MYELOABLATIVE THERAPY WITH BLOOD STEM-CELL TRANSPLANTATION IS EFFECTIVE IN MANTLE CELL LYMPHOMA

Long-term disease-free survival following conventional cytotoxic thera py is extremely rare in patients with advanced-stage mantle cell lymph oma (MCL). High-dose conditioning therapy consisting of hyperfractiona ted total body irradiation (TBI, 14.4 Gy) and cyclophosphamide (200 mg /kg) was therefore offered to 13 patients (four females/nine males) wi th advanced-stage MCL. The patients were relatively young with a media n age of 49 years (range 30-60). High-dose cytarabine and mitoxantrone with granulocyte colony-stimulating factor (G-CSF) support were given for second-line therapy and mobilization of peripheral blood stem cel ls (PBSC). During cytokine-stimulated marrow recovery, a median of two leukaphereses (range 1-4) were performed. Using direct immunofluoresc ence analysis including two-color staining, the proportion of CD19(+) B cells and CD34(+)/CD19(+) B lymphoid progenitor cells was found to b e extremely low with quantities below detection limit in approximately 50% of the autografts. At the time of autografting, nine patients (pt s) were in first partial (five pts) or complete (four pts) remission, while four patients had achieved a second complete remission. Followin g myeloablative therapy a median number of 7.5 x 10(6) CD34(+) cells/k g were autografted. The median time for neutrophil (greater than or eq ual to 0.5 x 10(9)/l) and platelet recovery (greater than or equal to 20 x 10(9)/l) was 13 and 10 days, respectively. Hematological recovery was delayed in a patient who received 5.8 x 10(6) positively selected CD34(+) cells/kg. There was one toxic death 17 days post-transplantat ion because of overwhelming interstitial pneumonia. Two patients with a history of previous treatment failure relapsed 10 and 11 months post -transplantation, respectively, at sites of previous disease. Ten pati ents are disease-free with a median follow-up time of 18 months (range 10-47). The results presented here suggest that PBSC-supported high-d ose therapy including TBI may provide long-term disease-free survival for patients with advanced-stage mantle cell lymphoma.