geriatric acute leukemia
Introduction
Introduction to senile acute leukemia The definition of senile leukemia is different. Generally, leukemia patients who are 60 years old and older, like leukemias of other age groups, are malignant diseases of primary hematopoietic stem cells with unknown etiology. basic knowledge Sickness ratio: 0.0001% Susceptible people: good for older people over 60 years old Mode of infection: non-infectious Complications: disseminated intravascular coagulation
Cause
Causes of senile acute leukemia
Virus (20%):
Leukemia virus has been isolated from spontaneous leukemia tissues of chickens, mice, cats, cattle and gibbons. It is a retrovirus and is mostly C-type under electron microscope. The etiology of human leukemia has been studied. Decades of history, but so far only adult T-cell leukemia has been caused by viruses. In 1976, Japans Gao Yueqing first reported adult T-cell leukemia or lymphoma (ATL), and later epidemiological investigations were found in southwestern Japan, the Caribbean. The sea area and Central Africa are high-risk areas. In 1980, ATL-related antigens were found in ATL cells, and virus particles were found under electron microscope. Gallo of the United States and Rizhao Reif of Japan separated from patient cultured cell lines. C-shaped reverse transcribed RNA viruses, named HTLV-I and ATLV, respectively, were confirmed to be consistent, which is a major contribution to the etiology of human leukemia virus. ATL high-incidence area is also a high-risk area of HTLV-I infection, HTLV -I is contagious and can be transmitted through mother-to-child transmission of milk, through sexual intercourse and transfusion, other viruses such as HTLV-II and hairy cell leukemia, Epstein-Barr virus and ALL-L3 Relational has not yet entirely sure, other types of leukemia is still unable to confirm the virus etiology is not contagious.
Ionizing radiation (15%):
Ionizing radiation has leukemia-like effects. Its effect is related to the size of the radiation dose and the irradiation site. One large dose or multiple small doses can cause leukemia. Whole body irradiation, especially bone marrow exposure, can cause bone marrow suppression and immunosuppression. The rupture and distortion of chromosomes can still be observed for several months. The number of leukemias in survivors in Hiroshima and Nagasaki in Japan in 1945 was 30 times and 17 times higher than that in unirradiated areas. Radiation therapy for ankylosing spondylitis and 32P treatment The incidence of leukemia and leukemia was higher than that of the control group. According to the survey from 1950 to 1980 in China, the incidence of leukemia in clinical X-ray workers was 9.61/100,000 (standardized rate was 9.67/100,000), while other medical staff was 2.74. 100/000 (standardized rate 2.77/100,000), radiation can induce acute non-lymphocytic leukemia (ANLL), acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML), and there is often a period of myelosuppression before onset The incubation period is 2 to 16 years. There is no exact basis for whether diagnostic radiation will cause leukemia, but intrauterine irradiation can increase leukemia in infants after birth. Dangerous.
Chemical substances (15%):
Benzene-induced leukemia is more positive, benzene-induced acute leukemia is mainly acute granules and erythroleukemia, benzene-induced chronic leukemia is mainly CML, alkylating agents and cytotoxic drugs can cause secondary leukemia is also more certain, most secondary leukemia It is a malignant tumor of the original lymphatic system and a malignant tumor that is prone to immunodeficiency. It occurs after long-term alkylating agent treatment. The interval between the two is 8 to 8 years. The secondary leukemia caused by chemotherapy is mainly ANLL, and there is often one before the onset. In the whole blood cell reduction period, in recent years, there have been reports of nearly 100 cases of secondary leukemia caused by B-morpholine. This drug is used to treat psoriasis. It is a very strong chromosomal aberration substance. After taking B-morpholine 1 Leukemia occurred in ~7 years.
Genetic factors (10%):
The incidence of certain leukemias is related to genetic factors. Single-oval twins such as one person suffer from leukemia, another person has a 20% chance of developing leukemia, familial leukemia accounts for 0.7% of leukemia cases, occasionally congenital leukemia, and some hereditary diseases often With high incidence of leukemia, including Down, Bloom, Klinefelter, Fanconi and Wiskott-Aldrich syndrome, such as Down syndrome, the incidence of acute leukemia is 20 times higher than the general population, most of the above hereditary diseases have chromosomal aberrations and fractures. But most leukemias are not hereditary diseases.
Pathogenesis
Leukemia originates from the malignant transformation of individual hematopoietic progenitor cells or stem cells of bone marrow, and then the malignant cells (clone) are replicated and expanded. The most prominent feature of this malignant cell is the maturation disorder, the level of ALL after the proto-lymphocytes, ANLL in the original The level of granules and promyelocytes loses the ability to differentiate and mature. This hyperproliferative and indifferent leukemia cells accumulate in the bone marrow, causing an increase in bone marrow pressure, rupture of the sinusoidal barrier, and entry of immature leukemia cells into the surrounding blood. Leukemia cells can also circulate to the tissue and maintain the ability to continue to proliferate, causing leukemia infiltration of organ tissues.
The reason why leukemia is malignant from a hematopoietic progenitor or stem cell is: 1 almost all ALL leukemia cells have cloned expression of immunoglobulin (Ig) or T cell receptor (TCR) gene rearrangement; 2 all of the same patient Leukemia cells have the same cytogenetic abnormalities, 6-phosphate glucose dehydrogenase (G-6PD) isoenzyme type and immunophenotype; 3 most patients with complete remission (CR) relapse, their leukemia cell genotype and The phenotype reproduces the cloning at diagnosis, and the mechanism of leukemia in hematopoietic cells remains unclear. Some chromosome abnormalities are directly related to the occurrence of leukemia. Chromosomal breaks and translocations can cause the location of oncogenes to move and be activated. The change of gene structure in chromosome can directly cause cell mutation. The chromosome rearrangement of leukemia cells changes the structure or regulation of cell oncogene, which causes the quality and quantity of gene products to change. The latter may be related to the occurrence and maintenance of leukemia. , such as APL (M3) with t (15; 17), the RAR gene located on the long arm of chromosome 17 and the promyelocytic white on the long arm of chromosome 15 The fusion of the blood disease gene (PML) produces the fusion receptor PML-RAR, which is the molecular basis for the effective treatment of APL and all-trans retinoic acid. t(9;22) produces an abnormal tyrosine kinase protein, t (8;14) produces overexpression of growth regulatory protein (myc), and t(1;19) forms a new DNA-binding protein, which may be associated with leukemia.
The exact mechanism of leukemia cell proliferation and normal hematopoietic cell suppression has not been determined, but growth factor, normal and growth factor receptors of leukemia cells, and growth factor receptor reactivity play an important role in the proliferation and inhibition of the two types of cells, growth Factor receptors or growth factor transcription signals from cell membranes to the nucleus are encoded by oncogenes expressed by leukemia cells. It has been observed that leukemia cells can produce colony-stimulating factor (CSF), which may be related to the infinite proliferation of leukemia cells; Normal CSF has a stimulating effect on leukemia clonal cells in vitro; peripheral red blood cells, thrombocytopenia, and leukemia cells in the bone marrow are the dominant hematological features of acute leukemia, presumably due to the exclusion of normal hematopoietic stem cells by leukemia cells, However, some patients have low bone marrow hyperplasia, which is difficult to explain by leukemia cell exclusion. It is believed that leukemia cells inhibit normal hematopoietic cells through cell-mediated or humoral mechanisms, and then it is confirmed that there is an inhibitory active substance in leukemia cell extract or medium, specifically Inhibition is at Normal progenitor colony forming units (CFU-C) during DNA synthesis; a variety of interleukin-2 receptors (IL-2R) are present on the surface of leukemia cells with multiple lymphocytic leukemias, which may block IL-2 as a blocking factor Normally activated lymphocyte binding affects the activity of normal lymphocytes and the release of lymphokines, thereby facilitating the proliferation of leukemia cells.
Prevention
Elderly acute leukemia prevention
(1) Avoid contact with excessive X-rays and other harmful radiation. Personal protection is required for those engaged in radiation work. Pregnant women and infants should especially be careful to avoid exposure to radiation.
(2) Prevention and treatment of various infections, especially viral infections. Such as C-type RNA virus.
(3) Use certain drugs with caution. Such as chloramphenicol, phenylbutazone, certain antiviral drugs, certain anti-tumor drugs and immunosuppressants, etc., should avoid long-term use or abuse.
(4) Avoid contact with certain carcinogens and do a good job in occupational protection and monitoring. For example, in the production of phenol, chlorobenzene, nitrobenzene, spices, pharmaceuticals, pesticides, synthetic fibers, synthetic rubber, plastics, dyes, etc., pay attention to avoid contact with harmful and toxic substances.
(5) For the high-risk groups of leukemia, regular census work should be done, paying special attention to leukemia sirens and early symptoms. Those who have the condition can take the Tianxian vital source for preventive treatment.
(6) Eat more natural foods and regular foods that have been tested for hygiene, such as fresh vegetables and whole grains.
Complication
Elderly acute leukemia complications Complications disseminated intravascular coagulation
(1) Bleeding: Leukemia patients with malignant hyperplasia of leukemia cells, platelets are significantly reduced, easy to cause respiratory, digestive tract, urinary bleeding, especially intracranial hemorrhage, so it is necessary to take active hemostasis according to the cause, including infusion of concentrated platelets.
(2) Pulmonary disorders: due to the normal mature neutrophils in leukemia patients, immune function is reduced, often leading to lung infection. In addition, leukemia cells, infiltration can block small blood vessels in the lungs, bronchial dyspnea, respiratory distress syndrome, chest X-ray can have hairy glass or miliary network, can be used for experimental treatment of lung radiation.
(3) Electrolyte imbalance: In the course of treatment of white backlog disease, excessive potassium is often destroyed due to excessive destruction of leukemia cells or chemotherapy-induced renal damage. Due to chemotherapy, the dietary taste is poor, the digestive system is dysfunctional, and the amount of hypoxia is low. Or due to the destruction of leukemia cells, the release of phosphorus increases, resulting in low calcium and the like. Therefore, attention should be paid to the electrolyte concentrations of potassium, calcium and sodium during the treatment.
(4) disseminated intravascular coagulation (DIC): disseminated blood vessels are a group of severe hemorrhagic syndrome.
Symptom
Symptoms of acute leukemia in the elderly Common symptoms: pale nosebleeds after labor, shortness of breath, dizziness, activity, shortness of breath, oral ulcers, gastrointestinal bleeding, eyeballs, protruding gum bleeding
Most of the acute leukemia in the elderly is slowly onset, gradually progressing, with fatigue, pale, poor appetite, and shortness of breath after labor; it can also be caused by lymph nodes, hepatomegaly, splenomegaly or joint pain; The symptoms of colds, some patients have been diagnosed because of skin purpura or bleeding after tooth extraction. Because the degree and sequence of leukemia cells infiltration in various systems are different, each patient's onset or first sight symptoms are different. The main clinical manifestations can be summarized as the symptoms caused by the reduction of normal hematopoietic cells, including infection and fever, anemia, hemorrhage, etc., as well as the clinical manifestations caused by leukemia cells infiltrating the whole body system, various organs, as follows.
Infection and fever
Half of the patients showed early fever, fever, chills, sweating, although leukemia itself can be fever, but higher fever often suggests secondary infection, but many patients are not easy to find infection, infection can be Occurred in various parts, such as stomatitis, gingivitis, pharyngitis is the most common, ulceration or necrosis can occur, lung infection, perianal inflammation, anal abscess is also common, severe sepsis can cause sepsis or bacteremia, the most common The pathogenic bacteria are Gram-negative bacilli, such as Klebsiella pneumoniae, Pseudomonas aeruginosa, aerogens, etc., others have Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus faecalis, etc., have long been used antibiotics, can Fungal infections, such as Candida, Aspergillus, Cryptococcus, etc., can cause viral infections such as herpes zoster after the patient's immune function is deficient, occasionally with K. pneumoniae.
2. Bleeding
It is one of the common symptoms of acute leukemia in the elderly. It is more common in skin stasis, ecchymosis, nosebleed, and gum bleeding. The visual fundus caused by retinal hemorrhage is also common. It often occurs simultaneously with other parts of the bleeding, which may be a precursor to intracranial hemorrhage. Intracranial hemorrhage has headache, vomiting, asymmetry of pupil, and even coma and death. Intra-auricular hemorrhage may have vestibular dysfunction and cochlear dysfunction. Clinical manifestations include dizziness, nausea, tinnitus, hard of hearing, walking and falling, etc., gastrointestinal bleeding A large amount of vomiting or blood in the stool may occur. Thrombocytopenia is the main cause of bleeding, but platelet dysfunction, clotting factor is reduced, leukemia cell infiltration and infection of toxins on blood vessels, and arteriosclerosis in the elderly become brittle, which may also cause bleeding. the elements of.
Anemia
Almost all patients have anemia symptoms in the early stage, which is aggravated with the progress of the disease. The clinical findings are pale, fatigue, palpitations, post-exercise shortness of breath and edema are all related to anemia. Half of the patients have severe anemia at the time of presentation, mainly due to normal erythropoiesis. Reduced, in addition, factors such as ineffective red blood cell production, hemolysis and blood loss are also related.
4. Infiltration performance
(1) lymphadenopathy: most acute lymphoblastic and about half of acute blast leukemia have lymphadenopathy, generally from peas to cherries, medium and hard texture, non-adhesive, no tenderness, extensive lymphadenopathy in the body can also be Occurred in acute lymphoblastic leukemia, but not as slow as drenching, occasionally swollen lymph nodes involving deep tissues, mediastinal lymphadenopathy is common in T-cell acute leukemia.
(2) Hepatosplenomegaly: Leukemia infiltration occurs most in the liver and spleen. Clinically, hepatosplenomegaly is most prominent in acute lymphadenopathy, but most of them do not exceed 4 cm below the costal margin. Individual spleens can reach the umbilicus, and the liver and spleen texture can be Medium hardness, smooth surface, no obvious pain, liver infiltration is common, but there is often no liver damage in the clinic. During the course of the disease, the spleen marrow can increase rapidly, resulting in infarction and spontaneous rupture. Deteriorating and rapidly developing can be used to predict the evolution of the disease.
(3) bones and joints: patients often have local tenderness at the lower end of the sternum, suggesting excessive proliferation of leukemia cells in the bone marrow cavity, which is helpful for diagnosis. Joint and bone marrow pain are more common in acute drenching, mainly due to dull pain and soreness, due to leukemia in the bone marrow cavity. A large number of cells proliferate, oppress and destroy nearby bones, occasionally severe pain, leukemia cells can also infiltrate the joints, causing joint pain is often misdiagnosed as "rheumatism."
(4) Central nervous system: In recent years, chemotherapy has improved the remission rate of leukemia, and the survival period has been prolonged. Because general chemotherapy drugs are difficult to pass the blood-cerebrospinal fluid barrier, leukemia cells hidden in the central nervous system cannot be effectively killed. In addition, cerebrospinal fluid The middle folate is three times higher than plasma, which is also beneficial to the growth of leukemia cells, thus causing dead central nervous system leukemia (CNS-L), and is considered to be an important factor leading to leukemia recurrence. CNS-L can occur in various stages of the disease. However, most patients have symptoms late, often occur in the remission period, more acute leaching than blast, white blood cell count less than 10.0 × 109 / L is less than 50.0 × 109 / L, early liver, spleen, lymph nodes Larger than no enlargement, the difference between the two is significant. The clinically mild manifestations of headache, dizziness, severe vomiting, neck stiffness, even convulsions, coma, but no fever, increased cerebrospinal fluid pressure, cranial nerve damage can occur Visual impairment and facial paralysis.
(5) Eye: granulocytic sarcoma or chloroma formed by granulocytic leukemia often involves the periosteum, which is the most common eyelid site, which can cause ocular protrusion, diplopia or blindness. Leukemia can directly infiltrate the optic nerve. The choroid, retina, etc. cause the corresponding symptoms.
(6) skin and mucous membrane: specific skin lesions are more common in urgency, which can be expressed as diffuse maculopapular rash, local nodules or masses, systemic pustular rash and exfoliative dermatitis, etc. And ecchymosis, there are urticaria, herpes zoster, blister papules, pleomorphic skin damage, gum swelling and oral ulcers are common in rush orders; gums can be extremely hyperplasia, and even the entire tooth is submerged in swelling like a sponge In the gingiva.
(7) Testicles: The testicles are infiltrated, and there is painless swelling, mostly on one side. Although the other side is not swollen, there is often leukemia cell infiltration during biopsy, which is second only to CNS-L. The root cause of recurrence.
In addition, leukemia can infiltrate other organs, tissues, such as the lungs, heart, digestive tract, urinary system, etc., but not necessarily clinical symptoms. When leukemia cells proliferate too much, uric acid metabolism is hyperactive and excretion is increased. Kidney stones occur, and renal failure can occur from uric acid crystals and kidney stone obstruction.
Examine
Examination of senile acute leukemia
Peripheral blood
(1) White blood cells: In most patients, the number of white blood cells increases, and the late leukemia increases more significantly. The highest one can exceed 100×109/L, which is called high cell leukemia. There are also many patients whose white blood cell count is normal or reduced. Can be <1.0×109/L, called leukocyte non-hypertrophic leukemia, blood samples can be found in the original cells or immature cells, generally accounting for 30% to 90%, or even more than 95%, but the leukocyte does not increase the case Or less naive cells can be found by careful sorting or centrifugation of the smear.
(2) red blood cells and hemoglobin: patients may have different degrees of anemia, the elderly anemia is slightly milder, mostly positive pigments, normal cell anemia, a small number of patients with red blood cells of different sizes and deformities, a small number of young red blood cells can be found in the blood. .
(3) platelets: most of the reduction, about 50% of patients with platelets below 60 × 109 / L, very early patients with platelet count may be normal or slightly reduced, late platelets tend to be extremely reduced, patients often have prolonged bleeding time and clot retraction bad.
2. Bone marrow
Bone marrow has a characteristic diagnostic value. The vast majority of patients with bone marrow hyperplasia are extremely or significantly active, and a small number of low-proliferative leukemia bone marrow is reduced, regardless of the active or reduced myeloproliferation, mainly the original leukemia (M3 type is early-young The cells, which usually account for 30% to 90% of non-erythroid cells, are arrested in the original (M3 type is early-young) cell stage, while the mature intermediate cells are absent, and a small number of mature granulocytes remain, forming the so-called "Rift hole" phenomenon, normal young red blood cells and megakaryocytes are reduced, and the morphology of leukemia primordial cells often changes abnormally, such as larger cell bodies, increased proportion of nucleoplasm, abnormal nuclear morphology (such as notch, depression, lobulation, etc.). The chromatin is rough, the arrangement is disordered, and the nucleolus is obvious. Some small granulocytes of acute blast leukemia resemble lymphoblasts, and the M6-type (erythroblastic) erythroid cells are often similar to megaloblastic anemia. The atypical form of cells needs to be identified by cytochemistry. Auer bodies help to identify acute lymphoblastic and acute non-leukemia, and Auer bodies are more common in cytoplasm of acute blast leukemia. Acute sputum and acute granulocyte-monocytic leukemia cell cytoplasm can also be seen sometimes, acute lymphocytic leukemia is not Auer corpuscle, due to the extreme proliferation of leukemia bone marrow cells, bone marrow fluid is too thick, may lead to puncture failure, leukemia cells infiltrate bone marrow Degree, the parts are not consistent, a single puncture may not be able to obtain a typical bone marrow, if necessary, should choose different parts of repeated puncture.
3. Cell chemistry
It is mainly used to assist in morphology and identify various types of leukemia. Generally, it can differentiate between three kinds of leukemias, such as granule, mononuclear and lymph, by peroxidase, Sudan black lipid, non-specific lipase and its inhibition test. (PAS) can be used to identify the above three kinds of cells, but also can be used to identify erythroleukemia (M6 type) and megaloblastic anemia. The former is often strongly positive, the latter reaction is not obvious, acute granulocyte leukemia neutrophil base The phosphatase (NAP) response was significantly reduced, while the neutrophil alkaline phosphatase response in acute leukemia was increased.
4. Immunological examination
The introduction of various monoclonal antibodies has laid the foundation for the immunophenotyping of leukemia and improved the accuracy of leukemia diagnosis. According to the immunological markers of leukemia cells, not only can acute lymphoblasts be differentiated from acute leukemia, but also T cells and B cells are rapidly differentiated from leukemia (Table 2). According to MIC typing, monoclonal antibodies can also divide acute leukemia into several subtypes.
5. Chromosome changes
Using high-resolution chromosome zoning technology, 80%-85% leukemia can detect chromosomal abnormalities, some group abnormalities are specific, for example, t(15;17) is only found in M3; the structural abnormality of chromosome 16 is most common in M4 Acid form and M2; t (8; 14) appear in B cells.
6. Culture of granulocyte-mononuclear progenitor cells (CFU-GM)
CFU-GM colonies of acute non-leukemia leukemia do not produce or produce little, but the number of clusters increases; colonies regain growth when remission, and colonies decrease before recurrence, so CFU-GM culture has a certain significance in estimating prognosis and preventing recurrence. .
7. Blood biochemical changes
During chemotherapy, serum uric acid concentration increased, urinary uric acid excretion increased, and even uric acid crystals appeared. Patients with DIC may have coagulation mechanism disorder, acute leukemia serum and urinary lytic acid activity increased, acute blast leukemia did not increase, and acute lymphoblastic Leukemia is often reduced.
8. In the presence of central nervous leukemia, the number of white blood cells in the cerebrospinal fluid increases (>0.01×109/L), the protein increases (>450 mg/L), and the amount of sugar decreases. The smear of cerebrospinal fluid can find leukemia cells.
According to the condition, clinical manifestations, symptoms, signs, choose to do electrocardiogram B-ultrasound, X-ray, CT, MRI and other tests.
Diagnosis
Diagnosis and diagnosis of acute leukemia in the elderly
According to the clinical manifestations, peripheral blood and bone marrow, acute leukemia diagnosis is generally not difficult, because the type of leukemia is different, the treatment plan and prognosis are not the same, therefore, after the diagnosis is established, the type should be further determined.
Differential diagnosis
1. Leukocytosis does not increase leukemia: Because it is often difficult to find "naive" cells in the blood, diagnosis can be difficult, sometimes easy to be confused with aplastic anemia, primary thrombocytopenic purpura and acute granule cell deficiency, in addition to Need to be differentiated from myelodysplastic syndrome, leukocyte abnormalities caused by certain infections.
2. Aplastic anemia: Concurrent infection is not as significant as acute leukemia, bleeding tendency may be mild; liver, spleen or lymph node enlargement is rare; repeated "blood or bone marrow examination" does not find "naive" cells can be clearly concluded.
3. Myelodysplastic syndrome: RAEB and RAEB-T in this disease, except for pathological hematopoiesis, a small amount of primitive and immature cells in the peripheral blood, complete blood cell reduction and chromosomal abnormalities, easily confused with leukemia, but primitive cells in the bone marrow No more than 30%, bone marrow biopsy is relatively specific.
4. Some leukocyte abnormalities caused by some infections: such as infectious mononucleosis, amorphous lymphocytes appear in the blood, but the morphology is different from that of the original cells, the serum heterophilic antibody titer is gradually increased, the course is short, and it can heal itself. When pertussis, infectious lymphocytosis, rubella and other viruses are infected, the lymphocytes in the blood are increased, but the lymphocytes are normal in shape and can be self-healing.
5. Idiopathic thrombocytopenic purpura: patients have a history of recurrent bleeding, usually without fever, the degree of anemia is proportional to the bleeding, there is no "naive" white blood cells in the surrounding blood, bone marrow examination can confirm the diagnosis.
6. Recovery period of acute granulocyte deficiency: In the recovery period of granulocytosis caused by drugs and certain infections, the myeloid and promyelocytic cells in the bone marrow are significantly increased, but the disease has a clear cause, normal platelets, and promyelocytic cells. There is no Auer body in the body, and the mature granulocytes of the bone marrow return to normal in a short period of time.
