Allogeneic transplantation for adult acute leukemia in first and second remission with a novel regimen incorporating daily intravenous busulfan, fludarabine, 400 CGY total-body irradiation, and thymoglobulin.
A myeloablative conditioning regimen incorporating daily intravenous busulfan, fludarabine, and 400 cGy total-body irradiation was given before allogeneic stem cell transplantation (SCT) to 64 adults with acute leukemia in first and second remission. Graft-versus-host disease (GVHD) prophylaxis included methotrexate, cyclosporine A, and rabbit antithymocyte globulin (Thymoglobulin). For 31 matched related (MRD) and 33 alternate donor (AD) SCT the incidence of acute GVHD grade II-IV was 11% +/- 6% versus 35% +/- 9% (P = .047), acute GVHD grade III-IV was 0% versus 10% +/- 6% (P = .09), and chronic GVHD was 40% +/- 9% versus 66% +/- 9% (P = NS), respectively. Overall transplant-related mortality (TRM) was 3% +/- 2%. Projected disease-free (DFS) and overall survival (OS) at 3 years for acute myelogenous leukemia (AML) (n = 36) are the same at 83% +/- 6%, and for acute lymphoblastic leukemia (ALL) (n = 28) are 65% +/- 10% and 78% +/- 8%, respectively. For MRD SCT DFS is 77% +/- 9%, OS 87% +/- 6%, for AD SCT the respective figures are 71% +/- 8% and 74% +/- 8%. OS and DFS in patients without and with high-risk features are 100% versus 71% +/- 7% (P = .007) and 88% +/- 8% versus 68% +/- 7% (P = .04), respectively. This combination appears relatively well tolerated, gives equivalent final outcomes from MRD and AD, and may be a reasonable alternative to conventional myeloablative regimens.
Russell
James A
JA
Alberta Blood and Bone Marrow Transplant Program, Department of Oncology, Foothills Hospital, Alberta, Canada. jamesrus@cancerboard.ab.ca <jamesrus@cancerboard.ab.ca>
Savoie
Mary Lynn
ML
Balogh
Alexander
A
Turner
A Robert
AR
Larratt
Loree
L
Chaudhry
M Ahsan
MA
Storek
Jan
J
Bahlis
Nizar J
NJ
Brown
Christopher B
CB
Quinlan
Diana
D
Geddes
Michelle
M
Stewart
Douglas A
DA
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000961:Antilymphocyte Serum; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002066:Busulfan / Q000008:administration & dosage; D016572:Cyclosporine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007262:Infusions, Intravenous; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000401:mortality* / Q000628:therapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000401:mortality* / Q000628:therapy; D012074:Remission Induction; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D015996:Survival Rate; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D016572:Cyclosporine; C512542:thymoglobulin; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008727:Methotrexate