Intravenous Busulfan Compared with Total Body Irradiation Pretransplant Conditioning for Adults with Acute Lymphoblastic Leukemia

• Published in: Biology of blood and marrow transplantation 2018-04, Vol.24 (4), p.726-733
• Main Authors: Kebriaei, Partow, Anasetti, Claudio, Zhang, Mei-Jie, Wang, Hai-Lin, Aldoss, Ibrahim, de Lima, Marcos, Khoury, H. Jean, Sandmaier, Brenda M., Horowitz, Mary M., Artz, Andrew, Bejanyan, Nelli, Ciurea, Stefan, Lazarus, Hillard M., Gale, Robert Peter, Litzow, Mark, Bredeson, Christopher, Seftel, Matthew D., Pulsipher, Michael A., Boelens, Jaap-Jan, Alvarnas, Joseph, Champlin, Richard, Forman, Stephen, Pullarkat, Vinod, Weisdorf, Daniel, Marks, David I., Hogan, William, Battiwalla, Minoo, Copelan, Edward, Hildebrandt, Gerhard, Ganguly, Sid, Majhail, Navneet, Woolfrey, Ann, Nivison-Smith, Ian, Hertzberg, Mark, Diaz, Miguel Angel, Jakubowski, Ann, Ustun, Celalettin, Yong, Agnes, Freytes, Cesar, DeFilipp, Zachariah, Inamoto, Yoshi, Cahn, Jean-Yves, Savani, Bipin, Yared, Jean, Bajel, Ashish, Bacher, Ulrike, Uy, Geoffrey, Rizzieri, David, Wieduwilt, Matthew, Schultz, Kirk, Grunwald, Michael, Kamble, Rammurti, Qayed, Muna, Brammer, Jonathan, Ballen, Karen, Khera, Nandita, Schouten, Harry, Bierings, Marc, Kanakry, Christopher, Wood, William Allen, Saad, Ayman, Savoie, Lynn, Hamilton, Betty Ky, Aljurf, Mahmoud, Vij, Ravi, Pawarode, Attaphol, Olsson, Richard, Wirk, B. Mona, Beitinjaneh, Amer, Seo, Sachiko, Cerny, Jan, Akpek, Gorgun, Norkin, Maxim, Nishihori, Taiga, Lazaryan, Aleksandr, Sabloff, Mitchell
• Format: Article
• Language: English
• Subjects: Acute lymphoblastic leukemia; Administration, Intravenous; Adolescent; Adult; Allogeneic transplant; Allografts; Busulfan; Busulfan - administration & dosage; Disease-Free Survival; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Survival Rate; Total body irradiation; Transplantation Conditioning; Whole-Body Irradiation
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2017.11.025

•TBI and Bu-based preparative regimens confer equivalent survival post-HCT in adult ALL.•More relapse, trend for less cGVHD for Bu-based regimens in multivariate analysis.•TBI-based regimens confer good disease control, but trend for more TRM. Total body irradiation (TBI) has been included in standard conditioning for acute lymphoblastic leukemia (ALL) before hematopoietic cell transplantation (HCT). Non-TBI regimens have incorporated busulfan (Bu) to decrease toxicity. This retrospective study analyzed TBI and Bu on outcomes of ALL patients 18–60 years old, in first or second complete remission (CR), undergoing HLA-compatible sibling, related, or unrelated donor HCT, who reported to the Center for International Blood and Marrow Transplant Research from 2005 to 2014. TBI plus etoposide (25%) or cyclophosphamide (75%) was used in 819 patients, and intravenous Bu plus fludarabine (41%), clofarabine (30%), cyclophosphamide (15%), or melphalan (13%) was used in 299 patients. Bu-containing regimens were analyzed together, since no significant differences for patient outcomes were noted between them. Bu patients were older, with better performance status; took longer to achieve first CR and receive HCT; were treated more recently; and were more likely to receive peripheral blood grafts, antithymocyte globulin, or tyrosine kinase inhibitors. With median follow-up of 3.6 years for Bu and 5.3 years for TBI, adjusted 3-year outcomes showed treatment-related mortality Bu 19% versus TBI 25% (P = .04); relapse Bu 37% versus TBI 28% (P = .007); disease-free survival (DFS) Bu 45% versus TBI 48% (P = .35); and overall survival (OS) Bu 57% versus TBI 53% (P = .35). In multivariate analysis, Bu patients had higher risk of relapse (relative risk, 1.46; 95% confidence interval, 1.15 to 1.85; P = .002) compared with TBI patients. Despite the higher relapse, Bu-containing conditioning led to similar OS and DFS following HCT for ALL.