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https://www.readbyqxmd.com/read/28711727/a-chemotherapy-only-regimen-of-busulfan-melphalan-and-fludarabine-and-rabbit-atg-followed-by-allogeneic-t-cell-depleted-hematopoietic-stem-cell-transplants-for-the-treatment-of-myeloid-malignancies
#1
Barbara Spitzer, Ann A Jakubowski, Esperanza B Papadopoulos, Kirsten Fuller, Patrick D Hilden, James W Young, Juliet Barker, Guenther Koehne, Miguel-Angel Perales, Katharine C Hsu, Marcel R M van den Brink, Nancy A Kernan, Susan E Prockop, Andromachi Scaradavou, Hugo Castro-Malaspina, Richard J O'Reilly, Farid Boulad
We sought to develop a myeloablative chemotherapeutic regimen to secure consistent engraftment of T-cell depleted (TCD) hematopoietic stem cell transplants (HSCT) without the need for total body irradiation, thereby reducing toxicity, while maintaining low rates of GvHD and without increasing relapse. We investigated the myeloablative combination of busulfan and melphalan, with the immunosuppressive agents fludarabine and rabbit anti-thymocyte gloubin (r-ATG) as cytoreduction prior to a T-cell depleted HSCT...
July 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28707754/non-sibling-hematopoietic-stem-cell-transplantation-using-myeloablative-conditioning-regimen-in-children-with-maroteaux-lamy-syndrome-a-brief-report
#2
Maryam Behfar, S Sharareh Dehghani, Tahereh Rostami, Ardeshir Ghavamzadeh, Amir Ali Hamidieh
Maroteaux-Lamy syndrome is a rare inherited lysosomal storage disorder with a progressive course. HSCT is a curable option for treatment in these patients. The following report describes our experience in HSCT for three patients with Maroteaux-Lamy syndrome using non-sibling donors. All of the patients received the same myeloablative regimen consisting of intravenous busulfan, cyclophosphamide, and rabbit antithymocyte globulin. Patients underwent HSCT from haploidentical other-related (n=1), full-matched other-related (n=1), and one-locus-mismatched unrelated donor...
August 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28691152/reduced-bucy-2-and-g-csf-primed-bone-marrow-associates-with-low-graft-versus-host-disease-and-transplant-related-mortality-in-allogeneic-hsct
#3
Eucario Leon Rodriguez, Monica M Rivera Franco, Sandra I Perez Alvarez
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the ideal treatment for several diseases. However, the morbidity and mortality associated with the procedure might limit its widespread use; therefore, we implemented reduced BUCY2 as conditioning method along with the use of G-CSF-primed bone marrow (G-BM) in order to reduce complications, including graft-versus-host-disease (GVHD), and to improve survival in these patients. An analysis of transplant characteristics, complications, and survival of patients undergoing an allo-HSCT using this conditioning regimen (busulfan 12 mg/kg and cyclophosphamide 80 mg/kg) plus G-BM was performed...
July 9, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28687222/tp53-and-idh2-somatic-mutations-are-associated-with-inferior-overall-survival-after-allogeneic-hematopoietic-cell-transplantation-for-myelodysplastic-syndrome
#4
Mohamed A Kharfan-Dabaja, Rami S Komrokji, Qing Zhang, Ambuj Kumar, Athanasios Tsalatsanis, Janelle Perkins, Taiga Nishihori, Teresa Field, Najla Al Ali, Asmita Mishra, David Sallman, Karma Z Salem, Ling Zhang, Lynn Moscinski, Hugo F Fernandez, Jeffrey Lancet, Alan List, Claudio Anasetti, Eric Padron
BACKGROUND: Next-generation sequencing has identified somatic mutations that are prognostic of cancer. PATIENTS AND METHODS: We evaluated the incidence and prognostic significance of somatic mutations in 89 myelodysplastic syndrome (MDS) patients who received an allogeneic hematopoietic cell transplantation. Next-generation sequencing was performed on paraffin embedded bone marrow, which was obtained at a median of 31 days before initiating the preparative regimen...
June 16, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28684379/pharmacokinetics-directed-intravenous-busulfan-combined-with-high-dose-melphalan-and-bortezomib-as-a-conditioning-regimen-for-patients-with-multiple-myeloma
#5
Stefan K Barta, Rishi Jain, Amithaba Mazumder, Jason Carter, Lawrence Almanzar, Roy Browne, Samira Shahnaz, Richard Elkind, David Kaminetzky, Ramakrishna Battini, Olga Derman, Noah Kornblum, Amit Verma, Ira Braunschweig
BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has a well-established role in the treatment of patients with multiple myeloma. Melphalan 200 mg/m(2) (Mel200) is the most commonly used preparative regimen. Several studies have provided evidence for potential synergism and safety when combining bortezomib (Btz) or busulfan (Bu) with melphalan (Mel). PATIENTS AND METHODS: We conducted a prospective phase II study to investigate the safety and efficacy of conditioning with pharmacokinetics (PK)-directed intravenous (IV) Bu with Btz and Mel...
June 17, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28681458/refined-methods-to-evaluate-the-in-vivo-hemostatic-function-and-viability-of-transfused-human-platelets-in-rabbit-models
#6
Naohide Watanabe, Masayuki Nogawa, Mariko Ishiguro, Hitomi Maruyama, Masayuki Shiba, Masahiro Satake, Koji Eto, Makoto Handa
BACKGROUND: To bridge the gap between in vitro function and clinical efficacy of platelet (PLT) transfusion products, reliable in vivo PLT functional assays for hemostasis and survival in animal models are required. However, there are no standardized methods for assessing the in vivo quality of transfused human PLTs. STUDY DESIGN AND METHODS: Plasma-depleted human PLT concentrates (PCs; Day 3, Day 5, Day 7, Day 10, and damaged) were transfused into busulfan-induced rabbits with thrombocytopenia with prolonged bleeding times 1 day after treatment with ethyl palmitate (EP) to block their reticuloendothelial systems...
July 5, 2017: Transfusion
https://www.readbyqxmd.com/read/28680354/an-lc-ms-assay-with-isocratic-separation-and-on-line-solid-phase-extraction-to-improve-the-routine-therapeutic-drug-monitoring-of-busulfan-in-plasma
#7
Cristiano Ialongo, Alessia Francesca Mozzi, Sergio Bernardini
BACKGROUND: Busulfan (Bu) requires therapeutic drug monitoring (TDM) in subjects undergoing a conditioning regimen for hematopoietic stem cell transplantation (HSCT). To speed up the procedure and increase reproducibility, we improved our routine LC-MS/MS assay using the on-line solid-phase extraction (SPE) of samples. METHODS: A protein precipitation (PP) step was performed before the on-line SPE of Bu from 200 µL of plasma spiked with octa-deuterated Bu (D8-Bu) as the internal standard...
April 2017: Journal of Medical Biochemistry
https://www.readbyqxmd.com/read/28647558/durable-chimerism-and-long-term-survival-after-unrelated-umbilical-cord-blood-transplantation-for-pediatric-hemophagocytic-lymphohistiocytosis-a-single-center-experience
#8
Sachit A Patel, Heather A Allewelt, Jesse D Troy, Paul L Martin, Timothy A Driscoll, Vinod K Prasad, Joanne Kurtzberg, Kristin M Page, Suhag H Parikh
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune dysregulation characterized by fever, hepatosplenomegaly, cytopenias, central nervous system disease, increased inflammatory markers, and hemophagocytosis. Currently, allogeneic hematopoietic stem cell transplantation is the only curative approach for patients with HLH, with reported survival ranging from 50% to 70% with myeloablative conditioning (MAC) regimens. However, donor availability and transplantation-related mortality associated with conventional MAC are major barriers to success...
June 21, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28617152/impact-of-immunoablation-and-autologous-hematopoietic-stem-cell-transplantation-on-gray-and-white-matter-atrophy-in-multiple-sclerosis
#9
Hyunwoo Lee, Kunio Nakamura, Sridar Narayanan, Robert Brown, Jacqueline Chen, Harold L Atkins, Mark S Freedman, Douglas L Arnold
BACKGROUND: Immunoablation and autologous hematopoietic stem cell transplantation (IA/aHSCT) halts relapses, white matter (WM) lesion formation, and pathological whole-brain (WB) atrophy in multiple sclerosis (MS) patients. Whether the latter was due to effects on gray matter (GM) or WM warranted further exploration. OBJECTIVE: To model GM and WM volume changes after IA/aHSCT to further understand the effects seen on WB atrophy. METHODS: GM and WM volume changes were calculated from serial baseline and follow-up magnetic resonance imaging (MRI) ranging from 1...
June 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28608322/long-evans-rat-spermatogonial-lines-are-effective-germline-vectors-for-transgenic-rat-production
#10
F Kent Hamra, Christopher T Richie, Brandon K Harvey
Long Evans rat strains are applied as research models in a broad spectrum of biomedical fields (>15,800 citations, NCBI PubMed). Here, we report an approach to genetically modify the Long Evans rat germline in donor spermatogonial stem cells. Long Evans rat spermatogonial lines were derived from freshly isolated laminin-binding spermatogonia. Laminin-binding spermatogonia were cultured over multiple passages on fibroblast feeder layers in serum-free culture medium containing GDNF and FGF2. Long Evans rat spermatogonial lines were genetically modified by transposon transduction to express a germline, tdTomato reporter gene...
August 2017: Transgenic Research
https://www.readbyqxmd.com/read/28606176/rituximab-containing-reduced-intensity-conditioning-improves-progression-free-survival-following-allogeneic-transplantation-in-b-cell-non-hodgkin-lymphoma
#11
Narendranath Epperla, Kwang Woo Ahn, Sairah Ahmed, Madan Jagasia, Alyssa DiGilio, Steven M Devine, Samantha Jaglowski, Vanessa Kennedy, Andrew R Rezvani, Sonali M Smith, Anna Sureda, Timothy S Fenske, Mohamed A Kharfan-Dabaja, Phillipe Armand, Mehdi Hamadani
BACKGROUND: In B cell non-Hodgkin lymphoma (B-NHL), rituximab-containing reduced-intensity conditioning regimens (R-RIC) have been shown to provide favorable outcomes in single-arm studies; however, large multicenter studies comparing R-RIC and non-rituximab-containing reduced-intensity conditioning regimens (nonR-RIC) have not been performed. Using the CIBMTR database, we report the outcomes of R-RIC versus nonR-RIC regimens in B-NHL. METHODS: We evaluated 1401 adult B-NHL patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) who received nonR-RIC (n = 1022) or R-RIC (n = 379) regimens...
June 12, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28604667/single-agent-gvhd-prophylaxis-with-tacrolimus-after-post-transplant-high-dose-cyclophosphamide-is-a-valid-option-for-haploidentical-transplantation-in-adults-with-hematological-malignancies
#12
A Esquirol, M J Pascual, M Ortiz, J L Piñana, C Ferra, I Garcia Cadenas, I Vilades, S Brunet, R Martino, J Sierra
Eighty-one patients with high-risk hematological malignancies received unmanipulated haploidentical stem cell transplants (haploSCT) using the same protocol at four Spanish institutions. The conditioning regimen was thiotepa, busulfan and fludarabine; following bone marrow or peripheral blood infusion. GvHD prophylaxis with high-dose cyclophosphamide on days +3 and +4, and IV tacrolimus from day +5 was administered. 62% were in complete remission, 17% had received previous allogeneic SCT and 44% had a high-very high refined disease risk index...
June 12, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28601505/heat-and-chemical-treatments-in-adult-cyprinus-carpio-pisces-cypriniformes-rapidly-produce-sterile-gonads
#13
Sullip Kumar Majhi, Avinash Rambhau Rasal, Basdeo Kushwaha, Sudhir Raizada
Several options have been proposed for eradication of germ cells (GCs) in mammals such as treatment with cytotoxic drugs, irradiation, cold ischemia and hyperthermic treatment. Some of these methods have been also tried in fish but conditions for complete sterilisation of gonads have not been established. Here, we report the production of sterile adult common carp Cyprinus carpio in 10 weeks by the heat and chemical treatments. The cytotoxic drug busulfan (40mg/kg) was intraperitoneally injected into the animals at 2-week intervals (5 doses in total), and they were maintained in water at 38°C between Weeks 1 and 10...
June 3, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28579394/primate-primordial-germ-cells-acquire-transplantation-potential-by-carnegie-stage-23
#14
Amander T Clark, Sofia Gkountela, Di Chen, Wanlu Liu, Enrique Sosa, Meena Sukhwani, Jon D Hennebold, Kyle E Orwig
Primordial germ cells (PGCs) are the earliest embryonic progenitors in the germline. Correct formation of PGCs is critical to reproductive health as an adult. Recent work has shown that primate PGCs can be differentiated from pluripotent stem cells; however, a bioassay that supports their identity as transplantable germ cells has not been reported. Here, we adopted a xenotransplantation assay by transplanting single-cell suspensions of human and nonhuman primate embryonic Macaca mulatta (rhesus macaque) testes containing PGCs into the seminiferous tubules of adult busulfan-treated nude mice...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28578006/increased-sat2-expression-is-associated-with-busulfan-induced-testicular-sertoli-cell-injury
#15
Yi Xian, Mingjun Wu, Yaping Liu, Jie Hao, Yu Wu, Xiaogang Liao, Gang Li
Busulfan is a chemotherapeutic agent used to treat chronic myelogenous leukemia and other myeloproliferative disorders. Increasing evidence has demonstrated that busulfan may induce testicular dysfunction by targeting genes that are expressed in the testis. Here, we showed that spermidine/spermine N1-acetyltransferase 2 (Sat2) was present in testicular Sertoli cells, and its expression was significantly increased by busulfan treatment. To investigate the implications of Sat2 upregulation for cell growth and function, a Sat2-overexpressing TM4 Sertoli cell model was established...
June 1, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28555420/limited-sampling-strategy-for-predicting-busulfan-exposure-in-hematopoietic-stem-cell-transplantation-recipients
#16
Jing-Jing Huang, Bing Chen, Jiong Hu, Wan-Hua Yang
Background Optimization of the area under the concentration-time curve (AUC) of busulfan, an essential component of conditioning regimens, improves the outcomes in patients undergoing hematopoietic stem cell transplantation (HSCT). Traditional sampling methods for calculating AUC require multiple sampling. Objective To establish a limited sampling strategy for predicting the AUC0-12 of intravenous busulfan for Chinese adult patients prior to HSCT. Methods The pharmacokinetics of twice-daily intravenous busulfan was studied in forty-five Chinese adult patients...
May 29, 2017: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/28552421/reduced-intensity-conditioning-with-busulfan-fludarabine-and-antithymocyte-globulin-for-hematopoietic-cell-transplantation-from-unrelated-or-haploidentical-family-donors-in-patients-with-acute-myeloid-leukemia-in-remission
#17
Kyoo-Hyung Lee, Je-Hwan Lee, Jung-Hee Lee, Dae-Young Kim, Han-Seung Park, Eun-Ji Choi, Sun-Hye Ko, Miee Seol, Young-Shin Lee, Young-A Kang, Mijin Jeon, Seunghyun Baek, You-Lee Kang, Sung-Han Kim, Sung-Cheol Yun, Hawk Kim, Jae-Cheol Jo, Yunsuk Choi, Young-Don Joo, Sung-Nam Lim
To investigate the role of antithymocyte globulin (ATG)-containing reduced-intensity conditioning (RIC) in hematopoietic cell transplantation (HCT) from unrelated (UD) or haploidentical family donors (HFD), we conducted a phase 2 trial of 237 patients (age range, 16 to 69 years) with acute myeloid leukemia (AML) in remission. Patients undergoing UD-HCT (n = 93) or HFD-HCT (n = 59) received RIC comprising busulfan, fludarabine, and ATG, 9 mg/kg, whereas those undergoing HCT from matched sibling donors (MSD, n = 85) received myeloablative busulfan and cyclophosphamide conditioning or aforementioned RIC with ATG, 4...
May 25, 2017: Biology of Blood and Marrow Transplantation
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
#18
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...
June 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28522109/gemcitabine-busulfan-and-melphalan-conditioning-for-autologous-stem-cell-transplants-in-multiple-myeloma
#19
Gösta Gahrton
No abstract text is available yet for this article.
June 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28490733/pharmacometabolomics-for-predicting-variable-busulfan-exposure-in-paediatric-haematopoietic-stem-cell-transplantation-patients
#20
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
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