Interleukin-2-induced increase of a monoclonal B-cell lymphocytosis. A novel in vivo interleukin-2 effect?
A 56-year-old man with refractory B-cell lymphocytic non-Hodgkin's lymphoma was treated in a Phase II study with interleukin-2 (IL-2) (Roussel-Uclaf, Romainville, France). The patient had involvement of multiple lymph nodes and medullary and peripheral blood (3.6 x 10(9) monoclonal CD19-positive [CD19+] B-lymphocytes/l). After a 5-day cycle of IL-2 treatment, an eightfold increase of the monoclonal CD19+ population was observed (27 x 10(9) monoclonal CD19+ cells). The lymphocytosis decreased dramatically during the second cycle (days 15 to 19) of IL-2 treatment, resulting in 6 x 10(9)/l peripheral lymphocytes, with 5.5 x 10(9) B-lymphocytes. As soon as day 20, peripheral B-cells again increased considerably, with 32 x 10(9) CD19+ cells/l at day 27. The CD19+ population remained monoclonal as assessed by kappa/lambda cell-surface phenotyping and kappa gene rearrangement evaluation. Kinetics of the monoclonal B-lymphocyte response to IL-2 paralleled the natural killer/lymphokine-activated killer and T-cell response, with a 4-day latency period, suggesting an indirect enhancing effect of IL-2. Before and during IL-2 treatment, peripheral B-lymphocytes never expressed detectable levels of the p55 IL-2 receptor. However, the p75 IL-2 receptor was expressed significantly in the IL-2-responsive monoclonal B-cell population. Tumor necrosis factor alpha, a known (in vitro) B-cell tumor growth factor, reached high serum levels during IL-2 treatment. Response evaluation at day 45 showed stability of the lymph node involvement and the marrow lymphocyte infiltrate. At day 45, peripheral B-cell lymphocytosis was 7.5 x 10(9)/l. To the knowledge of the authors, this is the first report of an in vivo IL-2-induced reversible increase of peripheral monoclonal B-cell lymphocytosis.
Tiberghien
P
P
Service d'Hematologie, Centre Hospitalier Universitaire J Minjoz, Besancon, France.
Racadot
E
E
Deschaseaux
M L
ML
Delain
M
M
Voillat
L
L
Billot
M
M
Flesch
M
M
Rozenbaum
A
A
Brandely
M
M
Cahn
J Y
JY
D001402:B-Lymphocytes / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000627:therapeutic use*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008218:Lymphocytosis / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000627:therapeutic use
D016207:Cytokines; D004273:DNA, Neoplasm; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins