The only curative treatment for<unk>  is a bone marrow transplant or an allogeneic stem cell transplant. Other than this there are four major mainstays of treatment in<unk> : treatment with tyrosine kinase inhibitors, myelosuppressive or leukopheresis therapy (to counteract the leukocytosis during early treatment), splenectomy and interferon alfa-2b treatment. Due to the high median age of patients with<unk>  it is relatively rare for<unk>  to be seen in pregnant women, despite this, however,<unk>  can be treated with relative safety at any time during pregnancy with Interferon-alpha hormones. Chronic phase In the past, antimetabolites (e.g., cytarabine, hydroxyurea), alkylating agents, interferon alfa 2b, and steroids were used as treatments of<unk>  in the chronic phase, but since the 2000s have been replaced by Bcr-Abl tyrosine-kinase inhibitors drugs that specifically target BCR-ABL, the constitutively activated tyrosine kinase fusion protein caused by the Philadelphia chromosome translocation. Despite the move to replacing cytotoxic antineoplastics (standard anticancer drugs) with tyrosine kinase inhibitors sometimes hydroxyurea is still used to counteract the high leukocyte counts encountered during treatment with tyrosine kinase inhibitors like imatinib; in these situations it may be the preferred myelosuppressive agent due to its relative lack of leukemogenic effects and hence the relative lack of potential for secondary haematologic malignancies to result from treatment. IRIS, an international study that compared interferon/cytarabine combination and the first of these new drugs imatinib, with long-term follow up, demonstrated the clear superiority of tyrosine-kinase-targeted inhibition over existing treatments. Imatinib The first of this new class of drugs was imatinib mesylate (marketed as Gleevec or Glivec), approved by the US Food and Drug Administration (FDA) in 2001. Imatinib was found to inhibit the progression of<unk>  in the majority of patients (65–75%) sufficiently to achieve regrowth of their normal bone marrow stem cell population (a cytogenetic response) with stable proportions of maturing white blood cells. Because some leukemic cells (as evaluated by RT-PCR) persist in nearly all patients, the treatment has to be continued indefinitely. Since the advent of imatinib,<unk>  has become the first cancer in which a standard medical treatment may give to the patient a normal life expectancy. Dasatinib, nilotinib, radotinib, bosutinib, and asciminib To overcome imatinib resistance and to increase responsiveness to TK inhibitors, four novel agents were later developed. The first, dasatinib, blocks several further oncogenic proteins, in addition to more potent inhibition of the BCR-ABL protein, and was approved in 2007, by the U.S. Food and Drug Administration (FDA) to treat<unk>  in people who were either resistant to or intolerant of imatinib. A second TK inhibitor, nilotinib, was approved by the FDA for the same indication. In 2010, nilotinib and dasatinib were also approved for first-line therapy, making three drugs in this class available for treatment of newly diagnosed<unk> . In 2012, radotinib joined the class of novel agents in the inhibition of the BCR-ABL protein and was approved in South Korea for people resistant to or intolerant of imatinib. Bosutinib received US FDA and EU European Medicines Agency approval on 4 September 2012, and 27 March 2013, respectively for the treatment of adults with Philadelphia chromosome-positive (Ph+)<unk>  <unk>  with resistance, or intolerance to prior therapy. Asciminib (Scemblix) was approved for medical use in the United States in October 2021. Treatment-resistant<unk>  While capable of producing significantly improved responses compared with the action of imatinib, neither dasatinib nor nilotinib could overcome drug resistance caused by one particular mutation found to occur in the structure of BCR-ABL1 known as the T315I mutation (in other words, where the 315th amino acid is mutated from a threonine residue to an isoleucine residue). Two approaches were developed to the treatment of<unk>  as a result: In 2007, Chemgenex released results of an open-label Phase 2/3 study (CGX-635-CML-202) that investigated the use of a non BCR-ABL targeted agent omacetaxine, administered subcutaneously (under the skin) in patients who had failed with imatinib and exhibited T315I kinase domain mutation. This is a study which is ongoing through 2014. In September 2012, the FDA approved omacetaxine for the treatment of<unk>  in the case of resistance to other chemotherapeutic agents. Independently, ARIAD pharmaceuticals, adapting the chemical structures from first and second-generation TK inhibitors, arrived at a new pan-BCR-ABL1 inhibitor which showed (for the first time) efficacy against T315I, as well as all other known mutations of the oncoprotein. The drug, ponatinib, gained FDA approval in December 2012 for treatment of patients with resistant or intolerant<unk> . Just as with second-generation TK inhibitors, early approval is being sought to extend the use of ponatinib to newly diagnosed<unk>  also. Vaccination In 2005, encouraging but mixed results of vaccination were reported with the BCR/ABL1 p210 fusion protein in patients with stable disease, with GM-CSF as an adjuvant.
Chronic myelogenous leukemia
Acute myeloid leukemia
Chronic neutrophilic leukemia
Myeloid leukemia
Chronic lymphocytic leukemia
Acute monocytic leukemia
Prolymphocytic leukemia
Lymphoid leukemia