Early stem cell transplantation for refractory acute leukemia after salvage therapy with high-dose etoposide and cyclophosphamide.
Primary refractory acute leukemia (AL) has a poor prognosis, although some patients can be salvaged with allogeneic stem cell transplantation (SCT). Induction of complete remission (CR) with conventional chemotherapy before SCT may improve outcome in this patient population. Between March 1991 and October 2003, 59 adults with primary refractory AL were treated with continuous-infusion etoposide (VP) 2.4 to 3.0 g/m(2) followed by cyclophosphamide (Cy) 6.0-7.2 g/m(2) intravenously over 3 to 4 days with the intention of proceeding to SCT in CR1. Forty-two patients had acute myelogenous leukemia (AML), 13 patients had acute lymphoblastic leukemia (ALL), and 4 patients had acute biphenotypic leukemia. The most frequent nonhematologic toxicities were oral mucosal, gastrointestinal, and hepatic toxicities (44%, 20%, and 15% of patients, respectively). Thirty-two (57%) of 56 evaluable patients entered CR1 with a median time to platelet and neutrophil recovery of 22 and 26 days, respectively. CR1 rates were similar in AML (54%) and ALL/acute biphenotypic leukemia (67%; P = .52), and analysis of baseline characteristics did not reveal any predictors of response to VP/Cy. Twenty-nine of 32 CR1 patients subsequently underwent SCT (24 allogeneic and 5 autologous). Estimated 5-year event-free survival (EFS) and overall survival for the entire cohort are 23% and 26%, respectively. In the allogeneic SCT group, 5-year EFS was 52% for AML patients and 14% for ALL patients (P = .04), and only male sex was predictive of a favorable outcome (P = .03). VP/Cy is able to induce CR1 in most patients with primary refractory AL with an acceptable toxicity profile. Subsequent allogeneic SCT can lead to long-term EFS in a significant proportion of patients.
The Leukemia/Bone Marrow Transplantation Program of British Columbia, Vancouver, British Columbia, Canada.
Asha
A
Johny
Kevin W
KW
Song
Stephen H
SH
Nantel
Julye C
JC
Lavoie
Cynthia L
CL
Toze
Donna E
DE
Hogge
Donna L
DL
Forrest
Heather J
HJ
Sutherland
Alan
A
Le
Janet Y
JY
Nitta
Michael J
MJ
Barnett
Clayton A
CA
Smith
John D
JD
Shepherd
Thomas J
TJ
Nevill
D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007938:Leukemia / Q000150:complications / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000401:mortality*; D033581:Stem Cell Transplantation / Q000401:mortality; D015996:Survival Rate
D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D003520:Cyclophosphamide