Intravenous BU plus Mel: an effective, chemotherapy-only transplant conditioning regimen in patients with ALL.
We investigated the administration of i.v. BU combined with melphalan (Mel) in patients with ALL undergoing allogeneic hematopoietic SCT. Forty-seven patients with a median age of 33 years (range 20-61) received a matched sibling (n=27) or matched unrelated donor transplant (n=20) for ALL in first CR (n=26), second CR (n=13), or with more advanced disease (n=8). BU was infused daily for 4 days, either at a fixed dose of 130 mg/m² (5 patients) or using pharmacokinetic (PK) dose adjustment (42 patients), to target an average daily area-under-the-curve (AUC) of 5000 μmol/min, determined by a test dose of i.v. BU at 32 mg/m². This was followed by a rest day, then two daily doses of Mel at 70 mg/m². Stem cells were infused on the following day. The 2-year OS, PFS and non-relapse mortality (NRM) rates were 35% (95% confidence interval (CI), 23-51%), 31% (95% CI, 21-48%) and 37% (95% CI, 23-50%), respectively. Acute NRM at 100 days was favorable at 12% (95% CI, 5-24%); however, the 2-year NRM was significantly higher for patients older than 40 years, 58% vs 20%, mainly due to GVHD.
Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. pkebriae@mdanderson.org
P
P
Kebriaei
T
T
Madden
X
X
Wang
P F
PF
Thall
C
C
Ledesma
M
M
de Lima
E J
EJ
Shpall
C
C
Hosing
M
M
Qazilbash
U
U
Popat
A
A
Alousi
Y
Y
Nieto
R E
RE
Champlin
R B
RB
Jones
B S
BS
Andersson
D000328:Adult; D000367:Age Factors; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D007262:Infusions, Intravenous; D008297:Male; D008558:Melphalan / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000517:prevention & control / Q000628:therapy*; D055502:Secondary Prevention; D016019:Survival Analysis; D013781:Texas; D019172:Transplantation Conditioning / Q000009:adverse effects; D014184:Transplantation, Homologous; D055815:Young Adult
D018906:Antineoplastic Agents, Alkylating; D019653:Myeloablative Agonists; D002066:Busulfan; D008558:Melphalan