High-dose infusional gemcitabine combined with busulfan and melphalan with autologous stem-cell transplantation in patients with refractory lymphoid malignancies.
We developed a new high-dose combination of infusional gemcitabine with busulfan and melphalan for lymphoid tumors. Gemcitabine dose was escalated by extending infusions at a fixed rate of 10 mg/m(2)/min in sequential cohorts, in daily, 3-dose or 2-dose schedules. Each gemcitabine dose immediately preceded busulfan (adjusted targeting area under the curve 4,000 μM/min(-1)/day × 4 days) or melphalan (60 mg/m(2)/day × 2 days). We enrolled 133 patients (80 Hodgkin lymphoma [HL], 46 non-Hodgkin lymphoma [NHL], 7 myeloma), median 3 prior regimens; primary refractory disease in 63% HL/45% NHL and positron emission tomography positive tumors at transplantation in 50% patients. Two patients died from early posttransplantation infections. The major toxicity was mucositis. The daily and 3-dose schedules caused substantial cutaneous toxicity. In contrast, the 2-dose schedule was better tolerated, which allowed us to extend the infusions from 15 to 270 minutes. Pretransplantation values of C-reactive protein, B-type natriuretic peptide, ferritin, or haptoglobin did not correlate with toxicity. Overall response and complete response rates were 87%/62% (HL), 100%/69% B large-cell lymphoma (B-LCL), 66%/66% (T-NHL), and 71%/57% (myeloma). At median follow-up of 24 months (range, 3-63 months), the event-free/overall survival rates were 54%/72% (HL), 60%/89% (B-LCL), 70%/70% (T-NHL), and 43%/43% (myeloma). In conclusion, gemcitabine/busulfan/melphalan is a feasible regimen with substantial activity against a range of lymphoid malignancies. This regimen merits further evaluation in phase II and III trials.
Department of Stem-Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030. ynieto@mdanderson.org
Yago
Y
Nieto
Peter
P
Thall
Ben
B
Valdez
Borje
B
Andersson
Uday
U
Popat
Paolo
P
Anderlini
Elizabeth J
EJ
Shpall
Roland
R
Bassett
Amin
A
Alousi
Chitra
C
Hosing
Partow
P
Kebriaei
Muzaffar
M
Qazilbash
Erin
E
Frazier
Alison
A
Gulbis
Christina
C
Chancoco
Qaiser
Q
Bashir
Stefan
S
Ciurea
Issa
I
Khouri
Simrit
S
Parmar
Nina
N
Shah
Laura
L
Worth
Gabriela
G
Rondon
Richard
R
Champlin
Roy B
RB
Jones
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D007262:Infusions, Intravenous; D008223:Lymphoma / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D052016:Mucositis / Q000209:etiology / Q000401:mortality; D012008:Recurrence; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D002066:Busulfan; D008558:Melphalan; D000093542:Gemcitabine