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https://www.readbyqxmd.com/read/28408108/busulfan-drug-monitoring-is-needed-in-patients-undergoing-allogeneic-stem-cell-transplantation
#1
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
#2
Jose 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 after allogeneic stem cell transplantation (RIC-allo-HSCT). This multicenter retrospective study evaluated risk factors of AKI defined by two classification systems (KDIGO score and "Grade 0-3 staging") in 186 consecutive RIC-allo-HSCT recipients with Tac-Sir as graft-versus-host disease prophylaxis. Conditioning regimens consisted of fludarabine and busulfan (n=53), or melphalan (n=83), or a combination of thiotepa, fludarabine and busulfan (n=50)...
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
#3
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
#4
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
#5
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
#6
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
#7
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-following-pediatric-allogeneic-stem-cell-transplantation
#8
H Pichler, K Horner, G Engstler, U Poetschger, E Glogova, S Karlhuber, M Martin, W Eibler, V Witt, W Holter, S 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 transplanted between 2001 and 2013 in our hospital, 138 of which were at risk for VOD. The VOD incidence was 7.4% for the total cohort...
March 27, 2017: Biology of Blood and Marrow Transplantation
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
#9
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
#10
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]
https://www.readbyqxmd.com/read/28351939/cytoreductive-conditioning-intensity-predicts-clonal-diversity-in-ada-scid-retroviral-gene-therapy-patients
#11
Aaron R Cooper, Georgia R Lill, Kit Shaw, Denise Carbonaro, Alejandra Davila, Robert Sokolic, Fabio Candotti, Matteo Pellegrini, Donald B Kohn
Retroviral gene therapy has proven efficacious for multiple genetic diseases of the hematopoietic system, but roughly half of clinical gene therapy trial protocols using gammaretroviral vectors have reported leukemias in some of the patients treated. In dramatic contrast, 39 ADA-SCID patients have been treated with four distinct gammaretroviral vectors without oncogenic consequence. We investigated clonal dynamics and diversity in a cohort of 15 ADA-SCID children treated with gammaretroviral vectors and found clear evidence of genotoxicity, indicated by numerous common integration sites near proto-oncogenes and by increased abundance of clones with integrations near MECOM and LMO2 These clones showed stable behavior over multiple years and never expanded to the point of dominance or dysplasia...
March 28, 2017: Blood
https://www.readbyqxmd.com/read/28346229/clinical-efficacy-of-gene-modified-stem-cells-in-adenosine-deaminase-deficient-immunodeficiency
#12
Kit L Shaw, Elizabeth Garabedian, Suparna Mishra, Provaboti Barman, Alejandra Davila, Denise Carbonaro, Sally Shupien, Christopher Silvin, Sabine Geiger, Barbara Nowicki, E Monika Smogorzewska, Berkley Brown, Xiaoyan Wang, Satiro de Oliveira, Yeong Choi, Alan Ikeda, Dayna Terrazas, Pei-Yu Fu, Allen Yu, Beatriz Campo Fernandez, Aaron R Cooper, Barbara Engel, Greg Podsakoff, Arumugam Balamurugan, Stacie Anderson, Linda Muul, G Jayashree Jagadeesh, Neena Kapoor, John Tse, Theodore B Moore, Ken Purdy, Radha Rishi, Kathey Mohan, Suzanne Skoda-Smith, David Buchbinder, Roshini S Abraham, Andrew Scharenberg, Otto O Yang, Kenneth Cornetta, David Gjertson, Michael Hershfield, Rob Sokolic, Fabio Candotti, Donald B Kohn
BACKGROUND: Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase-deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study. METHODS: Ten subjects with confirmed ADA-deficient SCID and no available matched sibling or family donor were enrolled between 2009 and 2012 and received transplantation with autologous hematopoietic CD34+ cells that were modified with the human ADA cDNA (MND-ADA) γ-retroviral vector after conditioning with busulfan (90 mg/m2) and ERT cessation...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28337172/bone-marrow-derived-cell-accumulation-in-the-spinal-cord-is-independent-of-peripheral-mobilization-in-a-mouse-model-of-amyotrophic-lateral-sclerosis
#13
Kyle Peake, John Manning, Coral-Ann Lewis, Kevin Tran, Fabio Rossi, Charles Krieger
Bone marrow-derived cells (BMDCs) are capable of migrating across the blood-brain barrier (BBB) and accumulating in the central nervous system (CNS) when transplanted into recipients conditioned with whole-body irradiation or chemotherapy. We used the chemotherapeutic agents busulfan and treosulfan to condition recipient mice for transplantation with bone marrow (BM) cells isolated from donor mice ubiquitously expressing green fluorescent protein. We attempted to increase the accumulation of BMDCs in the CNS by mobilization of BMDCs using either, or both, granulocyte colony-stimulating factor (GCSF) or plerixafor (AMD3100)...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28332262/haploidentical-peripheral-blood-stem-cell-transplantation-without-irradiation-or-busulfan-after-reduced-intensity-conditioning-for-kmt2a-mll-rearranged-infant-b-cell-precursor-acute-lymphoblastic-leukemia-report-of-two-cases
#14
Ai Yoshimi, Keisuke Kato, Sho Hosaka, Ryoko Suzuki, Hiroko Fukushima, Tomohei Nakao, Chie Kobayashi, Takashi Fukushima, Kazutoshi Koike, Ryo Sumazaki, Masahiro Tsuchida
We present two infants with KMT2A(MLL)-gene-R-associated BCP-ALL, who received HLA haploidentical PBSCT after RIC. The patients developed ALL at age 6 months and 3 months, respectively. Case 1 underwent PBSCT at the second CR with detectable KMT2A-AFF1(MLL-AF4) fusion gene transcript at 11 months of age, and Case 2 at the first CR without KMT2A-MLLT1(MLL-ENL) fusion gene transcript at 8 months of age. Both patients received G-CSF-mobilized unmanipulated peripheral blood mononuclear cells from their HLA haploidentical mothers after administration of FLU, MEL, and ATG...
March 22, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28328762/a-significant-influence-of-metronidazole-on-busulfan-pharmacokinetics-a-case-report-of-therapeutic-drug-monitoring
#15
Hyewon Chung, Kyung-Sang Yu, Kyung Taek Hong, Jung Yoon Choi, Che Ry Hong, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin, SeungHwan Lee
Busulfan is a cytotoxic agent used in preconditioning for hematopoietic stem cell transplantation (HSCT). Therapeutic drug monitoring of busulfan is necessary owing to its narrow therapeutic range. Patients undergoing preconditioning are susceptible to infection and might require co-administration of antibiotics. We present a case study of a three-year-old girl with precursor T-cell acute lymphoblastic leukemia who received intravenous busulfan before HSCT. Metronidazole was co-administered before the third dose of busulfan because of Clostridium difficile infection...
March 21, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28289609/the-regenerative-effect-of-bone-marrow-derived-stem-cells-in-spermatogenesis-of-infertile-hamster
#16
Akbar Vahdati, Alireza Fathi, Mehrdokht Hajihoseini, Ghaem Aliborzi, Ebrahim Hosseini
BACKGROUND: Infertility is a serious social problem in advanced nations, with male factor in half of all cases of infertility. This study was conducted to determine the regenerative effect of bone marrow-derived stem cells in spermatogenesis of infertile hamster. METHODS: Twelve adult male hamsters were equally divided into azoospermic and control groups. Busulfan was intraperitoneally used for induction of azoospermia, while the right testis was treated with bone marrow-derived stem cells (10(6) BM-SCs), labeled with sterile trypan blue, 35 days after busulfan injection...
January 2017: World Journal of Plastic Surgery
https://www.readbyqxmd.com/read/28288951/haploidentical-related-donor-hematopoietic-stem-cell-transplantation-for-dedicator-of-cytokinesis-8-deficiency-using-post-transplantation-cyclophosphamide
#17
Nirali N Shah, Alexandra F Freeman, Helen Su, Kristen Cole, Mark Parta, Niki M Moutsopoulos, Safa Baris, Elif Karakoc-Aydiner, Thomas E Hughes, Heidi H Kong, Steve M Holland, Dennis D Hickstein
Dedicator-of-cytokinesis 8 (DOCK8) deficiency, a primary immunodeficiency disease, can be reversed by allogeneic hematopoietic stem cell transplantation (HSCT); however, there are few reports describing the use of alternative donor sources for HSCT in DOCK8 deficiency. We describe HSCT for patients with DOCK8 deficiency who lack a matched related or unrelated donor using bone marrow from haploidentical related donors and post-transplantation cyclophosphamide (PT/Cy) for graft-versus-host disease (GVHD) prophylaxis...
March 10, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28288949/evaluation-of-the-pharmacokinetics-and-efficacy-of-a-busulfan-test-dose-in-adult-patients-undergoing-myeloablative-hematopoietic-cell-transplantation
#18
Elizabeth Weil, Felicia Zook, Carolyn Oxencis, Angela Canadeo, Angela Urmanski, Mindy Waggoner, Daniel Eastwood, Marcelo Pasquini, Mehdi Hamadani, Parameswaran Hari
Owing to interpatient variability in busulfan exposure, therapeutic monitoring of busulfan is often used in myeloablative allogeneic transplantation to ensure that patients are near the optimal steady-state goal of 900 ng/mL. One challenge in therapeutic monitoring of busulfan is the brief course of busulfan treatment, requiring prompt analysis and dose adjustments as needed. Pharmacokinetic evaluation of a busulfan test dose before the start of the conditioning regimen would allow for all conditioning regimen doses to be given at the calculated optimized dose...
March 10, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28286617/allogeneic-hematopoietic-stem-cell-transplantation-for-adult-acute-lymphoblastic-leukemia-results-from-a-single-center-1993-2011
#19
Ipek Yonal-Hindilerden, Sevgi Kalayoglu-Besisik, Nuray Gurses-Koc, Fehmi Hindilerden, Deniz Sargin
Background: For adult ALL patients, the indications and appropriate timing of allogeneic hematopoietic stem cell transplantation (AHSCT) continue to be debated. The primary aim of this single-institution study was to compare the results of our adult ALL patients that had been allografted with those reported in the current literature. Subjects and Methods: This study included 53 consecutive adults with acute lymphoblastic leukemia (ALL) who underwent allogeneic hematopoietic stem cell transplantation (AHSCT) with myeloablative (92%) and reduced-intensity (8%) conditioning between 1993 and 2011...
January 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/28259608/busulfan-and-melphalan-versus-carboplatin-etoposide-and-melphalan-as-high-dose-chemotherapy-for-high-risk-neuroblastoma-hr-nbl1-siopen-an-international-randomised-multi-arm-open-label-phase-3-trial
#20
Ruth Ladenstein, Ulrike Pötschger, Andrew D J Pearson, Penelope Brock, Roberto Luksch, Victoria Castel, Isaac Yaniv, Vassilios Papadakis, Geneviève Laureys, Josef Malis, Walentyna Balwierz, Ellen Ruud, Per Kogner, Henrik Schroeder, Ana Forjaz de Lacerda, Maja Beck-Popovic, Pavel Bician, Miklós Garami, Toby Trahair, Adela Canete, Peter F Ambros, Keith Holmes, Mark Gaze, Günter Schreier, Alberto Garaventa, Gilles Vassal, Jean Michon, Dominique Valteau-Couanet
BACKGROUND: High-dose chemotherapy with haemopoietic stem-cell rescue improves event-free survival in patients with high-risk neuroblastoma; however, which regimen has the greatest patient benefit has not been established. We aimed to assess event-free survival after high-dose chemotherapy with busulfan and melphalan compared with carboplatin, etoposide, and melphalan. METHODS: We did an international, randomised, multi-arm, open-label, phase 3 cooperative group clinical trial of patients with high-risk neuroblastoma at 128 institutions in 18 countries that included an open-label randomised arm in which high-dose chemotherapy regimens were compared...
April 2017: Lancet Oncology
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