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https://www.readbyqxmd.com/read/28212937/the-impact-of-alemtuzumab-scheduling-on-graft-versus-host-disease-following-unrelated-donor-fludarabine-and-melphalan-allografts
#1
Kile Green, Kim Pearce, Rob S Sellar, Laura Jardine, Phillip Lr Nicolson, Sandeep Nagra, Venetia Bigley, Graham Jackson, Anne M Dickinson, Kirsty Thomson, Stephen Mackinnon, Charles Craddock, Karl S Peggs, Matthew Collin
Alemtuzumab conditioning is highly effective at reducing the incidence of acute and chronic graft versus host disease (GVHD) in reduced intensity fludarabine and melphalan transplantation with ciclosporin monotherapy. Less frequent and lower dose scheduling may be used with sibling donors but an optimal regimen for matched unrelated donors has not been defined. In this retrospective observational study of 313 patients, the incidence and severity of GVHD was compared in patients receiving three different dose schedules: the standard 100mg regimen (20mg on day -7 to -3), 60mg (30mg day -4 and -2) or 50mg (10mg on day -7 to -3)...
February 14, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28206973/clinical-implications-of-hla-locus-mismatching-in-unrelated-donor-hematopoietic-cell-transplantation-a-meta-analysis
#2
REVIEW
Ruxiu Tie, Tiansong Zhang, Bo Yang, Huarui Fu, Biqing Han, Jian Yu, Yamin Tan, He Huang
It remains controversial that the impacts of individual HLA locus mismatches on clinical outcomes of patients receiving unrelated-donor hematopoietic cell transplantation (HCT), as compared to HLA allele matched controls. We conducted a meta-analysis to address these issues. Four databases (PubMed, Embase, Web of Science and the Cochrane Library) were searched to select eligible studies. All donor-recipient pairs were high-resolution typing for HLA-A, -B, -C, -DRB1, DQB1 and DPB1 loci. Multivariate-adjusted hazard ratios (HRs) were extracted and pooled using a random-effects model...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28205066/a-single-center-analysis-of-chronic-graft-versus-host-disease-free-relapse-free-survival-after-alternative-donor-stem-cell-transplantation-in-children-with-hematological-malignancies
#3
Jiro Inagaki, Reiji Fukano, Maiko Noguchi, Jun Okamura
We assessed the clinical outcomes of allogeneic hematopoietic stem cell transplantation (SCT) from alternative donors for pediatric patients with hematological malignancies, defining graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) as a composite endpoint. We also defined chronic GVHD-free, relapse-free survival (cGRFS) as survival without severe chronic GVHD, relapse, or death. The probabilities of 2-year disease-free survival from a human leukocyte antigen (HLA) matched unrelated donor (n = 57), related donor with HLA-1 antigen mismatch in the graft-versus-host direction (1Ag-GvH-MMRD, n = 28), and unrelated umbilical cord blood (n = 35) were 52...
February 15, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28199755/incidence-and-risk-factor-of-hemorrhagic-cystitis-after-allogeneic-transplantation-with-fludarabine-busulfan-and-anti-thymocyte-globulin-myeloablative-conditioning
#4
Wilson Lam, Jan Storek, Haocheng Li, Michelle Geddes, Andrew Daly
BACKGROUND: Hemorrhagic cystitis (HC) is a complication of allogeneic stem cell transplantation (SCT), associated with factors such as BK polyomavirus reactivation, age, conditioning regimen, and presence of graft-versus-host disease (GVHD). The incidence and impact of HC in patients receiving fludarabine (Flu), busulfan (Bu), and anti-thymocyte globulin (ATG) conditioning is unknown. METHODS: We conducted a case-control study of patients undergoing SCT at our center between January 1, 2003 and Dec 31, 2012, to determine the incidence of HC and its effect on patient outcomes including overall survival (OS), relapse, non-relapse mortality, GVHD, and healthcare resource use...
February 15, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28198173/delphi-based-study-and-analysis-of-key-risk-factors-for-invasive-fungal-infection-in-haematological-patients
#5
L Vázquez, M Salavert, J Gayoso, M Lizasoaín, I Ruiz Camps, N Di Benedetto
OBJECTIVE: Mortality caused by invasive fungal infections due to filamentous fungi (IFI-FF) is high. Predisposing factors to IFI-FF are multiple and should be stratified. The objective of this study was to identify key risk factors for IFI-FF in onco-haematological patients in different clinical settings. METHODS: Prospective national Delphi study. Risk factors for IFI-FF in patients with onco-haematological diseases were identified by a systematic review of the literature...
February 14, 2017: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
https://www.readbyqxmd.com/read/28169418/allogeneic-transplantation-using-cd34-selected-peripheral-blood-progenitor-cells-combined-with-non-mobilized-donor-t%C3%A2-cells-for-refractory-severe-aplastic-anaemia
#6
Enkhtsetseg Purev, Xin Tian, Georg Aue, Jeremy Pantin, Phuong Vo, Reem Shalabi, Robert N Reger, Lisa Cook, Catalina Ramos, Elena Cho, Tat'yana Worthy, Hanh Khuu, David Stroncek, Neal S Young, Richard W Childs
Allogeneic haematopoietic stem cell transplantation is curative for severe aplastic anaemia (SAA) unresponsive to immunosuppressive therapy. To reduce chronic graft-versus-host disease (GVHD), which occurs more frequently after peripheral blood stem cell (PBSC) transplantation compared to bone-marrow transplantation (BMT), and to prevent graft rejection, we developed a novel partial T-cell depleted transplant that infuses high numbers of granulocyte colony-stimulating factor-mobilized CD34(+) selected PBSCs combined with a BMT-equivalent dose of non-mobilized donor T-cells...
February 7, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28161606/the-absolute-number-of-regulatory-t-cells-in-unmanipulated-peripheral-blood-grafts-predicts-the-occurrence-of-acute-graft-versus-host-disease-post-haplo-identical-hematopoietic-stem-cell-transplantation
#7
Li Ding, Heng Zhu, Yang Yang, Hong-Min Yan, Hai-Hong Zhang, Dong-Mei Han, Zhi-Dong Wang, Xiao-Li Zheng, Jing Liu, Ling Zhu, Mei-Xue, Zi-Kuan Guo, Heng-Xiang Wang
CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) have been reported to play a central role in suppressing acute graft-versus-host disease (aGVHD), but whether the Treg contents of grafts correlates with the occurrence of aGVHD post haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) remains unclear. In the present study, changes in Tregs in peripheral blood (PB) were followed before and after granulocyte colony-stimulating factor (G-CSF) mobilization. In addition, functional analyses of Tregs in PB grafts and bone marrow (BM) grafts were performed...
January 18, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28154284/chronic-graft-versus-host-disease-presenting-with-multiple-punctate-intracranial-lesions-on-contrast-enhanced-magnetic-resonance-imaging
#8
Makoto Terada, Kiyotaka Nakamagoe, Naoshi Obara, Shinichi Ogawa, Noriaki Sakamoto, Taiki Sato, Seitaro Nohara, Shigeru Chiba, Akira Tamaoka
Central nervous system graft-versus-host disease can present quite a diagnostic challenge. We herein present a case of histologically-confirmed chronic graft versus host disease (GVHD) involving the central nervous system that occurred at 19 months after peripheral blood stem cell transplantation. Cranial magnetic resonance imaging showed areas of confluent hyperintensity in the deep/subcortical white matter with multiple punctate and curvilinear gadolinium enhancements, suggesting the disruption of the blood-brain barrier...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28151427/pd-1-modulates-regulatory-t-cell-homeostasis-during-low-dose-il-2-therapy
#9
Takeru Asano, Yusuke Meguri, Takanori Yoshioka, Yuriko Kishi, Miki Iwamoto, Makoto Nakamura, Yasuhisa Sando, Hideo Yagita, John Koreth, Haesook T Kim, Edwin P Alyea, Philippe Armand, Corey S Cutler, Vincent T Ho, Joseph H Antin, Robert J Soiffer, Yoshinobu Maeda, Mitsune Tanimoto, Jerome Ritz, Ken-Ichi Matsuoka
CD4+Foxp3+ regulatory T cells (Tregs) play a central role in the maintainance of immune tolerance after HSCT. We previously reported that low-dose IL-2 therapy increased circulating Tregs and improved clinical symptoms of chronic GVHD, however, the mechanisms which regulate Treg homeostasis during IL-2 therapy have not been well studied. To elucidate these regulatory mechanisms, we examined the role of inhibitory coreceptors on Tregs during IL-2 therapy in a murine model and in patients with chronic GVHD. Murine studies demonstrated that low-dose IL-2 selectively increased Treg and simultaneously enhanced the expression of Programmed death-1 (PD-1), especially on CD44(+)CD62L(+) central-memory Treg, while expression of other inhibitory molecules including CTLA-4, LAG-3 and TIM-3 remained stable...
February 1, 2017: Blood
https://www.readbyqxmd.com/read/28148718/role-of-myeloid-derived-suppressor-cells-in-allogeneic-hematopoietic-cell-transplantation
#10
REVIEW
Brent H Koehn, Bruce R Blazar
Graft-versus-host disease (GVHD) can be a devastating complication for as many as a third of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT). A role for myeloid cells in the amplification of GVHD has been demonstrated; however, less is understood about a potential regulatory role that myeloid cells play or whether such cells may be manipulated and applied therapeutically. Myeloid-derived suppressor cells (MDSCs) are a naturally occurring immune regulatory population that are engaged and expand shortly after many forms of immune distress, including cancer, trauma, and infection...
February 1, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28138397/a-combined-biomarker-and-clinical-panel-for-chronic-graft-versus-host-disease-diagnosis
#11
Joseph Pidala, Tara K Sigdel, Anyou Wang, Sue Hsieh, Yoshi Inamoto, Paul J Martin, Mary Ed Flowers, John A Hansen, Stephanie J Lee, Minnie M Sarwal
Whilst many chronic graft versus host disease (cGVHD) biomarkers have been previously reported, few have been verified in an independent cGVHD cohort. We aimed to verify the diagnostic accuracy of previously reported markers of cGVHD in a multi-centre Chronic GVHD Consortium. A total of 42 RNA and 18 protein candidate biomarkers were assessed amongst 59 cGVHD cases and 33 matched non-GVHD controls. Total RNA was isolated from PBMC, and RNA markers were quantified using PCR. Serum protein markers were quantified using ELISA...
January 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28134923/transforming-growth-factor-%C3%AE-1-functional-polymorphisms-in-myeloablative-sibling-hematopoietic-stem-cell-transplantation
#12
M Berro, M V Palau Nagore, M M Rivas, P Longo, C Foncuberta, A Vitriú, G Remaggi, J Martínez Rolon, G Jaimovich, A Requejo, L Feldman, K Padros, M B Rodríguez, B E Shaw, I Larripa, C B Belli, G D Kusminsky
Hematopoietic stem cell transplantation (HSCT) with sibling donors (s.d.) is a life-saving intervention for patients with hematological malignancies. Numerous genetic factors have a role in transplant outcome. Several functional polymorphisms have been identified in TGF-β1 gene, such as single-nucleotide polymorphism (SNP) at +29C>T within exon 1. Two hundred and forty five patient/donor pairs who underwent a s.d. HSCT in our centers were genotyped for this SNP. In the myeloablative cohort, +29CC donors were associated with an increase in severe chronic GvHD (32% vs 16%, hazard ratio (HR) 9...
January 30, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28131632/cd56-enriched-donor-cell-infusion-after-post-transplantation-cyclophosphamide-for-haploidentical-transplantation-of-advanced-myeloid-malignancies-is-associated-with-prompt-reconstitution-of-mature-natural-killer-cells-and-regulatory-t-cells-with-reduced-incidence
#13
Sarita Rani Jaiswal, Shamsur Zaman, Murugaiyan Nedunchezhian, Aditi Chakrabarti, Prakash Bhakuni, Margoob Ahmed, Kanika Sharma, Sheh Rawat, Paul O'donnell, Suparno Chakrabarti
We conducted a pilot study on the feasibility of CD56-enriched donor cell infusion after post-transplantation cyclophosphamide (PTCy) for 10 patients with advanced myeloid malignancies undergoing haploidentical peripheral blood stem cell transplantation with cyclosporine alone as graft-versus-host disease (GVHD) prophylaxis and compared the outcome and immune reconstitution with a control group of 20 patients undergoing the same without CD56-enriched donor cell infusion. An early and rapid surge of mature NK cells as well as CD4(+) T cells and regulatory T cells (Tregs) was noted compared with the control group...
January 25, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28124219/risk-factors-and-outcomes-of-invasive-fungal-infections-in-allogeneic-hematopoietic-cell-transplant-recipients
#14
Marisa H Miceli, Tracey Churay, Thomas Braun, Carol A Kauffman, Daniel R Couriel
Allogeneic hematopoietic cell transplant (HCT) recipients are at increased risk of invasive fungal infections (IFI), which are associated with a high mortality rate. We evaluated the impact of IFI in allogeneic HCT patients. In total, 541 consecutive allogeneic HCT recipients were included. The cumulative incidence of any IFI and mold infections at 1-year post-HCT was 10 and 7%, respectively. Median times to IFI and mold infection were 200 and 210 days, respectively. There was a trend toward fewer IFI and mold infections in the last several years...
January 25, 2017: Mycopathologia
https://www.readbyqxmd.com/read/28121342/clinical-applications-of-haploidentical-hematopoietic-stem-cell-transplantation-in-severe-aplastic-anemia
#15
P Zhang, K Feng, Y Xue, C-X Zhang, Y Wang, X-L Li
OBJECTIVE: The purpose of this study was to investigate the efficacy and safety of haploidentical allogeneic hemopoietic stem cell transplantation (allo-HSCT) in severe aplastic anemia (SAA) and prophylaxis of complications involved. PATIENTS AND METHODS: 8 patients with clinically diagnosed SAA (5 cases of SAA-I and 3 cases of SAA-II) were recruited, with the parents as the donors of hemopoietic stem cells. The conditioning regimen before HSCT included cyclophosphamide, fludarabine, pig anti-human lymphocyte immune globulin (p-ALG) and/or total body irradiation (TBI)...
January 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28119528/outcomes-of-ucb-transplantation-are-comparable-in-flt3-aml-results-of-cibmtr-eurocord-and-ebmt-collaborative-analysis
#16
C Ustun, F Giannotti, M-J Zhang, H-L Wang, C Brunstein, M Labopin, V Rocha, M de Lima, F Baron, B M Sandmaier, M Eapen, E Gluckman, A Nagler, D J Weisdorf, A Ruggeri
Allogeneic hematopoietic cell transplantation (HCT) from siblings or unrelated donors (URD) during complete remission (CR) may improve leukemia-free survival (LFS) in FLT3+ acute myeloid leukemia (AML) that has poor prognosis due to high relapse rates. Umbilical cord blood (UCB) HCT outcomes are largely unknown in this population. We found that compared with sibling HCT, relapse risks were similar after UCB (n=126), (HR 0.86, P=0.54) and URD (n=91) (HR 0.81, P=0.43). UCB HCT was associated with statistically higher non-relapse mortality compared with sibling HCT (HR 2...
January 25, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28118857/impact-of-in-vivo-t-cell-depletion-in-hla-identical-allogeneic-stem-cell-transplantation-for-acute-myeloid-leukemia-in-first-complete-remission-conditioned-with-a-fludarabine-iv-busulfan-myeloablative-regimen-a-report-from-the-ebmt-acute-leukemia-working-party
#17
Marie Thérèse Rubio, Maud D'Aveni-Piney, Myriam Labopin, Rose-Marie Hamladji, Miguel A Sanz, Didier Blaise, Hakan Ozdogu, Etienne Daguindeau, Carlos Richard, Stella Santarone, Giuseppe Irrera, Ibrahim Yakoub-Agha, Moshe Yeshurun, Jose L Diez-Martin, Mohamad Mohty, Bipin N Savani, Arnon Nagler
BACKGROUND: The impact of the use of anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation performed with HLA-identical sibling donors following fludarabine and 4 days intravenous busulfan myeloablative conditioning regimen has been poorly explored. METHODS: We retrospectively analyzed 566 patients who underwent a first HLA-identical allogeneic stem cell transplantation with this conditioning regimen for acute myeloid leukemia in first complete remission between 2006 and 2013 and compared the outcomes of 145 (25...
January 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28112750/investigating-the-temporal-course-relevance-and-risk-factors-of-fatigue-over-5-years-a-prospective-study-among-patients-receiving-allogeneic-hsct
#18
P Esser, K Kuba, A Mehnert, A Schwinn, L Schirmer, F Schulz-Kindermann, M Kruse, U Koch, A R Zander, N Kröger, G Schilling, H Götze, A Scherwath
Although allogeneic hematopoietic stem cell transplantation (HSCT) features severe physical and psychological strain, no previous study has prospectively investigated fatigue beyond 3 years after transplantation. We investigated the temporal course of fatigue over 5 years, compared patients with the general population (GP) and tested for treatment- and complication-related risk factors. Patients were assessed before conditioning (T0, N=239) and at 100-day (T1, N=150), 1-year (T2, N=102) and 5-year (T3, N=45) follow-up...
January 23, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28112745/a-high-migratory-capacity-of-donor-t-cells-in-response-to-the-lymph-node-homing-receptor-ccr7-increases-the-incidence-and-severity-of-gvhd
#19
I Portero-Sainz, V Gómez-García de Soria, C Cuesta-Mateos, C Fernández-Arandojo, L Vega-Piris, M Royg, B Colom-Fernández, A Marcos-Jiménez, B Somovilla-Crespo, A Ramírez-Mengíbar, V López-Huete, A de Rosendo-Serrano, A Kreutzman, C Muñoz-Calleja
The pathogenesis of GvHD involves migration of donor T-cells into the secondary lymphoid organs in the recipient, which is steered by two homing molecules, CD62L and CCR7. Therefore, we investigated whether the migratory capacity of donor T-cells is associated with GvHD. This single center prospective study included 85 donor-recipient pairs. In vitro chemotaxis assays of the lymphocytes of the apheresis product were performed in parallel to the analysis of CD62L and CCR7 by flow cytometry. The migratory index to the CCR7 ligands, CCL19 and CCL21, was higher in T-cells from donors whose recipients will develop GvHD...
January 23, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28108271/comparative-effectiveness-of-busulfan-and-fludarabine-versus-fludarabine-and-400-cgy-total-body-irradiation-conditioning-regimens-for-aml-mds
#20
Moaath Mustafa Ali, Donna M Abounader, Lisa A Rybicki, Melissa A Yurch, Jamie Starn, Christina Ferraro, Victoria Winslow, Betty K Hamilton, Aaron T Gerds, Hien Liu, Robert Dean, Brian T Hill, Brad Pohlman, Steven Andresen, Rabi Hanna, Matt Kalaycio, Brian J Bolwell, Navneet S Majhail, Ronald Sobecks
Allogeneic hematopoietic cell transplantation (alloHCT) conditioning regimen intensity has varied for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). A comparative effectiveness analysis was performed to assess outcomes of busulfan and fludarabine (BuFlu) versus fludarabine and 400 cGy total body irradiation (FluTBI) conditioning. Thirty-three subjects received BuFlu and 38 had FluTBI. The BuFlu group received more red blood cell transfusions (P=0.02) and had a longer time to platelet recovery (P=0...
January 17, 2017: Biology of Blood and Marrow Transplantation
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