Chronic myeloid leukemia in the elderly

Introduction to chronic myeloid leukemia in the elderly Chronic myelocytic leukemia (CML) is a malignant clonal disease of acquired hematopoietic stem cells that occurs in middle age. It mainly involves the myeloid lineage, which is characterized by persistent progressive peripheral blood leukocyte count and splenomegaly. The course of the disease is slow, and most of them die from acute changes. basic knowledge Probability ratio: 0.05% of the specific population Susceptible people: the elderly Mode of infection: non-infectious Complications: acute respiratory distress syndrome in the elderly

The cause of chronic myeloid leukemia in the elderly

(1) Causes of the disease

The cause is not well understood and may be related to radiation.

(two) pathogenesis

The results of cell proliferation kinetics demonstrated that the in vitro colony forming ability of CML bone marrow hematopoietic precursor cells did not exceed normal, but peripheral blood had more hematopoietic precursor cells in active proliferative phase, while only a small amount of stationary phase in normal peripheral blood. According to the above results, some scholars believe that CML is the result of inconsistent proliferation and differentiation. In recent years, some scholars believe that the myeloid cells in the bone marrow and peripheral blood increase in CML, and the different stages of granulocytes in peripheral blood. The reason can be attributed to the fact that the bcr/abl gene itself is an anti-programming death gene, which causes CML cells to not die in time. The cells in different stages of different stages of accumulation accumulate in hematopoietic tissue and blood, or are considered to be defects in the adhesion function of CML stem cells. Stem cells prematurely escape the bone marrow stromal layer and cause proliferation and differentiation inconsistency, and make immature cells easy to cross the bone marrow barrier into the blood circulation. The therapeutic mechanism of interferon alpha is that it can correct this adhesion defect of hematopoietic stem cells.

According to cytogenetics including karyotyping analysis, band-forming techniques and fluorescein chromosome in situ hybridization (FISH) and molecular techniques such as Southern blotting or reverse transcriptase chain reaction (RT-PCR) and other sensitive detection methods Clinically diagnosed as bone marrow or peripheral blood cells of CML patients, CML can be divided into three categories:

More than 190% of CML patients are Ph(+)CML.

More than 25% of CML is Ph negative, bcr gene rearrangement or RT-PCR bcr/abl mRNA positive, then Ph(-)bcr/abl(+)CML, ie the karyotype is normal but there is a fusion gene.

3 very few patients were Ph(-)RT-PCR(-)CML, of which 1 and 2 were typical CML, the clinical manifestations, the same course of disease, no significant difference in survival, and 3 and chronic monocytic leukemia. Similarly, the CML routine treatment response is poor, and the survival period is shorter.

Ph chromosome exists in myeloid, erythroid, megakaryocytic and T, B lymphocytes, but not in bone marrow fibroblasts or other tissue cells. In the chronic phase, granulocyte involvement is prominent, often accompanied by megakaryocytes, platelets. Over or even the peripheral blood three lines are significantly increased, more prominent in the rapid changes, or for acute granulation, or acute leaching, or acute megakaryocyte leukemia, its blood, bone marrow and acute leukemia, similar to CML It is a hematopoietic stem cell disease.

Elderly patients with chronic myeloid leukemia prevention

Risk factor

(1) Ionizing radiation: Ion irradiation is an important factor causing chronic myelogenous leukemia. Ion irradiation generally includes: X-ray diagnosis and treatment, radioactive drug intake and radiation therapy.

(2) Chemical factors: Many chemical agents are induced by leukemia. Perennial exposure to benzene compounds is closely related to the occurrence of leukemia. The risk of leukemia in patients with aplastic anemia caused by phenylbutazone and chloramphenicol is also increased. In addition, there are increasing reports of overlapping cancers in patients with cancer after the use of alkylating agents such as busulfan and cyclophosphamide. The incidence of radiotherapy and chemotherapy is increased more significantly.

(3) Viral factors: The data confirmed that the presence of RNA-dependent DNA polymers (also known as reverse transcriptase) in leukemia tumor cells further affirmed the virology of leukemia, which can alter the genetic code of intracellular DNA. Once transcription occurs, the DNA of the virus binds to the pre-transcriptional gene in the host's nucleus and is then translated to produce a transforming protein that causes a malignant transformation of the parasitized cells.

(4) Genetic factors: Clinical data found that the incidence of leukemia in the same twins is about 5 times higher than other populations. It is generally believed that the influence of genetic factors on leukemia is positive, but leukemia is by no means "family hereditary" disease.

2. Tertiary prevention

Primary prevention:

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

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

(3) For the application of radiopharmaceuticals and chemical preparations (especially alkanes), it is necessary to strictly control the indications and dosages of the drugs, avoid abuse, and at the same time or subsequently give corresponding protective drugs to reduce the occurrence of drug-induced slow particles.

(4) Take necessary protective measures for people who work in the radioactive environment for a long time, such as wearing anti-radiation isolation suits, regular treatment, supplementing with multivitamins, etc., and keeping and isolating radioactive instruments or articles to avoid surrounding Human radiation.

(5) Pregnant women should avoid ionizing radiation and unnecessary drug intake during pregnancy.

Secondary prevention: carry out crowd census, the elderly should experience it regularly, give blood to suspected cases, and further test the bone marrow image to achieve early detection, early diagnosis and early treatment.

Tertiary prevention: For patients who have been diagnosed as chronic granules, according to the condition of the body, the progress of the disease, and the treatment of various important organ functions, the disease is controlled, the quality of life of the patient is improved, and the survival time is prolonged.

Chronic myeloid leukemia complications in the elderly Complications, acute respiratory distress syndrome in the elderly

Major bleeding, spleen infarction, respiratory distress syndrome, systemic failure, etc.

Symptoms of Chronic Myeloid Leukemia in the Elderly Common Symptoms Weakness, Dizziness, Liver enlargement, dyspnea, skin infiltration, hyperthermia, lymphadenopathy, joint pain, severe pain, splenomegaly

The progress of most patients is concealed. The symptoms are directly proportional to the number of white blood cells. The number of white blood cells in peripheral blood is asymptomatic (30~50)×109/L (3~50,000/mm3), often due to other diseases or health. At the time of examination, it was found that the number of white blood cells was higher than normal or splenomegaly and was diagnosed. The number of white blood cells>(50-100)×109/L was weak, the weight was reduced, the upper abdomen was full, and some patients had ulcerative conditions mostly caused by basophil cells. Increased, or self-infected left upper abdomen with a mass.

About 90% of patients have splenomegaly, and the spleen can reach the spleen and pelvis. The degree is different. The hard and often obvious cuts, 50% of patients have mild to moderate hepatic enlargement, and a few patients have mild superficial superficial Lymph node enlargement and skin infiltration.

Sternal tenderness is more common, mostly in the sternum, but the range of tenderness is small, which is an important feature of this disease; the degree of pain is directly proportional to the infiltration of leukemia cells.

Chronic phase rarely fever, white blood cells are too high (such as >200 × 109 / L) prone to leukocyte retention, may have difficulty breathing, dizziness, thrombosis, neuropsychiatric symptoms, abnormal penile erection, etc., severe pain in the spleen is the spleen Infarct signs, high fever, severe bone and joint pain or extramedullary infiltration.

Japanese scholars Kamada and Uchino take CML as an example of Hiroshima atomic bomb survivors. It is speculated that CML has a long period of genetic instability before the number of white blood cells >10×109/L, and then forms a Ph chromosome, which is at least 4 to 5 years. It can be as long as 20 to 30 years, that is, the Ph chromosome appears first, then the number of white blood cells increases, and the number of white blood cells reaches 100×109/L. The symptoms are more obvious. The average life expectancy of the patients treated by the traditional method after diagnosis is 3 to 4 years.

Clinical stage: The whole course of chronic myelogenous leukemia can be divided into three stages, chronic stage (stable phase), accelerated phase (proliferative phase) and acute phase change. The chronic phase can last for 1-3 years. After entering the accelerated phase, patients often have Fever, weakness, weight loss, rapid swelling of the spleen, pain in the sternum and bones, anaemia and hemorrhage gradually, the original effective drug becomes invalid, and the laboratory test can have the following changes:

1 blood or bone marrow blast cells >10%;

2 peripheral blood basophils >20%;

3 progressive reduction or increase in platelets of unknown origin;

4 other chromosomal abnormalities appear in addition to the Ph chromosome;

In the culture of 5-monoblast progenitor cells (CFU-GM), the clusters increased and the colonies decreased. The accelerated phase lasted for several months to several years. The acute phase was the end stage of chronic myelogenous leukemia. The clinical manifestations were similar to those of acute leukemia. The laboratory can have the following performance:

1 The original cells in the bone marrow or the original leaching + young single 20%, generally 30% to 80%;

2 peripheral blood granules + promyelocytes > 30%;

3 in the bone marrow of the original particles + promyelocytes >50%;

4 extramedullary primordial cell infiltration, most of the acute reversal of acute granules develop, 20% to 30% of acute leaching, occasional mononuclear cells, megakaryocytes and red blood cells and other types of acute changes, acute prognosis Poor, often dying within a few months.

According to the splenomegaly, hematological changes, Ph chromosome positive can make a diagnosis, for those who are clinically consistent with chronic myeloid leukemia and whose Ph chromosome is negative, the bcr/abl fusion gene should be further tested.

Examination of chronic myeloid leukemia in the elderly

Blood picture

The number of peripheral blood leukocytes increased significantly. The peripheral blood leukocytes in the chronic phase can reach (20-300)×109/L. There are different mature stages of granulocytes in the classification. The original granules plus promyelocytes are <10%, medium and young. The majority of granulocytes, the percentage of acidophilic and basophils increased, the number of red blood cells and hemoglobin increased in most patients, about one third of patients with hemoglobin less than 110g / L, the increase in platelet count is more common, the decline in anemia and platelet count is a sign of worsening the condition .

2. Bone marrow

Proliferation is vigorous or extremely hyperplastic, the ratio of granules: red can reach 15:1 to 20:1, the proportion of each stage in the granules increases, and the granules and promyelocytes in the chronic phase 10%, basophils and eosinophils The number of megakaryocytes can reach several hundred/piece. As the disease progresses, the percentage of protoplasts plus promyelocytic cells increases. In the late stage or acute change, the erythroid is obviously inhibited, the megakaryocytes are reduced, and the platelets are correspondingly reduced. See Gaucher cells and Pelger-Hüet abnormalities, a small number of patients with Alder-Reilly abnormalities, suggesting a poor prognosis, CML often secondary to different degrees of myelofibrosis, resulting in bone marrow dry pumping, bone marrow biopsy should be performed in patients with CML to determine bone marrow The degree of fibrosis, the reduction or disappearance of alkaline or phosphatase in blood or bone marrow cells is one of the characteristics of CML.

3. Cytochemistry and Biochemistry

(1) The activity of neutrophil alkaline phosphatase (NAP) is significantly reduced in 90% of patients, the score is reduced or negative, but the NAP activity of the elderly can be increased.

(2) The patient's plasma folic acid activity was significantly reduced, serum vitamin B12 level increased, the ratio of cyanocobalamin I and II changed; peripheral blood serum lysozyme activity increased, and lysozyme urine, the latter patient's general prognosis Poor, peripheral blood basophils increased, blood histamine increased, serum uric acid can be moderately elevated, and gout can occur, but uric acid nephropathy is less common, serum albumin is normal, gamma globulin is moderately elevated However, monoclonal immunoglobulin peaks are rarely seen.

(3) In the chronic phase of chronic phase, accelerated phase and acute phase, serum lactate dehydrogenase (LDH) is elevated, especially the increase of LDH-3 isoenzyme, the positive rate is as high as 75% to 100%, and the relief The positive rate was only 13%. This experiment can be used as an indicator of disease activity and tumor burden in CML patients.

4. Chromosome examination

85% to 94% of chronic granule patients have Ph chromosomes. Nowell and Hungerford first described this abnormality and named it Ph chromosome. Ph chromosome is the long arm translocation of chromosome 22, and 90% is translocation to the first On the long arm of chromosome 9 [t(9q+;22q-)], the remaining 10% of patients can translocate to any other chromosome, and more are 2, 10, 13, 17, 19 and 21 Chromosome.

It can be seen that the key of the Ph chromosome is the loss or shortening of the long arm of chromosome 22, and the Ph chromosome is not found in somatic cells, only in the dividing bone marrow cells. This phenomenon indicates that CML evolved from pluripotent hematopoietic stem cell mutation. In the process of rapid leukemia leukemia, there may be other abnormalities, such as the trisomy of chromosome 8 (+8), the extra Ph chromosome or the isobaric chromosome of the long arm of chromosome 17.

5.bcr/abl fusion gene detection

The bcr/abl fusion gene can be detected in Ph-positive patients. The nature of the Ph chromosome is that the C-abl proto-oncogene normally localized on chromosome 9 breaks at the 5th end of its second exon and translocates to On the chromosome 22, a functional undefined gene bcr (breakpoint cluster region) within the 3rd end (M-bcr) of the 2nd or 3rd exon, at the break, C-abl and M-bcr are spliced into one The new chimeric cause, the bcr/abl gene, encodes a protein P210. P210 has stronger tyrosine kinase (PTK) activity than C-abl-encoded P145, and can transform hematopoietic cells in vitro and induce CML. Therefore, the formation of bcr/abl chimeric genes is a key link in the pathogenesis of chronic granules.

A small number of patients are negative for Ph chromosome, and there is also a bcr/abl fusion gene. It is generally believed that patients with CML can be classified into the Ph(+) CML category regardless of the presence or absence of the Ph chromosome, as long as the bcr/abl fusion gene is present.

6. X-ray examination: Skeletal X-ray examination is normal in most patients, even in patients with obvious bone pain and joint pain, a small number of patients can see single or multiple osteolytic changes, which are invasive destruction of leukemia Related, biopsy in the osteolytic altered area, can be found that granulocytes significantly hyperplasia, large osteolytic changes suggest that patients will have a possibility of rapid changes.

Diagnosis and diagnosis of chronic myeloid leukemia in the elderly

Chronic myeloid leukemia needs to be differentiated from the following diseases.

1.Ph (+) acute leukemia

Although the Ph chromosome is a chronic chromosome leukemia marker chromosome, it can also occur in 2% acute leukemia and 20% adult acute leukemia. The identification is as follows:

1 Although very few acute squamous leukemias may be associated with Ph chromosome, spleen and basophils increase, and additional chromosomal abnormalities other than Ph are characteristic of CML blast, Ph(+)ALL needs to be distinguished from CML acute phalanx: Ph(+) ALL is easy to reverse after complete remission, and reappears when recurring, while the Ph chromosome of CML is difficult to reduce, and more importantly, there is a difference between the two at the genetic level. About half of the bcr rearrangement in Ph(+)ALL The same CML occurs in M-bcr, and the other half of the bcr breakpoint is on the m-bcr of about 40 kb upstream of M-bcr. The fusion gene is e102, and its expression products are 7.5 kb mRNA and P190 protein, respectively. The primers and probes can distinguish the fusion gene. Once the CML changes rapidly, the treatment response is very poor. The life of the acute granules is rarely more than half a year. The acute leaching can be extended to 1.5 or 2 years, and Ph(+)ALL is better. The prognosis of Ph(-)ALL is poor, but the response to strong chemotherapy is still better than that of CML.

2. Other causes of splenomegaly

Schistosomiasis, chronic malaria, kala-azar, liver cirrhosis, hypersplenism, etc. have splenomegaly, but each disease has clinical features of primary disease, blood and bone marrow without chronic leukemia, Ph chromosome negative.

3. Leukemia-like reaction

Leukemia-like reactions often occur in serious infections, malignant tumors, etc., and the number of white blood cells can reach 50×109/L. However, the leukemia-like reactions have their own etiology and clinical manifestations. After the primary disease control, the leukemia-like reaction disappears. In addition, splenomegaly is not as prominent as chronic myeloid leukemia. There are often toxic granules and vacuoles in cytoplasmic cytoplasm. Eosinophils and basophils do not increase, NAP response is strongly positive, Ph chromosome is negative in cells, platelets and hemoglobin The amount is mostly normal.

4. Myelofibrosis

Primary medullary fibrosis splenomegaly, leukocytosis in blood, and emergence of granulocytes, can be confused with chronic myelogenous leukemia, but the number of peripheral blood leukocytes in myelofibrosis is generally less than that of chronic myelogenous leukemia, no more than 30 × 109/L, and the fluctuation is not large, NAP is positive. In addition, the young red blood cells continue to appear in the blood, and the red blood cell morphology is abnormal, especially the teardrop red blood cells are easy to see, the Ph chromosome is negative, and the disease course is long.

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