569 results on '"Cahn, J.-Y."'
Search Results
302. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. French Society of Haematology.
- Author
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Socié G, Mary JY, de Gramont A, Rio B, Leporrier M, Rose C, Heudier P, Rochant H, Cahn JY, and Gluckman E
- Subjects
- Adolescent, Adult, Anemia, Aplastic complications, Cause of Death, Child, Female, Follow-Up Studies, Hemoglobinuria, Paroxysmal complications, Humans, Male, Middle Aged, Multivariate Analysis, Prognosis, Risk Factors, Survival Analysis, Thrombosis complications, Time Factors, Hemoglobinuria, Paroxysmal mortality
- Abstract
Background: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired disorder of haematopoietic stem cells. Although knowledge about the pathophysiology of the disease is increasing, no multivariate analysis of factors influencing survival has been undertaken, mainly because the disease is rare. We undertook such an investigation., Methods: Data were collected on 220 patients with PNH diagnosed over a 46-year period (1950-1995) from participating French centres. Diagnosis of the disease required, at least, an unequivocally positive Ham's test., Findings: The Kaplan-Meier survival estimate was 65% (SE 4) at 10 years and 48% (6) at 15 years after diagnosis. 8-year cumulative incidence rates of the main complications (pancytopenia, thrombosis, and myelodysplastic syndrome) were 15% (3), 28% (4), and 5% (2), respectively. Demographic data, presenting features, initial treatment, complications, and causes of death were similar to those previously reported. In multivariate analysis, seven factors were significantly associated with survival in patients with PNH. Poor survival was associated with the occurrence of thrombosis as a complication (relative risk 10.2 [95% CI 6-17], p < 0.0001), evolution to pancytopenia (5.5 [2.8-11], p < 0.0001), myelodysplastic syndrome or acute leukaemia (19.1 [7.3-50], p < 0.001), age over 55 years at diagnosis (4 [2.4-6.9], p < 0.0001), need for additional treatment (2.1 [1.3-3.6], p < 0.003), and thrombocytopenia at diagnosis (2.2 [1.3-3.8, p < 0.003). Better survival was shown for patients in whom aplastic anaemia antedated PNH (0.32 [0.14-0.72], p < 0.02). Factors associated in multivariate analysis with a high risk of thrombosis during the disease course were thrombosis at diagnosis (5.1 [2.5-10.6], p = 0.0002), age over 54 years (2.6 [1.5-4.6, p = 0.0014), and infection at diagnosis (2.6 [1.3-5.2], p = 0.0099). The risk factors for progression to pancytopenia were absence at diagnosis of anaemia (4.03 [1.3-12.2], p = 0.03) and neutropenia (2.45 [1.1-5.7], p = 0.03). The risk factors for development of myelodysplastic syndrome or acute leukaemia were abdominal pain crisis at presentation (10.5 [2.5-44.0], p = 0.004) and year of diagnosis after 1983 (8.45 [1.8-40.7], p = 0.004)., Interpretation: This large number of cases permitted a detailed analysis of prognostic factors for the first time, in this rare disease. Estimates of PNH prognostic factors may serve as baseline data in the assessment of current and future treatments for this disease.
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- 1996
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303. Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study.
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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
304. Treatment of acute myelogenous leukaemia in patients aged 50-65: idarubicin is more effective than zorubicin for remission induction and prolonged disease-free survival can be obtained using a unique consolidation course. The Goelam Group.
- Author
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Pignon B, Witz F, Desablens B, Leprise PY, Francois S, Linassier C, Berthou C, Caillot D, Lioure B, Cahn JY, Casassus P, Sadoun A, Audhuy B, Guyotat D, Briere J, Vilque JP, Baranger L, Polin V, Berthaud P, Hurteloup P, Herve P, and Harousseau JL
- Subjects
- Aged, Daunorubicin therapeutic use, Disease-Free Survival, Female, Humans, Male, Middle Aged, Remission Induction, Survival Analysis, Survival Rate, Treatment Outcome, Antibiotics, Antineoplastic therapeutic use, Daunorubicin analogs & derivatives, Idarubicin therapeutic use, Leukemia, Myeloid, Acute drug therapy
- Abstract
From December 1987 to June 1992, 251 patients aged 50-65 with de novo acute myelogenous leukaemia (AML) were recruited to a multi-institutional randomized clinical trial. Induction therapy consisted of Ara-C (200 mg/ m2, continuous infusion, days 1-7) with either zorubicin (ZRB) (200 mg/m2, i.v., days 1-4) or idarubicin (IDR) (8 mg/ m2, i.v., days 1-5). Consolidation therapy consisted of a single course of intensive chemotherapy with high-dose Ara-C (3 g/m2, 3 h infusion, q 12 h, days 1-4) and m-Amsa (100 mg/m2/d, i.v., days 5-7). The complete remission (CR) rate was (73%) with Ara-C/ IDR versus (60%) with Ara-C/ZRB (P = 0.033). In multivariate analysis, factors found to be significant in predicting CR were normal karyotype and treatment with IDR. With a median follow-up of 73 months, the median disease-free survival (DFS) duration of all CR patients and the probability of CR at 6 years were 17 months and 29%. In multivariate analysis the only factor associated with an increased DFS duration was a normal karyotype. The median event-free survival (EFS) duration for all evaluable patients and the median overall survival duration for all eligible patients were respectively 7 and 12 months without any difference between induction arms. The study shows that in patients aged 50-65 idarabicin is more effective than zorubicin for remission induction. However, the type of anthracycline did not influence overall survival duration. Using a unique consolidation course, we observed a prolonged DFS which compares favourably with results obtained with more prolonged consolidation therapy or maintenance treatment.
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- 1996
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305. Factors influencing outcome in de novo myelodysplastic syndromes treated by allogeneic bone marrow transplantation: a long-term study of 71 patients Société Française de Greffe de Moelle.
- Author
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Sutton L, Chastang C, Ribaud P, Jouet JP, Kuentz M, Attal M, Reiffers J, Tigaud JM, Rio B, Dauriac C, Legros M, Dreyfus F, Lioure B, Troussard X, Milpied N, Witz F, Oriol P, Cahn JY, Michallet M, Gluckman E, Ifrah N, Pico JL, Vilmer E, and Leblond V
- Subjects
- Adult, Anemia, Refractory mortality, Anemia, Refractory therapy, Anemia, Refractory, with Excess of Blasts mortality, Anemia, Refractory, with Excess of Blasts therapy, Busulfan pharmacology, Cyclophosphamide pharmacology, Disease Progression, Disease-Free Survival, Female, Follow-Up Studies, France epidemiology, Humans, Life Tables, Male, Middle Aged, Myelodysplastic Syndromes mortality, Proportional Hazards Models, Remission Induction, Transplantation, Homologous, Treatment Outcome, Whole-Body Irradiation, Bone Marrow Transplantation mortality, Myelodysplastic Syndromes therapy
- Abstract
We report on 71 consecutive patients with de novo myelodysplastic syndromes referred to physicians belonging to the Société française de greffe de moelle from 1982 through 1991 and transplanted with marrow from HLA-identical siblings. There were 16 cases of refractory anemia, 27 of refractory anemia with excess of blast cells, and 28 of refractory anemia with excess of blast cells in transformation. Seventeen patients had received cytoreductive chemotherapy before the graft. The disease progressed in 17 patients between diagnosis and grafting. Twenty-three patients are alive with a median follow-up of 6 years, whereas 24 died from relapse and 24 from transplant-related complications. Kaplan-Meier estimates of event-free survival, relapse and transplant-related mortality at 7 years were 32%, 48%, and 39%, respectively. The log-rank test and Cox's model revealed better outcome among young patients, patients in an early stage of the French-American-British (FAB) classification or with a low percentage of marrow blasts before transplantation, patients who did not undergo cytoreductive chemotherapy before transplantation, and patients conditioned with total body irradiation and cyclophosphamide. The high rate of relapse in advanced FAB stages has led us to graft patients earlier in the course of the disease, and we are currently conducting a multicenter, randomized study to determine the value of intensive chemotherapy before grafting in patients with an excess of marrow blasts.
- Published
- 1996
306. [Hematopoietic stem cell transplantation].
- Author
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Deconinck E and Cahn JY
- Subjects
- Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Humans, Immunosuppressive Agents therapeutic use, Patient Isolation, Hematopoietic Stem Cell Transplantation nursing
- Published
- 1996
307. [Transplantation of hematopoietic stem cells. The transplantation unit. History and function].
- Author
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Morel N, Deconinck E, and Cahn JY
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- Hematopoietic Stem Cell Transplantation nursing, Hematopoietic Stem Cell Transplantation trends, Humans, Hematopoietic Stem Cell Transplantation methods, Intensive Care Units organization & administration
- Published
- 1996
308. Gene transfer applied to the modulation of alloreactivity.
- Author
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Tiberghien P, Cahn JY, Contassot E, Ferrand C, Reynolds CW, and Hervé P
- Subjects
- Humans, Leukemia therapy, Simplexvirus enzymology, Thymidine Kinase genetics, Transplantation, Homologous, Gene Transfer Techniques, Hematopoietic Stem Cell Transplantation
- Abstract
Allogenic hematopoietic stem cell transplantation is associated with a severe complication induced by the T-cells present in the graft: graft-vs-host disease (GVHD). While effectively preventing GVHD, ex vivo T-lymphocyte depletion of the graft unfortunately increases graft rejection and reduces the graft-vs-leukemia (GVL) effect. The ex vivo transfer to the herpes simplex thymidine kinase (HS-tk) suicide gene into T-cells before their infusion with the hematopoietic stem cells should allow for selective in vivo depletion of these T-cells with ganciclovir (GCV) if subsequent GVHD was to occur. In patients not experiencing GVHD, and therefore at a higher risk of relapse, one could preserve the beneficial effects of the donor T-cells on tumor control. Lastly, the early presence of donor T-cells in all patients should contribute to successful engraftment. We have demonstrated that retroviral-mediated transfer of HS-tk and Neomycine resistance genes in T-lymphocytes, followed by G418 selection, results in T-cells specifically inhibited by GCV with no bystander effect. In a phase I study, escalating amounts of HS-tk expressing T-cells will be infused in conjunction with a T-cell depleted marrow graft to allogenic HLA identical recipients. Toxicity, survival, alloreactivity and GCV-sensitivity of the gene-modified cells will be monitored. If successful, such an approach could significantly contribute to expanding the use of alloreactivity as a treatment modality.
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- 1996
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309. Evidence that a transient enhancement of endogenous hematopoiesis contributes significantly to the favorable outcome following interleukin 1 pretreatment and allogeneic bone marrow transplantation.
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Herve V, Mabed M, Laithier V, Pavy JJ, Angonin R, Contassot E, Certoux JM, Cahn JY, Herve P, and Tiberghien P
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- Animals, Graft Survival drug effects, Male, Mice, Mice, Inbred BALB C, Whole-Body Irradiation, Bone Marrow Transplantation immunology, Hematopoiesis drug effects, Interleukin-1 pharmacology, Radiation-Protective Agents pharmacology
- Abstract
The administration of IL-1, a potent radioprotective cytokine, before allogeneic BMT is associated with an early transient increase of circulating granulocytes, successful engraftment, and accelerated multilineage hematopoietic recovery. We have examined the effects of IL-1 alpha pretreatment on the engraftment of an allogeneic BMT unable to sustain survival by itself after a lethal irradiation: (1) transplantation of a limited amount of marrow cells and (2) transplantation several days after irradiation. IL-1 was unable to allow the engraftment of an early quantitatively inadequate BMT. However, delayed BMT with limited amounts of marrow cells was associated with engraftment in IL-1 pretreated recipients. Engraftment of a late (day 12) BMT in these IL-1-pretreated mice was comparable to the engraftment of a similar day 12 allogeneic BMT in non-IL-1-pretreated mice rescued from the lethal irradiation by an early (day 1) syngeneic graft. These findings demonstrate that IL-1 pretreatment can result in a dissociation between BMT-induced survival and engraftment and suggest that the favorable effects of IL-1 pretreatment in an allogeneic BMT setting are mainly mediated through a transient enhancement of endogenous hematopoiesis and not through a direct effect on the allogeneic stem cells present in the marrow graft.
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- 1996
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310. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma.
- Author
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Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, and Harousseau JL
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- Adolescent, Adult, Carmustine administration & dosage, Cisplatin administration & dosage, Combined Modality Therapy, Cyclophosphamide administration & dosage, Cytarabine administration & dosage, Dexamethasone administration & dosage, Etoposide administration & dosage, Female, Humans, Lymphoma, Non-Hodgkin mortality, Lymphoma, Non-Hodgkin radiotherapy, Male, Mesna administration & dosage, Middle Aged, Prospective Studies, Recurrence, Survival Analysis, Transplantation, Homologous, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Transplantation, Lymphoma, Non-Hodgkin drug therapy, Lymphoma, Non-Hodgkin therapy, Salvage Therapy
- Abstract
Background: High-dose chemotherapy followed by autologous bone marrow transplantation is a therapeutic option for patients with chemotherapy-sensitive non-Hodgkin's lymphoma who have relapses. In this report we describe a prospective randomized study of such treatment., Method: A total of 215 patients with relapses of non-Hodgkin's lymphoma were treated between July 1987 and June 1994. All patients received two courses of conventional chemotherapy. The 109 patients who had a response to chemotherapy were randomly assigned to receive four courses of chemotherapy plus radiotherapy (54 patients) or radiotherapy plus intensive chemotherapy and autologous bone marrow transplantation (55 patients)., Results: The overall rate of response to conventional chemotherapy was 58 percent; among patients with relapses after chemotherapy, the response rate was 64 percent, and among those with relapses during chemotherapy, the response rate was 21 percent. There were three deaths from toxic effects among the patients in the transplantation group, and none among those in the group receiving chemotherapy without transplantation. The two groups did not differ in terms of prognostic factors. The median follow-up time was 63 months. The response rate was 84 percent after bone marrow transplantation and 44 percent after chemotherapy without transplantation. At five years, the rate of event-free survival was 46 percent in the transplantation group and 12 percent in the group receiving chemotherapy without transplantation (P = 0.001), and the rate of overall survival was 53 and 32 percent, respectively (P = 0.038)., Conclusions: As compared with conventional chemotherapy, treatment with high-dose chemotherapy and autologous bone marrow transplantation increases event-free and overall survival in patients with chemotherapy-sensitive non-Hodgkin's lymphoma in relapse.
- Published
- 1995
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311. Treatment of acute graft-versus-host disease with methylprednisolone and cyclosporine with or without an anti-interleukin-2 receptor monoclonal antibody. A multicenter phase III study.
- Author
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Cahn JY, Bordigoni P, Tiberghien P, Milpied N, Brion A, Widjenes J, Lioure B, Michel G, Burdach S, and Kolb HJ
- Subjects
- Acute Disease, Adolescent, Adult, Child, Child, Preschool, Double-Blind Method, Female, Graft vs Host Disease drug therapy, Graft vs Host Disease physiopathology, Humans, Immunosuppression Therapy methods, Male, Middle Aged, Placebos, Transplantation, Homologous, Antibodies, Monoclonal therapeutic use, Bone Marrow Transplantation immunology, Cyclosporine therapeutic use, Graft vs Host Disease therapy, Immunosuppressive Agents therapeutic use, Methylprednisolone therapeutic use
- Abstract
A double-blind, placebo-controlled trial of BT563, including 13 European centers, was initiated in October 1989 to compare the efficacy of the combination of in vivo anti-CD25 mAb (BT 563), cyclosporine, and steroids versus placebo and CSA-steroids in the treatment of grade II and III acute graft-versus-host disease (GVHD). Sixty-nine patients participated in the study, which excluded non-genotypically identical allogeneic bone marrow transplant recipients. No statistically significant differences were observed, clinically or biologically, between the 2 groups before the onset of the treatment. Treatment responses were scored during and after the 3-week treatment period (mAb or placebo). Efficacy was evaluated on days 4, 10, 20, 30, and 60 or on any day the patient's condition was found to be deteriorating. Preceding and systemically untreated GVHD of grade I was observed in 59% of the cases. No statistically clinically significant differences between the 2 groups were observed during or upon completion of treatment in GVHD grade. Nine patients in the placebo group and 6 in the active group were withdrawn of the study. Thirteen of these 15 patients were withdrawn because of failure of GVHD therapy (9 in the placebo group and 4 in the BT563 group). At day 20 after onset of the treatment, the response rate was 63% and 70% for the placebo and BT563 groups, respectively (NS). Probability of survival at 1 year was 59% and 66% (NS) for the placebo and active groups, respectively. In conclusion, despite preliminary promising results in the treatment of steroid-resistant acute GVHD, the role of first-line treatment with an in vivo anti-interleukin-2 receptor mAb remains to be determined.
- Published
- 1995
312. [Pseudomonas aeruginosa septicemia. Host-related risk factors in 82 episodes].
- Author
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Roche O, Beuhorry-Sassus F, Boillot A, Dupont MJ, Plésiat P, Talon D, Cahn JY, and Michel-Briand Y
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- Adolescent, Adult, Aged, Aged, 80 and over, Analysis of Variance, Anti-Bacterial Agents therapeutic use, Bacteremia drug therapy, Child, Child, Preschool, Female, Humans, Infant, Male, Middle Aged, Multivariate Analysis, Prognosis, Pseudomonas Infections drug therapy, Retrospective Studies, Risk Factors, Bacteremia mortality, Pseudomonas Infections mortality
- Abstract
Objectives: The prognosis of septicaemia due to Pseudomonas aeruginosa is severe with mortality ranging from 32 to 73%. We retrospectively studied 82 episodes in order to determine whether risk factors could be identified., Methods: Eighty-two episodes of Pseudomonas aeruginosa septicaemia, observed between 1986 and 1991, were analyzed. Risk of death within 2 days of the first positive blood culture (mortality = 19.5%) were assessed with univariate and multivariate analyses., Results: Patient age ranged from 1 to 92 years. Most had been hospitalized in medical wards (49%) or intensive care units (28%) (NS). The type of septicaemia (several bacteria in 21%), the source of the infection (nosocomial in 78%), portal, predisposing factors (cancer, haematologic disease: 54%) and MacCabe index were not significantly correlated with risk of death at two days following first positive blood culture. With univariate analysis body temperature below 38,5 degrees C was significant (p = 0.007) for death at day 2 and appropriate antibiotic treatment after diagnosis was significant (p < 0.001) for absence of death on day 2. For multivariate analysis, chemotherapy and shock syndrome were significant (p = 0.005 and 0.09 respectively) for death at day 2 and appropriate antibiotic treatment was significant (p = 0.005) for absence of death on day 2., Conclusion: Antibiotic prescription appears to be the most easily controlled significant factor predictive of outcome in Pseudomonas aeruginosa septicaemia.
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- 1995
313. Recombinant alpha-interferon as treatment for chronic myelogenous leukemia in relapse after allogeneic bone marrow transplantation: a report from the Société Française de Greffe de Moelle.
- Author
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Pigneux A, Devergie A, Pochitaloff M, Rio B, Archimbaud E, Cahn JY, Leblond V, Michallet M, Jouet JP, and Guilhot F
- Subjects
- Adolescent, Adult, Biomarkers, Tumor analysis, Female, France epidemiology, Fusion Proteins, bcr-abl analysis, Humans, Interferon alpha-2, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Life Tables, Male, Middle Aged, Neoplasm Proteins analysis, Recombinant Proteins, Remission Induction, Reoperation, Retrospective Studies, Survival Analysis, Treatment Outcome, Bone Marrow Transplantation, Immunologic Factors therapeutic use, Interferon-alpha therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Salvage Therapy
- Abstract
Thirty three patients with Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) in relapse after allogenic bone marrow transplantation (BMT) were treated with recombinant alpha-interferon (IFN). Ten patients received IFN for cytogenetic relapse (group I) and 23 (group II) for hematologic relapse. The starting dose of IFN varied from 1.7 to 6 million units/m2/day (median 3 x 10(6) U/m2/day). Among the 10 group I patients, 3 subsequently developed hematologic relapse. Of the other 7, a cytogenetic response was observed in 6 (complete 4, minor 2). Three of these responders are alive in complete cytogenetic remission. Of the 23 group II patients, 3 did not respond to IFN but 20 achieved a complete (CHR) (n = 14) or a partial hematologic response (PHR) (n = 6). Thirteen of the 14 CHR patients subsequently achieved a cytogenetic response (complete 7, minor 6). Seven of the latter 13 patients are still alive in complete cytogenetic remission (CCR). Thus, for the entire group of 33 patients, IFN was followed by CCR in 11 cases (33%); all these patients are still alive and the median follow-up in CCR is now 60.7 months (range 35.3-72.5 months). The BCR-ABL rearrangement was not detected by RT-PCR in 5 of the 10 patients analyzed. Eleven other patients developed either blast crisis or acceleration. The 3-year probability of survival from the start of IFN therapy probability of survival from the start of IFN therapy was 70 +/- 16% (95% CI) and was statistically higher for patients who achieved CCR than for the others.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1995
314. Sequential use of three monoclonal antibodies in corticosteroid-resistant acute GVHD: a multicentric pilot study including 15 patients.
- Author
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Racadot E, Milpied N, Bordigoni P, Cahn JY, Plouvier E, Lioure B, Lutz P, Wijdenes J, and Herve P
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- Acute Disease, Adolescent, Adrenal Cortex Hormones therapeutic use, Adult, Child, Cytokines blood, Drug Resistance, Drug Therapy, Combination, Female, Graft vs Host Disease immunology, Humans, Male, Middle Aged, Pilot Projects, Recombinant Proteins immunology, Antibodies, Monoclonal therapeutic use, Bone Marrow Transplantation immunology, CD2 Antigens immunology, Graft vs Host Disease drug therapy, Interleukin-2 immunology, Tumor Necrosis Factor-alpha immunology
- Abstract
We previously demonstrated the potential of anti-IL-2R and anti-TNF alpha moAbs in the treatment of acute graft-versus-host disease (GVHD). However, one major problem was the recurrence of acute GVHD on treatment discontinuation. To target the two main effectors of acute GVHD lesions, T and NK cells on the one hand and TNF alpha on the other, we combined anti-CD2 and anti-TNF alpha moAbs. Then to prevent acute GVHD recurrence, we administered anti-IL-2R moAbs known for their inhibitory effect on activated cells. We included 15 patients with steroid-resistant acute GVHD. Seven were grafted from a genotypically-identical sibling, 5 from HLA-matched unrelated donors and 3 from partially-matched related donor. Prophylaxis of acute GVHD consisted of cyclosporin A +/- methotrexate or corticosteroids. Before treatment 6 patients had grade II, 2 patients grade III and 7 patients grade IV acute GVHD. Anti-TNF alpha (B-C7) moAbs (10 mg/day/4 days) were combined with anti-CD2 (B-E2) moAbs (10 mg/day/10 days) on the fifth day (day 5), anti-IL-2 receptor (B-B10) moAbs were given at 10 mg/day/10 days followed by 5 mg every other day for another 50 days. On day 15, 5 patients achieved a complete remission, 4 a very good partial response (62% a good response), 2 had a partial response and 4 did not respond. GVHD recurred in 4 of the 9 responders, although anti-IL-2R moAb treatment was maintained. Three patients are long-term survivors without chronic GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1995
315. Allogeneic bone marrow transplantation for chronic myeloid leukemia in first chronic phase: a randomized trial of busulfan-cytoxan versus cytoxan-total body irradiation as preparative regimen: a report from the French Society of Bone Marrow Graft (SFGM).
- Author
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Devergie A, Blaise D, Attal M, Tigaud JD, Jouet JP, Vernant JP, Bordigoni P, Ifrah N, Dauriac C, and Cahn JY
- Subjects
- Adolescent, Adult, Busulfan adverse effects, Child, Cyclophosphamide adverse effects, Disease-Free Survival, Female, Humans, Immunosuppressive Agents pharmacology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Leukemia, Myelogenous, Chronic, BCR-ABL Positive radiotherapy, Leukemia, Myeloid, Chronic-Phase drug therapy, Leukemia, Myeloid, Chronic-Phase radiotherapy, Life Tables, Male, Middle Aged, Prospective Studies, Survival Analysis, Treatment Outcome, Bone Marrow Transplantation, Busulfan therapeutic use, Cyclophosphamide therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Leukemia, Myeloid, Chronic-Phase therapy, Whole-Body Irradiation adverse effects
- Abstract
From March 1988 to March 1991, 19 French bone marrow transplant (BMT) centers participated in a prospective randomized trial comparing two conditioning regimens for patients with chronic myeloid leukemia transplanted in first chronic phase with an HLA identical sibling donor. A total of 120 consecutive patients were randomized to receive either 120 mg/kg of cyclophosphamide followed by total body irradiation (CY-TBI; n = 55) or 16 mg/kg of busulfan followed by 120 mg/kg of CY (BU-CY; n = 65). Two different TBI regimens were used. Thirteen patients received a 10-Gy single-dose TBI (SDTBI), and 42 received a fractionated TBI (FTBI). Median time between diagnosis and BMT was 315 days. Overall 5-year actuarial survival was 62.9% (65.8% +/- 12.5% for CY-TBI and 60.6 +/- 11.7% for BU-CY; P = .5), and overall disease-free survival was 55% (51% +/- 14% for CY-TBI and 59.1% +/- 11.8% for BU-CY; P = .75). All patients conditioned with CY-TBI experienced sustained engraftment; in contrast, 4 of 65 patients conditioned with BU-CY rejected the graft (P = .18). There was no significant statistical difference between the two groups regarding transplant-related mortality (29% for CY-TBI and 38% for BU-CY; P = .44). So far, with a median follow up of 42 months, 11 patients have relapsed; 9 relapses occurred after CY-TBI, mostly after FTBI (8 of 9) and 2 after BU-CY (P = .02). The actuarial risk of relapse was 4.4% +/- 6.7% after BU-CY, 11.1% +/- 20.8% after SDTBI, and 31.3% +/- 18.1% after FTBI (P = .039). In addition, independently of the conditioning regimen, the increase of posttransplant immunosuppression in 16 patients with an anti-interleukin-2 receptor monoclonal antibody (MoAb) in addition to a short course of methotrexate and cyclosporine was shown to increase the actuarial risk of relapse (57% +/- 30% with MoAb v 9% +/- 7.3% without MoAb; P = .001). We conclude that BU is an acceptable alternative to TBI for patients with chronic myeloid leukemia in first chronic phase receiving BMT from HLA identical sibling donors. Both BU-CY and CY-TBI regimens gave similar transplant-related mortality, and the antileukemic efficiency of BU-CY regimen was either similar or even higher than that of CY-TBI.
- Published
- 1995
316. Autologous bone marrow transplantation for first remission acute myeloblastic leukemia in patients older than 50 years: a retrospective analysis of the European Bone Marrow Transplant Group.
- Author
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Cahn JY, Labopin M, Mandelli F, Goldstone AH, Eberhardt K, Reiffers J, Ferrant A, Franklin I, Hervé P, and Gratwohl A
- Subjects
- Acute Disease, Age Factors, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Purging, Cause of Death, Cohort Studies, Combined Modality Therapy, Europe, Feasibility Studies, Female, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Myeloid drug therapy, Leukemia, Myeloid mortality, Male, Middle Aged, Multivariate Analysis, Remission Induction, Retrospective Studies, Risk Factors, Survival Analysis, Treatment Outcome, Whole-Body Irradiation, Bone Marrow Transplantation, Leukemia, Myeloid therapy
- Abstract
High-dose chemotherapy, with or without radiotherapy, followed by autologous stem-cell rescue is used increasingly for the intensification of first remission in acute myeloblastic leukemia (AML). However, these treatments have been limited to young patients due to the increased risks of regimen-related toxicities and mortality with age. Several investigators have recently published the upper age limit for autologous bone marrow transplant (ABMT) in AML because of encouraging results. The results of ABMT for AML were studied in 111 patients > or = 50 years of age intensified in first remission. Median age at transplant was 53 years (range, 50 to 63 years). Fifty patients were conditioned with total body irradiation and 61 with polychemotherapy: 23 with busulfancyclophosphamide, 11 with the University College Hospital (UCH; London, UK) regimen, 6 with BAVC, and 21 with various other treatments. Marrow was purged in only 11 cases. Results were compared with 786 ABMTs performed for AML in patients between 16 and 49 years of age (median, 35 years). For AML in first remission, the probability of leukemia-free survival (LFS) at 4 years was 34% +/- 5% for patients aged 50 years or more and 43% +/- 2% for patients less than 50 years of age (P = .004), with a survival probability of 35% +/- 6% and 48% +/- 2%, respectively (P = .004). The probability of relapse was not significantly different between the two groups (52% +/- 7% v 50% +/- 2%), but transplant-related mortality was significantly higher in the older age group (28% +/- 5% v 14% +/- 2%; P < .0001) and mainly due to infectious complications. In a multivariate analysis, age less than 50 years was a favorable risk factor for LFS, treatment-related mortality (TRM), and survival but not for relapse incidence. These data suggest that ABMT should be considered in older AML patients.
- Published
- 1995
317. [Listeriosis in patients with malignant hemopathy. 3 cases in the same hospital ward].
- Author
-
Fontan J, Brion A, Deconinck E, Flesch M, Vuillier J, Rozenbaum A, Csaszar M, Dupont MJ, Michel-Briand Y, and Cahn JY
- Subjects
- Aged, Female, France epidemiology, Hospital Departments, Humans, Leukemia immunology, Listeriosis epidemiology, Listeriosis transmission, Lymphoma immunology, Male, Middle Aged, Retrospective Studies, Immunocompromised Host, Leukemia complications, Listeriosis etiology, Lymphoma complications
- Abstract
During the listeriosis epidemic which occurred in France in the summer 1992, three patients with malignant haematopathies hospitalized in our service contracted the disease. Although the retrospective investigations were hindered by the variable incubation period and the impossibility of examining the foods eaten at the time of infection, there was a high probability that two of the patients had been infected by cooked ham and dairy products at home. The third patient was apparently infected in hospital with well-cooked food found to be contaminated. The hypothesis of coinfection has been raised.
- Published
- 1995
318. Herpes virus-related lymphoproliferative disorders following allogeneic bone marrow transplantation: clinical and biological characteristics of six cases.
- Author
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Brion A, Cahn JY, Mougin C, Angonin R, Flesch M, Deschaseaux ML, Plouvier E, Deconinck E, Voillat L, and Racadot E
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Immunophenotyping, In Situ Hybridization, Leukemia therapy, Lymphoproliferative Disorders diagnosis, Male, Retrospective Studies, Transplantation, Homologous, Bone Marrow Transplantation adverse effects, Herpesviridae isolation & purification, Lymphoproliferative Disorders virology
- Abstract
The present paper describes six cases of lymphoproliferative disorders (LPD) occurring after bone marrow transplantation. Treatments were ineffective and disease was rapidly fatal in all patients, although immunotyping of cells in blood, bone marrow or cerebrospinal fluid was helpful to establish the diagnosis of LPD. Monoclonality was demonstrated in the 4 cases which it was possible to analyse. Herpes virus genome was present in tumoral cells of 4 in 4 cases tested for EBV, one in 3 cases tested for CMV, one in 3 cases tested for HHV6 and 3 in 3 cases tested for HSV. Patients developing LPD should benefit from earlier diagnosis and new therapeutic approaches such as donor lymphocyte infusions, while further studies are necessary to elucidate the role of Herpes viruses in the pathogenesis of LPD.
- Published
- 1995
319. Pharmacokinetics of a more reliable Chloraminophene formulation.
- Author
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Maboundou CW, Magnette J, Paintaud G, Dupond JL, Fest T, Najman A, Solary E, Xicluna A, Sirito A, and Cahn JY
- Subjects
- Aged, Aged, 80 and over, Capsules, Chlorambucil administration & dosage, Chlorambucil adverse effects, Cross-Over Studies, Female, Humans, Male, Middle Aged, Tablets, Therapeutic Equivalency, Chlorambucil pharmacokinetics
- Abstract
The pharmacokinetics of two formulations of chlorambucil, Chloraminophene capsules and Chloraminophene tablets, were compared in 12 patients in a randomized cross-over study. Chlorambucil concentrations in plasma were measured by HPLC over a period of 24 h after drug intake. The peak concentration (Cmax) occurred earlier after administration of capsules than after administration of tablets [median (range)]: 0.50 (0.33-0.66) h vs 2.00 (0.66-4.00) h (p < 0.01). Although values of Cmax and the area under the plasma concentration versus time curve (AUC) were not significantly different, the two formulations were not bioequivalent. Tolerance was in both cases acceptable, with only a transient decrease in haemoglobin one day after last drug intake. The variability of chlorambucil pharmacokinetics tended to be less important for capsules than for tablets: 38% vs 71% and 35% vs 113% for Cmax and AUC respectively. Capsules are therefore likely to be more reliable than tablets for clinical use.
- Published
- 1995
320. [Veno-occlusive disease of the liver after bone marrow transplantation. Report of the symposium Autograft in France and the group of study of bone marrow transplantation. France Auto-Greffe et le Groupe d'Etude de la Greffe de Moelle osseuse].
- Author
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Rio B, Cahn JY, Attal M, Drouet L, Scrobohaci ML, Degos F, Degott C, Bearman SI, Grañena A, and Blaise D
- Subjects
- Alprostadil therapeutic use, France epidemiology, Heparin therapeutic use, Hepatic Veno-Occlusive Disease diagnosis, Hepatic Veno-Occlusive Disease epidemiology, Hepatic Veno-Occlusive Disease therapy, Humans, Incidence, Leukemia surgery, Prognosis, Tissue Plasminogen Activator therapeutic use, Transplantation, Autologous, Bone Marrow Transplantation adverse effects, Hepatic Veno-Occlusive Disease etiology
- Abstract
Hepatic veno-occlusive disease is a frequent complication after high-dose chemo- or radiotherapy after bone marrow transplantation and is a major cause of mortality. During the 3 weeks following transplantation, acute major hepatic vascularization is observed together with portal hypertension and weight gain, ascitis and oedema of the lower limbs due to non-thrombotic obstruction of the centrilobular hepatic veins. This report summarizes the observations presented at a French symposium of France Autogreffe and Groupe d'Etude de la Greffe de Moelle osseuse. Different pathogenic processes are implicated including endothelial mechanisms due to toxic factor related to graft preparations and immunosuppressor treatments (methotrexate, cyclosporin), physical factors related to irradiation, immunological factors related to the expression of class II antigens on endothelial cells and viral factors, in particular cytomegalovirus infection. The incidence of veno-occlusive disease varies greatly from one series to another. Two French groups reported 5 and 3 cases among 1991 and 253 autologous grafts respectively (1.2 and 2.3%) while the Seattle group observed 53% among 355 consecutive grafts, although the same clinical criteria were used. Histological criteria include fibrosis around a non-thrombotic occlusion of the centrilobular veins, cytolysis and congestion of the sinuses. Other methods for diagnosis include transjugular biopsy, the suprahepatic pressure and imaging techniques. Prophylactic continuous infusion of low-dose heparin has been associated with a lower incidence. Trials using anti-tumour necrosis drugs and prostaglandin E1 have also been undertaken and show possible effects towards decreasing prevalence.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1994
321. Autologous stem cell transplantation in chronic myelogenous leukemia: a retrospective analysis of the European Group for Bone Marrow Transplantation. Chronic Leukemia Working Party of the EBMT.
- Author
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Reiffers J, Goldman J, Meloni G, Cahn JY, and Gratwohl A
- Subjects
- Adolescent, Adult, Bone Marrow Purging, Bone Marrow Transplantation, Child, Europe, Female, Follow-Up Studies, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Male, Middle Aged, Prognosis, Registries, Retrospective Studies, Risk Factors, Survival Rate, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy
- Abstract
Over a 3 year period (1989-1991), 49 patients who underwent autologous stem cell transplantation (ASCT) for chronic myelogenous leukemia (CML) in chronic phase were reported to the European Bone Marrow Transplant Registry. Most patients had bad prognostic factors. The results were analyzed by 1 September 1993. Hematological recovery was observed in 45 cases and was significantly quicker after blood stem cell transplantation (n = 30) than after BMT (n = 19). Five patients died early and five other patients did not achieve a complete hematological response (CHR) following ASCT. Of the 39 patients who achieved CHR, 34 are still alive 17 to 52 months after ABSCT. Fifteen of the 34 patients who had cytogenetic evaluation exhibited a major response (> or = 65%, Ph-negative metaphases). The actuarial risk of transformation for the 44 evaluable patients was 28.1 +/- 15% (95% CI) and the actuarial survival at three years was 81.5 +/- 15% (95% CI). No factors were found to significantly influence the response rate or the patients' survival. These encouraging results suggest that ASCT by itself could play a role in prolonging survival in CML patients.
- Published
- 1994
322. Prognostic factors for autologous bone marrow transplantation in acute leukaemia: a single centre study of 105 patients.
- Author
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Cordonnier JM, Mercier M, Plouvier E, Hervé P, and Cahn JY
- Subjects
- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Purging, Bone Marrow Transplantation mortality, Child, Child, Preschool, Combined Modality Therapy, Female, France epidemiology, Graft Survival, Humans, Leukemia therapy, Leukocyte Count, Life Tables, Male, Middle Aged, Prognosis, Proportional Hazards Models, Retrospective Studies, Risk Factors, Survival Analysis, Transplantation, Autologous, Treatment Outcome, Whole-Body Irradiation, Bone Marrow Transplantation statistics & numerical data
- Abstract
Since the treatment of leukaemia by autologous bone marrow transplantation is becoming increasingly frequent, a retrospective study was undertaken to ascertain factors influencing the evolution of the disease (death and relapse). Data were collected over a period of 11 years for 105 patients with acute leukaemia (60 lymphoid cases and 45 myeloid cases). Multivariate analysis by the Cox model was used to determine prognostic factors for survival and disease free survival (DFS). Overall survival for the entire population was 35% after 8 years while DFS was 33% after 3 years. The major prognostic criteria were granulocyte recovery time (p < 0.001 at 5 weeks) and platelet recovery time (p < 0.02 at 6 weeks). Patients conditioned by an association of polychemotherapy and total body irradiation (TBI) showed a better survival rate than those conditioned by polychemotherapy alone (p < 0.01), with an overall survival of 48% after 3 years for the former group as compared to 19% for the latter. Other parameters influencing survival were the number of graft CFU-GM, sex and age. A knowledge of these factors could provide a means of predicting the long term evolution of leukaemia following autologous bone marrow transplantation. However, the present results require validation by a prospective study taking into account recent therapeutic protocols with haematopoietic growth factors.
- Published
- 1994
323. Detection of cytomegalovirus-infected cells in bone marrow biopsy specimens obtained before allogeneic bone marrow transplantation from donors and recipients.
- Author
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Fest T, Angonin R, Mougin C, Deschaseaux M, Lab M, Cahn JY, and Herve P
- Subjects
- Adolescent, Adult, Biopsy, Child, Preschool, Humans, Middle Aged, Tissue Donors, Transplantation, Homologous, Bone Marrow microbiology, Bone Marrow Transplantation, Cytomegalovirus isolation & purification
- Published
- 1994
324. Variability of the alloreactive T-cell response to human leukemic blasts.
- Author
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Delain M, Tiberghien P, Racadot E, Billot M, Pariset J, Chabod J, Cahn JY, and Hervé P
- Subjects
- HLA-DR Antigens immunology, Humans, Leukemia, Myeloid, Acute pathology, Leukemia, T-Cell pathology, Lymphocyte Culture Test, Mixed, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma pathology, T-Lymphocytes, Cytotoxic transplantation, Leukemia, Myeloid, Acute immunology, Leukemia, T-Cell immunology, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma immunology, T-Lymphocytes, Cytotoxic immunology
- Abstract
Clinical and experimental data suggest a role for the immune response in preventing leukemic relapses after allogeneic bone marrow transplantation (BMT): the graft-versus-leukemia (GVL) effect. In this report, we have evaluated the response of normal donor lymphocytes against allogeneic leukemic cells as an in vitro model of the GVL effect. We used a limiting dilution technique in order to determine the frequency of cytotoxic T-lymphocyte precursors (pre-CTL) against allogeneic leukemic blasts among normal donor lymphocytes. We demonstrate a considerable variability of CTL precursor frequency. This variability depended on leukemic populations since, for a given leukemia, the pre-CTL frequency was comparable among our tested normal allogeneic donors. Moreover, when HLA-DR negative leukemias were used as allostimulators, the pre-CTL frequencies were extremely low. In order to verify the impact of leukemic DR expression on the stimulatory capacity of leukemic cells, we selected and analyzed in mixed lymphocyte tumor cell culture (MLTC), a panel of myelogenous and lymphoblastic leukemias with variable levels of DR expression, each against different allogeneic responders. Our results demonstrated a close correlation (r = 0.953, p < 0.0001) between the proliferative response of alloactivated lymphocytes and the percentage of stimulatory leukemic cells expressing HLA-DR molecules. Anti-MHC class II monoclonal antibodies inhibited the lymphocyte proliferation in the MLTC, confirming the preponderant role of DR in the generation of this response. Overall, our results demonstrate the extreme variability of leukemic cells in their allostimulatory capacity and the central role of DR expression in determining leukemic allo-recognition. In the setting of a clinical protocol, our data suggest that the infusion of allogeneic T lymphocytes in a DR negative leukemia will not lead to an alloreactive T-cell anti-tumor effect.
- Published
- 1994
325. Cytomegalovirus interstitial pneumonia in autologous bone marrow transplant recipients. Infectious Disease Working Party of the European Group for Bone Marrow Transplantation.
- Author
-
Ljungman P, Biron P, Bosi A, Cahn JY, Goldstone AH, Gorin NC, Link H, Messina C, Michallet M, and Richard C
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Europe epidemiology, Foscarnet therapeutic use, Ganciclovir therapeutic use, Humans, Immunoglobulins, Intravenous therapeutic use, Incidence, Lung Diseases, Interstitial epidemiology, Lung Diseases, Interstitial microbiology, Middle Aged, Retrospective Studies, Surveys and Questionnaires, Survival Analysis, Bone Marrow Transplantation adverse effects, Cytomegalovirus Infections drug therapy, Lung Diseases, Interstitial etiology
- Abstract
CMV pneumonia is rare following ABMT. No information has been presented concerning risk factors or outcome of antiviral therapy. Information concerning CMV pneumonia after ABMT was collected from bone marrow transplant centers in Europe. Twenty-one patients who fulfilled the diagnostic criteria of CMV pneumonia were reported. Eighteen of these patients were reported from centers who also reported the total number of ABMT performed. The CMV pneumonia frequency among 2252 reported ABMT patients was 0.8%, and this varied from 0% to 8.6% between different centers. Survival for > 30 days from diagnosis of pneumonia was 43%. Three patients suffered relapses, which were fatal, giving a total survival of 28%. Patients treated with or without TBI had a survival of 18% and 50%, respectively. Among patients given ganciclovir or foscarnet with or without intravenous immune globulin, survival at 30 days was 50% and total survival 28%. There was no difference in survival with or without the addition of intravenous immune globulin. CMV pneumonia is an infrequent but serious complication of ABMT.
- Published
- 1994
326. Autologous transplantation in chronic myelogenous leukemia: European results: Chronic Leukemia Working Party of the EBMT.
- Author
-
Reiffers J, Goldman J, Meloni G, Cahn JY, Faberes C, and Apperley J
- Subjects
- Adolescent, Adult, Child, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive blood, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Middle Aged, Survival Rate, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy
- Abstract
Autologous stem cell transplantation (ASCT) was performed in 95 patients with chronic myelogenous leukemia (CML) in chronic phase and their data were reported to the European Bone Marrow Transplant Registry. Most patients presented bad prognostic factors. The results were analysed by September 1, 1993. The actuarial proportion of patients who achieved a complete hematological response at one year was 87.3+/-7.5% (95% CI). The 3-year percentage of major cytogenetic response was 38.6+/--13% (95% CI). The actuarial risk of transformation for the evaluable patients was 31.5+/-14% (95% CI) and the actuarial survival at four years was 83.3+/-10% (95% CI). These encouraging results suggest that ASCT by itself could play a role to prolong survival in CML patients.
- Published
- 1994
327. Graft failure after T cell depleted HLA identical allogeneic bone marrow transplantation: risk factors in leukemic patients.
- Author
-
Delain M, Cahn JY, Racadot E, Flesch M, Plouvier E, Mercier M, Tiberghien P, Pavy JJ, Deschaseaux M, and Deconinck E
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Survival Rate, Transplantation, Homologous, Bone Marrow Transplantation adverse effects, Leukemia therapy, Lymphocyte Depletion, T-Lymphocytes physiology
- Abstract
In a retrospective analysis of T cell depleted bone marrow transplantation, we have looked at different parameters in order to determine risk-factors of graft-failure after allogeneic bone marrow transplantation for leukemia. Fifty-one patients with acute leukemia or chronic myeloid leukemia have been analysed. For 33 of them, the pretransplant conditioning regimen consisted of fractionated total body irradiation (TBI) at 12 Gy prior to cyclophosphamide (120 mg/kg). The other patients received various reinforced preparative regimens. T-cell depletion consisted of treating marrow cells with pan-T monoclonal antibodies (CD2+CD3 or CD2-CD5-CD7) followed by complement mediated cytolysis. No post-transplant immunosuppressive prophylaxis was administered except for the first nine patients who received Methotrexate alone. In this group of 51 patients, 12 died within 3 months from graft-related complications and 10 developed graft failure (no engraftment or rejection). Among the possible risk factors associated with this failure, two graft-related parameters appeared significant: the number of CFU-GM progenitors and the number of viable T cells injected with the marrow inoculum. No correlation with graft failure was found with other parameters including diagnosis, disease status at transplant, conditioning regimen, age, sex, and CMV status of donor/host pairs. However, the interpretation must remain cautious because of the relatively small samples in each group.
- Published
- 1993
- Full Text
- View/download PDF
328. Autologous blood stem-cell transplantation and recombinant interferon alfa in chronic myeloid leukemia.
- Author
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Reiffers J, Montastruc M, Cahn JY, Souillet G, Troncy J, Leblond V, Caillot D, Troussard X, Marit G, and Fabères C
- Subjects
- Adult, Bone Marrow Purging, Humans, Middle Aged, Recombinant Proteins, Transplantation, Autologous, Interferon Type I therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Stem Cell Transplantation
- Published
- 1993
329. [Comparison between bone marrow autograft and intensive chemotherapy as treatment for maintenance of complete remission in acute myeloblastic leukemia in the adult. GOELAM Group].
- Author
-
Harousseau JL, Pignon B, and Cahn JY
- Subjects
- Adolescent, Adult, Humans, Middle Aged, Remission Induction methods, Transplantation, Autologous, Antineoplastic Agents therapeutic use, Bone Marrow Transplantation, Leukemia, Myeloid, Acute therapy
- Published
- 1993
330. Interleukin-1 treatment before allogeneic bone marrow transplantation: pre-clinical studies.
- Author
-
Tiberghien P, Laithier V, Mabed M, Racadot E, Pavy JJ, Angonin R, Cahn JY, Noir A, and Hervé P
- Subjects
- Animals, Blood Cells drug effects, Bone Marrow drug effects, Bone Marrow Cells, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Spleen cytology, Transplantation, Homologous, Bone Marrow Transplantation methods, Interleukin-1 therapeutic use
- Published
- 1993
331. Interleukin-1 administration before lethal irradiation and allogeneic bone marrow transplantation: early transient increase of peripheral granulocytes and successful engraftment with accelerated leukocyte, erythrocyte, and platelet recovery.
- Author
-
Tiberghien P, Laithier V, Mabed M, Racadot E, Reynolds CW, Angonin R, Loumi R, Pavy JJ, Cahn JY, and Noir A
- Subjects
- Animals, Bone Marrow drug effects, Bone Marrow radiation effects, Granulocytes radiation effects, Hematopoiesis drug effects, Hematopoiesis radiation effects, Leukocyte Count radiation effects, Male, Mice, Mice, Inbred BALB C, Platelet Count radiation effects, Radiation Chimera, Spleen drug effects, Spleen radiation effects, Transplantation, Homologous, Bone Marrow Transplantation, Granulocytes drug effects, Interleukin-1 therapeutic use, Leukocyte Count drug effects, Platelet Count drug effects, Whole-Body Irradiation
- Abstract
Administration of interleukin-1 beta (IL-1 beta) before a lethal irradiation with or without allogeneic bone marrow transplantation (BMT) protects greater than 90% of the irradiated mice. To approach the mechanisms responsible for the radioprotective effect of IL-1, we examined the effects of IL-1 pretreatment on engraftment and kinetics of peripheral blood, spleen, and marrow cell reconstitution after irradiation and BMT. Although the BMT was not necessary for the survival of the IL-1-pretreated lethally irradiated mice, allogeneic marrow did engraft in these mice as evaluated in the spleen and marrow 2 months after BMT. IL-1 pretreatment significantly accelerated hematopoietic recovery versus transplanted saline-treated controls with a pronounced enhancement of peripheral leukocyte, platelet, and erythrocyte recovery. Leukocyte recovery in IL-1-pretreated mice was unique in that IL-1 first induced an early transient (maximum at day 7) increase of peripheral granulocytes before accelerating leukocyte recovery after day 11. IL-1 pretreatment also significantly enhanced marrow cell recovery after allogeneic BMT with an eightfold increase in marrow cellularity from day 4 to 11 versus control transplanted mice. When lethal irradiation was not followed by allogeneic BMT. IL-1 pretreatment also affected the peripheral reconstitution of leukocytes, platelets, and erythrocytes. Interestingly, in the absence of BMT, IL-1 also induced an early circulation of peripheral granulocytes. Overall, our data demonstrate that a single administration of IL-1 before lethal irradiation and allogeneic BMT can induce an early transient increase of circulating granulocytes, followed by an accelerated multilineage recovery and long-term allogeneic engraftment.
- Published
- 1993
332. Prevention and treatment of acute GvHD--new modalities.
- Author
-
Herve P, Tiberghien P, Racadot E, Plouvier E, and Cahn JY
- Subjects
- Graft vs Host Disease therapy, Humans, Drug Therapy trends, Graft vs Host Disease drug therapy, Graft vs Host Disease prevention & control
- Published
- 1993
333. Autologous bone marrow transplantation for intensification of first remission in adult patients with acute lymphoblastic leukemia.
- Author
-
Cahn JY, Flesch M, Vernant JP, and Fiere D
- Subjects
- Adolescent, Adult, Combined Modality Therapy, Humans, Middle Aged, Remission Induction, Transplantation, Autologous, Whole-Body Irradiation, Bone Marrow Transplantation, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Published
- 1992
334. Prevention of veno-occlusive disease of the liver after bone marrow transplantation: heparin or no heparin?
- Author
-
Cahn JY, Flesch M, Brion A, Deconinck E, Leconte Des Floris MF, Voillat L, Plouvier E, Amsallem D, Tiberghien P, and Fest T
- Subjects
- Humans, Bone Marrow Transplantation adverse effects, Heparin therapeutic use, Hepatic Veno-Occlusive Disease etiology, Hepatic Veno-Occlusive Disease prevention & control
- Published
- 1992
335. Interleukin-2-induced increase of a monoclonal B-cell lymphocytosis. A novel in vivo interleukin-2 effect?
- Author
-
Tiberghien P, Racadot E, Deschaseaux ML, Delain M, Voillat L, Billot M, Flesch M, Rozenbaum A, Brandely M, and Cahn JY
- Subjects
- B-Lymphocytes drug effects, Cytokines blood, Cytokines drug effects, DNA, Neoplasm analysis, Humans, Immunophenotyping, In Vitro Techniques, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Leukemia, Lymphocytic, Chronic, B-Cell immunology, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear immunology, Male, Middle Aged, Receptors, Interleukin-2 biosynthesis, Recombinant Proteins therapeutic use, Interleukin-2 therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell therapy, Lymphocytosis chemically induced
- Abstract
A 56-year-old man with refractory B-cell lymphocytic non-Hodgkin's lymphoma was treated in a Phase II study with interleukin-2 (IL-2) (Roussel-Uclaf, Romainville, France). The patient had involvement of multiple lymph nodes and medullary and peripheral blood (3.6 x 10(9) monoclonal CD19-positive [CD19+] B-lymphocytes/l). After a 5-day cycle of IL-2 treatment, an eightfold increase of the monoclonal CD19+ population was observed (27 x 10(9) monoclonal CD19+ cells). The lymphocytosis decreased dramatically during the second cycle (days 15 to 19) of IL-2 treatment, resulting in 6 x 10(9)/l peripheral lymphocytes, with 5.5 x 10(9) B-lymphocytes. As soon as day 20, peripheral B-cells again increased considerably, with 32 x 10(9) CD19+ cells/l at day 27. The CD19+ population remained monoclonal as assessed by kappa/lambda cell-surface phenotyping and kappa gene rearrangement evaluation. Kinetics of the monoclonal B-lymphocyte response to IL-2 paralleled the natural killer/lymphokine-activated killer and T-cell response, with a 4-day latency period, suggesting an indirect enhancing effect of IL-2. Before and during IL-2 treatment, peripheral B-lymphocytes never expressed detectable levels of the p55 IL-2 receptor. However, the p75 IL-2 receptor was expressed significantly in the IL-2-responsive monoclonal B-cell population. Tumor necrosis factor alpha, a known (in vitro) B-cell tumor growth factor, reached high serum levels during IL-2 treatment. Response evaluation at day 45 showed stability of the lymph node involvement and the marrow lymphocyte infiltrate. At day 45, peripheral B-cell lymphocytosis was 7.5 x 10(9)/l. To the knowledge of the authors, this is the first report of an in vivo IL-2-induced reversible increase of peripheral monoclonal B-cell lymphocytosis.
- Published
- 1992
- Full Text
- View/download PDF
336. More on high-dose busulfan and seizure prophylaxis.
- Author
-
Tiberghien P, Flesch M, Paintaud G, and Cahn JY
- Subjects
- Adult, Bone Marrow Purging, Bone Marrow Transplantation, Epilepsy complications, Female, Humans, Leukemia, Myeloid, Acute surgery, Male, Middle Aged, Myelodysplastic Syndromes surgery, Seizures prevention & control, Busulfan adverse effects, Phenytoin therapeutic use, Seizures chemically induced
- Published
- 1992
337. Treatment of poor prognosis Burkitt's lymphoma in adults with the Société Française d'Oncologie Pédiatrique LMB Protocol--a study of the Federation Nationale des Centres de Lutte Contre le Cancer (FNLCC).
- Author
-
Philip T, Meckenstock R, Deconnick E, Carrie C, Bailly C, Colombat P, Dauriac C, Demaille MC, Salles B, and Cahn JY
- Subjects
- Adolescent, Adult, Burkitt Lymphoma pathology, Cyclophosphamide administration & dosage, Cytarabine administration & dosage, Female, Humans, Male, Methotrexate administration & dosage, Middle Aged, Neoplasm Staging, Prognosis, Prospective Studies, Time Factors, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Burkitt Lymphoma drug therapy
- Abstract
14 adult patients between 16 and 50 years old with small non-cleaved cell lymphoma (Burkitt's lymphoma) were prospectively treated from 1982 to 1990 with the LMB protocols of the Société Française d'Oncologie Pédiatrique (SFOP). No HIV-positive patients were included. All patients had extensive disease with bad prognosis factors, i.e. 10 patients had Murphy stage III and 4 had stage IV with bone marrow involvement. The LMB protocols were characterised by high-dose fractionated cyclophosphamide, high-dose methotrexate (HD-MTX), and cytosine arabinoside. No local or central nervous system irradiation was used. Treatment duration ranged from 5 (LMB 84) to 12 (LMB 81) months. There were no therapy-related deaths. All patients achieved complete remission (CR). 6 patients relapsed between 2 and 30 months following CR. 8 of the 14 patients (57%) are still alive and disease-free after treatment by LMB protocol alone. 2 patients were salvaged with bone marrow transplantation after relapse and a total of 10 out of 14 patients (71%) are disease-free at the time of this report. Our results showed the high curability of advanced Burkitt's lymphoma using a paediatric protocol, even in adult patients. The LMB protocol may be applied to adult patients but requires intensive care during the induction period.
- Published
- 1992
- Full Text
- View/download PDF
338. [Angioimmunoblastic lymphadenopathy: a pathogenetic intersection between dysimmune, viral and lymphomatous diseases].
- Author
-
Fest T, Angonin R, Dupond JL, and Cahn JY
- Subjects
- Antibodies, Monoclonal immunology, Clone Cells, Cytogenetics, Humans, Immune System Diseases diagnosis, Immune System Diseases immunology, Immunoblastic Lymphadenopathy immunology, Immunohistochemistry, Lymphoma, T-Cell diagnosis, Lymphoma, T-Cell immunology, Virus Diseases diagnosis, Virus Diseases immunology, Immunoblastic Lymphadenopathy diagnosis
- Abstract
Angioimmunoblastic lymphadenopathy (AIL) still is a clinico-pathological syndrome with little known physiopathology. The advent of molecular biology has improved our understanding of this syndrome by characterization of the clonal cell. With this technique, combined with cytogenetics and immunohistochemistry, three pathological states have been individualized: 1) true AIL without evidence of monoclonal proliferation; 2) transformed AIL, and 3) AIL-like T-cell lymphoma. This clinical complex can be integrated in an evolutive continuum, starting with simple lymphoid hyperplasia and ending with frank malignant T-cell lymphoma.
- Published
- 1991
- Full Text
- View/download PDF
339. Soluble CD8, IL-2 receptor, and tumor necrosis factor-alpha levels in steroid-resistant acute graft-versus-host disease. Relation with subsequent response to anti-IL-2 receptor monoclonal antibody treatment.
- Author
-
Tiberghien P, Racadot E, Lioure B, Delain M, Girard A, Wijdenes J, Plouvier E, Flesch M, Cahn JY, and Herve P
- Subjects
- Adolescent, Adrenal Cortex Hormones therapeutic use, Adult, CD8 Antigens, Child, Child, Preschool, Drug Resistance, Female, Graft vs Host Disease therapy, Humans, Male, Receptors, Interleukin-2 immunology, Antibodies, Monoclonal therapeutic use, Antigens, CD analysis, Antigens, Differentiation, T-Lymphocyte analysis, Bone Marrow Transplantation adverse effects, Graft vs Host Disease immunology, Receptors, Interleukin-2 blood, Tumor Necrosis Factor-alpha analysis
- Abstract
Serial determination of soluble CD8 (sCD8), soluble IL-2 receptors (sIL-2R), and tumor necrosis factor-alpha serum levels were performed in bone marrow transplant patients upon initiation, day 0 (D0) and at D10 of an anti-IL-2 receptor (alpha chain) monoclonal antibody (B-B10) in vivo treatment for steroid-resistant grade greater than or equal to 2 acute graft-versus-host disease (aGVHD). D0 and D10 sCD8 serum levels correlated strongly with response to B-B10 treatment (p = .003 and .001, respectively); 76% of the patients with D0 sCD8 levels less than 500 U/ml responded favorably to B-B10 treatment, versus only a 30% response if the sCD8 levels were greater than 500 U/ml (p = .02). Likewise, D0 tumor necrosis factor-alpha levels significantly correlated with subsequent response to B-B10 treatment (p = .03). D0 sIL-2R levels were not significantly different in B-B10-responsive and nonresponsive aGVHD patients. These results suggest that the serial determination of sCD8 and TNF serum levels could provide valuable predictive information as to steroid-resistant aGVHD responsiveness to anti-IL-2R treatment.
- Published
- 1991
- Full Text
- View/download PDF
340. Use of monoclonal antibodies in vivo as a therapeutic strategy for acute GvHD in matched and mismatched bone marrow transplantation.
- Author
-
Herve P, Bordigoni P, Cahn JY, Flesch M, Tiberghien P, Racadot E, Milpied N, Bergerat JP, Plouvier E, and Roche C
- Subjects
- Adolescent, Adult, Antibodies, Monoclonal pharmacokinetics, Child, Child, Preschool, Histocompatibility, Humans, Pilot Projects, Receptors, Interleukin-2 immunology, Tumor Necrosis Factor-alpha immunology, Antibodies, Monoclonal therapeutic use, Bone Marrow Transplantation immunology, Graft vs Host Disease therapy
- Published
- 1991
341. Ex vivo and conditioning chemotherapy for autologous bone marrow transplantation.
- Author
-
Hervé P and Cahn JY
- Subjects
- Antibodies, Monoclonal therapeutic use, Combined Modality Therapy, Hematopoiesis drug effects, Humans, Transplantation, Autologous, Antineoplastic Agents therapeutic use, Bone Marrow Transplantation methods, Leukemia therapy
- Published
- 1991
- Full Text
- View/download PDF
342. The TAM regimen prior to allogeneic and autologous bone marrow transplantation for high-risk acute lymphoblastic leukemias: a cooperative study of 62 patients.
- Author
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Cahn JY, Bordigoni P, Souillet G, Pico JL, Plouvier E, Reiffers J, Benz-Lemoine E, Bergerat JP, Lutz P, and Colombat P
- Subjects
- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Child, Child, Preschool, Combined Modality Therapy, Cytarabine administration & dosage, Humans, Melphalan administration & dosage, Pilot Projects, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma radiotherapy, Survival Analysis, Transplantation, Autologous, Transplantation, Homologous, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Transplantation, Precursor Cell Lymphoblastic Leukemia-Lymphoma surgery, Whole-Body Irradiation
- Abstract
A total of 62 patients with high-risk acute lymphoblastic leukemia (ALL) were treated with fractionated total body irradiation, high-dose cytosine arabinoside and melphalan followed by bone marrow transplantation (BMT). Thirty-six patients received allogeneic and 26 autologous BMT. Eight patients were treated in CR1, 36 in CR2 (first relapse occurring on therapy for 32), seven in further CR, 10 in relapse (five early first relapse, four second relapse and one fourth relapse) and one with refractory ALL. Severe toxicity occurred in 26 of the 62 patients (42%) and 14 died (22.5%) from non-leukemic causes. The actuarial event-free survival at 3.6 years was 28% after autologous BMT and 52% after allogeneic BMT with actuarial relapse rates of 62% and 35%, respectively. The results of this pilot study seem promising for this group of poor risk ALL, but the relapse rate remains high after autologous BMT and needs to be improved.
- Published
- 1991
343. The role of BMT for neuroblastoma relapse patients. A report of the EBMT-STR.
- Author
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Ladenstein R, Chauvin F, Garaventa A, Bernard JL, Zucker JM, Lutz P, Bordigoni P, Plouvier E, Cahn JY, and Frappaz D
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Combined Modality Therapy, Europe epidemiology, Humans, Neoplasm Metastasis, Neoplasm Recurrence, Local mortality, Neuroblastoma drug therapy, Neuroblastoma mortality, Prognosis, Remission Induction, Reoperation, Survival Analysis, Bone Marrow Transplantation mortality, Neoplasm Recurrence, Local surgery, Neuroblastoma surgery
- Published
- 1991
344. Bone marrow transplantation from donors other than HLA identical siblings. What have we learned from previous experiences?
- Author
-
Hervé P, Cahn JY, Tiberghien P, Racadot E, Plouvier E, Flesch M, and Wijdenes J
- Subjects
- Adolescent, Adult, Bone Marrow Transplantation adverse effects, Child, Child, Preschool, Graft Survival, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Graft vs Host Disease therapy, Humans, Infant, Leukemia immunology, Bone Marrow Transplantation immunology, HLA Antigens, Leukemia surgery
- Published
- 1990
345. Treatment of corticosteroid resistant acute graft-versus-host disease by in vivo administration of anti-interleukin-2 receptor monoclonal antibody (B-B10)
- Author
-
Hervé P, Wijdenes J, Bergerat JP, Bordigoni P, Milpied N, Cahn JY, Clément C, Béliard R, Morel-Fourrier B, and Racadot E
- Subjects
- Adolescent, Adult, Antibodies, Monoclonal immunology, Antibodies, Monoclonal therapeutic use, Antibody Formation, Child, Child, Preschool, Drug Evaluation, Drug Resistance immunology, Female, France, Graft vs Host Disease immunology, Graft vs Host Disease mortality, Humans, Infant, Male, Multicenter Studies as Topic, Pilot Projects, Receptors, Interleukin-2 blood, Adrenal Cortex Hormones immunology, Antibodies, Monoclonal administration & dosage, Graft vs Host Disease drug therapy, Receptors, Interleukin-2 immunology
- Abstract
In a multicenter pilot study, 32 patients showing steroid-resistant acute graft-versus-host disease (GVHD) were treated by in vivo administration of anti-interleukin-2 (IL-2) receptor monoclonal antibody (MoAb B-B10). Twenty-three patients received marrow from HLA-matched related donors, four from matched unrelated donors and five from partially matched related donors. The overall grade of GVHD was II in 16 patients, III in two, and IV in five. Five milligrams of B-B10 MoAb was infused in bolus daily for 10 days and then every second day for a further 10 days in an attempt to reduce GVHD recurrence. No clinical side effects were noted during the B-B10 treatment period. A complete response (CR) acute GVHD was achieved in 21 patients (65.6%). Six patients (18.7%) showed partial improvement (PR) and 5 patients (15.6%) no response (NR). A significant factor associated with GVHD response was the delay between the onset of the GVHD and the first day of B-B10 infusion. The earlier B-B10 was introduced, the greater the probability of CR (P = .03). There was no correlation between the serum B-B10 level and GVHD response (P = .69). There was, however, a significant correlation between the clinical response and the B-B10 kinetics as a function of time: serum B-B10 levels attained a plateau level more rapidly in the CR group than in the PR/NR group. Among the 26 complete and partial evaluable responders, GVHD recurred in 10 cases (38.4%). Host anti-B-B10 MoAb immune response occurred in only one (7.1%) of the 14 patients analyzed. Fourteen of the 32 patients (43.7%) are currently alive between 2 and 14 months after GVHD treatment with B-B10 was completed.
- Published
- 1990
346. Bone marrow transplantation for chronic myelogenous leukemia. Results of the French Cooperative Group (GEGMO).
- Author
-
Devergie A, Reiffers J, Vernant JP, Cahn JY, Guyotat D, Maraninchi D, Rio B, Michallet M, Jouet JP, and Milpied N
- Subjects
- Acute Disease, Chronic Disease, Combined Modality Therapy, Follow-Up Studies, Graft vs Host Disease etiology, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Pulmonary Fibrosis epidemiology, Pulmonary Fibrosis etiology, Recurrence, Retrospective Studies, Survival Rate, Bone Marrow Transplantation adverse effects, Leukemia, Myelogenous, Chronic, BCR-ABL Positive surgery
- Abstract
Data on 281 patients with chronic myelogenous leukemia who received bone marrow transplants were analyzed. The median follow-up time was 48 months. One hundred and seventy patients were in 1st chronic phase, 111 were in more advanced disease. The overall actuarial survival was 50% at 5 years. In multivariate analyses, the probability of relapse was correlated with the phase of the disease, the method of total body irradiation, the T cell depletion of the marrow and the occurrence of a chronic GVHD. The probability of disease free survival was significantly better for the patients who received a non T cell depleted marrow than for recipients of T cell depleted marrow. Bone marrow transplantion in first chronic phase with an HLA identical non T cell depleted marrow offers the better chance of prolonged leukemia free survival.
- Published
- 1990
347. BEAM protocol and autologous bone marrow transplantation in first chemosensitive relapse of non-Hodgkin's lymphomas.
- Author
-
Colombat P, Biron P, Laporte JP, Cahn JY, Herve P, Gorin NC, Lamagnere JP, and Philip T
- Subjects
- Adolescent, Adult, Bone Marrow Transplantation, Carmustine administration & dosage, Child, Cytarabine administration & dosage, Etoposide administration & dosage, Female, Humans, Lymphoma, Non-Hodgkin surgery, Male, Melphalan administration & dosage, Middle Aged, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Non-Hodgkin drug therapy
- Published
- 1990
- Full Text
- View/download PDF
348. Autologous bone marrow transplantation for acute leukemia using transplant chemopurified with metabolite of oxazaphosphorines (ASTA Z 7557, INN mafosfamide). First clinical results.
- Author
-
Hervé P, Cahn JY, Plouvier E, Flesch M, Tamayo E, Leconte des Floris R, and Peters A
- Subjects
- Adult, Cell Division drug effects, Cell Separation, Child, Child, Preschool, Colony-Forming Units Assay, Cyclophosphamide pharmacology, Drug Evaluation, Female, Humans, Male, Transplantation, Autologous, Bone Marrow Transplantation, Cyclophosphamide analogs & derivatives, Hematopoietic Stem Cells drug effects, Leukemia, Lymphoid therapy, Leukemia, Myeloid, Acute therapy, Neoplastic Stem Cells drug effects, Stem Cells drug effects
- Abstract
The contamination of autologous marrow with clonogenic tumor cells has been the main argument against ABMT in acute leukemia. In a preclinical study we evaluated an active cyclophosphamide derivative named "ASTA Z 7557". We observed that the toxic effect of this drug on CFU-GM growth was dependent on nucleated cell concentration as well as on red blood cell contamination. The potency of the drug was in close relationship with the incubation temperature. The growth of leukemic CFU was inhibited with an ASTA Z dose higher than 30 micrograms/ml. In our system, beyond 40 micrograms/ml more than 95% of committed stem cells are destroyed. Fifteen patients had autotransplant because of AML for 10 patients and because of ALL for 5 patients (4 patients were grafted in relapse and 11 patients in remission). We demonstrated that the marrow take was possible although the inoculum is CFU-GM depleted. Five of the 10 AML patients are alive and remain disease-free at 45+, 65+, 190+, 345+ and 570+ days from ABMT without any maintenance treatment. Four of the 5 ALL patients are alive, three of them in complete remission (40+, 110+, 250+ days). The number of patients reported in this clinical study was relatively small and more cases should be evaluated to be conclusive. Nevertheless the feasibility of chemopurified ABMT was demonstrated.
- Published
- 1984
- Full Text
- View/download PDF
349. Successful graft-versus-host disease prevention without graft failure in 32 HLA-identical allogeneic bone marrow transplantations with marrow depleted of T cells by monoclonal antibodies and complement.
- Author
-
Hervé P, Cahn JY, Flesch M, Plouvier E, Racadot E, Noir A, Couteret Y, Goldstein G, Bernard A, and Lenys R
- Subjects
- Adolescent, Adult, Antibodies, Monoclonal immunology, Child, Child, Preschool, Complement System Proteins immunology, Female, Graft Survival, HLA Antigens immunology, Humans, Leukemia therapy, Male, Multiple Myeloma therapy, T-Lymphocytes immunology, Transplantation, Homologous, Bone Marrow Transplantation, Cell Separation methods, Graft vs Host Disease prevention & control, T-Lymphocytes cytology
- Abstract
Thirty-two patients with acute leukemia, chronic granulocytic leukemia, or multiple myeloma received a T lymphocyte-depleted HLA-identical marrow. After being treated with pan-T monoclonal antibodies (MoAbs) and one round of baby rabbit complement, the mean percentage of T cell depletion was 94% +/- 4%. The number of residual viable T cell infused to the patient was 0.99 +/- 0.65 X 10(6) per kg body weight. The patients were conditioned with fractionated total body irradiation (TBI) (12 Gy) preceding high doses of cyclophosphamide (120 mg/kg). Methotrexate was used as an additional immunosuppressant in the first ten patients. For the following 22 patients no posttransplant immunoprophylaxis was administered. Eight patients died within three months due to complications related to transplantation. Engraftment was achieved in all evaluable patients, and no patient has a late graft failure. The proof of total chimerism was established in 24 patients. Twenty-four of 27 evaluable patients (88%) did not have an acute graft-v-host disease (GVHD) greater than grade 0 to 1. Two patients had a grade 2 (skin only), and one patient had a grade 4 acute GVHD (the latter had only 80% of T cell depletion). A medullary relapse occurred in 11 patients (nine of them had previously been defined as "high risk leukemia"). Our data suggest that it may not be necessary to deplete nearly all T cells to prevent acute GVHD in recipients of HLA-identical marrow.
- Published
- 1987
350. T cell-depleted allogeneic bone marrow transplantation in a case of childhood idiopathic myelofibrosis.
- Author
-
Cahn JY, Plouvier E, Flesch M, Carbillet JP, and Herve P
- Subjects
- Bone Marrow Cells, Child, Chimera, Colony-Forming Units Assay, Hematopoietic Stem Cells cytology, Humans, Male, Bone Marrow Transplantation, Primary Myelofibrosis therapy, T-Lymphocytes immunology
- Abstract
An 11-year-old boy developed primary myelofibrosis. Nine months after diagnosis he received high-dose chemoradiotherapy followed by T cell-depleted allogeneic bone marrow transplantation as primary therapy. Sixteen months after grafting the patient is well, with reversal of the marrow sclerosis and no evidence of chronic graft-versus-host disease.
- Published
- 1987
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