Quality of life-adjusted survival analysis of high-dose therapy with autologous bone marrow transplantation versus sequential chemotherapy for patients with aggressive lymphoma in first complete remission

Evaluating high-dose therapy (HDT) with autologous stem cell transplantatio n (ASCT) in term of both duration and quality of life (QOL) presents major interests for patients with non-Hodgkin lymphoma. The quality-adjusted time without symptom and toxicity (Q-TWIST) methodology was applied to the LNH8 7-2 trial comparing HDT with ASCT versus sequential chemotherapy in 541 pat ients in first complete remission (CR), Overall survival (OS) and disease-f ree survival (DFS) curves were used to estimate duration of 4 health states : acute short-term toxicity (Tox1), secondary toxicity (Tox2), time without symptom and toxicity (TWIST), and relapse (Rel). Areas under survival curv es (AUC) were retrospectively weighted according to QOL coefficients. HDT i ncreased, but not significantly, TWIST (+2.4 months in AUG, P = .17) and de creased Rel (-3 months, P < .01), Survival estimates did not differ between the 2 treatments (AUC 47.7 months for OS, 39.7 months for DFS), High-risk patients treated by HDT versus chemotherapy had a significant benefit in DF S (AUC 28.8 versus 24.9 months, P < .01) but not in OS (AUC 37.3 versus 36 months, P = .27). Sensitivity analysis, performed by varying QOL coefficien ts, demonstrated significant quality-adjusted survival gain in high-risk pa tients treated by HDT. In low-risk patients, a diagram provided an aid to c linical decisionmaking. This analysis supports the use of HDT in these pati ents with adverse prognostic factors in the first CR, even after adjusting for QOL using the Q-TWIST method. (C) 2000 by The American Society of Hemat ology.