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Trade names | Ceplene |
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Routes of administration | Subcutaneous injection, topical |
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CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.000.272 |
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Formula | C5H11Cl2N3 |
Molar mass | 184.06 g·mol−1 |
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Histamine dihydrochloride (INN, trade name Ceplene) is a salt of histamine that is used as a drug for the prevention of relapse in patients diagnosed with acute myeloid leukemia (AML).
It is also an FDA-approved [1] active ingredient for topical analgesic use for the temporary relief of minor aches and pains of muscles and joints associated with arthritis, simple backache, bruises, sprains, and strains and is available in over-the-counter (OTC) products such as Australian Dream and Golden Creme. [2] [3]
Histamine dihydrochloride is administered in conjunction with low doses of the immune-activating cytokine interleukin-2 (IL-2) in the post-remission phase of AML, i.e. when patients have completed the initial chemotherapy. This combination has been reported to significantly reduce the risk of relapse in AML. [4] The effect is particularly pronounced in patients in their first remission who are below the age of 60. [5]
The combination of histamine dihydrochloride and interleukin-2 was approved for use in AML patients within the European Union in October 2008 [6] and will be marketed in the EU by the Swedish pharmaceutical company Meda. The drug is also available through a named patient program in several other countries (excluding the US).
Histamine dihydrochloride acts by improving the immune-enhancing properties of IL-2, and laboratory studies have shown that this combination can induce immune-mediated killing of leukemic cells. [7] The treatment (in the form of subcutaneous injections) is given in 3-week cycles by the patients at home for 18 months, thus coinciding with the period of highest relapse risk. The side-effects include transient flush and headache, whereas IL-2 may induce low-grade fever and inflammation at the site of injection. Histamine dihydrochloride has been developed by researchers at the University of Gothenburg, Sweden.
Acute promyelocytic leukemia is a subtype of acute myeloid leukemia (AML), a cancer of the white blood cells. In APL, there is an abnormal accumulation of immature granulocytes called promyelocytes. The disease is characterized by a chromosomal translocation involving the retinoic acid receptor alpha (RARA) gene and is distinguished from other forms of AML by its responsiveness to all-trans retinoic acid therapy. Acute promyelocytic leukemia was first characterized in 1957 by French and Norwegian physicians as a hyperacute fatal illness, with a median survival time of less than a week. Today, prognoses have drastically improved; 10-year survival rates are estimated to be approximately 80-90% according to one study.
A myeloid sarcoma is a solid tumor composed of immature white blood cells called myeloblasts. A chloroma is an extramedullary manifestation of acute myeloid leukemia; in other words, it is a solid collection of leukemic cells occurring outside of the bone marrow.
Gemtuzumab ozogamicin, sold under the brand name Mylotarg, is an antibody-drug conjugate that is used to treat acute myeloid leukemia.
Interleukin 7 (IL-7) is a protein that in humans is encoded by the IL7 gene.
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may include feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection. Occasionally, spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly, and is typically fatal within weeks or months if left untreated.
The interleukin-3 receptor (CD123) is a molecule found on cells which helps transmit the signal of interleukin-3, a soluble cytokine important in the immune system.
Cluster of differentiation antigen 135 (CD135) also known as fms like tyrosine kinase 3, receptor-type tyrosine-protein kinase FLT3, or fetal liver kinase-2 (Flk2) is a protein that in humans is encoded by the FLT3 gene. FLT3 is a cytokine receptor which belongs to the receptor tyrosine kinase class III. CD135 is the receptor for the cytokine Flt3 ligand (FLT3L).
Lestaurtinib is a tyrosine kinase inhibitor structurally related to staurosporine. This semisynthetic derivative of the indolocarbazole K252a was investigated by Cephalon as a treatment for various types of cancer. It is an inhibitor of the kinases fms-like tyrosine kinase 3 (FLT3), Janus kinase 2 (JAK2), tropomyosin receptor kinase (trk) A (TrkA), TrkB and TrkC.
Biphenotypic acute leukaemia (BAL) is an uncommon type of leukemia which arises in multipotent progenitor cells which have the ability to differentiate into both myeloid and lymphoid lineages. It is a subtype of "leukemia of ambiguous lineage".
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy. It was initially regarded as a form of lymphocyte-derived cutaneous lymphoma and alternatively named CD4+CD56+ hematodermic tumor, blastic NK cell lymphoma, and agranular CD4+ NK cell leukemia. Later, however, the disease was determined to be a malignancy of plasmacytoid dendritic cells rather than lymphocytes and therefore termed blastic plasmacytoid dendritic cell neoplasm. In 2016, the World Health Organization designated BPDCN to be in its own separate category within the myeloid class of neoplasms. It is estimated that BPDCN constitutes 0.44% of all hematological malignancies.
Immunotransplant is a maneuver used to make vaccines more powerful. It refers to the process of infusing vaccine-primed T lymphocytes into lymphodepleted recipients for the purpose of enhancing the proliferation and function of those T cells and increasing immune protection induced by that vaccine.
Childhood leukemia is leukemia that occurs in a child and is a type of childhood cancer. Childhood leukemia is the most common childhood cancer, accounting for 29% of cancers in children aged 0–14 in 2018. There are multiple forms of leukemia that occur in children, the most common being acute lymphoblastic leukemia (ALL) followed by acute myeloid leukemia (AML). Survival rates vary depending on the type of leukemia, but may be as high as 90% in ALL.
Autologous immune enhancement therapy (AIET) is a treatment method in which immune cells are taken out from the patient's body which are cultured and processed to activate them until their resistance to cancer is strengthened and then the cells are put back in the body. The cells, antibodies, and organs of the immune system work to protect and defend the body against not only tumor cells but also bacteria or viruses.
Midostaurin, sold under the brand name Rydapt & Tauritmo both by Novartis, is a multi-targeted protein kinase inhibitor that has been investigated for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and advanced systemic mastocytosis. It is a semi-synthetic derivative of staurosporine, an alkaloid from the bacterium Streptomyces staurosporeus.
In haematology atypical localization of immature precursors (ALIP) refers to finding of atypically localized precursors on bone marrow biopsy. In healthy humans, precursors are rare and are found localized near the endosteum, and consist of 1-2 cells. In some cases of myelodysplastic syndromes, immature precursors might be located in the intertrabecular region and occasionally aggregate as clusters of 3 ~ 5 cells. The presence of ALIPs is associated with worse prognosis of MDS. Recently, in bone marrow sections of patients with acute myeloid leukemia cells similar to ALIPs were defined as ALIP-like clusters. The presence of ALIP-like clusters in AML patients within remission was reported to be associated with early relapse of the disease.
Venetoclax, sold under the brand names Venclexta and Venclyxto, is a medication used to treat adults with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or acute myeloid leukemia (AML).
Gilteritinib, sold under the brand name Xospata, is an anti-cancer drug. It acts as an inhibitor of FLT3, hence it is a tyrosine kinase inhibitor.
Camidanlumab tesirine is an antibody-drug conjugate (ADC) composed of a human antibody that binds to the protein CD25, conjugated to a pyrrolobenzodiazepine dimer toxin. The experimental drug, developed by ADC Therapeutics is being tested in clinical trials for the treatment of B-cell Hodgkin's lymphoma (HL) and non-Hodgkin lymphoma (NHL), and for the treatment of B-cell acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).
Thomas A. Waldmann was an American immunologist who has worked on therapeutic monoclonal antibodies to the IL-2 receptor, Interleukin 15 (IL-15), and Adult T-cell Leukemia (ATL). Until the week he died, he was an active distinguished investigator at the Lymphoid Malignancies Branch of the National Cancer Institute.
Bisantrene is an anthracenyl bishydrazone with anthracycline-like antineoplastic activity and an antimetabolite. Bisantrene intercalates with and disrupts the configuration of DNA, resulting in DNA single-strand breaks, DNA-protein crosslinking, and inhibition of DNA replication. This agent is similar to doxorubicin in chemotherapeutic activity, but unlike anthracyclines like doxorubicin, it exhibits little cardiotoxicity.