Quantitative Assessment of Molecular Remission Following Autologous Stem Cell Transplantation Predicts Long Term Remission in Mantle Cell Lymphoma.

Mantle cell lymphoma (MCL) is characterized by a poor response to cytostatic therapy and a short survival with a median of less than 3 years. High-dose chemotherapy followed by autologous peripheral stem cell transplantation (ASCT) provides a potential curative option for the treatment of younger patients. The prognostic relevance of minimal residual disease (MRD) detection after intensive conventional treatment and high dose therapy has been proven for follicular lymphoma but is still under debate in MCL.

Aim of this study was the quantitative evaluation of MRD and the evaluation of its prognostic impact on progression free survival and long-term remission in patients with MCL after ASCT.

Quantitative Real-Time PCR for clonal IGH rearrangements (IGH-RQ-PCR) was performed in 29 patients with MCL treated with CHOP-like induction, stem-cell mobilisation with DexaBEAM. and subsequent ASCT. Quantitative MRD assessment was performed prior and during treatment as well as 3,6 and 12 months after PBSCT by IGH-RQ-PCR. 14/27 patients evaluable for MRD after ASCT achieved a complete clinical and molecular remission, whereas 13 patients had detectable MRD within the first year after ASCT. Molecular remission after ASCT was strongly predictive for improved outcome with a median PFS of 95 months in the MRD negative group compared to 21 months in the MRD positive group (p<0.0001). Overall survival differed significantly with 55.8 months in the MRD positive group, whereas median OS of the MRD negative group has not been reached (p<0.003). In multivariate analysis, molecular remission and bulky disease were independent prognostic factors for PFS (p=0.0007 and p=0.0210 respectively). Quantitative MRD measured in the stem cell products of 28 patients was not predictive for achieving molecular remission. We conclude that sequential quantitative monitoring of residual disease after ASCT is a powerful indicator for treatment outcome in MCL and defines subgroups of patients with a significantly different prognosis.