High dose sequential chemotherapy with autologous transplantation versus dose-dense chemotherapy MegaCEOP as first line treatment in poor-prognosis diffuse large cell lymphoma: an "Intergruppo Italiano Linfomi" randomized trial.
OBJECTIVE
Poor prognosis diffuse large cell lymphoma (DLCL) responds poorly to standard chemotherapy. Randomized studies comparing high-dose chemotherapy with autologous stem-cell transplantation (ASCT) against standard chemotherapy have produced conflicting results. Dose-dense chemotherapy with granulocyte colony-stimulating factor (G-CSF) support seems to hold promise. The purpose of this multicenter, randomized trial was to compare failure-free and overall survival in patients with poor prognosis DLCL treated with high-dose sequential (HDS) chemotherapy followed by ASCT or an outpatient dose-dense chemotherapy regimen (MegaCEOP).


METHODS
Between 1996 and 2001, 130 DLCL patients, aged < or = 60 years, with intermediate-high or high-risk disease, according to the International Prognostic Index score, and/or bone marrow involvement were enrolled. Sixty were randomized to HDS chemotherapy plus high-dose mitoxantrone and melphalan with ASCT (arm A) and 66 to the MegaCEOP regimen (6-8 courses of an escalated dose of cyclophosphamide and epirubicin plus vincristine and prednisone with G-CSF every 2-weeks) (arm B); 4 patients were considered ineligible.


RESULTS
The complete remission rate was 59% in arm A and 70% in arm B (p = 0.18). After a median follow-up of 78 months, the 6-year failure-free survival was 45% in arm A and 48% in arm B (hazard ratio = 1.15, 95% confidence intervals = 0.72-1.84, p = 0.56). The 5-year overall survival was 49% in arm A and 63% in arm B (hazard ratio = 1.67, 95% confidence interval = 0.98-2.85, p = 0.06). Two cases of secondary acute myeloid leukemia were observed after treatment in group A.


CONCLUSIONS
HDS and ASCT as initial therapy for patients with poor-prognosis DLCL does not provide a benefit over that of outpatient dose-dense MegaCEOP chemotherapy.
Vitolo
Umberto
U
Ematologia, Azienda Ospedaliera S. Giovanni Battista, Corso Bramante 88, 10126 Turin, Italy. uvitolo@molinette.piemonte.it
Liberati
Anna Marina
AM
Cabras
Maria Giuseppina
MG
Federico
Massimo
M
Angelucci
Emanuele
E
Baldini
Luca
L
Boccomini
Carola
C
Brugiatelli
Maura
M
Calvi
Roberta
R
Ciccone
Giovannino
G
Genua
Angelo
A
Deliliers
Giorgio Lambertenghi
GL
Levis
Alessandro
A
Parvis
Guido
G
Pavone
Enzo
E
Salvi
Flavia
F
Sborgia
Marco
M
Gallo
Eugenio
E
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D014182:Transplantation, Autologous; D014750:Vincristine / Q000008:administration & dosage
D000970:Antineoplastic Agents; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D014750:Vincristine; D003520:Cyclophosphamide; D008942:Mitoxantrone; D008558:Melphalan; D011241:Prednisone