The addition of 400 cGY total body irradiation to a regimen incorporating once-daily intravenous busulfan, fludarabine, and antithymocyte globulin reduces relapse without affecting nonrelapse mortality in acute myelogenous leukemia.
A combination of fludarabine (Flu) and daily i.v. busulfan (Bu) is well tolerated and effective in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML). The addition of rabbit antithymocyte globulin (ATG) may reduce morbidity and mortality from graft-versus-host disease (GVHD), but lead to increased relapse. To compensate for this effect, we added 400 cGy of total body irradiation (TBI) to the Flu/Bu regimen in 89 patients, and compared outcomes with those achieved in 90 patients who received the drug combination alone. Although nonrelapse mortality (NRM) at 3 years did not differ between the groups, the inclusion of TBI significantly reduced relapse (hazard ratio [HR] = 0.29; 95% confidence interval [CI] = 0.15-0.54; P = .0001). Consequently, both overall survival (OS; HR = 0.50; 95% CI = 0.3-0.84; P = .009) and disease-free survival (DFS; HR = 0.43; 95% CI = 0.26-0.72; P = .001) were improved with the inclusion of TBI. This study confirms the importance of regimen intensity in allogeneic HSCT for AML. The combination of daily i.v. Bu, Flu, 400 cGy TBI, and ATG provides a well-tolerated regimen with antileukemic activity in AML comparable to that of other, conventional myeloablative (MA) regimens.
Russell
James A
JA
Department of Medicine and Oncology, Foothills Hospital and Tom Baker Cancer Centre, 1331 29th Street NW, Calgary, Alberta, Canada. jamesrus@cancerboard.ab.ca
Irish
William
W
Balogh
Alexander
A
Chaudhry
M Ahsan
MA
Savoie
Mary Lynn
ML
Turner
A Robert
AR
Larratt
Loree
L
Storek
Jan
J
Bahlis
Nizar J
NJ
Brown
Christopher B
CB
Quinlan
Diana
D
Geddes
Michelle
M
Zacarias
Nancy
N
Daly
Andrew
A
Duggan
Peter
P
Stewart
Douglas A
DA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007275:Injections, Intravenous; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation; D055815:Young Adult
D000961:Antilymphocyte Serum; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine