Treatment outcome and prognostic factors for relapse after high-dose chemotherapy and peripheral blood stem cell rescue for patients with poor risk high grade non-Hodgkin's lymphoma

The aim of the study was to determine treatment outcome and identify a part icularly high risk group in a consecutive series of 66 patients with poor p rognosis high grade lymphoma (NHL) treated with conventional induction chem otherapy followed by high-dose chemotherapy (HDCT) and peripheral blood ste m cells (PBSC) rescue. Fifty-one patients with intermediate grade NHL (Kiel ) and two or three adverse prognostic features as defined by the age-adjust ed International Prognostic Index (IPI) received induction treatment with 7 weeks of doxorubicin, cyclophosphamide, vincristine, bleomycin, etoposide, prednisolone and methotrexate (VAPEC-B) followed by three cycles of ifosfa mide/cytarabine. Fifteen patients with high grade Burkitt's and lymphoblast ic NHL received 11 weeks of VAPEC-B followed by three cycles of high-dose m ethotrexate. HDCT for all 66 patients consisted of busulphan/cyclophosphami de followed by autologous PBSC rescue. Thirty-one patients (47%) received H DCT in first complete remission (CR/CRu) and 34 patients (52%) in first par tial remission (PR) after conventional chemotherapy, Following HDCT, 42 pat ients (64%) were in CR/CRu, 19 patients (29%) in PR and one patient had pro gressive disease. There were four toxic deaths. After a median follow-up pe riod of 27 months (range 7-73) in 46 surviving patients, the actuarial 3-ye ar estimates of overall survival, event-free survival (EFS) and freedom fro m progression (FFP) were 67%, 65% and 70%, respectively. In univariate anal ysis, prognostic factors associated with reduced EFS were mediastinal bulk (P = 0.02), greater than or equal to 3 extra-nodal sites (P = 0.02), remiss ion status prior to HDCT (P = 0.05), low albumin (P = 0.08) and raised ESR (P = 0.09). No significant difference was observed between patients with in termediate or high grade NHL or between patients with two or three adverse IPI features. Multivariate analysis identified mediastinal bulk (P = 0.01), greater than or equal to 3 extra-nodal sites (P = 0.01) and low albumin (P = 0.03) as joint predictors of poor EFS. Remission status prior to HDCT wa s not found to be significantly associated with reduced EFS, FFP or surviva l, suggesting early introduction of HDCT may benefit patients with a PR. Ba sed on these three adverse features, three groups (0, 1 or greater than or equal to 2 features) could be identified with differing EFS, survival and f reedom from progression (FFP) rates at 3 years; 85%, 63% and 20%, respectiv ely for EFS, 84%, 64% and 25% for survival and 85%, 66% and 33%, respective ly for FFP. This prognostic model may identify patients with a particularly poor prognosis despite HDCT, who may benefit from other therapeutic approa ches.