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  • 1
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1826-1826
    Abstract: Introduction: Primary mediastinal B cells lymphoma (PMBCL) is a rare subtype of aggressive non Hodgkin lymphoma (NHL). Despite therapeutic progresses, 10 to 30% of PMBCL patients are primary refractory or experience early relapses (R/R). Despite Autologous hematopoietic cell transplantation (auto-HCT) after bridging therapy or new therapies such as PD-1 inhibitors or CAR-T cells, R/R PMBL patients have a very poor outcome. Allogeneic stem cell transplantation (allo-HCT) is thus a potentially curative treatment for patients who relapsed after salvage therapies. Only limited data have been published about allo-SCT in R/R PMBCL (Herrera A. F, BBMT 2019). In the present study conducted on behalf the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) and the lymphoma study association (LYSA) group, we investigated the outcomes of allo-transplanted adult R/R PMBCL. Methods This multicenter retrospective study included all adult R/R PMBCL patients reported to the SFGM-TC and who underwent an allo-HCT between 1999 and 2018. Data have been obtained through ProMISe (internet-based system shared by all European transplantation centers) and completed by consulting the medical files of the LYSA group centers. All patients have given signed informed consent. Results Thirty-three patients with R/R PMBCL from 19 French (n=29) and 3 Belgium (n=4) centers were included. The median age at transplant was 33 y (18-61), with a predominance of female patients (58%). Majority of patients had a low HCT-CI score [0 = 9/17 (53%), data missing in 16 patients]. Seventy-six percent of patients had an IPI score between 1 and 2 and Ann Harbor score was ≥ 3 in 56.6% at diagnosis. Median number of treatment lines before allo-HCT was 3 (1-6). All patients received poly-chemotherapies with anthracyclines and anti-CD20 as first-line therapy. Most sixty-one percent of patients had previously undergone auto-HCT and one patient received CAR-T before allo-HCT. Forty one percent of patients were primary refractory. At time of transplant, 50% of patients were in complete response, 40% in partial response, and 10% had a progressive disease. Conditioning regimen was reduced intensity regimen in 63%. Stem cell source was PBSC in 88%. Donors were sibling in 42% or matched related donor in 39%. An alternative donor was chosen in 18%. GVHD prophylaxis included antithymocyte globulin in 61%, and calcineurin inhibitor in 97%. Median follow up was 78 months (3.5-157). Considering the whole cohort, 2y OS, DFS, NRM, and cumulative incidence of relapse were 48% (95%CI: 33-70), 60% (95%CI: 44-82), 18% (95%CI: 7-34), and 34% (95%CI: 18-50) respectively. Cumulative incidences of day 100 grade I-II and III-IV acute GVHD 36% and 0%, respectively. Cumulative incidence was 32% among whom 33% had an extensive cGVHD. Patients with progressive disease at transplantation had worst 2y PFS and OS (PFS: HR: 6.12, 95%CI: 1.32-28.31, p=0.02 and OS: HR: 7.04, 95%CI: 1.52-32.75, p=0.013). Conclusion: To our knowledge, this is the largest published study evaluating outcomes of allo-HCT for R/R PMBCL. Although this is a retrospective study with a limited number of patients, the outcomes suggest that allo-HCT is a therapeutic option providing durable remissions for patients with R/R PMBCL. Introduction: Primary mediastinal B cells lymphoma (PMBCL) is a rare subtype of aggressive non Hodgkin lymphoma (NHL). Despite therapeutic progresses, 10 to 30% of PMBCL patients are primary refractory or experience early relapses (R/R). Despite Autologous hematopoietic cell transplantation (auto-HCT) after bridging therapy or new therapies such as PD-1 inhibitors or CAR-T cells, R/R PMBL patients have a very poor outcome. Allogeneic stem cell transplantation (allo-HCT) is thus a potentially curative treatment for patients who relapsed after salvage therapies. Only limited data have been published about allo-SCT in R/R PMBCL (Herrera A. F, BBMT 2019). In the present study conducted on behalf the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) and the lymphoma study association (LYSA) group, we investigated the outcomes of allo-transplanted adult R/R PMBCL. Methods This multicenter retrospective study included all adult R/R PMBCL patients reported to the SFGM-TC and who underwent an allo-HCT between 1999 and 2018. Data have been obtained through ProMISe (internet-based system shared by all European transplantation centers) and completed by consulting the medical files of the LYSA group centers. All patients have given signed informed consent. Results Thirty-three patients with R/R PMBCL from 19 French (n=29) and 3 Belgium (n=4) centers were included. The median age at transplant was 33 y (18-61), with a predominance of female patients (58%). Majority of patients had a low HCT-CI score [0 = 9/17 (53%), data missing in 16 patients]. Seventy-six percent of patients had an IPI score between 1 and 2 and Ann Harbor score was ≥ 3 in 56.6% at diagnosis. Median number of treatment lines before allo-HCT was 3 (1-6). All patients received poly-chemotherapies with anthracyclines and anti-CD20 as first-line therapy. Most sixty-one percent of patients had previously undergone auto-HCT and one patient received CAR-T before allo-HCT. Forty one percent of patients were primary refractory. At time of transplant, 50% of patients were in complete response, 40% in partial response, and 10% had a progressive disease. Conditioning regimen was reduced intensity regimen in 63%. Stem cell source was PBSC in 88%. Donors were sibling in 42% or matched related donor in 39%. An alternative donor was chosen in 18%. GVHD prophylaxis included antithymocyte globulin in 61%, and calcineurin inhibitor in 97%. Median follow up was 78 months (3.5-157). Considering the whole cohort, 2y OS, DFS, NRM, and cumulative incidence of relapse were 48% (95%CI: 33-70), 60% (95%CI: 44-82), 18% (95%CI: 7-34), and 34% (95%CI: 18-50) respectively. Cumulative incidences of day 100 grade I-II and III-IV acute GVHD 36% and 0%, respectively. Cumulative incidence was 32% among whom 33% had an extensive cGVHD. Patients with progressive disease at transplantation had worst 2y PFS and OS (PFS: HR: 6.12, 95%CI: 1.32-28.31, p=0.02 and OS: HR: 7.04, 95%CI: 1.52-32.75, p=0.013). Conclusion: To our knowledge, this is the largest published study evaluating outcomes of allo-HCT for R/R PMBCL. Although this is a retrospective study with a limited number of patients, the outcomes suggest that allo-HCT is a therapeutic option providing durable remissions for patients with R/R PMBCL. Disclosures Sibon: Abbvie: Consultancy; Takeda: Consultancy; iQone: Consultancy; Roche: Consultancy; Janssen: Consultancy. Loschi: AbbVie: Ended employment in the past 24 months, Honoraria; CELGENE/BMS: Honoraria; Gilead: Ended employment in the past 24 months, Honoraria; Novartis: Ended employment in the past 24 months, Honoraria; Servier: Ended employment in the past 24 months, Honoraria; MSD: Honoraria. Dulery: Novartis: Honoraria; Takeda: Consultancy; Gilead: Other: Travel support and registration fees for scientific meetings .
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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    detail.hit.zdb_id: 80069-7
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  • 2
    Online Resource
    Online Resource
    Elsevier BV ; 2020
    In:  Current Research in Translational Medicine Vol. 68, No. 3 ( 2020-08), p. 93-104
    In: Current Research in Translational Medicine, Elsevier BV, Vol. 68, No. 3 ( 2020-08), p. 93-104
    Type of Medium: Online Resource
    ISSN: 2452-3186
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2848806-4
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  • 3
    Online Resource
    Online Resource
    Elsevier BV ; 2020
    In:  Current Research in Translational Medicine Vol. 68, No. 3 ( 2020-08), p. 83-91
    In: Current Research in Translational Medicine, Elsevier BV, Vol. 68, No. 3 ( 2020-08), p. 83-91
    Type of Medium: Online Resource
    ISSN: 2452-3186
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2848806-4
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  • 4
    In: Bone Marrow Transplantation, Springer Science and Business Media LLC, Vol. 58, No. 5 ( 2023-05), p. 506-513
    Type of Medium: Online Resource
    ISSN: 0268-3369 , 1476-5365
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2004030-1
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  • 5
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 38-39
    Abstract: Aim: Dynamic assessment of trends over time in patient- and transplant-specific characteristics and outcomes for patients undergoing 1st allogeneic haematopoietic cell transplant (allo-HCT) for Myelofibrosis (MF). Methods and Results: A total of 4142 MF patients were analysed who underwent allo-HCT between 1995-2018 (24-year period) across 278 centres based on data reported to the European Society for Blood and Marrow Transplantation. For analysis, 4 cohorts were considered based on year of allo-HCT: & lt;2006 n=389 (9.4%), 2006-2010 n=910 (22%), 2011-2014 n=1148 (27.7%) and 2015-2018 n=1695 (40.9%). A steady increase in MF allo-HCT activity over time was apparent paralleled with increasing numbers of participating transplant centres. A total of 2603 (62.8%) patients were male, 3239 (78.2%) had Primary MF, 409 (9.9%) and 494 (11.9%) post-Polycythaemia Vera and post-Essential Thrombocythaemia MF, respectively. An increased median interval (lnterquartile range (IQR)) between diagnosis and transplant was evident over time ( & lt;2006 median 20.8 (8.9-62.2) months versus 36.2 (11.6-107.5) months in 2015-2018 period;p & lt;0.001), potentially reflecting increased availability of therapeutics in recent eras (untreated patients & lt;2006= 59.4% versus 2015-2018=23.7%). Median recipient age (IQR) increased over time by ~ a decade between earliest cohort and most recent: & lt;2006, 49.4 years (43.1-55.3) versus 59.3 years (53.4-64.8)2015-2018. Prior to 2006, patients & gt;60 years accounted for 8.7% of adults undergoing allo-HCT whereas for 2015-2018 this was 47%. Over time, increasing number of patients with a Karnofsky performance status (KPS) & lt;90 underwent allo-HCT ( & lt;2006=19.7% versus 36.1% 2015-18; p & lt;0.001). Peripheral Blood (PB) was the predominant stem cell source and utilisation increased over time, accounting for 74.8% & lt;2006 and 92.2% within 2015-2018 cohort. Cord blood utilisation was limited to & lt;1% throughout the 24-year study period. Significant shifts towards use of unrelated donors (URD) in more recent periods was apparent (p & lt;0.001). Moreover, increased use of mismatched related donors (MMRD) was particularly evident in 2015-2018 cohort; n=152 (9%) versus n=74 (3%) cumulative for other 3 cohorts combined; p & lt;0.001. Decreased use of myeloablative and TBI- based conditioning was evident over time (p & lt;0.001). Specifically, there was increased use of busulphan-based regimens ( & lt;2006: 44.2% versus 2015-2018: 72%). Regarding T cell depletion, trends demonstrated increased use of anti-thymocyte globulin (ATG) over time ( & lt;2006=37.3% vs 69.9% 2015-2018; p & lt;0.001). Median time to both neutrophil (median 18 days across all cohorts) and platelet engraftment was similar in all 4 cohorts, with no significant variation when stratified by period of transplantation. Allo-HCT outcomes, survival, GVHD and relapse endpoints are shown for all 4 cohorts in Table 1. Overall for the entire group, significant factors associated with worse OS, RFS and NRM remained older age and a poor KPS ( & lt;90). No significant differences between cohorts were noted for either estimated 3-year OS ( & lt;2006=55% (50-60%), 2006-2010=60% (56-63%), 2011-2014 and 2015-2018= 58% (55-61%); p=0.299) or non-relapse mortality (NRM (Table 1); p=0.523), despite increasing numbers of older, less fit patients, and more frequent HLA-mismatched transplants over time. To investigate survival findings in more detail an adjusted model will be presented including period of allo-HCT and transplant-related variables. Cumulative incidence of relapse at 3 years was similar across all cohorts, suggesting no significant changes with time. Most common causes of death across all 4 cohorts remained GVHD and infection. Of note, rates of acute (a)GVHD grade II-IV by day +100 decreased from the earliest cohort & lt;2006 compared to the later groups (p=0.027) as did rates of overall chronic (c) GVHD whereby this was evident in 57% (95% CI 52-62%) & lt;2006 cohort compared to 44% (95% CI 42-47%) in the 2015-2018 group, predominantly reflected by reductions in extensive cGVHD (Table 1). Conclusions: Despite a marked increase over this 24-year period in recipient age, RIC regimen utilisation and use of both URD and MMRD, this comprehensive analysis demonstrates stable OS and EFS rates. However, rates of GVHD have decreased over time, in particular extensive cGVHD. Further work is required to improve both the considerable NRM and relapse rates which remain significant. Disclosures McLornan: JAZZ PHARMA: Honoraria, Speakers Bureau; CELGENE: Honoraria, Speakers Bureau; NOVARTIS: Honoraria, Speakers Bureau. Platzbecker:Amgen: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Geron: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding. Chevallier:Incyte Corporation: Honoraria. Martínez-Lopez:Altum, Hosea: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Vivia Biotech: Honoraria; Amgen: Speakers Bureau; Takeda: Speakers Bureau; Roche: Speakers Bureau; Janssen: Speakers Bureau; Incyte: Research Funding, Speakers Bureau; Bristol Myers Squibb: Research Funding, Speakers Bureau; Novartis: Research Funding. Yakoub-Agha:Celgene: Honoraria; Jazz Pharmaceuticals: Honoraria; Novartis: Honoraria; Gilead/Kite: Honoraria, Other: travel support; Janssen: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 2079-2079
    Abstract: Chimerism analysis after allogeneic hematopoietic stem cells transplantation (HSCT) allows documentation and understanding of important clinical events such as engraftment, graft failure, and/or relapse. Few data are available on whether T-cell chimerism might be more informative than global chimerism. In this study, we focused on selective CD3+ T-cell chimerism and its interest to predict events after allogeneic HSCT. Methods This is a single center retrospective study. Only patients with a survival more than 3 months were included. Information concerning donors, recipients, conditioning regimen, graft harvesting and follow-up were collected in our center using prospective forms from Promise database. Evaluation of T-cell chimerism was performed on CD3+ blood cells after immunomagnetic sorting, by PCR-STR (short-tandem repeats) multiplex technique using 15 different markers. Analysis of the tandem repeat polymorphism was performed by sequencer and Genscan software (Applied Biosystem Inc.). Chimerism was evaluated in 2 ways: positive or negative, and % of recipient. An analysis with repeated measures was also performed to determine the utility of a positive measure of chimerism, independently of the date of sample after allograft, to predict a relapse. Results Between January 2006 and December 2011, 148 patients (pts) were admitted in our unit for allogeneic HSCT (32% with myeloablative conditioning and 68% with reduced conditioning). Median age was 54.3 years, 59 male, 89 female. Diagnosis included AML/MDS (n=77), ALL (n=23), Aplastic anemia (n=4), lymphoma and CLL (n=23), myeloma (n= 8) and myeloproliferative disorders (n=13). The donor was matched sibling (n=51), matched unrelated (10/10) (n=74) or mismatched unrelated (9/10)(n=23). Graft source was PBSC (n=97), BM (n=33) or CB (n=18). At transplant, 108 pts (73%) were in complete remission, 19 (13%) presented partial response and 21 (14%) have progressive disease. At time of analysis, median follow-up was 1.75 years. Median overall Survival (OS) was estimated at 2 years. Forty-seven pts (32%) presented relapse. Seventy pts (47%) are still alive. Main causes of death were HSCT related (n=38), relapse or progression (n=33) and other (n=7). Acute GVHD grade II-IV incidence was 32% (13.5% grade III-IV) and 58% for chronic GVHD. At day +30, 56% of pts presented a mixed T-cell chimerism with 36 (24.3%) pts with a chimerism higher than 25% recipient. At day +90, 41% have remained positive. For NRM, aGVHD and age were the only prognostic parameters statistically identified. For PFS, only T-cell chimerism with a positive 25% cut-off at D+30 was identified as a prognostic factor (p=.0017, HR(IC 95%) 2.52(1.39; 4.58). PFS was not reached if T-cell chimerism was inferior to 25% at D+30 versus 1.35 years (figure 1). The results were concordant in a subgroup analysis performed according to the myeloid or lymphoid neoplasia status. Otherwise, cGVHD incidence was higher if T-cell chimerism was less than 25% at D+30 (70% vs. 18%). Finally, the analysis with repeated measures confirmed that positive T-cell chimerism is strongly correlated with relapse (p=.001; HR (CI95%) 90.18(30.11; 270.13)). Conclusion After allogeneic HSCT, mixed T-cell chimerism higher than 25% at day +30 is strongly correlated with poor PFS, independently of source of cells, donors, intensity of conditioning, diagnosis or disease status at transplant. Considering this high-risk population, early intervention should probably be considered. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    In: Journal of Medical Virology, Wiley, Vol. 92, No. 12 ( 2020-12), p. 3665-3673
    Abstract: Recipients of allogeneic hematopoietic stem cell transplantation (allo‐HCT) with positive cytomegalovirus (CMV) serology are at increased risk of morbidity and mortality. The primary objective of this study was to assess the association between treated CMV infection and overall mortality within 1 year after allo‐HCT in adult CMV‐seropositive Recipients (R+). Secondary objectives included overall 5‐year mortality after allo‐HCT, risk factors for treated CMV infection, associations between treated CMV infection and allo‐HCT complications and medical costs. Methods A multicenter retrospective cohort study was conducted in adult CMV‐seropositive recipients (R+) who underwent to allo‐HCT between 1st January 2010 and 31st December 2014. Results Five hundred seventy two CMV‐seropositive patients (mean age, 50.2 years) undergoing allo‐HCT between 2010 and 2014 were included; 55.9% of donors were CMV seropositive. CMV infection treated with antiviral therapy was reported in 227 patients (39.7%) after transplantation. One‐year overall mortality was significantly increased in patients with treated CMV infections (hazard ratio, 1.86; 95% CI, 1.16‐3.00; P  = .011). Mean medical costs during the first post‐HCT year were higher in patients with CMV infection (€46 853 vs €31 318; P   〈  .0001). Conclusion In this large cohort of CMV‐seropositive patients undergoing allo‐HCT, treated CMV infection was significantly associated with an increased 1‐year risk of overall mortality, with increased length of stay and with hospitalization cost. The burden of CMV disease in allo‐HCT could be reduced in the future by appropriate prophylactic strategies.
    Type of Medium: Online Resource
    ISSN: 0146-6615 , 1096-9071
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 752392-0
    detail.hit.zdb_id: 1475090-9
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  • 8
    In: Annales de Dermatologie et de Vénéréologie - FMC, Elsevier BV, Vol. 1, No. 8 ( 2021-12), p. A256-
    Type of Medium: Online Resource
    ISSN: 2667-0623
    Language: French
    Publisher: Elsevier BV
    Publication Date: 2021
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  • 9
    In: Annals of Pharmacotherapy, SAGE Publications, Vol. 56, No. 9 ( 2022-09), p. 1007-1015
    Abstract: Defibrotide is indicated for patients who develop severe sinusoidal obstructive syndrome following allogeneic hematopoietic cell transplantation (allo-HCT). Preclinical data suggested that defibrotide carries a prophylactic effect against acute graft-versus-host disease (aGVHD). Objective The purpose of this study was to investigate the effect of defibrotide on the incidence and severity of aGVHD. Methods This single-center retrospective study included all consecutive transplanted patients between January 2014 and December 2018. A propensity score based on 10 predefined confounders was used to estimate the effect of defibrotide on aGVHD via inverse probability of treatment weighting (IPTW). Results Of the 482 included patients, 64 received defibrotide (defibrotide group) and 418 did not (control group). Regarding main patient characteristics and transplantation modalities, the two groups were comparable, except for a predominance of men in the defibrotide group. The median age was 55 years (interquartile range [IQR]: 40-62). Patients received allo-HCT from HLA-matched related donor (28.6%), HLA-matched unrelated donor (50.8%), haplo-identical donor (13.4%), or mismatched unrelated donor (7.0%). Stem cell source was either bone marrow (49.6%) or peripheral blood (50.4%). After using IPTW, exposure to defibrotide was not significantly associated with occurrence of aGVHD (HR = 0.97; 95% CI 0.62-1.52; P = .9) or occurrence of severe aGVHD (HR = 1.89, 95% CI: 0.98-3.66; P = .058). Conclusion and Relevance Defibrotide does not seem to have a protective effect on aGVHD in patients undergoing allo-HCT. Based on what has been reported to date and on these results, defibrotide should not be considered for the prevention of aGVHD outside clinical trials.
    Type of Medium: Online Resource
    ISSN: 1060-0280 , 1542-6270
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
    detail.hit.zdb_id: 2053518-1
    SSG: 15,3
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  • 10
    In: Bone Marrow Transplantation, Springer Science and Business Media LLC
    Type of Medium: Online Resource
    ISSN: 0268-3369 , 1476-5365
    RVK:
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2004030-1
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