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

Partow Kebriaei, Claudio Anasetti, Mei Jie Zhang, Hai Lin Wang, Ibrahim Aldoss, Marcos de Lima, H. Jean Khoury, Brenda M. Sandmaier, Mary M. Horowitz, Andrew Artz, Nelli Bejanyan, Stefan Ciurea, Hillard M. Lazarus, Robert Peter Gale, Mark R Litzow, Christopher Bredeson, Matthew D. Seftel, Michael A. Pulsipher, Jaap Jan Boelens, Joseph AlvarnasRichard Champlin, Stephen Forman, Vinod Pullarkat, Daniel Weisdorf, Nandita D Khera

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
JournalBiology of Blood and Marrow Transplantation
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Busulfan
Whole-Body Irradiation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cell Transplantation
Recurrence
Cyclophosphamide
Disease-Free Survival
Conditioning (Psychology)
Transplants
Unrelated Donors
Melphalan
Antilymphocyte Serum
Survival
Etoposide
Protein-Tyrosine Kinases
Siblings
Multivariate Analysis
Retrospective Studies

Keywords

  • Acute lymphoblastic leukemia
  • Allogeneic transplant
  • Busulfan
  • Total body irradiation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Intravenous Busulfan Compared with Total Body Irradiation Pretransplant Conditioning for Adults with Acute Lymphoblastic Leukemia. / 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 R; Bredeson, Christopher; Seftel, Matthew D.; Pulsipher, Michael A.; Boelens, Jaap Jan; Alvarnas, Joseph; Champlin, Richard; Forman, Stephen; Pullarkat, Vinod; Weisdorf, Daniel; Khera, Nandita D.

In: Biology of Blood and Marrow Transplantation, 01.01.2018.

Research output: Contribution to journalArticle

Kebriaei, P, Anasetti, C, Zhang, MJ, Wang, HL, Aldoss, I, de Lima, M, Khoury, HJ, Sandmaier, BM, Horowitz, MM, Artz, A, Bejanyan, N, Ciurea, S, Lazarus, HM, Gale, RP, Litzow, MR, Bredeson, C, Seftel, MD, Pulsipher, MA, Boelens, JJ, Alvarnas, J, Champlin, R, Forman, S, Pullarkat, V, Weisdorf, D & Khera, ND 2018, 'Intravenous Busulfan Compared with Total Body Irradiation Pretransplant Conditioning for Adults with Acute Lymphoblastic Leukemia', Biology of Blood and Marrow Transplantation. https://doi.org/10.1016/j.bbmt.2017.11.025
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 R ; Bredeson, Christopher ; Seftel, Matthew D. ; Pulsipher, Michael A. ; Boelens, Jaap Jan ; Alvarnas, Joseph ; Champlin, Richard ; Forman, Stephen ; Pullarkat, Vinod ; Weisdorf, Daniel ; Khera, Nandita D. / Intravenous Busulfan Compared with Total Body Irradiation Pretransplant Conditioning for Adults with Acute Lymphoblastic Leukemia. In: Biology of Blood and Marrow Transplantation. 2018.
@article{f29796dc14254d5abe950ce89f53ca06,
title = "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.",
keywords = "Acute lymphoblastic leukemia, Allogeneic transplant, Busulfan, Total body irradiation",
author = "Partow Kebriaei and Claudio Anasetti and Zhang, {Mei Jie} and Wang, {Hai Lin} and Ibrahim Aldoss and {de Lima}, Marcos and Khoury, {H. Jean} and Sandmaier, {Brenda M.} and Horowitz, {Mary M.} and Andrew Artz and Nelli Bejanyan and Stefan Ciurea and Lazarus, {Hillard M.} and Gale, {Robert Peter} and Litzow, {Mark R} and Christopher Bredeson and Seftel, {Matthew D.} and Pulsipher, {Michael A.} and Boelens, {Jaap Jan} and Joseph Alvarnas and Richard Champlin and Stephen Forman and Vinod Pullarkat and Daniel Weisdorf and Khera, {Nandita D}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.bbmt.2017.11.025",
language = "English (US)",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Intravenous Busulfan Compared with Total Body Irradiation Pretransplant Conditioning for Adults with Acute Lymphoblastic Leukemia

AU - Kebriaei, Partow

AU - Anasetti, Claudio

AU - Zhang, Mei Jie

AU - Wang, Hai Lin

AU - Aldoss, Ibrahim

AU - de Lima, Marcos

AU - Khoury, H. Jean

AU - Sandmaier, Brenda M.

AU - Horowitz, Mary M.

AU - Artz, Andrew

AU - Bejanyan, Nelli

AU - Ciurea, Stefan

AU - Lazarus, Hillard M.

AU - Gale, Robert Peter

AU - Litzow, Mark R

AU - Bredeson, Christopher

AU - Seftel, Matthew D.

AU - Pulsipher, Michael A.

AU - Boelens, Jaap Jan

AU - Alvarnas, Joseph

AU - Champlin, Richard

AU - Forman, Stephen

AU - Pullarkat, Vinod

AU - Weisdorf, Daniel

AU - Khera, Nandita D

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Acute lymphoblastic leukemia

KW - Allogeneic transplant

KW - Busulfan

KW - Total body irradiation

UR - http://www.scopus.com/inward/record.url?scp=85041917243&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041917243&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2017.11.025

DO - 10.1016/j.bbmt.2017.11.025

M3 - Article

C2 - 29197676

AN - SCOPUS:85041917243

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

ER -