Autologous Stem Cell Transplant Followed by Low Dose Rituxan Maintenance in CR1 Is Effective for the Treatment of Mantle Cell Lymphoma.

Conventional chemotherapy is non-curative for mantle cell lymphoma (MCL). Although the addition of Rituxan has improved the outcome of these patients, many patients still relapsed and died of their disease. High dose chemotherapy followed by autologous stem cell transplant (ASCT) has been investigated but produced conflicting results, ranging from no demonstrable benefit to a 2-year event-free survival (EFS) of 77%. A recent randomized study compared ASCT with interferon-a maintenance and showed benefits in both the EFS and overall survival for patients in the ASCT study arm. The conflicting results are probably related to the use of different chemotherapeutic agents as conditioning regimens for the transplant and also to different post-transplant therapy.

In this study, we have chosen to induce patients with advanced MCL with R-CHOP and consolidate these patients with high dose single agent melphalan, a cytotoxic that has not been previously tested as a single agent in MCL. Since most patients relapsed within the first two years after transplant, low dose maintenance Rituxan therapy is given three-monthly during the first 2 years after ASCT. Following consent from the patients, 8 consecutive patients with advanced Stage III or IV MCL were treated. There were 5 male and 3 female, with a median age of 642 years (range 46–72 years). One patient had Stage III and the other 7 Stage IV diseases. All eight patients received remission + 2 courses of R-CHOP as induction chemotherapy. Autologous stem cells were harvested upon recovery from the last course of R-CHOP and ASCT carried out within 6 weeks from the last course of R-CHOP. High dose intravenous melphalan (200 mg/m2) was administered followed, 24 hours afterward, by the infusion of a minimum of 2 × 10⁶/kg of CD34+ autologous stem cells. Rituxan maintenance therapy was initiated at a dose of 375 mg/m2 given as a single infusion once every three months starting Day +100.

As of August 2006, with a median follow-up of 45.5 months from diagnosis (range 10–57 months) and 39 months from ASCT (range 4–52 months), seven patients are alive lymphoma-free, as defined by clinical and PET-CT examination. One patient died in CR of a myocardial infarction. Adverse effects were as expected from the high dose melphalan, except that delayed immunoglobulin reconstitution, as reported previously, was observed in all eight patients. Four of these hypogammaglobulinemic patients had recurrent infections (three with recurrent respiratory tract infection and one with a chronic diarrhea that was Vancomycin sensitive) and two required monthly intravenous immunoglobulin replacement. The result presented here is, therefore, extremely encouraging for a group of patients who normally have a very poor clinical outcome and warrants confirmation in larger multicenter study.