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https://www.readbyqxmd.com/read/30117176/optimal-conditioning-regimen-for-haplo-identical-stem-cell-transplantation-in-adult-patients-with-acquired-severe-aplastic-anemia-prospective-de-escalation-study-of-tbi-and-atg-dose
#1
Sung-Eun Lee, Sung Soo Park, Young-Woo Jeon, Jae-Ho Yoon, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Hee-Je Kim, Seok-Goo Cho, Dong-Wook Kim, Jong Wook Lee
This prospective study explored an optimal conditioning regimen to ensure engraftment with minimal toxicity in adult patients with severe aplastic anemia (SAA) who received haplo-identical stem cell transplantation from a related mismatched donor (Haplo-SCT). We explored a safe and sufficient dose of rabbit ATG (Thymoglobulin®) in combination with 800 cGy total body irradiation (TBI) and fludarabine (Flu, 30 mg/m2 /day) for 5 days using step-by-step dose de-escalation. The dose of ATG was de-escalated from 10 mg/kg (group 1), to 7...
August 17, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/30115642/computational-modeling-and-confirmation-of-leukemia-associated-minor-histocompatibility-antigens
#2
Jefferson L Lansford, Udara Dharmasiri, Shengjie Chai, Sally A Hunsucker, Dante S Bortone, James E Keating, Ian M Schlup, Gary L Glish, Edward J Collins, Gheath Alatrash, Jeffrey J Molldrem, Paul M Armistead, Benjamin G Vincent
T-cell responses to minor histocompatibility antigens (mHAs) mediate both antitumor immunity (graft-versus-leukemia [GVL]) and graft-versus-host disease (GVHD) in allogeneic stem cell transplant. Identifying mHAs with high allele frequency, tight binding affinity to common HLA molecules, and narrow tissue restriction could enhance immunotherapy against leukemia. Genotyping and HLA allele data from 101 HLA-matched donor-recipient pairs (DRPs) were computationally analyzed to predict both class I and class II mHAs likely to induce either GVL or GVHD...
August 28, 2018: Blood Advances
https://www.readbyqxmd.com/read/30100330/outcomes-of-intermediate-risk-karyotype-acute-myeloid-leukemia-in-first-remission-undergoing-autologous-stem-cell-transplantation-compared-with-allogeneic-stem-cell-transplantation-and-chemotherapy-consolidation-a-retrospective-propensity-score-adjusted-analysis
#3
Wasithep Limvorapitak, Michael J Barnett, Donna E Hogge, Donna L Forrest, Thomas J Nevill, Sujaatha Narayanan, Maryse M Power, Stephen H Nantel, Raewyn Broady, Kevin W Song, Cynthia L Toze, Yasser Abou Mourad, Heather J Sutherland, Alina S Gerrie, Jennifer White, David S Sanford
INTRODUCTION: Optimal post-remission therapy (PRT) for intermediate risk acute myeloid leukemia remains an area of ongoing research. We aimed to retrospectively compare outcomes following autologous stem cell transplantation (autoSCT) with allogeneic SCT (alloSCT) and consolidation chemotherapy (CMT) in patients with intermediate-risk karyotype AML in first complete remission. PATIENTS AND METHODS: We compared overall survival (OS) and leukemia-free survival (LFS) using propensity score (PS)-adjusted analysis of patients receiving PRT with autoSCT, matched sibling (MSD) alloSCT, unrelated/mismatch (UD/MM) alloSCT, and CMT...
July 17, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/30080246/effects-of-all-trans-retinoic-acid-atra-in-addition-to-chemotherapy-for-adults-with-acute-myeloid-leukaemia-aml-non-acute-promyelocytic-leukaemia-non-apl
#4
REVIEW
Yasemin Küley-Bagheri, Karl-Anton Kreuzer, Ina Monsef, Michael Lübbert, Nicole Skoetz
BACKGROUND: Acute myeloid leukaemia (AML) is the most common acute leukaemia affecting adults. Most patients diagnosed with AML are at advanced age and present with co-morbidities, so that intensive therapy such as stem cell transplantation (SCT) is impossible to provide or is accompanied by high risks for serious adverse events and treatment-related mortality. Especially for these patients, it is necessary to find out whether all-trans retinoic acid (ATRA), an intermediate of vitamin A inducing terminal differentiation of leukaemic cell lines, added to chemotherapy confers increased benefit or harm when compared with the same chemotherapy alone...
August 6, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/30058442/a-unique-schedule-of-palonosetron-ondansetron-and-dexamethasone-for-the-prevention-of-delayed-nausea-and-vomiting-in-patients-receiving-myeloablative-chemotherapy
#5
J LaPorte, K Leone, X Zhang, K Holland, L Morris, A Bashey, M Solh, S Solomon
Myeloablative chemotherapy administered prior to autologous stem cell transplantation (auto-SCT) is associated with a significant amount of chemotherapy-induced nausea and vomiting (CINV). We conducted a phase II trial to assess the safety, efficacy, and impact on quality of life when palonosetron (PAL) 0.25 mg combined with dexamethasone were given on the final or only day of myeloablative chemotherapy for auto-SCT. The primary end point of this study was the incidence of achieving a delayed CINV complete response defined as no emetic episode and no use of rescue medications during the 24-120 h period post chemotherapy...
July 29, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/30053029/secondary-bone-soft-tissue-sarcoma-in-childhood-cancer-survivors-a-nationwide-hospital-based-case-series-study-in-japan
#6
Yasushi Ishida, Miho Maeda, Souichi Adachi, Takeshi Rikiishi, Maho Sato, Hiroshi Kawaguchi, Atsushi Manabe, Mika Tokuyama, Hiroki Hori, Jun Okamura, Atsushi Ogawa, Hiroaki Goto, Ryoji Kobayashi, Shinji Yoshinaga, Junichiro Fujimoto, Tatsuo Kuroda
Background: Secondary cancer is the most life-threatening late effect of childhood cancer. We investigated the clinical features of secondary bone/soft tissue sarcoma among childhood cancer survivors (CCSs). Methods: We conducted a retrospective case-series study of 10 069 CCSs newly diagnosed with cancer between 1980 and 2009 across 15 Japanese hospitals. Twenty-one cases of pathologically diagnosed secondary bone/soft tissue sarcoma were selected, and the respective clinical courses were determined using additional questionnaires...
July 25, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/30051172/the-pharmacokinetics-and-pharmacodynamics-of-busulfan-when-combined-with-melphalan-as-conditioning-in-adult-autologous-stem-cell-transplant-recipients
#7
Abbey Willcox, Eric Wong, Christa Nath, Brett Janson, Simon J Harrison, Rosemary Hoyt, Ashish Bajel, Peter Shaw, David Ritchie, Andrew Grigg
Busulfan (Bu) is an alkylating agent widely used in conditioning regimes prior to stem cell transplantation (SCT), most commonly in combination with cyclophosphamide (Bu-cy) or fludarabine (Bu-flu) as myeloablative conditioning prior to allograft or with high-dose melphalan (Bu-mel) prior to autologous SCT. Despite many decades of Bu use, initially orally but now intravenously (IV), a paucity of pharmacokinetic (PK) and pharmacodynamic (PD) data exists to inform evidence-based guidelines as how best to balance the efficacy and toxicity of this agent...
July 26, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/30048413/association-of-sickle-cell-trait-and-hemoglobin-s-percentage-with-physical-fitness
#8
Bryant J Webber, Colby C Uptegraft, Nathaniel S Nye, Francis G O'Connor
PURPOSE: This study aimed to determine the association between sickle cell trait (SCT) as a binary variable and hemoglobin S percentage as a stratified categorical variable with aerobic and anaerobic fitness. METHODS: This retrospective cohort study included all recruits who entered U.S. Air Force basic training between January 2009 and December 2014. Fitness parameters among recruits with and without SCT were compared using a standardized fitness assessment of a 1...
July 13, 2018: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/30040145/immunoglobulin-light-chain-amyloidosis-2018-update-on-diagnosis-prognosis-and-treatment
#9
Morie A Gertz
DISEASE OVERVIEW: Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include restrictive cardiomyopathy, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical multiple myeloma." DIAGNOSIS: Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for diagnosis...
July 24, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/30037340/influence-of-pre-transplant-minimal-residual-disease-on-prognosis-after-allo-sct-for-patients-with-acute-lymphoblastic-leukemia-systematic-review-and-meta-analysis
#10
Zhenglei Shen, Xuezhong Gu, Wenwen Mao, Liefen Yin, Ling Yang, Zhe Zhang, Kunmei Liu, Lilan Wang, Yunchao Huang
BACKGROUND: This meta-analysis was performed to explore the impact of minimal residual disease (MRD) prior to transplantation on the prognosis for patients with acute lymphoblastic leukemia (ALL). METHODS: A systematic search of PubMed, Embase, and the Cochrane Library was conducted for relevant studies from database inception to March 2016. A total of 21 studies were included. RESULTS: Patients with positive MRD prior to allogeneic stem cell transplantation (allo-SCT) had a significantly higher rate of relapse compared with those with negative MRD (HR = 3...
July 23, 2018: BMC Cancer
https://www.readbyqxmd.com/read/30033639/thiotepa-busulfan-and-fludarabine-compared-to-busulfan-and-cyclophosphamide-as-conditioning-regimen-for-allogeneic-stem-cell-transplant-from-matched-siblings-and-unrelated-donors-for-acute-myeloid-leukemia
#11
Francesco Saraceni, Eric Beohou, Myriam Labopin, William Arcese, Francesca Bonifazi, Polina Stepensky, Mahmoud Aljurf, Benedetto Bruno, Pietro Pioltelli, Jakob Passweg, Gerard Sociè, Stella Santarone, Ibrahim Yakoub-Agha, Francesco Lanza, Bipin N Savani, Mohamad Mohty, Arnon Nagler
Busulfan plus cyclophosphamide (BuCy) is the traditional conditioning regimen for allogeneic stem cell transplant (allo-SCT) for young, fit patients with acute myeloid leukemia (AML). The thiotepa-busulfan-fludarabine (TBF) protocol has recently demonstrated promising outcome in cord blood and haploidentical SCT; however, there is limited evidence about this regimen in transplant from matched siblings (MSD) and unrelated donors (UD). We retrospectively compared outcomes of 2523 patients aged 18-50 with AML in remission, undergoing transplant from MSD or UD prepared with either TBF or BuCy conditioning...
July 23, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/30030033/multiple-myeloma-treatment-in-real-world-clinical-practice-results-of-a-prospective-multinational-noninterventional-study
#12
Mohamad Mohty, Evangelos Terpos, Maria-Victoria Mateos, Michele Cavo, Sandra Lejniece, Meral Beksac, Mohamed Amine Bekadja, Wojciech Legiec, Meletios Dimopoulos, Svetlana Stankovic, Maria Soledad Durán, Valerio De Stefano, Alessandro Corso, Yulia Kochkareva, Edward Laane, Christian Berthou, Hans Salwender, Zvenyslava Masliak, Valdas Pečeliūnas, Wolfgang Willenbacher, João Silva, Vernon Louw, Damir Nemet, Zita Borbényi, Uri Abadi, Robert Schou Pedersen, Peter Černelč, Anna Potamianou, Catherine Couturier, Caroline Feys, Florence Thoret-Bauchet, Mario Boccadoro
BACKGROUND: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. PATIENTS AND METHODS: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months...
June 25, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/30028016/low-incidence-of-symptomatic-osteonecrosis-after-allogeneic-hsct-in-children-with-high-risk-or-relapsed-all-results-of-the-all-sct-2003-trial
#13
Michaela Kuhlen, Peter Bader, Martin Sauer, Michael H Albert, Bernd Gruhn, Tayfun Güngör, Gabriele Kropshofer, Peter Lang, Anita Lawitschka, Markus Metzler, Falk Pentek, Claudia Rossig, Paul G Schlegel, Martin Schrappe, Johanna Schrum, Ansgar Schulz, Wolfgang Schwinger, Arend von Stackelberg, Brigitte Strahm, Meinolf Suttorp, Irene Teichert-von Luettichau, Wilhelm Wößmann, Arndt Borkhardt, Roland Meisel, Ulrike Poetschger, Evgenia Glogova, Christina Peters
Osteonecrosis (ON) was prospectively assessed in 557 children and adolescents in the Berlin-Frankfurt-Münster Stem Cell Transplantation in children with acute lymphoblastic leukaemia 2003 trial. Median age at haematopoietic stem cell transplantation (HSCT) was 10·3 years (range 0·5-26). Cumulative incidence of symptomatic ON (sON) was 9% at 5 years (standard deviation 1%), median time from HSCT to diagnosis of sON was 12·4 months (range 1-126). Multivariate analysis identified age at HSCT [10-15 years vs...
July 20, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29996314/-clinicopathologic-and-molecular-characterizations-of-sertoli-cell-tumor-not-otherwise-specified-of-the-testis
#14
M Zhao, D H Zhao, H Y He, X Zhang, G Q Ru, X L He, Z Wang, X D Teng
Objective: To investigate the histomorpholgic spectrum, immunophenotypic, and molecular genetic features of Sertoli cell tumor, not otherwise specified (SCT, NOS) of the testis. Methods: Seven cases of SCT, NOS of the testis were analyzed(4 from Peking University Third Hospital and 3 from Zhejiang Provincial People's Hospital) between 2008 and 2017. The histopathologic features were examined based on HE staining, and EnVision method was used for immunohistochemistry staining of calretinin, inhibin, β-catenin, cyclinD1, CD10, CKpan, neuroendocrine markers, WT1, Melan A, vimentin, SALL4, GATA3, PAX8, and S-100 protein...
July 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29988061/haploidentical-versus-matched-donor-stem-cell-transplantation-for-patients-with-hematological-malignancies-a-systemic-review-and-meta-analysis
#15
Bo Yang, Ruili Yu, Lili Cai, Bin Guo, Hongfei Chen, Haomin Zhang, Peifeng He, Xuechun Lu
We compared the safety and efficacy of haploidentical stem cell transplantation (haplo-SCT) to matched donor SCT (matched-SCT) in treating hematological malignancies. The Medline, Cochrane, EMBASE, and Google Scholar databases were searched through 21 June 2017 using the search term "(hematological disease) AND matched AND (haploidentical OR haplo-identical OR haplo identical OR haplo transplantation OR haplo transplant OR haplo-SCT OR haplo-HSCT OR haplo-HCT)." Twenty-five studies enrolling 11,359 patients (haplo-SCT: 2677; matched-SCT: 8682) were included...
July 9, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29977037/knockout-of-secretin-receptor-reduces-biliary-damage-and-liver-fibrosis-in-mdr2-mice-by-diminishing-senescence-of-cholangiocytes
#16
Tianhao Zhou, Nan Wu, Fanyin Meng, Julie Venter, Thao K Giang, Heather Francis, Konstantina Kyritsi, Chaodong Wu, Antonio Franchitto, Domenico Alvaro, Marco Marzioni, Paolo Onori, Romina Mancinelli, Eugenio Gaudio, Shannon Glaser, Gianfranco Alpini
Secretin receptor (SR), only expressed by cholangiocytes, plays a key role in the regulation of biliary damage and liver fibrosis. The aim of this study was to determine the effects of genetic depletion of SR in Mdr2-/- mice on intrahepatic biliary mass, liver fibrosis, senescence, and angiogenesis. 12 wk SR-/- , Mdr2-/- , and SR-/- /Mdr2-/- mice with corresponding wild-type mice were used for the in vivo studies. Immunohistochemistry or immunofluorescence was performed in liver sections for (i) biliary expression of SR; (ii) hematoxylin and eosin; (iii) intrahepatic biliary mass by CK-19; (iv) fibrosis by Col1a1 and α-SMA; (v) senescence by SA-β-gal and p16; and (vi) angiogenesis by VEGF-A and CD31...
July 5, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29970351/the-regulation-of-normal-and-neoplastic-hematopoiesis-is-dependent-on-microenvironmental-cells
#17
REVIEW
Kenneth Kaushansky, Huichun Zhan
Each day the adult human produces 4 × 1011 red blood cells, 1 × 1011 white blood cells and 1 × 1011 platelets, levels of production which can increase 10-20 fold in times of heightened demand. Hematopoiesis, or the formation of the ten different types of blood and marrow cells, is a complex process involving hematopoietic stem cells (HSCs), cytokine growth factors and cell surface adhesion molecules, and both specific and ubiquitous transcription factors. The marrow micro-environmental niche is defined as the site at which HSCs reside and are nurtured, receiving the signals that lead to their survival, replication and/or differentiation...
June 27, 2018: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29953253/lipid-malabsorption-from-altered-hormonal-signaling-changes-early-gut-microbial-responses
#18
Natalie A Terry, Lucie V Ngaba, Benjamin J Wilkins, Danielle Pi, Nishi Gheewala, Klaus H Kaestner
Infants with congenital diarrheal disorders caused by enteroendocrine cell dysgenesis, or the loss of intestinal endocrine cells, by itself causes severe malabsorptive diarrhea though the mechanism is unknown. The transcription factor 'Aristaless-related homeobox' (Arx), is specifically expressed in intestinal endocrine cells. This study seeks to characterize the early malabsorptive phenotype of mice deficient for Arx using cell-type specific gene ablation in Villin-Cre; ArxloxP/Y (Arxint ) mice. In neonatal mice, loss of intestinal Arx caused loss of intestinal hormones, such as cholecystokinin (CCK), secretin (Sct), neurotensin (Nts), glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide 1 (GLP-1) and GLP-2 but also upregulation of somatostatin (Sst)...
June 28, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29951735/re-induction-chemotherapy-using-flag-mitoxantrone-for-adult-patients-with-relapsed-acute-leukemia-a-single-center-experience-from-united-arab-emirates
#19
Inaam Bashir Hassan, Jorgen Kristensen, Khalid Al Qawasmeh, Arif Alam
We studied the outcome of 47 adult patients with relapsed acute leukaemia (AML = 25 and ALL = 22) treated with FLAG-mitoxantrone regimen. Median time to relapse was 10.7 months (range 1.9-27.7). Complete remission (CR2) was 60.1% which was significantly more frequent in ALL compared to AML (P = 0.049). WBC count < 100 × 109 /L at initial diagnosis and time to relapse > 1 year were significantly predictor for CR2 in AML (P = 0.005 for both). Induction death was significantly higher in ALL compared to AML (P = 0...
June 27, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29950692/the-impact-of-individual-comorbidities-on-non-relapse-mortality-following-allogeneic-hematopoietic-stem-cell-transplantation
#20
Joshua A Fein, Avichai Shimoni, Myriam Labopin, Noga Shem-Tov, Ronit Yerushalmi, Hila Magen, Nadav Furie, Eli Kopel, Ivetta Danylesko, Arnon Nagler, Roni Shouval
Comorbidity burden is a well-established risk factor for non-relapse mortality (NRM) following allogeneic stem cell transplantation (allo-SCT). We evaluated whether individual comorbidities could better characterize NRM risk. Furthermore, given differing toxicity profiles of conditioning agents, we hypothesized that the hazard of comorbidities is exerted in a regimen-specific manner. This retrospective study included 875 adults treated with an allo-SCT. Six conditioning regimens were considered. Across the entire cohort and within each regimen, the hazard ratio (HR) for NRM associated with individual comorbidities was assessed using multivariable Cox regressions...
June 27, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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