Therapies using medication Systemic therapy is the use of medication to destroy cancer cells. This type of medication is given through the bloodstream to reach cancer cells throughout the body. Systemic therapies are generally prescribed by a medical oncologist or a hematologist. Common ways to give systemic therapies include an intravenous (IV) tube placed into a vein using a needle or in a pill or capsule that is swallowed (orally). The types of systemic therapies used for CML include: Targeted therapy Chemotherapy Immunotherapy There currently 5 TKIs available for CML: Imatinib (Gleevec). Imatinib was the first targeted therapy approved by the U.S Food and Drug Administration (FDA) for CML in 2001. It is taken as a pill once or twice a day. It works better than chemotherapy to treat CML and causes fewer side effects (see below). Nearly all patients with chronic phase CML have their blood counts return to healthy levels and their spleen shrink after receiving this drug. Most impoantly, 80% to 90% of patients newly diagnosed with chronic phase CML who receive imatinib no longer have detectable levels of cells with the Philadelphia chromosome. Imatinib may also be used to treat other types of cancer, such as acute lymphoblastic leukemia (ALL) with the presence of the Philadelphia chromosome. Dasatinib (Sprycel). Dasatinib is approved by the FDA as an initial treatment for patients with newly-diagnosed chronic phase CML and when other drugs are not working. It is a pill that is usually taken once a day, or sometimes twice a day depending on the dose. The side effects include anemia, a low level of white blood cells called neutropenia, a low level of platelets called thrombocytopenia, and lung problems that include fluid around the lung and/or pulmonary hypeension. The doctor will monitor a patient's blood counts frequently after staing dasatinib and may adjust the dose or stop giving the drug temporarily if the patient's blood counts drop too low. Dasatinib may also cause bleeding, fluid retention, diarrhea, rash, headache, fatigue, and nausea. Dasatinib requires stomach acid in order to be absorbed so patients should not take any anti-acid medications. Nilotinib (Tasigna). Nilotinib is also approved by the FDA as an initial treatment for patients with newly-diagnosed chronic phase CML and when other drugs are not working. It is a capsule that patients take by mouth twice a day on an empty stomach. Common side effects include low blood counts, rash, headache, nausea, diarrhea, and itching. Other possible but uncommon serious side effects include high blood sugar levels, fluid build-up, and inflammation of the pancreas or liver. The most serious side effect of nilotinib includes possibly life-threatening hea and blood vessel problems that can lead to an irregular heabeat, narrowing of the blood vessels, stroke, and possible sudden death. These side effects are very rare, but patients may need testing to check their hea health during treatment. There can be interactions with other medications that may increase these risks, so be sure to talk with your doctor about all medications you are taking. Bosutinib (Bosulif). In 2012, bosutinib was approved by the FDA to treat CML when 1 of the other TKIs was not effective or if a patient experienced too many side effects. The most common side effects include diarrhea, nausea and vomiting, low levels of blood cells, abdominal pain, fatigue, fever, allergic reactions, and liver problems. Ponatinib (Iclusig). Ponatinib was also approved by the FDA in 2012 for patients when 1 of the other TKIs was not effective or if a patient experienced too many side effects. Ponatinib also targets CML cells that have a paicular mutation, known as T315I, which makes these cells resistant to other currently approved TKIs. The most common side effects include high blood pressure, rash, abdominal pain, fatigue, headache, dry skin, constipation, fever, joint pain, and nausea. Ponatinib may also cause hea problems, severe narrowing of blood vessels, blood clots, stroke, or liver problems. For CML, the target is the unique protein called the BCR-ABL tyrosine kinase enzyme. Drugs that target the BCR-ABL tyrosine kinase enzyme are called tyrosine kinase inhibitors or TKIs. These types of drugs can stop the BCR-ABL enzyme from working, which causes the CML cells to die quickly Bone marrow transplantation/stem cell transplantation A bone marrow transplant is a medical procedure in which bone marrow that contains leukemia is replaced by highly specialized cells, called hematopoietic stem cells, that develop into healthy bone marrow. Hematopoietic stem cells are blood-forming cells found both in the bloodstream and in the bone marrow. Today, this procedure is more commonly called a stem cell transplant, rather than bone marrow transplant, because it is the stem cells in the blood that are typically being transplanted, not the actual bone marrow tissue. Before recommending transplantation, doctors will talk with the patient about the risks of this treatment. They will also consider several other factors, such as the phase of CML, results of any previous treatment, and patient's age and general health. Although a bone marrow transplant is the only treatment that can cure CML, it is used less often now. This is because bone marrow transplants have a lot of side effects, while TKIs are very effective for CML and have fewer side effects. There are 2 types of stem cell transplantation depending on the source of the replacement blood stem cells: allogeneic (ALLO) and autologous (AUTO). ALLO uses donated stem cells, while AUTO uses the patient's own stem cells. In both types, the goal is to destroy cancer cells in the marrow, blood, and other pas of the body using chemotherapy and/or radiation therapy and then allow replacement blood stem cells to create healthy bone marrow. Only ALLO transplants are used to treat CML. Ref Davidson 23rd edition pg 786