Long-term survival after autologous bone marrow transplantation for follicular lymphoma in first remission

Abstract

The role of autologous stem cell transplantation (ASCT) in the treatment of follicular lymphoma is still being defined in the era of antibody therapy. Here we report the long-term 12-year clinical outcomes of patients treated with autologous bone marrow transplantation (ABMT) for follicular non-Hodgkin's lymphoma (NHL) in first remission. Between 1988 and 1993, advanced-stage follicular NHL patients in need of initial therapy were enrolled in 2 consecutive prospective treatment trials of either standard-dose CHOP induction (83 patients) or high-dose CHOP plus granulocyte-colony stimulating factor (G-CSF) (20 patients). Patients who achieved an adequate remission with induction therapy underwent conditioning with cyclophosphamide and total body irradiation (TBI) followed by ABMT in first remission using bone marrow (BM) purged in vitro with anti-B cell monoclonal antibodies and rabbit complement (96 patients). At 12-year follow-up, 61% of the patients are alive and 43% remain in continuing complete remission. The only predictors of decreased progression-free survival proved to be histologic BM involvement at time of harvest (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.3-3.9, P<.004) and PCR detectable disease in the BM product after purging (HR 4.18, 95% CI 1.99-8.8, P=.0002). No significant predictors of overall survival were identified. These results at 12-year follow-up suggest that a subset of follicular lymphoma patients can experience prolonged survival with ABMT in first remission.

Figures

Figure 1

A. Overall Survival: At a median follow-up of 12 years, 61% (95% CI 49.5-70.1) of patients are alive. B: Progression-Free Survival: At a median follow-up of 12 years, 43% (95% CI 32.3-52.7%) of patients remain in ongoing complete remission.

Figure 1

A. Overall Survival: At a median follow-up of 12 years, 61% (95% CI 49.5-70.1) of patients are alive. B: Progression-Free Survival: At a median follow-up of 12 years, 43% (95% CI 32.3-52.7%) of patients remain in ongoing complete remission.

Figure 2. Cumulative Incidence of Relapse

The cumulative incidence of relapse, with death in remission taken as a competing risk, was 37% at 5 years and 47% at 10 and 15 years.

Figure 3. Cumulative Incidence of Second Malignancy

The cumulative incidence of second malignancy, with death without second malignancy taken as a competing risk, was 16% at 10 years and 38% at 15 years.

Figure 4. PCR Detectable Disease After Purging Predicts PFS

12 year PFS was 66.7% (95% CI 46.9-80.5; n=30) for those patients whose post-purging bone marrow was negative by PCR, compared to 26.3% (95% CI 13.6-40.9%; n=40) for those with positive PCR (p = 0.001 log-rank test). No effect was observed on OS (76.7% for PCR negative and 50.7% for PCR positive, p = 0.08 log-rank test).