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https://www.readbyqxmd.com/read/28522110/high-dose-gemcitabine-busulfan-and-melphalan-for-autologous-stem-cell-transplant-in-patients-with-relapsed-or-refractory-myeloma-a-phase-2-trial-and-matched-pair-comparison-with-melphalan
#1
Yago Nieto, Benigno C Valdez, Sai R Pingali, Roland Bassett, Ruby Delgado, John Nguyen, Nina Shah, Uday Popat, Roy B Jones, Borje S Andersson, Alison Gulbis, Sairah Ahmed, Qaiser Bashir, Simrit Parmar, Krina Patel, Alan Myers, Gabriela Rondon, Robert Z Orlowski, Richard Champlin, Muzaffar Qazilbash
BACKGROUND: High-dose melphalan is of little benefit as a regimen for patients with relapsed or refractory myeloma undergoing an autologous stem-cell transplant (ASCT). The poor performance of single-agent melphalan in this setting prompted us to study a new high-dose combination of infused gemcitabine, busulfan, and melphalan. METHODS: We did a phase 2 trial at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). We enrolled patients with primary refractory or relapsed myeloma who had received treatment with bortezomib, an immunomodulatory drug, or both, or who were receiving a salvage ASCT...
May 15, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28522109/gemcitabine-busulfan-and-melphalan-conditioning-for-autologous-stem-cell-transplants-in-multiple-myeloma
#2
Gösta Gahrton
No abstract text is available yet for this article.
May 15, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28490733/pharmacometabolomics-for-predicting-variable-busulfan-exposure-in-paediatric-haematopoietic-stem-cell-transplantation-patients
#3
Bora Kim, Ji Won Lee, Kyung Taek Hong, Kyung-Sang Yu, In-Jin Jang, Kyung Duk Park, Hee Young Shin, Hyo Seop Ahn, Joo-Youn Cho, Hyoung Jin Kang
Owing to its narrow therapeutic range and high pharmacokinetic variability, optimal dosing for busulfan is important to minimise overexposure-related systemic toxicity and underexposure-related graft failure. Using global metabolomics, we investigated biomarkers for predicting busulfan exposure. We analysed urine samples obtained before busulfan administration from 59 paediatric patients divided into 3 groups classified by area under the busulfan concentration-time curve (AUC), i.e., low-, medium-, and high-AUC groups...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28483347/the-potentiality-of-two-dimensional-preantral-follicle-culture-as-an-in-vitro-model-in-predicting-premature-ovarian-failure
#4
Ting Zhang, Ying Chen, Yang Yang, Zhonghui Wang, Qi Pan, Sichong Xu, Zuyue Sun
The purpose of this study is to identify the potential of a two-dimensional preantral follicle culture as an in vitro model of predicting premature ovarian failure. The two-dimensional preantral follicles culture method was established by cultivating preantral follicles collected from ICR F1 hybrids (aged 12-14days) for 12days. The preantral follicles were incubated with 0.54mg/ml cyclophosphamide, 0.5mg/ml busulfan, 0.12mg/ml cisplatin, 3.12mg/ml 4-vinylcyclohexene diepoxide, 5mg/ml D (+) galactose, and 0...
May 5, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28479418/development-of-an-assay-for-cellular-efflux-of-pharmaceutically-active-agents-and-its-relevance-to-understanding-drug-interactions
#5
Benigno C Valdez, Moustapha Hassan, Borje S Andersson
Drug interactions may dictate the failure or success of a treatment. Patients undergoing hematopoietic stem cell transplantation (HSCT) are exposed to various types of drugs and it is of utmost importance to understand how these drugs interact. The pharmacokinetics of busulfan, melphalan and cyclophosphamide, commonly used drugs in HSCT, are known to be affected by a variety of drugs with differing molecular structures. We hypothesized that these structurally-unrelated drugs affect the transport of DNA alkylating agents...
May 4, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28472509/multicenter-phase-ii-study-of-temozolomide-and-myeloablative-chemotherapy-with-autologous-stem-cell-transplant-for-newly-diagnosed-anaplastic-oligodendroglioma
#6
Alissa A Thomas, Lauren E Abrey, Robert Terziev, Jeffrey Raizer, Nina L Martinez, Peter Forsyth, Nina Paleologos, Matthew Matasar, Craig S Sauter, Craig Moskowitz, Stephen D Nimer, Lisa M DeAngelis, Thomas Kaley, Sean Grimm, David N Louis, J Gregory Cairncross, Katherine S Panageas, Samuel Briggs, Geraldine Faivre, Nimish A Mohile, Jayesh Mehta, Philip Jonsson, Debyani Chakravarty, Jianjiong Gao, Nikolaus Schultz, Cameron W Brennan, Jason T Huse, Antonio Omuro
Background: Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytomas (AOA) are chemotherapy-sensitive tumors with prolonged survival after radiochemotherapy. We report a prospective trial using induction temozolomide (TMZ) followed by myeloablative high-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT), as a potential strategy to defer radiotherapy. Methods: Patients with AO/AOA received 6 cycles of TMZ (200mg/m2 X5/28-day). Responding patients were eligible for HDC (thiotepa 250mg/m2/day X3 days then busulfan 3...
May 2, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28468095/-the-mechanism-of-bone-marrow-derived-mesenchymal-stem-cells-excessive-senescence-in-severe-aplastic-anemia-mouse-model
#7
Y Q Ou, H Y Liu, W Lu, M J Wen, H Liu
Objective: To explore the mechanism of excessive senescence in bone marrow-derived mesenchymal stem cells (BM-MSC) of mouse model with severe aplastic anemia (SAA) . Methods: 40 BALB/c mice were randomly assigned to two groups of control (n=20) and AA (n=20) . SAA mouse model was induced by intraperitoneal injection with IFN-γ and intragastric infusion with busulfan. BM-MSC were isolated and cultured from bone marrow of SAA and healthy mice. The cell morphology was observed by inverted microscope and cell cytoskeleton was stained by Rhodamine-Phalloidin; The level of proliferation was analyzed by CCK-8 method, and cell cycle was tested by flow cytometry...
April 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28463633/dose-reduced-versus-standard-conditioning-followed-by-allogeneic-stem-cell-transplantation-for-patients-with-myelodysplastic-syndrome-a-prospective-randomized-phase-iii-study-of-the-ebmt-ricmac-trial
#8
Nicolaus Kröger, Simona Iacobelli, Georg-Nikolaus Franke, Uwe Platzbecker, Ruzena Uddin, Kai Hübel, Christof Scheid, Thomas Weber, Marie Robin, Matthias Stelljes, Boris Afanasyev, Dominik Heim, Giorgio Lambertenghi Deliliers, Francesco Onida, Peter Dreger, Massimo Pini, Stefano Guidi, Liisa Volin, Andreas Günther, Wolfgang Bethge, Xavier Poiré, Guido Kobbe, Marleen van Os, Ronald Brand, Theo de Witte
Purpose To compare a reduced-intensity conditioning regimen (RIC) with a myeloablative conditioning regimen (MAC) before allogeneic transplantation in patients with myelodysplastic syndrome (MDS) within a randomized trial. Patients and Methods Within the European Society of Blood and Marrow Transplantation, we conducted a prospective, multicenter, open-label, randomized phase III trial that compared a busulfan-based RIC with MAC in patients with MDS or secondary acute myeloid leukemia. A total of 129 patients were enrolled from 18 centers...
May 2, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28450182/cervical-papanicolaou-smears-in-hematopoietic-stem-cell-transplant-recipients-high-prevalence-of-therapy-related-atypia-during-the-acute-phase
#9
Shan-Chi Yu, Huai-Hsuan Huang, Chi-Cheng Li, Jih-Luh Tang, Yi-Hsuan Lee, Tsui-Lien Mao, Kuan-Ting Kuo, Chien-Ting Lin, Jia-Hau Liu, Bor-Sheng Ko, Ming Yao
Hematopoietic stem cell transplant (HSCT) recipients have a higher risk of cervical cancer. Papanicolaou (Pap) smear is the standard tool for screening cervical cancer, but there is limited research about the cervical cytology in HSCT recipients. Here, we retrospectively included adult female patients who underwent allogeneic or autologous HSCT at National Taiwan University Hospital during 2009 to 2015 and reviewed their Pap smears before and after HSCT. There were 248 allogeneic and 131 autologous HSCT recipients in our study...
April 24, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28445850/simultaneous-quantification-of-busulfan-clofarabine-and-f-ara-a-using-isotope-labelled-standards-and-standard-addition-in-plasma-by-lc-ms-ms-for-exposure-monitoring-in-hematopoietic-cell-transplantation-conditioning
#10
Arjen M Punt, Jurgen B Langenhorst, Annelies C Egas, Jaap Jan Boelens, Charlotte van Kesteren, Erik M van Maarseveen
In allogeneic hematopoietic cell transplantation (HCT) it has been shown that over- or underexposure to conditioning agents have an impact on patient outcomes. Conditioning regimens combining busulfan (Bu) and fludarabine (Flu) with or without clofarabine (Clo) are gaining interest worldwide in HCT. To evaluate and possibly adjust full conditioning exposure a simultaneous analysis of Bu, F-ARA-A (active metabolite of Flu) and Clo in one analytical run would be of great interest. However, this is a chromatographical challenge due to the large structural differences of Bu compared to F-ARA-A and Clo...
April 15, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28444774/protective-effect-of-l-carnitine-and-l-arginine-against-busulfan-induced-oligospermia-in-adult-rat
#11
A M Abd-Elrazek, O A H Ahmed-Farid
Busulfan is an anticancer drug caused variety of adverse effects for patients with cancer. But it could cause damage to the male reproductive system as one of its adverse effects. This study aimed to investigate the protective effect of L-carnitine and L-arginine on semen quality, oxidative stress parameters and testes cell energy after busulfan treatment. Adult male rats were divided into four groups: control (Con), busulfan (Bus), busulfan plus L-arginine (Bus + L-arg) and busulfan plus L-carnitine (Bus + L-car)...
April 25, 2017: Andrologia
https://www.readbyqxmd.com/read/28435146/prognostic-analysis-of-absolute-lymphocyte-and-monocyte-counts-after-autologous-stem-cell-transplantation-in-children-adolescents-and-young-adults-with-refractory-or-relapsed-hodgkin-lymphoma
#12
Jorge Galvez Silva, Ossama M Maher, Minjeong Park, Diane Liu, Fiorela Hernandez, Priti Tewari, Yago Nieto
Previous studies in adults have shown that peripheral blood absolute lymphocyte and monocyte count ratio (ALC/AMC) after autologous stem cell transplantation (ASCT) can predict outcome in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL). We retrospectively reviewed all of our children, adolescent, and young adult (CAYA) patients (age ≤26) who underwent transplantation for R/R HL between 2004 and 2015. Seventy-six patients (median age, 21; range, 10 to 26 years) who reached day 100 disease free were analyzed; 33% of them had positron emission tomography (PET)-positive tumors before ASCT...
April 20, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28408108/busulfan-drug-monitoring-is-needed-in-patients-undergoing-allogeneic-stem-cell-transplantation
#13
Bushra Salman, Mohammed Al-Zaabi, Mohammed Al-Huneini, David Dennison, Abdulhakeem Al-Rawas, Salam Al-Kindi, Khalil Al-Farsi, Melanie Tauro, Murtadha Al-Khabori
Busulfan (Bu)-based preparative regimens in hematopoietic stem cell transplantation are commonly used. Previous studies have shown that Bu at a fixed dose of 3.2mg/kg/day (FBD) given intravenously decreases variability in drug pharmacokinetics and this decreases the dependency on therapeutic drug monitoring (TDM) of Bu. We compared the Bu dose given using TDM with the FBD of 3.2mg/kg/day. Seventy-three patients with acute leukemia, myelodysplasia, chronic myeloid leukemia, thalassemia major, and sickle cell disease were included...
April 6, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28396159/a-time-to-event-model-for-acute-kidney-injury-after-reduced-intensity-conditioning-stem-cell-transplantation-using-a-tacrolimus-and-sirolimus-based-graft-versus-host-disease-prophylaxis
#14
José Luis Piñana, Alejandro Perez-Pitarch, Irene Garcia-Cadenas, Pere Barba, Juan Carlos Hernandez-Boluda, Albert Esquirol, María Laura Fox, María José Terol, Josep M Queraltó, Jaume Vima, David Valcarcel, Rafael Ferriols-Lisart, Jorge Sierra, Carlos Solano, Rodrigo Martino
There is a paucity of data evaluating acute kidney injury (AKI) incidence and its relationship with the tacrolimus-sirolimus (Tac-Sir) concentrations in the setting of reduced-intensity conditioning (RIC) after allogeneic stem cell transplantation (allo-HSCT). This multicenter retrospective study evaluated risk factors of AKI defined by 2 classification systems, Kidney Disease Improving Global Outcome (KDIGO) score and "Grade 0-3 staging," in 186 consecutive RIC allo-HSCT recipients with Tac-Sir as graft-versus-host disease prophylaxis...
April 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28394191/the-parp-inhibitor-olaparib-enhances-the-cytotoxicity-of-combined-gemcitabine-busulfan-and-melphalan-in-lymphoma-cells
#15
Benigno C Valdez, Yang Li, David Murray, Yan Liu, Yago Nieto, Richard E Champlin, Borje S Andersson
The combination of gemcitabine (Gem), busulfan (Bu), and melphalan (Mel) is a promising regimen for autologous stem-cell transplantation (SCT) for lymphomas. To further improve the efficacy of [Gem + Bu + Mel], we added poly(ADP-ribose) polymerase (PARP) inhibitor olaparib (Ola). We hypothesized that Ola would inhibit the repair of damaged DNA caused by [Gem + Bu + Mel]. Exposure of J45.01 and Toledo cell lines to IC10-20 of individual drug inhibited proliferation by 6-16%; [Gem + Bu + Mel] by 20-27%; and [Gem + Bu + Mel + Ola] by 61-67%...
April 10, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28381685/influences-of-flu-bu-and-flu-mel-on-incidence-and-severity-of-oral-mucositis-among-allogeneic-hematopoietic-stem-cell-transplantation-patients
#16
Sayaka Torihata, Takao Mukai, Takayuki Uchihashi, Kazuhide Matsunaga, Hitomi Miki, Mio Yasumoto, Natsumi Yasutake, Ayana Ashida, Akifumi Enomoto, Suguru Hamada, Takashi Ashida
In the present study, we compared the incidence and severity of oral mucositis among patients undergoing allogeneic hematopoietic stem cell transplantation after fludarabine-based regimens with busulfan 12.8 mg/kg (FB12.8), with busulfan less than or equal to 9.6 mg/kg (FB9.6), and with melphalan 140 mg/m(2) (FM). The incidence of oral mucositis after FB12.8 was the highest among these 3 groups. After FM, all of the patients had developed oral mucositis by day 7. The mean disease duration of oral mucositis after FB12...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28373495/spermatogonial-stem-cell-transplantation-to-the-testis
#17
Shaun Goodyear, Ralph Brinster
Spermatogonial stem cells (SSCs) are located in the basal region of the seminiferous tubules and provide a self-renewing reservoir from which progenitor spermatogonia arise and transiently amplify in number before transition to a differentiating state. SSC transplantation involves grafting mouse testicular cells into the seminiferous tubules of an aspermic recipient testis that is generated either by chemical (e.g., busulfan) treatment or genetic mutations.
April 3, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28370238/pediatric-patients-undergoing-hematopoietic-stem-cell-transplantation-can-greatly-benefit-from-a-novel-once-daily-intravenous-busulfan-dosing-nomogram
#18
Su-Jin Rhee, Ji Won Lee, Kyung-Sang Yu, Kyung Taek Hong, Jung Yoon Choi, Che Ry Hong, Kyung Duk Park, Hee Young Shin, Sang Hoon Song, Hyoung Jin Kang, Howard Lee
Busulfan, a bifunctional alkylating agent, has been used as a conditioning regimen prior to allogeneic hematopoietic stem cell transplantation (HSCT). The aims of this study were to derive a novel once-daily intravenous (IV) busulfan dosing nomogram for pediatric patients undergoing HSCT using a population pharmacokinetic (PK) model. A population PK analysis was performed using 2,183 busulfan concentrations in 137 pediatric patients (age: 0.6 - 22.2 years), who received IV busulfan once-daily for 4 days before undergoing HSCT...
March 28, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28369839/high-dose-chemotherapy-with-thiotepa-busulfan-and-cyclophosphamide-and-autologous-stem-cell-transplantation-for-patients-with-primary-central-nervous-system-lymphoma-in-first-complete-remission
#19
Zachariah DeFilipp, Shuli Li, Areej El-Jawahri, Philippe Armand, Lakshmi Nayak, Nancy Wang, Tracy T Batchelor, Yi-Bin Chen
BACKGROUND: High-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT) is a therapeutic option for patients with primary central nervous system lymphoma (PCNSL). To the authors' knowledge, data are limited regarding its use among patients in first complete remission (CR1) with the CNS-directed conditioning regimen of thiotepa, busulfan, and cyclophosphamide (TBC). METHODS: A retrospective analysis of patients with PCNSL in CR1 who underwent transplantation using a TBC-based conditioning regimen at 2 academic institutions was performed...
April 3, 2017: Cancer
https://www.readbyqxmd.com/read/28359910/cost-effectiveness-of-defibrotide-in-the-prophylaxis-of-veno-occlusive-disease-after-pediatric-allogeneic-stem-cell-transplantation
#20
Herbert Pichler, Karolina Horner, Gernot Engstler, Ulrike Poetschger, Evgenia Glogova, Susanne Karlhuber, Manuel Martin, Werner Eibler, Volker Witt, Wolfgang Holter, Susanne Matthes-Martin
Veno-occlusive disease (VOD) remains a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). Prophylactic use of defibrotide (DF) might further reduce VOD rates but has no impact on the incidence of severe VOD or VOD-associated mortality. We investigated the cost-effectiveness of prophylactic DF according to the BCSH/BSBMT guidelines in 348 children who underwent transplantation between 2001 and 2013 in our hospital, 138 of whom were at risk for VOD. The VOD incidence was 7.4% for the total cohort...
March 27, 2017: Biology of Blood and Marrow Transplantation
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