Abstract
For more than 25 years, chemotherapy with the CHOP (cyclophosphamide, doxombicin, vincristine, and prednisone) regimen set the standard for the treatment of aggressive lymphomas. The recognition that treatment results depend mainly on patient selection led to the identification of pretreatment factors that allowed for the definition of prognostic subgroups based on the number of risk factors according to the International Prognostic Index (IPI). According to the IPI, ‘young’ patients are those up to 60 years of age. Young good-prognosis patients comprise the low and low-intermediate risk group (0 and 1 risk factor according to the age-adjusted IPI), and poor-prognosis patients comprise the high-intermediate and high-risk groups (≥2 risk factors). While some improvement has been achieved by the addition of etoposide to CHOP and by shortening the treatment interval from 3 to 2 weeks (CHOEP-14), the best results in young good-prognosis patients have been achieved with six cycles of CHOP-like chemotherapy in combination with the anti-CD20 antibody rituximab. With this approach, 2-ycar event-free survival (EFS) rates of >90% and overall survival (OS) of 95% have been achieved in the ‘very favorable’ prognostic subgroup of patients (patients without an IPI risk factor and no bulky disease), while further improvement is needed for those in the ‘less favorable’ subgroup (IPI score = 1 and/or bulky disease; 2-year EFS: 77%). The role of additional radiotherapy in this setting remains to be determined. For young poor-prognosis patients, the 5-ycar survival is around 50%, and progress has not been convincingly and specifically demonstrated in these patients. Ongoing studies will determine whether dose-dense conventional or high-dose chemotherapy regimens requiring stem-cell support in combination with rituximab will result in similar improvements for young poor-prognosis patients, as has been recently demonstrated for young patients with good-prognosis aggressive lymphoma.
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