High-Dose Therapy and Autologous Stem Cell Transplant (HD-ASCT) for Transformed Non-Hodgkin Lymphoma (NHL) In the Rituximab Era

The transformation of indolent non-Hodgkin's lymphoma (NHL) to a more aggressive histology remains a therapeutic challenge. For younger patients with a favorable performance status, high-dose therapy and autologous stem cell transplantation (HD-ASCT) results in a prolonged progression-free survival (PFS) in a substantial subset, based upon retrospective single and multi-institutional experiences. Rituximab improves PFS and overall survival (OS) in both follicular and aggressive NHL when combined with chemotherapy. However, the impact of prior rituximab on outcome of HD-ASCT for transformed NHL has not been elucidated.

We therefore analyzed consecutive patients with indolent NHL (including follicular lymphoma and marginal zone lymphoma) who developed histologically confirmed transformation to diffuse large B-cell lymphoma (DLBCL) and subsequently underwent HD-ASCT at the University of Rochester Medical Center between 1998 – 2009. Patients who transformed within 6 months of the diagnosis of indolent lymphoma were excluded from the study. Progression free survival (PFS) was defined as time from HD-ASCT to date of disease relapse, progression, or death due to any cause. Kaplan-Meier survival curves were estimated, and differences in PFS between those who received rituximab prior to transformation versus those who were rituximab-naïve at transformation were assessed using the log-rank test.

19 patients were identified, (10 female) who received rituximab-containing therapy at transformation. The median age at HD-ASCT was 59 years (range 40–66). Patients were treated with a median of 3 (range 1–9) chemotherapy regimens prior to HD-ASCT. Median time from the diagnosis of indolent lymphoma to transformation was 55 months (range 8–276). Conditioning regimens at HD-ASCT were BEAM (N=15), BEAC (N=1) and Cy/TBI (N=3). With a median follow-up of 47 months, the 2-year PFS was 58% and the 2-year OS was 84%. There were no treatment-related mortalities. Seven patients relapsed after HD-ASCT (2 with indolent histologies and 5 with DLBCL); 3 of these patients have died. Two additional patients have died of myelodysplastic syndrome-acute myeloid leukemia after HD-ASCT. Eight patients did not receive rituximab for indolent disease prior to transformation; this group had a significantly better PFS at 2 years (86% vs 36%, p = 0.049) compared to 11 patients who were treated with rituximab for indolent disease prior to ASCT. The patients who did not receive rituxmiab prior to ASCT had similar characteristics to patients who received rituximab, except that the time from indolent diagnosis to transformation was longer in the rituximab-naïve group (90 months vs 39 months).

HD-ASCT remains an effective therapeutic option for transformed NHL in the rituximab era. However, transformed patients exposed to rituximab prior to HD-ASCT appear to have inferior outcomes, similar to the experience of patients with de novo NHL treated with rituximab prior to HD-ASCT in the recently reported CORAL study (JCO, published online ahead of print July 26, 2010). Patients who transform after rituximab-containing therapy may represent a higher risk group of patients with a unique biology, who may benefit from novel conditioning and maintenance regimens in the setting of HD-ASCT.

No relevant conflicts of interest to declare.