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Busulfan fludarabin

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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/28687222/tp53-and-idh2-somatic-mutations-are-associated-with-inferior-overall-survival-after-allogeneic-hematopoietic-cell-transplantation-for-myelodysplastic-syndrome
#2
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/28647558/durable-chimerism-and-long-term-survival-after-unrelated-umbilical-cord-blood-transplantation-for-pediatric-hemophagocytic-lymphohistiocytosis-a-single-center-experience
#3
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/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
#4
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/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
#5
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/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
#6
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...
June 15, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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
#7
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...
July 2017: Biology of Blood and Marrow Transplantation
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
#8
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/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/28288951/haploidentical-related-donor-hematopoietic-stem-cell-transplantation-for-dedicator-of-cytokinesis-8-deficiency-using-post-transplantation-cyclophosphamide
#10
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/28286617/allogeneic-hematopoietic-stem-cell-transplantation-for-adult-acute-lymphoblastic-leukemia-results-from-a-single-center-1993-2011
#11
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/28214159/is-surveillance-for-colonization-of-carbapenem-resistant-gram-negative-bacteria-important-in-adult-bone-marrow-transplantation-units
#12
Hayati Demiraslan, Fatma Cevahir, Elife Berk, Gokhan Metan, Mustafa Cetin, Emine Alp
BACKGROUND: The aim of this study was to investigate the rate of carbapenem-resistant gram-negative bacilli (CRGNB) colonization and to analyze the risk factors associated with CRGNB colonization. METHODS: This prospective study was conducted in adult patients hospitalized in hematopoietic stem cell transplantation (HSCT) units over a period of 8 months. Rectal swab samples were obtained from each participant every Monday, and patients CRGNB positive on admission were excluded...
July 1, 2017: American Journal of Infection Control
https://www.readbyqxmd.com/read/28199755/incidence-and-risk-factor-of-hemorrhagic-cystitis-after-allogeneic-transplantation-with-fludarabine-busulfan-and-anti-thymocyte-globulin-myeloablative-conditioning
#13
Wilson Lam, Jan Storek, Haocheng Li, Michelle Geddes, Andrew Daly
BACKGROUND: Hemorrhagic cystitis (HC) is a complication of allogeneic stem cell transplantation (SCT), associated with factors such as BK polyomavirus reactivation, age, conditioning regimen, and presence of graft-versus-host disease (GVHD). The incidence and impact of HC in patients receiving fludarabine (Flu), busulfan (Bu), and anti-thymocyte globulin (ATG) conditioning is unknown. METHODS: We conducted a case-control study of patients undergoing SCT at our center between January 1, 2003 and Dec 31, 2012, to determine the incidence of HC and its effect on patient outcomes including overall survival (OS), relapse, non-relapse mortality (NRM), GVHD, and healthcare resource use...
February 15, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28179273/radiation-free-alternative-donor-hct-for-fanconi-anemia-patients-results-from-a-prospective-multi-institutional-study
#14
Parinda A Mehta, Stella M Davies, Thomas Leemhuis, Kasiani Myers, Nancy A Kernan, Susan E Prockop, Andromachi Scaradavou, Richard J O'Reilly, David A Williams, Leslie Lehmann, Eva Guinan, David Margolis, K Scott Baker, Adam Lane, Farid Boulad
Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized by chromosomal fragility, progressive marrow failure, and cancer predisposition. Hematopoietic cell transplantation (HCT) is curative for FA-related marrow failure or leukemia, but both radiation exposure during transplant and graft-versus-host disease (GVHD) may increase risk of later malignancies of the head and neck and anogenital area. In this study, we tested a radiation-free conditioning regimen with a T-cell-depleted graft to eliminate radiation exposure and minimize early and late toxicities of transplant...
April 20, 2017: Blood
https://www.readbyqxmd.com/read/28118857/impact-of-in-vivo-t-cell-depletion-in-hla-identical-allogeneic-stem-cell-transplantation-for-acute-myeloid-leukemia-in-first-complete-remission-conditioned-with-a-fludarabine-iv-busulfan-myeloablative-regimen-a-report-from-the-ebmt-acute-leukemia-working-party
#15
Marie Thérèse Rubio, Maud D'Aveni-Piney, Myriam Labopin, Rose-Marie Hamladji, Miguel A Sanz, Didier Blaise, Hakan Ozdogu, Etienne Daguindeau, Carlos Richard, Stella Santarone, Giuseppe Irrera, Ibrahim Yakoub-Agha, Moshe Yeshurun, Jose L Diez-Martin, Mohamad Mohty, Bipin N Savani, Arnon Nagler
BACKGROUND: The impact of the use of anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation performed with HLA-identical sibling donors following fludarabine and 4 days intravenous busulfan myeloablative conditioning regimen has been poorly explored. METHODS: We retrospectively analyzed 566 patients who underwent a first HLA-identical allogeneic stem cell transplantation with this conditioning regimen for acute myeloid leukemia in first complete remission between 2006 and 2013 and compared the outcomes of 145 (25...
January 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28108271/comparative-effectiveness-of-busulfan-and-fludarabine-versus-fludarabine-and-400%C3%A2-cgy-total-body-irradiation-conditioning-regimens-for-acute-myeloid-leukemia-myelodysplastic-syndrome
#16
Moaath Mustafa Ali, Donna M Abounader, Lisa A Rybicki, Melissa A Yurch, Jamie Starn, Christina Ferraro, Victoria Winslow, Betty K Hamilton, Aaron T Gerds, Hien Liu, Robert Dean, Brian T Hill, Brad Pohlman, Steven Andresen, Rabi Hanna, Matt Kalaycio, Brian J Bolwell, Navneet S Majhail, Ronald M Sobecks
Allogeneic hematopoietic cell transplantation conditioning regimen intensity has varied for patients with acute myeloid leukemia and myelodysplastic syndrome. A comparative effectiveness analysis was performed to assess outcomes of busulfan and fludarabine (BuFlu) versus those of fludarabine and 400 cGy total body irradiation (FluTBI) conditioning. Thirty-three subjects received BuFlu and 38 received FluTBI. The BuFlu group received more red blood cell transfusions (P = .02) and had a longer time to platelet recovery (P = ...
January 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28049637/low-immunosuppressive-burden-after-hla-matched-related-or-unrelated-bmt-using-posttransplantation-cyclophosphamide
#17
Christopher G Kanakry, Javier Bolaños-Meade, Yvette L Kasamon, Marianna Zahurak, Nadira Durakovic, Terry Furlong, Marco Mielcarek, Marta Medeot, Ivana Gojo, B Douglas Smith, Jennifer A Kanakry, Ivan M Borrello, Robert A Brodsky, Douglas E Gladstone, Carol Ann Huff, William H Matsui, Lode J Swinnen, Kenneth R Cooke, Richard F Ambinder, Ephraim J Fuchs, Marcos J de Lima, Borje S Andersson, Ravi Varadhan, Paul V O'Donnell, Richard J Jones, Leo Luznik
The intensive and prolonged immunosuppressive therapy required to prevent or treat graft-versus-host disease (GVHD) after allogeneic blood or marrow transplantation (alloBMT) puts patients at substantial risk for life-threatening infections, organ toxicity, and disease relapse. Posttransplantation cyclophosphamide (PTCy) can function as single-agent GVHD prophylaxis after myeloablative, HLA-matched related (MRD), or HLA-matched unrelated (MUD) donor T-cell-replete bone marrow allografting, obviating the need for additional prophylactic immunosuppression...
March 9, 2017: Blood
https://www.readbyqxmd.com/read/28018447/targeted-busulfan-and-fludarabine-based-conditioning-for-bone-marrow-transplantation-in-chronic-granulomatous-disease
#18
Hee Young Ju, Hyoung Jin Kang, Che Ry Hong, Ji Won Lee, Hyery Kim, Sang Hoon Song, Kyung-Sang Yu, In-Jin Jang, June Dong Park, Kyung Duk Park, Hee Young Shin, Joong-Gon Kim, Hyo Seop Ahn
Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by impaired phagocytic function. Hematopoietic stem cell transplantation (HSCT) is a definitive cure for CGD; however, the use of HSCT is limited because of associated problems, including transplantation-related mortality and engraftment failure. We report a case of a patient with CGD who underwent successful HSCT following a targeted busulfan and fludarabine reduced-toxicity myeloablative conditioning. Intravenous busulfan was administered once daily for 4 consecutive days (days -8 to -5), and the target area under the curve was 75,000 µg·hr/L...
November 2016: Korean Journal of Pediatrics
https://www.readbyqxmd.com/read/27991894/fludarabine-with-pharmacokinetically-guided-iv-busulfan-is-superior-to-fixed-dose-delivery-in-pretransplant-conditioning-of-aml-mds-patients
#19
B S Andersson, P F Thall, B C Valdez, D R Milton, G Al-Atrash, J Chen, A Gulbis, D Chu, C Martinez, S Parmar, U Popat, Y Nieto, P Kebriaei, A Alousi, M de Lima, G Rondon, Q H Meng, A Myers, J Kawedia, L L Worth, M Fernandez-Vina, T Madden, E J Shpall, R B Jones, R E Champlin
We hypothesized that IV busulfan (Bu) dosing could be safely intensified through pharmacokinetic (PK-) dose guidance to minimize the inter-patient variability in systemic exposure (SE) associated with body-sized dosing, and that this should improve outcome of AML/MDS patients undergoing allogeneic stem cell transplantation. To test this hypothesis, we treated 218 patients (median age 50.7 years, male/female 50/50%) with fludarabine 40 mg/m(2) once daily x4, each dose followed by IV Bu, randomized to 130 mg/m(2) (N=107) or PK-guided to average daily SE, AUC of 6000 μM min (N=111), stratified for remission status and allo-grafting from HLA-matched donors...
April 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27914967/survival-advantage-and-comparable-toxicity-in-reduced-toxicity-treosulfan-based-versus-reduced-intensity-busulfan-based-conditioning-regimen-in-myelodysplastic-syndrome-and-acute-myeloid-leukemia-patients-after-allogeneic-hematopoietic-cell-transplantation
#20
Ioanna Sakellari, Despina Mallouri, Eleni Gavriilaki, Ioannis Batsis, Maria Kaliou, Varnavas Constantinou, Apostolia Papalexandri, Chrysavgi Lalayanni, Chrysanthi Vadikolia, Anastasia Athanasiadou, Evangelia Yannaki, Damianos Sotiropoulos, Christos Smias, Achilles Anagnostopoulos
Treosulfan has been incorporated in conditioning regimens for sustained remission without substantial toxicity and treatment-related mortality (TRM). We aimed to analyze the safety and efficacy of a fludarabine 150 mg/m(2) and treosulfan 42 g/m(2) (FluTreo) conditioning regimen in medically infirm patients. Outcomes were compared with those of a similar historical group treated with fludarabine 150 mg/m(2) to 180 mg/m(2), busulfan 6.4 mg/kg, and antithymocyte globulin (ATG) 5 mg/kg to 7.5 mg/kg (FluBuATG)...
November 30, 2016: Biology of Blood and Marrow Transplantation
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