Post-consolidation immunotherapy with histamine dihydrochloride and interleukin-2 in AML.
The initial chemotherapy in acute myeloid leukaemia (AML) comprises a first phase of induction and a second phase of consolidation. In the majority of patients, the induction treatment leads to complete remission (CR), defined as microscopic disappearance of leukaemic disease along with the return of normal haematopoiesis. However, despite the introduction of more efficacious consolidation regimens, a worryingly large proportion of AML patients in CR will subsequently experience relapses with poor prospects of long-term survival. A relapse is assumed to be the result of expansion of residual leukaemic cells that have escaped the initial chemotherapy. The anti-leukaemic functions of T cells and natural killer (NK) cells has formed the background to the use of interleukin-2 (IL-2), a T- and NK cell-activating cytokine, with the aim to eliminate residual leukaemia and hence reduce the relapse rate in AML, but the clinical trials using IL-2 monotherapy have yielded disappointment. A recent phase III study has demonstrated that post-consolidation treatment with the combination of histamine dihydrochloride (HDC) and IL-2 significantly prevents relapse in AML patients. Here we account for the preclinical background to the use of HDC/IL-2 in AML along with a review of clinical results.
Romero
A I
AI
Department of Infectious Diseases, University of Gothenburg, S-41346 Gothenburg, Sweden.
Thorén
F B
FB
Aurelius
J
J
Askarieh
G
G
Brune
M
M
Hellstrand
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006632:Histamine / Q000627:therapeutic use*; D017442:Histamine Agonists / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D017442:Histamine Agonists; D007376:Interleukin-2; D006632:Histamine