116 research outputs found
Mobilized Peripheral Blood Stem Cells Versus Unstimulated Bone Marrow As a Graft Source for T-Cell-Replete Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide.
Purpose T-cell-replete HLA-haploidentical donor hematopoietic transplantation using post-transplant cyclophosphamide was originally described using bone marrow (BM). With increasing use of mobilized peripheral blood (PB), we compared transplant outcomes after PB and BM transplants. Patients and Methods A total of 681 patients with hematologic malignancy who underwent transplantation in the United States between 2009 and 2014 received BM (n = 481) or PB (n = 190) grafts. Cox regression models were built to examine differences in transplant outcomes by graft type, adjusting for patient, disease, and transplant characteristics. Results Hematopoietic recovery was similar after transplantation of BM and PB (28-day neutrophil recovery, 88% v 93%, P = .07; 100-day platelet recovery, 88% v 85%, P = .33). Risks of grade 2 to 4 acute (hazard ratio [HR], 0.45; P \u3c .001) and chronic (HR, 0.35; P \u3c .001) graft-versus-host disease were lower with transplantation of BM compared with PB. There were no significant differences in overall survival by graft type (HR, 0.99; P = .98), with rates of 54% and 57% at 2 years after transplantation of BM and PB, respectively. There were no differences in nonrelapse mortality risks (HR, 0.92; P = .74) but relapse risks were higher after transplantation of BM (HR, 1.49; P = .009). Additional exploration confirmed that the higher relapse risks after transplantation of BM were limited to patients with leukemia (HR, 1.73; P = .002) and not lymphoma (HR, 0.87; P = .64). Conclusion PB and BM grafts are suitable for haploidentical transplantation with the post-transplant cyclophosphamide approach but with differing patterns of treatment failure. Although, to our knowledge, this is the most comprehensive comparison, these findings must be validated in a randomized prospective comparison with adequate follow-up
The European Society for Blood and Marrow Transplantation (EBMT) consensus recommendations for donor selection in haploidentical hematopoietic cell transplantation
The number of HLA-haploidentical hematopoietic cell transplants continues to increase worldwide due to recent improvements in outcomes, allowing more patients with hematological malignancies and non-malignant disorders to benefit from this procedure and have a chance to cure their disease. Despite these encouraging results, questions remain as multiple donors are usually available for transplantation, and choosing the best HLA-haploidentical donor for transplantation remains a challenge. Several approaches to haploidentical transplantation have been developed over time and, based on the graft received, can be grouped as follows: T-cell depleted haploidentical transplants, either complete or partial, or with T-cell replete grafts, performed with post-transplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, or G-CSF-primed bone marrow graft and enhanced GVHD prophylaxis. Carefully selecting the donor can help optimize transplant outcomes for recipients of haploidentical donor transplants. Variables usually considered in the donor selection include presence of donor-specific antibodies in the recipient, donor age, donor/recipient gender and ABO combinations, and immunogenic variables, such as natural killer cell alloreactivity or KIR haplotype. Here we provide a comprehensive review of available evidence for selecting haploidentical donors for transplantation, and summarize the recommendations from the European Society for Blood and Marrow Transplantation (EBMT) on donor selection for different transplant platforms
Allogeneic Hematopoietic Cell Transplantation Provides Effective Salvage Despite Refractory Disease or Failed Prior Autologous Transplant in Angioimmunoblastic T-Cell Lymphoma: A CIBMTR Analysis
Background: There is a paucity of data on the role of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with angioimmunoblastic T-cell lymphoma (AITL). Using the CIBMTR registry, we report here the outcomes of AITL patients undergoing an allo-HCT.
Methods: We evaluated 249 adult AITL patients who received their first allo-HCT during 2000â2016.
Results: The median patient age was 56 years (rangeâ=â21â77). Majority of the patients were Caucasians (86%), with a male predominance (60%). Graft-versus-host disease (GVHD) prophylaxis was predominantly calcineurin inhibitor-based approaches while the most common graft source was peripheral blood (97%). Median follow-up of survivors was 49 months (rangeâ=â4â170 months). The cumulative incidence of grade 2â4 and grade 3â4 acute GVHD at day 180 were 36% (95% CIâ=â30â42) and 12 (95% CIâ=â8â17), respectively. The cumulative incidence of chronic GVHD at 1 year was 49% (95%CI 43â56). The 1-year non-relapse mortality (NRM) was 19% (95% CIâ=â14â24), while the 4-year relapse/progression, progression-free survival (PFS), and overall survival (OS) were 21% (95% CIâ=â16â27), 49% (95% CIâ=â42â56), and 56% (95% CIâ=â49â63), respectively. On multivariate analysis, chemoresistant status at the time of allo-HCT was associated with a significantly higher risk for therapy failure (inverse of PFS) (RRâ=â1.73 95% CIâ=â1.08â2.77), while KPS \u3câ90% was associated with a significantly higher risk of mortality (inverse of OS) (RRâ=â3.46 95% CIâ=â1.75â6.87).
Conclusion: Our analysis shows that allo-HCT provides durable disease control even in AITL patients who failed a prior auto-HCT and in those subjects with refractory disease at the time of allografting
Allogeneic hematopoietic cell transplantation provides effective salvage despite refractory disease or failed prior autologous transplant in angioimmunoblastic T-cell lymphoma: a CIBMTR analysis
Abstract
Background
There is a paucity of data on the role of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with angioimmunoblastic T-cell lymphoma (AITL). Using the CIBMTR registry, we report here the outcomes of AITL patients undergoing an allo-HCT.
Methods
We evaluated 249 adult AITL patients who received their first allo-HCT during 2000â2016.
Results
The median patient age was 56Â years (rangeâ=â21â77). Majority of the patients were Caucasians (86%), with a male predominance (60%). Graft-versus-host disease (GVHD) prophylaxis was predominantly calcineurin inhibitor-based approaches while the most common graft source was peripheral blood (97%). Median follow-up of survivors was 49Â months (rangeâ=â4â170Â months). The cumulative incidence of grade 2â4 and grade 3â4 acute GVHD at day 180 were 36% (95% CIâ=â30â42) and 12 (95% CIâ=â8â17), respectively. The cumulative incidence of chronic GVHD at 1Â year was 49% (95%CI 43â56). The 1-year non-relapse mortality (NRM) was 19% (95% CIâ=â14â24), while the 4-year relapse/progression, progression-free survival (PFS), and overall survival (OS) were 21% (95% CIâ=â16â27), 49% (95% CIâ=â42â56), and 56% (95% CIâ=â49â63), respectively. On multivariate analysis, chemoresistant status at the time of allo-HCT was associated with a significantly higher risk for therapy failure (inverse of PFS) (RRâ=â1.73 95% CIâ=â1.08â2.77), while KPS <â90% was associated with a significantly higher risk of mortality (inverse of OS) (RRâ=â3.46 95% CIâ=â1.75â6.87).
Conclusion
Our analysis shows that allo-HCT provides durable disease control even in AITL patients who failed a prior auto-HCT and in those subjects with refractory disease at the time of allografting.https://deepblue.lib.umich.edu/bitstream/2027.42/146782/1/13045_2018_Article_696.pd
Clinical applications of donor lymphocyte infusion from an HLA-haploidentical donor: consensus recommendations from the Acute Leukemia Working Party of the EBMT
Donor lymphocyte infusion has been used in the management of relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation. It can eradicate minimal residual disease or be used to rescue a hematologic relapse, being able to induce durable remissions in a subset of patients. With the increased use of haploidentical hematopoietic cell transplantation, there is renewed interest in the use of donor lymphocytes to either treat or prevent disease relapse post transplant. Published retrospective and small prospective studies have shown encouraging results with therapeutic donor lymphocyte infusion in different haploidentical transplantation platforms. In this consensus paper, finalized on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we summarize the available evidence on the use of donor lymphocyte infusion from haploidentical donor, and provide recommendations on its therapeutic, pre-emptive and prophylactic use in clinical practice
Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide
Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P =.002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P <.001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P =.01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P =.01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival
Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis
Background: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). Patients and methods: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. Results: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. Conclusion: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.Fil: Efe, Cumali. Harran University Hospita; TurquĂaFil: Lammert, Craig. University School of Medicine Indianapolis; Estados UnidosFil: TaĆçılar, Koray. Universitat Erlangen-Nuremberg; AlemaniaFil: Dhanasekaran, Renumathy. University of Stanford; Estados UnidosFil: Ebik, Berat. Gazi Yasargil Education And Research Hospital; TurquĂaFil: Higuera de la Tijera, Fatima. Hospital General de MĂ©xico; MĂ©xicoFil: CalıĆkan, Ali R.. No especifĂca;Fil: Peralta, Mirta. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Gerussi, Alessio. UniversitĂ degli Studi di Milano; ItaliaFil: Massoumi, Hatef. No especifĂca;Fil: Catana, Andreea M.. Harvard Medical School; Estados UnidosFil: Purnak, Tugrul. University of Texas; Estados UnidosFil: Rigamonti, Cristina. UniversitĂ del Piemonte Orientale ; ItaliaFil: Aldana, Andres J. G.. Fundacion Santa Fe de Bogota; ColombiaFil: Khakoo, Nidah. Miami University; Estados UnidosFil: Nazal, Leyla. Clinica Las Condes; ChileFil: Frager, Shalom. Montefiore Medical Center; Estados UnidosFil: Demir, Nurhan. Haseki Training And Research Hospital; TurquĂaFil: Irak, Kader. Kanuni Sultan Suleyman Training And Research Hospital; TurquĂaFil: MelekoÄlu Ellik, Zeynep. Ankara University Medical Faculty; TurquĂaFil: Kacmaz, HĂŒseyin. Adıyaman University; TurquĂaFil: Balaban, Yasemin. Hacettepe University; TurquĂaFil: Atay, Kadri. No especifĂca;Fil: Eren, Fatih. No especifĂca;Fil: Alvares da-Silva, Mario R.. Universidade Federal do Rio Grande do Sul; BrasilFil: Cristoferi, Laura. UniversitĂ degli Studi di Milano; ItaliaFil: Urzua, Ălvaro. Universidad de Chile; ChileFil: EĆkazan, TuÄçe. CerrahpaĆa School of Medicine; TurquĂaFil: Magro, Bianca. No especifĂca;Fil: Snijders, Romee. No especifĂca;Fil: Barutçu, Sezgin. No especifĂca;Fil: Lytvyak, Ellina. University of Alberta; CanadĂĄFil: Zazueta, Godolfino M.. Instituto Nacional de la NutriciĂłn Salvador Zubiran; MĂ©xicoFil: Demirezer Bolat, Aylin. Ankara City Hospital; TurquĂaFil: Aydın, Mesut. Van Yuzuncu Yil University; TurquĂaFil: AmorĂłs MartĂn, Alexandra NoemĂ. No especifĂca;Fil: De Martin, Eleonora. No especifĂca;Fil: Ekin, Nazım. No especifĂca;Fil: Yıldırım, SĂŒmeyra. No especifĂca;Fil: Yavuz, Ahmet. No especifĂca;Fil: Bıyık, Murat. Necmettin Erbakan University; TurquĂaFil: Narro, Graciela C.. Instituto Nacional de la NutriciĂłn Salvador Zubiran; MĂ©xicoFil: Bıyık, Murat. Uludag University; TurquĂaFil: Kıyıcı, Murat. No especifĂca;Fil: KahramanoÄlu Aksoy, Evrim. No especifĂca;Fil: Vincent, Maria. No especifĂca;Fil: Carr, Rotonya M.. University of Pennsylvania; Estados UnidosFil: GĂŒnĆar, Fulya. No especifĂca;Fil: Reyes, Eira C.. Hepatology Unit. Hospital Militar Central de MĂ©xico; MĂ©xicoFil: HarputluoÄlu, Murat. InönĂŒ University School of Medicine; TurquĂaFil: Aloman, Costica. Rush University Medical Center; Estados UnidosFil: Gatselis, Nikolaos K.. University Hospital Of Larissa; GreciaFil: ĂstĂŒndaÄ, YĂŒcel. No especifĂca;Fil: Brahm, Javier. Clinica Las Condes; ChileFil: Vargas, Nataly C. E.. Hospital Nacional Almanzor Aguinaga Asenjo; PerĂșFil: GĂŒzelbulut, Fatih. No especifĂca;Fil: Garcia, Sandro R.. Hospital Iv VĂctor Lazarte Echegaray; PerĂșFil: Aguirre, Jonathan. Hospital Angeles del Pedregal; MĂ©xicoFil: Anders, Margarita. Hospital AlemĂĄn; ArgentinaFil: Ratusnu, Natalia. Hospital Regional de Ushuaia; ArgentinaFil: Hatemi, Ibrahim. No especifĂca;Fil: Mendizabal, Manuel. Universidad Austral; ArgentinaFil: Floreani, Annarosa. UniversitĂ di Padova; ItaliaFil: Fagiuoli, Stefano. No especifĂca;Fil: Silva, Marcelo. Universidad Austral; ArgentinaFil: Idilman, Ramazan. No especifĂca;Fil: Satapathy, Sanjaya K.. No especifĂca;Fil: Silveira, Marina. University of Yale. School of Medicine; Estados UnidosFil: Drenth, Joost P. H.. No especifĂca;Fil: Dalekos, George N.. No especifĂca;Fil: N.Assis, David. University of Yale. School of Medicine; Estados UnidosFil: Björnsson, Einar. No especifĂca;Fil: Boyer, James L.. University of Yale. School of Medicine; Estados UnidosFil: Yoshida, Eric M.. University of British Columbia; CanadĂĄFil: Invernizzi, Pietro. UniversitĂ degli Studi di Milano; ItaliaFil: Levy, Cynthia. University of Miami; Estados UnidosFil: Montano Loza, Aldo J.. University of Alberta; CanadĂĄFil: Schiano, Thomas D.. No especifĂca;Fil: Ridruejo, Ezequiel. Universidad Austral; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones MĂ©dicas e Investigaciones ClĂnicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Wahlin, Staffan. No especifĂca
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Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission.
HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cyâbased Haplo-HCT and 869 underwent MSD using calcineurin inhibitorâbased graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs 7%), consistent with current practice. In multivariable analysis, Haplo-HCT and MSD groups were not different with regard to overall survival (P 5 .15), leukemia-free survival (P 5 .50), nonrelapse mortality (P 5 .16), relapse (P 5 .90), or grade II-IV acute GVHD (P 5 .98). However, the Haplo-HCT group had a significantly lower rate of chronic GVHD (hazard ratio, 0.38; 95% confidence interval, 0.30-0.48; P, .001). Results of subgroup analyses by conditioning intensity and graft source suggested that the reduced incidence of chronic GVHD in Haplo-HCT is not limited to a specific graft source or conditioning intensity. Center effect and minimal residual diseaseâdonor type interaction were not predictors of outcome. Our results indicate a lower rate of chronic GVHD after PT-Cyâbased Haplo-HCT vs MSD using calcineurin inhibitorâbased GVHD prophylaxis, but similar other outcomes, in patients with AML in CR1. Haplo-HCT is a viable alternative to MSD in these patients. © 2019 American Society of Hematology. All rights reserved
Analysis of CD57+ natural killer cells and CD8+ T lymphocytes in periapical granulomas and radicular cysts
Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide
Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival
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