Originally published as JCO Early Release 10.1200/JCO.2008.21.3116 on August 3 2009

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Google Scholar Articles by Andersen, N. S. Articles by Geisler, C. H. PubMed PubMed Citation Articles by Andersen, N. S. Articles by Geisler, C. H. Social Bookmarking                            What's this?

Pre-Emptive Treatment With Rituximab of Molecular Relapse After Autologous Stem Cell Transplantation in Mantle Cell Lymphoma

From the Department of Hematology, Rigshospitalet, Copenhagen; Department of Hematology, Aarhus University Hospital, Aarhus; Department of Hematology, Herlev University Hospital, Herlev, Denmark; Department of Hematology, Uppsala University Hospital, Uppsala; Department of Hematology, Sahlgrenska University Hospital, Gothenburg; Department of Hematology, Karolinska Institute, Stockholm; Department of Oncology, Jönköping Hospital, Jönköping; Department of Oncology, Lund University Hospital, Lund; Department of Medicine, Skövde Hospital, Skövde, Sweden; Department of Hematology, Helsinki University Central Hospital, Helsinki; Department of Radiation Sciences, Oncology, Umeå University, Umeå, Finland; Department of Oncology, Norwegian Radium Hospital, Oslo; and Department of Oncology, Haukeland University Hospital, Bergen, Norway.

Corresponding author: Niels S. Andersen, MD, PhD, Department of Hematology L-4041, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; e-mail: ns_andersen{at}msn.com.

Purpose Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell transplantation (ASCT).

Patients and Materials MCL patients enrolled onto the study, who had polymerase chain reaction (PCR) detectable molecular markers and underwent ASCT, were followed with serial PCR assessments of MRD in consecutive bone marrow and peripheral blood samples after ASCT. In case of molecular relapse with increasing MRD levels, patients were offered pre-emptive treatment with rituximab 375 mg/m² weekly for 4 weeks.

Results Of 160 MCL patients enrolled, 145 underwent ASCT, of whom 78 had a molecular marker. Of these, 74 were in complete remission (CR) and four had progressive disease after ASCT. Of the CR patients, 36 underwent a molecular relapse up to 6 years (mean, 18.5 months) after ASCT. Ten patients did not receive pre-emptive treatment mainly due to a simultaneous molecular and clinical relapse, while 26 patients underwent pre-emptive treatment leading to reinduction of molecular remission in 92%. Median molecular and clinical relapse-free survival after pre-emptive treatment were 1.5 and 3.7 years, respectively. Of the 38 patients who remain in molecular remission for now for a median of 3.3 years (range, 0.4 to 6.6 years), 33 are still in clinical CR.

Conclusion Molecular relapse may occur many years after ASCT in MCL, and PCR based pre-emptive treatment using rituximab is feasible, reinduce molecular remission, and may prevent clinical relapse.

Supported by grants from the Danish Cancer Society, The Nordic Cancer Union, The John and Birthe Meyer Foundation, and the Novo Nordisk Foundation.

Presented in part at the 49th Annual Meeting of the American Society of Hematology December 8-11, 2007, Atlanta, GA.

Written on behalf of the Nordic Lymphoma Group.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: ISRCTN87866680 [controlled-trials.com] .

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?