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Simonsson et al.
inhibit IL-2 induced killing of AML blasts and that histamine maintains this IL-2
induced killing despite increases in monocyte numbers.
AML patients have been treated with histamine dihydrochloride (0.3-0.7 mg
b.i.d.) and IL-2 (1 ug s.c. b.i.d.) in repeated courses of 21 days. Thirty-six patients
with AML in CR1 (n=24) and CR>1 (n=12) have been included. The courses of
histamine + IL-2 have been continued until relapse or until a CR duration of 24
months. Most patients treated in CR >1 have also received low-dose chemotherapy
(cytarabine and thioguanine) between the initial courses.
In CR1, median time to relapse has not been reached after a median follow-up
of 23 months. For patients in CR 2-4, median time to relapse is 21 months after a
median follow-up of 32 months. Eight of 11 évaluable patients have achieved a
longer remission compared with their own previous remission.
Although there were local inflammatory reactions, fever, musculoskeletal
discomfort, fatigue, short-lasting flush, headache, transient hypotension, and
tachycardia, this treatment did not seem to have an impact on the quality of life of
these patients. We conclude that treatment with IL-2 + histamine is safe and
feasible and gives promising clinical results in a phase II study. These results,
however, remain to be confirmed. We have therefore initiated a phase III study in
which IL-2 + histamine is compared with no treatment in AML in CR1 or CR >1.
The study has been initiated in the U.S., Canada, Australia, New Zealand, Israel,
and Europe.
The general conclusion is that we were unable to confirm a positive effect of
linomide in AML after autoBMT. This lack of efficacy may be due to inhibition of
NK and T cell activity by monocytes. Since histamine inhibits the effect of
monocytes on NK and T cells in vitro and based on a promising phase II study, we
have initiated a multinational study to evaluate the role of IL-2 combined with
histamine in prolonging leukemia-free survival in AML.
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