Dose intensity of chemotherapy in patients with relapsed Hodgkin's lymphoma.
OBJECTIVE
High-dose chemotherapy (HDCT) followed by autologous stem-cell transplantation (PBSCT) has become the standard treatment for patients with relapsed Hodgkin's lymphoma (HL). The intensity of treatment needed is unclear. This European intergroup study evaluated the impact of sequential high-dose chemotherapy (SHDCT) before myeloablative therapy.


METHODS
Patients with histologically confirmed, relapsed HL were treated with two cycles of dexamethasone, cytarabine, and cisplatin, and those without disease progression were randomly assigned. In the standard arm (A), patients received myeloablative therapy with carmustine, BEAM (carmustine, etoposide, cytarabine, and melphalan) followed by PBSCT. Patients in the experimental arm (B) also received sequential cyclophosphamide, methotrexate, and etoposide in high-doses before BEAM. Freedom from treatment failure (FFTF) was the primary end point. Remission rates, overall survival (OS), and toxicity of treatment were secondary end points.


RESULTS
From a total of 284 patients included, 241 responding patients were randomly assigned after two cycles of dexamethasone, cytarabine, and cisplatinum. Patients treated in arm B had longer treatment duration and experienced more toxicity and protocol violations (P < .05). Mortality was similar in both arms (20% and 18%). With a median observation time of 42 months, there was no significant difference in terms of FFTF (P = .56) and OS (P = .82) between arms. FFTF at 3 years was 62% (95% CI, 56% to 68%) and OS was 80% (95% CI, 75% to 85%). Patients with stage IV, early relapse, multiple relapse, anemia, or B symptoms had a higher risk of recurrence (P < .001).


CONCLUSIONS
Compared with conventional high-dose chemotherapy, additional SHDCT is associated with more adverse effects and does not improve the prognosis of patients with relapsed HL.
University of Cologne, German Hodgkin Study Group, Köln, Germany.
Andreas
A
Josting
Horst
H
Müller
Peter
P
Borchmann
Joke W
JW
Baars
Bernd
B
Metzner
Hartmut
H
Döhner
Igor
I
Aurer
Lenka
L
Smardova
Thomas
T
Fischer
Dietger
D
Niederwieser
Kerstin
K
Schäfer-Eckart
Norbert
N
Schmitz
Anna
A
Sureda
Jan
J
Glossmann
Volker
V
Diehl
Daphne
D
DeJong
Martin-Leo
ML
Hansmann
John
J
Raemaekers
Andreas
A
Engert
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D006801:Humans; D053208:Kaplan-Meier Estimate; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D036102:Peripheral Blood Stem Cell Transplantation; D011379:Prognosis
D003561:Cytarabine; D005047:Etoposide; D003907:Dexamethasone; D003520:Cyclophosphamide; D002945:Cisplatin; D008727:Methotrexate