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Older patients with Burkitt lymphoma/leukemia (BL) have inferior outcomes. Because cyclophosphamide is highly active in BL and can be dose-escalated without stem-cell rescue, we designed a short, cyclophosphamide-intensive regimen without anthracyclines for patients aged ≥ 30 with untreated, non-HIV-associated BL/atypical BL. Two cycles involving cyclophosphamide 1500 mg/m(2), vincristine, rituximab, prednisone, methotrexate 3 g/m(2), and intrathecal cytarabine were delivered 2 weeks apart, followed by intensification with high-dose cyclophosphamide (50 mg/kg/day for 4 days) and rituximab. Of 21 patients, median age 53 (range, 34-75), 71% had stage IV, 95% were high-risk and 29% had performance status 3-4. Response occurred in all evaluable patients post-cycle 2 and in 76% post-intensification. Five non-relapse deaths occurred (four before intensification). The estimated 1-year and 3-year event-free survival was 52%; 1-year and 3-year overall survival was 57%. Seventeen (81%) received intensification (median 30 days to intensification). Brief, anthracycline-sparing, intensive cyclophosphamide (BASIC) therapy yields durable remissions in poorer-risk BL/atypical BL.

Rituximab, an anti-CD20 monoclonal antibody used to treat B cell lymphoproliferative disorders and autoimmune diseases, kills cells through complement dependent cytotoxicity, antibody-dependent cellular toxicity and apoptosis. A mechanism of resistance to rituximab is upregulation of the complement regulatory proteins, CD59 and CD55. Paroxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic disorder caused by PIGA mutations that lead to a loss of all glycosylphospatidylinositol (GPI)-anchored proteins including, CD55 and CD59. We compared the cytotoxic activity of rituximab against a PNH B cell line, LD -, and the isogenic cell line LD - PIGA + in which GPI-anchor expression was restored by stable transfection of PIGA. The PNH cell line was more sensitive to rituximab-mediated killing than the LD - PIGA + cells. Biochemical disruption of GPI anchors with phosphatidylinositol specific phospholipase C (PIPLC), a phospholipase that cleaves GPI-anchored proteins, also increased rituximab-mediated killing. Thus, genetic and biochemical interruption of GPI anchor proteins augments sensitivity to rituximab.