42 results on '"Castagna, L."'
Search Results
2. Review for "Prognostic impact of complex karyotype on post‐transplant outcomes of myelofibrosis"
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Castagna, L, primary
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- 2022
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3. AR AND VR FOR ENHANCING MUSEUMS’ HERITAGE THROUGH 3D RECONSTRUCTION OF FRAGMENTED STATUE AND ARCHITECTURAL CONTEXT
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Spallone, R., Lamberti, F., Olivieri, L. M., Ronco, F., and Castagna, L.
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Settore L-OR/16 - Archeologia e Storia Dell'Arte Dell'India e dell'Asia Centrale ,Archaeological heritage ,Museum heritage ,Augmented reality ,Gandhāra ,Augmented reality, Virtual reality, Reconstructive modelling, Museum heritage, Archaeological heritage, Gandhāra ,Reconstructive modelling ,Virtual reality - Abstract
This paper presents the results of multidisciplinary research in which reconstructive digital modelling operates on different areas of heritage and at different scales to realize an analysis, interpretation, and communication experience in the field of museum valorization. It is, in fact, a work that includes both the philological reconstruction of the lost parts of a Buddha statue of Gandhāra, dating back to the second century b.C. and kept at the Museum of Oriental Art (MAO) in Turin, and its contextualization within a coeval architectural complex, recognized as philologically compatible, located in Balo-Kale, in the region of Gandhāra. The reconstructive models are finally used with communicative purposes for augmented reality (AR) and virtual reality (VR) applications inside the museum.
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- 2022
4. AR AND VR FOR ENHANCING MUSEUMS’ HERITAGE THROUGH 3D RECONSTRUCTION OF FRAGMENTED STATUE AND ARCHITECTURAL CONTEXT
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Spallone, R., primary, Lamberti, F., additional, Olivieri, L. M., additional, Ronco, F., additional, and Castagna, L., additional
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- 2022
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5. Long‐term outcome of patients receiving haematopoietic allogeneic stem cell transplantation as first transplant for high‐risk Hodgkin lymphoma: a retrospective analysis from the Lymphoma Working Party‐EBMT
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Gutiérrez‐García, G., primary, Martínez, C., additional, Boumendil, A., additional, Finel, H., additional, Malladi, R., additional, Afanasyev, B., additional, Tsoulkani, A., additional, Wilson, K. M. O., additional, Bloor, A., additional, Nikoloudis, M., additional, Richardson, D., additional, López‐Corral, L., additional, Castagna, L., additional, Cornelissen, J., additional, Giltat, A., additional, Collin, M., additional, Fanin, R., additional, Bonifazi, F., additional, Robinson, S., additional, Montoto, S., additional, Peggs, K. S., additional, and Sureda, A., additional
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- 2021
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6. Prognostic factors for cellular therapies ‐ CART and allogeneic SCT ‐ in relapsed /refractory large B cell lymphoma (LBCL).
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Glass, B., Sureda, A., Boumendil, A., Dreger, P., Corradini, P., Ram, R., Kroeger, N., Castagna, L., Pabst, T., Kwon, M., Wulf, G., García‐Sancho, A. M., Solano, C., Stelljes, M., Reinhardt, H. C., Rubio, M. T., Malladi, R., Blaise, D., Besley, C., and Forcade, E.
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B cell lymphoma ,CD19 antigen ,PROGNOSIS ,CELLULAR therapy - Abstract
In multivariate analysis patients with IPI (o-2) low risk at cell therapy show better OS (HR 0.81, 95% CI 0.59-1.1, I p i < 0.0001) and PFS (HR 0.62, CI: 0.46-0.83, I p i = 0.00145), comparable RI and lower NRM (HR 0.21 CI: 0.11-0.42, I p i = 0.00001) with CART compared to allo SCT. B Introduction: b Allogeneic stem cell transplantation (alloSCT) was the only curative option for younger patients (pts) with relapsed/ refractory (r/ r) LBCL (DLBCL, tFL, PMBCL). Prognostic factors for cellular therapies - CART and allogeneic SCT - in relapsed /refractory large B cell lymphoma (LBCL). [Extracted from the article]
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- 2023
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7. Long‐term outcome of patients receiving haematopoietic allogeneic stem cell transplantation as first transplant for high‐risk Hodgkin lymphoma: a retrospective analysis from the Lymphoma Working Party‐EBMT.
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Gutiérrez‐García, G., Martínez, C., Boumendil, A., Finel, H., Malladi, R., Afanasyev, B., Tsoulkani, A., Wilson, K. M. O., Bloor, A., Nikoloudis, M., Richardson, D., López‐Corral, L., Castagna, L., Cornelissen, J., Giltat, A., Collin, M., Fanin, R., Bonifazi, F., Robinson, S., and Montoto, S.
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HEMATOPOIETIC stem cell transplantation ,HODGKIN'S disease ,TRANSPLANTATION of organs, tissues, etc. ,LYMPHOMAS ,TREATMENT effectiveness - Abstract
Summary: We analysed long‐term outcome of patients receiving haematopoietic allogeneic stem cell transplantation (allo‐HSCT) as a first transplant for high‐risk Hodgkin lymphoma (HL). One hundred and ninety patients were included in this study, 63% of them had previously received brentuximab vedotin and/or checkpoint inhibitors. Seventy patients (37%) received an unrelated donor allo‐HSCT, 99 (51%) had myeloablative conditioning (MAC) and 60% had in vivo T‐cell/depleted grafts (TCD). The 100‐day cumulative incidence (CI) of grade II‐IV acute graft‐versus‐host disease (GVHD) was 25% and the 3‐year CI of chronic GVHD was 38%. The 3‐year CI of non‐relapse mortality (NRM) and relapse rate were 21% and 38% respectively. After a median follow‐up of 58 months, 3‐year overall survival (OS) and progression‐free survival (PFS) were 58% and 41% respectively. Multivariate analysis showed that, in comparison to reduced‐intensity conditioning regimens with or without TCD, MAC using TCD had similar NRM and a lower risk of relapse leading to significantly better OS and PFS. MAC without TCD was associated with higher NRM and worse survival outcomes. These results suggest that in patients with high‐risk HL and candidates of allo‐HSCT, a MAC strategy with TCD might be the best option. [ABSTRACT FROM AUTHOR]
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- 2022
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8. Post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis in HLA-matched and haploidentical donor transplants for patients with Hodgkin lymphoma: a comparative study of the LWP EBMT.
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Montoro, J, Boumendil, A, Finel, H, Bramanti, S, Castagna, L, Blaise, D, Dominietto, A, Kulagin, A, Yakoub-Agha, I, Tbakhi, A, Solano, C, Giebel, S, Gulbas, Z, López Corral, L, Pérez-Simón, J.A, Díez Martín, J.L, Sanz, J, Farina, L, Koc, Y, Socié, G, Arat, M, Jurado, M, Bermudez, A, Labussière-Wallet, H, Villalba, M, Ciceri, F, Martinez, C, Nagler, A, Sureda, A, and Glass, B
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•HSCT efficacy and safety in Hodgkin lymphoma using HLA-matched and haploidentical donors with PTCy GVHD prophylaxis.•HLA-matched had lower NRM, resulting in higher OS compared to haploidentical.•Our study supports HLA-matched donors with PTCy GVHD prophylaxis over haploidentical donors.
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- 2023
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9. Post-transplant cyclophosphamide in one-antigen mismatched unrelated donor transplantation versus haploidentical transplantation in acute myeloid leukemia: a study from the Acute Leukemia Working Party of the EBMT
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Giorgia Battipaglia, Jacques-Emmanuel Galimard, Myriam Labopin, Anna Maria Raiola, Didier Blaise, Annalisa Ruggeri, Yener Koc, Zafer Gülbas, Antonin Vitek, Simona Sica, Jose Luiz Diez-Martin, Luca Castagna, Benedetto Bruno, Montserrat Rovira, Ivan Moiseev, Massimo Martino, Giovanni Grillo, Mercedes Colorado Araujo, Claude Eric Bulabois, Stéphanie Nguyen, Gerard Socié, Mutlu Arat, Jiri Pavlu, Johanna Tischer, Hans Martin, Lucia Lopez Corral, Goda Choi, Edouard Forcade, Andrew McDonald, Fabrizio Pane, Ali Bazarbachi, Fabio Ciceri, Arnon Nagler, Mohamad Mohty, Battipaglia, G., Galimard, J. -E., Labopin, M., Raiola, A. M., Blaise, D., Ruggeri, A., Koc, Y., Gulbas, Z., Vitek, A., Sica, S., Diez-Martin, J. L., Castagna, L., Bruno, B., Rovira, M., Moiseev, I., Martino, M., Grillo, G., Araujo, M. C., Bulabois, C. E., Nguyen, S., Socie, G., Arat, M., Pavlu, J., Tischer, J., Martin, H., Corral, L. L., Choi, G., Forcade, E., Mcdonald, A., Pane, F., Bazarbachi, A., Ciceri, F., Nagler, A., Mohty, M., Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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Cyclophosphamide ,Humans ,Retrospective Studies ,Transplantation Conditioning ,Transplantation, Haploidentical ,Unrelated Donors ,Graft vs Host Disease ,Hematopoietic Stem Cell Transplantation ,Leukemia, Myeloid, Acute ,Myeloid ,endocrine system ,Transplantation ,Leukemia ,Leukemia, Myeloid, Acute/therapy ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Hematology ,Acute ,Haploidentical ,Cyclophosphamide/pharmacology ,hemic and lymphatic diseases ,Acute/therapy - Abstract
International audience; Whether to choose Haploidentical (Haplo) or one-antigen mismatched unrelated donor (1Ag-MMUD) hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy) remains an unanswered question. We compared PTCy- Haplo-HCT to PTCy-1Ag-MMUD-HCT for acute myeloid leukemia (AML) in complete remission (three groups: 1Ag-MMUD using peripheral blood (1Ag-MMUD-PB; n = 155); Haplo using bone marrow (Haplo-BM; n = 647) or peripheral blood (Haplo-PB; n = 949)). Haplo-BM and Haplo-PB had a higher non-relapse mortality (NRM) compared to 1Ag-MMUD-PB (HR 2.28, 95% CI 1.23-4.24, p
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- 2022
10. Allogeneic transplantation after PD-1 blockade for classic Hodgkin lymphoma
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Didier Blaise, Tycel Phillips, Jason T. Romancik, Roch Houot, Robert Lowsky, Martina Sollini, Jean Marc Schiano De Colella, Amer Beitinjaneh, Gunjan L. Shah, Lazaros J. Lekakis, Stephen D. Smith, Paolo Corradini, Mohamad Mohty, Maryam Rahimian, Luca Castagna, Taiga Nishihori, Asad Bashey, Talha Badar, Reid W. Merryman, Mehdi Hamadani, Carmelo Carlo-Stella, Dipenkumar Modi, Sally Arai, Kamal Bouabdallah, Valter Torri, Joseph P. McGuirk, Guillaume Manson, Anna Guidetti, Yi-Bin Chen, Hatcher J. Ballard, Julio C. Chavez, Pier Luigi Zinzani, Tatyana Feldman, Sunita Nathan, Anurag K. Singh, Massimo Magagnoli, Marie Pierre Moles-Moreau, Beatrice Casadei, Anthony Serritella, Michael Byrne, Radhakrishnan Ramchandren, Miguel-Angel Perales, Chiara De Philippis, Samantha Jaglowski, Justin Kline, Remy Dulery, Laura Giordano, Alex F. Herrera, Jonathon B. Cohen, Philippe Armand, Armando Santoro, Aspasia Stamatoulas, Stephen M. Ansell, Michael A. Spinner, Lori Dahncke, Corentin Orvain, Chloé Spilleboudt, Geoffrey Shouse, Robin Joyce, Vincent T. Ho, Matthew J. Frigault, Ryan C. Lynch, Uttam Rao, Jakub Svoboda, David A. Bond, Yago Nieto, Dana-Farber Cancer Institute [Boston], Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Università degli Studi di Milano = University of Milan (UNIMI), University of Bologna/Università di Bologna, Ohio State University [Columbus] (OSU), Stanford University, Memorial Sloane Kettering Cancer Center [New York], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Bordeaux [Bordeaux], Humanitas University [Milan] (Hunimed), P01 CA23766, U.S. Department of Health & Human Services | National Institutes of Health, U.S. Department of Health & Human Services | National Institutes of Health, 20575, Associazione Italiana per la Ricerca sul Cancro, Università degli Studi di Milano [Milano] (UNIMI), University of Bologna, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Merryman R.W., Castagna L., Giordano L., Ho V.T., Corradini P., Guidetti A., Casadei B., Bond D.A., Jaglowski S., Spinner M.A., Arai S., Lowsky R., Shah G.L., Perales M.-A., De Colella J.M.S., Blaise D., Herrera A.F., Shouse G., Spilleboudt C., Ansell S.M., Nieto Y., Badar T., Hamadani M., Feldman T.A., Dahncke L., Singh A.K., McGuirk J.P., Nishihori T., Chavez J., Serritella A.V., Kline J., Mohty M., Dulery R., Stamatoulas A., Houot R., Manson G., Moles-Moreau M.-P., Orvain C., Bouabdallah K., Modi D., Ramchandren R., Lekakis L., Beitinjaneh A., Frigault M.J., Chen Y.-B., Lynch R.C., Smith S.D., Rao U., Byrne M., Romancik J.T., Cohen J.B., Nathan S., Phillips T., Joyce R.M., Rahimian M., Bashey A., Ballard H.J., Svoboda J., Torri V., Sollini M., De Philippis C., Magagnoli M., Santoro A., Armand P., Zinzani P.L., and Carlo-Stella C.
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,allogenic stem cell transplantation, PD-1 blockade, Hodgkin lymhpoma ,[SDV]Life Sciences [q-bio] ,Programmed Cell Death 1 Receptor ,Salvage therapy ,0302 clinical medicine ,Young adult ,Immune Checkpoint Inhibitors ,ComputingMilieux_MISCELLANEOUS ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Prognosis ,Hodgkin Disease ,3. Good health ,Survival Rate ,surgical procedures, operative ,030220 oncology & carcinogenesis ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Allogeneic transplantation ,Cyclophosphamide ,Adolescent ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,Young Adult ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Survival rate ,Aged ,Retrospective Studies ,Salvage Therapy ,business.industry ,Retrospective cohort study ,[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy ,Blockade ,Transplantation ,030104 developmental biology ,Drug Resistance, Neoplasm ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies - Abstract
International audience; Anti-PD-1 monoclonal antibodies yield high response rates in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but most patients will eventually progress. Allogeneic hematopoietic cell transplantation (alloHCT) after PD-1 blockade may be associated with increased toxicity, raising challenging questions about the role, timing, and optimal method of transplantation in this setting. To address these questions, we assembled a retrospective cohort of 209 cHL patients who underwent alloHCT after PD-1 blockade. With a median follow-up among survivors of 24 months, the 2-year cumulative incidences (CIs) of non-relapse mortality and relapse were 14 and 18%, respectively; the 2-year graft-versus-host disease (GVHD) and relapse-free survival (GRFS), progression-free survival (PFS), and overall survival were 47%, 69%, and 82%, respectively. The 180-day CI of grade 3-4 acute GVHD was 15%, while the 2-year CI of chronic GVHD was 34%. In multivariable analyses, a longer interval from PD-1 to alloHCT was associated with less frequent severe acute GVHD, while additional treatment between PD-1 and alloHCT was associated with a higher risk of relapse. Notably, post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis was associated with significant improvements in PFS and GRFS. While awaiting prospective clinical trials, PTCy-based GVHD prophylaxis may be considered the optimal transplantation strategy for this patient population.
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- 2021
11. Post-Transplantation Cyclophosphamide for Graft-versus- Host Disease Prophylaxis in Multiple Myeloma Patients Who Underwent Allogeneic Hematopoietic Cell Transplantation
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Firoozeh Sahebi, Jaap van Doesum, Emanuele Angelucci, Fabio Ciceri, Anna Proia, Yener Koc, Didier Blaise, Edouard Forcade, Montserrat Rovira, Simona Sammassimo, Meral Beksac, Linda Koster, Nicolaus Kröger, David Valcárcel, Dirk-Jan Eikema, Friedrich Stölzel, Stefan Schönland, I. Yakoub-Agha, Johanna Tischer, Concepcion Herrera Arroyo, Jaime Sanz, Patrick Hayden, Luca Castagna, James F. Sanchez, Andrew McDonald, Ellen Meijer, Hematology, CCA - Cancer Treatment and quality of life, Sahebi, F., Eikema, D. -J., Koster, L., Kroger, N., Meijer, E., van Doesum, J. A., Rovira, M., Koc, Y., Angelucci, E., Blaise, D., Sammassimo, S., Mcdonald, A., Arroyo, C. H., Sanchez, J. F., Forcade, E., Castagna, L., Stolzel, F., Sanz, J., Tischer, J., Ciceri, F., Valcarcel, D., Proia, A., Hayden, P. J., Beksac, M., Yakoub-Agha, I., and Schonland, S.
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medicine.medical_specialty ,Platelet Engraftment ,Cyclophosphamide ,Graft vs Host Disease ,Gastroenterology ,Bone Marrow ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,Cumulative incidence ,Multiple myeloma ,Retrospective Studies ,Hematology ,business.industry ,hematology ,Hematopoietic Stem Cell Transplantation ,Cell Biology ,medicine.disease ,United States ,Transplantation ,Calcineurin ,multiple myeloma ,Graft-versus-host disease ,surgical procedures, operative ,clinical research ,Molecular Medicine ,Neoplasm Recurrence, Local ,business ,Unrelated Donors ,engraftment ,medicine.drug ,transplantation - Abstract
Graft-versus-host disease (GVHD) remains among the major causes of treatment failure in patients with multiple myeloma (MM) undergoing allogeneic hematopoietic cell transplantation (allo-HCT). The use of post-transplantation cyclophosphamide (PT-Cy) is now a well-established and widely used method for GVHD prophylaxis after HLA haploidentical HCT. However, the rationale for using PT-Cy in the setting of matched donor transplantation is less apparent, given the lesser degree of bidirectional alloreactivity. In this retrospective study, we investigated the role of PT-Cy as GVHD prophylaxis in patients with multiple myeloma underoing allo-HCT, among different donor types, to determine cumulative incidence of acute and chronic GVHD and impact on engraftment, progression-free survival (PFS), GVHD-free/relapse- free survival (GRFS), overall survival (OS), and NRM A total of 295 patients with MM underwent allo-HCT using grafts from a matched related donor (MRD; n = 67), matched unrelated donor (MUD; n = 72), mismatched related or unrelated donor (MMRD/MMUD, 1 antigen; n = 27), or haploidentical donor (haplo; n = 129) using PT-Cy between 2012 and 2018. In addition to PT-Cy, agents used in GVHD prophylaxis included calcineurin inhibitors in 239 patients (81%), with mycophenolate mofetil in 184 of those 239 (77%). For grade II-IV acute GVHD, the cumulative incidence at day +100 was 30% (95% confidence interval [CI], 25% to 36%), 9% (95% CI, 5% to 12%) for grade III-IV acute GVHD, and 27% (95% CI, 21% to 32%) for chronic GVHD (limited, 21%; extensive, 6%), with no differences by donor type. The median time to neutrophil engraftment was 19d (95% CI, 18-19), with no significant difference by donor type. The median time to platelet engraftment was delayed in haploidentical donor graft recipients (27 days versus 21 days; P < .001). Two-year OS, PFS, GRFS, and NRM were 51% (95% CI, 45% to 58%), 26% (95% CI, 20% to 32%), 24% (95% CI, 18% to 30%), and 19% (95% CI, 14% to 24%), respectively, with no significant difference between different donor types. In multivariable analyses, compared with the haplo donors, the use of MRDs was associated with significantly better OS (hazard ratio [HR], 0.6; 95% CI, 0.38 to 0.95; P = .029), and the use of MUDs was associated with a significantly higher GRFS (HR, 0.63; 95% CI, 0.42 to 0.97; P = .034). There was a trend toward improved PFS with use of MUDs (HR, 0.69; 95% CI, 0.46 to 1.04; P = .08). Our data show that PT-Cy in MM patients undergoing allo-HCT resulted in low rates of acute and chronic GVHD and led to favorable survival, especially in the matched related donor setting. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
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- 2021
12. ASTCT Consensus Recommendations on Testing and Treatment of Patients with Donor-specific Anti-HLA Antibodies.
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Kongtim P, Vittayawacharin P, Zou J, Srour S, Shaffer B, Shapiro RM, Varma A, McGuirk J, Dholaria BR, McCurdy SR, DeZern AE, Bejanyan N, Bashey A, Furst S, Castagna L, Mariotti J, Ruggeri A, Bailen R, Teshima T, Xiao-Jun H, Bonfim C, Aung F, Cao K, Carpenter PA, Hamadani M, Askar M, Fernandez-Vina M, Girnita A, and Ciurea SO
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Donor-specific anti-HLA antibodies (DSA) are an important cause of engraftment failure and may negatively impact survival outcomes of patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) using an HLA-mismatched allograft. The incidence of DSA varies across studies, depending on individual factors, detection or identification methods and thresholds considered clinically relevant. Although DSA testing by multiplex bead arrays remains semiquantitative, it has been widely adopted as a standard test in most transplant centers. Additional testing to determine risk of allograft rejection may include assays with HLA antigens in natural conformation, such as flow cytometric crossmatch, and/or antibody binding assays, such as C1q testing. Patients with low level of DSA (<2,000 mean fluorescence intensity; MFI) may not require treatment, while others with very high level of DSA (>20,000 MFI) may be at very high-risk for engraftment failure despite current therapies. By contrast, in patients with moderate or high level of DSA, desensitization therapy can successfully mitigate DSA levels and improve donor cell engraftment rate, with comparable outcomes to patients without DSA. Treatment is largely empirical and multimodal, involving the removal, neutralization, and blocking of antibodies, as well as inhibition of antibody production to prevent activation of the complement cascade. Desensitization protocols are based on accumulated multicenter experience, while prospective multicenter studies remain lacking. Most patients require a full intensity protocol that includes plasma exchange, while protocols relying only on rituximab and intravenous immunoglobulin may be sufficient for patients with lower DSA levels and negative C1q and/or flow cytometric crossmatch. Monitoring DSA levels before and after HSCT could guide preemptive treatment when high levels persist after stem cell infusion. This paper aims to standardize current evidence-based practice and formulate future directions to improve upon current knowledge and advance treatment for this relatively rare, but potentially serious complication in allogeneic HSCT recipients., Competing Interests: Declaration of competing interest PK - none for this work; other COI - consulting for CareDx and reseach funding from Eurofins Viracor PV - none declared JZ - none declared SS - none declared BS - none declared RMS - none declared AV - none declared JM - none for this work; other COI - honoraria from Kite, AlloVir, Bristol Myers Squibb, Novartis, CRISPR, Nektar Therapeutics, Caribou Bio, Sana Technologies, Legend Biotech and Cargo Therapeutics. BRD - none declared SRM – none declared AED - none for this work; participated in advisory boards, and/or had a consultancy with and received honoraria from Celgene/BMS, Agios, Regeneron, Sobi, Novartis, Astellas, Gilead. AED served on clinical trial steering committees or DSMB for Novartis, Abbvie, Kura, Geron and Celgene/BMS. NB – none for this work; consulting, advisory role or research funding with Magenta Therapeutics, Medexus Pharmaceuticals, CTI BioPharma, CareDx Pharma, Orca Bio, Allovir and CRISPR Therapeutics. AB – none declared SF – none declared LC – none declared JM – none declared AR - none declared RB - none for this work; travel & accommodation: Pfizer, Jazz Pharmaceuticals, Gilead Sciences, Sanofi. Research Funding: Jazz Pharmaceuticals. Speaker: Pfizer, Gilead Sciences. TT – none declared XH - none declared CB – none declared FA – none declared KC – none declared PAC – none for this work; consulting or advisory roles and/or research funding with Incyte, AbbVie and Sanofi MH - none for this work; research support/funding from ADC Therapeutics; Spectrum, Pharmaceuticals; Astellas Pharma, consultancy for ADC Therapeutics, Omeros, BMS, Kite, Abbvie, Genmab, Allovir, CRISPR, Caribou, Autolus, Forte Biosciences, and speaker's bureau for ADC Therapeutics, AstraZeneca, Kite, Beigene MA – none for this work; director clinical services, Be The Match/National Marro Donor Program (NMDP), Minneapolis, MN MFV – none declared AG – none declared SOC – none for this work; reports participation is advisory board for Hansa Therapeutics, CardDx, Spetrum/Achrotech, Kiadis Pharma, Magenta, Allogene, Cellularity, MolMed, Pharmacyclics and received research funds from Miltenyi and Kiadis Pharma., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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13. Busulfan-fludarabine versus busulfan-cyclophosphamide for allogeneic transplant in acute myeloid leukemia: long term analysis of GITMO AML-R2 trial.
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Cavallaro G, Grassi A, Pavoni C, Micò MC, Busca A, Cavattoni IM, Santarone S, Borghero C, Olivieri A, Milone G, Chiusolo P, Musto P, Saccardi R, Patriarca F, Pane F, Saporiti G, Rivela P, Terruzzi E, Cerretti R, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Bernasconi P, Iori AP, Castagna L, Mordini N, Oldani E, Di Grazia C, Bacigalupo A, and Rambaldi A
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- Humans, Middle Aged, Adult, Female, Male, Aged, Follow-Up Studies, Busulfan administration & dosage, Busulfan therapeutic use, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute drug therapy, Vidarabine analogs & derivatives, Vidarabine administration & dosage, Vidarabine therapeutic use, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage, Hematopoietic Stem Cell Transplantation methods, Transplantation Conditioning methods, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Transplantation, Homologous
- Abstract
We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40-65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches., (© 2024. The Author(s).)
- Published
- 2024
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14. Insidious Cases of Enlarged Vestibular Aqueduct (EVA) Syndrome Resembling Otosclerosis: Clinical Features for Differential Diagnosis and the Role of High-Resolution Computed Tomography in the Pre-Operative Setting.
- Author
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Motta G, Allosso S, Castagna L, Trifuoggi G, Di Meglio T, Testa D, Mesolella M, and Motta G
- Abstract
Background: Enlarged vestibular aqueduct (EVA) syndrome can mimic otosclerosis in adults, presenting with an air-bone gap (ABG) and even absent stapedial reflexes. The ABG in inner-ear disorders is currently the object of several authors' studies and seems to be related to a third mobile window (TMW) phenomenon. This can lead to misdiagnosis and inappropriate treatment. Given that it would be inappropriate and harmful to perform CT scans in all patients with a clinical diagnosis of otosclerosis, this study aims to highlight some clinical features useful for the differential diagnosis between otosclerosis and these rare cases of EVA presenting with an ABG, thus enabling the identification of suspected cases to be tested with CT scans., Methods: Between April and May 2024, a narrative review was conducted focusing on the differential diagnosis between some rare cases of EVA and otosclerosis. Clinical, audiological, and radiologic features of both conditions were investigated., Results: This review demonstrates the diagnostic challenge in differentiating atypical cases of EVA from otosclerosis in a subset of patients. Clinical and audiological features are important for differential diagnosis, but may not always be sufficient. Therefore, high-resolution computed tomography (HRCT) of the temporal bone plays a pivotal role in definitive diagnosis., Conclusions: In some specific cases, pre-operative imaging assessment using HRCT emerges as an essential tool for differentiating these two conditions and avoiding unnecessary stapes surgery.
- Published
- 2024
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15. Allogeneic Stem Cell Transplantation in Refractory Acute Myeloid Leukaemia.
- Author
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Bono R, Sapienza G, Tringali S, Rotolo C, Patti C, Mulè A, Calafiore V, Santoro A, and Castagna L
- Subjects
- Humans, Transplantation Conditioning methods, Graft vs Host Disease prevention & control, Leukemia, Myeloid, Acute therapy, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation methods
- Abstract
Refractory acute myeloid leukaemia is very difficult to treat and represents an unmet clinical need. In recent years, new drugs and combinations of drugs have been tested in this category, with encouraging results. However, all treated patients relapsed and died from the disease. The only curative option is allogeneic transplantation through a graft from a healthy donor immune system. Using myeloablative conditioning regimens, the median overall survival regimens is 19%. Several so-called sequential induction chemotherapies followed by allogeneic transplantation conditioned by reduced intensity regimens have been developed, improving the overall survival to 25-57%. In the allogeneic transplantation field, continuous improvements in practices, particularly regarding graft versus host disease prevention, infection prevention, and treatment, have allowed us to observe improvements in survival rates. This is true mainly for patients in complete remission before transplantation and less so for refractory patients. However, full myeloablative regimens are toxic and carry a high risk of treatment-related mortality. In this review, we describe the results obtained with the different modalities used in more recent retrospective and prospective studies. Based on these findings, we speculate how allogeneic stem cell transplantation could be modified to maximise its therapeutic effect on refractory acute myeloid leukaemia.
- Published
- 2024
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16. Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis in HLA-Matched and Haploidentical Donor Transplantation for Patients with Hodgkin Lymphoma: A Comparative Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation.
- Author
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Montoro J, Boumendil A, Finel H, Bramanti S, Castagna L, Blaise D, Dominietto A, Kulagin A, Yakoub-Agha I, Tbakhi A, Solano C, Giebel S, Gulbas Z, López Corral L, Pérez-Simón JA, Díez Martín JL, Sanz J, Farina L, Koc Y, Socié G, Arat M, Jurado M, Bermudez A, Labussière-Wallet H, Villalba M, Ciceri F, Martinez C, Nagler A, Sureda A, and Glass B
- Subjects
- Humans, Retrospective Studies, Bone Marrow, Neoplasm Recurrence, Local complications, Cyclophosphamide therapeutic use, Unrelated Donors, Hodgkin Disease drug therapy, Lymphoma complications, Lymphoma drug therapy, Graft vs Host Disease prevention & control
- Abstract
Post-transplantation cyclophosphamide (PTCy) has emerged as a promising approach for preventing graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is a lack of studies examining the impact of this GVHD prophylaxis when different donor types are used in patients with Hodgkin lymphoma (HL). This study compared the outcomes of patients with HL undergoing HSCT from HLA-matched donors, including matched sibling donors (MSDs) and matched unrelated donors (MUDs), and haploidentical donors, using PTCy as the GVHD prophylaxis approach in all cohorts. We retrospectively compared outcomes of allo-HSCT from 166 HLA-matched donors (96 sibling and 70 unrelated donors) and 694 haploidentical donors using PTCy-based GVHD prophylaxis in patients with HL registered in the European Society for Blood and Marrow Transplantation database from 2010 to 2020. Compared to HLA-matched HSCT, haploidentical donor HSCT was associated with a significantly lower rate of platelet engraftment (86% versus 94%; P < .001) and a higher rate of grade II-IV acute GVHD (34% versus 24%; P = .01). The 2-year cumulative incidence of nonrelapse mortality (NRM) was significantly lower in the HLA-matched cohort compared to the haploidentical cohort (10% versus 18%; P = .02), resulting in a higher overall survival (OS) rate (82% versus 70%; P = .002). There were no significant differences between the 2 cohorts in terms of relapse, progression-free survival, or GVHD-free relapse-free survival. In multivariable analysis, haploidentical HSCT was associated with an increased risk of grade II-IV acute GVHD and NRM and worse OS compared to HLA-matched HSCT. Our findings suggest that in the context of PTCy-based GVHD prophylaxis, transplantation from HLA-matched donors appears to be a more favorable option compared to haploidentical HSCT., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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17. Persistence of KIR neg NK cells after haploidentical hematopoietic stem cell transplantation protects from human cytomegalovirus infection/reactivation.
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Di Vito C, Coianiz N, Calvi M, Terzoli S, Zaghi E, Puccio S, Frigo A, Mariotti J, De Philippis C, Mannina D, Sarina B, Mineri R, Le-Trilling VTK, Trilling M, Castagna L, Bramanti S, Santoro A, and Mavilio D
- Subjects
- Humans, Killer Cells, Natural, Cytomegalovirus, Cytomegalovirus Infections prevention & control, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Haploidentical hematopoietic stem cell transplantation (h-HSCT) is a therapeutic option to cure patients affected by hematologic malignancies. The kinetics and the quality of immune-reconstitution (IR) impact the clinical outcome of h-HSCT and limit the onset of life-threatening Human Cytomegalovirus (HCMV) infection/reactivation. Natural Killer (NK) cells are the first lymphocytes that recover after h-HSCT and they can provide rapid innate immune responses against opportunistic pathogens. By performing a longitudinal single-cell analysis of multiparametric flow-cytometry data, we show here that the persistence at high frequencies of CD158b1b2j
neg /NKG2Apos /NKG2Cneg /NKp30pos /NKp46pos (KIRneg ) NK cells is associated with HCMV infection/reactivation control. These KIRneg NK cells are "unlicensed", and are not terminal-differentiated lymphocytes appearing early during IR and mainly belonging to CD56bright /CD16neg and CD56bright /CD16pos subsets. KIRneg NK cells are enriched in oxidative and glucose metabolism pathways, produce interferon-γ, and are endowed with potent antiviral activity against HCMV ex vivo . Decreased frequencies of KIRneg NK cells early during IR are associated with clinically relevant HCMV replication. Taken together, our findings indicate that the prolonged persistence of KIRneg NK cells after h-HSCT could serve as a biomarker to better predict HCMV infection/reactivation. This phenomenon also paves the way to optimize anti-viral immune responses by enriching post-transplant donor lymphocyte infusions with KIRneg NK cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Di Vito, Coianiz, Calvi, Terzoli, Zaghi, Puccio, Frigo, Mariotti, De Philippis, Mannina, Sarina, Mineri, Le-Trilling, Trilling, Castagna, Bramanti, Santoro and Mavilio.)- Published
- 2024
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18. Selected memory T cells infused post-haploidentical hematopoietic stem cell transplantation persist and hyperexpand.
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van Beek JJP, Puccio S, Di Vito C, De Paoli F, Zaghi E, Calvi M, Scarpa A, Peano C, Basso G, Cibella J, De Philippis C, Sarina B, Timofeeva I, Capizzuto R, Mannina D, Mineri R, Mariotti J, Crocchiolo R, Santoro A, Castagna L, Bramanti S, Mavilio D, and Lugli E
- Subjects
- Humans, Memory T Cells, Prospective Studies, Cyclophosphamide therapeutic use, Cytomegalovirus, Hematopoietic Stem Cell Transplantation adverse effects, Cytomegalovirus Infections
- Abstract
Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplant cyclophosphamide is a curative treatment for many hematological malignancies, yet a majority of patients still suffers from recurrent infections. Post-transplant infusion of memory T-cells could potentially enhance immunological protection without increasing the risk of eliciting acute graft-versus-host disease, which is mainly induced by naïve T-cells. Here, we performed longitudinal analysis of the lymphocyte compartment in 19 patients who underwent haplo-HSCT previously enrolled in a phase II prospective clinical trial (www.clinicaltrials.gov as #NCT04687982), in which they received post-transplant CD45RA-depleted donor lymphocyte infusions (DLI). T-cell receptor sequencing analysis showed that, surprisingly, CD45RA-depleted DLI do not increase T-cell clonal diversity, but lead to prominent expansion of a selected number of infused memory T-cell clones, suggesting recruitment of these cells in the immune response. Pathogen-specific memory T-cells, including cytomegalovirus (CMV)-specific cells, were engrafted and were able to persist for at least 1 month. Deep immunophenotyping revealed strong polyfunctional effector CMV-specific T-cell responses in the majority of patients, with their expansion correlating with the frequency of CMV-specific cells in the donor. These findings provide a rationale behind the suggested improved protection against viral infections in patients receiving CD45RA-depleted DLI., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2023
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19. Don't forget cord blood in non-remission acute myeloid leukaemia!
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Castagna L, Patti K, and Mulè A
- Subjects
- Humans, Retrospective Studies, Fetal Blood, Tissue Donors, Transplantation, Homologous, Leukemia, Myeloid, Acute therapy, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease
- Abstract
Transplantation from haploidentical donors is widely used, with progressive reduction of cord blood (CB) as alternative donor. The paper by Matsuda and colleagues, the largest analysing the outcome in non-remission acute myeloid leukaemia (AML) transplanted with haploidentical donor or CB, suggests that CB is still a viable option when considering allogeneic transplantation for advanced AML. Commentary on: Matsuda et al. Comparison of transplant outcomes between haploidentical transplantation and single cord blood transplantation in non-remission acute myeloid leukaemia: A nationwide retrospective study. Br J Haematol. 2023;201:106-113., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2023
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20. Reduced post-transplant cyclophosphamide doses in haploidentical hematopoietic cell transplantation for elderly patients with hematological malignancies.
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Duléry R, Goudet C, Mannina D, Bianchessi A, Granata A, Harbi S, Maisano V, Chabannon C, Malard F, Brissot E, Sestili S, Banet A, Van de Wyngaert Z, Belhocine R, Ederhy S, Castagna L, Bramanti S, Blaise D, Mohty M, Fürst S, and Devillier R
- Subjects
- Humans, Aged, Middle Aged, Neoplasm Recurrence, Local drug therapy, Cyclophosphamide therapeutic use, Transplantation Conditioning, Hematopoietic Stem Cell Transplantation, Hematologic Neoplasms, Graft vs Host Disease
- Abstract
Although post-transplant cyclophosphamide (PT-Cy) is effective for graft-versus-host disease (GVHD) prophylaxis, it is associated with toxicities, which might be dose-dependent. We compared the outcomes with PT-Cy at 80 mg/kg to those with PT-Cy at 100 mg/kg in elderly patients undergoing haploidentical hematopoietic cell transplantation (HCT). Inclusion criteria included peripheral blood stem cells, hematological malignancy, and age>65 years (or age>60 years if cardiac event history). Thirty-eight patients received PT-Cy at 80 mg/kg and 55 100 mg/kg, divided in two doses. The cumulative incidences (CI) of acute grade II-IV, acute grade III-IV, and moderate/severe chronic GVHD were 32%, 16%, and 13% with PT-Cy at 80 mg/kg compared to 33%, 13%, and 16% with 100 mg/kg, respectively. In multivariable analysis, reducing PT-Cy dose had no significant impact on GVHD. Neutrophil and platelet engraftments were significantly improved, and CI of BK virus-associated hemorrhagic cystitis was reduced with 80 mg/kg of PT-Cy compared to 100 mg/kg. At 2 years, non-relapse mortality was 16% and 31%, progression-free survival 65% and 49%, overall survival 70% and 56%, and GVHD-free, relapse-free survival 52% and 36% with 80 mg/kg and 100 mg/kg, respectively. Reducing PT-Cy dose to 80 mg/kg is safe and associated with improved hematological recovery and lower CI of hemorrhagic cystitis in elderly patients undergoing haploidentical HCT., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2023
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21. Neural pressure support ventilation as a novel strategy to improve patient-ventilator synchrony in adult respiratory distress syndrome.
- Author
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Colombo SM, Scaravilli V, Castagna L, Zanella A, Brioni M, Abbruzzese C, and Grasselli G
- Subjects
- Adult, Humans, Lung, Ventilators, Mechanical, Respiration, Respiration, Artificial, Positive-Pressure Respiration, Respiratory Distress Syndrome therapy
- Published
- 2023
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22. Haploidentical Versus Matched Unrelated Donor Transplants Using Post-Transplantation Cyclophosphamide for Lymphomas.
- Author
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Mussetti A, Kanate AS, Wang T, He M, Hamadani M, Finel H Sr, Boumendil A Sr, Glass B, Castagna L, Dominietto A, McGuirk J, Blaise D, Gülbas Z, Diez-Martin J, Marsh SGE, Paczesny S, Gadalla SM, Dreger P, Zhang MJ, Spellman SR, Lee SJ, Bolon YT, and Sureda A
- Subjects
- Adult, Humans, Adolescent, Unrelated Donors, Retrospective Studies, Neoplasm Recurrence, Local complications, Cyclophosphamide therapeutic use, Lymphoma complications, Lymphoma drug therapy, Graft vs Host Disease prevention & control
- Abstract
When using post-transplantation cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis for lymphoma patients, it is currently unknown whether a matched unrelated donor (MUD) or a haploidentical related donor is preferable if both are available. In this study we wanted to test whether using a haploidentical donor has the same results of a MUD. A total of 2140 adults (34% Center for International Blood and Marrow Transplant Research, 66% European Society for Blood and Marrow Transplantation registry) aged ≥18 years who received their first haploidentical hematopoietic cell transplantation (haplo-HCT) or MUD-HCT (8/8 match at HLA-loci A, B, C, and DRB1) for lymphoma using PTCy-based GVHD prophylaxis from 2010 to 2019 were retrospectively analyzed. The majority of both MUD and haploidentical HCTs received reduced intensity/nonmyeloablative conditioning (74% and 77%, respectively) and used a peripheral blood stem cell graft (91% and 60%, respectively) and a 3-drug GVHD prophylaxis (PTCy + calcineurin inhibitor + MMF in 54% and 90%, respectively). Haploidentical HCT has less favorable results versus MUD cohort in terms of overall mortality (hazard ratio [HR= = 1.69; 95% confidence interval [CI], 1.30-2.27; P < .001), progression-free survival (HR=1.39; 95% CI, 1.10-1.79; P = .008), nonrelapse mortality (HR = 1.93; 95% CI, 1.21-3.07; P = .006), platelet engraftment (HR = 0.69; 95% CI, 0.59-0.80; P < .001), acute grade 2-4 GVHD incidence (HR = 1.65; 95% CI, 1.28-2.14; P < .001), and chronic GVHD (HR = 1.79; 95% CI, 1.30-2.48, P < .001). No significant differences were observed in terms of relapse and neutrophil engraftment. Adjusting for propensity score yielded similar results. Whenever MUD is available in a timely manner, it should be preferred over a haploidentical donor when using PTCy-based GVHD prophylaxis for patients with lymphoma., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. All rights reserved.)
- Published
- 2023
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23. Post-transplant cyclophosphamide in acute leukemia patients receiving more than 5/10 HLA-mismatched allogeneic hematopoietic cell transplantation from related donors: A study on behalf of the ALWP of the EBMT.
- Author
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Wieczorek M, Labopin M, Castagna L, Brissot E, Socié G, Raiola AM, Angelucci E, Rodríguez AB, Yakoub-Agha I, Aljurf M, Crawley C, Mear JB, Musso M, Fanin R, Avenoso D, Turlure P, Tecchio C, Sanz J, Ciceri F, Nagler A, and Mohty M
- Subjects
- Humans, Cyclophosphamide therapeutic use, Tissue Donors, Retrospective Studies, Transplantation Conditioning, Unrelated Donors, Leukemia, Myeloid, Acute therapy, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control
- Published
- 2023
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24. Retrospective analysis of hematopoietic cell transplantation for blastic plasmacytoid dendritic cell neoplasm: conditioning intensity matters.
- Author
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Bruch PM, Dietrich S, Finel H, Boumendil A, Greinix H, Heinicke T, Bethge W, Beelen D, Schmid C, Martin H, Castagna L, Scheid C, Schäfer-Eckart K, Bittenbring J, Finke J, Sengeloev H, Heiblig M, Cornelissen J, Chevallier P, Mohty M, Robinson S, Montoto S, and Dreger P
- Subjects
- Adult, Aged, Humans, Middle Aged, Young Adult, Acute Disease, Dendritic Cells pathology, Neoplasm Recurrence, Local pathology, Retrospective Studies, Transplantation Conditioning, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Myeloproliferative Disorders pathology, Skin Neoplasms pathology
- Abstract
Blastic plasmacytoid dendritic cell neoplasia (BPDCN) is a rare myeloid malignancy with a generally poor prognosis. Although preliminary evidence suggests that hematopoietic cell transplantation (HCT) could improve outcome in patients with BPDCN, the individual contributions of conditioning and graft-versus-tumor (GVT) effects to HCT success are undefined. We present a retrospective study of 162 adult patients who underwent a first HCT (allogeneic 146, autologous 16) between 2009 and 2017, and were registered with the EBMT. Median age was 57 (range 20-73) years, and disease status at HCT was first complete remission (CR1) in 78%. Among patients receiving allogeneic HCT (alloHCT), myeloablative conditioning (MAC), reduced intensity conditioning (RIC) and in-vivo T-cell depletion (TCD) were used in 54%, 46%, and 59% respectively. Total body irradiation (TBI) was the conditioning backbone in 61% of MAC and 26% of RIC transplants. One-year overall survival (OS) and progression-free survival (PFS) rates were comparable after alloHCT and autologous HCT (autoHCT). Among alloHCT recipients, MAC with TBI significantly improved OS and PFS, independently of CR1, age, Karnofsky index and TCD. Accordingly, MAC (ideally based on TBI) should be preferred for alloHCT recipients with BPDCN. In patients who are not elegible for MAC alloHCT, autoHCT could be considered., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2023
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25. Correction: Donor lymphocyte infusions after haploidentical stem cell transplantation with PTCY: A study on behalf of the EBMT cellular therapy & immunobiology working party.
- Author
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Santoro N, Mooyaart JE, Devillier R, Koc Y, Vydra J, Castagna L, Gülbas Z, Martin JD, Araujo MC, Kulagin A, Arat M, Arroyo CH, Martelli MP, Di Ianni M, Hoogenboom JD, de Wreede LC, Ruggeri A, and Chabannon C
- Published
- 2023
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26. Donor lymphocyte infusions after haploidentical stem cell transplantation with PTCY: A study on behalf of the EBMT cellular therapy & immunobiology working party.
- Author
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Santoro N, Mooyaart JE, Devillier R, Koc Y, Vydra J, Castagna L, Gülbas Z, Martin JD, Araujo MC, Kulagin A, Arat M, Arroyo CH, Martelli MP, Di Ianni M, Hoogenboom JD, de Wreede LC, Ruggeri A, and Chabannon C
- Subjects
- Humans, Prospective Studies, Cyclophosphamide therapeutic use, Immunotherapy, Adoptive adverse effects, Lymphocyte Transfusion adverse effects, Lymphocytes, Retrospective Studies, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease etiology
- Abstract
Donor lymphocyte infusion (DLI) is a treatment option to prevent or treat relapse after allogeneic hematopoietic cell transplantation (HCT). We here report data for 173 patients who received one or multiple DLIs after haploidentical-HCT with post-transplant cyclophosphamide (PTCY) at 47 EBMT centers from 2009 to 2018. Indication for DLI was: prophylactic for 59 (34.3%), preemptive for 20(11.6%), and therapeutic for 93(54.1%). For the prophylactic group, the median number of DLIs was 1 (IQR:1-2.5) with a median first dose of 0.1 × 10
6 CD3+ T cell/kg, for the preemptive 2 (IQR:1-3) with 0.5 × 106 CD3+ T cell/kg, for the therapeutic 1 (IQR:1-3) with 1 × 106 CD3+ Tcell/kg, respectively. OS after first DLI was 61% (46-75%) for prophylactic, 40% (19-61%) for preemptive, and 22% (13-31%) for therapeutic. CI of II-IV aGVHD and cGVHD was 17% (7-27%) and 53% (40-67%) for the prophylactic, 20% (2-38%) and 21% (3-39%) for the preemptive, 17% (9-24%) and 24% (15-33%) for the therapeutic group, respectively. Our data show great variability in the indications and modalities of DLI across responding EBMT centers. Survival rates remain relatively low in patients with active disease. While the cumulative incidence of aGVHD appears acceptable, we showed a high incidence of cGVHD in the prophylactic group, compared with preemptive and therapeutic DLI. These data should be investigated further in prospective clinical trials., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2023
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27. The place of allogeneic stem cell transplantation in aggressive B-cell non-Hodgkin lymphoma in the era of CAR-T-cell therapy.
- Author
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Castagna L, Bono R, Tringali S, Sapienza G, Santoro A, Indovina A, Tarantino V, Di Noto L, Maggio A, and Patti C
- Abstract
Chimeric antigen receptor T (CAR-T) cells are a treatment option for patients with relapse/refractory (R/R) non-Hodgkin lymphoma (NHL), acute lymphoid leukemia and multiple myeloma. To date, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL) have been successfully treated with CAR-T cells directed against the CD19 antigen. However, when R/R disease persists after several treatment lines, patients with these diseases are often referred to transplantation centres to receive allogeneic stem cell transplantation (ALLO-SCT). ALLO-SCT and CAR-T cells share mechanism of actions, inducing immune effects of T -cells (and other cells after transplantation) against lymphoma cells, but they differ in several other characteristics. These differences justify unique positioning of each therapy within treatment algorithms. In this paper, we analyzed the results obtained after ALLO-SCT and CAR-T-cell therapy in patients with aggressive lymphomas (large B-cell lymphoma and MCL) to identify the ideal scenarios in which these 2 immunological therapies should be employed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Castagna, Bono, Tringali, Sapienza, Santoro, Indovina, Tarantino, Di Noto, Maggio and Patti.)
- Published
- 2022
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28. Impact of second-degree related donor on the outcomes of T cell-replete haploidentical transplantation with post-transplant cyclophosphamide.
- Author
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Mariotti J, Raiola AM, Evangelista A, Harbi S, Patriarca F, Carella MA, Martino M, Risitano A, Busca A, Giaccone L, Brunello L, Merla E, Savino L, Loteta B, Console G, Fanin R, Sperotto A, Marano L, Marotta S, Frieri C, Sica S, Chiusolo P, Chabannon C, Furst S, Santoro A, Bacigalupo A, Bruno B, Blaise D, Mavilio D, Bramanti S, Devillier R, Angelucci E, and Castagna L
- Subjects
- Humans, Transplantation, Haploidentical, Retrospective Studies, T-Lymphocytes, Cyclophosphamide therapeutic use, Transplantation Conditioning methods, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation methods
- Abstract
Donor selection may contribute to improve clinical outcomes of T cell-replete haploidentical stem cell transplantation (Haplo-SCT) with post-transplant cyclophosphamide (PT-Cy). Impact of second-degree related donor (SRD) was not fully elucidated in this platform. We retrospectively compared the outcome of patients receiving Haplo-SCT either from a SRD (n = 31) or a first-degree related donor (FRD, n = 957). Median time to neutrophil and platelet recovery did not differ between a SRD and a FRD transplant (p = 0.599 and 0.587). Cumulative incidence of grade II-IV acute graft-versus host disease (GVHD) and moderate-severe chronic GVHD was 13% and 19% after SRD vs 24% (p = 0.126) and 13% (p = 0.395) after FRD transplant. One-year cumulative incidence of non-relapse mortality (NRM) was 19% for SRD and 20% for FRD (p = 0.435) cohort. The 3-year probability of overall survival (OS) and progression-free survival (PFS) was 42% vs 55% (p = 0.273) and 49% vs 35% (p = 0.280) after SRD and FRD transplant, respectively. After propensity score adjustment or matched pair analysis, the outcome of patients receiving Haplo-SCT from a SRD or a FRD did not differ in terms of NRM, OS, PFS, acute and chronic GVHD. Our results suggest that a SRD is a viable option for Haplo-SCT with PT-Cy when a FRD is not available., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2022
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29. Comparison of Outcomes after Unrelated Double-Unit Cord Blood and Haploidentical Peripheral Blood Stem Cell Transplantation in Adults with Acute Myelogenous Leukemia: A Study on Behalf of Eurocord and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
- Author
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Ruggeri A, Galimard JE, Labopin M, Rafii H, Blaise D, Ciceri F, Diez-Martin JL, Cornelissen J, Chevallier P, Sanchez-Guijo F, Nicholson E, Castagna L, Forcade E, Kuball J, Rovira M, Koc Y, Pavlu J, Gulbas Z, Vydra J, Baron F, Sanz J, Spyridonidis A, Savani B, Gluckman E, Nagler A, and Mohty M
- Subjects
- Acute Disease, Adult, Alemtuzumab, Antilymphocyte Serum, Bone Marrow, Cyclophosphamide therapeutic use, Fetal Blood, Humans, Recurrence, Graft vs Host Disease prevention & control, Leukemia, Myeloid, Acute therapy, Peripheral Blood Stem Cell Transplantation
- Abstract
Unmanipulated haploidentical hematopoietic stem cell transplantation (HCT) with post-transplantation cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis (haplo-PTCY) and unrelated double-unit umbilical cord blood transplantation (dUCBT) are feasible options for treating patients with high-risk acute myelogenous leukemia (AML). This study compared outcomes after dUCBT and haplo-HCT using peripheral blood stem cells (PBSCs) in adult patients with AML in complete remission (CR) who underwent transplantation in European Society for Blood and Marrow Transplantation (EBMT)-affiliated centers. In a population of adults with de novo AML in first or second CR, we compared outcomes after dUCBT (n = 165) and after haplo-PTCY PBSC (n = 544) performed between January 2013 and December 2018. Patients receiving in vivo antithymocyte globulin, Campath, or ex vivo T cell depletion were excluded. The median follow-up was 33 months for the haplo-PTCY arm and 52 months for the dUCBT arm. No statistically significant differences were observed between the 2 arms in the rates of grade II-IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 1.31; P = .18), grade III-IV acute GVHD (HR, 1.17; P = .56), chronic GVHD (HR, .86; P = .48), relapse (HR, 1.07; P = .77), nonrelapse mortality (NRM) (HR, .94; P = .77), leukemia-free survival (LFS) (HR, .99; P = .95), or overall survival (OS) (HR, .99; P = .97). Favorable cytogenetic risk was the sole factor predictive of lower relapse incidence (RI). Younger age at transplantation was associated with lower NRM and higher LFS and OS. Both dUCBT and haplo-PTCY with PBSCs can be considered valid approaches for adult AML patients in CR. New strategies should be investigated in both settings to define the most appropriate conditioning regimen and potentially decrease RI and NRM through better immune reconstitution and optimal supportive care., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2022
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30. Impact of the Addition of Antithymocyte Globulin to Post-Transplantation Cyclophosphamide in Haploidentical Transplantation with Peripheral Blood Compared to Post-Transplantation Cyclophosphamide Alone in Acute Myelogenous Leukemia: A Retrospective Study on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
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Battipaglia G, Labopin M, Blaise D, Diez-Martin JL, Bazarbachi A, Vitek A, Chevallier P, Castagna L, Grillo G, Daguindau E, López-Jiménez J, Koc Y, Ruggeri A, Nagler A, and Mohty M
- Subjects
- Antilymphocyte Serum, Bone Marrow, Cyclophosphamide, Cyclosporine, Humans, Middle Aged, Mycophenolic Acid, Retrospective Studies, Transplantation, Haploidentical, Graft vs Host Disease, Leukemia, Myeloid, Acute
- Abstract
The use of haploidentical hematopoietic cell transplantation (haplo-HCT) with peripheral blood stem cells (PBSCs) to treat acute myelogenous leukemia (AML) is increasing. We explored whether the addition of antithymocyte globulin (ATG) to post-transplantation cyclophosphamide (PTCy) allows better outcomes compared with PTCy alone in haplo-HCT with PBSCs (haplo-PBSCT). We included 441 adult patients undergoing a first haplo-PBSCT for AML in first or second complete remission; graft-versus-host disease (GVHD) prophylaxis contained either PTCy alone (n = 374) or ATG plus PTCy (n = 67), in addition to cyclosporine A (CsA) and mycophenolate mofetil (MMF) as other immunosuppressive agents. All transplantations were performed between 2011 and 2019. No major imbalances were observed between the 2 groups. For both groups, the median patient age was 56 years, and the median year of haplo-PBSCT was 2017. Most patients received a reduced-intensity conditioning regimen (57% in the PTCy group and 61% in the ATG+PTCy group; P = .54). The median follow-up was 19 months in the PTCy group versus 15 months in the ATG+PTCy group (P = .59), and the rate of neutrophil engraftment in the 2 groups was 97% and 98%, respectively. In univariate analysis, there were no statistical differences in transplantation outcomes between the 2 groups. In multivariate analysis, ATG+PTCy was associated with a lower risk of chronic GVHD compared with PTCy alone (hazard ratio, .46; 95% confidence interval, .23 to .93; P = .03). No between-group differences in the other transplantation outcomes were seen. In haplo-PBSCT, the addition of ATG to PTCy (with CsA and MMF) is feasible and better at preventing chronic GVHD and is associated with survival and transplantation outcomes comparable to those with PTCy alone, without increasing transplantation toxicity, mortality, or relapse incidence., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2022
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31. Reduced intensity versus non-myeloablative conditioning regimen for haploidentical transplantation and post-transplantation cyclophosphamide in complete remission acute myeloid leukemia: a study from the ALWP of the EBMT.
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Devillier R, Galimard JE, Labopin M, Blaise D, Raiola AM, Pavlu J, Castagna L, Socié G, Chalandon Y, Martino M, Stölzel F, Bug G, Bruno B, Vrhovac R, Charbonnier A, Olivieri A, Bay JO, Arroyo H, Yakoub-Agha I, Avenoso D, Neubauer A, Nguyen S, Forcade E, Brissot E, Savani B, Nagler A, and Mohty M
- Subjects
- Aged, Busulfan therapeutic use, Cyclophosphamide therapeutic use, Humans, Recurrence, Retrospective Studies, Transplantation Conditioning adverse effects, Transplantation, Haploidentical adverse effects, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute complications, Leukemia, Myeloid, Acute therapy
- Abstract
The optimal conditioning regimen prior haploidentical stem cell transplantation (Haplo-SCT) with post transplantation cyclophosphamide (PT-Cy) for acute myeloid leukemia (AML) remains unknown. A non-myeloablative conditioning (NMAC) regimen (cyclophosphamide + fludarabine + TBI 2 Gy [CyFluTBI]) is a safe approach, but relapse incidence remains high in this setting. Alternatively, a reduced intensity conditioning (RIC) regimen combining thiotepa and reduced-dose busulfan with fludarabine (TBF) may decrease AML relapse. However, an excess of toxicity may counterbalance this potential benefit. We retrospectively compared CyFluTBI vs. TBF in CR AML patients who underwent Haplo-SCT with PT-Cy, in two different populations based on age. We analyzed 490 patients. In patients aged <60 years (n = 203), we observed a higher RI (HR = 3.59, 95% CI = 1.75-7.37, p < 0.01), lower LFS (HR = 1.98, 95% CI = 1.22-3.22, p < 0.01) and lower OS (HR = 1.73, 95% CI = 1.04-2.88, p = 0.04) in the CyFluTBI group, without significant difference in NRM. In older patients (n = 287), we observed that conditioning regimen did not significantly influence LFS (HR = 0.90, 95% CI = 0.56-1.44, p = 0.65), OS (HR = 0.81, 95% CI = 0.49-1.32, p = 0.39) and RI (HR = 1.78, 95% CI = 0.90-3.50, p = 0.10), but showed that CyFluTBI was associated with a significantly lower risk of NRM (HR = 0.48, 95% CI = 0.25-0.92, p = 0.03). Thus, younger patients seem to benefit from conditioning intensification from CyFluTBI to TBF regimens prior PT-Cy Haplo-SCT for CR AML, while older ones do not., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2022
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32. Impact of donor kinship on non-T-cell depleted haploidentical stem cell transplantation with post transplantation cyclophosphamide for acute leukemia: From the ALWP of the EBMT.
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Danylesko I, Peczynski C, Labopin M, Polge E, Tischer J, Blaise D, Koc Y, Gülbas Z, Ciceri F, Arat M, Castagna L, Bruno B, Raiola AM, Botella-Garcia C, Savani BN, Piemontese S, Ruggeri A, Nagler A, and Mohty M
- Subjects
- Acute Disease, Child, Cyclophosphamide therapeutic use, Humans, Middle Aged, Retrospective Studies, Siblings, Transplantation Conditioning, Unrelated Donors, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute
- Abstract
Non-T-cell depleted haploidentical hematopoietic cell transplantation (Haplo-HCT) is a unique transplantation setting in which several donors are available. We assessed the impact of donor kinship on outcome of Haplo-HCT with post-transplantation cyclophosphamide in a cohort of 717 acute leukemia patients. We compared sibling with parent donors in patients ≤45 years, and child with sibling donors in patients >45 years. Donor kinship was not associated with worse outcomes in multivariate analysis. For patients ≤45 years, the hazard ratio (HR) for leukemia-free survival (LFS), overall survival (OS), relapse incidence (RI), and chronic graft-versus-host disease (cGVHD) was 0.87 (p = 0.75), 1.19 (p = 0.7), 0.52 (p = 0.19), and 0.99 (p = 0.97) for parents versus siblings, respectively, and for patients >45 years the HR was 0.93 (p = 0.8), 0.98 (p = 0.94), 1.3 (p = 0.53), and 0.98 (p = 0.95) for children versus siblings, respectively. Univariate incidence of acute GVHD grade II-IV was significantly higher in patients transplanted from siblings versus children (p = 0.002). Factors associated with inferior outcome were advanced disease and earlier transplant. In patients ≤45 years, acute lymphocytic leukemia and peripheral blood stem cell graft were additional prognostic factors for OS. We did not find a significant impact of donor kinship on transplantation outcome when analyzing by age group (≤45 and >45 years)., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2022
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33. Post-transplant cyclophosphamide in one-antigen mismatched unrelated donor transplantation versus haploidentical transplantation in acute myeloid leukemia: a study from the Acute Leukemia Working Party of the EBMT.
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Battipaglia G, Galimard JE, Labopin M, Raiola AM, Blaise D, Ruggeri A, Koc Y, Gülbas Z, Vitek A, Sica S, Diez-Martin JL, Castagna L, Bruno B, Rovira M, Moiseev I, Martino M, Grillo G, Araujo MC, Bulabois CE, Nguyen S, Socié G, Arat M, Pavlu J, Tischer J, Martin H, Corral LL, Choi G, Forcade E, McDonald A, Pane F, Bazarbachi A, Ciceri F, Nagler A, and Mohty M
- Subjects
- Cyclophosphamide pharmacology, Cyclophosphamide therapeutic use, Humans, Retrospective Studies, Transplantation Conditioning, Transplantation, Haploidentical, Unrelated Donors, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy
- Abstract
Whether to choose Haploidentical (Haplo) or one-antigen mismatched unrelated donor (1Ag-MMUD) hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy) remains an unanswered question. We compared PTCy- Haplo-HCT to PTCy-1Ag-MMUD-HCT for acute myeloid leukemia (AML) in complete remission (three groups: 1Ag-MMUD using peripheral blood (1Ag-MMUD-PB; n = 155); Haplo using bone marrow (Haplo-BM; n = 647) or peripheral blood (Haplo-PB; n = 949)). Haplo-BM and Haplo-PB had a higher non-relapse mortality (NRM) compared to 1Ag-MMUD-PB (HR 2.28, 95% CI 1.23-4.24, p < 0.01; HR 2.65, 95% CI 1.46-4.81, p < 0.01, respectively). Haplo groups experienced a lower leukemia-free survival (LFS) compared to 1Ag-MMUD-PB (Haplo-BM: HR 1.51, 95% CI 1.06-2.14, p = 0.02; Haplo-PB: 1.47, 95% CI 1.05-2.05, p = 0.02); overall survival (OS) was also lower in Haplo-HCT (Haplo-BM: HR 1.50, 95% CI 1.02-2.21, p = 0.04; Haplo-PB: HR 1.51, 95% CI 1.05-2.19, p = 0.03). No differences were observed for graft-versus-host/relapse-free survival (GRFS) and relapse incidence (RI). Haplo-BM was associated with a lower risk of grade III-IV acute graft-versus-host disease (GVHD) (HR 0.44, 95% CI 0.24-0.81; p < 0.01), while no statistical differences were observed between groups for grade II-IV aGVHD and for cGVHD. Use of PTCy in 1Ag-MMUD-HCT is a valid alternative to consider when using alternative donors. Larger analysis of 1Ag-MMUD versus Haplo-HCT are warranted., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2022
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34. The association of graft-versus-leukemia effect and graft-versus host disease in haploidentical transplantation with post-transplant cyclophosphamide for AML.
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Shimoni A, Labopin M, Angelucci E, Blaise D, Ciceri F, Koc Y, Gülbas Z, Diez-Martin JL, Bruno B, Castagna L, Martino M, Rovira M, Mohty M, and Nagler A
- Subjects
- Cyclophosphamide pharmacology, Cyclophosphamide therapeutic use, Humans, Recurrence, Retrospective Studies, Transplantation Conditioning, Transplantation, Haploidentical, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy
- Abstract
The association of graft-versus-host disease (GVHD) and graft-versus-leukemia effect after stem-cell transplantation (SCT) is well established but with limited data in the setting of haploidentical SCT (haploSCT) with post-transplant cyclophosphamide (PTCy). We used a series of landmark analyses to investigate this association in 805 AML patients following haploSCT. On day +100, 707 patients were alive and leukemia-free, 500 had no prior acute GVHD, 137 had acute GVHD grade II and 70 had grade III-IV. Subsequent relapse rates were 20.3%, 23.2% and 15.0%, respectively (P = 0.52). Subsequent non-relapse mortality (NRM) was 8.6%, 17.8% and 38.6%, respectively (P < 0.0001). Leukemia-free survival (LFS) was 71.0%, 59.0% and 46.3%, respectively (P < 0.0001). Multivariate analysis showed that acute GVHD grade II and grade III-IV were not associated with relapse (HR 1.21, P = 0.37 and HR 1.03, P = 0.94), but were associated with increased NRM (HR 2.09, P = 0.005 and HR 6.41, P < 0.0001) and lower LFS (HR 1.47, P = 0.02 and HR 2.59, P = < 0.0001). Chronic GVHD was not associated with subsequent relapse. Extensive chronic GVHD was associated with higher NRM (HR 6.72, P < 0.0001) and inferior LFS (HR 3.29, P = < 0.0001). GVHD of any type or grade is not associated with lower relapse after haploSCT with PTCy. Severe forms are associated with higher NRM and lower survival., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2022
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35. Risk Factors for Early Cytomegalovirus Reactivation and Impact of Early Cytomegalovirus Reactivation on Clinical Outcomes after T Cell-Replete Haploidentical Transplantation with Post-Transplantation Cyclophosphamide.
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Mariotti J, Legrand F, Furst S, Giordano L, Magri F, Richiardi L, Granata A, De Philippis C, Maisano V, Faraci D, Sarina B, Giaccone L, Harbi S, Mannina D, Valli V, Tordato F, Mineri R, Bramanti S, Santoro A, Bruno B, Devillier R, Blaise D, and Castagna L
- Subjects
- Cyclophosphamide therapeutic use, Humans, Retrospective Studies, Risk Factors, T-Lymphocytes, Transplantation, Haploidentical adverse effects, United States, Cytomegalovirus, Cytomegalovirus Infections drug therapy
- Abstract
Risk factors for cytomegalovirus (CMV) reactivation and the impact of CMV reactivation on patient outcomes have been extensively investigated after matched related or unrelated donor transplantation, but little is known in the setting of haploidentical stem cell transplantation (Haplo-SCT) with post-transplantation cyclophosphamide (PT-Cy), in which recipients are considered more severely immunocompromised. We retrospectively analyzed a cohort of 554 consecutive patients undergoing Haplo-SCT with PT-Cy at 3 different centers. Early CMV reactivation (occurring within the first 120 days post-transplantation) occurred in 242 patients, for an estimated cumulative incidence of 44%. Among those patients, 74 (30%) had recurrent CMV and 20 (8%) had CMV disease. On multivariable analysis, positive recipient CMV serostatus (hazard ratio [HR] >2.5; P < .001), disease histology (lymphoid versus myeloid: HR, 0.66; P = .003) and increasing recipient age (HR, 1.01; P = .015) were independent predictors of CMV reactivation. At a 4-month landmark analysis, CMV reactivation was associated with higher 1-year and 5-year cumulative incidence of nonrelapse mortality (NRM) relative to patients without reactivation: 13% versus 5% and 22% versus 9%, respectively (P < .001). On multivariable analysis, CMV reactivation was an independent negative predictor of NRM (HR, 2.69; P < .001) and was close to statistically significant for overall survival (HR, 1.38; P = .062). Our results suggest that CMV reactivation plays an important role at determining NRM. Because patient CMV serostatus is the main predictor of CMV reactivation, it should be considered when evaluating strategies for preventing CMV reactivation. 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2022
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36. Outcome of allogeneic transplantation for mature T-cell lymphomas: impact of donor source and disease characteristics.
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Hamadani M, Ngoya M, Sureda A, Bashir Q, Litovich CA, Finel H, Chen Y, Boumendil A, Zain J, Castagna L, Cashen AF, Blaise D, Shadman M, Pastano R, Khimani F, Arat M, Dietrich S, Schmitz N, Glass B, Kharfan-Dabaja MA, Corradini P, Sauter CS, Montoto S, Kwon M, Herrera AF, and Dreger P
- Subjects
- Adult, Humans, Neoplasm Recurrence, Local, Transplantation, Homologous adverse effects, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Lymphoma, T-Cell, Peripheral therapy
- Abstract
Mature T-cell lymphomas constitute the most common indication for allogeneic hematopoietic cell transplantation (allo-HCT) of all lymphomas. Large studies evaluating contemporary outcomes of allo-HCT in mature T-cell lymphomas relative to commonly used donor sources are not available. Included in this registry study were adult patients who had undergone allo-HCT for anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma (AITL), or peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) between 2008 and 2018. Hematopoietic cell transplantation (HCT) platforms compared were posttransplant cyclophosphamide-based haploidentical (haplo-)HCT, matched sibling donor (MSD) HCT, matched unrelated donor HCT with in vivo T-cell depletion (MUD TCD+), and matched unrelated donor HCT without in vivo T-cell depletion (MUD TCD-). Coprimary end points were overall survival (OS) and progression-free survival (PFS); secondary end points included nonrelapse mortality (NRM), and relapse/progression incidence (RI). A total of 1942 patients were eligible (237 haplo-HCT; 911 MSD; 468 MUD TCD+; 326 MUD TCD-). Cohorts were comparable for baseline characteristics with the exception of higher proportions of patients with decreased performance status (PS) and marrow graft recipients in the haplo-HCT group. Using univariate and multivariate comparisons, OS, PFS, RI, and NRM were not significantly different among the haplo-HCT, MSD, MUD TCD+, and MUD TCD- cohorts, with 3-year OS and PFS of 60%, 63%, 59%, and 64%, respectively, and 50%, 50%, 48%, and 52%, respectively. Significant predictors of inferior OS and PFS on multivariate analysis were active disease status at HCT and decreased PS. AITL was associated with significantly reduced relapse risk and better PFS compared with PTCL-NOS. Allo-HCT can provide durable PFS in patients with mature T-cell lymphoma (TCL). Outcomes of haplo-HCT were comparable to those of matched donor allo-HCT., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2022
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37. Extracellular Vesicles as Biomarkers of Acute Graft-vs.-Host Disease After Haploidentical Stem Cell Transplantation and Post-Transplant Cyclophosphamide.
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Lia G, Di Vito C, Bruno S, Tapparo M, Brunello L, Santoro A, Mariotti J, Bramanti S, Zaghi E, Calvi M, Comba L, Fascì M, Giaccone L, Camussi G, Boyle EM, Castagna L, Evangelista A, Mavilio D, and Bruno B
- Subjects
- Adult, Aged, Cyclophosphamide administration & dosage, Female, Graft vs Host Disease diagnosis, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation methods, Humans, Immunophenotyping, Male, Middle Aged, Postoperative Care, Prognosis, Proportional Hazards Models, ROC Curve, Transplantation, Haploidentical, Treatment Outcome, Young Adult, Biomarkers, Cyclophosphamide therapeutic use, Extracellular Vesicles metabolism, Graft vs Host Disease etiology, Graft vs Host Disease metabolism, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Even with high-dose post-transplant cyclophosphamide (PT-Cy) which was initially introduced for graft-versus-host disease (GvHD) prevention in the setting of HLA-haploidentical transplantation, both acute and chronic GvHDs remain a major clinical challenge. Despite improvements in the understanding of the pathogenesis of both acute and chronic GvHDs, reliable biomarkers that predict their onset have yet to be identified. We recently studied the potential correlation between extracellular vesicles (EVs) and the onset of acute (a)GvHD in transplant recipients from related and unrelated donors. In the present study, we further investigated the role of the expression profile of membrane proteins and their microRNA (miRNA) cargo (miRNA100, miRNA155, and miRNA194) in predicting the onset of aGvHD in haploidentical transplant recipients with PT-Cy. Thirty-two consecutive patients were included. We evaluated the expression profile of EVs, by flow cytometry, and their miRNA cargo, by real-time PCR, at baseline, prior, and at different time points following transplant. Using logistic regression and Cox proportional hazard models, a significant association between expression profiles of antigens such as CD146, CD31, CD140a, CD120a, CD26, CD144, and CD30 on EVs, and their miRNA cargo with the onset of aGvHD was observed. Moreover, we also investigated a potential correlation between EV expression profile and cargo with plasma biomarkers (e.g., ST2, sTNFR1, and REG3a) that had been associated with aGVHD previously. This analysis showed that the combination of CD146, sTNFR1, and miR100 or miR194 strongly correlated with the onset of aGvHD (AUROC >0.975). A large prospective multicenter study is currently in progress to validate our findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lia, Di Vito, Bruno, Tapparo, Brunello, Santoro, Mariotti, Bramanti, Zaghi, Calvi, Comba, Fascì, Giaccone, Camussi, Boyle, Castagna, Evangelista, Mavilio and Bruno.)
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- 2022
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38. Post-Transplantation Cyclophosphamide for Graft-versus- Host Disease Prophylaxis in Multiple Myeloma Patients Who Underwent Allogeneic Hematopoietic Cell Transplantation: First Comparison by Donor Type. A Study from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation.
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Sahebi F, Eikema DJ, Koster L, Kroger N, Meijer E, van Doesum JA, Rovira M, Koc Y, Angelucci E, Blaise D, Sammassimo S, McDonald A, Arroyo CH, Sanchez JF, Forcade E, Castagna L, Stölzel F, Sanz J, Tischer J, Ciceri F, Valcarcel D, Proia A, Hayden PJ, Beksac M, Yakoub-Agha I, and Schönland S
- Subjects
- Bone Marrow, Cyclophosphamide therapeutic use, Humans, Neoplasm Recurrence, Local, Retrospective Studies, United States, Unrelated Donors, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Multiple Myeloma therapy
- Abstract
Graft-versus-host disease (GVHD) remains among the major causes of treatment failure in patients with multiple myeloma (MM) undergoing allogeneic hematopoietic cell transplantation (allo-HCT). The use of post-transplantation cyclophosphamide (PT-Cy) is now a well-established and widely used method for GVHD prophylaxis after HLA haploidentical HCT. However, the rationale for using PT-Cy in the setting of matched donor transplantation is less apparent, given the lesser degree of bidirectional alloreactivity. In this retrospective study, we investigated the role of PT-Cy as GVHD prophylaxis in patients with multiple myeloma underoing allo-HCT, among different donor types, to determine cumulative incidence of acute and chronic GVHD and impact on engraftment, progression-free survival (PFS), GVHD-free/relapse- free survival (GRFS), overall survival (OS), and NRM A total of 295 patients with MM underwent allo-HCT using grafts from a matched related donor (MRD; n = 67), matched unrelated donor (MUD; n = 72), mismatched related or unrelated donor (MMRD/MMUD, 1 antigen; n = 27), or haploidentical donor (haplo; n = 129) using PT-Cy between 2012 and 2018. In addition to PT-Cy, agents used in GVHD prophylaxis included calcineurin inhibitors in 239 patients (81%), with mycophenolate mofetil in 184 of those 239 (77%). For grade II-IV acute GVHD, the cumulative incidence at day +100 was 30% (95% confidence interval [CI], 25% to 36%), 9% (95% CI, 5% to 12%) for grade III-IV acute GVHD, and 27% (95% CI, 21% to 32%) for chronic GVHD (limited, 21%; extensive, 6%), with no differences by donor type. The median time to neutrophil engraftment was 19d (95% CI, 18-19), with no significant difference by donor type. The median time to platelet engraftment was delayed in haploidentical donor graft recipients (27 days versus 21 days; P < .001). Two-year OS, PFS, GRFS, and NRM were 51% (95% CI, 45% to 58%), 26% (95% CI, 20% to 32%), 24% (95% CI, 18% to 30%), and 19% (95% CI, 14% to 24%), respectively, with no significant difference between different donor types. In multivariable analyses, compared with the haplo donors, the use of MRDs was associated with significantly better OS (hazard ratio [HR], 0.6; 95% CI, 0.38 to 0.95; P = .029), and the use of MUDs was associated with a significantly higher GRFS (HR, 0.63; 95% CI, 0.42 to 0.97; P = .034). There was a trend toward improved PFS with use of MUDs (HR, 0.69; 95% CI, 0.46 to 1.04; P = .08). Our data show that PT-Cy in MM patients undergoing allo-HCT resulted in low rates of acute and chronic GVHD and led to favorable survival, especially in the matched related donor setting. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2021
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39. Cytokine release syndrome after haploidentical hematopoietic cell transplantation: an international multicenter analysis.
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Abboud R, Wan F, Mariotti J, Arango M, Castagna L, Romee R, Hamadani M, and Chhabra S
- Subjects
- Cyclophosphamide, Cytokine Release Syndrome, Humans, Retrospective Studies, Transplantation Conditioning, Transplantation, Haploidentical adverse effects, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Haploidentical related donor transplantation (haplo-HCT) is associated with cytokine release syndrome (CRS). We conducted a multicenter retrospective study to analyze risk factors for CRS and outcomes after haplo-HCT. We included 451 patients from four academic centers receiving both peripheral blood and bone marrow grafts. Severe CRS was more common with PB vs. BM grafts (19.5% vs 4.9%, OR 2.9, p = 0.05). Multivariable analysis identified recipient CMV sero-positivity, prior transplant, HCT-CI score and donor-recipient sex mismatch as risk factors for severe CRS. Outcomes were analyzed with no CRS as the comparison group. Overall survival (OS) was superior with mild CRS (HR 0.64, p = 0.05) and worst with severe CRS (HR 2.12, p = 0.0038). Relapse risk was significantly decreased in both mild CRS (HR 0.38, p < 0.0001) and severe CRS (HR 0.17, p < 0.0001) groups. The risk of non-relapse mortality was notably higher in severe CRS group (HR 8.0, p < 0.0001), but not in mild CRS group. Acute GVHD was similar among groups. Chronic GVHD at 1 year was 18.5% for no CRS, 23% for mild CRS, and 4.3% for severe CRS (p = 0.0023), with the competing risk of early mortality and short follow up of surviving patients contributing to the low chronic GVHD rates in the severe CRS group., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2021
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40. Feasibility and Efficacy of a Pharmacokinetics-Guided Busulfan Conditioning Regimen for Allogeneic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Adult Patients with Hematologic Malignancies.
- Author
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Bramanti S, De Philippis C, Bartoli A, Giordano L, Mariotti J, Sarina B, Mannina D, Valli V, De Gregori S, Roperti M, Pieri G, and Castagna L
- Subjects
- Busulfan therapeutic use, Cyclophosphamide therapeutic use, Feasibility Studies, Humans, Neoplasm Recurrence, Local, Graft vs Host Disease prevention & control, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation
- Abstract
Busulfan (Bu) is an alkylating agent routinely used for conditioning regimens before allogeneic stem cell transplantation (allo-SCT). Bu shows wide pharmacokinetic (PK) variability among patients. Patients can have a higher systemic exposure (expressed as area under the curve [AUC]) with an increased risk of toxicity or a lower AUC with a higher probability of graft rejection and/or disease relapse. After i.v. administration, an optimal Bu therapeutic window (AUC target of 16,000 to 24,000 μM·minute) has been identified. The use of PK-guided Bu dosing leads to improved overall survival (OS) and progression-free survival (PFS) compared with fixed-dose administration in a variety of hematologic diseases. The aim of this study was to evaluate the outcomes and feasibility of a reduced-toxicity conditioning (RTC) regimen comprising thiotepa, Bu, and fludarabine (TBF) with therapeutic drug monitoring of Bu in patients with hematologic disorders. We report on 41 adult patients with myeloid or lymphoid malignancies who underwent an allo-SCT with a PK-guided Bu-based RTC regimen between January 2019 and October 2020. Patients received a total Bu dose to achieve a target AUC of 16,000 μM·minute in combination with Flu and thiotepa. The median time to absolute neutrophil count recovery and transfusion-independent platelet count recovery was 23 days (range, 15 to 42 days) and 29 days (range, 14 to 97 days), respectively. The cumulative incidence (CI) of nonrelapse mortality was 7% at 100 days and 13% at 1 year. Grade 3 liver toxicity was observed in 6 patients. One patient developed sinusoidal obstruction syndrome at day +27. Grade 3 mucositis occurred in 18 patients. Looking at grade ≥3 infections, the CI was 29% at 30 days, 34% at 60 days, 44% at 100 days, and 56% at 1 year. The 180-day CI of grade II-IV acute graft-versus-host disease (GVHD) was 15%, and the 1-year CI of overall chronic GVHD was 20%. With a median follow-up of alive patients of 14.4 months (range, 3.2 to 24 months), the CI of relapse at 1 year was 6%. The 1-year PFS was 81%, and 1-year OS was 84%. In conclusion, these data support the efficacy of PK-guided Bu dose in the context of a TBF conditioning regimen and the feasibility of therapeutic dosage monitoring of i.v. Bu for patients with hematologic diseases. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2021
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41. Single-cell profiling reveals the dynamics of cytomegalovirus-specific T cells in haploidentical hematopoietic stem cell transplantation.
- Author
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Van Beek JJP, Puccio S, Roberto A, De Paoli F, Graziano G, Salviato E, Alvisi G, Zanon V, Scarpa A, Zaghi E, Calvi M, Di Vito C, Mineri R, Sarina B, De Philippis C, Santoro A, Mariotti J, Bramanti S, Ferrari F, Castagna L, Mavilio D, and Lugli E
- Subjects
- Cytomegalovirus, Humans, T-Lymphocytes, Transplantation Conditioning, Cytomegalovirus Infections, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation
- Published
- 2021
- Full Text
- View/download PDF
42. Allogeneic transplantation after PD-1 blockade for classic Hodgkin lymphoma.
- Author
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Merryman RW, Castagna L, Giordano L, Ho VT, Corradini P, Guidetti A, Casadei B, Bond DA, Jaglowski S, Spinner MA, Arai S, Lowsky R, Shah GL, Perales MA, De Colella JMS, Blaise D, Herrera AF, Shouse G, Spilleboudt C, Ansell SM, Nieto Y, Badar T, Hamadani M, Feldman TA, Dahncke L, Singh AK, McGuirk JP, Nishihori T, Chavez J, Serritella AV, Kline J, Mohty M, Dulery R, Stamatoulas A, Houot R, Manson G, Moles-Moreau MP, Orvain C, Bouabdallah K, Modi D, Ramchandren R, Lekakis L, Beitinjaneh A, Frigault MJ, Chen YB, Lynch RC, Smith SD, Rao U, Byrne M, Romancik JT, Cohen JB, Nathan S, Phillips T, Joyce RM, Rahimian M, Bashey A, Ballard HJ, Svoboda J, Torri V, Sollini M, De Philippis C, Magagnoli M, Santoro A, Armand P, Zinzani PL, and Carlo-Stella C
- Subjects
- Adolescent, Adult, Aged, Female, Follow-Up Studies, Hodgkin Disease drug therapy, Hodgkin Disease pathology, Humans, Male, Middle Aged, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local pathology, Prognosis, Retrospective Studies, Survival Rate, Transplantation, Homologous, Young Adult, Drug Resistance, Neoplasm, Hematopoietic Stem Cell Transplantation mortality, Hodgkin Disease therapy, Immune Checkpoint Inhibitors adverse effects, Neoplasm Recurrence, Local therapy, Programmed Cell Death 1 Receptor antagonists & inhibitors, Salvage Therapy
- Abstract
Anti-PD-1 monoclonal antibodies yield high response rates in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but most patients will eventually progress. Allogeneic hematopoietic cell transplantation (alloHCT) after PD-1 blockade may be associated with increased toxicity, raising challenging questions about the role, timing, and optimal method of transplantation in this setting. To address these questions, we assembled a retrospective cohort of 209 cHL patients who underwent alloHCT after PD-1 blockade. With a median follow-up among survivors of 24 months, the 2-year cumulative incidences (CIs) of non-relapse mortality and relapse were 14 and 18%, respectively; the 2-year graft-versus-host disease (GVHD) and relapse-free survival (GRFS), progression-free survival (PFS), and overall survival were 47%, 69%, and 82%, respectively. The 180-day CI of grade 3-4 acute GVHD was 15%, while the 2-year CI of chronic GVHD was 34%. In multivariable analyses, a longer interval from PD-1 to alloHCT was associated with less frequent severe acute GVHD, while additional treatment between PD-1 and alloHCT was associated with a higher risk of relapse. Notably, post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis was associated with significant improvements in PFS and GRFS. While awaiting prospective clinical trials, PTCy-based GVHD prophylaxis may be considered the optimal transplantation strategy for this patient population., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)
- Published
- 2021
- Full Text
- View/download PDF
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