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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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M Mohty,
M Labopin,
M L Balère,
G Socié,
N Milpied,
R Tabrizi,
N Ifrah,
Y Hicheri,
N Dhedin,
M Michallet,
A Buzyn,
J-Y Cahn,
J-H Bourhis, D Blaise,
C Raffoux,
H Espérou,
I Yakoub-Agha
[show abstract]
[hide abstract]
ABSTRACT: This retrospective report assessed the impact of rabbit antithymocyte globulins (ATG), incorporated within a standard myeloablative conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT) using human leukocyte antigen-matched unrelated donors (HLA-MUD), on the incidence of acute and chronic graft-vs-host disease (GVHD). In this series of leukemia patients, 120 patients (70%) did not receive ATG ('no-ATG' group), whereas 51 patients received ATG ('ATG' group). With a median follow-up of 30.3 months, the cumulative incidence of grade 3-4 acute GVHD was 36% in the no-ATG group and 20% in the ATG group (P = 0.11). The cumulative incidence of extensive chronic GVHD was significantly lower in the ATG group as compared to the no-ATG group (4 vs 32%, respectively; P = 0.0017). In multivariate analysis, the absence of use of ATG was the strongest parameter associated with an increased risk of extensive chronic GVHD (relative risk) = 7.14, 95% CI: 1.7-33.3, P = 0.008). At 2 years, the probability of nonrelapse mortality, relapse, overall and leukemia-free survivals was not significantly different between the no-ATG and ATG groups. We conclude that the addition of ATG to GVHD prophylaxis resulted in decreased incidence of extensive chronic GVHD without an increase in relapse or nonrelapse mortality, and without compromising survival after myeloablative allo-SCT from HLA-MUD.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 09/2010; 24(11):1867-74. · 8.30 Impact Factor
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Bone marrow transplantation 02/2010; 45(10):1574-5. · 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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P Chevallier,
T Prebet,
A Pigneux,
M Hunault,
J Delaunay,
F Perry,
L Lode,
S Richebourg,
O Blanchet,
N Vey,
N Ifrah,
N Milpied, D Blaise,
J-L Harousseau,
M Mohty
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 10/2009; 24(2):467-9. · 8.30 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: This was a retrospective multicenter study including 44 acute leukaemia patients who have received allogeneic haematopoietic SCT (allo-HSCT) after prior exposure to Gemtuzumab Ozogamicin (GO) + chemotherapy. Median interval between last administration of GO and allo-HSCT was 4.2 (range, 0.8-26.3) months. At time of allo-HSCT, 33 patients were in CR. The majority of patients (n=36) received a reduced-intensity conditioning (RIC) regimen before allo-HSCT. All but one patient received low-dose heparin for veno-occlusive disease (VOD) prophylaxis. With a median follow-up of 15 (range, 1.1-63) months, overall survival and disease-free survival after allo-HSCT were 45% (95% confidence interval (CI), 30-61%) and 38% (95% CI, 24-54%) at 2 years, respectively. The cumulative incidence of grade 3-4 hyperbilirubinemia was 13.5% (n=6), with this being 21% in patients with a short (< or =3.5 months) GO-allo-HSCT interval (n=4/19) vs 8% in all others (P=NS). Overall, the cumulative incidence of VOD was 7% (n=3), with this being 10.5% (n=2/19) in patients with a short GO-allograft interval (< or =3.5 months) vs 4% (n=1/25) for all others (P=NS), and 5.5% (n=2/36) in patients receiving an RIC regimen vs 12.5% for the others (n=1/8) (P=NS). These results suggest that GO-based chemotherapy before allo-HSCT is feasible and does not result in an excessive rate of liver toxicity, especially VOD, after allo-HSCT.
Bone marrow transplantation 08/2009; 45(1):165-70. · 3.00 Impact Factor
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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]
[hide abstract]
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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N T Ueno,
J D Rizzo,
T Demirer,
Y C Cheng,
U Hegenbart,
M-J Zhang,
M Bregni,
A Carella, D Blaise,
A Bashey,
J D Bitran,
B J Bolwell,
G J Elfenbein,
K K Fields,
C O Freytes,
R P Gale,
H M Lazarus,
R E Champlin,
P J Stiff,
D Niederwieser
[show abstract]
[hide abstract]
ABSTRACT: We reviewed 66 women with poor-risk metastatic breast cancer from 15 centers to describe the efficacy of allogeneic hematopoietic cell transplantation (HCT). Median follow-up for survivors was 40 months (range, 3-64). A total of 39 patients (59%) received myeloablative and 27 (41%) reduced-intensity conditioning (RIC) regimens. More patients in the RIC group had poor pretransplant performance status (63 vs 26%, P=0.002). RIC group developed less chronic GVHD (8 vs 36% at 1 year, P=0.003). Treatment-related mortality rates were lower with RIC (7 vs 29% at 100 days, P=0.03). A total of 9 of 33 patients (27%) who underwent immune manipulation for persistent or progressive disease had disease control, suggesting a graft-vs-tumor (GVT) effect. Progression-free survival (PFS) at 1 year was 23% with myeloablative conditioning and 8% with RIC (P=0.09). Women who developed acute GVHD after an RIC regimen had lower risks of relapse or progression than those who did not (relative risk, 3.05: P=0.03), consistent with a GVT effect, but this did not affect PFS. These findings support the need for preclinical and clinical studies that facilitate targeted adoptive immunotherapy for breast cancer to explore the benefit of a GVT effect in breast cancer.
Bone Marrow Transplantation 04/2008; 41(6):537-45. · 3.75 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: We report the experience of the EBMT Solid Tumours Working Party (STWP) using high-dose chemotherapy (HDCT) with PBPC support in patients with non-small cell lung cancer (NSCLC). Between 1989 and 2004, 36 NSCLC patients (27 men and 9 women), median age 53.5 years (range: 24-62) were treated with 63 HDCT courses. A high-dose carboplatin-based regimen was used in 53% of the cases. Thirty-two patients had relapsed/metastatic disease, while four classified as stage IIIB received HDCT followed by radiotherapy. No treatment-related death occurred. Of 25 patients who were planned to receive multi-cycle HDCT, 4 cases (16%) interrupted the treatment early due to prolonged severe toxicities and 4 (16%) due to progressive disease. Of 36 evaluable patients, 3 (8%) achieved a complete remission and 13 (36%) had a partial remission at an overall response rate of 44%. Of these, one patient with stage IIIB and one with stage IV are alive disease free at 71+ and 149+ months, respectively. After a median follow-up of 48 months (range: 6-149), median survival was 7 months (range: 1-149). Despite one anecdotal case, HDCT did not show significant activity, but induced relevant morbidity in NSCLC patients.
Bone Marrow Transplantation 01/2008; 40(11):1045-8. · 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
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A-L Herr,
M Labopin, D Blaise,
N Milpied,
M Potter,
M Michallet,
W Heit,
F Ferrara,
J Esteve,
W Arcese, [......],
J M Rowe,
G Kobbe,
A Rosselet,
D Bunjes,
B Rio,
M Brune,
A Nagler,
N C Gorin,
F Frassoni,
V Rocha
[show abstract]
[hide abstract]
ABSTRACT: We conducted a retrospective registry-based analysis to compare the outcome of 361 allogeneic human leukocyte antigen (HLA)-identical peripheral blood stem cell transplants (PBSCT) with reduced intensity conditioning (RIC) to that of 1369 autologous (auto) PBSCT in patients aged 50 years or older with de novo acute myeloid leukemia (AML), performed from 1997 until 2003 and reported to the European Group for Blood and Marrow Transplantation. Median age was 58 and 57 years in the RIC and auto groups, respectively. RIC patients had more advanced disease at the time of transplant. At a median follow-up of 24 months for RIC and 16 months for auto, multivariate analysis showed a lower risk for relapse (RR 0.77, P=0.013) without increased non-relapse mortality (NRM) in RIC patients (RR 1.26, P=0.28). Moreover, leukemia-free survival (RR 1.22, P=0.02) and overall survival (OS) (RR 1.32, P=0.005) were superior in the RIC group. In patients in 1st (CR), fewer relapses were counterbalanced by significantly increased NRM. Therefore, there was no survival advantage in this subgroup. In patients in 2nd or subsequent CR, LFS and OS were superior in the RIC group. RIC transplants show encouraging results in this older patient population with de novo AML.
Leukemia 02/2007; 21(1):129-35. · 9.56 Impact Factor
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L Barkholt,
M Bregni,
M Remberger, D Blaise,
J Peccatori,
G Massenkeil,
P Pedrazzoli,
A Zambelli,
J-O Bay,
S Francois,
R Martino,
C Bengala,
M Brune,
S Lenhoff,
A Porcellini,
M Falda,
S Siena,
T Demirer,
D Niederwieser,
O Ringdén
[show abstract]
[hide abstract]
ABSTRACT: An allogeneic antitumour effect has been reported for various cancers. We evaluated the experience of allogeneic haematopoietic stem cell transplantation (HSCT) for renal cell carcinoma (RCC) in 124 patients from 21 European centres.
Reduced intensity conditioning and peripheral blood stem cells from an HLA-identical sibling (n = 106), a mismatched related (n = 5), or an unrelated (n = 13) donor were used. Immunosuppression was cyclosporine alone, or combined with methotrexate or mycophenolate mofetil. Donor lymphocyte infusions (DLI) were given to 42 patients. The median follow-up was 15 (range 3-41) months.
All but three patients engrafted. The cumulative incidence of moderate to severe, grades II-IV acute GVHD was 40% and for chronic GVHD it was 33%. Transplant-related mortality was 16% at one year. Complete (n = 4) or partial (n = 24) responses, median 150 (range 42-600) days post-transplant, were associated with time from diagnosis to HSCT, mismatched donor and acute GVHD II-IV. Factors associated with survival included chronic GVHD (hazards ratio, HR 4.12, P < 0.001), DLI (HR 3.39, P < 0.001), <3 metastatic sites (HR 2.61, P = 0.002) and a Karnofsky score >70 (HR 2.33, P = 0.03). Patients (n = 17) with chronic GVHD and given DLI had a 2-year survival of 70%.
Patients with metastatic RCC, less than three metastatic locations and a Karnofsky score >70% can be considered for HSCT. Posttransplant DLI and limited chronic GVHD improved the patient survival.
Annals of Oncology 08/2006; 17(7):1134-40. · 6.43 Impact Factor
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H de Lavallade,
C Faucher,
S Fürst,
J El-Cheikh,
N Vey,
D Coso,
R Bouabdallah,
A-M Stoppa,
J-A Gastaut, D Blaise,
M Mohty
Bone Marrow Transplantation 05/2006; 37(7):709-10. · 3.75 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: La greffe allogénique de cellules souches hématopoïétiques (allo-SCH) représente la forme d’immunothérapie cellulaire la plus
employée. Le pouvoir curatif de l’allo-SCH est classiquement fondé sur deux mécanismes d’action: le conditionnement par fortes
doses de chimiothérapie et/ou radiothérapie induisant une cytoréduction importante des cellules tumorales et le contrôle antitumoral
immunologique assuré par des effecteurs immuns allogéniques appelé effet GVL (effet du greffon contre la leucémie). Cette
thérapeutique est actuellement en phase de mutation en raison d’une meilleure compréhension des mécanismes de l’effet allogénique
et de développements technologiques et médicamenteux, ayant permis l’émergence des conditionnements atténués ou à intensité
réduite, visant à réduire la toxicité en limitant l’intensité chimiothérapique du conditionnement, et en favorisant l’effet
immunologique. Appliquée aux leucémies aigues myéloïdes, l’allo-SCH avec un conditionnement atténué a permis d’obtenir des
résultats prometteurs, y compris chez des patients à haut risque, justifiant son développement et son affinement pour un bénéfice
potentiel attendu chez de nombreux patients.
Allogeneic stem cell transplantation (allo-SCT) is the most widely used form of immunotherapy. The curative potential of allo-SCT
is classically based on the cytoreduction of tumoral cells induced during the high dose chemo- and/or radiotherapy-based conditioning
regimen and the immune control mediated by allogeneic immune effectors (graft versus leukemia effect, GVL). Allo-SCT is currently
under important mutations because of better understanding of the GVL mechanisms and the development of new treatment techniques
that lead to the development of reduced intensity conditioning regimens aiming to reduce the toxicity while favoring the immune
component of the anti-tumoral effect. Several studies have already established the potential benefit of RIC allo-SCT in patients
with acute myeloid leukemia (AML), including high risk patients highlighting the need to further refine this approach because
of the potential benefit that can be expected in different patients’ subgroups.
Oncologie 04/2006; 8(4):344-349. · 0.17 Impact Factor
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N Dhédin,
H Dombret,
X Thomas,
V Lhéritier,
J-M Boiron,
F Rigal-Huguet,
N Vey,
M Kuentz,
O Reman,
F Witz,
A Delannoy,
T Kovacsovics,
K Bradstock,
C Charrin,
C Boucheix,
J Gabert, D Blaise,
D Fière,
J-P Vernant
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the results of autologous stem cell transplantation (ASCT) in a large population of adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR), we performed an individual data-based overview of the last three trials from the LALA group. Overall, 349 patients with ALL prospectively randomized in the consecutive LALA-85, -87, and -94 trials to receive either ASCT or chemotherapy as post-CR treatment were analyzed. Eligibility criteria were 15-50-year-old patients without sibling donors in both LALA-85/87 trials and 15-55-year-old patients with high-risk ALL and no sibling donors in the LALA-94 trial. Intent-to-treat analysis, which compared 175 patients from the ASCT arm to 174 patients from the chemotherapy arm, showed that ASCT was associated with a lower cumulative incidence of relapse (66 vs 78% at 10 years; P=0.05), without significant gain in disease-free or overall survival. Despite a possible lack of statistical power, a nested case-control analysis performed in 85 patient pairs adjusted for time to transplant and prognostic covariates confirmed these intent-to-treat results in patients actually transplanted. Of interest, the reduced relapse risk after ASCT translated in better disease-free survival in the 300 rapid responders who reached CR after the first induction course.
Leukemia 03/2006; 20(2):336-44. · 9.56 Impact Factor
