Once daily i.v. busulfan and fludarabine (i.v. Bu-Flu) compares favorably with i.v. busulfan and cyclophosphamide (i.v. BuCy2) as pretransplant conditioning therapy in AML/MDS.
We postulated that fludarabine (Flu) instead of cyclophosphamide (Cy) combined with i.v. busulfan (Bu) as preconditioning for allogeneic hematopoietic stem cell transplantation (HSCT) would improve safety and retain antileukemic efficacy. Sixty-seven patients received BuCy2, and subsequently, 148 patients received Bu-Flu. We used a Bayesian method to compare outcomes between these nonrandomized patients. The groups had comparable pretreatment characteristics, except that Bu-Flu patients were older (46 versus 39 years, P < .01), more often had unrelated donors (47.3% versus 20.9%, P < .0003), and had shorter median follow-up (39.7 versus 74.6 months). To account for improved supportive care and other unidentified factors that may affect outcome ("period" effects), 78 acute myelogenous leukemia (AML) patients receiving Melphalan-Flu (MF), treated in parallel during this time (1997-2004) were used to estimate the period effect. The MF patients' outcomes worsened during this period. Therefore, the period effect is unlikely to explain the greatly improved outcome with Bu-Flu. Patients transplanted with Bu-Flu in the first complete remission (CR1) had a 3-year overall survival and event-free-survival (EFS) of 78% and 74%, respectively, whereas CR1 patients younger than age 41 had a 3-year EFS of 83%. These results support replacing BuCy +/- ATG with Bu-Flu +/- rabbit-antithymocyte globulin (ATG), and warrant a prospective comparison between allogeneic HSCT and conventional induction/consolidation chemotherapy for AML in CR1.
Andersson
Borje S
BS
Department of Stem Cell Transplantation and Cellular Therapy, U.T. M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 423, Houston, TX 77030-4009, USA. Bandersson@mdanderson.org
de Lima
Marcos
M
Thall
Peter F
PF
Wang
Xuemei
X
Couriel
Daniel
D
Korbling
Martin
M
Roberson
Soonja
S
Giralt
Sergio
S
Pierre
Betty
B
Russell
James A
JA
Shpall
Elizabeth J
EJ
Jones
Roy B
RB
Champlin
Richard E
RE
D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001499:Bayes Theorem; D002066:Busulfan / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000601:surgery*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage*; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000601:surgery*; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000706:statistics & numerical data; D016019:Survival Analysis; D013601:T-Lymphocytes; D014019:Tissue Donors / Q000706:statistics & numerical data; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000961:Antilymphocyte Serum; D000970:Antineoplastic Agents; D019653:Myeloablative Agonists; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008558:Melphalan