Remission maintenance therapy with histamine and interleukin‐2 in acute myelogenous leukaemia

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Abstract
Peripheral blasts recovered from patients with acute myelogenous leukaemia (AML) were efficiently lysed by interleukin‐2 (IL‐2)‐activated heterologous natural killer (NK) cells in vitro. The IL‐2‐induced killing of AML blasts was inhibited by monocytes, recovered from peripheral blood by centrifugal elutriation. Histamine, of concentrations within the micromolar range, abrogated the monocyte‐induced inhibition of NK‐cells; thereby, histamine and IL‐2 synergistically induced NK‐cell‐mediated killing of AML blasts. The effect of histamine was apparently mediated by H2‐type histamine receptors (H2R), since the H2R antagonist ranitidine completely blocked the response.Based on these in vitro findings, seven patients with AML in first (n=2), second (n=3) or third (n=2) complete remission (CR) were given home therapy with interleukin‐2 (IL‐2; 0.9×106 IU×2 s.c.) and histamine (0.4–0.7 mg×2 s.c.) in cycles of 21 d, separated by 6‐week intervals. The patients also received treatment with low‐dose cytarabine and thioguanine between cycles of histamine/IL‐2. Toxicity was moderate and included local reactions to IL‐2 at the site of injection and short‐lasting flush, hypotension, and headache to histamine. The addition of histamine to treatment with IL‐2 significantly enhanced the accumulation of CD25+ T cells in peripheral blood as compared to treatment with IL‐2 alone (Pin vitro, and (ii) histamine/IL‐2 is a safe and feasible approach to immunotherapy of AML which merits further investigation.

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