TNFα therapy activates human B-lymphoma cells in vivo and may protect myelopoiesis

In vitro TNF alpha induces proliferation and expression of predominantly type A TNF-receptors on B-lymphoma cells. In a pilot study we treated 2 patients with refractory B lymphomas with two courses of TNF alpha and consecutive aggressive chemotherapy (high dose Ara-C and mitoxantrone). TNF alpha was applied on days 1-4, chemotherapy on days 2-4 (TNF-AraM). The TNF-AraM therapy was repeated on day 43. Both patients responded to therapy. TNF alpha therapy induced expression of the 75 kD TNF receptor and the interleukin 2 receptor (CD25) and weakly the 55 kD TNF receptor on leukemic B lymphocytes. Interleukin 3, interleukin 6 and GM-CSF were induced and measured in the serum of patients. The mean time of severe granulocytopenia (less than 0.5/nl) was 9 days (range 8-10 days), the mean time of thrombocytopenia (less than 20/nl) was 5 days (range 2-6 days). In 7 patients, who were treated with high dose Ara-C and mitoxantrone (AraM) mean time of granulocytopenia (less than 0.5/nl) was 23 days (range 18-34 days), and of thrombocytopenia (less than 20/nl) was 13.3 (range 3-27 days). We conclude that TNF alpha can activate tumor B cells in vivo and may exhibit also myeloprotective effects when applied before aggressive chemotherapy.