Rituximab-augmented myeloablation for first-line autologous stem cell transplantation for mantle cell lymphoma: effects on molecular response and clinical outcome.

BACKGROUND AND OBJECTIVES: Autologous stem cell transplantation (ASCT) is effective in mantle cell lymphoma (MCL). We investigated whether incorporation of rituximab into the high-dose regimen might further improve the results of ASCT in patients with MCL. DESIGN AND METHODS: In a prospective phase II study, patients with newly diagnosed MCL were treated with a sequential dose-escalating therapy comprising standard chemotherapy for remission induction, intensive ara-C-containing chemotherapy for mobilization of stem cells, and myeloablative therapy followed by ASCT. The myeloablative regimen consisted of total body irradiation and high-dose cyclophosphamide supplemented with two doses (375 mg/m3) of rituximab. Outcome parameters (toxicity, clinical and molecular response as assessed by allele-specific IGH real-time quantitative polymerase chain reaction (RQ-PCR), event-free survival, and overall survival) were compared with those of 34 historical controls treated identically but without rituximab. RESULTS: Thirty-four patients were accrued. Whereas engraftment, toxicity and clinical response were not different from those in controls, event-free survival was significantly increased with rituximab (not reached vs. 43 months; hazard ratio 0.38; p=0.036). This was associated with a trend for a superior molecular response rate in 11 study vs. 10 control patients with a marker available (73% vs. 30%, p=0.086) despite similar levels of lymphoma contamination of the stem cell inocula infused. INTERPRETATION AND CONCLUSIONS: Incorporation of two standard doses of rituximab into the myeloablative regimen might improve outcome of up front ASCT for MCL, allowing long-term disease control to an extent previously not reached in this disease.

Relapse in common lymphoma subtypes: salvage treatment options for follicular lymphoma, diffuse large cell lymphoma and Hodgkin disease.

Over the last decade diagnostic techniques such as immunophenotyping as well as cytogenetic and molecular profiling gave new insights into the pathogenesis of malignant lymphoma and helped to establish the WHO classification. The recognition of well-defined biological entities with distinct response and relapse patterns led to the development of more specific treatment strategies for individual lymphoma subtypes. New treatment modalities such as the monoclonal antibody rituximab have improved the results of first-line treatment of patients with certain B-cell lymphoma subtypes substantially. Furthermore, new prognostic factors were described for different lymphoma entities leading to further differentiation of treatment. As a consequence, the quality of relapse after first-line therapy has changed and treatment strategies for relapsed disease need to be redefined. This review summarises current salvage treatment options for common lymphoma subtypes taking into account variables which should be considered before an individual patient is treated. We focus on follicular lymphoma, diffuse large B-cell lymphoma and Hodgkin disease since these are most frequent and evidence-based salvage strategies are beginning to emerge.