Nov 16, 2006 - spectively comparing for each patient the event-free survival (EFS) after ASCT with the duration ... During their clinical course, indolent lymphoma patients are exposed to multiple .... phase (eg, maintenance therapy, change in chemother- ..... upfront with high-dose sequential chemotherapy and auto- graft.
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High-Dose Therapy and Autologous Stem-Cell Transplantation Can Improve Event-Free Survival for Indolent Lymphoma A Study Using Patients As Their Own Controls
Ste´phane Vignot, MD Nicolas Mounier, MD Je´roˆ me Larghero, PharmD Pauline Brice, MD Laurent Quero, MD Ce´dric de Bazelaire, MD Marjan Ertault, MD Josette Brie`re, MD Isabelle Madelaine, PharmD Christian Gisselbrecht, MD
BACKGROUND. High-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) remain controversial for indolent lymphoma patients.
METHODS. The study was designed to evaluate the benefit of this strategy by retrospectively comparing for each patient the event-free survival (EFS) after ASCT with the duration of the disease phase just before the phase including ASCT (ie, the last qualifying phase, LQP).
RESULTS. A total of 109 indolent lymphoma (mostly follicular lymphoma) patients were treated with HDT and ASCT. Before ASCT, patients experienced a median of 2 disease phases (range, 1–4). After a median 5-year follow-up from ASCT, overall survival was 67% and EFS was 43%. When each of the 92 patients experiencing recurrence was taken as her/his own control, EFS was longer after ASCT than the
Institut Universitaire d’Hematologie, INSERM U728, H^opital Saint-Louis, Paris, France.
duration of LQP (62%, P < .01). During LQP, 86 patients (93%) experienced recurrence in less than 5 years, compared with only 58 (63%) who experienced recurrence in the 5 years after ASCT (P 8 g/dL and a platelet count >20 G/L.
Statistical Analyses EFS was measured from the date of ASCT to that of disease progression, recurrence, or death from any cause. Overall survival (OS) was measured from the date of ASCT to death from any cause. The primary endpoint of the study was EFS. OS and EFS were established using the Kaplan-Meier method and compared using the log-rank test. The clinical course was studied considering disease phases. A disease phase was defined by any tumor progression after the achievement of CR, CRu, or PR. The number of phases was different from the number of chemotherapy regimens recorded because patients could receive several different chemotherapy regimens during the same disease phase (eg, maintenance therapy, change in chemother-
apy due to toxicity or nonresponding patient, or physician’s decision). For recurring patients, the duration of LQP and EFS after ASCT were compared using the patient as her/his own control by the paired Wilcoxon test. This approach is illustrated in Figure 1. If a patient had not experienced recurrence at the stopping date and if the follow-up from ASCT was longer than the duration of LQP, the impact of ASCT on EFS was considered as positive for that patient. Patients who had not experienced recurrence and whose follow-up after ASCT was shorter than the duration of LQP were censored. Differences between the results of comparative tests were considered significant if the 2-sided P-value was
