Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in the Western world and is considered incurable. New discoveries, however, have led to an improved quality of life and longer life expectancy for patients affected by the disease.
What is chronic lymphocytic leukemia
Leukemia can be distinguished as:
- acute, a fast-growing leukemia with worsening symptoms
- chronic, like CLL, a slow-growing leukemia with gradual development
Chronic lymphocytic leukemia starts when B lymphocytes, that are present among the cells that make up our immune system, begin to grow out of control. Excess lymphocytes then accumulate in the blood, lymph nodes and spleen. The original causes of the disease are unknown and, unlike other forms of this illness, there is no direct relationship established between ionizing radiation and the onset of chronic lymphocytic leukemia. There may be familial predisposition since family members of patients with CLL were found to have other types of lymphoproliferative disorders, including CLL.
Chronic lymphocytic leukemia is often considered an asymptomatic disease that does not need treatment but does accompany the patient for his or her entire lifetime.
Each year in Italy, there are 5-7 new cases per 100,000 people. Incidence in Western countries is estimated at 5 in 100,000 per year. In Eastern countries the disease is very rare, which reinforces the hypothesis of hereditary transmission. Chronic lymphocytic leukemia mainly affects older adults; 40% of the cases diagnosed are in people over 75 years of age while 15% of the cases are in people under 50. The average age at the time of diagnosis is around 70 and is slightly more prevalent in men than in women.
On average, the life expectancy of people diagnosed with chronic lymphocytic leukemia normally exceeds ten years after diagnosis.
What are the symptoms?
As mentioned, chronic lymphocytic leukemia is often asymptomatic. As such, the majority of patients diagnosed with the disease appear healthy but find out they have CLL when carrying out blood tests for routine check-ups or for other health problems that are not evidently linked to chronic lymphocytic leukemia. In any case, a high white blood cell count is the number one reason doctors are consulted, second being an increase in the size of lymph nodes in the spleen. In rarer cases, and particularly in people in advanced stages of CLL, a doctor is consulted for symptoms of anemia with fatigue and pallor or for hemorrhaging due to a reduced number of platelets.
When is treatment needed?
Normally treatment is prescribed only when the disease progresses and even then, there is a careful case-by-case evaluation. Clinical trials are done to assess the clinical stage of the disease, which serves as an indication of bone marrow impairment (the presence of thrombocytopenia or anemia, or rather, a decreased number of platelets and red blood cells) and infiltration in organs such as the spleen, liver and lymph nodes. Treatment usually begins when clinical signs begin to gradually worsen- the number of lymphocytes continually rises, the patient becomes anemic or shows symptoms of weight loss, chronic weakness, fever, or night sweats. In these cases, chronic lymphocytic leukemia may take an aggressive course and for this reason treatment is sought out. Treatment is avoided in patients with no symptoms because it is either useless or possibly harmful.
Causes: no self-recognition in receptors
A study recently published on Nature Communications by a group of researchers from the San Raffaele Institute in Milan, in collaboration with the Italian Association for Cancer Research (AIRC), highlights for the first time a fundamental aspect in understanding and fighting this form of leukemia. The development of the disease is caused by the lack of recognition between identical receptors on the surface of B lymphocytes. These receptors come into contact with other receptors on the surface of the same cell or nearby cells, but do not recognize the other receptors as their “identical twin”. They see themselves as a foreign identity and get to work, reproducing themselves.
This discovery has been fundamental because it has allowed researchers to study new approaches to the disease through new drugs and to study more effective therapies with drugs that are already on the market, all with the objective of impeding false recognition among B lymphocytes. “This is a significant step forward for a disease that currently has no personalized therapy, using the same treatments even for different forms of chronic lymphocytic leukemia”, explains Paolo Ghia, Professor at the Vita-Salute San Raffaele University and director of the Strategic Program on Chronic Lymphocytic Leukemia.
The “magic bullets” and inhibitors
“For decades chemotherapy has been the only weapon in our possession to treat this disease”, explains Marco Montillo, director of the treatment program for chronic lymphoproliferative disorders at the Niguarda Ca’ Granda Hospital in Milan, “but for over ten years now we’ve added monoclonal antibodies, or rather “magic bullets”, to our therapeutic armory because they target tumor cells more directly than chemotherapy. More recently we have also introduced more specific drugs, simply defined as inhibitors, that block the mechanism that makes neoplastic cells reproduce. Venetoclax, for example, is the first drug, recently approved in Italy, that is able to selectively inhibit the function of the BCL-2 protein, which is responsible for the survival of neoplastic cells, by triggering apoptosis, or rather, the death of neoplastic lymphocytes present in chronic lymphatic leukemia”.
“The approval of Venetoclax is an important step forwards for patients in Italy with chronic lymphocytic leukemia”, states Robin Foà, director of the Hematology Department at Policlinico Umberto 1, Sapienza University in Rome. “The results generated by the clinical experimentation program have demonstrated that this new oral therapy is able to offer important global response rates. Now that the drug has been approved, we are able to offer an innovative therapeutic alternative to patients with specific pathological conditions of chronic lymphocytic leukemia that are difficult to treat”.
The results obtained in the last few years with this new class of drugs provides a new optimistic view on increasing the life expectancy of patients affected by malignant blood tumors and, in particular, patients with chronic lymphocytic leukemia.
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