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

Abstract

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.

Hematopoietic stem cell transplantation for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission: a position statement of the European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL) and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

“…busulfan was relatively small (n = 40). Kebriaei et al [49] compared results of 819 patients who received TBI combined with etoposide or cyclophosphamide and 299 patients treated with i.v. busulfan combined with either cyclophosphamide, melphalan, fludarabine or clofarabine [49].…”

“…Kebriaei et al [49] compared results of 819 patients who received TBI combined with etoposide or cyclophosphamide and 299 patients treated with i.v. busulfan combined with either cyclophosphamide, melphalan, fludarabine or clofarabine [49]. In a multivariate model the use of busulfan was associated with a significantly higher risk of relapse (HR = 1.46, p = 0.002) but similar NRM, LFS and OS.…”

“…The authors concluded that i.v. busulfanbased conditioning is a valuable option for patients who cannot tolerate TBI [49]. Alternative approaches include the use of regimens based on high doses of thiotepa.…”

Total Body Irradiation–Based versus Chemotherapy-Based Myeloablative Conditioning for Allogeneic Hematopoietic Cell Transplant

“…A recent retrospective study [26] compared outcomes of ALL patients (approximately 75% in first remission and 25% in second remission; 83% B cell lineage) given CY/TBI or VP16/TBI conditioning (TBI doses ranging from 1200 to 1600 cGy-no information on dose schedules or rates or lung shielding) with BU/FLU, BU/clofarabine, BU/melphalan, or BU/CY. The TBIbased cases (n = 819) and 67 BU-based cases were from the CIBMTR database, which included results from 504 transplant centers.…”

TBI: To Be (Irradiated) or Not To Be? That Remains the Question

“…Most data evaluating this is also in myeloid neoplasms, and there may be a larger impact for TBI in lymphoid malignancies. A recent Center for International Blood and Marrow Transplant Research report by Kebriaei et al [23] evaluated the use of intravenous Bu-based regimens compared with TBI in acute lymphoblastic leukemia, reporting similar overall and disease-free survival, with significantly decreased TRM with intravenous Bu-based regimens compared with TBI but at the cost of significantly higher relapse (37% vs 28%).…”