Publications by authors named "Martin Carre"

17 Publications

  • Page 1 of 1

Characteristics and outcome of patients with low-/intermediate-risk acute promyelocytic leukemia treated with arsenic trioxide - an international collaborative study.

Haematologica 2021 May 27. Epub 2021 May 27.

Gemeinschaftsklinikum Mittelrhein gGmbH, Koblenz.

The aim of this study was to characterize a large series of 154 patients with acute promyelocytic leukemia (APL; median age, 53 years; range, 18-90 years) and evaluate real-life outcome after up-front treatment with arsenic trioxide (ATO) and alltrans retinoic acid (ATRA). All patients were included in the prospective NAPOLEON registry (NCT02192619) between 2013 and 2019. APL was de novo in 91% (n=140) and therapy-related in 9% (n=14); 13% (n=20) were older than 70 years. At diagnosis bleeding/hemorrhage was present in 38% and thrombosis in 3%. Complete remission was achieved in 152 patients (99%), whereas two patients (1%) experienced induction death within 18 days after start of therapy. With a median follow-up of 1.99 years (95%-CI, 1.61-2.30 years) 1-year and 2-years overall survival (OS) rates were 97% (95%-CI, 94-100%) and 95% (95%-CI, 91-99%), respectively. Age above 70 years was associated with a significantly shorter OS (P<0.001) as compared to younger patients. So far no relapses were observed. Six patients (4%) died in CR after in median 0.95 years after diagnosis (range, 0.18-2.38 years). Our data confirm the efficiency and durability of ATO/ATRA in the primary management of adult low-/ intermediate-risk APL patients in the real life setting, irrespective of age.
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http://dx.doi.org/10.3324/haematol.2021.278722DOI Listing
May 2021

Molecular classification and prognosis in younger adults with acute myeloid leukemia and intermediate-risk cytogenetics treated or not by gemtuzumab ozogamycin: Final results of the GOELAMS/FILO acute myeloid leukemia 2006-intermediate-risk trial.

Eur J Haematol 2021 Jul 18;107(1):111-121. Epub 2021 Apr 18.

Hématologie Clinique, Hôpital Cochin, AP-HP, Paris, France.

In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m of gemtuzumab ozogamycin (GO) to standard chemotherapy could improve outcome of younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk cytogenetics. GO arm was prematurely closed after 254 inclusions because of toxicity. A similar complete remission rate was observed in both arms. Neither event-free survival nor overall survival were improved by GO in younger AML patients (<60 years) ineligible for allogeneic stem-cell transplantation. (P = .086; P = .149, respectively). Using unsupervised hierarchical clustering based on mutational analysis of seven genes (NPM1, FLT3-ITD, CEBPA, DNMT3A, IDH1, IDH2, and ASXL1), six clusters of patients with significant different outcome were identified. Five clusters were based on FLT3-ITD, NPM1, and CEBPA mutations as well as epigenetic modifiers (DNMT3A, IDH1/2, ASXL1), whereas the last cluster, representing 25% of patients, had no mutation and intermediate risk. One cluster isolated FLT3-ITD mutations with higher allelic ratio and a very poor outcome. The addition of GO had no impact in these molecular clusters. Although not conclusive for GO impact in AML patients <60 years, this study provides a molecular classification that distinguishes six AML clusters influencing prognosis in younger AML patients with intermediate-risk cytogenetic.
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http://dx.doi.org/10.1111/ejh.13626DOI Listing
July 2021

Risk factors of BK viral hemorrhagic cystitis in allogenic hematopoietic stem cell transplantation.

Transpl Infect Dis 2021 Mar 16:e13601. Epub 2021 Mar 16.

Department of Hematology, Bone Marrow Transplant Unit, CHU Grenoble Alpes, Grenoble, France.

Reactivation of BK virus (BKV) can occur during intensive immunosuppression such as in allogenic hematopoietic stem cell transplant (AHSCT) recipients for whom a systematic PCR urine test for BKV will be positive in 50% to 100% of patients. Only 5% to 40% will develop BKV hemorrhagic cystitis (HC). Thus, BKV PCR testing is useful to confirm a diagnosis of BKV-HC but not to predict its occurrence. The aim of this retrospective study was to ascertain the risk factors of developing BKV HC, mostly in patients receiving posttransplant cyclophosphamide. The study looked at data from Grenoble Alpes University Hospital included in the national retrospective register ProMISe, administered by the "Société Francophone de Greffe de Moelle et de Thérapie Cellulaire". Urine BKV PCR was performed when patients presented grade ≥ 2 hematuria with clinical symptoms of cystitis. BKV-HC was defined as an association of clinical symptoms of cystitis, grade ≥ 2 hematuria and BKV viruria > 7 log copies/ml. From January 2014 to January 2018, 168 AHSCTs were considered for analysis, of which 43 (25.6%) developed BKV-HC and 44.9% of the subgroup that received posttransplant cyclophosphamide. After logistic regression, the risk factors associated with BKV-HC were reduced to posttransplantation exposure to cyclophosphamide (OR 4.25, [1.66; 10.87], P = .02), age < 40 y (OR 3.85 [1.51; 9.80], P = .005) and corticosteroid therapy (OR 3.86, [1.59; 9.36], P = .003). Exposure to cyclophosphamide, younger age (<40) and corticosteroid therapy are potential risk factors for BKV-HC.
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http://dx.doi.org/10.1111/tid.13601DOI Listing
March 2021

Treatment and outcome of Philadelphia chromosome-positive acute lymphoblastic leukemia in adults after relapse.

Expert Rev Anticancer Ther 2020 10 15;20(10):879-891. Epub 2020 Oct 15.

Hospices Civils de Lyon, Service d'Hématologie Clinique, Centre Hospitalier Lyon-Sud , Pierre-Bénite, France.

Introduction: Despite the significant progress that has been made over the last years in the front-line treatment of Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL), relapses are frequent and their treatment remains a challenge, especially among patients with resistant mutations.

Areas Covered: This manuscript reviews available data for the treatment of adult patients with relapsed/refractory Ph-positive ALL, with a focus on the role of tyrosine kinase inhibitors (TKIs), monoclonal antibodies, and immunotherapy.

Expert Opinion: Although a majority of patients with first relapsed Ph-positive ALL respond to subsequent salvage chemotherapy plus TKI combination, their outcomes remain poor. The main predictor of survival is the achievement of major molecular response anytime during the morphological response. More treatment strategies to improve survival are under investigation. Monoclonal antibodies and bispecific antibody constructs hold considerable promise in improving the outcomes of patients with relapsed ALL including Ph-positive ALL.
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http://dx.doi.org/10.1080/14737140.2020.1832890DOI Listing
October 2020

[Indications and management of hematologic microtransplantation: Recommendations of the French Society of Bone Marrow transplantation and cellular Therapy (SFGM-TC)].

Bull Cancer 2020 Dec 16;107(12S):S130-S139. Epub 2020 Jun 16.

Hôpital Huriez, CHRU de Lille, maladie du sang, 3, rue Michel-Polonowsky, 59000 Lille, France.

Microtransplantation (MT) is based on injection of HLA-mismatched G-CSF mobilized hematopoietic stem cells, in combination with chemotherapy but without use of conditioning regimen nor immunosuppressive drugs. As a result, a transient microchimerism is induced without engraftment. Its efficacy relies both on host immune system stimulation (recipient versus tumor) and on a graft versus tumor effect. Data are scarce and concern mostly Asian patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (HR-MDS). In comparison to conventional treatment without MT, higher complete remission rates and longer disease free survival and overall survival have been reported. Safety seems acceptable. The most frequent adverse event is non-severe cytokine release syndrome. Risk of GVHD remains very low. Here, we summarize the published data and detail the practical aspects of the procedure. Current data are not strong enough to provide recommendations on indications. Nevertheless, it seems reasonable to propose MT to patients with AML or HR-MDS, regardless of age, presenting an indication for allogeneic stem cell transplantation but ineligible for it. MT is still under investigation and rather be proposed within clinical trials.
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http://dx.doi.org/10.1016/j.bulcan.2020.03.016DOI Listing
December 2020

Role of Age and Hematopoietic Cell Transplantation-Specific Comorbidity Index in Myelodysplastic Patients Undergoing an Allotransplant: A Retrospective Study from the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation.

Biol Blood Marrow Transplant 2020 03 21;26(3):451-457. Epub 2019 Oct 21.

Hopital St. Louis, Paris, France.

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative option for myelodysplastic syndromes (MDSs) but is severely limited by nonrelapse mortality (NRM), especially in this mostly older population. Comorbidity assessment is crucial to predict NRM and often assessed with the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI). Moreover, the impact of age on NRM still remains a matter of debate. In recent years, the age at which transplants are made has been progressively increasing, and patients with comorbidities have become more common. Extricating the respective roles of age and comorbidities in toxic mortality is all the more important. This study by the European Group for Blood and Marrow Transplantation registry included 1245 adult patients who underwent a first allogeneic stem cell transplantation for MDSs between 2003 and 2014. Overall, 4-year NRM and overall survival were 32% and 47%, respectively. When considered as continuous predictors, HCT-CI score and age were associated with an increased hazard ratio (HR) for NRM. In multivariate analysis, age band (HR, 1.13; 95% CI, 1.02 to 1.25; P= .016), HCT-CI ≥3 (HR, 1.34; 95% CI, 1.04 to 1.73; P = .022), and Karnofsky Performance Status ≤80 (HR, 2.03; 95% CI, 1.52 to 2.73; P< .0001) were significantly predictive of a worse NRM. In our large cohort, both comorbidities, evaluated by the original HCT-CI score, and chronological age significantly affected NRM. Thus, age should be part of the transplant decision-making process and should be integrated in future scoring systems predicting outcomes of HSCT in MDSs.
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http://dx.doi.org/10.1016/j.bbmt.2019.10.015DOI Listing
March 2020

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

Scoring System Based on Post-Transplant Complications in Patients after Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome: A Study from the SFGM-TC.

Curr Res Transl Med 2019 02 8;67(1):8-15. Epub 2018 Sep 8.

CHU de Lille, LIRIC, INSERM U995, Université de Lille, 59000 Lille, France. Electronic address:

Purpose: We developed a prognostic scoring system to evaluate the prognosis of myelodysplastic syndrome (MDS) patients surviving more than 100 days allogeneic hematopoietic cell transplantation after (allo-HCT).

Patients And Methods: We performed a landmark analysis on a derivation cohort of 393 cases to identify prognostic factors for 3-year overall survival. Potential predictor variables included demographic and clinical data, transplantation modalities and early post-transplant complications. The scoring system was tested against a validation cohort which included 391 patients.

Results: Complications occurring before day 100 such as relapse [HR = 6.7; 95%CI, 4.5-10.0] (4 points), lack of platelet recovery [HR, 3.6; 95%CI, 2.2-5.8] (2 points), grade-II acute GVHD [HR = 1.7; 95%CI, 1.2-2.5] (1 point) and grade-III/IV [HR = 2.6; 95%CI, 1.8 -3.8] (2 points) were the only independent predictors of 3-year OS. The 3-year OS associated with low (0), intermediate (1-3) and high (≥4) risk scores was respectively 70%, 46% and 6%. The model performed consistently in both cohorts, with good calibration.

Conclusion: This post-transplant scoring system is a powerful predictor of outcome after allo-HCT for MDS, and can provide useful guidance for clinicians. Additional studies are required to evaluate this scoring system for other hematologic malignancies.
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http://dx.doi.org/10.1016/j.retram.2018.08.003DOI Listing
February 2019

Similar outcome of allogeneic stem cell transplantation after myeloablative and sequential conditioning regimen in patients with refractory or relapsed acute myeloid leukemia: A study from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire.

Am J Hematol 2018 03 8;93(3):416-423. Epub 2018 Jan 8.

Hematology department, Hôpital Saint Louis, Paris, France.

Patients with acute myeloid leukemia (AML) in relapse or refractory to induction therapy have a dismal prognosis. Allogeneic hematopoietic stem cell transplantation is the only curative option. In these patients, we aimed to compare the results of a myeloablative transplant versus a sequential approach consisting in a cytoreductive chemotherapy followed by a reduced intensity conditioning regimen and prophylactic donor lymphocytes infusions. We retrospectively analyzed 99 patients aged 18-50 years, transplanted for a refractory (52%) or a relapsed AML not in remission (48%). Fifty-eight patients received a sequential approach and 41 patients a myeloablative conditioning regimen. Only 6 patients received prophylactic donor lymphocytes infusions. With a median follow-up of 48 months, 2-year overall survival was 39%, 95% confidence interval (CI) (24-53) in the myeloablative group versus 33%, 95% CI (21-45) in the sequential groups (P = .39), and 2-year cumulative incidence of relapse (CIR) was 57% versus 50% respectively (P = .99). Nonrelapse mortality was not higher in the myeloablative group (17% versus 15%, P = .44). In multivariate analysis, overall survival, CIR and nonrelapse mortality remained similar between the two groups. However, in multivariate analysis, sequential conditioning led to fewer acute grade II-IV graft versus host disease (GVHD) (HR for sequential approach = 0.37; 95% CI: 0.21-0.65; P < .001) without a significant impact on chronic GVHD (all grades and extensive). In young patients with refractory or relapsed AML, myeloablative transplant and sequential approach offer similar outcomes except for a lower incidence of acute GvHD after a sequential transplant.
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http://dx.doi.org/10.1002/ajh.25004DOI Listing
March 2018

Impact of body-surface area on patients' outcome in younger adults with acute myeloid leukemia.

Eur J Haematol 2017 May 1;98(5):443-449. Epub 2017 Mar 1.

Department of Hematology, CHU Grenoble Alpes, La Tronche, France.

Objectives: Anthracyclines and cytarabine are cornerstones for intensive chemotherapy in acute myeloid leukemia (AML). The goals of this study were to comprehensively assess deviations from theoretical doses and the impact of body-surface area (BSA) on patients' characteristics, physicians' strategy, dose adjustment, and clinical outcome.

Methods: The GOELAMS 2001 phase III trial included 823 AML patients below 60 years of age. In the course of treatment, anthropomorphic parameters and chemotherapy doses were prospectively registered.

Results: Very high BSA (≥2.15 m ) was the factor most significantly associated with the physician's decision to reduce chemotherapy doses during induction and postremission therapy. Despite similar AML characteristics and therapeutic strategies, the very high BSA group exhibited a significantly worse survival (5-years OS of 27%) compared to the low (BSA≤1.5 m ), intermediate (1.5 m
Conclusion: The presence of a very high BSA is the main reason prompting physicians to reduce chemotherapy doses in adult AML. Furthermore, these patients display a poor outcome and could benefit from full doses calculated on actual BSA.
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http://dx.doi.org/10.1111/ejh.12850DOI Listing
May 2017

Long-Term Follow-Up of the French Stop Imatinib (STIM1) Study in Patients With Chronic Myeloid Leukemia.

J Clin Oncol 2017 Jan 31;35(3):298-305. Epub 2016 Oct 31.

Gabriel Etienne and François-Xavier Mahon, Institut Bergonié, Bordeaux; Joëlle Guilhot and François Guilhot, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire (CHU) de Poitiers, Poitiers; Delphine Rea, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP); Bruno Varet, Hôpital Necker, AP-HP et Université Paris Descartes, Paris; Françoise Rigal-Huguet, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse; Franck Nicolini, Centre Hospitalier Lyon Sud, Pierre Bénite; Aude Charbonnier, Institut Paoli Calmette, Marseille; Agnès Guerci-Bresler, CHU Brabois Vandoeuvre, Nancy; Laurence Legros, Hôpital de l'Archet, Centre Hospitalier Universitaire de Nice, Nice; Martine Gardembas, CHU d'Angers, Angers; Viviane Dubruille, CHU Hôtel-Dieu, Nantes; Michel Tulliez, Hôpital Henri Mondor, Créteil; Marie-Pierre Noel, Hôpital Claude Huriez, Centre Hospitalier Regional Universitaire de Lille, Lille; Jean-Christophe Ianotto, CHU Morvan, Brest; Bruno Villemagne, Centre Hospitalier Départemental La Roche-Sur-Yon, La Roche-Sur-Yon; Martin Carré, Hôpital Albert Michallon, CHU de Grenoble, Grenoble; Philippe Rousselot, Hôpital André Mignot, Le Chesnay; and François-Xavier Mahon, CHU de Bordeaux, INSERM U1218, Bordeaux, France.

Purpose Imatinib (IM) can safely be discontinued in patients with chronic myeloid leukemia (CML) who have had undetectable minimal residual disease (UMRD) for at least 2 years. We report the final results of the Stop Imatinib (STIM1) study with a long follow-up. Patients and Methods IM was prospectively discontinued in 100 patients with CML with UMRD sustained for at least 2 years. Molecular recurrence (MR) was defined as positivity of BCR-ABL transcript in a quantitative reverse transcriptase polymerase chain reaction assay confirmed by a second analysis point that indicated an increase of one log in relation to the first analysis point at two successive assessments or loss of major molecular response at one point. Results The median molecular follow-up after treatment discontinuation was 77 months (range, 9 to 95 months). Sixty-one patients lost UMRD after a median of 2.5 months (range, 1 to 22 months), and one patient died with UMRD at 10 months. Molecular recurrence-free survival was 43% (95% CI, 33% to 52%) at 6 months and 38% (95% CI, 29% to 47%) at 60 months. Treatment was restarted in 57 of 61 patients with MR, and 55 patients achieved a second UMRD with a median time of 4 months (range, 1 to 16 months). None of the patients experienced a CML progression. Analyses of the characteristics of the study population identified that the Sokal risk score and duration of IM treatment were significantly associated with the probability of MR. Conclusion With a median follow-up of more than 6 years after treatment discontinuation, the STIM1 study demonstrates that IM can safely be discontinued in patients with a sustained deep molecular response with no late MR.
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http://dx.doi.org/10.1200/JCO.2016.68.2914DOI Listing
January 2017

Dynamics of Epstein-Barr viral load after hematopoietic stem cell transplantation and effect of preemptive rituximab therapy.

Transpl Infect Dis 2016 Dec 24;18(6):889-895. Epub 2016 Nov 24.

Infectious Disease Unit, University Hospital, Grenoble, France.

Background: Epstein-Barr virus (EBV) displays oncogenic properties, particularly in the immunocompromised host. Notably, hematopoietic stem cell transplantation (HSCT) recipients with a detectable blood EBV viral load (BEBVL) are considered at higher risk of post-transplant lymphoproliferative diseases (PTLD). Therefore, BEBVL is monitored after HSCT, and preemptive rituximab may be used in patients with high values. However, little is known about post-HSCT BEBVL dynamics, and the threshold that should lead to anti-CD20 therapy is poorly defined.

Methods: We retrospectively analyzed the post-HSCT BEBVL of 332 adult HSCT recipients in our center from 2005 to 2013, including the effect of rituximab.

Results: Detection of BEBVL >100, 1000, 5000, 10 000, and 50 000 copies/mL occurred in, respectively, 77.7%, 69.6%, 37.0%, 27.1%, and 7.5% of the patients after a respective median time of 9, 14, 15, 16, and 14 weeks. No BEBVL threshold was associated with an overall survival difference. Seventy-eight patients received rituximab, with a BEBVL decrease in most. Among patients with detectable BEBVL, long-term survival did not differ in rituximab treated and non-treated, except for patients with BEBVL ≥50 000. Only one case of PTLD was observed.

Conclusions: BEBVL is frequently detectable after HSCT, but suggests no strong association with survival. Preemptive rituximab therapy threshold remains to be defined.
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http://dx.doi.org/10.1111/tid.12618DOI Listing
December 2016

Quantification of Howell-Jolly body-like inclusions in ganciclovir toxicity using CellaVision DM96 analyser.

Br J Haematol 2016 08 12;174(4):637-9. Epub 2015 Oct 12.

Therex, TIMC-IMAG, CNRS University, Grenoble Alpes, France.

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http://dx.doi.org/10.1111/bjh.13784DOI Listing
August 2016

Alemtuzumab for severe steroid-refractory gastrointestinal acute graft-versus-host disease.

Biol Blood Marrow Transplant 2014 Sep 6;20(9):1451-4. Epub 2014 Jun 6.

Clinique d'hématologie, CHU de Grenoble, UMR 5525 CNRS-UJF, France.

Acute graft-versus-host disease (aGVHD) still remains the main cause of morbidity and mortality after allogeneic stem cell transplantation. Moreover, patients who did not respond to first-line treatment with glucocorticosteroids have a very poor outcome. Some studies suggested that alemtuzumab (a humanized monoclonal antibody against the CD52 antigen) might be effective for treatment of refractory aGVHD. Here we report a single-center experience with alemtuzumab in refractory gastrointestinal aGVHD. From September 2009 to April 2012 at the Grenoble medical university center, 24 patients who had presented a refractory gastrointestinal aGVHD to corticosteroid, or after another immunosuppressive drug, were retrospectively analyzed. Most patients (n = 19) presented stage 4 gastrointestinal aGVHD. Response to treatment (either complete or partial) was observed in 15 patients (62.4%). The overall survival rate at 1 year for all patients was 33.3% (95% confidence interval [CI], 15.9% to 51.9%) and for responders, 53.3% (95% CI, 26.3% to 74.4%). Two patients died from infection, 5 patients from recurrent GVHD, and 1 from an uncontrolled post-transplant lymphoproliferative disorder.
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http://dx.doi.org/10.1016/j.bbmt.2014.05.031DOI Listing
September 2014

Early matched sibling hematopoietic cell transplantation for adult AML in first remission using an age-adapted strategy: long-term results of a prospective GOELAMS study.

Blood 2012 Mar 9;119(12):2943-8. Epub 2012 Feb 9.

Department of Hematology, CHU, Strasbourg, France.

The LAM2001 phase 3 trial, involving 832 patients with acute myeloid leukemia (AML; median: 46 years) proposed HLA-identical sibling allograft HSCT for all patients with an identified donor. The trial compared reduced-intensity conditioning (RIC) for patients older than 50 years of age (N = 47) and myeloablative conditioning for younger patients (N = 117). BM HSCT was performed in the younger patients, while the older ones received a consolidation course, followed by peripheral blood allo-HSCT using RIC. The incidence of grade II-IV acute GVHD, was 51.9% (95% confidence interval [CI]: 42.1-61.8) and 11.3% (1.6-21.2) after myeloablative or RIC, respectively (P < .0001) and that of chronic GVHD 45.8% (95% CI: 34.8-56.7) and 41.7% (24.7-58.6; NS). Cumulative incidence of nonrelapse mortality at 108 months was 15.8% (95% CI: 9.8-23.2) for myeloablative, and 6.5% (0.2-16.2) for RIC (NS). CI of relapse at 108 months was 21.7% (95% CI: 13.9-28.6) and 28.6% (16.5-43.4; NS). Overall survival at 108 months was 63.4% (95% CI: 54.6-72.2) and 65.8% (52.2-72.2), respectively, after myeloablative or RIC (NS). RIC peripheral blood stem cell allo-HSCT is prospectively feasible for patients between the ages of 51 and 60 years without excess of relapse or nonrelapse mortality, and compares favorably with myeloablative marrow allo-HSCT proposed to younger patients.
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http://dx.doi.org/10.1182/blood-2011-05-352989DOI Listing
March 2012

[Should we treat patients over 65 years with acute myeloblastic leukemia?].

Rev Prat 2010 Dec;60(10):1423-6

CHU Grenoble, hôpital Michallon, université Joseph-Fourier, BP 217, 38043 Grenoble cedex 9.

The incidence of acute myeloblastic leukemia increases with age. The unfavorable biology of the disease, comorbidities, and significant side effects of the intensive treatment make treatment decisions difficult. New and less toxic targeted approaches are under investigations in this setting and the main problem remains to determine which strategy for patients over 65 years of age. Some of them will be treated successfully using intensive chemotherapy, while a majority of them will fail. Older patients are heterogeneous and enrolling them in investigational therapy is justified, according to proven methods to stratify them.
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December 2010
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