Treatment for Chronic, Accelerated, and Blast Phase Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is a type of cancer in which the bone marrow starts producing too many white blood cells. Also known as chronic myelogenous leukemia, this cancer begins to gradually get worse if left untreated. It may progress from the chronic phase to the accelerated phase and then to the blast phase. If you have chronic myeloid leukemia, there are different treatment plans based on which phase of the disease you have. Here’s everything you need to know about the treatment for chronic myeloid leukemia by phase – chronic, accelerated, and blast phase.

Overview of Chronic Myeloid Leukemia (CML)

Chronic myeloid leukemia is a form of cancer that affects the blood-forming cells of the body that are present in the bone marrow.(1, 2) Blood-forming cells are cells that are capable of growing and changing into white or red blood cells or even into platelets. If you have chronic myeloid leukemia, a certain type of white blood cells will begin to grow uncontrollably. These abnormal and immature white blood cells are known as blasts.(3, 4) As more and more blasts begin to form in the bone marrow, it starts to create an overabundance of them, thus crowding out the other types of blood cells. This form of cancer progresses more slowly than other forms of leukemia, but it is still going to get worse if you don’t seek treatment. This is what makes this a type of chronic leukemia instead of an acute leukemia. However, in some cases, chronic myeloid leukemia can also become aggressive and spread to other parts of the body through the bloodstream.(5, 6)

Let us now look at each phase of the disease and the treatment options available.

Treatment of Chronic Phase Chronic Myeloid Leukemia (CML)

Chronic myeloid leukemia is considered to be most treatable when it gets diagnosed early on in the chronic phase. To treat this cancer in its chronic phase, your doctor will prescribe a type of medication known as a tyrosine kinase inhibitor (TKI).(7, 8)

There are many types of TKI drugs that are available for the treatment of chronic myeloid leukemia. These include:

  • dasatinib (brand name: Spryrcel)
  • nilotinib (brand name: Tasigna)
  • imatinib (brand name: Gleevec)
  • ponatinib (brand name: Iclusig)
  • bosutinib (brand name: Bosulif)

Typically, Gleevec is the first type of TKI that is prescribed for treating chronic myeloid leukemia.(9) However, your doctor may even prescribe Sprycel or Tasigna as the first line of treatment against this cancer.(10)

If these types of TKI medications don’t seem to be working well for your condition, or they stop working after some time, or you are having intolerable side effects due to the medicines, your doctor may prescribe Bosulif.(11)

Doctors only prescribe Iclusig if the cancer does not respond well to any of the other types of TKIs or it develops a gene mutation known as the T315I mutation.(12)

If the body does not respond well to TKIs at all, your doctor is likely to prescribe chemotherapy drugs or a type of medication known as interferon to help treat chronic phase CML. In some rare cases, a stem cell transplant may also be recommended. However, this treatment is usually only used to treat the accelerated phase of chronic myeloid leukemia.

Treatment of Accelerated Phase Chronic Myeloid Leukemia (CML)

In people with accelerated phase chronic myeloid leukemia, the leukemia cells start to multiply more quickly. These cells also often develop certain gene mutations that increase their growth and also reduce the overall effectiveness of treatment. If you have accelerated phase CML, your doctor will recommend a treatment plan based on the treatments you have received in the past. And if you have never received any treatment for chronic myeloid leukemia in the past, your doctor is likely to start the treatment by prescribing a TKI drug first.

If you are already taking a TKI, your doctor may increase the dosage or even decide to switch you over to another type of TKI. In case your cancer cells develop the T315I mutation, they may prescribe the drug Iclusig.

If TKIs are not working for you, your doctor will move on to prescribe a treatment with interferon.(13)

In some cases, you may need to add chemotherapy to your treatment plan. Chemotherapy drugs may help in bringing your cancer into remission, though they often tend to stop working overtime. If you are relatively healthy and young, your doctor may recommend a stem cell transplant after you have gone through the other treatments. This will help replenish the blood-forming cells in the body.

During an allogeneic stem cell transplant, your doctor will introduce stem cells from a well-matched donor. This transplant may also be followed by an infusion of white blood cells from the same donor.(14,15)

During an autologous stem cell transplant, your doctor will work with some of your own stem cells before you get the treatment. After the treatment, your doctor will infuse your own stem cells back into your body.(16)

Your doctor will make all attempts to bring your cancer into remission with medications before they go ahead and recommend a stem cell transplant.

Treatment of Blast Phase Chronic Myeloid Leukemia (CML)

In the blast phase of chronic myeloid leukemia, the cancer cells begin to multiply rapidly and start causing more noticeable symptoms. Treatments at this stage tend to be less effective as compared to the earlier stages of the disease. As a result of this, most people who are in blast phase CML cannot be cured of the cancer.

If you develop blast phase chronic myeloid leukemia, your doctor will take your previous treatment history into consideration. Again, if you have not received any prior treatment for chronic myeloid leukemia, your doctor may prescribe high doses of a TKI drug. And if you are already taking a TKI, they are likely to increase your dosage, or they may advise you to change over to another type of TKI. If it is found that your leukemia cells have the T315I mutation, you will be prescribed Iclusig.

Your doctor may also prescribe chemotherapy along with your medications to help shrink the cancer or alleviate the symptoms of CML. However, by the time you reach the blast phase, chemotherapy tends to become less effective as compared to the earlier phases.(17)

If your condition responds well to treatment with medication in the blast phase, your doctor may recommend that you undergo a stem cell transplant. However, again, this treatment also tends to be less effective in the blast phase.(18)

What Are The Other Treatments For Chronic Myeloid Leukemia?

Apart from the treatments described above, your doctor may also prescribe certain therapies to help alleviate your symptoms or treat some of the potential complications of chronic myeloid leukemia. For instance, your doctor may prescribe:

  • Growth factors to promote recovery of the bone marrow if you have gone through chemotherapy.
  • A procedure known as leukapheresis to remove white blood cells from the bloodstream.
  • Surgery to remove the spleen if it has become enlarged.
  • Antibiotic, antifungal, or antiviral medications if you develop any infections.
  • Radiation therapy if you develop bone pain or an enlarged spleen.
  • Plasma or blood transfusions.

Your doctor may also recommend mental health support or counseling if you are finding it challenging to cope with the emotional or social effects of your cancer. In some cases, doctors may even encourage you to enroll yourself in a clinical trial to receive some experimental treatment for chronic myeloid leukemia. Several new treatments are currently being developed and tested for this disease.(19,20)

Monitoring of your Treatment

While you are undergoing treatment for chronic myeloid leukemia, your doctor is going to keep prescribing regular blood tests to monitor how your body is responding. If your current treatment plan seems to be working well, your doctor might advise you to continue with the same treatment plan. However, if your current treatment does not seem to be working well or it has become less effective over time, your doctor is likely to prescribe some different medications or other treatments. Most people with chronic myeloid leukemia need to be on a TKI drug for several years or even indefinitely.

Conclusion

If you have chronic myeloid leukemia, your doctor will recommend a treatment plan depending on what phase of the disease you have, along with your overall health, past history of treatment, and your age. There are several treatments available to help slow down the growth of the cancer, relieve symptoms, and even shrink the tumors.

However, treatment starts to become less effective as the disease progresses. You should talk to your doctor to find out more about the various treatment options available, including the potential benefits and side effects of the different treatment approaches.

References:

  1. Sawyers, C.L., 1999. Chronic myeloid leukemia. New England Journal of Medicine, 340(17), pp.1330-1340.
  2. Faderl, S., Talpaz, M., Estrov, Z., O’Brien, S., Kurzrock, R. and Kantarjian, H.M., 1999. The biology of chronic myeloid leukemia. New England Journal of Medicine, 341(3), pp.164-172.
  3. Deininger, M.W., Goldman, J.M. and Melo, J.V., 2000. The molecular biology of chronic myeloid leukemia. Blood, The Journal of the American Society of Hematology, 96(10), pp.3343-3356.
  4. Goldman, J.M. and Melo, J.V., 2003. Chronic myeloid leukemia—advances in biology and new approaches to treatment. New England Journal of Medicine, 349(15), pp.1451-1464.
  5. Melo, J.V., Hughes, T.P. and Apperley, J.F., 2003. Chronic myeloid leukemia. ASH Education Program Book, 2003(1), pp.132-152.
  6. Goldman, J.M., 2010, October. Chronic myeloid leukemia: a historical perspective. In Seminars in hematology (Vol. 47, No. 4, pp. 302-311). WB Saunders.
  7. Ross, D.M., Arthur, C., Burbury, K., Ko, B.S., Mills, A.K., Shortt, J. and Kostner, K., 2018. Chronic myeloid leukaemia and tyrosine kinase inhibitor therapy: assessment and management of cardiovascular risk factors. Internal medicine journal, 48, pp.5-13.
  8. Mahon, F.X., 2001. Chronic myeloid leukemia and tyrosine kinase inhibitors. La Revue de medecine interne, 22(9), pp.894-899.
  9. Henkes, M., van der Kuip, H. and Aulitzky, W.E., 2008. Therapeutic options for chronic myeloid leukemia: focus on imatinib (Glivec®, Gleevec™). Therapeutics and clinical risk management, 4(1), p.163.
  10. Saglio, G., Kim, D.W., Issaragrisil, S., Le Coutre, P., Etienne, G., Lobo, C., Pasquini, R., Clark, R.E., Hochhaus, A., Hughes, T.P. and Gallagher, N., 2010. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. New England Journal of Medicine, 362(24), pp.2251-2259.
  11. Doan, V., Wang, A. and Prescott, H., 2015. Bosutinib for the treatment of chronic myeloid leukemia. American Journal of Health-System Pharmacy, 72(6), pp.439-447.
  12. Nicolini, F.E., Mauro, M.J., Martinelli, G., Kim, D.W., Soverini, S., Müller, M.C., Hochhaus, A., Cortes, J., Chuah, C., Dufva, I.H. and Apperley, J.F., 2009. Epidemiologic study on survival of chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia patients with BCR-ABL T315I mutation. Blood, The Journal of the American Society of Hematology, 114(26), pp.5271-5278.
  13. Bonifazi, F., de Vivo, A., Rosti, G., Guilhot, F., Guilhot, J., Trabacchi, E., Hehlmann, R., Hochhaus, A., Shepherd, P.C., Steegmann, J.L. and Kluin-Nelemans, H.C., 2001. Chronic myeloid leukemia and interferon-α: a study of complete cytogenetic responders. Blood, The Journal of the American Society of Hematology, 98(10), pp.3074-3081.
  14. Or, R., Shapira, M.Y., Resnick, I., Amar, A., Ackerstein, A., Samuel, S., Aker, M., Naparstek, E., Nagler, A. and Slavin, S., 2003. Nonmyeloablative allogeneic stem cell transplantation for the treatment of chronic myeloid leukemia in first chronic phase. Blood, The Journal of the American Society of Hematology, 101(2), pp.441-445.
  15. Jamieson, C.H., 2008. Chronic myeloid leukemia stem cells. ASH Education Program Book, 2008(1), pp.436-442.
  16. Pigneux, A., Faberes, C., Boiron, J.M., Mahon, F.X., Cony-Makhoul, P., Agape, P., Lounici, A., Bernard, P., Bilhou-Nabera, C., Bouzgarrou, R. and Marit, G., 1999. Autologous stem cell transplantation in chronic myeloid leukemia: a single center experience. Bone marrow transplantation, 24(3), pp.265-270.
  17. Cortes, J., Kim, D.W., Raffoux, E., Martinelli, G., Ritchie, E., Roy, L., Coutre, S., Corm, S., Hamerschlak, N., Tang, J.L. and Hochhaus, A., 2008. Efficacy and safety of dasatinib in imatinib-resistant or-intolerant patients with chronic myeloid leukemia in blast phase. Leukemia, 22(12), pp.2176-2183.
  18. Saußele, S. and Silver, R.T., 2015. Management of chronic myeloid leukemia in blast crisis. Annals of hematology, 94(2), pp.159-165.
  19. Guilhot, J., Baccarani, M., Clark, R.E., Cervantes, F., Guilhot, F., Hochhaus, A., Kulikov, S., Mayer, J., Petzer, A.L., Rosti, G. and Rousselot, P., 2012. Definitions, methodological and statistical issues for phase 3 clinical trials in chronic myeloid leukemia: a proposal by the European LeukemiaNet. Blood, The Journal of the American Society of Hematology, 119(25), pp.5963-5971.
  20. Pfirrmann, M., Hochhaus, A., Lauseker, M., Saußele, S., Hehlmann, R. and Hasford, J., 2011. Recommendations to meet statistical challenges arising from endpoints beyond overall survival in clinical trials on chronic myeloid leukemia. Leukemia, 25(9), pp.1433-1438.