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Busulfan fludarabin

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 remissions without substantial toxicity and treatment related mortality (TRM). We aimed to analyze the safety and efficacy of FluTreo conditioning regimen (fludarabine 150mg/m(2), treosulfan 42g/m(2)) in medically infirm patients. Patients' outcome was compared with a similar historical group treated with FluBuATG (fludarabine 150-180mg/m(2), busulfex 6.4mg/Kg, thymoglobulin-ATG 5-7.5mg/kg). Thirty one consecutive patients suffering from AML (21), MDS (6) or treatment-related AML (4) received FluTreo conditioning...
November 30, 2016: Biology of Blood and Marrow Transplantation
Xin He, YongBin Ye, XiaoJun Xu, Jing Wang, YuXian Huang, GuangYang Weng, MingWan Zhang, KunYuan Guo
Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and a major cause of nonrelapse mortality after allo-HSCT. A conditioning regimen plays a pivotal role in the development of aGVHD. To provide a platform for studying aGVHD and evaluating the impact of different conditioning regimens, we established a murine aGVHD model that simulates the clinical situation and can be conditioned with Busulfan-Cyclophosphamide (Bu-Cy) and Fludarabine-Busulfan (Flu-Bu)...
2016: BioMed Research International
Florent Malard, Myriam Labopin, Gernot Stuhler, Jörg Bittenbring, Arnold Ganser, Johanna Tischer, Mauricette Michallet, Nicolaus Kröger, Christoph Schmid, Anne Huynh, Michael Hallek, Bipin N Savani, Mohamad Mohty, Arnon Nagler
Post-transplant relapse is the leading cause of treatment failure in acute myeloid leukemia (AML) patients after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT). To improve their outcome, we evaluated the outcome of a sequential intermediate-intensity conditioning regimen combining fludarabine, cytosine arabinoside, amsacrine, cyclophosphamide, and either total body irradiation or busulfan (FLAMSA) in patients with intermediate or high-risk AML in first or second complete remission (CR)...
November 2, 2016: Biology of Blood and Marrow Transplantation
Patrice Chevallier, Myriam Labopin, Regis Peffault de La Tour, Bruno Lioure, Claude-Eric Bulabois, Anne Huynh, Didier Blaise, Pascal Turlure, Etienne Daguindau, Natacha Maillard, Ibrahim Yakoub-Agha, Gaelle Guillerm, Jeremy Delage, Nathalie Contentin, Jacques-Olivier Bay, Florence Beckerich, Jean-Henri Bourhis, Marie Detrait, Stéphane Vigouroux, Sylvie François, Faezeh Legrand, Thierry Guillaume, Mohamad Mohty
We have retrospectively compared survivals between acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients who received either a clofarabine/busulfan (CloB2A2) or a fludarabine/busulfan (FB2A2) RIC regimen for allogeneic stem cell transplantation. Between 2009 and 2014, 355 allotransplanted cases were identified from the SFGM-TC registry as having received either the FB2A2 (n = 316, 56% males, median age: 59.2 years, AML 78.5%, first complete remission [CR1] 72%, median follow-up: 20 months) or the CloB2A2 (n = 39, 62% males, median age: 60...
November 2016: Cancer Medicine
Alberto Mussetti, Nancy A Kernan, Susan E Prockop, Andromachi Scaradavou, Rachel Lehrman, Julianne M Ruggiero, Kevin Curran, Rachel Kobos, Richard O'Reilly, Farid Boulad
Nonmalignant hematologic disorders (NMHD) of childhood comprise a variety of disorders, including acquired severe aplastic anemia and inherited marrow failure syndromes. Patients with high-risk NMHD without matched related donors fare poorly with allogeneic hematopoietic alternative donor stem cell transplantation (allo-HSCT) and are at high risk for developing graft-versus-host disease following unmodified grafts. The authors retrospectively analyzed data on 18 patients affected by NMHD, lacking a human leukocyte antigen (HLA)-identical sibling donor, who underwent an alternative donor allo-HSCT at their institution between April 2005 and May 2013...
October 7, 2016: Pediatric Hematology and Oncology
Ting Yang, Qiaoxian Lin, Jinhua Ren, Ping Chen, Xiaohong Yuan, Xiaofeng Luo, Tingbo Liu, Jing Zheng, Zhihong Zheng, Xiaoyun Zheng, Xinji Chen, Langhui Zhang, Hao Zheng, Zaisheng Chen, Xueling Hua, Shaohua Le, Jian Li, Zhizhe Chen, Jianda Hu
Haplo-HSCT has been used when HLA-matched siblings are not available. Conditioning regimens aim to reduce tumor burden prior to HSCT and provide sufficient immunoablation. We report the outcome of haplo-HSCT in 63 consecutive patients from 2/2013 to 12/2015 (19 females/44 males) with high-risk or relapsed/refractory hematological malignancies (n=29-AML; 8-sAML; 19-ALL; 5-advanced-MDS; 2-CML-BC). Median age was 20 years (range: 1.1-49). Twenty-one patients achieved remission prior to transplant, while 42 did not...
October 1, 2016: Oncotarget
Jérôme Cornillon, Marie Balsat, Aurélie Cabrespine, Emmanuelle Tavernier-Tardy, Eric Hermet, Aurélien Mulliez, Karine Augeul-Meunier, Denis Guyotat, Jacques-Olivier Bay
Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT) is often proposed for patients with comorbidities. To enhance engraftment and limit graft-versus-host disease (GVHD), antithymoglobulin (ATG) is usually used. However, the dose needed remains unclear unlike myeloablative conditioning. In order to clarify this point, we conducted a retrospective study on patients who received a reduced intensity conditioning allo-HSCT based on a 2-day fludarabine and busulfan treatment with either 1 or 2 days of ATG treatment...
2016: Acta Haematologica
Hassan Sibai, Umberto Falcone, Uday Deotare, Fotios V Michelis, Jieun Uhm, Vikas Gupta, John Kuruvilla, Jeffrey H Lipton, Matthew D Seftel, Hans A Messner, Dennis Dong Hwan Kim
Reduced-intensity conditioning (RIC) has been shown to have similar overall survival (OS) but higher relapse rates compared with myeloablative (MAC) regimens in patients with myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Using propensity score matching (PSM) analysis, well-balanced pairs of different variables can be compared effectively. We retrospectively compared allo-HSCT recipients with acute myeloid leukemia or myelodysplasia receiving a RIC regimen (FBT200; fludarabine 30 mg/m(2)/day for 4 days, busulfan 3...
September 3, 2016: Biology of Blood and Marrow Transplantation
Pooja Khandelwal, Jacob J Bleesing, Stella M Davies, Rebecca A Marsh
Myeloablative conditioning (MAC) regimens are commonly used in transplantation for chronic granulomatous disease (CGD) but are associated with toxicity. Reduced-intensity conditioning (RIC) regimens have lower toxicity but may fail to achieve stable donor chimerism. We report a comparison between 4 patients who received a RIC regimen consisting of alemtuzumab (1 mg/kg), fludarabine (150 mg/m(2)), and melphalan (140 mg/m(2)) and 14 patients who received a MAC regimen consisting of busulfan (area under the curve, 1800 to 2000 µMol/min twice daily × 4 days), cyclophosphamide (50 mg/kg/day × 4), and antithymocyte globulin (15 mg/kg twice daily on days -2 and -1, then daily on days +1 and +2)...
November 2016: Biology of Blood and Marrow Transplantation
Surapol Issaragrisil, Chutima Kunacheewa
PURPOSE OF REVIEW: Bone marrow transplantation is the only curative treatment for severe thalassemia. Since its successful first report in 1981, more than 4000 patients with this disease worldwide underwent bone marrow transplantation. The purpose of this review is to update the most recent reports of matched sibling donor hematopoietic stem cell transplantation in thalassemia. RECENT FINDINGS: Advanced and improved transplant techniques result in the improved outcomes in those transplants from a matched sibling donor with transplant-related mortality less than 5%...
November 2016: Current Opinion in Hematology
Natasha Kekre, Francisco J Marquez-Malaver, Monica Cabrero, Jl Piñana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, M J Terol, Rodrigo Martino, Joseph H Antin, L Lopez-Corral, Carlos Solano, Philippe Armand, Jose A Pérez-Simon
There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014...
October 2016: Biology of Blood and Marrow Transplantation
Stephanie E Smetsers, Frans J Smiers, Dorine Bresters, Martine C Sonnevelt, Marc B Bierings
This article presents the haematopoietic stem cell transplantation (SCT) results of the complete Dutch Fanconi anaemia (FA) patient cohort. Sixty-eight Dutch FA patients have been transplanted since 1972. In total, 63 (93%) patients engrafted, 54 after first SCT and 9 after second SCT. Fludarabine (FLU)-based conditioning was associated with decreased graft failure (odds ratio 0·21, P = 0·01), decreased early mortality (hazard ratio 0·25, P = 0·01) and improved 5-year overall survival (FLU 87·8% [standard error (SE) 5·1%] versus non-FLU 59·3% [SE 9·5%], P = 0·01)...
September 2016: British Journal of Haematology
Emmanuel Katsanis, Lauren N Sapp, Luz Pelayo-Katsanis, Katherine Whitney, Yi Zeng, Lisa M Kopp
Busulfan, fludarabine, and melphalan as hematopoietic cell transplant conditioning, was used in 6 patients aged 1 to 19 years with very high-risk myeloid malignancies. This dose regimen had an acceptable toxicity profile resulting in complete donor engraftment even following transplantation of small 2/6 antigen disparate umbilical cord blood grafts. It provided excellent disease control as all patients had high-risk features in terms of cytogenetics, therapy-related leukemia, and/or significant measurable disease before transplant...
November 2016: Journal of Pediatric Hematology/oncology
Hawk Kim, Je-Hwan Lee, Young-Don Joo, Sung-Hwa Bae, Sang Min Lee, Jae-Cheol Jo, Yunsuk Choi, Jung-Hee Lee, Dae-Young Kim, Hun Mo Ryoo, Kyoo-Hyung Lee
We performed a study on allogeneic hematopoietic cell transplantation (alloHCT) from an HLA-haplo-identical familial donor (haploFD) using a busulfan-fludarabine-antithymocyte globulin conditioning regimen for severe aplastic anemia (sAA) and hypoplastic myelodysplastic syndrome. For the comparison between a haploFD and an alternative donor (AD; matched unrelated or partially matched donor) for sAA in adults, we collected haploFD data retrospectively and prospectively. Forty-eight AD cases were selected for the comparison with 16 haploFD cases...
2016: Acta Haematologica
Gheath Alatrash, Peter F Thall, Benigno C Valdez, Patricia S Fox, Jing Ning, Haven R Garber, Selma Janbey, Laura L Worth, Uday Popat, Chitra Hosing, Amin M Alousi, Partow Kebriaei, Elizabeth J Shpall, Roy B Jones, Marcos de Lima, Gabriela Rondon, Julianne Chen, Richard E Champlin, Borje S Andersson
Pretransplant conditioning regimens critically determine outcomes in the setting of allogeneic stem cell transplantation (allo-SCT). The use of nucleoside analogs such as fludarabine (Flu) in combination with i.v. busulfan (Bu) has been shown to be highly effective as a pretransplant conditioning regimen in acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS). Because leukemia relapse remains the leading cause of death after allo-SCT, we studied whether clofarabine (Clo), a nucleoside analog with potent antileukemia activity, can be used to complement Flu...
October 2016: Biology of Blood and Marrow Transplantation
Vanessa E Kennedy, Bipin N Savani, John P Greer, Adetola A Kassim, Brian G Engelhardt, Stacey A Goodman, Salyka Sengsayadeth, Wichai Chinratanalab, Madan Jagasia
Reduced-intensity conditioning (RIC) has been used increasingly for allogeneic hematopoietic cell transplantation to minimize transplant-related mortality while maintaining the graft-versus-tumor effect. In B cell lymphoid malignancies, reduced-intensity regimens containing rituximab, an antiCD20 antibody, have been associated with favorable survival; however, the long-term outcomes of rituximab-containing versus nonrituximab-containing regimens for allogeneic hematopoietic cell transplantation in B cell lymphoid malignancies remain to be determined...
October 2016: Biology of Blood and Marrow Transplantation
Wataru Yamamoto, Taiki Andou, Megumi Itabashi, Satoshi Koyama, Yoshimi Ishii, Ayumi Numata, Kenji Motohashi, Maki Hagihara, Kenji Matsumoto, Shin Fujisawa
Objective Fludarabine plus melphalan (FM) and fludarabine plus busulfan (FB) are two major conditioning regimens for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods We retrospectively analyzed patients who underwent allo-HSCT after a conditioning regimen consisting of FM or FB with/without total body irradiation for hematological malignancies between 2005 and 2014. Results There were 41 patients who met the criteria. The median follow-up time for the survivors was 3 years. Thirty-two patients received allo-HSCT after the FM regimen and nine patients received allo-HSCT after the FB regimen...
2016: Internal Medicine
Hisashi Yamamoto, Naoyuki Uchida, Mitsuhiro Yuasa, Kosei Kageyama, Hikari Ota, Daisuke Kaji, Aya Nishida, Kazuya Ishiwata, Shinsuke Takagi, Masanori Tsuji, Yuki Asano-Mori, Go Yamamoto, Koji Izutsu, Kazuhiro Masuoka, Atsushi Wake, Akiko Yoneyama, Shigeyoshi Makino, Shuichi Taniguchi
A pilot study of a novel, reduced-toxicity, myeloablative conditioning regimen using intravenous busulfan 12.8 mg/kg, fludarabine 180 mg/m(2), and melphalan 80 mg/m(2) for single cord blood transplantation (CBT) was conducted at our institution. Fifty-one patients with myeloid malignancies not in remission were included in this study. Their median age was 59 years (range, 19 to 70 years), with a median hematopoietic cell transplantation-specific comorbidity index score of 3. With a median observation period of 39...
October 2016: Biology of Blood and Marrow Transplantation
Benigno C Valdez, Jonathan E Brammer, Yang Li, David Murray, Esmeralda C Teo, Yan Liu, Chitra Hosing, Yago Nieto, Richard E Champlin, Borje S Andersson
Novel approaches to pre-transplant conditioning are needed to improve treatment of advanced T-cell malignancies. We investigated the synergism of fludarabine (Flu), clofarabine (Clo), busulfan (Bu), and romidepsin (Rom) in T-cell lines and patient-derived cell samples. [Flu+Clo+Bu+Rom] had combination indexes of 0.4-0.5 at ∼50% cytotoxicity in PEER and SUPT1 cells, suggesting synergism. Drug exposure resulted in histone modifications, DNA-damage response (DDR), increased reactive oxygen species (ROS), decreased glutathione (GSH) and mitochondrial membrane (MM) potential, and apoptosis...
August 2016: Leukemia Research
Moussab Damlaj, Hassan B Alkhateeb, Mehrdad Hefazi, Daniel K Partain, Shahrukh Hashmi, Dennis A Gastineau, Aref Al-Kali, Robert C Wolf, Naseema Gangat, Mark R Litzow, William J Hogan, Mrinal M Patnaik
Fludarabine with busulfan (FB) and fludarabine with melphalan (FM) are commonly used reduced-intensity conditioning (RIC) regimens. Pharmacokinetic dosing of busulfan (Bu) is frequently done for myeloablative conditioning, but evidence for its use is limited in RIC transplants. We compared transplant outcomes of FB versus FM using i.v. Bu targeted to the area under the curve (AUC). A total of 134 RIC transplants (47 FB and 87 FM) for acute myelogenous leukemia and myelodysplastic syndrome were identified, and median follow-up of the cohort was 40 months (range, 0 to 63...
August 2016: Biology of Blood and Marrow Transplantation
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