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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2271-2278.
Prepublished online as a Blood First Edition Paper on December 6, 2005; DOI 10.1182/blood-2005-07-2845.
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Submitted July 18, 2005
Accepted October 12, 2005
Quantitative assessment of molecular remission following high-dose therapy with autologous stem cell transplantation predicts long term remission in mantle cell lymphoma
Christiane Pott*, Carsten Schrader, Stefan Gesk, Lana Harder, Markus Tiemann, Thorsten Raff, Monika Bruggemann, Matthias Ritgen, Benedikt Gahn, Michael Unterhalt, Martin Dreyling, Wolfgang Hiddemann, Reiner Siebert, Peter Dreger, and Michael Kneba
Second Medical Department, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Institute of Hematopathology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Department of Internal Medicine III, University of Munich, Grosshadern, Munich, Germany
Department of Medicine V, University of Heidelberg, Heidelberg, Germany
* Corresponding author; email: c.pott{at}med2.uni-kiel.de.
To evaluate the prognostic impact of minimal residual disease (MRD) quantitative Real-Time PCR of clonal IGH rearrangements was performed in 29 patients with mantle cell lymphoma (MCL) treated with high-dose radiochemotherapy and autologous stem cell transplantation (ASCT). 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 92 months in the MRD negative group compared to 21 months in the MRD positive group (p< 0.0001). Median overall survival (OS) was 44 months in the MRD positive group, and has not been reached in the MRD negative group (p< 0.003). In multivariate analysis, molecular remission and bulky disease were independent prognostic factors for PFS (p=0.001 and p=0.021 respectively). Whilst CHOP-like cytoreduction had only modest influence, ara-C-containing mobilization and myeloablative radiochemotherapy significantly reduced MRD. Quantitative MRD measured in the stem cell products of 27 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.
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