Созылмалы лимфолейкоз: көріністері, диагностикасы және емдеуі

Early stage CLL in asymptomatic cases responds better to careful observation, as there is no evidence that early intervention treatment can alter the course of the disease. Immune defects occur early in the course of CLL and these increase the risk of developing serious infection, which should be treated appropriately with antibiotics. As of 2021, BTK inhibitors such as ibrutinib and acalabrutinib are often recommended for first line treatment of CLL. The medications fludarabine, cyclophosphamide, and rituximab were previously the initial treatment in those who are otherwise healthy. CLL affected about 904,000 people globally in 2015 and resulted in 60,700 deaths. In 2021, the estimated incidence of CLL in the United States is 21,250 new cases and 4,320 deaths. The disease most commonly occurs in people over the age of 65, due to the accumulation of genetic mutations that occur over time. Men are diagnosed around twice as often as women (6.8 to 3.5 ratio). It is much less common in people from Asia. These people generally have no symptoms. Less commonly, the disease comes to light only after the cancerous cells overwhelm the bone marrow, resulting in low red blood cells, neutrophils, or platelets. Whereas, with CLL, diseased cells propagate from within the bone marrow, in SLL they propagate from within the lymphatic tissue. CLL/SLL MBL consist of two groups: low count CLL/SLL MBL has monoclonal B cell blood counts of <0.5x9 cells/liter (i. e. 0.5x9/L) while high count CLL/SLL MBL has blood monoclonal B cell counts ≥0.5x9/L but <5x109/L. Individuals with blood counts of these monoclonal B cells >5x9/L are diagnosed as having CLL. Low count CLL/SLL MBL rarely if ever progresses to CLL while high count CLL/SLL MBL does so at a rate of 1 2% per year. Thus, CLL may present in individuals with a long history of having high count CLL/SLL MBL. There is no established treatment for these individuals except monitoring for development of the disorder's various complications (see treatment of MBL complications) and for their progression to CLL. CLL has also been reported to convert into other more aggressive diseases such as lymphoblastic lymphoma, hairy cell leukemia, high grade T cell lymphomas, acute myeloid leukemia, lung cancer, brain cancer, melanoma of the eye or skin, salivary gland tumors, and Kaposi's sarcomas. While some of these conversions have been termed RTs, the World Health Organization and most reviews

Gastrointestinal (GI) involvement can rarely occur with chronic lymphocytic leukemia. Some of the reported manifestations include intussusception, small intestinal bacterial contamination, colitis, and others. Usually, GI complications with CLL occur after Richter transformation. Two cases to date have been reported of GI involvement in chronic lymphocytic leukemia without Richter's transformation.

CLL can also be caused by a number of epigenetic changes, which are adaptations that add a tag to specific DNA sequences, rather than altering the sequence itself. In CLL, these changes can be classified into the addition of three different methyl subgroups (naïve B cell like, memory B cell like, and intermediate), which impact how much that DNA sequence is transcribed. Some relevant genetic mutations may be inherited. Since there is no one single mutation that is associated with CLL in all cases, an individual's susceptibility may be impacted when multiple mutations that are associated with an increase in the risk of CLL are co inherited. Up until 2020, 45 susceptibility loci have been identified. Of these loci, 93% are linked to the alteration of 30 gene expressions involved in immune response, cell survival, or Wnt signaling. Exposure to Agent Orange increases the risk of CLL, and exposure to hepatitis C virus may increase the risk. There is no clear association between ionizing radiation exposure and the risk of developing CLL.

The combination of the microscopic examination of the peripheral blood and analysis of the lymphocytes by flow cytometry to confirm clonality and marker molecule expression is needed to establish the diagnosis of CLL. Both are easily accomplished on a small amount of blood. A flow cytometer instrument can examine the expression of molecules on individual cells in fluids. This requires the use of specific antibodies to marker molecules, with fluorescent tags recognized by the instrument. In CLL, the lymphocytes are all genetically identical since they are derived from the same B cell lineage, expressing common B cell markers CD19 and CD20, with abnormal expression of surface markers CD5 and CD23. Smudge cells are due to cancer cells lacking in vimentin, a type of cytoskeleton proteins which is a structural component in a cell which maintains the cell's internal shape and mechanical resilience).

The atypical molecular pattern on the surface of the cell includes the coexpression of cell surface markers clusters of differentiation 5 (CD5) and 23. In addition, all the CLL cells within one individual are clonal, that is, genetically identical. In practice, this is inferred by the detection of only one of the mutually exclusive antibody light chains, kappa or lambda, on the entire population of the abnormal B cells. Normal B lymphocytes consist of a stew of different antibody producing cells, resulting in a mixture of both kappa and lambda expressing cells. The lack of the normal distribution of these B cells is one basis for demonstrating clonality, the key element for establishing a diagnosis of any B cell malignancy (B cell non Hodgkin lymphoma). The Matutes's CLL score allows the identification of a homogeneous subgroup of classical CLL, that differs from atypical/mixed CLL for the five markers' expression (CD5, CD23, FMC7, CD22, and immunoglobulin light chain)
Matutes's CLL scoring system is very helpful for the differential diagnosis between classical CLL and the other B cell chronic lymphoproliferative disorders, but not for the immunological distinction between mixed/atypical CLL and mantle cell lymphoma (MCL malignant B cells). Discrimination between CLL and MCL can be improved by adding non routine markers such as CD54 and CD200. Among routine markers, the most discriminating feature is the CD20/CD23 mean fluorescence intensity ratio. In contrast, FMC7 expression can surprisingly be misleading for borderline cases.

In the past, cases with similar microscopic appearance in the blood but with a T cell phenotype were referred to as T cell CLL. However, these are now recognized as a separate disease group and are currently classified as T cell prolymphocytic leukemias (T PLL). An accurate diagnosis of T PLL is important as it is a rare and aggressive disease. CLL should not be confused with acute lymphoblastic leukemia, a highly aggressive leukemia most commonly diagnosed in children, and highly treatable in the pediatric setting.

Targeted therapy attacks cancer cells at a specific target, with the aim of not harming normal cells. Targeted drugs used in CLL include venetoclax (a Bcl 2 inhibitor), ibrutinib and acalabrutinib (Bruton's tyrosine kinase inhibitors), idelalisib and duvelisib (inhibitors of some forms of the enzyme phosphoinositide 3 kinase), as well as monoclonal antibodies against CD20 (rituximab, ofatumumab and obinutuzumab) and CD52 (alemtuzumab). Notably, some of the effects of the targeted therapies such as BCR inhibitors can be attributed to disrupting the interaction of CLL cells with tumour promoting T cells.

Autologous stem cell transplantation, using the recipient's own cells, is not curative.

"Refractory" CLL is a disease that no longer responds favorably to treatment within six months following the last cancer therapy.

Leukemia is rarely associated with pregnancy, affecting only about one in 10,000 pregnant women.

Prognosis can be affected by the type of genetic mutation that the person with CLL has. Some examples of genetic mutations and their prognoses are: mutations in the IGHV region are associated with a median overall survival (OS) of more than 20–25 years, while no mutations in this region is associated with a median OS of 8–10 years; deletion of chromosome 13q is associated with a median OS of 17 years; and trisomy of chromosome 12, as well as deletion of chromosome 11q, is associated with a median OS of 9–11 years. Telomere length has been suggested to be a valuable prognostic indicator of survival. In addition, a person's sex has been found to have an impact on CLL prognosis and treatment efficacy. More specifically, females have been found to survive longer (without disease progression) than males, when treated with certain medications.

CLL is the most common type of leukaemia in the Western world compared to non Western regions such as Asia, Latin America, and Africa. It is observed globally that males are twice as likely than females to acquire CLL. The median age of diagnosis is 70 years. In older people, however, this difference becomes less pronounced: after the age of 80 years, new cases of CLL are diagnosed equally between men and women. In that same year, 2,620 males and 1,700 females (total of 4,320 people) are expected to die from CLL. In Western populations, subclinical "disease" can be identified in 3.5% of normal adults, and in up to 8% of individuals over the age of 70. That is, small clones of B cells with the characteristic CLL phenotype can be identified in many healthy elderly persons. The clinical significance of these cells is unknown. In contrast, CLL is rare in Asian countries, such as Japan, China, and Korea, accounting for less than 10% of all leukemias in those regions. A low incidence is seen in Japanese immigrants to the US, and in African and Asian immigrants to Israel. People who live near areas with considerable industrial pollution have an elevated risk of developing leukemia, particularly CLL.

In light of new therapies such as targeted agents, the role of bone marrow transplants is decreasing. Bone marrow transplants are not recommended as a front line therapy, and only recommended in specific cases where front line therapies have either failed or there is a lack of response to BCL 2 inhibitors. Researchers at the Abramson Cancer Center of the University of Pennsylvania School of Medicine reported preliminary success in the use of gene therapy, through genetically modified T cells, to treat CLL. The findings, which were published in August 2011, were based on data from three patients who had modified T cells injected into their blood. The T cells had been modified to express genes that would allow the cells to proliferate in the body and destroy B cells including those causing the leukemia. Two patients went into remission, while the presence of leukemia in the third patient reduced by 70%. One of the patients had been diagnosed with CLL for 13 years, and his treatment was failing before he participated in the clinical trial. One week after the T cells were injected, the leukemia cells in his blood had disappeared. The T cells were still found in the bloodstream of the patients six months after the procedure, meaning they would be able to fight the disease should leukemia cells return. Research is also investigating therapies targeting B cell receptor signalling. Syk inhibitors fostamatinib and entospletinib are currently in trials. The trial of a combination of ibrutinib and venetoclax had encouraging results in a small number of people. People with CLL undergoing immunotherapy with chimeric antigen receptor T cells have been found to have a high response rate.