of HIV-HD patients recorded between 1987 and 1989 were analysed and compared with those of primary HD patient and with those of HIV-associated non-Hodgkin's lymphoma (HIV-NHL), registered during the same period.The 45 cases of HD collected by the French registry of HIV-associated tumors between January 1987 and December 1989 were included in this study. All patients were clinically staged according to the Ann Arbor system. To compare HIV-HD characteristics with those of primary HD, we used a cohort of 407 patients with clinical stages (CS) IA to IVB, who were enrolled between September 1981 and August 1988 in a multicentric clinical trial. To identify the relationship between HIV-HD and the course of HIV infection we studied, when available, the routes of infection, initial CD4 cell count at the moment of HD diagnostic as well as the CDC class of HIV infection and compared these data with the same parameters observed in 142 HIV-NHL enrolled in the registry during the same period.HIV-HD is characterized by an increase in mixed-cellularity histology (49%), with a predominance of advanced stages (75%) and B symptoms (80%). A unique observation is made regarding mediastinal involvement, present in only 13% of HIV-HD (71% in primary HD). The HIV-HD/HIV-NHL ratio was significantly higher in intravenous drug abusers than in male homosexuals. Median CD4 cell count was 306/microliters at HIV-HD diagnosis, and only 11% of the cases were preceded by an AIDS manifestation. With standard therapy, 79% of the patients achieved complete remission, but hematological and infectious complications were very frequent. The progression to AIDS rate was 94% at two years and opportunistic infections were the most frequent cause of death. Overall two-year survival was 41% with 71% for patients with initial CD 4 cell counts higher than 300/microliter and 0% for those with CD4 cell counts lower than 300/microliter (P0.01).HIV-HD has a particular clinico-pathological profile when compared to primary HD, with a predominance of mixed-cellularity type, a high frequency of advanced stages and a high proportion of patients without mediastinal involvement. Moreover, HIV-HD seems to occur preferentially in the group of subjects infected by needle sharing. Standard HD therapy seems to be efficient but excessively toxic.
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- 1993
10. Contents, Vol. 42, 1986
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Victor Chan, G. Bianchi, Ricardo Boland, S. Kircher, William B. Guiney, G. Rifle, T. Bertoni, Andrew P. Goldberg, Eberhard Ritz, Gary S. Hoffman, D. Behringer, B. Desablens, Gurreri G, M. Tolani, James M. Hagberg, P.E. Rolan, Jordi Camps, Roger Foster, Schafferhans K, M. Scabini, A. Fournier, Edward M. Geltman, A. Pruna, Enrique Quintero, Alex B. Magil, Marc Wijnen, E. Solary, G. Vezzoli, Antoni Rimola, Gennaro Salvidio, Jeffrey M. Rimmer, Giacomo Deferrari, Margaret Sussman, J.F. Claisse, Gian Marco Ghiggeri, Robert M. Carney, J. Merke, Eugene E. Wells, Herschel R. Harter, Joan Rodés, August Heidland, Pere Ginès, W. Kortlandt, Roberta G. Reed, Dino Docci, C. Mohl, James A. Delmez, M. Muirhead, P. Fievet, Roger Gabriel, E.J. Dorhout Mees, Joan Gaya, Cristina Robaudo, P. Craswell, M. Stoeppler, Norman O. Oldroyd, Vicente Arroyo, A.R. Clarkson, Giacomo Garibotto, Mary H. Oldfield, Rüdiger Götz, H.A. Koomans, John Gennari, Anna D. Naumovich, P.F. Westeel, A. Elli, Gert Lubec, Ana Guevara, P. Palazzi, Miquel Rodamilans, Douglas Webber, F. Quarto di Palo, J.F. Cabanne, A.B. Geers, Y. Tanter, E. Ritz, Ekkehart Heidbreder, and James R. Gavin
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Traditional medicine ,business.industry ,Medicine ,business - Published
- 1986
11. Hemolytic-Uremic Syndrome after Cancer Chemotherapy without Mitomycin C
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A. Pruna, P. Fievet, J.F. Claisse, P.F. Westeel, Albert Fournier, M. Tolani, and B. Desablens
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Oncology ,medicine.medical_specialty ,Text mining ,Cancer chemotherapy ,Transfusion reaction ,business.industry ,Melanoma ,Internal medicine ,Mitomycin C ,medicine ,Combined Modality Therapy ,medicine.disease ,business - Published
- 1986
12. Results of a Prospective Study of High-Dose or Conventional Anthracycline-Cyclophosphamide Regimen Plus Radiotherapy for Localized Adult Non-Hodgkin's Primary Bone Lymphoma.
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Schmidt-Tanguy A, Houot R, Lissandre S, Abgrall JF, Casassus P, Rodon P, Desablens B, Marolleau JP, Garidi R, Lamy T, Moles-Moreau MP, and Damaj G
- Abstract
Background. Primary bone lymphoma (PBL) is a rare entity that has only been reviewed in one prospective and small retrospective studies, from which it is difficult to establish treatment guidelines. We prospectively evaluated high-dose or conventional anthracycline-cyclophosphamide dose and radiotherapy for PBL. Patients and Methods. The GOELAMS prospective multicenter study (1986-1998) enrolled adults with localized high-grade PBL according to age and performance status (PS). Patients <60 years received a high-dose CHOP regimen (VCAP) and those ≥60 years a conventional anthracycline-cyclophosphamide regimen (VCEP-bleomycin); all received intrathecal chemotherapy and local radiotherapy. Results. Among the 26 patients included (VCAP: 19; VCEP-bleomycin: 7), 39% had poor PS ≥2. With a median follow-up of 8 years, overall survival, event-free survival, and relapse-free survival were 64%, 62%, and 65%, respectively, with no significant difference between treatment groups. Poor PS was significantly associated with shorter OS and EFS. Conclusions. Our results confirm the efficacy of our age-based therapeutic strategy. High-doses anthracycline-cyclophosphamide did not improve the outcome. VCEP-bleomycin is effective and well tolerated for old patients. The intensification must be considered for patients with PS ≥2, a poor prognostic factor.
- Published
- 2014
- Full Text
- View/download PDF
13. High-dose therapy followed by autologous purged stem cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by the GOELAMS with final results after a median follow-up of 9 years.
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Gyan E, Foussard C, Bertrand P, Michenet P, Le Gouill S, Berthou C, Maisonneuve H, Delwail V, Gressin R, Quittet P, Vilque JP, Desablens B, Jaubert J, Ramée JF, Arakelyan N, Thyss A, Moluçon-Chabrot C, Delépine R, Milpied N, Colombat P, and Deconinck E
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- Adolescent, Adult, Cyclophosphamide administration & dosage, Disease-Free Survival, Female, Follow-Up Studies, Humans, Immunotherapy methods, Male, Middle Aged, Myeloablative Agonists administration & dosage, Survival Rate, Transplantation, Autologous, Whole-Body Irradiation, Bone Marrow Purging, Lymphoma, Follicular mortality, Lymphoma, Follicular therapy, Neoplasms, Second Primary mortality, Stem Cell Transplantation, Transplantation Conditioning
- Abstract
Autologous stem cell transplantation (ASCT) as first-line therapy for follicular lymphoma (FL) remains controversial. The multicenter study randomized 172 patients with untreated FL for either immunochemotherapy or high-dose therapy (HDT) followed by purged ASCT. Conditioning was performed with total body irradiation (TBI) and cyclophosphamide. The 9-year overall survival (OS) was similar in the HDT and conventional chemotherapy groups (76% and 80%, respectively). The 9-year progression-free survival (PFS) was higher in the ASCT than the chemotherapy group (64% vs 39%; P = .004). A PFS plateau was observed in the HDT group after 7 years. On multivariate analysis, OS and PFS were independently affected by the per-formance status score, the number of nodal areas involved, and the treatment group. Secondary malignancies were more frequent in the HDT than in the chemotherapy group (6 secondary myelodysplastic syndrome/acute myeloid leukemia and 6 second solid tumor cancers vs 1 acute myeloid leukemia, P = .01). The occurrence of a PFS plateau suggests that a subgroup of patients might have their FL cured by ASCT. However, the increased rate of secondary malignancies may discourage the use of purged ASCT in combination with TBI as first-line treatment for FL. This trial has been registered with ClinicalTrials.gov under identifier NCT00696735.
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- 2009
- Full Text
- View/download PDF
14. ZAP-70 tyrosine kinase is constitutively expressed and phosphorylated in B-lineage acute lymphoblastic leukemia cells.
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Guillaume N, Alleaume C, Munfus D, Capiod JC, Touati G, Pautard B, Desablens B, Lefrère JJ, Gouilleux F, Lassoued K, and Gouilleux-Gruart V
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- Adult, Antigens, CD34 biosynthesis, Bone Marrow metabolism, Child, Child, Preschool, Female, Humans, Infant, Male, Middle Aged, Phosphorylation, Burkitt Lymphoma genetics, Burkitt Lymphoma metabolism, Gene Expression Regulation, Neoplastic, ZAP-70 Protein-Tyrosine Kinase biosynthesis, ZAP-70 Protein-Tyrosine Kinase genetics
- Abstract
Background and Objectives: Zeta-associated protein 70 (ZAP-70), a member of the Syk family of protein tyrosine kinases, is normally expressed in T and NK cells. While little is known about ZAP-70 expression in normal human B cells, it has been reported that ZAP-70 is expressed in a subset of patients with chronic lymphocytic leukemia (CLL) with a poor prognosis. In this study, we examined the expression and phosphorylation status of ZAP-70 in B-lineage acute lymphoblastic leukemia (Blin-ALL)., Design and Methods: First, ZAP-70 protein expression was assessed by Western blotting and flow cytometry and ZAP-70 mRNA transcripts were analyzed by reverse transcription polymerase chain reaction (RT-PCR) on human precursor B cell lines. Experiments were then carried out on cells obtained from 18 patients with Blin-ALL and from normal human bone marrow., Results: ZAP-70 was constitutively expressed and phosphorylated on tyr319 in human precursor Blin-ALL cell lines as well as in primary B leukemic cells from all examined Blin-ALL patients with pro-B, pre-B and B phenotypes, but not in malignant myeloid cells. Importantly, analysis of normal human bone marrow revealed expression of ZAP-70 transcripts only in the CD34+ cell fraction (either CD19-CD10- or CD19+CD10+) but not in the CD34- cell fraction (CD19+sIgM- pre-B cells or CD19+sIgM+ immature B cells)., Interpretation and Conclusions: ZAP-70 was found to be expressed in the CD34+ normal bone marrow compartment including earlier B-cell progenitors, but not in CD34- pre-B and immature B cells. By contrast, ZAP-70 was consistently expressed and phosphorylated in Blin-ALL cells. Further studies are required to determine whether ZAP-70 may play a pathophysiological role in Blin-ALL.
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- 2005
15. Long-term outcome of localized high-grade non-Hodgkin's lymphoma treated with high dose CHOP regimen and involved field radiotherapy: results of a GOELAMS study.
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Bernard M, Cartron G, Rachieru P, LeMevel A, Branger B, Le Maignan C, Berthou C, Ghandour C, Delwail V, Milpied N, Cassasus P, Celigny PS, Guyotat D, Lamy T, and Desablens B
- Subjects
- Adolescent, Adult, Combined Modality Therapy, Cyclophosphamide therapeutic use, Disease-Free Survival, Doxorubicin therapeutic use, Female, Follow-Up Studies, Humans, Male, Middle Aged, Multicenter Studies as Topic, Prednisolone therapeutic use, Prednisone therapeutic use, Prospective Studies, Recurrence, Remission Induction, Time Factors, Treatment Outcome, Vincristine therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Non-Hodgkin drug therapy, Lymphoma, Non-Hodgkin radiotherapy
- Abstract
Background and Objectives: Most patients with localized high-grade non-Hodgkin's lymphoma (NHL) can be cured with or without adjuvant radiotherapy. However few data are available on the long-term outcome of these patients. Here we report the results of a prospective study, started in 1984, which was conducted to evaluate the long-term outcome of patients with localized high-grade NHL., Design and Methods: In this multicenter, prospective study by the GOELAMS group, 253 patients with localized high-grade NHL were treated with 3 cycles of vindesine, cyclophosphamide, adriamycin and prednisone (VCAP, a high-dose CHOP regimen) followed by involved field radiotherapy (40 Gy)., Results: After completion of chemotherapy, 213 patients (84%) entered complete remission (CR) and 30 (12%) obtained a partial remission. Treatment failed in 6 patients (2.5%) and there were 4 toxic deaths (1.5%). Following radiotherapy, 239 (94%) of all patients were in CR. With a median follow-up of 88 months, overall survival and disease-free survival rates were 84% and 85% respectively at five years, and 78% and 82% respectively at ten years. The response to chemotherapy was decisive to survival. We observed 43 relapses (17%) at a median time of 20 months after CR, and 9 patients relapsed after five years. Eleven patients (3%) developed another malignancy in the follow-up period., Interpretation and Conclusions: High-dose CHOP followed by locoregional radiotherapy is a feasible treatment for localized high-grade NHL. It has very few complications, a good CR rate and the OS is 78% at 10 years.
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- 2005
16. Intensive therapy before or during the conditioning regimen of allogeneic marrow transplantation in adult acute lymphoblastic leukemia patients: we must choose to reduce Toxicity--a Groupe Ouest-Est d'Etude des Leucemies et Autres Maladies du Sang study.
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Deconinck E, Hunault M, Milpied N, Bernard M, Renaud M, Desablens B, Delain M, Witz F, Lioure B, Pignon B, Guyotat D, Berthou C, Jouet JP, Casassus P, Ifrah N, and Boiron JM
- Subjects
- Adolescent, Adult, Female, Humans, Male, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Randomized Controlled Trials as Topic, Survival Analysis, Transplantation, Homologous, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Bone Marrow Transplantation mortality, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Transplantation Conditioning methods, Transplantation Conditioning mortality
- Abstract
To improve the results in the treatment of adult acute lymphoblastic leukemia patients, different strategies have been proposed. The intensification could concern the induction and early consolidation phases, the conditioning regimen before allogeneic bone marrow transplantation (alloBMT), or both. We analyzed 2 consecutive trials for adult patients in first remission and with the same prognostic features. The Leucemie Aigue Lymphoblastique Paris-Ouest-France (LALPOF) protocol proposed alloBMT with standard conditioning after a classic induction and intensified consolidation scheme; the Groupe Ouest Est des Leucemies Aigues Lymphoblastiques (GOLEAL1) protocol tested an intensified induction and consolidation course before alloBMT with a reinforced conditioning regimen. The 4-year survival rates after alloBMT for LALPOF and GOELAL1 were, respectively, 71% +/- 12% and 36% +/- 13% ( P = .009). The 4-year disease-free survival reached 75% +/- 11% in the LALPOF study and 69% +/- 13% in the GOELAL1 study ( P = .30). The toxic death rate was significantly lower in the LALPOF (2/18) than in the GOELAL1 (6/15) group. Event-free survival at 4 years was significantly higher in LALPOF than in GOELAL1: 66% +/- 11% and 35% +/- 11%, respectively ( P = .02). For adult acute lymphoblastic leukemia patients in first remission, the intensification of chemotherapy before a reinforced conditioning regimen before alloBMT may lead to an increased toxic death rate.
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- 2005
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17. High-dose therapy followed by autologous purged stem-cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by GOELAMS.
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Deconinck E, Foussard C, Milpied N, Bertrand P, Michenet P, Cornillet-LeFebvre P, Escoffre-Barbe M, Maisonneuve H, Delwail V, Gressin R, Legouffe E, Vilque JP, Desablens B, Jaubert J, Ramee JF, Jenabian A, Thyss A, Le Pourhiet-Le Mevel A, Travade P, Delepine R, and Colombat P
- Subjects
- Adult, Disease Progression, Doxorubicin adverse effects, Feasibility Studies, Female, Follow-Up Studies, France, Humans, Lymphoma, Follicular drug therapy, Lymphoma, Follicular surgery, Male, Middle Aged, Neoplasm Staging, Recurrence, Survival Rate, Transplantation, Autologous, Doxorubicin therapeutic use, Lymphoma, Follicular pathology, Lymphoma, Follicular therapy, Stem Cell Transplantation
- Abstract
Doxorubicin-based immunochemotherapy, with interferon, has been shown to improve survival in patients with advanced follicular lymphoma. High-dose chemotherapy with stem-cell support is effective in follicular lymphoma in relapse but remains controversial as a first-line therapy. In a randomized study using a purged autologous stem-cell support, we compared these 2 approaches in patients with advanced follicular lymphoma. Newly diagnosed advanced follicular lymphoma patients (172 patients) were randomly assigned either to an immunochemotherapy regimen (cyclophosphamide, doxorubicin, teniposide, prednisone, and interferon) or to a high-dose therapy followed by purged autologous stem-cell transplantation. Compared with the patients who received chemotherapy and interferon, patients treated with high-dose therapy had a higher response rate (69% vs 81%, P = .045) and a longer median event-free survival (not reached vs 45 months). This did not translate into a better survival rate due to an excess of secondary malignancies after transplantation. The Follicular Lymphoma Prognostic Index identified a subgroup of patients with a significantly higher event-free survival rate after high-dose therapy. Autologous stem-cell transplantation cannot be considered as the standard first-line treatment of follicular lymphoma for patients younger than 60 years old with a high tumor burden.
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- 2005
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18. Long-term follow-up of a randomized trial of fludarabine-mitoxantrone, compared with cyclophosphamide, doxorubicin, vindesine, prednisone (CHVP), as first-line treatment of elderly patients with advanced, low-grade non-Hodgkin's lymphoma before the era of monoclonal antibodies.
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Foussard C, Colombat P, Maisonneuve H, Berthou C, Gressin R, Rousselet MC, Rachieru P, Pignon B, Mahé B, Ghandour C, Desablens B, Casassus P, Lamy T, Delwail V, and Deconinck E
- Subjects
- Age Factors, Aged, Cyclophosphamide administration & dosage, Disease-Free Survival, Doxorubicin administration & dosage, Female, Follow-Up Studies, Humans, Lymphoma, Non-Hodgkin pathology, Male, Middle Aged, Mitoxantrone administration & dosage, Prednisone administration & dosage, Risk Factors, Vidarabine administration & dosage, Vindesine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Non-Hodgkin drug therapy, Lymphoma, Non-Hodgkin immunology, Vidarabine analogs & derivatives
- Abstract
Background: This randomized study compared the efficacy and safety of fludarabine-mitoxantrone (FM) with mini-CHVP (cyclophosphamide, doxorubicin, vindesine, prednisone) in elderly patients with advanced, low-grade non-Hodgkin's lymphoma., Patients and Methods: End points were remission rates [overall response (OR) and complete response (CR)], failure-free survival (FFS), survival and toxicity. One hundred and fifty-five patients were randomized, 144 were evaluable for safety and 142 for response. Each treatment arm was given as six monthly cycles, followed by three bimonthly cycles. FM comprised fludarabine (20 mg/m(2) i.v.), days 1-5, plus mitoxantrone (10 mg/m(2) i.v.), day 1. CHVP cycles comprised cyclophosphamide (750 mg/m(2) i.v. infusion), doxorubicin (25 mg/m(2) i.v.) and vindesine (3 mg/m(2) i.v.) on day 1, and prednisone (50 mg/m(2)) on days 1-5., Results: FM therapy resulted in superior remission rates (OR 81% versus 64%, CR 49% versus 17%; P = 0.0004). Median FFS for FM patients was 36 months, compared with 19 months for CHVP patients, and has not yet been reached for early CR patients at 53 months. Treatment arm was the major risk factor influencing survival. Both treatments were well tolerated, with only few infectious complications., Conclusion: FM was more effective than CHVP in achieving OR and CR, and favorably affected the outcome.
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- 2005
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19. Comparison of initial characteristics and long-term outcome of patients with lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma at clinical stages IA and IIA prospectively treated by brief anthracycline-based chemotherapies plus extended high-dose irradiation.
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Feugier P, Labouyrie E, Djeridane M, Jenabian A, Dubruille V, Berthou C, Ghandour C, Desablens B, Chaït Y, Casassus P, Delwail V, Ifrah N, Le Mevel A, Lamy T, Brière J, Colonna P, and Andrieu JM
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Clinical Trials as Topic, Combined Modality Therapy, Disease-Free Survival, Female, Heart Diseases etiology, Hodgkin Disease complications, Hodgkin Disease mortality, Humans, Longitudinal Studies, Male, Middle Aged, Neoplasms, Second Primary etiology, Radiotherapy methods, Retrospective Studies, Survival Rate, Anthracyclines therapeutic use, Hodgkin Disease classification, Hodgkin Disease therapy, Lymphocytes pathology
- Abstract
Lymphocyte-predominant Hodgkin lymphoma (LPHL), according to the Revised European-American Lymphoma classification, was considered on a retrospective basis as a specific clinical entity with a large majority of patients at clinical stage (CS) IA or IIA. Of the 500 patients with CS IA/IIA Hodgkin lymphoma (HL) prospectively treated between 1981 and 1996 by one or 3 courses of anthracycline-based chemotherapies combined with high-dose extended irradiation, disease in 42 patients was reclassified as LPHL. These 42 patients, none of whom had mediastinal involvement (MI), were compared with the 458 patients with classical HL (cHL), 144 without MI and 314 with MI. Surprisingly, the male-female ratio, age, first site involved, hemoglobin level, lymphocyte count, and sedimentation rate of patients with LPHL and cHL without MI were identical and significantly different from those of patients with cHL with MI. Moreover, 15-year HL mortality rates were similarly low in patients with LPHL (2.4%) and cHL without MI (0.7%). Overall survival rates were also similar (86% and 82%) and as high as 100% and 95% in patients treated before the age of 40 years. This study demonstrated that LPHL and cHL without MI shared the same presenting characteristics and the same excellent long-term prognosis after a brief anthracycline-based chemotherapy plus high-dose extended irradiation.
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- 2004
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20. Three cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) or epirubicin, bleomycin, vinblastine, and methotrexate (EBVM) plus extended field radiation therapy in early and intermediate Hodgkin disease: 10-year results of a randomized trial.
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le Maignan C, Desablens B, Delwail V, Dib M, Berthou C, Vigier M, Ghandour C, Atmani S, Casassus P, Maisonneuve H, Le Mevel A, Traulle C, Bernard M, Briere J, Colonna P, and Andrieu JM
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bleomycin adverse effects, Bleomycin therapeutic use, Combined Modality Therapy, Dacarbazine adverse effects, Dacarbazine therapeutic use, Disease-Free Survival, Doxorubicin adverse effects, Doxorubicin therapeutic use, Epirubicin administration & dosage, Epirubicin adverse effects, Female, France epidemiology, Hodgkin Disease mortality, Humans, Male, Methotrexate administration & dosage, Methotrexate adverse effects, Middle Aged, Survival Rate, Time Factors, Vinblastine adverse effects, Vinblastine therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hodgkin Disease drug therapy, Hodgkin Disease radiotherapy
- Abstract
From 1990 to 1996, a total of 386 adult patients with early/intermediate Hodgkin disease (HD) were randomly assigned to receive 3 cycles of adriamycin, bleomycin, vinblastine, dacarbazine (an alkylating agent), and methylprednisolone (ABVDm, arm A) or epirubicin, bleomycin, vinblastine, methotrexate, and methylprednisolone (EBVMm, arm E), a combination without alkylating agent. Responding patients received extended field radiation therapy (RT). Postchemotherapy complete remission and 10-year freedom from progression rates were higher in arm A (79.5% and 91.4%) than in arm E (70.4%, P =.04, and 80%, P <.002). HD mortality (HDM), treatment-related mortality (TRM), and overall survival (OS) were similar in both arms (A, 2.1%, 7.5%, and 90.4%; B, 3.9%, 5.5%, and 90.3%). However TRM and OS rates were lower in patients aged 40 years or older (P <.005), reflecting the increasing incidence of background fatal events with increasing age. Finally, event-free survival (EFS) was higher in arm A (84.6%) than in arm E (74.9%, P <.02). In patients aged younger than 40 years in arm A (74%), 10-year EFS and OS rates were 88.9% and 95.4% with HDM and TRM rates as low as 0.7% and 3%. Three courses of ABVDm plus RT are the best available option for treating early or intermediate HD.
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- 2004
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21. Myelodysplastic syndrome after acute promyelocytic leukemia: the European APL group experience.
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Lobe I, Rigal-Huguet F, Vekhoff A, Desablens B, Bordessoule D, Mounier C, Ferrant A, Sanz M, Fey M, Chomienne C, Chevret S, Degos L, and Fenaux P
- Subjects
- Adolescent, Adult, Aged, Antibiotics, Antineoplastic therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Child, Cytarabine therapeutic use, Cytogenetic Analysis, Female, Follow-Up Studies, Humans, Incidence, Leukemia, Promyelocytic, Acute drug therapy, Leukemia, Promyelocytic, Acute epidemiology, Male, Middle Aged, Myelodysplastic Syndromes epidemiology, Remission Induction, Retrospective Studies, Tretinoin therapeutic use, Leukemia, Promyelocytic, Acute complications, Myelodysplastic Syndromes etiology
- Abstract
With improved treatment of acute promyelocytic leukemia (APL) by all trans retinoic acid (ATRA) combined to anthracycline-aracytin chemotherapy (CT), a larger number of those patients may be at risk of late complications. Recently, the Rome group reported five cases of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML, non-APL) occurring during the course of 77 APL patients (6.5%) in complete remission (CR). From 1991 to 1998, we treated 677 newly diagnosed cases of APL, and 617 of them achieved CR with ATRA combined to CT (n=579) or CT alone (n=38); 246 of them received subsequent maintenance CT with 6 mercaptopurine and methotrexate. With a median follow-up of 51 months, 6 patients (0.97%) developed MDS, 13-74 months after the diagnosis of APL. In all six cases, t(15;17) and PML-RARalpha rearrangement were absent at the time of MDS diagnosis, and karyotype mainly showed complex cytogenetic abnormalities involving chromosomes 5 and/or 7, typical of MDS observed after treatment with alkylating agents, although none of the six patients had received such agents for the treatment of APL. Our findings suggest that MDS can indeed be a long-term complication in APL, although probably at lower incidence than that previously reported.
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- 2003
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22. Multicenter, randomized comparative trial of fludarabine and the combination of cyclophosphamide-doxorubicin-prednisone in 92 patients with Waldenström macroglobulinemia in first relapse or with primary refractory disease.
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Leblond V, Lévy V, Maloisel F, Cazin B, Fermand JP, Harousseau JL, Remenieras L, Porcher R, Gardembas M, Marit G, Deconinck E, Desablens B, Guilhot F, Philippe G, Stamatoullas A, and Guibon O
- Subjects
- Adult, Aged, Alopecia chemically induced, Antineoplastic Agents, Alkylating toxicity, Antineoplastic Combined Chemotherapy Protocols toxicity, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Drug Resistance, Female, Humans, Male, Middle Aged, Mouth Mucosa, Prednisone administration & dosage, Recurrence, Salvage Therapy, Stomatitis chemically induced, Survival Analysis, Therapeutic Equivalency, Treatment Outcome, Vidarabine toxicity, Waldenstrom Macroglobulinemia complications, Waldenstrom Macroglobulinemia mortality, Antineoplastic Agents, Alkylating administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Waldenstrom Macroglobulinemia drug therapy
- Abstract
Few reports are available on the treatment of patients with Waldenström macroglobulinemia (WM) and primary or secondary resistance to alkylating-agent-based regimens. From December 1993 through December 1997, 92 patients with WM resistant to first-line therapy (42) or with first relapse (50) after alkylating-agent therapy were randomly assigned to receive fludarabine (25 mg/m(2) of body-surface area on days 1-5) or cyclophosphamide, doxorubicin (Adriamycin), and prednisone (CAP; 750 mg/m(2) cyclophosphamide and 25 mg/m(2) doxorubicin on day 1 and 40 mg/m(2) prednisone on days 1-5). The first end point evaluated was the response rate after 6 treatment courses. Forty-five patients received CAP and 45 received fludarabine. Two patients died before the first course of chemotherapy. No statistical differences were observed between the 2 treatment arms with respect to hematologic toxicity or infections. Mucositis and alopecia occurred significantly more often in patients treated with CAP. Partial responses were obtained in 14 patients (30%) treated with fludarabine and 5 patients (11%) treated with CAP (P =.019). Responses were more durable in patients treated with fludarabine (19 months versus 3 months), and the event-free survival rate was significantly higher in this group (P <.01). Forty-four patients died, 22 in the fludarabine group and 22 in the CAP group. There was no statistical difference in the median overall survival time in the 2 study arms. Fludarabine was thus more active than CAP in salvage therapy of WM and should be tested as first-line therapy in a randomized comparison with alkylating agents.
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- 2001
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23. Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients.
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Leporrier M, Chevret S, Cazin B, Boudjerra N, Feugier P, Desablens B, Rapp MJ, Jaubert J, Autrand C, Divine M, Dreyfus B, Maloum K, Travade P, Dighiero G, Binet JL, and Chastang C
- Subjects
- Aged, Antimetabolites, Antineoplastic adverse effects, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cisplatin administration & dosage, Cisplatin adverse effects, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Disease Progression, Doxorubicin administration & dosage, Doxorubicin adverse effects, Female, Follow-Up Studies, Hospitalization statistics & numerical data, Humans, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Lymphocyte Count, Male, Middle Aged, Neoplasm Staging, Phosphoramide Mustards administration & dosage, Phosphoramide Mustards adverse effects, Prednisone administration & dosage, Prednisone adverse effects, Prognosis, Proportional Hazards Models, Sample Size, Survival Rate, Time Factors, Vidarabine Phosphate adverse effects, Vincristine administration & dosage, Vincristine adverse effects, Antimetabolites, Antineoplastic therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Vidarabine Phosphate analogs & derivatives, Vidarabine Phosphate therapeutic use
- Abstract
To comparatively assess first-line treatment with fludarabine and 2 anthracycline-containing regimens, namely CAP (cyclophosphamide, doxorubicin plus prednisone) and ChOP (cyclophosphamide, vincristine, prednisone plus doxorubicin), in advanced stages of chronic lymphocytic leukemia (CLL), previously untreated patients with stage B or C CLL were randomly allocated to receive 6 monthly courses of either ChOP, CAP, or fludarabine (FAMP), stratified based on the Binet stages. End points were overall survival, treatment response, and tolerance. From June 1, 1990 to April 15, 1998, 938 patients (651 stage B and 287 stage C) were randomized in 73 centers. Compared to ChOP and FAMP, CAP induced lower overall remission rates (58.2%; ChOP, 71.5%; FAMP; 71.1%; P <.0001 for each), including lower clinical remission rates (CAP, 15.2%; ChOP, 29.6%; FAMP, 40.1%; P =.003). By contrast, median survival time did not differ significantly according to randomization (67, 70, and 69 months in the ChOP, CAP, and FAMP groups, respectively). Incidences of infections (< 5%) and autoimmune hemolytic anemia (< 2%) during the 6 courses were similar in the randomized groups, whereas fludarabine induced, compared to ChOP and CAP, more frequent protracted thrombocytopenia (P =.003) and less frequent nausea-vomiting (P =.003) and hair loss (P <.0001). For patients with stage B and C CLL first-line fludarabine and ChOP regimens both provided similar overall survival and close response rates, and better results than CAP. However, there was an increase in clinical remission rate and a trend toward a better tolerance of fludarabine over ChOP that may influence the choice between these regimens as front-line treatments in patients with CLL.
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- 2001
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24. Daunorubicin continuous infusion induces more toxicity than bolus infusion in acute lymphoblastic leukemia induction regimen: a randomized study.
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Hunault-Berger M, Milpied N, Bernard M, Jouet JP, Delain M, Desablens B, Sadoun A, Guilhot F, Casassus P, and Ifrah N
- Subjects
- Adolescent, Adult, Aged, Antibiotics, Antineoplastic administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Asparaginase administration & dosage, Bone Marrow Transplantation, Carmustine administration & dosage, Combined Modality Therapy, Cyclophosphamide administration & dosage, Cytarabine administration & dosage, Daunorubicin administration & dosage, Etoposide administration & dosage, Female, Gram-Negative Bacterial Infections etiology, Humans, Immunocompromised Host, Infusions, Intravenous, Injections, Intravenous, Life Tables, Male, Methotrexate administration & dosage, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Prednisone administration & dosage, Remission Induction, Survival Analysis, Thrombocytopenia chemically induced, Treatment Outcome, Vincristine administration & dosage, Antibiotics, Antineoplastic adverse effects, Daunorubicin adverse effects, Neutropenia chemically induced, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
We report the first randomized study assessing the efficacy and safety of daunorubicin (DNR) continuous infusion (CI) compared to the more conventional 30-min infusion (i.v.) in newly diagnosed adult acute lymphoblastic leukemia (ALL). Seventy-seven patients were initially randomized to receive either a 24-h CI DNR (60 mg/m2 days 2-4) (40 patients) or bolus DNR at the same dosage (37 patients) with vincristine (2 mg i.v. days 1, 8, 15) and oral prednisone (60 mg/m2 days 1-15), without hematopoietic growth factor support, as an induction regimen. The distribution of adverse prognostic factors was comparable in the two-induction arm. Acute toxicity was more important in the CI arm. Gram negative infection (9 vs 1 gram negative septicemia, P = 0.01) and infection-related deaths (6 vs 1 deaths, P = NS) occurred more frequently in the CI arm during the induction treatment than in the i.v. arm, leading to the study interruption. Neutropenia but not thrombopenia duration was significantly longer in the CI arm than in the i.v. arm (18 days vs 14 days, P > 0.05 and 16 days vs 12 days, P > 0.05, respectively). Despite a similar CR rate according to the method of DNR administration (68% in the CI DNR arm vs 76% in the i.v. arm after the first course), there was a trend toward higher freedom from relapse (FFR) after DNR CI (48% vs 28% in the i.v. arm at 5 years, P = NS), suggesting that despite this high toxicity, DNR CI may improve the CR quality and decrease further the residual disease.
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- 2001
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25. Fatal pulmonary fibrosis after a low cumulated dose of bleomycin: role of alpha1-antitrypsin deficiency?
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Alliot C, Tabuteau S, Desablens B, Aubry P, and Andrejak M
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hodgkin Disease drug therapy, Humans, Male, Middle Aged, Antimetabolites, Antineoplastic adverse effects, Bleomycin adverse effects, Pulmonary Fibrosis chemically induced, alpha 1-Antitrypsin Deficiency complications
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- 1999
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26. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group.
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Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E, Fey M, Rayon C, Huguet F, Sotto JJ, Gardin C, Makhoul PC, Travade P, Solary E, Fegueux N, Bordessoule D, Miguel JS, Link H, Desablens B, Stamatoullas A, Deconinck E, Maloisel F, Castaigne S, Preudhomme C, and Degos L
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Drug Administration Schedule, Female, Humans, Infant, Leukemia, Promyelocytic, Acute pathology, Leukemia, Promyelocytic, Acute physiopathology, Male, Mercaptopurine administration & dosage, Methotrexate administration & dosage, Middle Aged, Remission Induction, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Leukemia, Promyelocytic, Acute drug therapy, Tretinoin administration & dosage
- Abstract
All transretinoic acid (ATRA) followed by daunorubicin (DNR)-AraC chemotherapy (CT) has improved the outcome of acute promyelocytic leukemia (APL) by comparison to CT alone. In a randomized trial, (1) we compared 2 induction schedules (ATRA followed by CT [ATRA-->CT] and ATRA plus CT [ATRA+CT, with CT added on day 3 of ATRA treatment]) and (2) we assessed the role of maintenance treatment. Four hundred thirteen patients =75 years of age and with newly diagnosed APL were included. Induction treatment was stratified on white blood cell (WBC) count and age: patients =65 years of age and with an initial WBC count of =5,000/microL (n = 208) were randomized between ATRA-->CT and ATRA+CT (initially randomized patients); patients with a WBC count greater than (high WBC count group, n = 163) and patients 66 to 75 years of age with a WBC count greater than 5,000/microL (elderly group, n = 42) were not initially randomized and received ATRA+CT from day 1 and ATRA -->CT, respectively. All patients achieving CR received 2 additional DNR-AraC courses (only 1 in patients 66 to 75 years of age) and were then randomized for maintenance between no treatment, intermittent ATRA (15 days every 3 months) for 2 years, continuous low-dose CT (6 mercaptopurine + methotrexate) for 2 years, or both, using a 2-by-2 factorial design. Overall, 381 (92%) of the patients achieved complete remission (CR), 31 (7%) suffered an early death, and only 1 patient had leukemic resistance. ATRA syndrome occurred in 64 patients (15%) and was fatal in 5 cases. The CR rate was similar in all induction treatment groups. Event-free survival (EFS) was significantly lower in the high WBC group (P =.0002) and close to significance in the elderly group (P =.086) as compared with initially randomized patients. Relapse at 2 years was estimated at 6% in the ATRA+CT group, versus 16% in the ATRA-->CT group (P =.04, relative risk [RR] =.41). EFS at 2 years was estimated at 84% in the ATRA+CT group, versus 77% in the ATRA-->CT group (P =.1, RR =.62). Two hundred eighty-nine patients were randomized for maintenance. The 2-year relapse rate was 11% in patients randomized to continuous maintenance CT and 27% in patients randomized to no CT (P =.0002) and 13% in patients randomized to intermittent ATRA and 25% in patients randomized to no ATRA (P =.02). An additive effect of continuous maintenance CT and intermittent ATRA was seen, and only 6 of the 74 patients who received both maintenance treatments had relapsed. Overall survival was improved in patients who received maintenance CT (P =.01), and there was a trend for better survival in patients who received maintenance ATRA (P =.22). Our findings strongly suggest that early addition of chemotherapy to ATRA and maintenance therapy combining continuous CT and intermittent ATRA can reduce the incidence of relapse in APL. This effect already translates into significantly better survival for maintenance treatment with continuous CT.
- Published
- 1999
27. A placebo-controlled study of recombinant human granulocyte-macrophage colony-stimulating factor administered during and after induction treatment for de novo acute myelogenous leukemia in elderly patients. Groupe Ouest Est Leucémies Aiguës Myéloblastiques (GOELAM).
- Author
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Witz F, Sadoun A, Perrin MC, Berthou C, Brière J, Cahn JY, Lioure B, Witz B, François S, Desablens B, Pignon B, Le Prisé PY, Audhuy B, Caillot D, Casassus P, Delain M, Christian B, Tellier Z, Polin V, Hurteloup P, and Harousseau JL
- Subjects
- Age Factors, Aged, Humans, Infusions, Intravenous, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute pathology, Middle Aged, Recombinant Proteins administration & dosage, Remission Induction, Survival Analysis, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Granulocyte-Macrophage Colony-Stimulating Factor administration & dosage, Leukemia, Myeloid, Acute drug therapy
- Abstract
The complete remission (CR) rate after intensive chemotherapy for acute myelogenous leukemia (AML) remains low in elderly patients, mainly because of a higher infectious mortality rate related to neutropenia and an increased incidence of adverse prognostic factors. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to potentially recruit leukemic blasts into cell cycle and improve cytotoxic effects when given during chemotherapy, and to shorten the duration of neutropenia when administered after chemotherapy. Two hundred forty patients aged 55 to 75 years who had newly diagnosed AML were randomly assigned to receive placebo or Escherichia coli-derived GM-CSF (5 micrograms/kg/d by 6-hour intravenous infusion) starting during induction chemotherapy on day 1 and continued through and after chemotherapy until recovery of neutrophils, or evidence of regrowth of leukemia, or up to day 28. Induction chemotherapy consisted of idarubicin (8 mg/m2/d on days 1 to 5) and cytarabine (100 mg/m2/d on days 1 to 7). The study drug was not administered subsequent to the induction course. Patients who achieved a CR received continuous maintenance therapy for 1 year with four quarterly reinduction courses; in the 55- to 64-year age subgroup, patients were randomly assigned to receive or not a consolidation course before maintenance therapy. The CR rate was similar in the GM-CSF and placebo groups (63% and 60.5%, respectively; P = .79). The mortality, rate of resistant disease, and rate of regrowth of leukemia were also similar in both groups. The time to neutrophil recovery was shorter in patients who received GM-CSF (24 v 29 days; P = .0001), but the incidence and characteristics of infectious events were not different. The 2-year disease-free survival (DFS) rate was significantly improved in the GM-CSF group (48% v 21% in the placebo group; P = .003). This effect was highly significant in the cohort of patients aged 55 to 64, but only marginal in patients >/=65 years of age. There was a trend toward a longer overall survival (OS) in the GM-CSF group (P = .082). In summary, the administration of GM-CSF, concomitantly with chemotherapy and thereafter during induction course in AML, shortened the time to neutrophil recovery, but did not improve the CR rate in patients aged 55 to 75. Nonetheless, DFS and OS were significantly prolonged in patients aged 55 to 64 treated with GM-CSF. These results are promising and further evaluation of myeloid growth factors in AML is warranted.
- Published
- 1998
28. Ten-year results of a strategy combining three cycles of ABVD and high-dose extended irradiation for treating Hodgkin's disease at advanced stages.
- Author
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Andrieu JM, Jais JP, Colonna P, Desablens B, Brière J, François S, Harousseau JL, Casassus P, Lemevel A, Le Prisé PY, Ghandour C, Guilhot F, and Lejeune F
- Subjects
- Adult, Bleomycin administration & dosage, Combined Modality Therapy, Dacarbazine administration & dosage, Doxorubicin administration & dosage, Female, Follow-Up Studies, Humans, Lymphatic Metastasis, Male, Multivariate Analysis, Prospective Studies, Survival Analysis, Vinblastine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hodgkin Disease drug therapy, Hodgkin Disease radiotherapy, Lymphatic Irradiation
- Abstract
Background: The treatment of Hodgkin's disease (HD) at advanced stages relies mainly upon multi-agent chemotherapies (CT), while the role of radiation therapy has not been definitely identified. The aim of this report is to analyze the 10-year results of a prospective study including 133 patients with HD clinical stages (CS) IIIA to IVB treated by three monthly courses of ABVD (adriamycin, bleomycin, vinblastin, and dacarbazine) followed by high-dose subtotal or total lymphoid irradiation [(S)TLI]., Patients and Methods: From 1 October 1981 to 30 September 1988, 133 adult patients with HD CS IIIA (45), IIIB (33), IVA (seven) and IVB (48) were entered in the non-randomized multicentric prospective trial POF81/34. The number of involved nodal areas (NINA), and the number of visceral sites (NVIS) involved were registered in all patients; patients with bulky mediastinal tumor (BuMT) (mediastinal mass ratio > or = 0.45) were also identified. All patients received three monthly cycles of ABVD. Patients in complete remission (CR) or partial remission (PR) after completion of CT received a (S)TLI including the spleen (involved sites 40 Gy, non-involved 30 Gy); initially involved lung(s) and liver received 18 and 20 Gy, respectively; and patients not in CR or PR after CT or RT received salvage treatments. Univariate and multivariate analyses were performed to identify the factors contributing significantly to the prognosis; initial characteristics, as well as status after the three cycles of CT, were entered in the model., Results: Of the 133 patients, 74 (55.6%) entered in CR after CT and 116 (87.2%) after completion of radiation therapy. Ten-year freedom from progression (FFP), freedom from tumor mortality (FFTM) and survival rates were 70.4%, 78.9% and 70.6%, respectively. According to univariate analysis the NVIS (< or = one vs. > or = two) was the only initial factor simultaneously influencing 10-year FFP (73.9% vs. 38.2%) FFTM (82.5 vs. 34.1%) and survival (73.5% vs. 17.3%) rates; on the other hand, the NINA (< or = four vs. > or = five) influenced FFP (81.4% vs. 60.7%) and FFTM rates (87.3% vs. 71.4%) while symptoms (A vs. B) influenced FFP (80.7% vs. 63.3%) and survival (82.8% vs, 61.2%) rates. Finally, age (< 40 vs. > or = 40) influenced survival rate only (79.2% vs. 50%). According to multivariate analysis, NVIS and NINA had an independent impact on FFP and FFTM, while survival was modified by the NVIS and age. The post-CT status (CR vs. no CR) had a major impact on FFP (85.3% vs. 64.9%) FFTM (92.1% vs. 63.3%) as well as on survival (78.6% vs. 54.7%) rates in both univariate and multivariate analyses. Complications of therapy were mainly due to RT: 11 patients acquired second malignancies, six developed lung fibrosis or severe pulmonary infections, three developed intestinal obstructions and six developed angina pectoris or carotid stenosis., Conclusions: Tumor burden (identified by the number of involved nodal areas and the number of visceral sites) and the response to initial CT were the two independent factors influencing the outcome of this group of 133 patients with HD, CSIII and IV treated by three cycles of ABVD followed by high-dose [(S)TLI].
- Published
- 1998
- Full Text
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29. Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. The Groupe Ouest Est Leucémies Aiguës Myéloblastiques (GOELAM).
- Author
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Harousseau JL, Cahn JY, Pignon B, Witz F, Milpied N, Delain M, Lioure B, Lamy T, Desablens B, Guilhot F, Caillot D, Abgrall JF, Francois S, Briere J, Guyotat D, Casassus P, Audhuy B, Tellier Z, Hurteloup P, and Herve P
- Subjects
- Acute Disease, Adolescent, Adult, Antibiotics, Antineoplastic therapeutic use, Antimetabolites, Antineoplastic therapeutic use, Cytarabine therapeutic use, Daunorubicin analogs & derivatives, Daunorubicin therapeutic use, Humans, Idarubicin therapeutic use, Leukemia, Myeloid drug therapy, Middle Aged, Multivariate Analysis, Outcome Assessment, Health Care, Prognosis, Remission Induction, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Transplantation, Leukemia, Myeloid therapy
- Abstract
Three intensive consolidation strategies are currently proposed to younger adults with acute myeloid leukemia (AML) in first complete remission (CR): allogeneic or autologous bone marrow transplantation (BMT) and intensive consolidation chemotherapy (ICC). Patients aged 15 to 50 years with de novo AML received an induction treatment with 7 days of cytarabine and either idarubicin or rubidazone. After achievement of a CR, patients up to the age of 40 and having an HLA-identical sibling were assigned to undergo an allogeneic BMT. All the other patients received a first course of ICC with high-dose cytarabine and the same anthracycline as for induction. They were then randomly assigned to either receive a second course of ICC with amsacrine and etoposide or a combination of busulfan and cyclosphosphamide followed by an unpurged autologous BMT. Of 517 eligible patients, 367 had a CR, but only 219 (59.5%) actually received the planned intensive postremission treatment (73 allogeneic BMT, 75 autologous BMT, and 71 ICC). With a median follow-up of 62 months, the 4-year disease-free survival (DFS) of the 367 patients in CR was 39.5%. The 4-year overall survival (OS) of the 517 eligible patients was 40.5%. In multivariate analysis, DFS and OS were influenced only by the initial white blood cell count and by the French-American-British classification. The type of postremission therapy had no significant impact on the outcome. There was no difference in the 4-year DFS and OS between 88 patients for whom an allogeneic BMT was scheduled (respectively, 44% and 53%) and 134 patients of the same age category and without an HLA-identical sibling (respectively, 38% and 53%). Similarly, there was no difference in the outcome between autologous BMT and ICC. The 4-year DFS was 44% for the 86 patients randomly assigned to autologous BMT and 40% for the 78 patients assigned to ICC (P = .41). The 4-year OS was similar in the two groups (50% v 54.5%, P = .72). The median duration of hospitalization and thrombocytopenia were longer after autologous BMT (39 v 32 days, P = .006, and 109.5 v 18.5 days, P = .0001, respectively). After a first course of ICC, a second course of chemotherapy is less myelotoxic than an unpurged autologous BMT but yields comparable DFS and OS rates.
- Published
- 1997
30. Is the International Prognostic Index for aggressive lymphomas useful for low-grade lymphoma patients? Applicability to stage III-IV patients. The GOELAMS Group, France.
- Author
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Foussard C, Desablens B, Sensebe L, François S, Milpied N, Deconinck E, Delwail V, Dugay J, Lamy T, Ghandour C, Le Mevel A, Maisonneuve H, Casassus P, and Colombat P
- Subjects
- Humans, L-Lactate Dehydrogenase blood, Lymphoma, Non-Hodgkin therapy, Middle Aged, Neoplasm Staging, Predictive Value of Tests, Prognosis, Prospective Studies, Survival Analysis, Treatment Outcome, Lymphoma, Non-Hodgkin mortality, Lymphoma, Non-Hodgkin pathology, Severity of Illness Index
- Abstract
Background: The International Prognostic Index (IPI) is widely used to predict outcome of patients with aggressive lymphomas. Our goal was to assess the prognostic value of this index for low-grade lymphoma., Patients and Methods: One hundred eighty-two patients with disseminated (stage III or IV) low-grade lymphoma were enrolled in a prospective multicenter trial. According to the initial features, treatment either was started immediately or was deferred until indicated by disease progression. Patients received the same polychemotherapy regimen, given monthly for six cycles. They were assigned to one of four risk groups according to the number of presenting risk factors: low-risk (0 or 1), low-intermediate-risk (2), high-intermediate-risk (3), high-risk groups (4)., Results: Survival curves (Kaplan-Meier method) demonstrated a high significant difference for the four groups (log-rank: P < 0.0001). Median survival for the low-risk group has yet to be reached, while that for the three other groups are, respectively, 65, 34, and 12 months., Conclusions: In this study, the IPI has been found to be an important prognostic tool in low-grade lymphoma and may be used in the selection of appropriate therapeutic approaches for individual patients.
- Published
- 1997
31. Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study.
- Author
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Solary E, Witz B, Caillot D, Moreau P, Desablens B, Cahn JY, Sadoun A, Pignon B, Berthou C, Maloisel F, Guyotat D, Casassus P, Ifrah N, Lamy Y, Audhuy B, Colombat P, and Harousseau JL
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism, Acute Disease, Cells, Cultured, Female, Hematopoiesis drug effects, Humans, Male, Middle Aged, Antineoplastic Agents administration & dosage, Cytarabine administration & dosage, Drug Resistance, Multiple, Leukemia drug therapy, Mitoxantrone administration & dosage, Quinine administration & dosage
- Abstract
A phase III prospective randomized multicenter study was performed to determine whether quinine could improve the response rate of poor-risk acute leukemias (ALs) to standard chemotherapy including a multidrug resistance (MDR)-related cytotoxic agent. The rationale of the study was based on the negative prognostic value of MDR phenotype in ALs and the ability of quinine to reverse this phenotype both in vitro and ex vivo. Three hundred fifteen patients (median age, 49 years; range, 16 to 65) with relapsed (n = 108) or refractory (n = 32) acute myeloblastic leukemia (AML), relapsed (n = 27) or refractory (n = 9) acute lymphoblastic leukemia (ALL), secondary AL (n = 22) or blastic transformation of myelodysplastic syndrome ([MDS] n = 74) or myeloproliferative syndrome ([MPS] n = 43) were randomly assigned to receive mitoxantrone ([MXN] 12 mg/m2/d, days 2 to 5) and cytarabine ([Ara-C] 1 g/m2/12 h, days 1 to 5) alone or in combination with quinine (30 mg/kg/d, days 1 to 5; continuous intravenous infusion beginning 24 hours before MXN infusion). Side effects of quinine were observed in 56 of 161 quinine-treated patients and disappeared in all but four cases after one or two 20% dose decreases. Sera from quinine-treated patients showed increased MXN uptake in an MDR-positive cell line compared with matched sera obtained before quinine infusion. Quinine induced a significant increase in the incidence of nausea, vomiting, mucositis, and cardiac toxicity. A complete response (CR) was observed in 85 of 161 patients (52.8%) from the quinine-treated group versus 70 of 154 patients (45.5%) in the control group (P = .19). The most important differences between quinine and control group CR rates were observed in patients with refractory AMLs and blastic transformation of MDS and MPS. The CR rate was higher in P-glycoprotein-positive cases, although the difference was not significant. Failure of the regimen due to blastic persistence or blast number increase was higher in the control group (61 of 154 patients) than in the quinine group (45 of 161, P = .04). Early death was observed in eight cases (four in each arm) and death in aplasia in 27 cases (20 in quinine group v seven in control group, P = .01). The significant increase of toxicity in the quinine arm could have masked the clinical benefit of MDR reversion in poor-risk ALs.
- Published
- 1996
32. Hodgkin's disease during HIV1 infection: the French registry experience. French Registry of HIV-associated Tumors.
- Author
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Andrieu JM, Roithmann S, Tourani JM, Levy R, Desablens B, le Maignan C, Gastaut JA, Brice P, Raphael M, and Taillan B
- Subjects
- Adolescent, Adult, Aged, Female, France epidemiology, HIV Infections epidemiology, Hodgkin Disease epidemiology, Hodgkin Disease mortality, Humans, Lymphoma, AIDS-Related epidemiology, Lymphoma, AIDS-Related etiology, Male, Middle Aged, Prognosis, Registries, Survival Rate, HIV Infections complications, HIV-1, Hodgkin Disease complications
- Abstract
Background: The first cases of Hodgkin's disease (HD) associated with HIV infection were reported in 1984. Since then, short series of seropositive patients suffering from HD have been published. In order to identify the characteristics, treatment response and outcome of HIV-associated Hodgkin's disease (HIV-HD), the data of HIV-HD patients recorded between 1987 and 1989 were analysed and compared with those of primary HD patient and with those of HIV-associated non-Hodgkin's lymphoma (HIV-NHL), registered during the same period., Patients and Methods: The 45 cases of HD collected by the French registry of HIV-associated tumors between January 1987 and December 1989 were included in this study. All patients were clinically staged according to the Ann Arbor system. To compare HIV-HD characteristics with those of primary HD, we used a cohort of 407 patients with clinical stages (CS) IA to IVB, who were enrolled between September 1981 and August 1988 in a multicentric clinical trial. To identify the relationship between HIV-HD and the course of HIV infection we studied, when available, the routes of infection, initial CD4 cell count at the moment of HD diagnostic as well as the CDC class of HIV infection and compared these data with the same parameters observed in 142 HIV-NHL enrolled in the registry during the same period., Results: HIV-HD is characterized by an increase in mixed-cellularity histology (49%), with a predominance of advanced stages (75%) and B symptoms (80%). A unique observation is made regarding mediastinal involvement, present in only 13% of HIV-HD (71% in primary HD). The HIV-HD/HIV-NHL ratio was significantly higher in intravenous drug abusers than in male homosexuals. Median CD4 cell count was 306/microliters at HIV-HD diagnosis, and only 11% of the cases were preceded by an AIDS manifestation. With standard therapy, 79% of the patients achieved complete remission, but hematological and infectious complications were very frequent. The progression to AIDS rate was 94% at two years and opportunistic infections were the most frequent cause of death. Overall two-year survival was 41% with 71% for patients with initial CD 4 cell counts higher than 300/microliter and 0% for those with CD4 cell counts lower than 300/microliter (P < 0.01)., Conclusion: HIV-HD has a particular clinico-pathological profile when compared to primary HD, with a predominance of mixed-cellularity type, a high frequency of advanced stages and a high proportion of patients without mediastinal involvement. Moreover, HIV-HD seems to occur preferentially in the group of subjects infected by needle sharing. Standard HD therapy seems to be efficient but excessively toxic.
- Published
- 1993
- Full Text
- View/download PDF
33. Home treatment of febrile neutropenia: an empirical oral antibiotic regimen.
- Author
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Gardembas-Pain M, Desablens B, Sensebe L, Lamy T, Ghandour C, and Boasson M
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Amoxicillin administration & dosage, Anti-Bacterial Agents administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Clavulanic Acid, Clavulanic Acids administration & dosage, Drug Administration Schedule, Female, Fever drug therapy, Fever etiology, Humans, Leukopenia chemically induced, Lymphoma complications, Lymphoma drug therapy, Male, Middle Aged, Neutropenia chemically induced, Pefloxacin administration & dosage, Prospective Studies, Drug Therapy, Combination therapeutic use, Neutropenia drug therapy
- Abstract
Between May 1988 and November 1989, 68 consecutive febrile courses supervening after polychemotherapy for lymphoma outpatients (median age 50 years) were treated by the combination of oral Pefloxacin/Amoxicillin Clavulanic acid. In terms of median data, neutropenia appeared on d9 [d1-d17], and lasted 5 days [2-9] with a PMN nadir observed at 0.104 x 10(9) [0-0.5 x 10(9)/l], while fever rose on d10 [1-24]. In 59 cases (87%), fever and/or focal symptoms disappeared within 3 days, after which treatment was maintained for 7 days. Nine failures were observed, of which 2 were due to abandonment of treatment, 2 to vomiting and 5 to persistence of the original symptoms. Meti Susceptible-Staphylococci were found in blood samples from 2 patients, one of whom, with grade IV lymphoma that had proved resistant to chemotherapy, died. The treatment was found to be effective and well tolerated, offering a good alternative to hospitalization during a transient chemotherapy-induced neutropenia.
- Published
- 1991
- Full Text
- View/download PDF
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