57 results on '"Bailén, R."'
Search Results
2. P1423: CIRCULATING CELL-FREE DNA KINETICS MEASURED BY DIGITAL PCR IN LYMPHOMA PATIENTS UNDERGOING CD19-CAR-T THERAPY
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López-Esteban, M., primary, Carbonell, D., additional, Bastos-Oreiro, M., additional, de la Iglesia, I., additional, Pérez-Corral, A., additional, Chicano, M., additional, Muñiz, P., additional, Sanz-Villanueva, L., additional, Bailén, R., additional, Oarbeascoa, G., additional, Anguita, J., additional, Kwon, M., additional, Díez-Martín, J. L., additional, Buño, I., additional, and Martínez-Laperche, C., additional
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- 2022
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3. P391: FLT3-ITD MEASUREMENT AT DIAGNOSIS AND FOR THE ASSESSMENT OF MINIMAL RESIDUAL DISEASE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN PATIENTS WITH ACUTE MYELOID LEUKEMIA: CDNA VS. DNA
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Carbonell, D., primary, Chicano, M., additional, Cardero-Illán, A., additional, Rodriguez-Macías, G., additional, Muñiz, P., additional, Bailén, R., additional, Oarbeascoa, G., additional, Gómez-Centurión, I., additional, Anguita, J., additional, Kwon, M., additional, Díez-Martín, J. L., additional, Buño, I., additional, and Martínez-Laperche, C., additional
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- 2022
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4. P1427: MONITORING CAR-T CELL IN B-CELL LYMPHOMA PATIENTS THROUGH SINGLE CHAIN VARIABLE FRAGMENT BY DIGITAL PCR
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De La Iglesia San Sebastián, I., primary, Carbonell, D., additional, Pérez Corral, A., additional, Bastos, M., additional, Bailén, R., additional, Silvia, M., additional, Chicano, M., additional, Muñíz, P., additional, Oarbeascoa, G., additional, Anguita, J., additional, Kwon, M., additional, Díez-Martín, J. L., additional, Buño, I., additional, and Martínez-Laperche, C., additional
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- 2022
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5. RELAPSE CHARACTERIZATION IN DIFFUSE LARGE B CELL LYMPHOMA PATIENTS UNDERGOING COMMERCIAL CAR‐T CELL THERAPY: EXPERIENCE FROM A SINGLE CENTRE
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Bastos‐Oreiro, M., primary, Bailén, R., additional, Silva, P., additional, Monsalvo, S., additional, Pérez Corral, A., additional, Carbonell, D., additional, Díaz Crespo, F., additional, Gómez‐Fernández, I., additional, Oarbeascoa, G., additional, Dorado, N., additional, Muñoz, C., additional, Sabell, S., additional, Menarguez, J., additional, Martínez‐Laperche, C., additional, Buño, I., additional, Anguita Velasco, J., additional, Díez‐Martín, J. L., additional, and Kwon, M., additional
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- 2021
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6. Post-transplant cyclophosphamide for GVHD prophylaxis compared to ATG-based prophylaxis in unrelated donor transplantation
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Bailén R, Kwon M, Pascual-Cascón MJ, Ferrà C, Sanz J, Gallardo-Morillo A, García-Sola A, Torrent A, Jiménez-Lorenzo MJ, Piñana JL, Montoro J, Oarbeascoa G, Dorado N, Gómez-Centurión I, Muñoz C, Martínez-Laperche C, Anguita J, Buño I, and Díez-Martín JL
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GVHD prophylaxis, Post-transplant cyclophosphamide, Unrelated donor HSCT ,surgical procedures, operative ,immune system diseases - Abstract
Post-transplant cyclophosphamide (PTCY) effectively prevents graft-versus-host disease after unmanipulated HLA-haploidentical HSCT. The use of PTCY in the unrelated donor HSCT setting is less explored. We conducted a retrospective study of 132 consecutive patients undergoing a matched or 9/10 mismatched unrelated donor HSCT in 4 centers in Spain, 60 with anti-thymocyte globulin (ATG)-based prophylaxis combined with MTX-CsA, and 72 using a PTCY-based regimen. Peripheral blood stem cells were used as graft in most patients (111 patients, 84%); mMUD donors were balanced between groups. Cumulative incidences of grades II-IV and III-IV acute GVHD at 100 days were lower in the PTCy group (46% vs. 67%, p = 0.008; 3% vs. 34%, p = 0.003), without statistically significant differences in the 2-year cumulative incidence of chronic moderate-severe GVHD. At 2 years, no significant differences were observed in overall survival, event-free survival, cumulative incidence of relapse, and non-relapse mortality. GVHD was the most frequent cause of NRM in the ATG group. No differences were observed between groups in the composite endpoint of GVHD-free and relapse-free survival. In this study, PTCy combined with additional immunosuppression after MUD/mMUD HSCT showed a reduction of aGVHD rate with safety results comparable to those obtained with the ATG-based prophylaxis.
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- 2020
7. S1640 POLYMORPHISMS IN CYTOKINES, CHEMOKINES AND THEIR RECEPTORS GENES CONTRIBUTED TO CYTOMEGALOVIRUS REACTIVATION AFTER ALLOGENEIC STEM CELL TRANSPLANTATION
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Vallejo, M., primary, Muñiz, P., additional, Carbonell, D., additional, Kwon, M., additional, Solán, L., additional, Chicano, M., additional, Bailén, R., additional, Dorado, N., additional, Díez-Martín, J.L., additional, Soria, E., additional, Ramírez, N., additional, Martinez-Laperche, C., additional, and Buño, I., additional
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- 2019
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8. Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease after Unmanipulated Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide: A Study on Behalf of the Spanish Hematopoietic Stem Cell Transplantation and Cellular Therapy Group (GETH)
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Gómez-Centurión, I., Gallardo Morillo, A.I., Pérez Martínez, A., Cabrero Calvo, M., Chinea, A., González, L., Pedraza, A., Jiménez Lorenzo, M.J., Robles, M. Calbacho, Bailén, R., Cascón, M. J. Pascual, Cabero, A., Piñana Sánchez, J.L., Luna, A., Perera Alvarez, M., Rovira, M., Torrent Catarineu, A., Sánchez-Pina, J., and Kwon, M.
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•This study describes characteristics of patients with SOS/VOD after haplo-HSCT with PT-Cy.•Among the 797 haplo-HSCT recipients, 46 patients (5.77%) were diagnosed from SOS/VOD.•Most of the patients developed very severe SOS/VOD according to revised EBMT severity criteria.•Despite a promising SOS/VOD CR rate (65%), 100-day mortality remained high (43%).
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- 2024
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9. Diffuse large B cell lymphoma presenting with a bilateral serous macular detachment
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Reche-Sainz, J.A., Peral-Ortiz de la Torre, M.J., Carpio-Bailén, R., and Toledano-Fernández, N.
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linfoma B difuso de célula grande ,genetic structures ,macula ,lymphoma ,serous detachment ,linfoma ,mácula ,Retina ,diffuse large B cell lymphoma ,desprendimiento seroso - Abstract
Caso clínico: Un varón de 42 años fue atendido por pérdida visual bilateral subaguda. Como antecedentes presentaba una hepatitis C crónica activa y un síndrome de Evans. Mediante funduscopia se observaron múltiples focos de desprendimiento neurosensorial y de EPR en ambas polos posteriores. A los pocos días empeoró su estado general (fiebre alta y múltiples adenopatías). La biopsia de las adenopatías laterocervicales objetivó un linfoma B difuso de células grandes. Se le trató con quimioterapia y experimentó una paulatina reaplicación de los focos de desprendimiento seroso con mejoría visual progresiva. Discusión: El desprendimiento seroso macular bilateral puede ser una manifestación precoz de un linfoma B difuso de célula grande. El curso de estas lesiones intraoculares puede ser favorable con la remisión del linfoma. Clinical case: A 42 year-old male was assessed for a subacute, bilateral and progressive visual loss. His medical history included chronic hepatitis C infection and Evans syndrome. On fundal examination, multiple areas of neurosensorial and retinal pigmented epithelium detachment were observed in the region of both macula. A few days later, his general health deteriorated and he was noted to have a high fever and adenopathy. Biopsy of an enlarged lateral cervical lymph node demonstrated the existence of a diffuse large B cell lymphoma. After several cycles of chemotherapy, he experienced a progressive and bilateral improvement of his vision, which was accompanied by a reattachment of the previously detached areas. Discussion: A bilateral and serous macular detachment may be the initial manifestation of a diffuse large B cell lymphoma. The prognosis of these retinal lesions may be favourable if lymphoma remission is achieved.
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- 2007
10. Desprendimiento seroso macular bilateral como forma de presentación de linfoma B difuso de célula grande
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Reche-Sainz, J.A., primary, Peral-Ortiz de la Torre, M.J., additional, Carpio-Bailén, R., additional, and Toledano-Fernández, N., additional
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- 2007
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11. Real‐world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B‐cell lymphoma
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Lucía López Corral, Anna Sureda, Carlos Solano, Pau Abrisqueta, Juan-Manuel Sancho, Pere Barba, Guillermo Villacampa, Javier Briones, Rafael Hernani, Mi Kwon, Geltamo Spanish Groups Geth, Manuel Guerreiro, Gloria Iacoboni, José María Raya Sánchez, Alberto Mussetti, Ana Carolina Caballero, Alejandro Martin Garcia-Sancho, Juan Luis Reguera-Ortega, Rebeca Bailén, Nuria Martínez-Cibrian, Institut Català de la Salut, [Iacoboni G, Abrisqueta P, Barba P] Servei d’Hematologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Villacampa G] Oncology Data Science, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Martinez-Cibrian N] Department of Hematology, University Hospital Virgen del Rocio, Sevilla, Spain. [Bailén R] Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain. Gregorio Marañón Health Research Institute (IiSGM), Madrid, Spain. [Lopez Corral L] Hematology Department, Hospital Clínico Universitario de Salamanca, IBSAL, CIBERONC, Salamanca, Spain. Centro de Investigación del Cáncer-IBMCC, Salamanca, Spain. [Sanchez JM] Hematology Department, Hospital 12 de Octubre, Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Male ,0301 basic medicine ,aminoácidos, péptidos y proteínas::proteínas::proteínas de membranas::receptores de superficie celular::receptores inmunológicos::receptores de antígenos::receptores de antígenos de linfocitos T [COMPUESTOS QUÍMICOS Y DROGAS] ,Cancer Research ,non‐Hodgkin's lymphoma ,Best Overall Response ,hematological cancer ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Non- Hodgkin's lymphoma ,Gastroenterology ,0302 clinical medicine ,Medicine research ,Other subheadings::/therapeutic use [Other subheadings] ,Càncer ,B-cell lymphoma ,RC254-282 ,Cancer ,Original Research ,Receptors, Chimeric Antigen ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,non‐ ,Standard of Care ,Middle Aged ,Patologia ,Hodgkin&apos ,Progression-Free Survival ,Cytokine release syndrome ,clinical cancer research ,Oncology ,neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B::linfoma de células B grandes difuso [ENFERMEDADES] ,030220 oncology & carcinogenesis ,Cytokines ,Female ,Lymphoma, Large B-Cell, Diffuse ,non-Hodgkin's lymphoma ,medicine.medical_specialty ,Receptors, Antigen, T-Cell ,Cèl·lules B - Tumors - Tractament ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Investigació mèdica ,Real world evidence ,03 medical and health sciences ,s lymphoma ,Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, Large B-Cell, Diffuse [DISEASES] ,Refractory ,clinical observations ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Leukapheresis ,Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Antigen::Receptors, Antigen, T-Cell [CHEMICALS AND DRUGS] ,Aged ,Retrospective Studies ,Otros calificadores::/uso terapéutico [Otros calificadores] ,business.industry ,Teràpia cel·lular ,Clinical Cancer Research ,medicine.disease ,Malaltia de Hodgkin ,Non-Hodgkin's lymphoma ,Lymphoma ,030104 developmental biology ,Hodgkin's disease ,Neoplasm Recurrence, Local ,business - Abstract
Tisagenlecleucel (tisa‐cel) is a second‐generation autologous CD19‐targeted chimeric antigen receptor (CAR) T‐cell therapy approved for relapsed/refractory (R/R) large B‐cell lymphoma (LBCL). The approval was based on the results of phase II JULIET trial, with a best overall response rate (ORR) and complete response (CR) rate in infused patients of 52% and 40%, respectively. We report outcomes with tisa‐cel in the standard‐of‐care (SOC) setting for R/R LBCL. Data from all patients with R/R LBCL who underwent leukapheresis from December 2018 until June 2020 with the intent to receive SOC tisa‐cel were retrospectively collected at 10 Spanish institutions. Toxicities were graded according to ASTCT criteria and responses were assessed as per Lugano 2014 classification. Of 91 patients who underwent leukapheresis, 75 (82%) received tisa‐cel therapy. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 5% and 1%, respectively; non‐relapse mortality was 4%. Among the infused patients, best ORR and CR were 60% and 32%, respectively, with a median duration of response of 8.9 months. With a median follow‐up of 14.1 months from CAR T‐cell infusion, median progression‐free survival and overall survival were 3 months and 10.7 months, respectively. At 12 months, patients in CR at first disease evaluation had a PFS of 87% and OS of 93%. Patients with an elevated lactate dehydrogenase showed a shorter PFS and OS on multivariate analysis. Treatment with tisa‐cel for patients with relapsed/refractory LBCL in a European SOC setting showed a manageable safety profile and durable complete responses., This article provides real‐world European data on the results of relapsed/refractory large B‐cell lymphoma patients treated with tisagenlecleucel.
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- 2021
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12. Successful allogeneic CD34 + hematopoietic stem cell boost for prolonged cytopenias following CAR T-cell therapy in B-cell acute lymphoblastic leukemia. On behalf of the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC).
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Molinos-Quintana Á, Martínez-Cibrian N, Alonso-Saladrigues A, Galán-Gómez V, Bailén R, Buendía-López S, Fuentes-Socorro C, Kwon M, González-Vincent M, Pérez de Soto C, González-Martínez B, Rives S, Pérez-Hurtado JM, Ortiz-Maldonado V, and Pérez-Simón JA
- Abstract
Competing Interests: Competing interests The authors declare no competing interests. Ethics The study involving humans was approved by the local institutional ethics committee: CEI de los Hospitales Universitarios Virgen Macarena y Virgen del Rocı́o (Code: 0600-N-22). The study was conducted in accordance with the local legislation and institutional requirements. Written Informed consent was obtained from all subjects or participants’ legal guardians protected by the GETH-TC.
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- 2024
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13. Post-transplant cyclophosphamide compared to sirolimus/tacrolimus in reduced intensity conditioning transplants for patients with lymphoid malignancies.
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Fox ML, García-Cadenas I, Navarro V, Martínez AP, Kara M, Bazán IS, Ferra Coll C, Bailén R, Bento L, Parody R, Esquirol A, Ortí G, Mussetti A, Salamero O, Martino R, González AP, Barba P, Kwon M, Solano C, Bosch F, and Valcárcel D
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- Humans, Female, Male, Adult, Middle Aged, Aged, Young Adult, Adolescent, Cyclophosphamide therapeutic use, Tacrolimus therapeutic use, Tacrolimus administration & dosage, Sirolimus therapeutic use, Sirolimus pharmacology, Sirolimus administration & dosage, Transplantation Conditioning methods, Hematopoietic Stem Cell Transplantation methods, Graft vs Host Disease prevention & control, Graft vs Host Disease etiology
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Despite novel cellular and immunomodulatory therapies, allogeneic hematopoietic stem cell transplantation (HSCT) remains a treatment option for lymphoid malignancies. Post-transplant cyclophosphamide (PTCY) is increasingly employed for graft vs. host disease (GVHD) prophylaxis. This study aims to evaluate the safety and efficacy of PTCY in reduce intensity (RIC) HSCT for patients with lymphoid neoplasms compared to sirolimus with tacrolimus (SIR/TAC). The primary endpoint was to compare grade III-IV acute GVHD, severe chronic GVHD, and relapse-free survival (GRFS) between the two GVHD prophylaxis strategies. This study, conducted from January 2012 to December 2020, included 171 consecutive patients (82 in the PTCY and 89 in the SIR/TAC group). Results revealed a significantly decreased incidence of moderate and severe forms of chronic GVHD in PTCY cohort (5.8% [95% CI, 1.8 to 13.1]) versus the SIR/TAC cohort (39.6% [95% CI, 29.3 to 49.7] (p < 0.001)). Other outcomes, including GRFS (PTCY [45.9% (95% CI, 35.8-58.7)] and SIR/TAC groups [36.8% (95% CI, 28-48.4)], (p = 0.72)), non-relapse mortality (NRM), relapse and overall survival (OS) were similar in both groups. Interestingly, the failure to achieve GRFS was mainly attributed to GVHD in the SIR/TAC group, while disease relapse was the primary reason in the PTCY cohort., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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14. Anti-CD19 CAR-T Cell Therapy in Elderly Patients: Multicentric Real-World Experience from GETH-TC/GELTAMO.
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Bailén R, Iacoboni G, Delgado J, López-Corral L, Hernani-Morales R, Ortiz-Maldonado V, Guerreiro M, Caballero AC, Guerra-Domínguez ML, Sánchez-Pina JM, Peña M, Torrent A, Pérez-Martínez A, Bastos-Oreiro M, Reguera-Ortega JL, Martín A, Hernandez-Boluda JC, Martínez-Cibrián N, Sanz J, Briones J, Henriquez HL, Calbacho M, Mussetti A, Sancho JM, Barba P, and Kwon M
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- Humans, Aged, Male, Female, Retrospective Studies, Middle Aged, Antigens, CD19 therapeutic use, Antigens, CD19 immunology, Aged, 80 and over, Lymphoma, Large B-Cell, Diffuse therapy, Lymphoma, Large B-Cell, Diffuse immunology, Lymphoma, Large B-Cell, Diffuse mortality, Treatment Outcome, Adult, Biological Products therapeutic use, Receptors, Chimeric Antigen therapeutic use, Receptors, Antigen, T-Cell, Immunotherapy, Adoptive adverse effects, Immunotherapy, Adoptive methods
- Abstract
Chimeric antigen receptor (CAR)-T cell therapy is approved for the treatment of relapsed/refractory (R/R) large B cell lymphoma (LBCL). However, elderly patients might not be candidates for this therapy due to its toxicity, and criteria for candidate selection are lacking. Our aim was to analyze efficacy and toxicity results of CAR-T cell therapy in the population of patients 70 years and older as compared to those obtained in younger patients in the real-world setting. A multicentric retrospective study was performed including patients with R/R aggressive LBCL who received commercial CAR-T cell therapy with either tisagenlecleucel or axicabtagene ciloleucel within the Spanish Group of Hematopoietic Transplant and Cell Therapy/Spanish Group of Lymphomas and Autologous Transplant (GETH-TC/GELTAMO) centers between 2019 and 2023. As of August 2023, 442 adult patients with aggressive LBCL underwent apheresis for CAR-T cell therapy as third or subsequent line and follow-up data was collected. Of 412 infused patients, 71 (17%) were 70 years or older. Baseline characteristics, product selection, and characteristics at apheresis (including disease status, Ann Arbor stage, revised international prognosis index (R-IPI), bulky disease, lactate dehydrogenase [LDH] and ECOG [Eastern Cooperative Group performance status]) were comparable between groups. Median time from both approval to infusion and apheresis to infusion did not differ. No differences were found between groups in overall and complete response rates at 1 and 3 months. With a median follow-up of 12.2 months (range 1-44), 12-month progression-free survival (PFS) and overall survival (OS) were comparable between groups (35.2% in <70 years vs. 35.9% in ≥70 years (P = .938) and 51.1% and 52.1% (P = .885), respectively). Age ≥70 years did not affect PFS (hazard ratio (HR) 0.98, P = .941) and OS (HR 0.97, P = .890) in the univariate and multivariate analysis. Cytokine release syndrome (CRS) was observed in 82% of patients <70 years old and 84.5% in ≥ 70 years old (P = .408). Grade ≥3 CRS was more frequent in the older group (5% vs. 15%, P = .002). In the multivariate analysis, age ≥70 years was associated with an increased risk of grade ≥3 CRS (OR 3.7, P = .013). No differences were observed in terms of overall neurotoxicity (35% vs. 42%, P = .281) or grade ≥3 (12% vs. 17%, P = .33). The proportion of patients with infections, admission to the intensive care unit within the first month, and non-relapse mortality were similar between both groups. CAR-T cell therapy in patients older than 70 years showed similar efficacy to that observed in younger patients in the real-world setting. However, age ≥70 years was an independent risk factor for grades 3-4 CRS. The need for additional strategies to reduce toxicity in this population should be addressed in future studies., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2024
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15. Identification of predictive models including polymorphisms in cytokines genes and clinical variables associated with post-transplant complications after identical HLA-allogeneic stem cell transplantation.
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Muñiz P, Martínez-García M, Bailén R, Chicano M, Oarbeascoa G, Triviño JC, de la Iglesia-San Sebastian I, Fernández de Córdoba S, Anguita J, Kwon M, Díez-Martín JL, Olmos PM, Martínez-Laperche C, and Buño I
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- Humans, Male, Female, Adult, Middle Aged, Young Adult, Adolescent, Hematologic Neoplasms therapy, Hematologic Neoplasms genetics, Hematologic Neoplasms mortality, HLA Antigens genetics, HLA Antigens immunology, Polymorphism, Genetic, Aged, Hematopoietic Stem Cell Transplantation adverse effects, Cytokines genetics, Graft vs Host Disease genetics, Graft vs Host Disease etiology, Transplantation, Homologous adverse effects
- Abstract
Backgrounds: Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies, it can be associated with relevant post-transplant complications. Several reports have shown that polymorphisms in immune system genes are correlated with the development of post-transplant complications. Within this context, this work focuses on identifying novel polymorphisms in cytokine genes and developing predictive models to anticipate the risk of developing graft-versus-host disease (GVHD), transplantation-related mortality (TRM), relapse and overall survival (OS)., Methods: Our group developed a 132-cytokine gene panel which was tested in 90 patients who underwent an HLA-identical sibling-donor allo-HSCT. Bayesian logistic regression (BLR) models were used to select the most relevant variables. Based on the cut-off points selected for each model, patients were classified as being at high or low-risk for each of the post-transplant complications (aGVHD II-IV, aGVHD III-IV, cGVHD, mod-sev cGVHD, TRM, relapse and OS)., Results: A total of 737 polymorphisms were selected from the custom panel genes. Of these, 41 polymorphisms were included in the predictive models in 30 cytokine genes were selected (17 interleukins and 13 chemokines). Of these polymorphisms, 5 (12.2%) were located in coding regions, and 36 (87.8%) in non-coding regions. All models had a statistical significance of p<0.0001., Conclusion: Overall, genomic polymorphisms in cytokine genes make it possible to anticipate the development all complications studied following allo-HSCT and, consequently, to optimize the clinical management of patients., 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 © 2024 Muñiz, Martínez-García, Bailén, Chicano, Oarbeascoa, Triviño, de la Iglesia-San Sebastian, Fernández de Córdoba, Anguita, Kwon, Díez-Martín, Olmos, Martínez-Laperche and Buño.)
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- 2024
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16. Efficacy and safety of bendamustine-containing bridging therapy in R/R LBCL patients receiving CD19 CAR T-cells.
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Iacoboni G, Sánchez-Salinas MA, Rejeski K, Martín-López AÁ, Kwon M, Navarro V, Jalowiec KA, Hernani R, Reguera-Ortega JL, Gallur L, Blumenberg V, Herrero-García M, Roddie C, Benzaquén A, Delgado-Serrano J, Bailén R, Carpio C, Amat P, López-Corral L, Martín-Martín L, Bastos M, Subklewe M, O'Reilly M, and Barba P
- Abstract
Bridging therapy (BT) after leukapheresis is required in most relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients receiving chimeric antigen receptor (CAR) T cells. Bendamustine-containing regimens are a potential BT option. We aimed to assess if this agent had a negative impact on CAR-T outcomes when it was administered as BT. We included R/R LBCL patients from six centers who received systemic BT after leukapheresis from February 2019 to September 2022; patients who only received steroids or had pre-apheresis bendamustine exposure were excluded. Patients were divided into two BT groups, with and without bendamustine. Separate safety and efficacy analyses were carried out for axi-cel and tisa-cel. Of 243 patients who received BT, bendamustine (benda) was included in 62 (26%). There was a higher rate of BT progressors in the non-benda group (62% vs. 45%, p = 0.02). Concerning CAR-T efficacy, complete responses were comparable for benda versus non-benda BT cohorts with axi-cel (70% vs. 53%, p = 0.12) and tisa-cel (44% vs. 36%, p = 0.70). Also, 12-month progression-free and overall survival were not significantly different between BT groups with axi-cel (56% vs. 43% and 71% vs. 63%) and tisa-cel (25% vs. 26% and 52% vs. 48%); there were no differences when BT response was considered. CAR T-cell expansion for each construct was similar between BT groups. Regarding safety, CRS G ≥3 (6% vs. 6%, p = 0.79), ICANS G ≥3 (15% vs. 17%, p = 0.68), severe infections, and neutropenia post-infusion were comparable among BT regimens. BT with bendamustine-containing regimens is safe for patients requiring disease control during CAR T-cell manufacturing., Competing Interests: Gloria Iacoboni: Consultancy and Honoraria: Novartis, Roche, Kite/Gilead, Bristol‐Myers Squibb, Abbvie, Janssen, Sandoz, Miltenyi, AstraZeneca. Mario A. Sánchez‐Salinas Honoraria for presentations: Kite. Support for attending meetings: Takeda. Kai Rejeski: Kite/Gilead: Research Funding, Consultancy, Honoraria and travel support; Novartis: Honoraria; BMS/Celgene: Consultancy, Honoraria; Pierre‐Fabre: travel support. Mi Kwon Consulting and lectures: Gilead, Jazz, Pfizer. Katarzyna A. Jalowiec Honoraria: Kite/Gilead. Rafael Hernani: Research: Gilead. Travel support: Gilead. Honoraria: Gilead, Janssen, MSD, Celgene, Novartis. Viktoria Blumenberg: BMS/Celgene: Research Funding; Kite/Gilead: Consultancy, Honoraria, Research Funding; Janssen: Research Funding, Honoraria; Novartis: Research Funding, Honoraria; Roche: Consultancy, Research Funding; Takeda: Research Funding. Claire Roddie: Honoraria from Kite/Gilead, Novartis, BMS, Amgen. Javier Delgado‐Serrano: Honoraria from Kite‐Gilead, Novartis, Bristol Myers Squibb, Janssen. Rebeca Bailén: Speaker and travel: Kite. Cecilia Carpio: Regeneron: Consultancy/Advisory, BMS: Consultancy/Advisory, Takeda: Consultancy/Advisory/Honoraria, Novartis: Honoraria. Marion Subklewe: receives industry research support from Amgen, Bristol‐Myers Squibb/Celgene, Gilead, Janssen, Miltenyi Biotec, Morphosys, Novartis, Roche, Seattle Genetics, and Takeda, and serves as a consultant/advisor to AvenCell, CDR‐Life, Ichnos Sciences, Incyte Biosciences, Janssen, Molecular Partners, and Takeda. She serves on the speakers' bureau at Amgen, AstraZeneca, BMS/Celgene, Gilead, GSK, Janssen, Novartis, Pfizer, Roche, and Takeda. Maeve O'Reilly: Honoraria from Kite, Novartis, Janssen. Advisory boards Kite and Autolus. Travel grant Kite and Novartis. Pere Barba: Allogene: Honoraria; Amgen: Honoraria; BMS: Honoraria; Kite/Gilead: Honoraria; Janssen: Honoraria; Jazz Pharmaceuticals: Honoraria; Miltenyi: Honoraria; Novartis: Honoraria; Nektar: Honoraria., (© 2024 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.)
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- 2024
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17. Dynamics of virological and immunological markers of HIV persistence after allogeneic haematopoietic stem-cell transplantation in the IciStem cohort: a prospective observational cohort study.
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Salgado M, Gálvez C, Nijhuis M, Kwon M, Cardozo-Ojeda EF, Badiola J, Gorman MJ, Huyveneers LEP, Urrea V, Bandera A, Jensen BO, Vandekerckhove L, Jurado M, Raj K, Schulze Zur Wiesch J, Bailén R, Eberhard JM, Nabergoj M, Hütter G, Saldaña-Moreno R, Oldford S, Barrett L, Ramirez MLM, Garba S, Gupta RK, Revollo B, Ferra-Coll C, Kuball J, Alter G, Sáez-Cirión A, Diez-Martin JL, Duke ER, Schiffer JT, Wensing A, and Martinez-Picado J
- Subjects
- Humans, Male, Prospective Studies, Female, Adult, Middle Aged, HIV-1 immunology, Transplantation, Homologous, Biomarkers blood, Viral Load, HIV Antibodies blood, Hematopoietic Stem Cell Transplantation adverse effects, HIV Infections immunology, HIV Infections virology
- Abstract
Background: Allogeneic haematopoietic stem-cell transplantation (allo-HSCT) markedly reduces HIV reservoirs, but the mechanisms by which this occurs are only partly understood. In this study, we aimed to describe the dynamics of virological and immunological markers of HIV persistence after allo-HSCT., Methods: In this prospective observational cohort study, we analysed the viral reservoir and serological dynamics in IciStem cohort participants with HIV who had undergone allo-HSCT and were receiving antiretroviral therapy, ten of whom had received cells from donors with the CCR5Δ32 mutation. Participants from Belgium, Canada, Germany, Italy, the Netherlands, Spain, Switzerland, and the UK were included in the cohort both prospectively and retrospectively between June 1, 2014 and April 30, 2019. In the first 6 months after allo-HSCT, participants had monthly assessments, with annual assessments thereafter, with the protocol tailored to accommodate for the individual health status of each participant. HIV reservoirs were measured in blood and tissues and HIV-specific antibodies were measured in plasma. We used the Wilcoxon signed-rank test to compare data collected before and after allo-HSCT in participants for whom longitudinal data were available. When the paired test was not possible, we used the Mann-Whitney U test. We developed a mathematical model to study the factors influencing HIV reservoir reduction in people with HIV after allo-HSCT., Findings: We included 30 people with HIV with haematological malignancies who received a transplant between Sept 1, 2009 and April 30, 2019 and were enrolled within the IciStem cohort and included in this analysis. HIV reservoirs in peripheral blood were reduced immediately after full donor chimerism was achieved, generally accompanied by undetectable HIV-DNA in bone marrow, ileum, lymph nodes, and cerebrospinal fluid, regardless of donor CCR5 genotype. HIV-specific antibody levels and functionality values declined more slowly than direct HIV reservoir values, decaying significantly only months after full donor chimerism. Mathematical modelling suggests that allogeneic immunity mediated by donor cells is the main viral reservoir depletion mechanism after massive reservoir reduction during conditioning chemotherapy before allo-HSCT (half-life of latently infected replication-competent cells decreased from 44 months to 1·5 months)., Interpretation: Our work provides, for the first time, data on the effects of allo-HSCT in the context of HIV infection. Additionally, we raise the question of which marker can serve as the last reporter of the residual viraemia, postulating that the absence of T-cell immune responses might be a more reliable marker than antibody decline after allo-HSCT., Funding: amfAR (American Foundation for AIDS Research; ARCHE Program), National Institutes of Health, National Institute of Allergy and Infectious Diseases, and Dutch Aidsfonds., Competing Interests: Declaration of interests AB reports grants from Gilead Sciences and participating on the advisory board of ViiV Healthcare. AW reports funding for this manuscript from the American Foundation for AIDS Research (amfAR) and Aidsfunds; grants from Gilead and NOW; consulting fees from ViiV Healthcare/GSK, MSD, and Gilead Sciences; participating on the board of the Dutch Federation of Medical Microbiology, the board of the European Society for Translational Antiviral Research, chair on the IAS-USA mutations work group, the Committee of ZonMW (Dutch research organization) Research, and the Committee of the Dutch Federation for Long Covid; and received funding from Ark. AS-C reports funding for this manuscript from amfAR; grants from ANRS, the National Institutes of Health (NIH), Institute Pasteur, and MSDAVENIR; honoraria from MSD, ViiV Healthcare, and Gilead Sciences; and is chair of the Scientific and Medical Committee of Sidaction. B-EOJ reports consulting fees from Gilead Sciences, ViiV Healthcare, and Merck Sharp & Dohme; honoraria from Gilead Sciences and ViiV Healthcare; travel expenses for attending meetings from Gilead; and is scientific secretary for the German AIDS Society. BR reports honoraria from Gilead Sciences, Janssen, and ViiV Healthcare; payment for advice from ViiV Healthcare; and travel expenses for attending meetings and travel from ViiV Healthcare and Gilead Sciences. GH reports travel expenses for attending the meeting and travel for the HIV Persistence Workshop 2022. JB reports receiving honoraria from AbbVie, Pfizer, and Gilead Sciences; and travel expenses for attending meetings from AbbVie, Pfizer, and Gilead Sciences. JK reports grants from Novartis and Miltenyi Biotech; royalties from GADETA and Miltenyi Biotech; a patent with GADETA; and holds stock interest in GADETA. JM-P reports funding for this manuscript from amfAR. JSZW reports funding for this manuscript from The German Center for Infection Research, EU H2020 Research and Innovation Programme, HW & J Hector Foundation, the German Research Foundation, The Hamburg Investment and Development Bank, and amfAR; and honoraria from Nobite, GSK, and Gilead Sciences. JTS reports funding for this manuscript from the NIH and National Institute of Allergy and Infectious Diseases. LB report grants from Abbvie and Gilead Sciences; consulting fees from Abbvie and Gilead Sciences; and honoraria from AbbVie and Gilead Sciences. LV reports receiving grants from ViiV Healthcare and Gilead Sciences; and consulting fees from ViiV Healthcare and Gilead Sciences. MJG and GA declare being an employee of Ragon Institute of Mass General, MIT, and Harvard during the study; and an employee of Moderna afterwards. MNi reports receiving consulting fees from Gilead Sciences; and honoraria for lectures from ViiV Healthcare. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2024
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18. Correction: Need for ICU and outcome of critically ill patients with COVID-19 and haematological malignancies: results from the EPICOVIDEHA survey.
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Lahmer T, Salmanton-García J, Marchesi F, El-Ashwah S, Nucci M, Besson C, Itri F, Jaksic O, Čolović N, Weinbergerová B, Seval GC, Adžić-Vukičević T, Szotkowski T, Sili U, Dargenio M, van Praet J, van Doesum J, Schönlein M, Ráčil Z, Žák P, Poulsen CB, Magliano G, Jiménez M, Bonuomo V, Piukovics K, Dragonetti G, Demirkan F, Blennow O, Valković T, Gomes Da Silva M, Maertens J, Glenthøj A, Fernández N, Bergantim R, Verga L, Petzer V, Omrani AS, Méndez GA, Machado M, Ledoux MP, Bailén R, Duarte RF, Del Principe MI, Farina F, Martín-Pérez S, Dávila-Valls J, Marchetti M, Bilgin YM, Fracchiolla NS, Cattaneo C, Espigado I, Cordoba R, Collins GP, Labrador J, Falces-Romero I, Prezioso L, Meers S, Passamonti F, Buquicchio C, López-García A, Kulasekararaj A, Ormazabal-Vélez I, Cuccaro A, Garcia-Vidal C, Busca A, Navrátil M, de Jonge N, Biernat MM, Guidetti A, Abu-Zeinah G, Samarkos M, Anastasopoulou A, de Ramón C, González-López TJ, Hoenigl M, Finizio O, Pinczés LI, Ali N, Vena A, Tascini C, Stojanoski Z, Merelli M, Emarah Z, Kohn M, Barać A, Mladenović M, Mišković B, Ilhan O, Çolak GM, Čerňan M, Gräfe SK, Ammatuna E, Hanakova M, Víšek B, Cabirta A, Nordlander A, Nunes Rodrigues R, Hersby DS, Zambrotta GPM, Wolf D, Núñez-Martín-Buitrago L, Arellano E, Aiello TF, García-Sanz R, Prattes J, Egger M, Limongelli A, Bavastro M, Cvetanoski M, Dibos M, Rasch S, Rahimli L, Cornely OA, and Pagano L
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- 2024
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19. Need for ICU and outcome of critically ill patients with COVID-19 and haematological malignancies: results from the EPICOVIDEHA survey.
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Lahmer T, Salmanton-García J, Marchesi F, El-Ashwah S, Nucci M, Besson C, Itri F, Jaksic O, Čolović N, Weinbergerová B, Seval GC, Adžić-Vukičević T, Szotkowski T, Sili U, Dargenio M, van Praet J, van Doesum J, Schönlein M, Ráčil Z, Žák P, Poulsen CB, Magliano G, Jiménez M, Bonuomo V, Piukovics K, Dragonetti G, Demirkan F, Blennow O, Valković T, Gomes Da Silva M, Maertens J, Glenthøj A, Fernández N, Bergantim R, Verga L, Petzer V, Omrani AS, Méndez GA, Machado M, Ledoux MP, Bailén R, Duarte RF, Del Principe MI, Farina F, Martín-Pérez S, Dávila-Valls J, Marchetti M, Bilgin YM, Fracchiolla NS, Cattaneo C, Espigado I, Cordoba R, Collins GP, Labrador J, Falces-Romero I, Prezioso L, Meers S, Passamonti F, Buquicchio C, López-García A, Kulasekararaj A, Ormazabal-Vélez I, Cuccaro A, Garcia-Vidal C, Busca A, Navrátil M, de Jonge N, Biernat MM, Guidetti A, Abu-Zeinah G, Samarkos M, Anastasopoulou A, de Ramón C, González-López TJ, Hoenigl M, Finizio O, Pinczés LI, Ali N, Vena A, Tascini C, Stojanoski Z, Merelli M, Emarah Z, Kohn M, Barać A, Mladenović M, Mišković B, Ilhan O, Çolak GM, Čerňan M, Gräfe SK, Ammatuna E, Hanakova M, Víšek B, Cabirta A, Nordlander A, Nunes Rodrigues R, Hersby DS, Zambrotta GPM, Wolf D, Núñez-Martín-Buitrago L, Arellano E, Aiello TF, García-Sanz R, Prattes J, Egger M, Limongelli A, Bavastro M, Cvetanoski M, Dibos M, Rasch S, Rahimli L, Cornely OA, and Pagano L
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- Humans, Male, Middle Aged, Female, Aged, Surveys and Questionnaires, Adult, COVID-19 epidemiology, Hematologic Neoplasms complications, Hematologic Neoplasms epidemiology, Critical Illness, Intensive Care Units statistics & numerical data, SARS-CoV-2
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- 2024
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20. Digital PCR Improves Sensitivity and Quantification in Monitoring CAR-T Cells in B Cell Lymphoma Patients.
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de la Iglesia-San Sebastián I, Carbonell D, Bastos-Oreiro M, Pérez-Corral A, Bailén R, Chicano M, Muñiz P, Monsalvo S, Escudero-Fernández A, Oarbeascoa G, Fernández-Caldas P, Gómez-Centurión I, Pion M, Gayoso J, Anguita J, Kwon M, Díez-Martín JL, Buño I, and Martínez-Laperche C
- Subjects
- Humans, Immunotherapy, Adoptive adverse effects, T-Lymphocytes, Polymerase Chain Reaction, Receptors, Chimeric Antigen genetics, Lymphoma, B-Cell etiology
- Abstract
Chimeric antigen receptor T cells (CAR-T) has emerged as a promising therapy, over 60% of patients fail to sustain a long-term response. The underlying factors that leads to the effectiveness of this therapy are not completely understood, CAR-T cell persistence and monitoring seems to be pivotal for ensuring a successful response. Various monitoring methods such as multiparametric flow cytometry (MFC) or quantitative PCR (qPCR) have been applied. Our objective is to develop digital PCR (dPCR) assays for detection and quantification of CAR-T cells, comparing them with MFC and qPCR. Samples taken at different follow-up times from 45 patients treated with CAR-T therapy were analyzed to assess the correlation between the different methodologies. dPCR presented a high correlation with MFC and qPCR (r = 0.97 and r = 0.87, respectively), while offering a higher sensitivity (0.01%) compared to MFC (0.1%) and qPCR (1%). dPCR emerged as an alternative and highly sensitivity method for monitoring CAR-T cell dynamics. This technique is well-suited for implementation in clinical practice as a complementary technique to MFC., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2024
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21. Recent Bendamustine Treatment Before Apheresis Has a Negative Impact on Outcomes in Patients With Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy.
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Iacoboni G, Navarro V, Martín-López AÁ, Rejeski K, Kwon M, Jalowiec KA, Amat P, Reguera-Ortega JL, Gallur L, Blumenberg V, Gutiérrez-Herrero S, Roddie C, Benzaquén A, Delgado-Serrano J, Sánchez-Salinas MA, Bailén R, Carpio C, López-Corral L, Hernani R, Bastos M, O'Reilly M, Martín-Martín L, Subklewe M, and Barba P
- Subjects
- Humans, Bendamustine Hydrochloride adverse effects, Immunotherapy, Adoptive adverse effects, Antigens, CD19, Cell- and Tissue-Based Therapy, Receptors, Chimeric Antigen, Blood Component Removal, Lymphoma, Large B-Cell, Diffuse
- Abstract
Purpose: Approximately 30%-40% of patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) infused with CD19-targeted chimeric antigen receptor (CAR) T cells achieve durable responses. Consensus guidelines suggest avoiding bendamustine before apheresis, but specific data in this setting are lacking. We report distinct outcomes after CAR T-cell therapy according to previous bendamustine exposure., Methods: The study included CAR T-cell recipients from seven European sites. Safety, efficacy, and CAR T-cell expansion kinetics were analyzed according to preapheresis bendamustine exposure. Additional studies on the impact of the washout period and bendamustine dose were performed. Inverse probability treatment weighting (IPTW) and propensity score matching (PSM) analyses were carried out for all efficacy comparisons between bendamustine-exposed and bendamustine-naïve patients., Results: The study included 439 patients with R/R LBCL infused with CD19-targeted commercial CAR T cells, of whom 80 had received bendamustine before apheresis. Exposed patients had significantly lower CD3
+ cells and platelets at apheresis. These patients had a lower overall response rate (ORR, 53% v 72%; P < .01), a shorter progression-free survival (PFS, 3.1 v 6.2 months; P = .04), and overall survival (OS, 10.3 v 23.5 months; P = .01) in comparison with the bendamustine-naïve group. Following adjustment methods for baseline variables, these differences were mitigated. Focusing on the impact of bendamustine washout before apheresis, those with recent (<9 months) exposure (N = 42) displayed a lower ORR (40% v 72%; P < .01), shorter PFS (1.3 v 6.2 months; P < .01), and OS (4.6 v 23.5 months; P < .01) in comparison with bendamustine-naïve patients. These differences remained significant after IPTW and PSM analysis. Conversely, the cumulative dose of bendamustine before apheresis did not affect CAR-T efficacy outcomes., Conclusion: Recent bendamustine exposure before apheresis was associated with negative treatment outcomes after CD19-targeted CAR T-cell therapy and should be therefore avoided in CAR T-cell candidates.- Published
- 2024
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22. Cell-Free DNA Dynamic Concentration and Other Variables Are Predictors of Early Progression after Chimeric Antigen Receptor T Cell Therapy in Patients with Diffuse Large B Cell Lymphoma.
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Bastos-Oreiro M, Sanz-Villanueva L, Muñiz P, Bailén R, Chicano M, Oarbeskoa G, Gómez I, Gutiérrez A, Iglesia I, Carbonell D, Diaz-Crespo FJ, Menarguez J, Diez-Martín JL, Kwon M, Buño I, and Martínez-Laperche C
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- Humans, Male, Immunotherapy, Adoptive adverse effects, Biomarkers, Cell- and Tissue-Based Therapy, Receptors, Chimeric Antigen genetics, Receptors, Chimeric Antigen therapeutic use, Cell-Free Nucleic Acids therapeutic use, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse therapy
- Abstract
We propose a novel biomarker that can identify patients at high risk of early progression after chimeric antigen receptor (CAR) T cell therapy. Calculation of cell-free DNA (cfDNA) with a pre-apheresis (PA) and pre-lymphodepletion (PL) sample allows monitoring of tumor dynamics (∆cfDNA). In the present study, ∆cfDNA and other biomarkers and clinical variables were evaluated in 58 patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL). ∆cfDNA (>11 ng/mL plasma; P =.003), C-reactive protein (CRP) PL (>1.06 mg/dL; P = .004), lactate dehydrogenase (LDH) PL (>304; P = .006), disease status PL (progressive disease; P = .035) and sex (male; P = .016) were highly correlated with 1 month progression. After adjusting for ∆cfDNA, CRP PL, and LDH PL, disease status PL, and sex, ∆cfDNA remained associated with 1-month progression after CAR T cell infusion., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2023
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23. Poor graft function after haploidentical stem cell transplantation with post-transplant cyclophosphamide.
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Gómez-Centurión I, Martin Rojas RM, Bailén R, Muñoz C, Sabell S, Oarbeascoa G, Fernández-Caldas P, Carbonell D, Gayoso J, Martínez-Laperche C, Buño I, Anguita J, Díez-Martin JL, and Kwon M
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- Adult, Humans, Retrospective Studies, Cyclophosphamide therapeutic use, Transplantation Conditioning adverse effects, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Cytomegalovirus Infections complications
- Abstract
This is a retrospective cohort study of consecutive adult patients who received a haploidentical-SCT (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) in a single centre. Poor graft function (PGF) was defined as the occurrence of either persistent neutropenia (ANC < 0.5 × 10
9 /µL) with poor response to granulocyte colony-stimulating factors (G-CSF) and/or thrombocytopenia (platelets < 20 × 109 /L) with transfusion dependence, with complete donor chimerism and without concurrent severe GVHD or underlying disease relapse, during the first 12 months after transplantation. Forty-four (27.5%) out of 161 patients were diagnosed with PGF. Previous CMV reactivation was significantly more frequent in patients with PGF (88.6% versus 73.5%, p = 0.04) and the number of reactivations was also higher in these patients. Besides, early CMV reactivations in the first 6 months post-SCT were also significantly more frequent among patients with PGF (88.6% versus 71.8% p = 0.025). Thirty-two percent of patients with PGF were treated with increasing doses of thrombopoietin-receptor agonists (TRA) and 7 patients were treated with a donor CD34 + selected boost. In total, 93.2% of patients reached adequate peripheral blood counts in a median time of 101 days (range 11-475) after diagnosis. PGF is a frequent complication after haplo-SCT with PT-Cy. CMV reactivation might be the most relevant factor associated to its development. Even when most patients recover peripheral counts with support therapy, there is a group of patients with persistent cytopenias who can effectively be treated with TRA and/or a boost of CD34 + selective cells., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2023
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24. Results of haploidentical transplant in patients with donor-specific antibodies: a survey on behalf of the Spanish Group of Hematopoietic Transplant and Cell Therapy.
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Bailén R, Alenda R, Herruzo-Delgado B, Acosta-Fleitas C, Vallés A, Esquirol A, Fonseca M, Solán L, Sánchez-Vadillo I, Bautista G, Bento L, López-Godino O, Pérez-Martínez A, Torrent A, Zanabili J, Calbacho M, Moreno MÁ, Pascual-Cascón MJ, Guerra-Domínguez L, Chinea A, García-Cadenas I, López-Corral L, Boix-Giner F, López Lorenzo JL, Humala K, Duarte R, Sampol A, Heras I, Vicario JL, Balas A, Oarbeascoa G, Fernández-Caldas P, Anguita J, and Kwon M
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- Pregnancy, Humans, Female, Male, Tissue Donors, Cell- and Tissue-Based Therapy, Immunoglobulin G, Transplantation, Haploidentical, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Background: Donor-specific antibodies (DSAs) are IgG allo-antibodies against mismatched donor HLA molecules and can cause graft failure (GF) in the setting of haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Our aim was to report the experience of the Spanish Group of Hematopoietic Transplant (GETH-TC) in DSA-positive patients who had undergone haplo-HSCT., Methods: We conducted a survey of patients who underwent haplo-HSCT in GETH-TC centers between 2012 and 2021. Data were collected on the DSA assay used, monitoring strategy, complement fixation, criteria for desensitization, desensitization strategies and transplant outcomes., Results: Fifteen centers from the GETH-TC responded to the survey. During the study period, 1,454 patients underwent haplo-HSCT. Seventy of the transplants were performed in 69 DSA-positive patients, all of whom lacked a suitable alternative donor; 61 (88%) patients were female (90% with prior pregnancies). All patients received post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis. Regarding baseline DSA intensity, 46 (67%) patients presented mean fluorescence intensity (MFI) >5,000, including 21 (30%) with MFI >10,000 and three (4%) with MFI >20,000. Six patients did not receive desensitization treatment, four of them with MFI <5,000. Of 63 patients receiving desensitization treatment, 48 (76%) were tested after desensitization therapy, and a reduction in intensity was confirmed in 45 (71%). Three patients (5%) experienced an increase in MFI after desensitization, two of whom experienced primary GF. Cumulative incidence of neutrophil engraftment at day 28 was 74% in a median of 18 days (IQR, 15─20); six patients died before engraftment due to toxicity or infection and eight patients had primary GF despite desensitization in seven of them. After a median follow-up of 30 months, two-year overall and event-free survival were 46.5% and 39%, respectively. The two-year cumulative incidence of relapse was 16% and non-relapse mortality (NRM) was 43%. Infection was the most frequent cause of NRM, followed by endothelial toxicity. Multivariate analysis identified baseline MFI >20,000 as an independent risk factor for survival and an increase in titers after infusion as an independent risk factor for GF., Conclusions: Haplo-HSCT is feasible in DSA-positive patients, with high rates of engraftment after desensitization guided by DSA intensity. Baseline MFI >20,000 and increased intensity after infusion are risk factors for survival and GF., 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 © 2023 Bailén, Alenda, Herruzo-Delgado, Acosta-Fleitas, Vallés, Esquirol, Fonseca, Solán, Sánchez-Vadillo, Bautista, Bento, López-Godino, Pérez-Martínez, Torrent, Zanabili, Calbacho, Moreno, Pascual-Cascón, Guerra-Domínguez, Chinea, García-Cadenas, López-Corral, Boix-Giner, López Lorenzo, Humala, Duarte, Sampol, Heras, Vicario, Balas, Oarbeascoa, Fernández-Caldas, Anguita and Kwon.)
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- 2023
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25. Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma.
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Kwon M, Iacoboni G, Reguera JL, Corral LL, Morales RH, Ortiz-Maldonado V, Guerreiro M, Caballero AC, Domínguez MLG, Pina JMS, Mussetti A, Sancho JM, Bastos-Oreiro M, Catala E, Delgado J, Henriquez HL, Sanz J, Calbacho M, Bailén R, Carpio C, Ribera JM, Sureda A, Briones J, Hernandez-Boluda JC, Cebrián NM, Martin JLD, Martín A, and Barba P
- Subjects
- Humans, Adaptor Proteins, Signal Transducing, Antigens, CD19, Retrospective Studies, Immunotherapy, Adoptive adverse effects, Lymphoma, Large B-Cell, Diffuse therapy
- Abstract
Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P=0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P=0.003, and 42% vs. 16%, P<0.001, respectively). Infections in the first 6 months post-infusion were also more common in patients treated with axi-cel (38% vs. 25%, P=0.033). Non-relapse mortality was not significantly different between the axi-cel and tisa-cel groups (7% and 4%, respectively, P=0.298). With a median follow-up of 9.2 months, median PFS and OS were 5.9 and 3 months, and 13.9 and 11.2 months for axi-cel and tisa-cel, respectively. The 12-month PFS and OS for axi-cel and tisa-cel were 41% and 33% (P=0.195), 51% and 47% (P=0.191), respectively. Factors associated with lower OS in the multivariate analysis were increased lactate dehydrogenase, ECOG ≥2 and progressive disease before lymphodepletion. Safety and efficacy results in our real-world experience were comparable with those reported in the pivotal trials. Patients treated with axi-cel experienced more toxicity but similar non-relapse mortality compared with those receiving tisa-cel. Efficacy was not significantly different between both products.
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- 2023
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26. Allogeneic CD34-selected stem cell boost as salvage treatment of life-threatening infection and severe cytopenias after CAR-T cell therapy.
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de Tena PS, Bailén R, Oarbeascoa G, Gómez-Centurión I, Pérez-Corral A, Carbonell D, Martínez-Laperche C, Sancho M, Bastos-Oreiro M, Conde-Royo D, Fernández-Caldas P, Muñoz C, Sabell S, Buño I, Anguita J, Díez-Martín JL, and Kwon M
- Subjects
- Antifungal Agents therapeutic use, Antigens, CD34, Female, Granulocyte Colony-Stimulating Factor therapeutic use, Humans, Immunotherapy, Adoptive adverse effects, Salvage Therapy, Thrombopoietin, Hematopoietic Stem Cell Transplantation adverse effects, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Receptors, Chimeric Antigen, Thrombocytopenia etiology
- Abstract
Background: A variable incidence of profound cytopenia has been described in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). This complication leads to severe infection in some cases, especially those who present additional risk factors including prior hematopoietic stem cell transplantation (HSCT)., Study Design and Methods: We report a case of breakthrough invasive fungal infection in a patient with prolonged neutropenia after CAR-T cell therapy administered for relapsed B-cell ALL after allogeneic haploidentical HSCT., Results: After disease progression was discarded, therapy with antifungal agents, G-CSF and thrombopoietin analogue was started. However, no sign of haematological recovery or infection improvement was observed. A fresh mobilized selected CD34-stem cell boost from her haploidentical transplant donor was infused without further conditioning. Within 15 days of mobilized CD34-boost administration the patient showed complete resolution of both the aplasia and fungal infection., Discussion: This case illustrates as proof-of-concept the efficacy and safety of selected CD34-stem cell boost from prior donor as salvage treatment of prolonged cytopenias after CAR-T cell therapy., (© 2022 AABB.)
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- 2022
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27. Association between gene polymorphisms in the cyclophosphamide metabolism pathway with complications after haploidentical hematopoietic stem cell transplantation.
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Muñiz P, Andrés-Zayas C, Carbonell D, Chicano M, Bailén R, Oarbeascoa G, Suárez-González J, Gómez Centurión I, Dorado N, Gallardo D, Anguita J, Kwon M, Díez-Martín JL, Martínez-Laperche C, and Buño I
- Subjects
- Alkylating Agents, Cyclophosphamide adverse effects, Cytochrome P-450 CYP2B6, Cytochrome P-450 CYP2C19, Cytochrome P-450 CYP2C8, Cytochrome P-450 CYP2C9, DNA, Glutathione, Humans, Polymorphism, Genetic, Transferases, Graft vs Host Disease genetics, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute therapy
- Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for patients with hematologic malignances. Haploidentical HSCT (Haplo-HSCT) is an alternative option for patients who do not have an HLA-matched donor. The use of post-transplantation high dose cyclophosphamide (PT-Cy) is commonly employed for graft-versus-host disease (GVHD) prophylaxis in haplo-HSCT. Cyclophosphamide (Cy) is an alkylating agent with antineoplastic and immunosuppressive activity, whose bioactivation requires the activity of polymorphic enzymes in the liver to produce phosphoramide mustard, which is a DNA alkylating agent. To identify polymorphisms in the genes of Cy metabolism and correlate them with post-HSCT complications [GVHD, sinusoidal obstruction syndrome (SOS), hemorrhagic cystitis (HC) and transplant-related mortality (TRM)], we designed a custom next-generation sequencing panel with Cy metabolism enzymes. We analyzed 182 patients treated with haplo-HSCT with PT-Cy from 2007 to 2019, detecting 40 variants in 11 Cy metabolism genes. Polymorphisms in CYP2B6, a major enzyme involved in Cy activation, were associated with decreased activity of this enzyme and a higher risk of Graf-versus-host disease (GVHD). Variants in other activation enzymes (CYP2A6, CYP2C8, CYP2C9, CYP2C19) lead to decreased enzyme activity and were associated with GVHD. Polymorphisms in detoxification genes such as glutathione S-transferases decreased the ability to detoxify cyclophosphamide metabolites due to lower enzyme activity, which leads to increased amounts of toxic metabolites and the development of III-IV acute GVHD. GSMT1*0 a single nucleotide polymorphism previously recognized as a risk factor for SOS was associated with a higher risk of SOS. We conclude that polymorphisms of genes involved in the metabolism of cyclophosphamide in our series are associated with severe grades of GVHD and toxicities (SOS and TRM) after haplo-HSCT and could be used to improve the clinical management of transplanted patients., 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 Muñiz, Andrés-Zayas, Carbonell, Chicano, Bailén, Oarbeascoa, Suárez-González, Gómez Centurión, Dorado, Gallardo, Anguita, Kwon, Díez-Martín, Martínez-Laperche and Buño.)
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- 2022
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28. FLT3 -ITD Expression as a Potential Biomarker for the Assessment of Treatment Response in Patients with Acute Myeloid Leukemia.
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Carbonell D, Chicano M, Cardero AJ, Gómez-Centurión I, Bailén R, Oarbeascoa G, Martínez-Señarís D, Franco C, Muñiz P, Anguita J, Kwon M, Díez-Martín JL, Buño I, and Martínez-Laperche C
- Abstract
FLT3 -internal tandem duplication (ITD) analysis is not typically performed in cDNA samples and is not considered an appropriate marker for monitoring measurable residual disease (MRD). The aims of this study were to compare FLT3 -ITD mutation analysis in DNA and cDNA samples at diagnosis and to demonstrate the usefulness of its expression measurement as an MRD marker after allogeneic stem cell transplantation (allo-HSCT) or FLT3 inhibitor (FLT3i) administration. A total of 46 DNA and cDNA diagnosis samples, 102 DNA and cDNA post-allo-HSCT samples from 34 patients and 37 cDNA samples from 7 patients with refractory/relapse AML treated with FLT3i were assessed for the FLT3 -ITD mutation through fragment analysis. In terms of sensitivity, the analysis of cDNA was superior to that of DNA, quantifying higher allelic ratio values in most cases at diagnosis, and thus optimizing the detection of minor clones and prognostic classification. Regarding the last sample before post-HSCT relapse, cDNA analysis anticipated relapse in most cases, unlike DNA analyses. With regard to the post-FLT3i follow-up, FLT3 -ITD expression was reduced after the first FLT3i cycle when the treatment was effective, whereas it was not reduced in refractory patients. FLT3 -ITD expression could be a useful additional biomarker at diagnosis and for the assessment of MRD after allo-HSCT and FLT3i in AML.
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- 2022
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29. Risk prediction of CMV reactivation after allogeneic stem cell transplantation using five non-HLA immunogenetic polymorphisms.
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Vallejo M, Muñiz P, Kwon M, Solán L, Bailén R, Carbonell D, Chicano M, Suárez-González J, Catalán P, Bellón JM, Triviño JC, Dorado N, Gallardo D, Díez-Martín JL, Ramírez N, Martínez-Laperche C, and Buño I
- Subjects
- Cytomegalovirus genetics, Humans, Immunogenetics, Retrospective Studies, Transplantation, Homologous adverse effects, Cytomegalovirus Infections etiology, Cytomegalovirus Infections genetics, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Despite advances in the understanding of the pathophysiology of cytomegalovirus (CMV) infection, it remains as one of the most common infectious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of this study was to determine the genotype of cytokines and chemokines in donor and recipient and their association with CMV reactivation. Eighty-five patients receiving an allo-HSCT from an HLA-identical sibling donor were included in the study. Fifty genes were selected for their potential role in the pathogenesis of CMV infection. CMV DNAemia was evaluated until day 180 after allo-HSCT. CMV reactivation was observed in 51/85 (60%) patients. Of the 213 genetic variants selected, 11 polymorphisms in 7 different genes (CXCL12, IL12A, KIR3DL1, TGFB2, TNF, IL1RN, and CD48) were associated with development or protection from CMV reactivation. A predictive model using five of such polymorphisms (CXCL12 rs2839695, IL12A rs7615589, KIR3DL1 rs4554639, TGFB2 rs5781034 for the recipient and CD48 rs2295615 for the donor) together with the development of acute GVHD grade III/IV improved risk stratification of CMV reactivation. In conclusion, the data presented suggest that the screening of five polymorphisms in recipient and donor pre-transplantation could help to predict the individual risk of CMV infection development after HLA-identical allo-HSCT., (© 2022. The Author(s).)
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- 2022
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30. Post-Transplantation Cyclophosphamide After HLA Identical Compared to Haploidentical Donor Transplant in Acute Myeloid Leukemia: A Study on Behalf of GETH-TC.
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Bailén R, Pascual-Cascón MJ, Guerreiro M, López-Corral L, Chinea A, Bermúdez A, Sampol A, Heras I, García-Torres E, Torres M, Roca JR, Herruzo B, Sanz J, Fonseca M, Herrera P, Colorado M, Bento L, López-Godino O, Martín-Calvo C, Fernández-Caldas P, Marcos-Jubilar M, Sánchez-Ortega I, Solano C, Noriega V, Humala K, Oarbeascoa G, Díez-Martín JL, and Kwon M
- Subjects
- Cyclophosphamide therapeutic use, Humans, Retrospective Studies, Unrelated Donors, Leukemia, Myeloid, Acute therapy, Transplantation Conditioning
- Abstract
Post-transplantation cyclophosphamide (PTCY) effectively prevents graft-versus-host disease (GVHD) after unmanipulated HLA-haploidentical hematopoietic stem cell transplantation (HSCT) and achieves low rates of GVHD in HLA-identical transplantation. To compare the outcomes of haploidentical versus HLA identical HSCT in patients undergoing HSCT for acute myeloid leukemia (AML) using PTCY. We conducted a retrospective study of 229 patients undergoing first HSCT for AML using PTCY with additional immunosuppression, 99 from matched sibling or unrelated donor (MSD/MUD) performed in 3 hospitals and 130 from haploidentical donors (haplo group) performed in 20 hospitals within the Spanish Group of Hematopoietic Stem Cell Transplantation and Cellular Therapy. Peripheral blood stem cells were used as graft in 89% of patients; myeloablative conditioning was used in 56%. There were significantly more patients with active disease (5% versus 20%, P = .001), high/very high disease risk index (DRI) (32% versus 67%, P = .000) and prior auto-HSCT (2% versus 11%, P = .010) in the haplo group. Median follow-up was 27 and 62.5 months for MSD/MUD and haplo, respectively. At 2 years, no significant differences were observed in overall survival (OS) (72% versus 62%, P = .07), event-free survival (EFS) (70% versus 54%, P = .055), cumulative incidence of relapse (19% versus 25%, P = .13), non-relapse mortality (14% versus 19%, P = .145), and the composite endpoint of GVHD and relapse-free survival (49% versus 42%, P = .249). Multivariate analysis identified only age and active disease as significant risk factors for OS and EFS; reduced-intensity conditioning, high/very high DRI, and haplo donor were nearly statistically significant for these outcomes. Grade II-IV acute GVHD was lower in MSD/MUD (14% versus 47%, P = .000). Cumulative incidences of grade III-IV acute GVHD (4% versus 9%, P = .14) and moderate-severe chronic GVHD (22% versus 19%, P = .28) were similar. Limitations of our study include limited sample size, differences between haplo and MSD/MUD groups and heterogeneous additional immunosuppression and PTCY timing in MSD/MUD. The use of an HLA-identical donor with PTCY in patients with AML showed lower incidence of clinically significant grade II-IV acute GVHD compared to haplo donors. Further studies with larger sample sizes should be performed to establish a possible benefit of HLA-identical donor on survival. © 2022 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved., (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. Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) following treatment with tisagenlecleucel.
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Martín-Rojas RM, Gómez-Centurión I, Bailén R, Bastos M, Diaz-Crespo F, Carbonell D, Correa-Rocha R, Pion M, Muñoz C, Sancho M, Gómez Fernández I, Oarbeascoa G, Pérez-Corral A, Martínez-Laperche C, Anguita J, Buño I, Menárguez J, Díez-Martín JL, and Kwon M
- Abstract
Chimeric antigen receptor (CAR) T cell-related HLH/MAS is an unusual manifestation of severe cytokine release syndrome (CRS) with poor prognosis and a challenging diagnosis. The establishment of specific diagnosis criteria is essential, and the combination of several techniques for CAR T-cell follow-up, allows a more precise management of this complication., Competing Interests: MK: Consultancy, Honoraria for Gilead and Novartis. RB: Speaker for Gilead (Kite). GO: Speaker for Gilead (Kite)., (© 2022 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)
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- 2022
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32. Implementation of a hospital-at-home (HAH) unit for hematological patients during the COVID-19 pandemic: safety and feasibility.
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Gómez-Centurión I, Oarbeascoa G, García MC, López Fresneña MC, Martínez Carreño MJ, Escudero Vilaplana V, González-Haba E, Bailén R, Dorado N, Juárez LM, Rodríguez Macías G, Font López P, Encinas C, Bastos-Oreiro M, Anguita J, Sanjurjo M, Díez-Martin JL, and Kwon M
- Subjects
- Adult, Aged, Aged, 80 and over, Disease Management, Feasibility Studies, Female, Hematopoietic Stem Cell Transplantation, Hospitalization, Humans, Leukemia, Myeloid, Acute therapy, Male, Middle Aged, Multiple Myeloma therapy, Myelodysplastic Syndromes therapy, Retrospective Studies, Transplantation, Autologous, Young Adult, COVID-19 epidemiology, Continuity of Patient Care, Hematologic Neoplasms therapy
- Abstract
Background: "Hospital-at-home" (HAH) programs have been shown to optimize resource utilization, shorten hospitalization and prevent nosocomial infection., Methods: We retrospectively analysed data regarding implementation of an HAH unit for caring patients with hematological malignancies in our center, during the COVID-19 pandemic., Results: Between January and November 2020, 105 patients were treated in the HAH unit for a total of 204 episodes. Nine patients with multiple myeloma (MM) received autologous HSCT (auto-HSCT). Three patients with acute myeloid leukemia (AML) received consolidation therapy, 32 patients underwent clinical and analytical monitoring, 20 were transplant recipients early discharged (5 auto-HSCT and 15 allo-HSCT) and 2 had received CART cells therapy. Azacitidine, bortezomib and carfilzomib were administered at home to 54 patients with AML, myelodysplastic syndrome (MDS) or MM. A median of 17 (IQR 13-19) days of admission per patient and a total of 239 visits to the Hematology day-care hospital were avoided. Overall, 28 patients (14% of all episodes) needed admission to the hospital, 4 of them due to COVID-19., Conclusions: Implementation of a Hematology HAH unit was feasible and safe, and provided thorough advanced care to a high-risk population. Advanced care-at-home strategies can be crucial during times of COVID-19 to minimize treatment interruptions and reduce the risk of cross-infections., (© 2021. Japanese Society of Hematology.)
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- 2022
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33. Age-Adjusted Endothelial Activation and Stress Index for Coronavirus Disease 2019 at Admission Is a Reliable Predictor for 28-Day Mortality in Hospitalized Patients With Coronavirus Disease 2019.
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Pérez-García F, Bailén R, Torres-Macho J, Fernández-Rodríguez A, Jiménez-Sousa MÁ, Jiménez E, Pérez-Butragueño M, Cuadros-González J, Cadiñanos J, García-García I, Jiménez-González M, Ryan P, and Resino S
- Abstract
Background: Endothelial Activation and Stress Index (EASIX) predict death in patients undergoing allogeneic hematopoietic stem cell transplantation who develop endothelial complications. Because coronavirus disease 2019 (COVID-19) patients also have coagulopathy and endotheliitis, we aimed to assess whether EASIX predicts death within 28 days in hospitalized COVID-19 patients. Methods: We performed a retrospective study on COVID-19 patients from two different cohorts [derivation ( n = 1,200 patients) and validation ( n = 1,830 patients)]. The endpoint was death within 28 days. The main factors were EASIX [(lactate dehydrogenase
* creatinine)/thrombocytes] and aEASIX-COVID (EASIX* age), which were log2 -transformed for analysis. Results: Log2 -EASIX and log2 -aEASIX-COVID were independently associated with an increased risk of death in both cohorts ( p < 0.001). Log2 -aEASIX-COVID showed a good predictive performance for 28-day mortality both in the derivation cohort (area under the receiver-operating characteristic = 0.827) and in the validation cohort (area under the receiver-operating characteristic = 0.820), with better predictive performance than log2 -EASIX ( p < 0.001). For log2 aEASIX-COVID, patients with low/moderate risk (<6) had a 28-day mortality probability of 5.3% [95% confidence interval (95% CI) = 4-6.5%], high (6-7) of 17.2% (95% CI = 14.7-19.6%), and very high (>7) of 47.6% (95% CI = 44.2-50.9%). The cutoff of log2 aEASIX-COVID = 6 showed a positive predictive value of 31.7% and negative predictive value of 94.7%, and log2 aEASIX-COVID = 7 showed a positive predictive value of 47.6% and negative predictive value of 89.8%. Conclusion: Both EASIX and aEASIX-COVID were associated with death within 28 days in hospitalized COVID-19 patients. However, aEASIX-COVID had significantly better predictive performance than EASIX, particularly for discarding death. Thus, aEASIX-COVID could be a reliable predictor of death that could help to manage COVID-19 patients., Competing Interests: PR reports grants and personal fees from GILEAD and MSD and personal fees from AbbVie and ViiV Healthcare, outside the submitted work. SR reports reports grants from GILEAD and MSD, outside the submitted work. The remaining 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 © 2021 Pérez-García, Bailén, Torres-Macho, Fernández-Rodríguez, Jiménez-Sousa, Jiménez, Pérez-Butragueño, Cuadros-González, Cadiñanos, García-García, Jiménez-González, Ryan and Resino.)- Published
- 2021
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34. Management of Donor-Specific Antibodies in Haploidentical Transplant: Multicenter Experience From the Madrid Group of Hematopoietic Transplant.
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Bailén R, Vicario JL, Solán L, Sánchez-Vadillo I, Herrera P, Calbacho M, Alenda R, López-Lorenzo JL, Humala K, Chinea A, Sánchez-Pina J, Balas A, Moreno MÁ, Arzuaga J, Pradillo V, Dorado N, Oarbeascoa G, Anguita J, Díez-Martín JL, and Kwon M
- Subjects
- Cohort Studies, Female, Graft Rejection mortality, HLA Antigens, Hematopoietic Stem Cell Transplantation, Humans, Male, Middle Aged, Retrospective Studies, Tissue Donors, Graft Rejection immunology, Transplantation, Haploidentical methods, Transplants immunology
- Abstract
Background: Donor specific antibodies (DSAs) can be responsible for graft failure (GF) in the setting of mismatched hematopoietic stem cell transplantation (HSCT). The aim of our study is to report the experience of the Madrid Group of Hematopoietic Transplant (GMTH) in patients with DSAs undergoing haplo-HSCT., Methods: Patients undergoing haplo-HSCT in centers from the GMTH from 2012 to 2020 were included in the study. DSAs were analyzed with a solid-phase single-antigen immunoassay; monitoring was performed during desensitization on days -14, -7, 0 and in a weekly basis until neutrophil engraftment. Desensitization strategies varied depending on center experience, immunofluorescence intensity, complement fixation and type of antibodies., Results: We identified a total of 20 haplo-HSCT in 19 patients performed with DSAs in 5 centers. 10 (53%) patients presented anti-HLA class I DSAs (6 of them with > 5000 mean fluorescence intensity (MFI)), 4 (21%) presented anti-HLA class II (1 with > 5000 MFI) and 5 (26%) presented both anti-HLA class I and II (5 with > 5000 MFI). 90% of patients received at least two treatments as desensitization strategy and all experienced a decrease of MFI after desensitization (mean reduction 74%). Only one patient who developed progressive increase of MFI after infusion developed GF. Desensitization treatments used included rituximab, immunoglobulins, therapeutic plasma exchange, incompatible platelets, buffy coat and immunosuppressors. Seventeen (90%) patients achieved neutrophil engraftment; one patient died before engraftment because of infection and one patient with class I DSAs developed primary GF despite an intensive desensitization. After a median follow-up of 10 months, OS and EFS were 60% and 58%, respectively, cumulative incidence of relapse was 5% and NRM was 32%., Conclusions: Despite the optimal strategy of DSAs desensitization remains unclear, the use of desensitization treatment guided by DSAs intensity kinetics constitute an effective approach with high rates of engraftment for patients with DSAs in need for an haplo-HSCT lacking an alternative suitable donor., 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 © 2021 Bailén, Vicario, Solán, Sánchez-Vadillo, Herrera, Calbacho, Alenda, López-Lorenzo, Humala, Chinea, Sánchez-Pina, Balas, Moreno, Arzuaga, Pradillo, Dorado, Oarbeascoa, Anguita, Díez-Martín and Kwon.)
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- 2021
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35. Real-world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B-cell lymphoma.
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Iacoboni G, Villacampa G, Martinez-Cibrian N, Bailén R, Lopez Corral L, Sanchez JM, Guerreiro M, Caballero AC, Mussetti A, Sancho JM, Hernani R, Abrisqueta P, Solano C, Sureda A, Briones J, Martin Garcia-Sancho A, Kwon M, Reguera-Ortega JL, and Barba P
- Subjects
- Aged, Cytokines metabolism, Female, Humans, Leukapheresis methods, Lymphoma, Large B-Cell, Diffuse metabolism, Male, Middle Aged, Neoplasm Recurrence, Local metabolism, Progression-Free Survival, Receptors, Chimeric Antigen metabolism, Retrospective Studies, Standard of Care, Lymphoma, Large B-Cell, Diffuse drug therapy, Neoplasm Recurrence, Local drug therapy, Receptors, Antigen, T-Cell therapeutic use
- Abstract
Tisagenlecleucel (tisa-cel) is a second-generation autologous CD19-targeted chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). The approval was based on the results of phase II JULIET trial, with a best overall response rate (ORR) and complete response (CR) rate in infused patients of 52% and 40%, respectively. We report outcomes with tisa-cel in the standard-of-care (SOC) setting for R/R LBCL. Data from all patients with R/R LBCL who underwent leukapheresis from December 2018 until June 2020 with the intent to receive SOC tisa-cel were retrospectively collected at 10 Spanish institutions. Toxicities were graded according to ASTCT criteria and responses were assessed as per Lugano 2014 classification. Of 91 patients who underwent leukapheresis, 75 (82%) received tisa-cel therapy. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 5% and 1%, respectively; non-relapse mortality was 4%. Among the infused patients, best ORR and CR were 60% and 32%, respectively, with a median duration of response of 8.9 months. With a median follow-up of 14.1 months from CAR T-cell infusion, median progression-free survival and overall survival were 3 months and 10.7 months, respectively. At 12 months, patients in CR at first disease evaluation had a PFS of 87% and OS of 93%. Patients with an elevated lactate dehydrogenase showed a shorter PFS and OS on multivariate analysis. Treatment with tisa-cel for patients with relapsed/refractory LBCL in a European SOC setting showed a manageable safety profile and durable complete responses., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2021
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36. Clinical Utility of the Detection of the Loss of the Mismatched HLA in Relapsed Hematological Patients After Haploidentical Stem Cell Transplantation With High-Dose Cyclophosphamide.
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Muñiz P, Kwon M, Carbonell D, Chicano M, Bailén R, Oarbeascoa G, Suárez-González J, Andrés-Zayas C, Menárguez J, Dorado N, Gómez-Centurión I, Anguita J, Díez-Martín JL, Martínez-Laperche C, and Buño I
- Subjects
- Adolescent, Adult, Aged, Cyclophosphamide therapeutic use, Female, Humans, Male, Middle Aged, Myeloablative Agonists therapeutic use, Neoplasm Recurrence, Local immunology, Recurrence, Tumor Escape immunology, Young Adult, HLA Antigens immunology, Hematologic Neoplasms immunology, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation methods, Transplantation, Haploidentical methods
- Abstract
Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) with high-dose cyclophosphamide (PTCy) has resulted in a low incidence of graft-vs.-host disease (GVHD), graft failure, and non-relapse mortality. However, post-transplantation relapse remains a common cause of treatment failure in high-risk patients. Unraveling the mechanisms of relapse is therefore crucial for designing effective relapse treatment strategies. One of these mechanisms is the loss of the mismatched HLA on the recipient's leukemic cells. To study the incidence and clinical relevance of this phenomenon, we analyzed 181 patients treated with Haplo-HSCT with PTCy (2007-2019), of which 37 relapsed patients after transplantation. According to the kit employed for HLA-loss analysis, among 22 relapsed patients, we identified HLA loss at relapse in 6 of the 22 patients (27%) studied. Based on the results obtained, the genomic loss of HLA was more common in females than males (66 vs. 33%) and HLA-loss relapses occurred later than classical relapses (345 vs. 166 days). Moreover, the patients with HLA-loss had a greater presence of active disease at the time of transplantation and had undergone a larger number of treatment lines than the group with classical relapses (66 vs. 43% and 66 vs. 18%, respectively). Four of these relapses were studied retrospectively, while two were studied prospectively, the results of which could be considered for patient management. Additionally, two relapsed patients analyzed retrospectively had myeloid neoplasms. One patient had not undergone any treatment, and three had undergone donor lymphocyte infusions (DLIs) and chemotherapy. All presented severe GVHD and disease progression. In contrast, the two patients studied prospectively had a lymphoid neoplasm and were not treated with DLIs. One of them was treated with chemotherapy but died from disease progression, and the other patient underwent a second Haplo-HSCT from a different donor and is still alive. We can conclude that the detection of HLA-loss at the onset of relapse after Haplo-HSCT with PTCy could help in clinical practice to select appropriate rescue treatment, thereby avoiding the use of DLIs or a second transplantation from the same donor., 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 © 2021 Muñiz, Kwon, Carbonell, Chicano, Bailén, Oarbeascoa, Suárez-González, Andrés-Zayas, Menárguez, Dorado, Gómez-Centurión, Anguita, Díez-Martín, Martínez-Laperche and Buño.)
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- 2021
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37. Post-transplant cyclophosphamide for GVHD prophylaxis compared to ATG-based prophylaxis in unrelated donor transplantation.
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Bailén R, Kwon M, Pascual-Cascón MJ, Ferrà C, Sanz J, Gallardo-Morillo A, García-Sola A, Torrent A, Jiménez-Lorenzo MJ, Piñana JL, Montoro J, Oarbeascoa G, Dorado N, Gómez-Centurión I, Muñoz C, Martínez-Laperche C, Anguita J, Buño I, and Díez-Martín JL
- Subjects
- Adolescent, Adult, Aged, Allografts, Disease-Free Survival, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Retrospective Studies, Survival Rate, Antilymphocyte Serum administration & dosage, Cyclophosphamide administration & dosage, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Peripheral Blood Stem Cell Transplantation, Unrelated Donors
- Abstract
Post-transplant cyclophosphamide (PTCY) effectively prevents graft-versus-host disease after unmanipulated HLA-haploidentical HSCT. The use of PTCY in the unrelated donor HSCT setting is less explored. We conducted a retrospective study of 132 consecutive patients undergoing a matched or 9/10 mismatched unrelated donor HSCT in 4 centers in Spain, 60 with anti-thymocyte globulin (ATG)-based prophylaxis combined with MTX-CsA, and 72 using a PTCY-based regimen. Peripheral blood stem cells were used as graft in most patients (111 patients, 84%); mMUD donors were balanced between groups. Cumulative incidences of grades II-IV and III-IV acute GVHD at 100 days were lower in the PTCy group (46% vs. 67%, p = 0.008; 3% vs. 34%, p = 0.003), without statistically significant differences in the 2-year cumulative incidence of chronic moderate-severe GVHD. At 2 years, no significant differences were observed in overall survival, event-free survival, cumulative incidence of relapse, and non-relapse mortality. GVHD was the most frequent cause of NRM in the ATG group. No differences were observed between groups in the composite endpoint of GVHD-free and relapse-free survival. In this study, PTCy combined with additional immunosuppression after MUD/mMUD HSCT showed a reduction of aGVHD rate with safety results comparable to those obtained with the ATG-based prophylaxis.
- Published
- 2021
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38. Transjugular Intrahepatic Portosystemic Shunt for Very Severe Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) after Unmanipulated Haploidentical Hematopoietic Stem Cell Transplantation with Post-transplantation Cyclophosphamide.
- Author
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Gómez-Centurión I, Bailén R, Oarbeascoa G, Muñoz C, Luque AÁ, Boyra ME, Calleja E, Rincón D, Dorado N, Barzallo P, Anguita J, Díez-Martín JL, and Kwon M
- Subjects
- Cyclophosphamide therapeutic use, Humans, Polydeoxyribonucleotides therapeutic use, Retrospective Studies, Hematopoietic Stem Cell Transplantation adverse effects, Hepatic Veno-Occlusive Disease drug therapy, Hepatic Veno-Occlusive Disease etiology, Portasystemic Shunt, Transjugular Intrahepatic
- Abstract
Hepatic veno-occlusive disease or sinusoidal obstruction syndrome (VOD/SOS) is a threatening complication after both autologous and allogeneic hematopoietic stem cell transplantation (HSCT), with high mortality rates despite early medical treatment, including the use of defibrotide (DF). We retrospectively analyzed 185 unmanipulated haploidentical (haplo-) HSCT with post-transplantation cyclophosphamide as graft-versus-host disease prophylaxis performed consecutively between 2011 and June 2019 in a single center. Seventeen patients (9.2%) were diagnosed with VOD/SOS. Based on revised European Society for Blood and Marrow Transplantation severity criteria, the VOD/SOS cases were classified as mild in 2 patients (11.7%), moderate in 2 (11.7%), severe in 2 (11.7%), and very severe in 11 (64.9%). Thirteen patients (76%) were treated with DF, including all patients with severe or very severe VOD/SOS, except 1 patient with CNS hemorrhage. Sixteen patients (94%) were alive at day +100 after HSCT. Seven patients (41%) with very severe VOD/SOS were treated with transjugular intrahepatic portosystemic shunt (TIPS) owing to rapid clinical or analytical deterioration or refractory hepatorenal syndrome despite medical treatment, including DF. TIPS insertion was performed at a median time since VOD/SOS diagnosis of 4 days (range, 1 to 28 days) without technical complications in any case. The median hepatic venous pressure gradient before and after TIPS treatment was 24 mmHg (range, 14 to 29 mmHg) and 7 mmHg (range, 2 to 11 mmHg), respectively, with a median drop of 16 mmHg (range, 9 to 19 mmHg). Following TIPS insertion, all patients showed clinical improvement with hepatomegaly, ascites, and renal failure resolution, and all showed analytical improvement with reduced alanine aminotransferase (ALT), creatinine, and international normalized ratio values, except for patient 2, whose indication for TIPS was refractory hepatorenal syndrome with a normal ALT level. The 6 patients who had initiated DF before TIPS insertion completed 21 days of treatment. All patients met the criteria for complete remission (CR) at a median of 8 days after TIPS insertion (range, 2 to 82 days). The 100-day overall survival was 100%. For patients with rapid progressive VOD/SOS, early TIPS insertion allowed completion of DF therapy. The use of TIPS together with DF resulted in CR and no associated complications with no VOD/SOS-associated mortality despite high severity. In our experience, timely and individualized use of TIPS significantly improves outcomes of very severe VOD/SOS after haplo-HSCT. Therefore, TIPS should be promptly considered in rapidly progressive cases., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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39. Cytokine release syndrome after allogeneic stem cell transplantation with posttransplant cyclophosphamide.
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Solán L, Landete E, Bailén R, Dorado N, Oarbeascoa G, Anguita J, Díez-Martín JL, and Kwon M
- Subjects
- Adolescent, Adult, Aged, Combined Modality Therapy, Cytokine Release Syndrome epidemiology, Cytokine Release Syndrome pathology, Female, Follow-Up Studies, Graft vs Host Disease epidemiology, Graft vs Host Disease pathology, Hematologic Neoplasms pathology, Humans, Incidence, Male, Middle Aged, Prognosis, Retrospective Studies, Spain epidemiology, Survival Rate, Transplantation Conditioning, Transplantation, Homologous, Young Adult, Antineoplastic Agents, Alkylating adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclophosphamide adverse effects, Cytokine Release Syndrome etiology, Graft vs Host Disease etiology, Hematologic Neoplasms drug therapy, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Cytokine release syndrome (CRS) is a systemic inflammatory response with aberrant immune activation and immune hyperstimulation, that leads to increased cytokine levels and inflammation. CRS has been described after antibody and cellular-based therapies. The use of posttransplant cyclophosphamide (PTCy) as graft-vs-host disease (GVHD) prophylaxis in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has led to the extension of allogeneic HSCT to patients without HLA-identical donors. Furthermore, PTCy has also been introduced in matched and unrelated donor HSCT. However, description of incidence and clinical impact of CRS on outcomes in these patients is scarce. We retrospectively analyzed 107 consecutive haplo-HSCT and 39 HLA-identical HSCT with PTCy from 2010 to 2017 in our institution. We used published CRS criteria to identify 76% and 14% of patients who developed CRS after haplo-HSCT and HLA-identical HSCT, respectively. Most patients presented CRS grades 1 and 2. Only one patient from the whole series presented grade 3 CRS and required tocilizumab therapy. The use of peripheral blood stem cells (PBSC), as well as total nucleated cells infused were associated with an increased risk of CRS. Patients who presented CRS developed grade II-IV acute GVHD more frequently than those who did not (60% vs 28.6% respectively, P = .012). The development of CRS was not significantly associated with nonrelapse mortality or overall survival. CRS is a frequent complication after PBSC haploidentical T-repleted HSCT, but significantly less frequent after HLA-identical HSCT. Most cases are mild. Prompt identification allows adequate management of severe forms., (© 2020 John Wiley & Sons Ltd.)
- Published
- 2020
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40. Short Tandem Repeats (STRs) as Biomarkers for the Quantitative Follow-Up of Chimerism after Stem Cell Transplantation: Methodological Considerations and Clinical Application.
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Navarro-Bailón A, Carbonell D, Escudero A, Chicano M, Muñiz P, Suárez-González J, Bailén R, Oarbeascoa G, Kwon M, Díez-Martín JL, Martínez-Laperche C, and Buño I
- Subjects
- Adolescent, Adult, Bone Marrow metabolism, Child, Chimerism, DNA genetics, Female, Follow-Up Studies, Hematopoietic Stem Cell Transplantation methods, Humans, Male, Middle Aged, Recurrence, Retrospective Studies, Young Adult, Biomarkers metabolism, Microsatellite Repeats genetics, Real-Time Polymerase Chain Reaction methods
- Abstract
Chimerism refers to the relative proportion of donor and recipient DNA after hematopoietic stem cell transplantation (HSCT) and its quantitative follow-up is of great clinical utility in this setting. PCR of short tandem repeats (STR-PCR) constitutes the gold standard method for chimerism quantification, although more sensitive PCR techniques (such as qPCR) have recently arisen. We compared the sensitivity and the quantification capacity of both techniques in patient samples and artificial mixtures and demonstrated adequate performance of both methods, with higher sensitivity of qPCR and better quantification skills of STR-PCR. By qPCR, we then prospectively followed up 57 patients that were in complete chimerism (CC) by STR-PCR. Twenty-seven patients (59%) showed 0.1-1% recipient DNA in the bone marrow. Only 4 patients presented 0.1-1% recipient DNA in peripheral blood (PB), and one of them relapsed. Finally, by qPCR, we retrospectively studied the last sample that showed CC by STR-PCR prior to relapse in 8 relapsed patients. At a median of 59 days prior to relapse, six patients presented mixed chimerism by qPCR in PB. Since both approaches have complementary characteristics, we conclude that different techniques should be applied in different clinical settings and therefore propose a methodological algorithm for chimerism follow-up after HSCT.
- Published
- 2020
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41. Evolution of the role of haploidentical stem cell transplantation: past, present, and future.
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Kwon M, Bailén R, and Díez-Martín JL
- Subjects
- Disease Management, Graft vs Host Disease diagnosis, Graft vs Host Disease etiology, Histocompatibility Testing, Humans, Immune Reconstitution, Lymphocyte Depletion adverse effects, Lymphocyte Depletion methods, Patient Outcome Assessment, Postoperative Complications, Tissue Donors, Transplantation Conditioning adverse effects, Transplantation Conditioning methods, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cell Transplantation trends, Transplantation, Haploidentical adverse effects, Transplantation, Haploidentical methods, Transplantation, Haploidentical trends
- Abstract
Introduction: The accessibility to haplo-donors has led to an increase in the number of haplo-HSCT worldwide. A systematic search of the PubMed database between 2000 to present was performed., Areas Covered: In this review, the authors discussed the most used approaches to perform haplo-HSCT and its results: T-cell depletion (TCD, including Perugia platform and its modifications) and T-cell repleted haplo (TCR, including the high-dose post-transplant cyclophosphamide strategy (Baltimore protocol) and the Beijing protocol). The improvements and modifications made to the different strategies have increased the indications of haplo-HSCT, including both malignant and nonmalignant disorders. Focusing on the Baltimore protocol, the authors review the results of the retrospective studies that have compared it to other donor transplants. The limitations of this strategy in terms of toxicity, graft complications, and GVHD are also discussed in detail. Finally, possible approaches to improve the outcomes of TCR haplo-HSCT are presented., Expert Opinion: The recent advances in the field of haplo-HSCT have allowed a large number of patients with incurable diseases to benefit from this procedure despite not having a matched donor. With all available strategies, virtually no patient who needs an allogeneic transplant should be excluded by the absence of a donor.
- Published
- 2020
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42. Posttransplant cyclophosphamide vs cyclosporin A and methotrexate as GVHD prophylaxis in matched sibling transplantation.
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Kwon M, Bailén R, Pascual-Cascón MJ, Gallardo-Morillo AI, García Sola A, Balsalobre P, Solán L, Dorado N, Muñoz C, Serrano D, Martínez-Laperche C, Buño I, Anguita J, and Díez-Martin JL
- Subjects
- Adolescent, Adult, Aged, Blood Cell Count, Drug Therapy, Combination, Female, Graft vs Host Disease diagnosis, Graft vs Host Disease mortality, Hematopoietic Stem Cell Transplantation methods, Histocompatibility Testing, Humans, Immunosuppressive Agents administration & dosage, Male, Middle Aged, Recurrence, Severity of Illness Index, Transplantation Conditioning adverse effects, Transplantation Conditioning methods, Transplantation, Homologous, Treatment Outcome, Unrelated Donors, Young Adult, Cyclophosphamide administration & dosage, Cyclosporine administration & dosage, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation adverse effects, Siblings
- Abstract
Posttransplant cyclophosphamide (PTCy) effectively prevents graft-versus-host disease (GVHD) after HLA-haploidentical hematopoietic stem cell transplantation (HSCT). The use of PTCy in HLA-identical HSCT is less explored. We conducted a retrospective study of 107 consecutive patients undergoing an HLA-identical sibling (10/10) HSCT in 2 centers in Spain, 50 with GVHD prophylaxis with methotrexate-cyclosporin A (MTX-CsA) and 57 using a PTCy-based regimen with additional immunosuppression. Graft source was unmanipulated mobilized peripheral blood stem cells (PBSC) in most patients (97 patients, 91%). Cumulative incidences of grade II to IV and III to IV acute GVHD at 100 days were lower in the PTCy group (22.6% vs 52.2%, P = .0015; 8.8% vs 24.4%, P = .016), without statistically significant differences in the 2-year cumulative incidence of chronic moderate to severe GVHD (16.7% vs 26%, P = .306). At 2 years, no statistically significant differences were observed in OS (78% vs 56%, P = .088), EFS (62.5% vs 48%, P = .054), relapse (28% vs 27%, P = .47), and NRM (8.8% vs 24%, P = .054). The composite endpoint of GVHD and relapse-free survival (GRFS) was favorable for the PTCy group (24% vs 48%, P = .011), PTCy being the sole independent factor identified in the multivariate analysis for this endpoint. In this study, PTCy combination with additional immunosuppression using mostly PBSCs grafts showed a reduction of acute GVHD rate and an impact on GRFS, with safety results comparable with those obtained with MTX-CsA. Further prospective studies are needed to confirm these observations.., (© 2019 by The American Society of Hematology.)
- Published
- 2019
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43. Factors predicting peripheral blood progenitor cell mobilization in healthy donors in the era of related alternative donors: Experience from a single center.
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Bailén R, Pérez-Corral AM, Pascual C, Kwon M, Serrano D, Gayoso J, Balsalobre P, Muñoz C, Díez-Martín JL, and Anguita J
- Subjects
- Adult, Age Factors, Aged, Body Weight, Granulocyte Colony-Stimulating Factor pharmacology, Healthy Volunteers, Humans, Male, Middle Aged, Platelet Count, Retrospective Studies, Antigens, CD34 blood, Blood Donors, Hematopoietic Stem Cell Mobilization standards, Peripheral Blood Stem Cells cytology
- Abstract
Background: Poor mobilization results are unexpected after G-CSF-induced peripheral blood stem cell collection in healthy donors. However, 2%-5% of the donors are poor mobilizers. Factors predicting CD34+-cell yield after mobilization in related alternative donors are still poorly known., Patients and Methods: Baseline characteristics and efficacy results of G-CSF induced mobilization of 159 adult healthy donors in our institution from 2008 to 2016 were retrospectively analyzed. All donors received 10 μg/kg of G-CSF once a day subcutaneously for 4 days. Leukapheresis started on the 5th day of G-CSF treatment. Donors were classified as poor mobilizers if they had less than 20 000 CD34 + cell/mL peripheral blood count in the 5th day of G-CSF treatment or if they needed three or more leukapheresis for graft collection., Results: Age, weight, and platelet count before and after mobilization were significantly different between poor and good mobilizers. Poor mobilizers (n = 16) were older (50.6 vs 41.7 years, P = 0.002), weight lower (64 vs 75 kg, P = 0.00) and showed a lower platelet count before (199.5 vs 219.0 × 10
9 /L, P = 0.03) and after (192.5 vs 206 × 109 /L, P = 0.019) mobilization. In the multivariate analysis only the 30% of the variability of mobilization was explained by the model (sensitivity 80%, specificity 70%)., Conclusion: In this cohort of healthy donors in a single institution, older age, less weight, and lower platelet count was associated with poorer mobilization. With clinical and analytic factors it is not possible to predict more than 30% of the variability. Further studies are needed to investigate new variables., (© 2019 Wiley Periodicals, Inc.)- Published
- 2019
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44. Mononuclear cell collection for extracorporeal photopheresis by using the "off-line" system: A comparative study between COBE Spectra and Spectra Optia devices.
- Author
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Pascual C, González-Arias E, Pérez-Corral AM, Bailén R, Gayoso J, Besson N, Serrano D, Kwon M, Anguita J, and Díez-Martín JL
- Subjects
- Adult, Blood Platelets cytology, Cell Count, Female, Granulocytes cytology, Humans, Leukapheresis methods, Leukapheresis standards, Leukocytes, Mononuclear cytology, Lymphocytes cytology, Male, Middle Aged, Photopheresis methods, Treatment Outcome, Graft vs Host Disease therapy, Leukapheresis instrumentation, Photopheresis instrumentation
- Abstract
Background: Extracorporeal photopheresis (ECP) is an efficient and established therapy to treat acute and chronic graft vs host disease (GVHD). Using an "off-line" method, the first step (mononuclear cell [MNC] collection) is decisive, as long as a high MNC yield and purity in the collected product is desirable. Two "off-line" devices were compared: the COBE Spectra and the Spectra Optia (Terumo BCT), using both continuous and intermittent protocols., Patients and Methods: Twelve patients with GvHD (7 acute/5 chronic) were enrolled between June 2014 and May 2015 and were alternatively assigned for each procedure to either the COBE Spectra or the Spectra Optia cell separator. Patients characteristics and procedure/product parameters were analyzed., Results: Two hundred procedures (100 per device) were included. The Spectra Optia system showed higher total nucleated cells and MNC collection efficiencies (18.6(10.2-29.7) vs 7.9(4.1-14.8)% and 43.6(20.3-59.5) vs 23.3(11.4-37.1)%, P < .001) and monocyte and lymphocyte collection efficiencies (55.2(17.7-83.2) vs 22.8(9-38.9)% and 38.3(26.7-53.4) vs 22.2(9-38.9)%, respectively, P < .001). Absolute platelet loss (PL) and PL per liter of blood processed were significantly lower in the Spectra Optia group (22.9(18.3-28.1) vs 33.6(26.5-41.1)%, P < .001 and 3.7(3.1-4.5) vs 4.3(3.5-4.2)%, P = .01, respectively). However, granulocyte contamination was higher (4.5(1.3-36) vs 1.2(0.4-5.7)%, P < .001) and a higher product haematocrit was obtained with the Spectra Optia (1(0.5-1.6) vs 0.3(0.2-0.5)%, P < .001), without an impact on irradiation time., Conclusions: In our study, Spectra Optia proved to be safe and effective in collecting MNC with high yield and purity for ECP in GvHD., (© 2018 Wiley Periodicals, Inc.)
- Published
- 2019
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45. Allogeneic stem-cell transplantation in HIV-1-infected patients with high-risk hematological disorders.
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Kwon M, Bailén R, Balsalobre P, Jurado M, Bermudez A, Badiola J, Esquirol A, Miralles P, López-Fernández E, Sanz J, Yañez L, Colorado M, Piñana JL, Dorado N, Solán L, Martínez Laperche C, Buño I, Anguita J, Serrano D, and Díez-Martin JL
- Subjects
- Adult, Anti-Retroviral Agents therapeutic use, Female, HIV Infections drug therapy, Humans, Male, Middle Aged, Retrospective Studies, Spain, Survival Analysis, Treatment Outcome, HIV Infections complications, Hematologic Neoplasms therapy, Stem Cell Transplantation, Transplantation, Homologous
- Abstract
Introduction: Although a number of patients with HIV infection and hematological disease have successfully undergone allogeneic hematopoietic stem-cell transplantation (HSCT), short and long-term outcomes remain not well known. We report the largest Spanish experience treating HIV-infected adult patients with high-risk hematological malignancies with allogeneic HSCT., Methods: We retrospectively reviewed 22 HIV-positive patients who received allogeneic HSCT in five centers in Spain., Results: A total of 22 patients with high-risk hematological malignancies were transplanted between 1999 and 2018. Median age was 44 years. With a median follow-up of 65 months (8-112), overall survival and event-free survival were 46%. Nonrelapse mortality was 14% at 12 months and relapse was 24% at 24 months. Grade II-IV acute graft-versus-host disease (GVHD) rate was 44%, and moderate/severe chronic GVHD rate was 41% at 24 months. All patients received combination antiretroviral therapy. Two patients showed severe toxicity related to drug interaction with antiretroviral therapy. 68% of patients showed infectious complications with viral infections as the most frequent cause. Two patients had invasive aspergillosis and one patient presented disseminated tuberculosis. All survivors except one maintained undetectable HIV load at last follow-up after HSCT., Conclusion: Allogeneic HSCT is an effective therapy for high-risk hematological malignancies in patients with HIV infection, and long-term HIV suppression with combination antiretroviral therapy is feasible. However, drug interactions with antiretroviral agents, occurrence of GVHD, and frequent infectious complications account for a complex procedure in this population. Selected HIV-infected patients with hematologic malignancies should be considered for allo-HSCT when indicated, in experienced centers.
- Published
- 2019
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46. Successful Treatment of Severe Aspergillosis with Isavuconazole Therapy after Allogeneic Stem Cell Transplantation.
- Author
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Oarbeascoa G, Dorado N, Bailén R, Serrano D, Balsalobre P, Pradillo V, Guinea J, Padilla B, Sancho M, Machado M, Buño I, Anguita J, Diez-Martin JL, and Kwon M
- Subjects
- Adult, Aspergillosis drug therapy, Aspergillus fumigatus genetics, Aspergillus fumigatus isolation & purification, DNA, Fungal metabolism, Graft vs Host Disease etiology, Humans, Male, Thorax diagnostic imaging, Transplantation, Homologous adverse effects, Antifungal Agents therapeutic use, Aspergillosis therapy, Hematopoietic Stem Cell Transplantation adverse effects, Nitriles therapeutic use, Pyridines therapeutic use, Triazoles therapeutic use
- Abstract
Invasive fungal infections are one of the main infectious complications in allogeneic stem cell transplantation (SCT). Triazoles (voriconazole, posaconazole) are the main prophylactic and therapeutic options for the treatment of invasive aspergillosis. However, pharmacological interactions and hepatotoxicity limit its use. Isavuconazole (ISV) is a recently approved azole with a promising interaction and safety profile. We present a case with invasive aspergillosis in the post-allogeneic SCT setting in a critically ill patient with severe multiorgan failure due to veno-occlusive disease. The patient was treated with ISV and B amphotericin during severe kidney and liver failure and multiple immunosuppressants, without significant drug-related toxicity and with favorable outcome. The interaction and safety profile of ISV is discussed along the reported experience. ISV can be an effective salvage therapy even in complex clinical situations with multiple potential interactions., (© 2019 S. Karger AG, Basel.)
- Published
- 2019
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47. Transient hemolysis due to anti-D and anti-A 1 produced by engrafted donor's lymphocytes after allogeneic unmanipulated haploidentical hematopoietic stem cell transplantation.
- Author
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Bailén R, Kwon M, Pérez-Corral AM, Pascual C, Buño I, Balsalobre P, Serrano D, Gayoso J, Díez-Martín JL, and Anguita J
- Subjects
- ABO Blood-Group System immunology, Adult, Blood Group Incompatibility, Female, Graft Survival, Humans, Isoantibodies blood, Anemia, Hemolytic etiology, Hematopoietic Stem Cell Transplantation adverse effects, Isoantibodies biosynthesis, Lymphocytes immunology, Rho(D) Immune Globulin biosynthesis
- Abstract
Background: Development of de novo alloantibodies against recipient's red blood cell (RBC) antigens by engrafted donor's lymphocytes is a known phenomenon in the setting of allogeneic hematopoietic stem cell transplantation (HSCT). This situation is usually clinically insignificant. We report a case of early clinically relevant hemolytic anemia in a blood group A
1 D+ patient, due to a limited production of anti-D and anti-A1 produced by nonpreviously sensitized newly engrafted donor's immune system., Case Report: A 31-year-old Caucasian woman, blood group A1 , D+, with Hodgkin's lymphoma, received an unmanipulated haploidentical allogeneic peripheral blood HSCT after a nonmyeloablative conditioning regimen. Donor blood group was A2 B, D-. The patient had an uneventful course until Day +34, when she developed clinically significant hemolytic anemia with a positive direct antiglobulin test. Anti-D and anti-A1 produced by the donor-engrafted lymphocytes were detected both in serum and in eluate. The hemolysis produced an accelerated group change, turning the patient's ABO group into A2 B 2 weeks after the detection of the alloantibodies. As the residual patient's RBCs progressively disappeared, anti-D and anti-A1 production decreased and were not detected in serum by Day +41., Conclusion: This case illustrates that de novo alloantibody production against ABO and D antigens by the newly engrafted donor's lymphocytes can occasionally cause clinically significant anemia. To our knowledge, this is the first case reported of clinically significant hemolytic anemia due to a transient anti-D anti-A1 alloimmunization after T-cell-repleted haploidentical HSCT., (© 2017 AABB.)- Published
- 2017
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48. Tubular urate transporter gene polymorphisms differentiate patients with gout who have normal and decreased urinary uric acid excretion.
- Author
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Torres RJ, de Miguel E, Bailén R, Banegas JR, and Puig JG
- Subjects
- Aged, Alleles, Female, Gout urine, Humans, Hyperuricemia urine, Male, Middle Aged, Gout genetics, Hyperuricemia genetics, Organic Anion Transporters genetics, Polymorphism, Single Nucleotide, Uric Acid urine
- Abstract
Objective: Primary gout has been associated with single-nucleotide polymorphisms (SNP) in several tubular urate transporter genes. No study has assessed the association of reabsorption and secretion urate transporter gene SNP with gout in a single cohort of documented primary patients with gout carefully subclassified as normoexcretors or underexcretors., Methods: Three reabsorption SNP (SLC22A12/URAT1, SLC2A9/GLUT9, and SLC22A11/OAT4) and 2 secretion transporter SNP (SLC17A1/NPT1 and ABCG2/BRCP) were studied in 104 patients with primary gout and in 300 control subjects. The patients were subclassified into normoexcretors and underexcretors according to their serum and 24-h urinary uric acid levels under strict conditions of dietary control., Results: Compared with control subjects, patients with gout showed different allele distributions of the 5 SNP analyzed. However, the diagnosis of underexcretor was only positively associated with the presence of the T allele of URAT1 rs11231825, the G allele of GLUT9 rs16890979, and the A allele of ABCG2 rs2231142. The association of the A allele of ABCG2 rs2231142 in normoexcretors was 10 times higher than in underexcretors. The C allele of NPT1 rs1165196 was only significantly associated with gout in patients with normal uric acid excretion., Conclusion: Gout with uric acid underexcretion is associated with transporter gene SNP related mainly to tubular reabsorption, whereas uric acid normoexcretion is associated only with tubular secretion SNP. This finding supports the concept of distinctive mechanisms to account for hyperuricemia in patients with gout with reduced or normal uric acid excretion.
- Published
- 2014
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49. Efficacy and safety of a urate lowering regimen in primary gout.
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Bailén R, González Senac NM, López MM, Llena ML, Migoya M, Rodríguez MT, de Miguel E, Torres RJ, and Puig JG
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Hospitals, Humans, Male, Middle Aged, Gout blood, Gout drug therapy, Safety, Uric Acid blood
- Abstract
Background and Objectives: Pharmacologic urate lowering therapy (ULT), at full maintenance doses, has been associated with acute gout arthritis (in up to 80% of patients). The American College of Rheumatology has recently advocated gradually titrating the maintenance dose upward to chosen serum urate target. Few studies have examined the efficacy and safety of a ULT in primary gout., Patients and Methods: The ULT regimen examined included allopurinol (50 mg/day, with increases of 50 mg/month up to 300 mg/day) and colchicine, as prophylaxis to prevent acute gouty attacks. The efficacy and safety of this regimen was examined in 42 patients in whom allopurinol was withheld for ≥3 months and restarted after this assessment and followed up for 12 months. The efficacy and safety of the ULT regimen was related to the serum urate decrease and to the incidence of acute gout flares, respectively., Results: Fifty-nine patients (mean age 59 years, 56 men) with primary gout received the gradually titrated ULT regimen. Baseline serum urate was (mean±SD) 8.4±0.8 mg/dL. At 3, 6, 9, and 12 months serum urate fell by a mean of 1.8, 2.5, 2.7, and 2.5 mg/dL, respectively (p<0.001). A serum urate level<6.0 mg/dL was achieved by 38/59 (64%) patients. During the 12 months following the start of the ULT we documented 10 acute arthritis episodes (17% of patients)., Conclusions: A gradually titrated hypouricemic regimen for 6 months in patients with primary gout appears to be effective and safe.
- Published
- 2014
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50. Metabolic syndrome in primary gout.
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González-Senac NM, Bailén R, Torres RJ, de Miguel E, and Puig JG
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Mediterranean Region epidemiology, Middle Aged, Prevalence, Gout complications, Metabolic Syndrome complications, Metabolic Syndrome epidemiology
- Abstract
Background and Objectives: Primary gout has traditionally been associated with obesity, arterial hypertension, and abnormal lipid and glucose homeostasis, but we do not know the prevalence of these vascular risk factors in patients with primary gout from a Mediterranean country., Patients and Method: All patients with primary gout and 2 or more acute arthritis episodes documented by a physician were selected for the study. The diagnosis of MS required ≥3 criteria (ATP III). Patients were classified in two groups: decreased (underexcretors) and normal (normoexcretors) uric acid excretion related to serum urate levels., Results: One hundred and four patients (mean age, 59 years; 100 males) with primary gout were included in the study. MS was diagnosed in 38 subjects (37%). The most frequent triad defining MS was an increased waist circumference, blood pressure, and trygliceride levels. The prevalence of type 2 diabetes mellitus (T2D) was significantly higher in patients with the MS (21/38, 55%) as compared with subjects without the MS (3/66, 5%; p<0.001). Mean serum urate level in patients with and without MS was identical (8.1 mg/dL), but mean 24-hour uric acid excretion was significantly lower in the former than in the latter (444±110 mg/24-hour/1,73 m2 versus 546±221 mg/day/1,73 m2; p=0.009)., Conclusions: The condition of the MS occurs in about one-third of the patients with primary gout. Increased waist circumference, blood pressure, and triglycerides levels is the most frequent MS triad. Diminished urinary uric acid excretion is more severe in gout patients with the MS.
- Published
- 2014
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