Outcome determinants for Transformed Indolent Lymphomas treated with or without Autologous Stem Cell Transplantation

INTRODUCTION: Transformation of indolent lymphomas (IL) to an aggressive histology (TIL) often results in a rapid clinical course, treatment refractoriness and shortened survival. Although rituximab-containing regimens (R-chemo) have become standard-of-care in CD20-positive TIL, the role of autologous stem-cell transplantation (ASCT) is still debated. The purpose of this study was to determine whether the outcome of TIL patients improved if they, at transformation, also received ASCT. Furthermore, we investigated the outcome of cases with histologically low- and high grade components diagnosed either simultaneously or after a period of overt indolent disease. We also analyzed, whether prior rituximab treatment during the indolent course of the disease affected outcome after transformation.

PATIENTS AND METHODS: Eighty-five patients (≤ 68 yrs) with histologically confirmed TIL were included. Five-year overall (OS) and progression-free survival (PFS) were calculated. Selected parameters were tested in a multivariate analysis. All analyses were conducted on three cohorts: (1) whole cohort ('all TIL'), (2) patients with co-existing evidence of both indolent and aggressive histology at diagnosis ('Composite/discordant TIL') and (3) patients transformed after prolonged prior indolent disease ('sequential TIL').

RESULTS: Fifty-four patients (64%) received ASCT consolidation and 31 (36%) did not. Within the 'all TIL' cohort, the 5-year OS and PFS for R-chemo+ASCT vs. R-chemo alone, were 67% vs. 48% (p=0.11) and 60% vs. 30% (p=0.02), respectively. Futhermore, in 'Composite/discordantTIL' R-chemo+ASCT showed no impact on OS (76% vs. 67%; p=0.66) or PFS (71% vs. 62%; p=0.54). Conversely, R-chemo+ASCT improved the outcome of 'sequential TIL' (OS 62% vs. 36%; p=0.07; PFS 53% vs. 6%; p=0.002), regardless of prior rituximab therapy. The beneficial effect of ASCT was significantly higher in patients who had not received rituximab at IL stage.

CONCLUSIONS: ASCT improved the outcome in sequential, but not composite/discordant TIL. The beneficial impact of ASCT was greater in patients, who were rituximab-naïve at transformation.