Ifosfamide and VP-16213 combination chemotherapy combined with ablative chemotherapy and autologous marrow transplantation as salvage treatment for malignant lymphoma.

Eighteen patients with high-grade malignant lymphoma were treated with ifosfamide-VP16213 combinations after failing to respond completely or after relapsing on CHOP-like therapy. Responders to the salvage therapy were subsequently treated with ablative chemotherapy (BCNU, VP-16213, Ara-C and melfalan) and autografted. Of these 18 patients six were in relapse, six were partial responders and six failed CHOP-like therapy. There were two complete remissions and seven partial responses to the ifosfamide-VP-16213 combinations. Of them, eight patients were transplanted, together with one non-responder. Four of these nine patients were disease-free survivors 18-34 months after autografting. There were two early deaths: one before and one during the autografting procedure. Using one of the best salvage therapy combinations followed by high-dose chemotherapy and autografting is feasible. The results in this pilot study suggest that an appreciable number of patients may be cured by this procedure.

Interferon-gamma preferentially reduces memory/effector CD8 T lymphocytes in healthy subjects.

To evaluate the influence of interferon-gamma (IFN-gamma) on leukocyte dynamics, with a focus on naive and memory T cells, we studied 6 healthy subjects twice in a placebo-controlled trial: once after the administration of recombinant human IFN-gamma (rhIFN-gamma; 100 microg/m2 subcutaneously) and at least 4 weeks later, after the administration of saline solution. Additionally, we studied the expression of adhesion molecules on T lymphocytes after in vitro incubation of whole blood with rhIFN-gamma. IFN-gamma induced a significant depletion in the number of T lymphocytes (P < .05 vs control), which was more severe in the CD8+ cell subset than in the CD4+ T cell subset. The numbers of naive CD4+ T cells and memory CD4+ T cells were equally affected by IFN-gamma, whereas within the CD8+ T cell subset, memory/effector cells disappeared preferentially as compared with naive cells (P < .05 vs control). In addition, IFN-gamma induced a decrease in B cells, NK cells, and monocytes. After an initial increase, granulocyte counts decreased significantly as compared with controls. These effects appeared not to be caused by the minimal rise in plasma cortisol levels (P < .05 vs control). In vitro, IFN-gamma did not up-regulate the expression of CD11a, NKI L16, CD11b, LFA-3, or VLA-4. We conclude that the administration of a single dose of IFN-gamma to healthy subjects profoundly affects the numbers of several leukocyte subsets in the peripheral blood compartment.

Cloning of T lymphocytes from bronchoalveolar lavage fluid.

We have prepared T-cell clones from bronchoalveolar lavage fluid (BALF) from four healthy, nonsmoking persons and from four patients with allergic asthma. T cells were cloned by direct limiting dilution and with the use of a fluorescent activated cell sorter with an automated cell deposition unit. T-cell clones from the blood (PB) were prepared as well. The cloning efficiencies of T cells from BALF ranged from 3 to 40% and were lower than those obtained from PB T cells (18 to 72%). The cloning conditions generated CD4+ as well as CD8+ clones. The very late antigen-4, VLA-4, was more frequently expressed on CD4+ T-cell clones from BALF than from the blood (P < 0.05). CD8+ clones from BALF were more frequently VLA-1+ than those from blood (P < < 0.01). Mitogen- and monoclonal antibody-driven proliferation of CD4+ clones showed that BALF clones were well responsive to proliferation stimuli similar to those from the blood. Analysis of interleukin-4 production by 10 BALF and 10 PB clones showed large variations between individual CD4+ clones (BALF: range, < 100 to 700 pg/ml; PB: range, < 100 to 1,100 pg/ml), indicating the generation of different types of clones, which was also clear from analysis of interferon-gamma production. The analysis of properties of BALF T-cell clones and their regulation will improve insight into immunologic reactions in the lungs.