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https://www.readbyqxmd.com/read/28439877/increased-non-relapse-mortality-due-to-high-dose-cytarabine-plus-cy-tbi-in-bmt-pbsct-for-acute-lymphoblastic-leukaemia-in-adults
#1
Yasuyuki Arai, Tadakazu Kondo, Akio Shigematsu, Junji Tanaka, Kazuteru Ohashi, Takahiro Fukuda, Toshiro Kawakita, Takehiko Mori, Takumi Hoshino, Makoto Onizuka, Yukiyasu Ozawa, Shuro Yoshida, Yasunori Ueda, Ishikazu Mizuno, Yoshiko Atsuta, Shuichi Mizuta
The efficacy of high-dose cytarabine (HDCA) plus cyclophosphamide/total-body irradiation (CY/TBI) has been proved in cord blood transplantation (CBT) for acute lymphoblastic leukaemia (ALL), but not in bone marrow or peripheral blood stem cell transplantation (BMT/PBSCT). In this cohort study, we compared the prognosis of CY/TBI (N = 1244) and HDCA/CY/TBI (N = 316) regimens in BMT/PBSCT for ALL. The addition of HDCA decreased post-transplant relapse, while significantly increasing non-relapse mortality (risk ratio, 1·33), and overall survival was not improved...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28438676/factors-associated-with-long-term-risk-of-relapse-after-unrelated-cord-blood-transplantation-for-children-with-acute-lymphoblastic-leukemia-in-remission
#2
Kristin M Page, Myriam Labopin, Annalisa Ruggeri, Gerard Michel, Cristina Diaz de Heredia, Tracey O'Brien, Alessandra Picardi, Mouhab Ayas, Henrique Bittencourt, Ajay J Vora, Jesse Troy, Carmen Bonfim, Fernanda Volt, Eliane Gluckman, Peter Bader, Joanne Kurtzberg, Vanderson Rocha
For pediatric patients with acute lymphoblastic leukemia (ALL), relapse is an important cause of treatment failure after unrelated cord blood transplant (UCBT). Compared to other donor sources, relapse is similar or even reduced after UCBT despite less graft-versus-host disease (GvHD). We performed a retrospective analysis to identify risk factors associated with the 5-year cumulative incidence (CI) of relapse after UCBT. In this retrospective, registry-based study, we examined the outcomes of 640 children (<18 years) with ALL in first (n=257, 40%) or second complete remission (CR; n=383, 60%) who received myeloablative conditioning followed by a single-unit UCBT from 2000-2012...
April 21, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28437188/further-characterization-of-the-mitigation-of-radiation-lethality-by-protective-wounding
#3
Joseph R Dynlacht, Joy Garrett, Rebecca Joel, Katharina Lane, Marc S Mendonca, Christie M Orschell
There continues to be a major effort in the United States to develop mitigators for the treatment of mass casualties that received high-intensity acute ionizing radiation exposures from the detonation of an improvised nuclear device during a radiological terrorist attack. The ideal countermeasure should be effective when administered after exposure, and over a wide range of absorbed doses. We have previously shown that the administration of a subcutaneous incision of a defined length, if administered within minutes after irradiation, protected young adult female C57BL/6 mice against radiation-induced lethality, and increased survival after total-body exposure to an LD50/30 X-ray dose from 50% to over 90%...
April 24, 2017: Radiation Research
https://www.readbyqxmd.com/read/28435051/akt1-nf%C3%AE%C2%BAb-signaling-pathway-activation-by-a-small-molecule-dma-confers-radioprotection-to-intestinal-epithelium-in-xenograft-model
#4
Vinod Tiwari, Mohammad Zahid Kamran, Atul Ranjan, Hemlata Nimesh, Manish Singh, Vibha Tandon
Normal tissue protection and recovery of radiation-induced damage are of paramount importance for development of radioprotector. Radioprotector which selectively protects normal tissues over cancerous tissues improves the therapeutic window of radiation therapy. In the present study, small bisbenzimidazole molecule, DMA (5-(4-methylpiperazin-1-yl)-2-[2'-(3,4-dimethoxy-phenyl)-5'-benzimidazolyl]-benzimidazole) was evaluated for in vivo radioprotective effects to selectively protect normal tissue over tumor with underlying molecular mechanism...
April 20, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28433882/hypothyroidism-following-allogeneic-hematopoietic-stem-cell-transplantation-for-acute-myeloid-leukemia
#5
Michael Medinger, Deborah Zeiter, Dominik Heim, Jörg Halter, Sabine Gerull, André Tichelli, Jakob Passweg, Nicole Nigro
BACKGROUND: Hypothyroidism may complicate allogeneic hematopoietic stem cell transplantation (allo-HSCT); we therefore analyzed risk factors in this study. PATIENTS AND METHODS: We studied 229 patients with acute myeloid leukemia (AML) who underwent an allo-HSCT between 2003 and 2013 with different conditioning regimens (myeloablative, reduced-intensity, chemotherapy-based, or total body irradiation-based). Thyroid-stimulating hormone (TSH) and free thyroxine levels (fT4) were available in 104 patients before and after allo-HSCT...
April 13, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28431920/the-microbiome-in-anti-cancer-therapy
#6
REVIEW
Stavros Bashiardes, Timur Tuganbaev, Sara Federici, Eran Elinav
The commensal microbiome constitutes an important modulator of host physiology and risk of disease, including cancer development and progression. Lately, the microbiome has been suggested to modulate the efficacy of anti-cancer treatment. Examples include chemotherapy and total body irradiation-induced barrier function disruption, leading to microbial efflux that drives activation of anti-tumorigenic T cells; Microbiome-driven release of reactive oxygen species contributing to the efficacy of platinum salts; and microbiome-induced immune priming promoting the anti-tumor effects of alkylating chemotherapy and immune checkpoint inhibitors...
April 18, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28424327/rig-i-mavs-and-sting-signaling-promote-gut-integrity-during-irradiation-and-immune-mediated-tissue-injury
#7
Julius C Fischer, Michael Bscheider, Gabriel Eisenkolb, Chia-Ching Lin, Alexander Wintges, Vera Otten, Caroline A Lindemans, Simon Heidegger, Martina Rudelius, Sébastien Monette, Kori A Porosnicu Rodriguez, Marco Calafiore, Sophie Liebermann, Chen Liu, Stefan Lienenklaus, Siegfried Weiss, Ulrich Kalinke, Jürgen Ruland, Christian Peschel, Yusuke Shono, Melissa Docampo, Enrico Velardi, Robert R Jenq, Alan M Hanash, Jarrod A Dudakov, Tobias Haas, Marcel R M van den Brink, Hendrik Poeck
The molecular pathways that regulate the tissue repair function of type I interferon (IFN-I) during acute tissue damage are poorly understood. We describe a protective role for IFN-I and the RIG-I/MAVS signaling pathway during acute tissue damage in mice. Mice lacking mitochondrial antiviral-signaling protein (MAVS) were more sensitive to total body irradiation- and chemotherapy-induced intestinal barrier damage. These mice developed worse graft-versus-host disease (GVHD) in a preclinical model of allogeneic hematopoietic stem cell transplantation (allo-HSCT) than did wild-type mice...
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28413062/assessment-of-mucosal-integrity-by-quantifying-neutrophil-granulocyte-influx-in-murine-models-of-acute-intestinal-injury
#8
Julius Clemens Fischer, Alexander Wintges, Tobias Haas, Hendrik Poeck
Intact epithelial body surfaces represent physical barriers which protect the organism from invading pathogens and loss of nutrients. Barrier malfunction is closely linked to disorders such as inflammatory bowel disease and graft-versus-host disease. In fact, several pharmacological or radiobiological therapeutic strategies have side effects that affect epithelial surfaces. In this context, assays that accurately assess epithelial barrier integrity in patients and animal models are crucial to create a better understanding of the mechanisms leading to disease or limiting therapeutic approaches due to barrier disruption...
April 11, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28408530/alternative-means-of-estimating-131-i-maximum-permissible-activity-to-treat-thyroid-cancer
#9
Kenneth J Nichols, William Robeson, Miyuki Yoshida-Hay, Pat B Zanzonico, Fritzgerald C Leveque, Kuldeep K Bhargava, Gene G Tronco, Christopher J Palestro
To protect bone marrow from over-irradiation, maximum permissible activity (MPA) of iodine-131 ((131)I) to treat thyroid cancer is that which limits absorbed dose to blood (as a surrogate of marrow) to < 200 cGy. The conventional approach (Method-1) requires repeated gamma-camera whole-body measurements along with blood samples. We sought to determine whether reliable MPA values can be obtained by simplified procedures. Methods: Data acquired over multiple time points were examined retrospectively for 65 thyroid cancer patients, referred to determine (131)I uptake and MPA for initial treatment following thyroidectomy (N = 39), including 17 patients with compromised renal function and 22 patients with known (N = 16) or suspected (N = 6) metastases...
April 13, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28396668/extracellular-vesicles-mediate-radiation-induced-systemic-bystander-signals-in-the-bone-marrow-and-spleen
#10
Tünde Szatmári, Dávid Kis, Enikő Noémi Bogdándi, Anett Benedek, Scott Bright, Deborah Bowler, Eszter Persa, Enikő Kis, Andrea Balogh, Lívia N Naszályi, Munira Kadhim, Géza Sáfrány, Katalin Lumniczky
Radiation-induced bystander effects refer to the induction of biological changes in cells not directly hit by radiation implying that the number of cells affected by radiation is larger than the actual number of irradiated cells. Recent in vitro studies suggest the role of extracellular vesicles (EVs) in mediating radiation-induced bystander signals, but in vivo investigations are still lacking. Here, we report an in vivo study investigating the role of EVs in mediating radiation effects. C57BL/6 mice were total-body irradiated with X-rays (0...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28396164/dose-escalation-of-total-marrow-irradiation-in-high-risk-patients-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#11
Susanta Hui, Claudio Brunstein, Yutaka Takahashi, Todd DeFor, Shernan G Holtan, Veronika Bachanova, Christopher Wilke, Darren Zuro, Celalettin Ustun, Daniel Weisdorf, Kathryn Dusenbery, Michael R Verneris
Patients with refractory leukemia or minimal residual disease (MRD) at transplant have increased risk of relapse. Augmentation of irradiation, especially to sites of disease (i.e., bone marrow) is one potential strategy to overcome this risk. We studied the feasibility of radiation dose escalation in high risk patients using total marrow irradiation (TMI) in a phase I dose-escalation trial. Four pediatric and 8 adult patients received conditioning with cyclophosphamide and fludarabine in conjunction with image-guided radiation to the bone marrow at 15 Gy and 18 Gy (in 3 Gy/fractions), while maintaining the total body irradiation (TBI) dose to the vital organs (lungs, hearts, eyes, liver, kidneys) at <13...
April 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28396162/phase-i-study-of-clofarabine-and-2-gy-total-body-irradiation-as-a-non-myeloablative-preparative-regimen-for-hematopoietic-stem-cell-transplantation-hsct-in-pediatric-patients-with-hematologic-malignancies-a-therapeutic-advances-in-childhood-leukemia-tacl-consortium
#12
Sandeep Soni, Hisham Abdel-Azim, Meghann McManus, Eneida Nemecek, Richard Sposto, Ann Woolfrey, Haydar Frangoul
Clofarabine is a purine nucleoside analog with immunosuppressive and anti-leukemic activity and its inclusion in reduced intensity regimens could potentially improve outcomes. We performed a prospective Phase I study of clofarabine combined with 2 Gy total body irradiation (TBI) as a non-myeloablative (NMA) preparative regimen for allogeneic stem cell transplantation in pediatric patients, who were considered at high risk of mortality from standard myeloablative regimens. The main goal of the study was to delineate the maximum feasible dose (MFD) of clofarabine in combination with 2 Gy TBI...
April 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28396160/allogeneic-hematopoietic-cell-transplantation-hct-for-adult-t-cell-acute-lymphoblastic-leukemia-t-all
#13
Betty Ky Hamilton, Lisa Rybicki, Donna Abounader, Kehinde Adekola, Anjali Advani, Ibrahim Aldoss, Veronika Bachanova, Asad Bashey, Stacey Brown, Marcos DeLima, Steven Devine, Christopher R Flowers, Siddharth Ganguly, Madan Jagasia, Vanessa E Kennedy, Dennis Dong Hwan Kim, Joseph McGuirk, Vinod Pullarkat, Rizwan Romee, Karamjeet Sandhu, Melody Smith, Masumi Ueda, Auro Viswabandya, Khoan Vu, Sarah Wall, Simon B Zeichner, Miguel-Angel Perales, Navneet S Majhail
Allogeneic hematopoietic cell transplantation (HCT) is recommended for T-cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (CR) and in high risk patients in first CR. Given its relative rarity, data on outcomes of HCT for T-ALL are limited. We conducted a multi-center retrospective cohort study using data from 208 adult patients transplanted from 2000-2014 to describe outcomes of allogeneic HCT for T-ALL in the contemporary era. Median age at HCT was 37 years and the majority of patients were transplanted in CR, using total body irradiation (TBI) based myeloablative conditioning regimens...
April 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28384957/radioprotective-effect-of-beta-d-glucan-and-vitamin-e-on-gamma-irradiated-mouse
#14
Faraj Tabeie, Seyed Mehdi Tabatabaei, Ali Mahmoud-Pashazadeh, Majid Assadi
INTRODUCTION: It is shown that beta-D-glucan is an immunologic system booster with radioprotectory effects. Radioprotectors are chemical components that can alleviate biological damage produced by ionizing radiation. AIM: This study was designed to investigate the synergistic radioprotectory effects of beta-D-glucan and vitamin E on irradiated mice with (60)Co source. MATERIALS AND METHODS: A total of 240 female mice were arranged in four, equal population groups of control group (C), treated group with beta D-glucan (G), treated group with vitamin E (E), and treated group with both beta D-glucan and vitamin E (G+E)...
February 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28378548/effect-of-coenzyme-q10-on-radiation-nephropathy-in-rats
#15
Yongkan Ki, Wontaek Kim, Yong Ho Kim, Donghyun Kim, Jin Sook Bae, Dahl Park, Hosang Jeon, Ju Hye Lee, Jayoung Lee, Jiho Nam
The kidney is one of the most radiosensitive organs in the abdominal cavity and is the dose-limiting structure in cancer patients receiving abdominal or total body irradiation. In the present study, the effect of coenzyme Q10 (CoQ10) on radiation nephropathy was evaluated in rats. A total of 72 rats were equally randomized into 4 groups: Control, CoQ10, irradiation with 10 Gy (RT) + placebo, or RT + CoQ10. The 2 RT groups received single 10 Gy of abdominal irradiation. The 2 CoQ10 groups were supplemented daily with 1 mL of soybean oil containing 10 mg/kg of CoQ10...
May 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28370630/long-term-follow-up-of-patients-with-multiple-myeloma-treated-with-total-body-irradiation-melphalan-conditioning
#16
Reinhold Munker, Ali Baghian, Yordanka Koleva, Patricia Andrews, Gunita S Matharoo, Ato E Wright, Nakhle Saba, Roy Weiner, Hanah Safah
BACKGROUND AND OBJECTIVES: Since a study published in 2002 showed a survival advantage of melphalan-only conditioning for stem cell transplantation (HSCT) over melphalan-total body irradiation (mel-TBI) in patients with multiple myeloma (MM), most centers abandoned mel-TBI. Mel-TBI causes more early toxicity and is more complicated to administer, but we speculated it may result in longer term survival with radiation as an independent treatment modality. Therefore, we analyzed the long-term outcome of patients with MM who received mel-TBI as part of conditioning at our center...
March 31, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28365241/adjuvant-ab-interno-tumor-treatment-after-proton-beam-irradiation
#17
Ira Seibel, Aline I Riechardt, Jens Heufelder, Dino Cordini, Antonia M Joussen
PURPOSE: This study was performed to show long-term outcomes concerning globe preservation in uveal melanoma patients after proton beam therapy with the main focus on outcomes according to different adjuvant ab interno surgical procedures. DESIGN: Retrospective cohort study METHODS: All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma between June 1998 and June 2015 were included. RESULTS: A total of 2499 patients underwent primary proton beam therapy, with local tumor control and globe preservation rates of 95...
March 29, 2017: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/28362168/impact-of-abbreviated-filgrastim-schedule-on-survival-and-hematopoietic-recovery-after-irradiation-in-four-mouse-strains-with-different-radiosensitivity
#18
Merriline Satyamitra, Vidya P Kumar, Shukla Biswas, Lynnette Cary, Leonora Dickson, Srinivasan Venkataraman, Sanchita P Ghosh
Filgrastim (Neupogen(®), granulocyte-colony stimulating factor) is among the few countermeasures recommended for management of patients in the event of lethal total-body irradiation. Despite the plethora of studies using filgrastim as a radiation countermeasure, relatively little is known about the optimal dose schedule of filgrastim to mitigate radiation lethality. We evaluated the efficacy of filgrastim in improving 30-day survival of CD2F1 mice irradiated with a lethal dose (LD70/30) in the AFRRI cobalt-60 facility...
March 31, 2017: Radiation Research
https://www.readbyqxmd.com/read/28358695/induction-of-tgf-%C3%AE-by-irradiation-or-chemotherapy-in-fanconi-anemia-fa-mouse-bone-marrow-is-modulated-by-small-molecule-radiation-mitigators-jp4-039-and-mms350
#19
Michael W Epperly, Byung-Han Rhieu, Darcy Franicola, Tracy Dixon, Shaonan Cao, Xichen Zhang, Donna Shields, Hong Wang, Peter Wipf, Joel S Greenberger
BACKGROUND/AIM: Total-body irradiation and/or administration of chemotherapy drugs in bone marrow transplantation induce cytokines that can suppress engraftment. Fanconi Anemia (FA) patients have a hyperactive responsiveness to the inhibitory cytokine, transforming growth factor-beta (TGF-β). Small molecule radiation mitigator drugs, JP4-039 and MMS350, were evaluated for suppression of irradiation or drug-induced TGF-β. MATERIALS AND METHODS: In vivo induction of TGF-β by total-body ionizing irradiation (TBI), L-phenylalanine mustard (L-PAM), busulfan or fludarabine, was quantified...
March 2017: In Vivo
https://www.readbyqxmd.com/read/28355720/-the-clinical-characteristics-of-adult-hemophagocytic-lymphohistiocytosis-treated-with-haploidentical-donor-hematopoietic-stem-cell-transplantation
#20
L Fu, N Wei, J S Wang, L Wu, Y N Wang, D Y Huang, J L Liu, Z Wang
Objective: To analyze the clinical characteristics of adult patients with hemophagocytic lymphohistiocytosis (HLH) receiving haploidentical donor hematopoietic stem cell transplantation (HID HSCT). Method: We retrospectively reviewed 20 adult patients with HLH from August 2009 to August 2014.The clinical features and outcome were analyzed. Results: Conditioning regimens consisted of total body irradiation/etoposide/cyclophosphamide (TBI/VP-16/CTX) and busulfan (Bu)/VP-16/CTX in HLH with anti-thymocyte globulin (ATG) 8 mg/kg...
April 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
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