Chronic lymphocytic leukemia in the elderly

Introduction to chronic lymphocytic leukemia Chronic lymphoblastic leukemia (CLL) is a malignant disease caused by the expansion of monoclonal small lymphocytes, which infiltrates bone marrow, blood, lymph nodes and other organs, eventually leading to normal hematopoietic failure. basic knowledge The proportion of the disease: the incidence of the disease in the middle-aged and elderly people over 50 years old is about 0.001%, very rare Susceptible people: the elderly Mode of infection: non-infectious Complications: anemia

The cause of chronic lymphoblastic leukemia in the elderly

(1) Causes of the disease

The study found that long-term exposure to low-frequency electromagnetic fields may be related to the pathogenesis of chronic colitis. The incidence of CLL in Europe and America is much more common than that in Asian countries. The risk of CLL in the immediate family members of CLL patients is three times higher than that of the general population. Men are easier than women. Suffering, indicating that genetic factors play a certain role in the pathogenesis of chronic colitis.

(two) pathogenesis

CLL is an acquired disease, which is confirmed by the immunophenotype of B-CLL. Most of them originate from the malignant transformation of B cells, and the B-CLL cell membrane expresses antigens close to the mature stage, such as CD19, CD20, CD21, CD23. CD24, HLA-DR and a light chain ( or ), but lacking the CD22 marker of normal mature B cells. B-CLL can differentiate into hair cells and plasma cells and have Ig secretion after induction by sterol in vitro. This indicates that CLL differentiation is blocked in the immature stage. Cell proliferation kinetics studies indicate that most CLL cells are in the GO stage, which determines the slow progression of CLL. In recent years, studies have shown that programmed cell death of CLL cells is suppressed, resulting in CLL cells in blood/bone marrow. Accumulation, not cleared in time, longer than normal B cells in the blood, these studies have proved that CLL is not a proliferative disease, but caused by differentiation, this blockage is reversible.

CD5+ cells are frequently increased in CLL, and CD5+ B cells play an important role in autoimmune diseases, which is also the cause of CLL with autoimmune hemolytic anemia or thrombocytopenia.

Decreased Ig secretion in CLL cells, resulting in patients with low gamma globulinemia, with the decrease of T helper cells, inhibition of cell growth and reduction of NK cells is the cause of repeated infections in patients with CLL.

The same karyotype abnormality as B cells cannot be detected in T cells of B-CLL patients. Therefore, it is currently considered that CLL T cells are not malignant clones, but 2% to 3% CLL is T-CLL, which may be derived from NK cells have an immunophenotype of CD3+, CD8+, and CD4+, and their clinical manifestations are similar to those of B-CLL, but they are prone to skin infiltration.

Elderly patients with chronic lymphocytic leukemia prevention

Risk factor

Radiation and chemical substances such as benzene and alkylating agents are not directly related to the pathogenesis of CLL. Although there have been reports of isolation of HTLV-I virus from the blood of CLL patients, there is still insufficient evidence for viral pathogenesis. The incidence of relatives is 2 to 4 times that of other people. At present, although the etiology of CLL is still unclear, more and more data indicate that the pathogenesis of CLL is a multi-step process, and the cytogenetics and gene regulation abnormalities of CLL, cells Cytokines and other aspects of the growth of the microenvironment are related.

2. Tertiary prevention

Primary prevention:

1 Eat more fresh fruits, vegetables, reasonable diet, proper physical exercise, and enhance the body's resistance.

2 Promote environmental protection and reduce pollution of natural resources (such as water, atmosphere, soil, etc.).

3 pregnant women should avoid ionizing radiation and unnecessary drug intake during pregnancy.

Secondary prevention: Screening of the population, middle-aged and elderly people should have regular physical examinations, in order to find asymptomatic leukemia patients, and provide necessary further examinations for suspicious cases, such as blood routine, white blood cell classification, B-ultrasound, lymph node puncture smear, etc. Early detection, early diagnosis, early treatment.

Tertiary prevention: Patients who have been diagnosed with chronic lymphocytic leukemia should be appropriately treated according to clinical stage, body condition, and complications, to control the condition, improve the quality of life of patients and prolong survival.

Elderly patients with chronic lymphocytic leukemia Complications anemia

Repeated infections, bleeding and anemia often occur.

Symptoms of chronic lymphocytic leukemia in the elderly Common symptoms Thrombocytopenia, fatigue, weight loss, hepatosplenomegaly, nodules, loss of appetite, lymphadenopathy, low fever, night sweats, immune hemolysis

Most of the patients are elderly, the average age of onset is 60-70 years old, the onset is very slow, often no symptoms, about 25% of patients are diagnosed due to other diseases to the hospital, early symptoms may have fatigue, late loss of appetite Symptoms such as weight loss, low fever, night sweats and anemia. Lymph node enlargement often causes the patient to pay attention first. The lymph nodes are mainly in the neck, ankle, and groin. The enlarged lymph nodes are not tender, more solid, movable, and even Obstructive symptoms occur due to enlarged lymph nodes compressing the biliary tract or ureter. 50% to 70% of patients have mild to moderate splenomegaly. Patients with advanced disease may have anemia, thrombocytopenia, purulent skin purpura, and T-cell slow-leukemia may develop skin. Thick, nodules and even erythroderma, etc., due to immune dysfunction, often susceptible to infection, about 8% of patients can be complicated by autoimmune hemolytic anemia.

Diagnostic staging:

Rai staging system:

Stage 0: Absolutely high lymphocytic leukemia (>15,000/l), no lymphadenopathy, hepatosplenomegaly, anemia or thrombocytopenia.

Stage I: The absolute value of lymphocytes is high, with enlarged lymph nodes, without hepatosplenomegaly, anemia, and thrombocytopenia.

Stage II: high absolute value of lymphocytes with hepatomegaly or splenomegaly, with or without lymphadenopathy, without anemia, thrombocytopenia.

Stage III: high absolute lymphocyte count and anemia (Hb<11g/dl), with or without lymphadenopathy, large liver and splenomegaly.

Stage IV: high absolute lymphocyte count and thrombocytopenia (<100,000/l), with or without lymphadenopathy, large liver, splenomegaly or anemia.

Binet staging:

Clinical stage A: no anemia or thrombocytopenia, less than 3 lymph node enlargements (Rai stage, 0, I, II).

Clinical stage B: no anemia or thrombocytopenia, with 3 or more lymph node enlargements (Rai stage I, II).

Clinical C: anemia and/or thrombocytopenia, regardless of the number of lymph nodes, (Rai stage III, IV).

Note: The lymph node area includes the neck, underarm, groin, liver and spleen.

Examination of chronic lymphocytic leukemia in the elderly

1. Blood: The number of white blood cells in peripheral blood increases, the absolute value of mature lymphocytes is >1.5×109/L (1500/mm3), lasting for more than 4 weeks, there may be a few atypical or immature lymphocytes, mild cases Without anemia or thrombocytopenia, broken cells are easy to see, neutrophil ratio is reduced, with the development of the disease, thrombocytopenia, anemia is gradually aggravated, such as autoimmune hemolytic anemia, 8% to 35% of patients anti-human globulin test (Coombs) was positive.

2. Bone marrow: showing nucleated cell proliferation, lymphocytes 40%, mainly mature lymphocytes, bone marrow biopsy suggests different degrees of lymphocyte infiltration, there are 4 different histological features, and related to disease prognosis:

1 nodular type (15%);

2 quality types (30%);

3 nodules and interstitial infiltration mixed type (30%);

4 diffuse infiltration (35%), usually in the early stage of the disease, common type 1 to 3, more common type 4 in the late stage of the disease.

3. Bone marrow cell immunophenotyping: More than 95% of CLL originates from B cell clones, so mature B cell markers such as CD19.CD20, CD21.CD23.CD24.HLA-DR are abnormally elevated or a light chain ( or Positive, about 50% of patients with CD25+, but CD10 is negative, T-CLL showed abnormal T cell markers, regardless of B or T-CLL, CD5+ percentage is high.

4. Immune function: the number of whole T cells and NK cells decreased, the ratio of T helper cells to T suppressor cells (CD4: CD8) was inverted, and the increase of CD5+ B cells was caused by autoimmune hemolysis or thrombocytopenia or pure red aplastic anemia. important reason.

5. Chromosome: About 50% of patients have chromosomal abnormalities, B-cell chronic lymphocytic leukemia is common with +12.14q+, 11q, 13q, etc. T-cell slow-leaching is common with INV(14).

6.20% to 60% of patients with hypogammaglobulinemia, including IgG, IgA and / or IgM type, can occur at any stage of the disease, varying in severity.

CT scan revealed a retroperitoneal, mesenteric lymph node enlargement.

Diagnosis and differential diagnosis of chronic lymphocytic leukemia

Diagnostic criteria

The absolute value of persistent peripheral blood lymphocytes for unknown reasons is >1.5×109/L, and the mature lymphocytes account for the vast majority. Whether with or without superficial lymphadenopathy or liver or splenomegaly, bone marrow aspiration or biopsy should be performed. Affirmative diagnosis, bone marrow showed hyperplasia, mature lymphocytes 40% is the diagnostic limit, the immune marker belongs to B-lineage, and the rare T-mark is used. After diagnosis, special examination such as B-ultrasound or CT is used to find whether there is chest or abdomen. The enlarged lymph nodes further clarify the extent of disease invasion, combined with anemia and thrombocytopenia to determine the stage of the disease.

1. Identification of benign lymphocytic diseases

Differential diagnosis

(1) Recovery period of chronic infection, especially tuberculosis: there should be a clear primary disease, which is more common in adolescents.

(2) Infectious mononucleosis: occurs mostly in adolescents, with special cell morphology, elevated serum IgM, positive heterophilic antibody agglutination test, and positive EB virus.

(3) Waldenström's macroglobulinemia: the number of blood lymphocytes is increased, the cells are plasma-like, often rich in basophilic cytoplasm, and there is a large amount of IgM in the membrane and cytoplasm, and the blood viscosity is obviously increased. There are swollen lymph nodes, liver and splenomegaly.

2. Identification with malignant lymphocytic disease

(1) Young lymphoblastic leukemia (PLL): occurs mostly in the elderly, the number of peripheral blood cells is significantly increased by naive lymphocytes, splenomegaly, bone marrow, blood immunophenotype is CD19.CD20, CD22.FMC7 positive, CD10 It can also be positive, and CD25 and CD38 are negative.

(2) adult T-cell leukemia: middle-aged disease, white blood cell count is normal or high, almost all patients have obvious lymphadenopathy, half of splenomegaly and skin infiltration, prone to hypercalcemia and osteolytic phenomenon, serum HTLV-I positive is characteristic.

(3) cutaneous T-cell lymphoma (Sezary syndrome): high incidence of middle-aged, normal or high white blood cell count, skin infiltration is prominent, easy to have superficial lymph nodes, but splenomegaly is rare, immune The phenotype is dominated by mature T cells.

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