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Kevin Rakszawski, Kosuke Miki, David Claxton, Henry Wagner, Hiroko Shike, Shin Mineishi, Seema Naik
Approximately 30-40% of patients with acute myeloid leukemia (AML) experience induction failures. In these patients who do not achieve remission with two cycles of standard induction therapies, the probability of achieving remission with subsequent inductions is very limited. Hematopoietic stem cell transplantation (HSCT) is the only curative option for these patients, but high relapse rate and transplant-related mortality often preclude them to proceed to transplant. Thus, AML not in remission at time of HSCT remains a huge unmet need in current HSCT practice, particularly if the patient does not have an HLA-matched donor identified by the time of two induction failures...
March 14, 2018: International Journal of Hematology
E Palmerini, R L Jones, E Setola, P Picci, E Marchesi, R Luksch, G Grignani, M Cesari, A Longhi, M E Abate, A Paioli, Z Szucs, L D'ambrosio, K Scotlandi, F Fagioli, S Asaftei, S Ferrari
BACKGROUND: Data on temozolomide (TEM) and irinotecan (IRI) activity in recurrent Ewing sarcoma (EWS), especially in adult patients, are limited. METHODS: Patients receiving TEM 100 mg/m2 /day oral, and IRI 40 mg/m2 /day intravenous, days 1-5, every 21 days, were included in this multi-institutional retrospective study. Disease control rate (DCR) [overall response rate (ORR) [complete response (CR) + partial response (PR)] + stable disease (SD)], 6-months progression-free survival (6-mos PFS) and 1-year overall survival (OS) were assessed...
March 13, 2018: Acta Oncologica
Chunyan Yue, Yingying Ding, Yang Gao, Li Li, Yan Pang, Zenghui Liu, Hang Zhang, Yang Xiao, Zujun Jiang, Haowen Xiao
OBJECTIVES: In patients with very severe aplastic anemia (VSAA), neutropenia is prolonged and persistent, resulting in refractory overwhelming infections. Hematopoiesis recovery is urgently needed. METHODS: Six patients with de novo VSAA lacking HLA-identical sibling donors and those who experienced refractory infections, underwent haploidentical related donor (HRD) hematopoietic stem cell transplantation (HSCT) as a first-line therapy. The conditioning regimen consisted of busulfan, cyclophosphamide and rabbit antithymocyte globulin...
March 12, 2018: European Journal of Haematology
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No abstract text is available yet for this article.
April 2018: Therapeutic Drug Monitoring
Christopher C Dvorak, Prakash Satwani, Elliot Stieglitz, Mitchell S Cairo, Ha Dang, Qinglin Pei, Yun Gao, Donna Wall, Tali Mazor, Adam B Olshen, Joel S Parker, Samir Kahwash, Betsy Hirsch, Susana Raimondi, Neil Patel, Micah Skeens, Todd Cooper, Parinda A Mehta, Stephan A Grupp, Mignon L Loh
BACKGROUND: Most patients with juvenile myelomonocytic leukemia (JMML) are curable only with allogeneic hematopoietic cell transplantation (HCT). However, the current standard conditioning regimen, busulfan-cyclophosphamide-melphalan (Bu-Cy-Mel), may be associated with higher risks of morbidity and mortality. ASCT1221 was designed to test whether the potentially less-toxic myeloablative conditioning regimen containing busulfan-fludarabine (Bu-Flu) would be associated with equivalent outcomes...
March 12, 2018: Pediatric Blood & Cancer
Ke Huang, Dun-Hua Zhou, Yang Li, Hong-Gui Xu, Li-Ping Que, Chun Chen, Hong-Man Xue, Hai-Xia Guo, Wen-Jun Weng, Shao-Liang Huang, Jian-Pei Fang
BACKGROUND: The objective of this study was to evaluate the feasibility of a modified conditioning regimen for the treatment of patients with β-thalassaemia major (TM), using unrelated donor peripheral blood stem cell transplantation (UD-PBSCT). METHODS: A modified conditioning regimen based on intravenous busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin was performed in 50 consecutive childhood patients with β-TM and a median age of 4.6 years (range, 2-12 years)...
March 7, 2018: Pediatric Blood & Cancer
Yago Nieto, Peter F Thall, Junsheng Ma, Benigno C Valdez, Sairah Ahmed, Paolo Anderlini, Uday Popat, Roy B Jones, Elizabeth J Shpall, Chitra Hosing, Muzaffar Qazilbash, Partow Kebriaei, Amin Alousi, Melissa Timmons, Alison Gulbis, Alan Myers, Yasuhiro Oki, Michelle Fanale, Bouthaina Dabaja, Chelsea Pinnix, Sarah Milgrom, Richard Champlin, Borje S Andersson
We conducted a prospective phase 2 trial of gemcitabine, busulfan and melphalan (Gem/Bu/Mel) with autologous stem-cell transplantation (ASCT) in Hodgkin's lymphoma (HL) patients with primary refractory or poor-risk relapsed disease (extranodal relapse or within 1 year of frontline therapy). The trial was powered to detect a 2-year progression-free survival (PFS) rate improvement from a historical 50% (using BEAM) to 65%. We compared the study population with all other concurrent patients who were eligible for the trial but instead received BEAM at our center...
March 1, 2018: Biology of Blood and Marrow Transplantation
Lixin Xu, Zhouyang Liu, Yamei Wu, Xueliang Yang, Yongbin Cao, Xiaohong Li, Bei Yan, Songwei Li, Wanming Da, Xiaoxiong Wu
BACKGROUND: This study not only evaluated the clinical effects of treatment using haploidentical hematopoietic stem cells (haplo-HSCs) combined with human umbilical cord mesenchymal stem cells (UC-MSCs) in patients with severe aplastic anemia (SAA), but also investigated the factors related to graft versus host disease (GVHD). METHODS: Cotransplantation of haplo-HSCs and UC-MSCs was performed in 24 SAA patients. The conditioning regimens consisted of rabbit anti-human T-lymphocyte immunoglobulin (ATG), cyclophosphamide, and fludarabine with or without busulfan...
March 1, 2018: European Journal of Medical Research
Xianfa Yang, Ran Wang, Xiongjun Wang, Guoqing Cai, Yun Qian, Su Feng, Fangzhi Tan, Kun Chen, Ke Tang, Xingxu Huang, Naihe Jing, Yunbo Qiao
Clinical therapies of pluripotent stem cells (PSCs)-based transplantation have been hindered by frequent development of teratomas or tumors in animal models and clinical patients. Therefore, clarifying the mechanism of carcinogenesis in stem cell therapy is of great importance for reducing the risk of tumorigenicity. Here we differentiate Oct4-GFP mouse embryonic stem cells (mESCs) into neural progenitor cells (NPCs) and find that a minority of Oct4+ cells are continuously sustained at Oct4+ state. These cells can be enriched and proliferated in a standard ESC medium...
February 22, 2018: Journal of Molecular Cell Biology
Can Boga, Mahmut Yeral, Ciğdem Gereklioglu, Suheyl Asma, Erkan Maytalman, Pelin Aytan, Ilknur Kozanoglu, Cagla Sariturk, Hakan Ozdogu
OBJECTIVE/BACKGROUND: Anti-T lymphocyte globulin Fresenius (rATG-F; ATG-Fresenius) and antithymocyte globulin (thymoglobulin), which are included in transplant protocols, are used to reduce the risk of chronic graft-versus-host disease (cGVHD) or suppress allograft rejection. Available clinical studies have been conducted in heterogenous patient populations and with different administration protocols including stem cell sources. Additionally, the pharmacokinetics of ATG is variable, and the clinically effective dose of rATG-F, in particular, is not exactly known...
February 20, 2018: Hematology/oncology and Stem Cell Therapy
Zimin Sun, Huilan Liu, Chenhui Luo, Liangquan Geng, Changcheng Zheng, Baolin Tang, Xiaoyu Zhu, Juan Tong, Xingbing Wang, Kaiyang Ding, Xiang Wan, Lei Zhang, Wen Yao, Kaiding Song, Xuhan Zhang, Yue Wu, Huizhi Yang, Yongsheng Han, Xin Liu, Weibo Zhu, Jingsheng Wu, Zuyi Wang
Cord blood transplantation (CBT) is an effective option for treating hematological malignancies, but graft failure (GF) remains the primary cause of therapy failure. Thus, based on myeloablative conditioning (MAC) of busulfan with cyclophosphamide (Bu/Cy) or total body irradiation with Cy (TBI/Cy), fludarabine (Flu) was added to Bu/Cy and cytarabine (CA) to TBI/Cy for a modified myeloablative conditioning (MMAC). To compare the prognosis of MMAC with MAC, we conducted a retrospective study including 58 patients who underwent CBT with MAC or MMAC from 2000 to 2011...
February 23, 2018: International Journal of Cancer. Journal International du Cancer
T Nava, N Kassir, M A Rezgui, C R S Uppugunduri, P Huezo-Diaz Curtis, M Duval, Y Théoret Y, L E Daudt, C Litalien, M Ansari, M Krajinovic, H Bittencourt
AIMS: To develop a population pharmacokinetic (PopPK) model for intravenous busulfan in children that incorporates variants of GSTA1, gene coding for the main enzyme in busulfan imetabolism. METHODS: Busulfan concentration-time data was collected from 112 children and adolescents (median 5.4 years old, range: 0.1 to 20) who received intravenous busulfan during the conditioning regimen prior to stem cell transplantation. Weight, sex, baseline disease (malignant vs...
February 22, 2018: British Journal of Clinical Pharmacology
Laura Hutchinson, Marlene Sinclair, Bernadette Reid, Kathryn Burnett, Bridgeen Callan
INTRODUCTION: Saliva, as a matrix, offers many benefits over blood in therapeutic drug monitoring (TDM), in particular for infantile TDM. However, the accuracy of salivary TDM in infants remains an area of debate. This review explored the accuracy, applicability and advantages of using saliva TDM in infants and neonates. METHODS: Databases were searched up to and including September 2016. Studies were included based on PICO as follows: P: Infants and neonates being treated with any medication, I: Salivary Therapeutic Drug Monitoring vs C: Traditional methods and O: accuracy, advantages/disadvantages and applicability to practice...
February 14, 2018: British Journal of Clinical Pharmacology
Javid Gaziev, Antonella Isgrò, Pietro Sodani, Katia Paciaroni, Gioia De Angelis, Marco Marziali, Michela Ribersani, Cecilia Alfieri, Alessandro Lanti, Tiziana Galluccio, Gaspare Adorno, Marco Andreani
We examined outcomes of haploidentical hematopoietic cell transplantation (haplo-HCT) using T-cell receptor αβ+ (TCRαβ+ )/CD19+ -depleted grafts (TCR group, 14 patients) in children with hemoglobinopathies. Patients received a preparative regimen consisting of busulfan, thiotepa, cyclophosphamide, and antithymocyte globulin preceded by fludarabine, hydroxyurea, and azathioprine. The median follow-up among surviving patients was 3.9 years. The 5-year probabilities of overall survival (OS) and disease-free survival (DFS) were 84% and 69%, respectively...
February 13, 2018: Blood Advances
Benigno C Valdez, Yang Li, David Murray, Yan Liu, Yago Nieto, Richard E Champlin, Borje S Andersson
Combination of drugs that target different aspects of aberrant cellular processes is an efficacious treatment for hematological malignancies. Hypomethylating agents (HMAs) and inhibitors of poly(ADP-ribose) polymerases (PARPis) and histone deacetylases (HDACis) are clinically active anti-tumor drugs. We hypothesized that their combination would be synergistically cytotoxic to leukemia and lymphoma cells. Exposure of AML and lymphoma cell lines to the combination of the PARPi niraparib (Npb), the HMA decitabine (DAC) and the HDACi romidepsin (Rom) or panobinostat (Pano) synergistically inhibited cell proliferation by up to 70% via activation of the ATM pathway, increased production of reactive oxygen species, decreased mitochondrial membrane potential, and activated apoptosis...
January 9, 2018: Oncotarget
Francesco Saraceni, Myriam Labopin, Rose-Marie Hamladji, Ghulam Mufti, Gerard Socié, Avichai Shimoni, Jeremy Delage, Eric Deconinck, Patrice Chevallier, Didier Blaise, Jaime Sanz, Anne Huynh, Edouard Forcade, Bipin N Savani, Mohamad Mohty, Arnon Nagler
Background: A preparatory regimen consisting of thiotepa-busulfan-fludarabine (TBF) has been associated with reduced relapse in patients with haematological malignancies after haploidentical and cord blood transplants; however, few data exist regarding TBF conditioning in sibling (MSD) and unrelated donor (URD) transplants for AML. Results: Among patients receiving a myeloablative (MAC) regimen, TBF-MAC was associated with significantly lower relapse (HR 0.47, p = 0...
January 9, 2018: Oncotarget
Yukiko Okubo, Hitomi Kaneko, Takuya Shimizu, Ryosuke Nomura, Mizuki Hyuga, Takaya Mitsuyoshi, Kohei Tada, Naoya Ukyo, Chisato Mizutani, Kazuo Hatanaka, Kazunori Imada
Primary central nervous system lymphoma (PCNSL) is more difficult to treat than other lymphomas. Recently, it has been suggested that high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is effective for treating PCNSL. In the present study, we retrospectively analyzed 12 patients with PCNSL at our hospital. Five young patients with good performance status (PS) received upfront ASCT. The conditioning regimen prior to ASCT with busulfan + cyclophosphamide + etoposide showed good prognosis (complete remission rate of 100%)...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Mark Parta, Nirali N Shah, Kristin Baird, Hind Rafei, Katherine R Calvo, Thomas Hughes, Kristen Cole, Meg Kenyon, Bazetta Blacklock Schuver, Jennifer Cuellar-Rodriguez, Christa S Zerbe, Steven M Holland, Dennis D Hickstein
Allogeneic hematopoietic stem cell transplantation (HSCT) reverses the bone marrow failure syndrome due to GATA2 deficiency. The intensity of conditioning required to achieve reliable engraftment and prevent relapse remains unclear. Here, we describe the results of a prospective study of HSCT in 22 patients with GATA2 deficiency using a busulfan-based conditioning regimen. The study included 2 matched related donor (MRD) recipients, 13 matched unrelated donor (URD) recipients, and 7 haploidentical related donor (HRD) recipients...
February 3, 2018: Biology of Blood and Marrow Transplantation
Chiara Messina, Marco Zecca, Franca Fagioli, Attilio Rovelli, Stefano Giardino, Pietro Merli, Fulvio Porta, Maurizio Aricò, Elena Sieni, Giuseppe Basso, Mimmo Ripaldi, Claudio Favre, Marta Pillon, Antonio Marzollo, Marco Rabusin, Simone Cesaro, Mattia Algeri, Maurizio Caniglia, Paolo Di Bartolomeo, Ottavio Ziino, Francesco Saglio, Arcangelo Prete, Franco Locatelli
We report on 109 patients with hemophagocytic lymphohistiocytosis (HLH) undergoing 126 procedures of allogeneic hematopoietic stem cell transplantation (HSCT) between 2000 and 2014 in centers associated with the Italian Pediatric Hematology Oncology Association. Genetic diagnosis was FHL2 (32%), FHL3 (33%) or other defined disorders known to cause HLH (15%); in the remaining patients, no genetic abnormality was found. Donor for first transplant was an HLA-matched sibling for 25 patients (23%), an unrelated donor for 73 (67%) and an HLA-partially matched family donor for 11 children (10%)...
February 1, 2018: Biology of Blood and Marrow Transplantation
Hyun-Jung Park, Won-Young Lee, Chankyu Park, Kwon-Ho Hong, Jin-Hoi Kim, Hyuk Song
Whereas stage-specific markers for spermatogonial cells have been well investigated in mouse, the specific markers of germ cells in the testis of domestic animals have not been well defined. Phosphoglycerate kinase (PGK), an enzyme that converts 1,3-bisphosphoglycerate and adenosine diphosphate to 3-phosphoglycerate and adenosine triphosphate, has two isozymes: PGK1 and PGK2. In mouse, PGK1 exists only during the early stages of spermatogenesis, and PGK2 is then expressed during the pachytene spermatocyte stage...
February 1, 2018: Theriogenology
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