Management of chronic myeloid leukemia (CML) has undergone a sea change over the last couple of decades with the advent of targeted therapies.
Tyrosine kinase inhibitors
These new drugs target specific parts of the cancer cells and are thus more successful than general anti-cancer drugs in treatment of CML. The drugs are known as tyrosine kinase inhibitors (TKIs).
Tyrosine kinase is a protein that helps in proliferation and growth of cancer cells. These drugs affect only the cancer cells and spare the normal cells. Their side effects thus are thus much lower than standard chemotherapy.
These TKIs however do have some side effects and should not be taken by pregnant mothers as they may harm the unborn baby.
Targeted therapies are started as soon as CML is detected. They work best on CML in its chronic phase. These are prescribed as once daily pills that need to be taken for life.
The tyrosine kinase inhibitors that are in use include Imatinib (Gleevec™), Dasatinib (Sprycel™), and Nilotinib (Tasigna™).
Imatinib or Greevec was the first TKI to be used. Nearly all patients respond to treatment with one of these drugs and the response seems to last for years of use. These drugs effectively slow the progression of the disease. The newer agents of this class include Bosutinib and Ponatinib (Iclusig™).
Side effects of TKIs include gastrointestinal upset including nausea, vomiting, diarrhea, as well as tiredness, muscle cramps, rash, edema and drop in levels of white blood cells and platelet.
Interferons for CML
Interferon is a group of chemical substances that are made by the body’s own immune system. Interferon, before the advent of TKIs was the mainstay of therapy of CML.
Interferon slows the growth and progression of the CML. They are given as injections every day for several years.
Common side effects with interferon include flu like reactions, muscle pains and aches, bone pain, headaches, nausea, vomiting, depression, low blood cell counts etc.
Anti cancer chemotherapy for CML
Anti cancer chemotherapy kills cancer cells in most diseases but is fraught with side effects since they also affect the healthy cells of the body. These drugs are of various types and some may be given as injections while some are taken as pills.
Chemotherapy was once the main treatment for patients with CML and is still used in advanced cases of the disease. Common side effects of chemotherapy include nausea, vomiting, loss of appetite, loss of hair, mouth sores, increased risk of infections, anemia and easy bruising or bleeding.
Radiation therapy for CML
Radiation therapy is used for many solid tumors but is not used commonly for CML. It may however be useful in some patients for example those with an enlarged organ (such as the spleen), where radiation can shrink the swelling.
Radiation may also be used for bone pain to kill the cancer cells growing within the bone marrow. Radiation is sometimes given to the whole body just prior to a stem cell transplant.
Surgery for CML
Leukemia affects the blood stream and thus surgery is not very useful unlike in solid tumors. Surgery, however, may be useful in some cases for example when the spleen in severely enlarged.
Bone marrow or peripheral blood stem cell transplant for CML
Chemotherapy can target cancerous as well as healthy cells and this often leads to severe side effects. A stem cell transplant uses very high dose chemotherapy that can kill all leukemia cells. However, healthy bone marrow is then injected into the patient so that he or she is free of the cancer. Transplanted stem cells thereafter restore the blood-making bone marrow stem cells. This is called a stem cell transplant (SCT).
Stem cells for transplants are collected from the bone marrow or from the bloodstream in a process called apheresis. For this sometimes umbilical cord stem cells are used. Earlier the cells were taken from bone marrow. Now most cases are performed by taking cells from the bloodstream. This is called peripheral blood stem cell transplant or PBSCT. These blood-forming stem cells can come from either the patient or from a donor whose tissue type closely matches that of the patient. The donor is most commonly a sibling but may be someone who is unrelated to the patient.
For the transplant, first the blood-forming stem cells are collected from either the patient or a matched donor. These cells are frozen and stored. The patient is then given high doses of chemotherapy to kill the cancer cells. Then they receive total body radiation to kill any remaining cancer cells.
Once the chemotherapy and radiation kills the cancer cells the stored stem cells are given to the patient into a vein like a blood transfusion. These stem cells then grow to produce healthy cells.
Patients over 55 years of age are incapable of withstanding a regular transplant that uses high doses of chemotherapy. They may be given a “mini transplant”. In this type of transplant patients get lower doses of chemotherapy and radiation which do not destroy the all cells in their bone marrow. Then they receive the donor stem cells.
Reviewed by April Cashin-Garbutt, BA Hons (Cantab)