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Long-Term Follow-Up of Indolent Lymphoma Patients Treated With High-Dose Sequential Chemotherapy and Autografting: Evidence That Durable Molecular and Clinical Remission Frequently Can Be Attained Only in Follicular Subtypes

From the U.O. Ematologia-Trapianto Midollo Osseo, Istituto Nazionale per Lo Studio e la Cura dei Tumori-Università di Milano, Milano; Dipartimento di Medicina ed Oncologia Sperimentale, Divisione Universitaria di Ematologia-Azienda Ospedaliera San Giovanni Battista; Servizio di Epidemiologia dei Tumori, Università di Torino, Turino; and Divisione di Ematologia, Università di Verona, Verona, Italy

Address reprint requests to Paolo Corradini, MD, Hematology, BMT Unit, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milano, Italy; e-mail: paolo.corradini{at}istitutotumori.mi.it

PURPOSE: To evaluate the prognostic relevance of molecular monitoring of minimal residual disease in indolent lymphomas receiving high-dose sequential chemotherapy and autografting.

PATIENTS, MATERIALS, AND METHODS: A polymerase chain reaction- (PCR-)based strategy was used to evaluate the presence of residual tumor cells in a panel of 70 indolent lymphoma patients: 40 with follicular (FCL), 14 with small lymphocytic (SLL), and 16 with mantle-cell (MCL) lymphomas. They were treated either with first-line (n = 61) or second-line (n = 9) therapy with an intensified high-dose chemotherapy program followed by peripheral-blood progenitor cells autografting. The Bcl-1, Bcl-2, and immunoglobulin gene rearrangements were used as lymphoma-specific markers. Overall, a molecular marker was obtained from the diagnostic tissue in 60 of 70 patients (86%).

RESULTS: The collection of PCR-negative cells and the achievement of posttransplantation molecular remission (MR) were common in patients with FCL subtype (54% and 70%, respectively), whereas they were not frequent among SLL and MCL (25% and 12.5%, respectively) patients. With a median molecular follow-up of 75 months, an 88% incidence of relapse was observed among patients never attaining MR. In contrast, relapse incidence was only 8% among patients attaining a durable MR (P < .005). At present, 26 patients (20 with FCL and six with non-FCL) are long-term survivors in absence of clinical and molecular disease.

CONCLUSION: Our results indicate that among indolent lymphomas, FCL and non-FCL subtypes show a significantly different behavior in terms of MR achievement, and MR after intensive chemotherapy and autografting is predictive for a prolonged disease-free survival, whereas persistent PCR positivity is associated with a high risk of relapse.

Supported in part by Associazione Italiana Ricerca sul Cancro and Compagnia di San Paolo Programma Oncologia.

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

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