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Advanced Unfavorable Hodgkin Lymphoma

    Drug combinations described in this section:

    • ABVD: doxorubicin plus bleomycin plus vinblastine plus dacarbazine.
    • BEACOPP: bleomycin plus etoposide plus doxorubicin plus cyclophosphamide plus vincristine plus procarbazine plus prednisone.
    • CEC: cyclophosphamide plus lomustine plus vindesine plus melphalan plus prednisone plus epidoxorubicin plus vincristine plus procarbazine plus vinblastine plus bleomycin.
    • COPP/ABVD: cyclophosphamide plus vincristine plus procarbazine plus prednisone/doxorubicin plus bleomycin plus vinblastine plus dacarbazine.
    • MOPP: mechlorethamine plus vincristine plus procarbazine plus prednisone.
    • MOPP alternating with ABVD: mechlorethamine plus vincristine plus procarbazine plus prednisone alternating with doxorubicin plus bleomycin plus vinblastine plus dacarbazine.
    • MOPP/ABV hybrid: mechlorethamine plus vincristine plus procarbazine plus prednisone/doxorubicin plus bleomycin plus vinblastine.
    • Stanford V: doxorubicin plus vinblastine plus mechlorethamine plus etoposide plus vincristine plus bleomycin plus prednisone.

    Patients are designated as having advanced unfavorable Hodgkin lymphoma (HL) if they have clinical stage III or stage IV disease and four or more risk factors on the International Prognostic Index for HL, which corresponds to a freedom-from-progression at worse than 50% at 5 years with combination chemotherapy.[1]

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    ABVD therapy for 6 to 8 months is as effective as 12 months of MOPP alternating with ABVD, and both are superior to MOPP alone in terms of failure-free survival (FFS) (50% vs. 36% with a 14-year median follow-up; P = .03).[2,3][Level of evidence: 1iiA] The Intergroup trial comparing ABVD with MOPP/ABV hybrid showed equivalent efficacy in FFS and overall survival (OS), but increased toxic effects in the hybrid arm, especially from second malignancies.[4][Level of evidence: 1iiA]

    The German Hodgkin Lymphoma Study Group (HD9 trial) randomly assigned 1,201 patients with advanced-stage disease to COPP/ABVD, BEACOPP, or to increased-dose BEACOPP, with most patients receiving consolidative radiation therapy to sites of initial bulky disease (≥5 cm).[5] The 10-year OS rates from time of treatment were 75% for COPP/ABVD, 80% for BEACOPP, and 86% for increased-dose BEACOPP (P = .19 for the comparison of COPP/ABVD with BEACOPP, P = .005 for the comparison of BEACOPP with increased-dose BEACOPP, and P < .001 for the comparison of COPP/ABVD with increased-dose BEACOPP).[5][Level of evidence: 1iiA] The actuarial rate of secondary acute leukemias 10 years after diagnosis of HL was 0.4% for COPP/ABVD, 1.5% for BEACOPP, and 3.0% for increased-dose BEACOPP (P = .03).

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