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G Venton,
R Crocchiolo,
S Fürst,
A Granata,
C Oudin,
C Faucher,
D Coso,
R Bouabdallah,
P Berger,
N Vey,
P Ladaique,
C Chabannon,
M le Merlin,
D Blaise, J El-Cheikh
[show abstract]
[hide abstract]
ABSTRACT: Cytomegalovirus (CMV) infection is a serious complication that may occur in the weeks or months following bone marrow transplantation. However, both Ganciclovir and the CMV infection itself can cause marrow toxicity, notably neutropenia, that may consequently expose these immunosuppressed patients to life-threatening bacterial and/or fungal infections. The aim of this retrospective study was to identify factors associated with the occurrence of grade III-IV neutropenia among patients receiving pre-emptive Ganciclovir therapy after allogeneic stem cell transplantation at our Institution. We identified 547 consecutive patients transplanted from January 2005 to June 2011 at our Institution. In all, 190 patients (35%) presented with CMV reactivation of whom 30 patients (5%) were excluded from the analysis because they already had neutropenia at the time of reactivation. Finally, 160 (29%) patients were analysed. According to multivariate analysis, at the time of treatment initiation, the risk factors significantly associated with a grade III-IV Ganciclovir-related neutropenia included a high viral load (hazard ratio (HR) = 2.68, 95% CI 1.25-5.737, p 0.01); an absolute neutrophil count >3000 was a protective factor (HR = 0.26, 95% CI 0.125-0.545, p <0001) whereas serum creatinine >2 mg/dL was associated with higher Ganciclovir-related neutropenia (HR = 2.4, 95% CI 1.11-5.17, p 0.002). This large analysis revealed three risk factors for Ganciclovir-related neutropenia among patients with CMV reactivation after allogeneic stem cell transplantation; prompt identification of patients at risk when antiviral therapy is started may allow clinicians to adopt adequate preventive measures, so reducing the morbidity and mortality associated with CMV reactivation.
Clinical Microbiology and Infection 03/2013; · 4.54 Impact Factor
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R Crocchiolo,
C Saillard,
A Signori,
S Fürst, J El Cheikh,
L Castagna,
C Oudin,
A Granata,
C Faucher,
R Devillier,
D Crocchiolo,
M P Sormani,
C Chabannon,
D Blaise
[show abstract]
[hide abstract]
ABSTRACT: It has been reported that chronic GvHD (cGvHD) is associated with significant morbidity and mortality after AlloSCT. Relapse risk is generally reduced when cGvHD is present, but prognosis may be affected by increased toxicity and/or infectious risk associated to immunosuppressive treatment (IST). We here performed a longitudinal data analysis of cGvHD including the evolution of cGvHD itself overtime, that is response to IST, on a monocenter cohort of 313 consecutive patients receiving AlloSCT. We found that lack of sustained response, without withdrawal of IST, within 6 months from cGvHD occurrence was associated with higher TRM (HR = 2.32; 95% CI: 1.24 - 4.33) than cGvHD-free patients. Conversely, response conferred better OS (HR= 0.42 (0.18-0.95)) than patients without cGvHD. In conclusion, the present analytical approach allowed to integrate the evolution of cGvHD in a predictive model of transplant outcome; notably, remission associated with permanent discontinuation of IST within the first 6 months from cGvHD occurrence seemed to best correlate with final outcome. Further confirmation from larger studies is warranted.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 12/2012; · 3.15 Impact Factor
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L Castagna,
R Boubdallah,
S Furst,
D Coso, J El Cheikh,
C Faucher,
R Crocchiolo,
A Granata,
C Chabannon,
C Lemarié,
B Calmels,
J M Boher,
M Mothy,
D Blaise
[show abstract]
[hide abstract]
ABSTRACT: We analyzed 113 patients with lymphoma who underwent allogeneic transplantation with reduced-intensity conditioning (allo-RIC) regimens at a single institution, from February 2001 through November 2009, searching for factors predictive of the outcome. At the time of transplantation, 60% of patients were in CR, 29% in PR and 11% had progressive or stable disease. At a median follow-up of 34 months (confidence interval (CI) 17-45), the 3-year OS and PFS were 59% (CI 48-68%) and 51% (CI 41-61%), respectively. The 100-day and 2-year nonrelapse mortalities (NRM) were 6% and 28% (CI 20-35%), respectively. Grade II-IV acute GVHD (aGVHD) incidence was 38%, and the global incidence of chronic GVHD was 33%. In univariate analysis, OS was influenced by disease status before allo-RIC; aGVHD negatively affected on survival. Similarly, PFS was influenced only by disease status. Histological subtype did not affect OS or PFS. We conclude that disease status at the time of transplantation significantly influences survival in patients receiving allo-RIC for lymphoma, whereas histological subtype does not. This reinforces the need to administer more effective debulking treatments to lymphoma patients, for optimal benefit of allogeneic immune recognition of minimal residual disease, independently from lymphoma histology.Bone Marrow Transplantation advance online publication, 10 December 2012; doi:10.1038/bmt.2012.225.
Bone marrow transplantation 12/2012; · 3.00 Impact Factor
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R Crocchiolo,
L Castagna,
S Fürst, J El-Cheikh,
C Faucher,
C Oudin,
A Granata,
R Bouabdallah,
D Coso,
C Chabannon,
M Balzarotti,
A Santoro,
D Blaise
[show abstract]
[hide abstract]
ABSTRACT: Allo-SCT is used to exploit GVL effect in high-risk relapsed non-Hodgkin's lymphoma (NHL). Here, we retrospectively analyzed 34 high-risk NHL patients who underwent auto-SCT followed closely by reduced-intensity allo-SCT ('tandem auto-allo') from January 2002 to November 2010. The search for an allogeneic donor was started at the beginning of salvage regimen. Median patients' age was 47 (27-68) years; histotypes were: diffuse large B-cell n=5, follicular n=14, transformed follicular n=4, mantle-cell n=5, plasmocytoid lymphoma n=1, anaplastic large T-cell n=2, peripheral T-cell n=3. Donors were HLA-identical siblings (n=29) or 10/10-matched unrelated individuals (n=5). Median interval between auto-SCT and allo-SCT was 77 days (36-197). At a median follow-up of 46 (8-108) months since allo-SCT, 5-year OS is 77% (61-93) and PFS is 68% (51-85). Disease relapse or progression occurred in six patients, 100-day TRM was 0%, 2-year TRM incidence was 6%. In conclusion, tandem transplantation is feasible in high-risk NHL patients having a HLA-identical donor. This approach could represent a suitable therapeutic option for those patients with high-risk NHL potentially benefitting from further therapy after auto-SCT. Donor searches should be started promptly whenever such an approach is chosen.Bone Marrow Transplantation advance online publication, 25 June 2012; doi:10.1038/bmt.2012.116.
Bone marrow transplantation 06/2012; · 3.00 Impact Factor
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Roberto Crocchiolo,
Christian Chabannon, Jean El-Cheikh,
Benjamin Esterni,
Claude Lemarié,
Sabine Fürst,
Luca Castagna,
Reda Bouabdallah,
Patrick Ladaique,
Diane Coso,
Jean Marc Schiano,
Anne Marie Stoppa,
Jerome Rey,
Vadim Ivanov,
Therese Aurran,
Catherine Faucher,
Didier Blaise,
Boris Calmels
Leukemia & lymphoma 06/2012; · 2.40 Impact Factor
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Roberto Crocchiolo,
Joseph Ciccolini, Jean El-Cheikh,
Sabine Fürst,
Luca Castagna,
Angela Granata,
Claire Oudin,
Samia Harbi,
Raynier Devillier,
Stevan Legall,
David Ternant,
Gilles Paintaud,
Bruno Lacarelle,
Didier Blaise
Leukemia & lymphoma 02/2012; 53(10):2063-5. · 2.40 Impact Factor
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R Devillier,
R Crocchiolo,
L Castagna,
S Fürst, J El Cheikh,
C Faucher,
T Prebet,
A Etienne,
C Chabannon,
N Vey,
B Esterni,
D Blaise
[show abstract]
[hide abstract]
ABSTRACT: We previously reported that reduced intensity conditioning (RIC) regimen with fludarabine, BU and 2.5 mg/kg of rabbit anti-thymocyte globulin (r-ATG) was effective but associated with a high rate of acute and chronic GVHD. Therefore, we increased the dose of r-ATG to 5 mg/kg. In this report, we analyzed 87 patients with AML or myelodysplastic syndrome (MDS) undergoing allo-SCT from an HLA-identical sibling donor from 2000 to 2010. RIC consisted of fludarabine, BU and r-ATG 2.5 mg/kg on 1 day (r-ATG1; n=53) or 2.5 mg/kg per day over 2 days (r-ATG2; n=22). Grade 2-4 acute GVHD incidence at day 100 was 30.2% and 8.8% in the r-ATG1 and r-ATG2 groups, respectively (P=0.038). Extensive chronic GVHD incidence was 60.4% and 12% in the r-ATG1 and r-ATG2 groups, respectively (P<0.001). The relapse incidences (RI) at 24 months were 18.9% and 28.5% in r-ATG1 and r-ATG2 groups, respectively (P=0.640). Overall and PFS were not different between the r-ATG1 and r-ATG2 groups. r-ATG dose at 5 mg/kg in the setting of RIC seems a good balance allowing GVHD prevention and antitumor effect with a remarkable reduction of GVHD incidence without an identical level of increased relapse rate.
Bone marrow transplantation 02/2012; 47(5):639-45. · 3.00 Impact Factor
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[show abstract]
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ABSTRACT: Treatment of multiple myeloma has evolved over the last decade, most notably with the introduction of highly effective novel agents. It is now possible to aim for deep disease responses in a greater number of patients in an attempt to prolong remission duration and survival. Initially introduced in the relapsed setting, the novel agents, namely thalidomide, bortezomib and lenalidomide, are now being increasingly incorporated into upfront treatment strategies, raising questions about the feasibility of 'retreatment' with such agents. Also, in a disease that is characterized by multiple relapses, the 'sequencing' of the different effective options is an important question. In the frontline setting, the first remission is likely to be the period during which patients will enjoy the best quality of life. Thus, the goal should be to achieve a first remission that is the longest possible by using the most effective treatment upfront. At relapse, the challenge is to select the optimal treatment for each patient while balancing efficacy and toxicity. The decision will depend on both disease- and patient-related factors. This review aimed to assess the available research data addressing 'retreatment' approaches, drug 'sequencing' and the long-term impact of upfront therapy with novel drugs.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 01/2012; 26(1):73-85. · 8.30 Impact Factor
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R Crocchiolo,
L Castagna, J El-Cheikh,
A Helvig,
S Fürst,
C Faucher,
A Vazquez,
A Granata,
D Coso,
R Bouabdallah,
D Blaise
[show abstract]
[hide abstract]
ABSTRACT: Rituximab is one of the most commonly used drugs in the treatment of B-cell non-Hodgkin lymphoma. Because of its ability to target CD20(+) lymphocytes, its use before allogeneic stem cell transplantation seemed to reduce risk of graft-vs.-host disease (GVHD) occurrence. We retrospectively analyzed the outcomes of adult patients diagnosed with CD20(+) lymphoproliferative disease undergoing allogeneic stem cell transplantation and receiving, or not receiving, rituximab up to 3 months before transplantation. Analysis on a cohort of 57 patients showed a protective role of rituximab on the occurrence of acute GVHD for those receiving anti-thymocyte globulin during conditioning (n = 39). Grade 2 to 4 and 3 to 4 acute GVHD occurred in 10% vs. 48% (p = 0.03) and 0% vs. 24% (p = 0.08) in the rituximab and no-rituximab groups, respectively. No impact on chronic GVHD was observed. These results confirm a protective role of rituximab on the occurrence of GVHD and enhance further investigation on future studies aimed at reducing GVHD incidence.
Experimental hematology 06/2011; 39(9):892-6. · 3.11 Impact Factor
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Bone marrow transplantation 02/2011; 46(2):317-8. · 3.00 Impact Factor
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Jean El Cheikh,
Elias Kfoury,
Boris Calmels,
Claude Lemarie,
Anne-Marie Stoppa,
Reda Bouabdallah,
Diane Coso,
Jean-Marc Schiano De Collela,
Patrick Ladaique,
Jean-Albert Gastaut,
Mohamad Mohty,
Christian Chabannon,
Didier Blaise
[show abstract]
[hide abstract]
ABSTRACT: The optimal treatment of patients with multiple myeloma (MM) is not well defined, in part because these patients are underrepresented in clinical studies. Autologous stem cell transplantation (auto-SCT) after high-dose melphalan chemotherapy can result in a prolonged response duration and survival in patients under 65 years of age.
Single-center, retrospective study of patients treated at Paoli-Calmettes Institute Cancer Centre, between January 1994 and January 2007 (96 months)
We compared the outcome of elderly (age >65 years) patients with younger patients aged between 60 and 65 years with MM.
We compared 82 elderly patients with 104 younger patients. Except for age, both groups had comparable demographic features, disease characteristics, and prognostic factors. Induction VAD chemotherapy was comparable between the elderly (87%) and younger (94%) group. Prior to auto-SCT, the calculated hematopoietic cell transplantation-specific co-morbidity index was also comparable. With a median follow-up of 41 months (range, 5-227 months) after auto-SCT, 120 patients were still alive. Disease progression (n=40; 61%) was the main cause of death, and it was comparable in the two groups. Auto-SCT-related mortality was 3.8% (n=4/104) in younger and 3.7% (n=3/82) in older patients. Comparing younger/older subjects, progression-free survival was significantly higher in the younger group (P<.0001). However, disease response rates after the first auto-SCT was comparable and overall survival (OS) was also comparable (57% vs. 54% at 5 years, P=NS; 32% vs. 24% at 10 years, P=NS). In a Cox multivariate analysis model, none of the relevant characteristics was shown to be a critical prognostic feature for OS.
Age was insignificant for both OS and transplant-related mortality. We conclude that there is no biological justification for an age-discriminate policy for MM therapy. Physiologic aging is likely more important than chronologic aging.
Hematology/ Oncology and Stem Cell Therapy 01/2011; 4(1):30-6.
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L Castagna,
S Fürst,
N Marchetti, J El Cheikh,
C Faucher,
M Mohty,
R Bouabdallah,
N Vey,
A M Stoppa,
B Esterni,
D Blaise
[show abstract]
[hide abstract]
ABSTRACT: In this retrospective study, 63 patients >60 years with hematological malignancies and treated with allo-SCT and with reduced-intensity conditioning (RIC) were reviewed. A total of 51% of patients suffered from AML or myelodysplastic syndromes. Disease status before transplantation was CR or PR 71 with 29% transplanted with active disease. Patients were classified according to three published prognostic indexes: (1) hematopoietic cell transplantation comorbidity index (HCT-CI); (2) European BMT (EBMT) score; and (3) Pretransplantation Assessment of Mortality (PAM) score. The 100-day and 1-year treatment-related mortality (TRM) were 6 and 22%, respectively, for the entire group. The 2-year OS and PFS were 60 and 58%, respectively. The incidence of grade II-IV acute GVHD (aGVHD) and extensive chronic GVHD was 46 and 48%, respectively. In a univariate analysis, neither the HCT-CI nor the EBMT score, nor the PAM score were predictive of TRM and OS. Only the occurrence of aGVHD affected the TRM and OS. ALLO-RIC is feasible in elderly patients. Even if those prognostic scores were not adapted to elderly patients, they did not predict for TRM and OS. aGVHD is the main cause of TRM and more efforts should be made to reduce its incidence without sacrificing graft vs tumor effect.
Bone marrow transplantation 10/2010; 46(7):1000-5. · 3.00 Impact Factor
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Jean El Cheikh,
Luca Castagna,
Ling Wang,
Benjamin Esterni,
Catherine Faucher,
Sabine Furst,
Segolene Duran,
Pierre Berger,
Stephane Ranque,
Mohamad Mohty,
Didier Blaise
[show abstract]
[hide abstract]
ABSTRACT: The liposomal formulation of amphotericin B (LAmB) has been shown to cause few and mild infusion-related reactions, while achieving high plasma and tissue concentrations compared with conventional amphotericin B. We investigated the efficacy and safety of high-dose LAmB (7.5 mg/kg once weekly) prophylaxis of fungal infections in allogeneic stem-cell transplanted (allo-SCT) patients with graft-versus-host disease (GvHD).
Retrospective, comparative, single-center.
Forty-two patients receiving high-dose prednisone for GvHD after allo-SCT had LAmB prophylaxis; 83 patients in the control group received other antifungal prophylaxis.
In the LAmB prophylaxis group, the median duration of treatment was 7 weeks. The cumulative incidence of invasive fungal infection was 8% at 1 year after transplantation, 8% at 2 years and 16% at 3 years in the LAmB group vs. 36% at 1 year, 44% at 2 years and 49% at 3 years in the other prophylaxis group (P=.008). Fungal infection-related mortality after transplantation was observed in none of the patients in the LAmB prophylaxis group vs. 12 patients (14%) at 1 year, 14 patients (17%) at 2 years and 16 patients (19%) at 3 years in the control group (P=.005). The tolerance of the treatment was good with only 5 patients (12%) having a reversible nephrotoxicity leading to temporary treatment discontinuation.
High-dose LAmB prophylaxis seems effective and well tolerated in this short series of allo-SCT patients with GvHD. Prospective clinical studies are required to confirm these results.
Hematology/ Oncology and Stem Cell Therapy 01/2010; 3(4):167-73.
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M Lioznov, J El-Cheikh,
F Hoffmann,
Y Hildebrandt,
F Ayuk,
C Wolschke,
D Atanackovic,
G Schilling,
A Badbaran,
U Bacher,
B Fehse,
A R Zander,
D Blaise,
M Mohty,
N Kröger
[show abstract]
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ABSTRACT: We investigated efficacy and toxicity of lenalidomide in 24 heavily pretreated myeloma patients with a median age of 59 years (range: 37-70) and relapse after allo-SCT. Lenalidomide was given at a dose of 15 mg (n=4), or 25 mg (n=20), orally once daily on day 1 to day 1 every 28 days, with (n=20) or without (n=4) DHAP. The median number of lenalidomide cycles was five (range: 2-17). Major side effects were leukopenia (grade 4: 4%, grade 3: 21% and grade 2: 17%) and thrombocytopenia (grade 3: 17% and grade 2: 29%); infectious complications were observed in 50%. Non-hematological toxicity consisted of muscle cramps (n=9), fatigue (n=5) and constipation (n=2). Mild grade I-II GVHD was seen in three patients. Response was achieved in 66%: CR in 8%, VGPR in 8%, PR in 50% and SD in 13%. The median time to progression was 9.7 months (95% confidence interval (CI): 7.5-11.9), and median OS was 19.9 months (95% CI: 17.3-22.5). Immunomonitoring after lenalidomide showed significant increase of activated NK (NKp44(+)) and T (HLA-DR(+)) cells, as well as regulatory T cells (CD4(+), CD25(+), CD127(lo)), supporting an immunomodulating anti-myeloma effect of lenalidomide.
Bone marrow transplantation 08/2009; 45(2):349-53. · 3.00 Impact Factor
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X Cahu,
M Mohty,
C Faucher,
P Chevalier,
N Vey, J El-Cheikh,
T Guillaume,
S Furst,
J Delaunay,
S Ayari,
P Moreau,
J A Gastaut,
J L Harousseau,
D Blaise
Bone marrow transplantation 09/2008; 42(10):689-91. · 3.00 Impact Factor
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H de Lavallade, J El-Cheikh,
C Faucher,
S Fürst,
A-M Stoppa,
D Coso,
R Bouabdallah,
C Chabannon,
J-A Gastaut,
D Blaise,
M Mohty
[show abstract]
[hide abstract]
ABSTRACT: The aim of this retrospective analysis was to assess the benefit of reduced-intensity conditioning allo SCT (RIC allo-SCT) in a cohort of 32 relapsed multiple myeloma (MM) patients. A total of 19 patients had an HLA-identical sibling donor ('donor' group), while 13 patients had no donor ('no-donor' group). There were no significant differences between these two groups as for prognosis risk factors. Eighteen patients from the 'donor' group could actually proceed to RIC allo-SCT. With a median follow-up of 36 (range, 21-60) months, six patients died from transplant-related toxicity (cumulative incidence, 33% (95% CI, 11-55%)). Only 4 patients from the 18 transplanted patients (22%; 95% CI, 7-48%) progressed after RIC allo-SCT, as compared to 12 (86%; 95% CI, 56-98%; P=0.0003) among the nontransplanted patients. In an 'intention-to-treat' analysis, the Kaplan-Meier estimate of PFS was significantly higher in the 'donor' group as compared to the 'no-donor' group (P=0.01; 46 versus 8% at 3 years). There was no difference in terms of overall survival. However, in multivariate analysis, actual performance of RIC allo-SCT was associated with better PFS (relative risk, 0.35; 95% CI, 0.15-0.82; P=0.01). These data suggest a potential benefit for RIC allo-SCT in the management of relapsed MM warranting further prospective investigations.
Bone Marrow Transplantation 07/2008; 41(11):953-60. · 3.75 Impact Factor
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M Mohty,
H de Lavallade, J El-Cheikh,
P Ladaique,
C Faucher,
S Fürst,
N Vey,
D Coso,
A-M Stoppa,
J-A Gastaut,
C Chabannon,
D Blaise
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 07/2008; 23(1):194-6. · 8.30 Impact Factor
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Bone Marrow Transplantation 06/2008; 41(10):909-11. · 3.75 Impact Factor
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Bone Marrow Transplantation 08/2007; 40(2):175-7. · 3.75 Impact Factor
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J El-Cheikh,
C Faucher,
S Fürst,
S Duran,
P Berger,
N Vey,
A-M Stoppa,
R Bouabdallah,
J-A Gastaut,
P Viens,
D Blaise,
M Mohty
[show abstract]
[hide abstract]
ABSTRACT: The use of high-dose corticosteroids for graft-versus-host disease (GVHD) treatment represents a major risk factor for long-term invasive fungal infections. The aim of this study was to investigate the safety and tolerance of weekly prophylactic administration of once-weekly high-dose (7.5 mg/kg) of liposomal amphotericin B (L-AmB) therapy in 21 adult patients receiving high-dose prednisone (2 mg/kg/day) for acute GVHD therapy after reduced intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT). Patients received a median of 4 (range, 1-8) infusions of L-AmB. Seven patients (33%; 95% confidence intervals (CI), 13-53%) discontinued taking the study drug owing to study drug-related adverse events, including elevated serum creatinine (>1.5 times from baseline values; n=5), hypotension and pain (n=1), and violent chest pain and arrhythmia (n=1). The overall frequency of infusion-related reactions was 29% (n=6; 95% CI, 10-48%), but these reactions were always transient and relieved by stopping the infusion. This safety data provide support for an efficacy study of this prophylaxis strategy, because this may help further improving the outcome of RIC or nonmyeloablative allo-SCT.
Bone Marrow Transplantation 03/2007; 39(5):301-6. · 3.75 Impact Factor
