Publications by authors named "Bruno Anglaret"

15 Publications

  • Page 1 of 1

Lymphomas with kidney involvement: the French multicenter retrospective LyKID study.

Leuk Lymphoma 2020 04 10;61(4):887-895. Epub 2020 Feb 10.

Hémato-Oncologie, APHP, Hôpital Saint-Louis, Paris, France.

The LyKID study is a nationwide survey in France of lymphoma patients with renal involvement based on biopsy and/or imaging, to evaluate its impact on disease outcome and renal function. A total of 87 adult cases of B or T-cell lymphomas were retrospectively analyzed. Interstitial topography was observed in most of the kidney biopsies (54/66; 80%). Kidney failure (glomerular filtration rate <60 mL/min/1.73 m) was present in 47% of patients and was associated with non-significantly different outcome. After lymphoma treatment, 44% of patients had persistent chronic kidney failure (CKF); kidney failure at diagnosis was the only parameter associated with CKF in multivariate analysis. DLBCL (diffuse large B-cell lymphomas) represented half of the series, with noticeably CNS (central neurological system) relapse in 17% patients, while fewer than one of two patients had received CNS prophylaxis. To our knowledge, the LyKID study represents the largest published non-autopsy lymphoma series with renal involvement.
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http://dx.doi.org/10.1080/10428194.2019.1697811DOI Listing
April 2020

Pattern of Care and Outcomes of Adolescent and Young Adults with Lymphoma Treated in the Rhône-Alpes Region.

J Adolesc Young Adult Oncol 2019 12 14;8(6):684-696. Epub 2019 Aug 14.

EAM SIS 4128, Centre Léon Bérard, Lyon, France.

Management of adolescent and young adults (AYAs) cancer is very heterogeneous. In the case of lymphomas, outcomes are mostly favorable but there is still room for improvement. We retrospectively collected the pattern of care of all institutional 13- to 25-year-old AYAs patients with classical Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) diagnosed in the Rhône-Alpes region between the years 2000 and 2005. Management, including adherence to Clinical Practice Guidelines (CPGs), and long-term survival were analyzed by comparing adult units (AU) and pediatric units (PU). 278 patients were included: 198 treated for HL (median age of 19 years), 80 treated for NHL (median age of 20 years). Among them, 74% were managed in AU and 26% in PU. The median time between diagnosis and starting treatment was significantly lower in PU than in AU. Sixty-five patients (23%) were included in clinical trials, mostly in AU. Five-year overall survival was 96% for HL [14 deaths, median follow-up 91 months (9-180)] and 90% for NHL [nine deaths, median follow-up 80 months (3-180)]. Secondary cancers occurred for 2% ( = 3) of HL patients and for none in NHL. Other major late complications included cardiovascular accidents in two patients and fatal pulmonary fibrosis in one patient. Major differences in chemotherapy and radiotherapy use are emphasized. Global management conformed to CPGs by 56%. Important differences between adult and pediatric management were reported, without any impact on survival. A few patients can be included in clinical trials: Homogeneity in management could improve specific care for AYAs.
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http://dx.doi.org/10.1089/jayao.2019.0016DOI Listing
December 2019

Dyserythropoiesis evaluated by the RED score and hepcidin:ferritin ratio predicts response to erythropoietin in lower-risk myelodysplastic syndromes.

Haematologica 2019 03 4;104(3):497-504. Epub 2018 Oct 4.

Department of Hematology, CHU Grenoble-Alpes, Grenoble.

Erythropoiesis-stimulating agents are generally the first line of treatment of anemia in patients with lower-risk myelodysplastic syndrome. We prospectively investigated the predictive value of somatic mutations, and biomarkers of ineffective erythropoiesis including the flow cytometry RED score, serum growth-differentiation factor-15, and hepcidin levels. Inclusion criteria were no prior treatment with erythropoiesis-stimulating agents, low- or intermediate-1-risk myelodysplastic syndrome according to the International Prognostic Scoring System, and a hemoglobin level <10 g/dL. Patients could be red blood cell transfusion-dependent or not and were given epoetin zeta 40 000 IU/week. Serum erythropoietin level, iron parameters, hepcidin, flow cytometry Ogata and RED scores, and growth-differentiation factor-15 levels were determined at baseline, and molecular analysis by next-generation sequencing was also conducted. Erythroid response (defined according to the International Working Group 2006 criteria) was assessed at week 12. Seventy patients, with a median age of 78 years, were included in the study. There were 22 patients with refractory cytopenia with multilineage dysplasia, 19 with refractory cytopenia with unilineage dysplasia, 14 with refractory anemia with ring sideroblasts, four with refractory anemia with excess blasts-1, six with chronic myelomonocytic leukemia, two with del5q-and three with unclassifiable myelodysplastic syndrome. According to the revised International Prognostic Scoring System, 13 had very low risk, 47 had low risk, nine intermediate risk and one had high-risk disease. Twenty patients were transfusion dependent. Forty-eight percent had an erythroid response and the median duration of the response was 26 months. At baseline, non-responders had significantly higher RED scores and lower hepcidin:ferritin ratios. In multivariate analysis, only a RED score >4 (=0.05) and a hepcidin:ferritin ratio <9 (=0.02) were statistically significantly associated with worse erythroid response. The median response duration was shorter in patients with growth-differentiation factor-15 >2000 pg/mL and a hepcidin:ferritin ratio <9 (=0.0008 and =0.01, respectively). In multivariate analysis, both variables were associated with shorter response duration. Erythroid response to epoetin zeta was similar to that obtained with other erythropoiesis-stimulating agents and was correlated with higher baseline hepcidin:ferritin ratio and lower RED score. .
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http://dx.doi.org/10.3324/haematol.2018.203158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395339PMC
March 2019

Bendamustine and rituximab in elderly patients with low-tumour burden follicular lymphoma. Results of the LYSA phase II BRIEF study.

Br J Haematol 2018 10 16;183(1):76-86. Epub 2018 Aug 16.

Lysa, University Hospital, Lyon, France.

The treatment of low-tumour burden follicular lymphoma (LTBFL) remains a challenge. Rituximab-based strategies may be improved by adding chemotherapy. This Lymphoma Study Association multicentre phase II study assessed rituximab and bendamustine in 63 patients with untreated LTBFL who were aged over 60 years old and had a follicular lymphoma International Prognostic Index (FLIPI) score ≥2. Induction comprised 4 weekly cycles of rituximab 375 mg/m intravenously combined with 2 cycles of bendamustine 90 mg/m days 1-2 with a 28-day interval, followed by twelve cycles of 375 mg/m rituximab maintenance therapy every 8 weeks. The primary endpoint was complete response (CR)/unconfirmed CR (CRu), at 12 weeks. Median age was 67·4 years and median FLIPI was 3. Ultimately, 18 patients (29%) had high tumour burden according to Groupe d'Etude des Lymphomes Folliculaires criteria. The 12-week CR/CRu rate was 54·0% and the overall response rate was 93·7%. Surprisingly, 3 patients died during maintenance (2 sepsis, 1 neoplasm). Progression-free survival was 85·4% at 24 months. In LTBFL patients with FLIPI ≥2, two cycles of rituximab and bendamustine result in a CR rate of 54·0%. However, the treatment-related deaths observed do not allow this regimen to be recommended for LTBFL patients aged over 60 years. EudraCT: 2010-020757-14; ClinicalTrials.gov: NCT01313611.
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http://dx.doi.org/10.1111/bjh.15513DOI Listing
October 2018

ABVD or BEACOPP along with involved-field radiotherapy in early-stage Hodgkin Lymphoma with risk factors: Results of the European Organisation for Research and Treatment of Cancer (EORTC)-Groupe d'Étude des Lymphomes de l'Adulte (GELA) H9-U intergroup randomised trial.

Eur J Cancer 2017 08 8;81:45-55. Epub 2017 Jun 8.

Centre de Traitement des Données du Cancéropôle Nord-Ouest, Centre François Baclesse, 3 Avenue Général Harris, 14076 Caen Cedex 05, France. Electronic address:

Purpose: For early-stage Hodgkin lymphoma (HL), optimal chemotherapy regimen and the number of cycles to be delivered remain to settle down. The H9-U trial compared three modalities of chemotherapy followed by involved-field radiotherapy (IFRT) in patients with stage I-II HL and risk factors (NCT00005584).

Patients And Methods: Patients aged 15-70 years with untreated supradiaphragmatic HL with at least one risk factor (age ≥ 50, involvement of 4-5 nodal areas, mediastinum/thoracic ratio ≥ 0.35, erythrocyte sedimentation rate (ESR) ≥ 50 without B-symptoms or ESR ≥ 30 and B-symptoms) were eligible for the randomised, open label, multicentre, non-inferiority H9-U trial. The limit of non-inferiority was set at 10% for the difference between 5-year event-free survival (EFS) estimates. From October 1998 to September 2002, 808 patients were randomised to receive either the control arm 6-ABVD-IFRT (n = 276), or one of the two experimental arms: 4-ABVD-IFRT (n = 277) or 4-BEACOPP-IFRT (n = 255).

Results: Results in the 4-ABVD-IFRT (5-year EFS, 85.9%) and the 4-BEACOPP-IFRT (5-year EFS, 88.8%) were not inferior to 6-ABVD-IFRT (5-year EFS, 89.9%): difference of 4.0% (90%CI, -0.7%-8.8%) and of 1.1% (90%CI,-3.5%-5.6%) respectively. The 5-year overall survival estimates were 94%, 93%, and 93%, respectively. Patients treated with combined modality treatment chemotherapeutic regimen comprising doxorubicin (Adriamycin), bleomycin, vincristine (Oncovin), cyclophosphamide, procarbazine, etoposide and prednisone (BEACOPP) more often developed serious adverse events requiring supportive measures and hospitalisation compared with patients receiving the chemotherapeutic regimen comprising doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD).

Conclusions: The trial demonstrates that 4-ABVD followed by IFRT yields high disease control in patients with early-stage HL and risk factors responding to chemotherapy. Although non-inferior in terms of efficacy, four cycles of BEACOPP were more toxic than four or six cycles of ABVD.
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http://dx.doi.org/10.1016/j.ejca.2017.05.005DOI Listing
August 2017

A phase II Bayesian sequential clinical trial in advanced Waldenström macroglobulinemia patients treated with bortezomib: interest of addition of dexamethasone.

Leuk Lymphoma 2017 11 10;58(11):2615-2623. Epub 2017 Apr 10.

u Service de Biostatistique et Informatique Médicale Hôpital Saint Louis APHP , Paris Cedex , France.

In patients with advanced Waldenström macroglobulinemia (WM), overall response rate (ORR) and median progression-free survival (PFS) achieved with bortezomib alone and bortezomib rituximab combination were 27-85% and 7.9 months, and 81% and 16.4 months, respectively. We checked the role of dexamethasone in combination with bortezomib by enrolling in a phase II trial 34 patients with relapsed/refractory WM. Bortezomib (1.3 mg/m IV D1, 4, 8, and 11 every 21 days) was used for six cycles. In non-responding patients, dexamethasone (20 mg daily for two days) was added to each infusion after the second cycle. After two cycles, the Bayes estimated ORR was 43.2 (95% Credible Interval: 28.0-59.1%) using the informative prior. Two-year survival rate was 84.0% and the median PFS 15.3 months without difference between patients treated with or without dexamethasone. We conclude that dexamethasone must be associated to bortezomib-based regimen.
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http://dx.doi.org/10.1080/10428194.2017.1307357DOI Listing
November 2017

Chromosomal abnormalities are major prognostic factors in elderly patients with multiple myeloma: the intergroupe francophone du myélome experience.

J Clin Oncol 2013 Aug 24;31(22):2806-9. Epub 2013 Jun 24.

Centre Hospitalier Universitaire, Toulouse, France.

Purpose: Chromosomal abnormalities, especially t(4;14) and del(17p), are major prognostic factors in patients with multiple myeloma (MM). However, this has been especially demonstrated in patients age < 66 years treated with intensive approaches. The goal of this study was to address this issue in elderly patients treated with conventional-dose chemotherapy.

Patients And Methods: To answer this important question, we retrospectively analyzed a series of 1,890 patients (median age, 72 years; range, 66 to 94 years), including 1,095 with updated data on treatment modalities and survival.

Results: This large study first showed that the incidence of t(4;14) was not uniform over age, with a marked decrease in the oldest patients. Second, it showed that both t(4;14) and del(17p) retained their prognostic value in elderly patients treated with melphalan and prednisone-based chemotherapy.

Conclusion: t(4;14) and del(17p) are major prognostic factors in elderly patients with MM, both for progression-free and overall survival, indicating that these two abnormalities should be investigated at diagnosis of MM, regardless of age.
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http://dx.doi.org/10.1200/JCO.2012.46.2598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718879PMC
August 2013

Survival impact of rituximab combined with ACVBP and upfront consolidation autotransplantation in high-risk diffuse large B-cell lymphoma for GELA.

Haematologica 2011 Aug 5;96(8):1136-43. Epub 2011 May 5.

Service Onco-Hématologie, Hôpital Saint Louis, 1 avenue Claude Vellefaux, Paris, France.

Background: As rituximab combined with CHOP improves complete remission and overall survival in diffuse large B-cell lymphoma, intensified chemotherapy followed by autologous stem-cell transplantation has also been advocated for high-risk patients. The aim of this study was to establish whether or not combining rituximab with high-dose chemotherapy and auto-transplantation also benefits patient survival.

Design And Methods: The LNH2003-3 study was a phase II trial including diffuse large B-cell lymphoma patients with 2 or 3 International Prognostic Index factors. They received four cycles of intensive biweekly chemotherapy with rituximab, doxorubicine, cyclophosphamide, vindesine, bleomycine, prednisolone (R-ACVBP) followed by auto-transplantation in responding patients. Two hundred and nine patients under 60 years of age were included in the study and 155 responding patients underwent auto-transplantation. In addition, a case-control study was performed by matching (1:1) 181 patients treated with R-ACVBP with ACVBP patients not given rituximab but submitted to auto-transplantation from the previous LNH1998-3 trial.

Results: With a median follow up of 45 months, 4-year progression-free survival and overall survival were estimated at 76% (CI: 69-81) and 78% (CI: 72-83), respectively. There was no difference between patients with 2 or 3 International Prognostic Index factors. Four year progression-free survival was significantly higher in R-ACVBP than ACVBP patients (74% vs. 58%; P=0.0005). There was also a significant increase in 4-year overall survival (76% vs. 68%; P=0.0494).

Conclusions: In high-risk diffuse large B-cell lymphoma patients, treatment with R-ACVBP followed by auto-transplantation results in a 78% 4-year overall survival which should be compared to other approaches.
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http://dx.doi.org/10.3324/haematol.2010.038109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148907PMC
August 2011

Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial.

Lancet 2007 Oct;370(9594):1209-18

Service d'Hématologie, Centre Hospitalier Universitaire, Lille, France.

Background: In multiple myeloma, combination chemotherapy with melphalan plus prednisone is still regarded as the standard of care in elderly patients. We assessed whether the addition of thalidomide to this combination, or reduced-intensity stem cell transplantation, would improve survival.

Methods: Between May 22, 2000, and Aug 8, 2005, 447 previously untreated patients with multiple myeloma, who were aged between 65 and 75 years, were randomly assigned to receive either melphalan and prednisone (MP; n=196), melphalan and prednisone plus thalidomide (MPT; n=125), or reduced-intensity stem cell transplantation using melphalan 100 mg/m2 (MEL100; n=126). The primary endpoint was overall survival. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00367185.

Findings: After a median follow-up of 51.5 months (IQR 34.4-63.2), median overall survival times were 33.2 months (13.8-54.8) for MP, 51.6 months (26.6-not reached) for MPT, and 38.3 months (13.0-61.6) for MEL100. The MPT regimen was associated with a significantly better overall survival than was the MP regimen (hazard ratio 0.59, 95% CI 0.46-0.81, p=0.0006) or MEL100 regimen (0.69, 0.49-0.96, p=0.027). No difference was seen for MEL100 versus MP (0.86, 0.65-1.15, p=0.32).

Interpretation: The results of our trial provide strong evidence to indicate that the use of thalidomide in combination with melphalan and prednisone should, at present, be the reference treatment for previously untreated elderly patients with multiple myeloma.
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http://dx.doi.org/10.1016/S0140-6736(07)61537-2DOI Listing
October 2007

A weekly regimen with dose escalation of doxorubicin for patients with advanced Hodgkin's lymphoma: results of a phase II study of the Groupe d'Etudes des Lymphomes de l'Adulte (GELA).

Leuk Lymphoma 2007 Apr;48(4):691-8

Department of Medicine, Institut de Cancerologie Gustave Roussy, Villejuif, France.

This multicenter phase II study assessed the feasibility and efficacy of a weekly chemotherapy regimen with a moderately escalated dose of doxorubicin administered over 16 weeks, followed by radiation therapy (RT) to bulky sites. From July 1996 to February 1998, 44 untreated patients with stage IIIB-IV Hodgkin's lymphoma (HL), and 0 - 2 risk factors described by the Memorial Sloan-Kettering Cancer Center, were treated. Chemotherapy was a combination of increased-dose doxorubicin with conventional doses of cyclophosphamide, vinblastine, prednisone, vindesine, bleomycin, and etoposide. Patients received four cycles of the weekly regimen for 16 weeks. Forty-one patients received the planned four cycles of chemotherapy, and RT was delivered to 36 patients. The incidence of WHO grade 3 - 4 neutropenia was 90%. A total of 39 patients achieved a complete remission (88.6%). The median follow-up was 95 months. The 7-years freedom from treatment failure and overall survival estimates were 57% (95% confidence interval (CI), 41% - 70%), and 93% (95% CI, 80 - 98%), respectively. The relapse rate was related to the short duration of chemotherapy, and the failure to prevent relapses with consolidation RT. In this study population the 16-week regimen and RT to bulky sites were not sufficient for disease control.
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http://dx.doi.org/10.1080/10428190601175369DOI Listing
April 2007

Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy.

Blood 2006 Feb 20;107(4):1292-8. Epub 2005 Sep 20.

Service des Maladies du Sang, Hôpital Huriez, CHU de Lille, rue Michel Polonovski, 59037 Lille, France.

Dexamethasone alone increases life expectancy in patients with relapsed multiple myeloma (MM); however, no large randomized study has compared dexamethasone and dexamethasone-based regimens with standard melphalan-prednisone in newly diagnosed MM patients ineligible for high-dose therapy. In the Intergroupe Francophone du Myélome (IFM) 95-01 trial, 488 patients aged 65 to 75 years were randomized between 4 regimens of treatment: melphalan-prednisone, dexamethasone alone, melphalan-dexamethasone, and dexamethasone-interferon alpha. Response rates at 6 months (except for complete response) were significantly higher among patients receiving melphalan-dexamethasone, and progression-free survival was significantly better among patients receiving melphalan (P < .001, for both comparisons), but there was no difference in overall survival between the 4 treatment groups. Moreover, the morbidity associated with dexamethasone-based regimens was significantly higher than with melphalan-prednisone, especially for severe pyogenic infections in the melphalan-dexamethasone arm and hemorrhage, severe diabetes, and gastrointestinal and psychiatric complications in the dexamethasone arms. Overall, these results indicated that dexamethasone should not be routinely recommended as first-line treatment in elderly patients with MM. In the context of the IFM 95-01 trial, the standard melphalan-prednisone remained the best treatment choice when efficacy and patient comfort were both considered. These results might be useful in the context of future combinations with innovative drugs.
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http://dx.doi.org/10.1182/blood-2005-04-1588DOI Listing
February 2006

All trans retinoic acid in combination with intermediate-dose cytarabine and idarubicin in patients with relapsed or refractory non promyelocytic acute myeloid leukemia: a phase II randomized trial.

Hematol J 2002 ;3(1):49-55

Service d'Hématologie, Hôpital Edouard Herriot, Lyon, France.

Introduction: All trans retinoic acid has shown a remarkable effectiveness in acute promyelocytic leukemia. These results have encouraged studies of treatment with ATRA in other acute myeloid leukemia subtypes.

Patients And Methods: In order to evaluate toxicity and antileukemic efficacy of all ATRA in patients with relapsed or refractory non promyelocytic AML, 95 patients (median age, 58 years; range, 20 to 80 years), with unclassified AML according to the FAB classification or secondary AML at diagnosis, or refractory or relapsing AML, received induction therapy with Idarubicin, 10 mg/m(2)/day, for 3 days and cytarabine, 1000 mg/m(2)/12 h, for 6 days, alone or combined, on a randomized basis, with ATRA, 45 mg/m(2)/day, from day 1 to complete remission. Patients in CR received maintenance therapy with 6 monthly courses combining Ida, 10 mg/m(2)/day, intravenously, on day 1 with Ara-C100 mg/m(2)/day, subcutaneously, from day 1 to day 5.

Results: Results were evaluated after one induction course. Overall 54 patients (57%, 26 with ATRA and 28 without ATRA) achieved CR including five patients treated at time of initial diagnosis, seven previously resistant, 38 in first relapse and four in further relapse. Thirty patients (31%) had resistant disease and 11 (12%) died from toxicity. Median time for neutrophil recovery to 0.5 x 10(9)/l and platelets to 20 x 10(9)/l was 31 and 21 days respectively. Severe toxicity (WHO grade >or=3) included infections (37%), diarrhea (9%), bleeding (3%), vomiting (16%), hyperbilirubinemia (5%), mucositis (6%) and hypercreatininemia (2%). No ATRA syndrome was noted in the ATRA arm. Median overall survival for the entire cohort was 6.3 months and median disease-free survival was 4.7 months. There were no statistical differences in terms of CR, DFS, and OS between the two arms.

Conclusion: We conclude that ATRA in combination with Ida and Ara-C can be administered safely to high-risk AML patients. However, in this setting, ATRA did not offer any advantage when compared to chemotherapy alone.
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http://dx.doi.org/10.1038/sj.thj.6200141DOI Listing
July 2003
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