Failure of a single cycle of high dose cyclophosphamide followed by intensive myeloablative therapy and autologous stem cell transplantation to improve outcome in relapsed disease.
BACKGROUND
This study attempted to determine the use of a single cycle of high dose cyclophosphamide (60 mg/kg/day x 2) with (N = 16) and without granulocyte macrophage colony stimulating factor (GM-CSF) (N = 12) followed by intensive treatment and autologous stem cell transplantation (ASCT) in patients with relapsed disease.


METHODS
Ten patients with multiple myeloma, eight with non-Hodgkin's lymphoma, three with Hodgkin's disease, six with breast cancer, and one with ovarian cancer were studied. Eighteen patients were in resistant relapse (RR) and 10 had sensitive relapses (SRs). All patients had marrow involvement with tumor and had received extensive prior therapy.


RESULTS
When responses were assessed just before undergoing ASCT, none of the patients achieved a complete response (CR). Overall, 17 of 28 patients (61%) achieved a partial response (PR). Seven of 18 patients with RR achieved PR (39%). All 10 patients with SR achieved a PR. There were three early deaths. Sixteen patients underwent peripheral blood stem cell (PBSC) collection. Ten of 16 patients received cyclophosphamide plus GM-CSF, and 6 received cyclophosphamide alone. In patients treated with cyclophosphamide plus GM-CSF and cyclophosphamide alone, a median of 5.52 x 10(6) CD34+ cells/kg (range, 0.26-30.49) and 5.72 x 10(6) (range, 1.25-15.66) were collected, respectively. There was no apparent improvement in collection efficiency with GM-CSF. Twenty-two of 28 patients proceeded to ASCT irrespective of response, a median of 45 days (range, 21-203 days) after cyclophosphamide administration. After transplantation, 11 achieved a CR (50%) and 6 a PR (27%). To date, eight patients are alive (median, 679 days; range, 215-1190 days) and five remain in CR more than 6 months (median, 321 days; range, 215-1190 days). All eight surviving patients achieved a PR after high dose cyclophosphamide.


CONCLUSIONS
High dose cyclophosphamide reduced the tumor burden by at least 50% in all patients with sensitive disease and in 39% of patients with refractory disease. However, only 5 of 22 patients (23%) remained in CR after ASCT, and all had sensitive disease before the administration of cyclophosphamide. These data suggest that high dose cyclophosphamide followed by intensive treatment and ABMT does not improve the fraction of long term disease free survivors in patients with refractory disease. Future trials would probably be required to demonstrate the utility of intensive treatment in patients with responsive relapse.
Demirer
T
T
Fred Hutchinson Cancer Research Center, University of Washington, Seattle 98104.
Buckner
C D
CD
Lilleby
K
K
Weaver
C
C
Longin
K
K
Appelbaum
F R
FR
Bensinger
W I
WI
D000328:Adult; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006689:Hodgkin Disease / Q000628:therapy; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy; D009369:Neoplasms / Q000628:therapy*; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous
D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide