# Histamine dihydrochloride and low-dose interleukin-2 in an emerging landscape of relapse prevention in acute myeloid leukemia

**Authors:** Malin S. Nilsson, Anna Martner, Lovisa Wennström, Markus Hansson, Fredrik B. Thorén, Kristoffer Hellstrand

PMC · DOI: 10.1177/20406207251351086 · 2025-06-28

## TL;DR

This paper reviews effective strategies to prevent relapse in acute myeloid leukemia, focusing on a promising immunotherapy combination.

## Contribution

The paper highlights histamine dihydrochloride and low-dose interleukin-2 as a novel relapse prevention strategy in AML.

## Key findings

- HDC/IL-2 immunotherapy shows promise for younger AML patients in maintaining remission.
- FLT3-mutated AML patients benefit from midostaurin or quizartinib during remission maintenance.
- Oral azacitidine is effective for older AML patients in preventing relapse.

## Abstract

Effective strategies to maintain complete remission in adults with acute myeloid leukemia (AML) are critically needed. Early clinical trials aimed at preventing relapse in the postconsolidation phase explored prolonged chemotherapy, single-agent immunotherapy, and hybrid chemo-immunotherapy, but none of these approaches produced practice-changing results. More recent trials have identified efficacious remission maintenance strategies, including (1) midostaurin or quizartinib for patients with FLT3-mutated AML, (2) oral azacitidine for older AML patients, and (3) immunotherapy with histamine dihydrochloride and low-dose interleukin-2 (HDC/IL-2) for younger patients. In this review, we examine key phase III trial and follow-up study results for approved remission maintenance therapies, with a particular focus on HDC/IL-2. We discuss clinical efficacy in relation to patient age and anti-leukemic immunity as well as leukemic cell chemosensitivity, chromosomal integrity, and mutational profiles. Finally, we propose a role for HDC/IL-2 within an evolving landscape of strategies to achieve durable remission in a broader population of AML patients.

## Linked entities

- **Genes:** FLT3 (fms related receptor tyrosine kinase 3) [NCBI Gene 2322]
- **Proteins:** IL2 (interleukin 15)
- **Chemicals:** histamine dihydrochloride (PubChem CID 5818), midostaurin (PubChem CID 9829523), quizartinib (PubChem CID 24889392), azacitidine (PubChem CID 9444)
- **Diseases:** acute myeloid leukemia (MONDO:0015667)

## Full-text entities

- **Genes:** FLT3 (fms related receptor tyrosine kinase 3) [NCBI Gene 2322] {aka CD135, FLK-2, FLK2, STK1}, HDC (histidine decarboxylase) [NCBI Gene 3067], IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}
- **Diseases:** AML (MESH:D015470), leukemic (MESH:D007938)
- **Chemicals:** azacitidine (MESH:D001374), Histamine dihydrochloride (MESH:D006632), quizartinib (MESH:C544967), midostaurin (MESH:C059539)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12206275/full.md

---
Source: https://tomesphere.com/paper/PMC12206275