High-dose chemotherapy and autologous peripheral blood progenitor cell transplant for the treatment of Hodgkin's disease.
This paper evaluates a comprehensive strategy of chemotherapy mobilization of peripheral blood progenitor cells (PBPCs) followed by high-dose chemotherapy for the treatment of refractory or relapsed Hodgkin's disease (HD). Patients with relapsed or refractory HD were enrolled to receive cyclophosphamide, etoposide +/- cisplatin (CE +/- P) and rhG-CSF mobilization of PBPCs. Patients achieving < or = 2.5 x 10(6) CD34+ cells/kg following initial mobilization were eligible to receive a second course of CE +/- P. Unmanipulated PBPCs alone were infused following administration of high-dose carmustine, etoposide, cytarabine arabinoside and cyclophosphamide (BEAC). Thirty-eight consecutive patients with relapsed or refractory HD were initially enrolled to receive CE +/- P. Analysis was performed on an intent-to-treat basis. A median of 6.4 x 10(6) CD34+ cells/kg (range 0.66-62.3) were collected with a median of 3 (range 2-9) leukaphereses. Twenty-eight of 38 (74%) patients achieved > or = 2.5 x 10(6) CD34+ cells/kg. Analysis of variables potentially effecting mobilization of CD34+ cells revealed that only the amount of prior chemotherapy statistically influenced collecting CD34+ cells (P = 0.005). Two of six patients undergoing a second mobilization procedure achieved > or = 2.5 x 10(6) CD34+ cells/kg for a total of 30 patients eligible to proceed with high-dose BEAC. The 3-year Kaplan-Meier estimate of overall survival (OS) and progression-free survival (PFS) for all 38 patients is 65 and 53%, respectively. The 3-year OS and PFS for the 28 patients receiving BEAC is 77 and 64% respectively vs 33 and 30% for the 10 patients not receiving BEAC. The strategy of CE +/- P and BEAC was well tolerated with a 100-day treatment-related mortality of 3.6%. All patients experienced rapid and sustained hematologic recovery with PBPCs alone. The median time to an ANC > or = 5 x 10(9)/1 and platelet transfusion independence was 10 days. Although development of better strategies to mobilize PBPCs may benefit additional patients, currently the best strategy to collect PBPCs is early before patients have received extensive chemotherapy treatment. Collection of PBPCs immediately following initial relapse or induction failure using CE +/- P for PBPC mobilization allows sufficient PBPCs to be collected in greater than 90% of patients. Treatment of refractory or relapsed HD utilizing a strategy of CE +/- P PBPC mobilization for hematopoietic reconstitution following high-dose BEAC is associated with acceptable toxicity and rapid engraftment. A 3-year PFS greater than 60% can be achieved in the community hospital setting.
Weaver
C H
CH
Clinical Trials Division of Response Technologies, Inc, Memphis, TN 38117, USA.
Schwartzberg
L
L
Li
W
W
Hazelton
B
B
West
W
W
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D015925:Cryopreservation; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000628:therapy*; D006801:Humans; D007937:Leukapheresis; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D014182:Transplantation, Autologous
D011994:Recombinant Proteins; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D003520:Cyclophosphamide; D002945:Cisplatin; D002330:Carmustine