Abstract: Some embodiments of the methods and compositions provided herein include methods of reducing surgery-induced metastases in a subject with cancer following surgery to remove at least one solid tumor, comprising an NADPH oxidase inhibitor to said subject.

Abstract: The present invention provides methods of treating cancer in a subject, preventing or delaying relapse to a cancer in a subject in remission, prolonging remission from cancer, increasing survival, and decreasing or alleviating cancer symptoms comprising a) administering histamine dihydrochloride and an inhibitor of the Programmed cell Death protein 1 (PD-1)/Programmed Death Ligand 1 (PD-L1) or b) administering an agent that decreases reactive oxygen species (ROS) optionally, together with a histamine receptor agonist. The present invention also provides methods of predicting the efficacy of a cancer treatment based on a re-distribution of cytotoxic T cells, frequency of NK cells, or other biochemical changes, and related methods of preventing relapse to cancer and for prolonging remission from a cancer. Related kits and compositions are also provided.

Abstract: Some embodiments provided herein relate to methods and compositions for reducing the risk of relapse of a hyperproliferative disorder, such as acute myeloid leukemia (AML), in a subject in which the hyperproliferative cells of the subject exhibit a normal karyotype and/or in a subject who has been administered no more than one induction therapeutic course. Some such embodiments include the administration of a NOX2 inhibitor, such as histamine dihydrochloride (HDC), in combination with a cytokine, such as interleukin-2 (L-2).

Abstract: Some embodiments of the methods and compositions provided herein relate to the treatment and amelioration of metastatic tumors and to the prevention of distant metastasis. In some embodiments, a metastatic tumor, such as a melanoma, can be treated by reducing the activity of NOX2 in a cell of a subject. In some embodiments, the activity of NOX2 can be reduced by administering a NOX2 inhibitor, such as histamine dihydrochloride (HDC).

Abstract: Disclosed herein include methods of delaying and preventing acute myeloid leukemia (AML) relapse in patients with mutant nucleophosmin 1 (NPM1) by co-administration of histamine, or derivatives thereof, and interleukin-2 (IL-2). In some embodiments, an unexpected delay in and/or prevention of relapse results in a surprising increase in leukemia- free survival rate and overall survival rate.