Chronic myeloid leukemia: the prognosis has improved with the introduction of targeted therapies

“The prognosis has improved dramatically with the introduction of targeted therapies. Thanks to these medications, the condition has become chronic. Based on STOP studies we can observe that a portion of patients probably recover successfully,” 

says on World CML Awareness Day Prof. Irena Preložnik Zupan, PhD, internist and hematologist at the Clinical Department of Hematology of the Internal Clinic at the University Medical Center Ljubljana.

From 10 to 15 percent of patients with leukemia have chronic myeloid leukemia. 

“Each year in Slovenia, 15 to 25 patients are diagnosed with this type of cancer. Currently, we have around 300 CML patients, and the Slovenian hematologists treat them following the accepted guidelines,” explains Prof. Preložnik Zupan.

Signs and symptoms of CML

Prof. Preložnik Zupan states that half the patients develop signs and symptoms of chronic myeloid leukemia as the cancer is detected, while the other 50% have practically no symptoms, and the cancer is detected randomly when checking the blood count for other reasons. The signs and symptoms of chronic myeloid leukemia are: fatigue, abdominal pain, pain in the bones or under the left rib cage, feeling bloated (even after ingesting a small amount of food), increased body temperature, regular sweating, shortness of breath and weight loss. 

The development of CML is caused by a defect in the genetic material 

Chronic myeloid leukemia develops in the red bone marrow, where in a healthy person blood cells are born. 

“A defect in our genetic material, chromosomes and genes is key for the development of this cancer. The swapping of parts between two chromosomes produces an altered chromosome 22, also named Philadelphia chromosome, and a new gene BCR::ABL. This gene provides the information required for the creation of a new protein, which stimulates bone marrow to create new leukemic cells. The growth of leukemic cells replaces the bone marrow’s healthy cells, erythrocytes, leukocytes and platelets. The lack of healthy cells and the multiplication and spread of leukemic cells causes physical symptoms and signs all over the body,” 

explains hematologist Prof. Preložnik Zupan. 

We can reasonably suspect CML only on the basis of a blood count. 

“The blood count reveals an abnormal increase of blood cells, mainly leukocytes with the typical appearance of young cells. There can also be an increase of platelets. Patients are immediately sent to be examined by a hematologist. The diagnosis is based on genetic tests performed on blood and/or bone marrow,” 

explains the diagnostic process of chronic myeloid leukemia Prof. Preložnik Zupan.

The main goal of CML treatment: reduce the number of leukemic cells as quickly as possible

Prof. Preložnik Zupan recollects that before 2001 there was no efficient treatment for CML. 

“The cancer mostly progressed. Most patients died within three to five years. The only efficient treatment was hematopoietic stem cell transplantation. Twenty-one years ago, the first targeted therapy for chronic myeloid leukemia, the tyrosine kinase inhibitor, was approved in the USA. Today, new generations of therapies are already available. From 2002, targeted therapies have also been available in Slovenia,” points out the hematologist. 

Tyrosine kinase inhibitors inhibit the function of the protein which triggers the development of leukemic cells. 

“The main goal of treatment of chronic myeloid leukemia is to reduce the number of leukemic cells as much as possible and as quickly as possible to prevent cancer from progressing. At the beginning of CML, the patients contain within their body an amount of leukemic cells the size of a melon, but once molecular remission of CML is achieved, these cells shrink to the size of a pepper seed. Targeted therapies are not without side effects. This is why next to monitoring the efficiency of the treatment, it is also important to monitor the side effects and treat them accordingly,” warns Prof. Preložnik Zupan.

We expect new solutions for the remaining patients

The hematologist is extremely happy to say that the survival rate of patients five years after being diagnosed with chronic myeloid leukemia and after treatment with tyrosine kinase inhibitors is today estimated at more than 85%. 

“Each patient requires an individual approach to treatment. We need to select the appropriate therapy. This prevents treatment-related complications, which can also be life threatening. Today, hematopoietic stem cell transplantation is performed exclusively for patients with specific CML characteristics that make the cancer unresponsive to targeted therapies. Patients must also be fit for transplantation,” explains Prof. Preložnik Zupan.

In spite of the significant progress in the treatment for chronic myeloid leukemia in the last 20 years, blood cancer and other serious blood disorders remain ruthless enemies. Patients with advanced CML who don’t respond well to available therapies or do not tolerate them are in need of new solutions. 

“For patients who are unresponsive and/or don’t tolerate tyrosine kinase inhibitors, scientists have already developed new solutions. We expect them to be available in Slovenia in the following years,” predicts hematologist Prof. Preložnik Zupan.