Intravenous busulfan plus melphalan is a highly effective, well-tolerated preparative regimen for autologous stem cell transplantation in patients with advanced lymphoid malignancies.
We investigated the administration of intravenous (i.v.) busulfan (Bu) combined with melphalan (Mel) in patients with advanced lymphoid malignancies undergoing autologous stem cell transplantation. Bu 130 mg/m(2) was infused daily for 4 days, either as a fixed dose per body surface area (BSA), or to target an average daily area under the curve of 5000 μmol-min, determined by a test dose of i.v. Bu at 32 mg/m(2) given 48 hours prior to the high-dose regimen, followed by a rest day, followed by 2 daily doses of Mel at 70 mg/m(2). Stem cells were infused the following day. Eighty patients had i.v. Bu delivered per test dose guidance. The median daily systemic Bu exposure was 4867 μmol-min. One hundred two patients (Hodgkin lymphoma n = 49, non-Hodgkin lymphoma n = 12, multiple myeloma = 41) with a median age of 44 years (range: 19-65 years) were treated. The 2-year overall survival and progression-free survival rates were 85% and 57%, respectively, for patients with Hodgkin lymphoma, 67% and 64%, respectively, for patients with non-Hodgkin lymphoma, and 82% and 42%, respectively, for patients with multiple myeloma. The regimen was very well tolerated with treatment-related mortality at 100 days, 1 year, and 2 years of 1%, 3%, and 3%, respectively. Intravenous Bu-Mel was well tolerated. Disease control wa encouraging, and should be explored in larger phase II studies.
Kebriaei
Partow
P
Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. pkebriae@mdanderson.org
Madden
Timothy
T
Kazerooni
Reza
R
Wang
Xuemei
X
Thall
Peter F
PF
Ledesma
Celina
C
Nieto
Yago
Y
Shpall
Elizabeth J
EJ
Hosing
Chitra
C
Qazilbash
Muzaffar
M
Popat
Uday
U
Khouri
Issa
I
Champlin
Richard E
RE
Jones
Roy B
RB
Andersson
Borje S
BS
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000188:drug therapy / Q000628:therapy; D006801:Humans; D007262:Infusions, Intravenous; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000628:therapy; D008232:Lymphoproliferative Disorders / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000628:therapy; D012720:Severity of Illness Index; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects*; D014182:Transplantation, Autologous; D055815:Young Adult
D018906:Antineoplastic Agents, Alkylating; D002066:Busulfan; D008558:Melphalan