6 results on '"Guy Sauvageau"'
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2. Bortezomib Maintenance After Allogeneic Transplantation in Newly Diagnosed Myeloma Patients Results in Decreased Incidence and Severity of Chronic GVHD
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Jean-Sébastien Claveau, Richard LeBlanc, Imran Ahmad, Jean-Sébastien Delisle, Sandra Cohen, Thomas Kiss, Nadia M. Bambace, Léa Bernard, Silvy Lachance, Denis Claude Roy, Guy Sauvageau, Olivier Veilleux, and Jean Roy more...
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Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Abstract
Allogeneic hematopoietic cell transplantation (HCT) has curative potential in myeloma but remains hampered by high rates of relapse and chronic graft-versus-host disease (GVHD). We hypothesized that bortezomib (BTZ) as maintenance therapy after allo HCT could not only decrease the incidence of relapse but also the incidence and severity of chronic GVHD. The primary endpoint of this study was to determine whether BTZ maintenance decreases the incidence and severity of chronic GVHD using National Institutes of Health (NIH) criteria. The secondary endpoints were to determine the immunosuppression burden, organ involvement and survival (overall survival, progression-free survival) in patients either receiving or not receiving BTZ. In this retrospective study, we compared the outcome of 46 myeloma patients who received BTZ after upfront tandem auto-allo HCT between 2008 and 2020 to 61 patients without maintenance. We explored the impact of BTZ maintenance on incidence and severity of chronic GVHD using the 2014 NIH criteria. At 2 years, incidences of overall (61.2% versus 83.6%; P = .001), and moderate/severe chronic GVHD (44.5% versus 77.0%; P = .001) were significantly lower in BTZ recipients who had less mouth (43% versus 67%; P = .018) and eyes (9% versus 41%; P = .001) involvement at initial diagnosis. We report a lower use of systemic steroids (45.1% versus 76.4%; P.001), mycophenolate mofetil (15.5% versus 28.2%; P = .031) and tacrolimus (34.5% versus 70.6%; P.001) in BTZ recipients. Probability of being alive and off systemic immunosuppressants at 3 years was 77% in BTZ recipients and 56% in controls (P = .046). To date, there is no difference in survival between both groups. In summary, BTZ maintenance improved incidence and severity of chronic GVHD and should be considered as a valid option in myeloma patients receiving upfront tandem auto-allo HCT. more...
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- 2022
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3. UM171 Expansion of Cord Blood Improves Donor Availability and HLA Matching For All Patients, Including Minorities
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Maude Dumont-Lagacé, Albert Feghaly, Marie-Christine Meunier, Marcie Finney, Wouter Van't Hof, Emeline Masson Frenet, Guy Sauvageau, and Sandra Cohen
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Adult ,Transplantation ,Ethnicity ,Molecular Medicine ,Immunology and Allergy ,Humans ,Cell Biology ,Hematology ,Cord Blood Stem Cell Transplantation ,Fetal Blood ,Minority Groups ,Retrospective Studies - Abstract
Cord blood (CB) stem cell transplantation offers a greater tolerance to HLA mismatches compared to adult-derived stem cell transplants (i.e., bone marrow or peripheral blood stem cells). Indeed, 4/6 or 5/8 HLA-matched CB transplantations are regularly performed for patients lacking a matched unrelated donor. Unfortunately, most banked CB units contain a stem cell dose that is too small to treat adult patients, resulting in only 4% to 5% of available CB units offering an adequate cell dose for prompt engraftment for adult patients. Ex vivo stem cell expansion appears to be an attractive strategy to circumvent this cell dose issue, while also enabling the selection of better HLA-matched CB units. In this study, we retrospectively performed HLA matching simulations to assess how the minimal cell content requirements associated with UM171 CB expansion may improve usability of existing CB unit inventories and donor availability for patients of different races and ethnicities. We analyzed a dataset of 58,971 adults for whom a donor search was initiated through the National Marrow Donor Program Be The Match registry against 142,942 CB units from major U.S. public CB banks listed on the Be The Match registry. Our results show that by enabling selection of smaller CB units, UM171-expanded CB transplantation increases donor availability from 72% to 84% for all patients compared to single unmanipulated CB transplantation. Furthermore, the low cell dose criteria for UM171-expanded CB also increases donor availability compared to double CB transplantation, while enabling better HLA matching between donor and recipient. UM171 expanded CB appears particularly beneficial for racial and ethnic minority patients as CB availability increases from 53% to 78% for African Americans, from 66% to 85% for Hispanics, and from 68% to 84% for Asians and Pacific Islanders, compared to single unmanipulated CB transplantation. In addition, UM171 expansion dramatically improves usability of CB units currently in inventories, as only 4.3% and 0.6% of banked CBs have sufficient cell doses for a 70 kg and 100 kg patient, respectively. UM171 raises this proportion to 53.8% and 20.2%, respectively, making CB banks potentially more cost effective. In conclusion, UM171 expansion allows the use of smaller CB units while also improving access to transplantation for racial and ethnic minorities. more...
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- 2021
4. Impact of Implementing a Bendamustine-Based Conditioning Regimen on Outcomes of Autologous Stem Cell Transplantation in Lymphoma while Novel Cellular Therapies Emerge
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Sylvie Lachance, Alex Bourguignon, Josie-Anne Boisjoly, Philippe Bouchard, Imran Ahmad, Nadia Bambace, Léa Bernard, Sandra Cohen, Jean-Sébastien Delisle, Isabelle Fleury, Thomas Kiss, Luigina Mollica, Denis-Claude Roy, Guy Sauvageau, Olivier Veilleux, Justine Zehr, Miguel Chagnon, and Jean Roy more...
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Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Abstract
With the advent of new cellular and targeted therapies, treatment options for relapsed and refractory (r/R) lymphomas have multiplied, and the optimal approach offering the best outcomes remains a matter of passionate debate. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is still considered a treatment option for patients with chemosensitive lymphoma when cure is the expected goal. The myeloablative conditioning regimen preceding the stem cell infusion is considered the effective component of this approach. Carmustine (BCNU)-based preparative regimens, such as BEAM and BEAC, are considered the standard of care and have shown efficacy and low nonrelapse mortality (NRM). Comparative studies between conditioning regimens have failed to identify a better option. After a BCNU drug shortage in Canada followed by a steep increase in price, we elected to substitute BCNU for bendamustine (benda) in the preparative regimen. The purpose of this substitution was to improve response while preserving safety and controlling costs. From May 2015 to May 2018, a total of 131 consecutive lymphoma patients received benda-EAM conditioning. These patients were compared with 96 consecutive patients who received BCNU-based conditioning from January 2012 to May 2015. Apart from conditioning, supportive care measures were the same in the 2 groups. Patients receiving benda were older (55.7 years versus 51.1 years; P = .002). The development of grade ≥3 mucositis was more frequent with benda conditioning (39.5% versus 7.8%; P.001) leading to a greater requirement for parenteral nutrition (48.9% versus 21.9%; P.001). A transient creatinine increase1.5 times the upper limit of normal (15.3% versus 4.2%; P.008) and intensive care unit admission (6.9% versus 1.1%; P.029) were more frequent with benda; however, there were no between-group differences in cardiac, pulmonary, or liver toxicity and NRM. With a median follow-up of 48 months for the benda group and 60 months for the BCNU group, benda was associated with significantly better progression-free survival (71% versus 61%; P = .040; hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.0 to 2.7) and overall survival (86% vs 71%; P = .0066; HR, 2.6; 95% CI, 1.3 to 5.4) compared with BCNU-based conditioning regimens. While novel therapies emerge, our study demonstrates that benda-EAM is safe and effective and should be considered a valid alternative to BCNU conditioning to improve outcomes of patients with chemosensitive r/R lymphomas undergoing ASCT. more...
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- 2023
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5. Substitution of Carmustine for Bendamustine in the Transplant Conditioning Regimen Improves Survival in Relapsed/Refractory Lymphoma Patients
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Silvy Lachance, Guy Sauvageau, Philippe Bouchard, Alex Bourguignon, Jean-Sébastien Delisle, Nadia M. Bambace, Denis-Claude Roy, Jean Roy, Miguel Chagnon, Sandra Cohen, Imran Ahmad, Léa Bernard, Justine Zehr, Thomas Kiss, and Josie-Anne Boisjoly more...
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Oncology ,Bendamustine ,Transplantation ,medicine.medical_specialty ,Carmustine ,Transplant Conditioning ,business.industry ,Cell Biology ,Hematology ,medicine.disease ,Lymphoma ,Regimen ,Internal medicine ,Relapsed refractory ,medicine ,Molecular Medicine ,Immunology and Allergy ,business ,medicine.drug - Published
- 2021
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6. UM171-Expanded Cord Blood Transplants Support Robust T Cell Reconstitution with Low Rates of Severe Infections
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Guillaume B Cardin, Jean-Sébastien Delisle, Léa Bernard, Maude Dumont-Lagacé, Claude Perreault, Cédric Carli, Denis-Claude Roy, Jean Roy, Sandra Cohen, Lambert Busque, Silvy Lachance, Ann Brasey, Imran Ahmad, Mégane Tanguay, Nadia M. Bambace, Qi Li, Guy Sauvageau, Simon F. Dufresne, Tibila Kientega, Francis Rodier, Jalila Chagraoui, Assya Trofimov, Sébastien Lemieux, and Thomas Kiss more...
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medicine.medical_specialty ,T-Lymphocytes ,T cell ,medicine.medical_treatment ,Immunology ,Recent Thymic Emigrant ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Biochemistry ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Retrospective Studies ,Transplantation ,business.industry ,ELISPOT ,T-cell receptor ,Cell Biology ,Hematology ,Fetal Blood ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cord blood ,Cohort ,Molecular Medicine ,Cord Blood Stem Cell Transplantation ,Stem cell ,business ,030215 immunology - Abstract
Introduction Rapid T cell reconstitution following hematopoietic stem cell transplantation is essential for protection against infections and has been associated with lower incidence of chronic graft-vs-host disease (cGVHD), relapse and transplant-related mortality (TRM). While cord blood (CB) transplants are associated with lower rates of cGVHD and relapse, their low stem cell content results in slower immune reconstitution and higher risk of graft failure, severe infections and TRM. Recently, results of a Phase I/II trial revealed that single UM171-expanded CB transplant allowed the use of smaller CB units without compromising engraftment. We now report on T cell reconstitution and immune function in patients transplanted with UM171-expanded CB grafts. Methods We performed a retrospective analysis of 20 patients treated with UM171-expanded CB and compared it to a contemporary cohort of 12 patients treated in the same institution who received unmanipulated CB transplant with similar conditioning regimens. Of note, no patient received ATG as part of the conditioning in either cohort. We used flow cytometry and TCR sequencing to evaluate T cell reconstitution, and virus-specific ELISpot assays to evaluate T cell function in the first year post-transplantation. We also categorized infectious events as per definitions of infection severity in the BMT CTN Technical MOP Version 3.0 and report the mean cumulative count of infectious events for each cohort. Results While median T cell dose in graft was at least 2-3x lower for the cohort of patients treated with UM171-expanded CB due to the selection of smaller cords and to cell loss occurring during CD34 selection process, numbers and phenotype of T cells at 3, 6 and 12 months post-transplant were similar in patients treated with UM171-expanded or unmanipulated CB transplant. TCR sequencing analyses revealed that UM171 patients had greater T cell diversity and higher numbers of T cell clonotypes at 12 months post-transplant compared to patients who received unmanipulated CB. Younger UM171 patients (i.e. Conclusion Our data show that the relative T-cell paucity of the UM171 graft is rapidly compensated after transplant with no significant difference observed between the two cohorts in terms of numbers and phenotypes of T cells at 3, 6 or 12 months post-transplant. Although it is difficult to dissect the relative contribution of homeostatic expansion and de novo thymopoiesis, recipients of UM171 grafts had a greater TCR diversity at one year, which was more evident among patients younger than 40 years of age. The prompt immune reconstitution observed in UM171 patients translated into a low rate of severe (grade 2-3) infections and no infection-related mortality. These results support rapid and functional T cell reconstitution following UM171 expanded CB transplantation, which likely contributes to the absence of moderate/severe cGVHD, infection-related mortality and late TRM observed in this cohort. Figure legend: Mean cumulative counts of infectious events in patients transplanted with UM171-expanded (blue) or unmanipulated (red) CB. Mean cumulative counts are shown for all infectious events (A), bacterial (B) and viral (C) infections. Events were categorized by type and severity as per BMT CTN guidelines (Appendix 4A). Infectious events of grade 1-3 are shown in pale colors, while more severe events (grade 2-3) are shown in dark colors. Censored patients (including those who relapsed) are indicated with white circles. Figure 1 Disclosures Dumont-Lagacé: ExCellThera: Current Employment. Busque:Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria. Sauvageau:ExCellThera: Current equity holder in private company, Other: CEO, Patents & Royalties. Cohen:ExCellThera: Consultancy, Other: principal investigator of an ongoing UM171 clinical trial. more...
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- 2021
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