Leukemia is a malignant clonal disease of hematopoietic stem and progenitor cells. Due to abnormal proliferation, differentiation, and apoptosis, leukemic cells arrest at various stages of development. The massive proliferation and accumulation of leukemic cells suppresses normal hematopoiesis and infiltrates other organs and tissues. Clinically, symptoms include varying degrees of anemia, bleeding, infection, fever, enlargement of the liver, spleen, and lymph nodes, and bone pain. Some leukemia patients can achieve remission or alleviation of symptoms with active and effective treatment, ensuring long-term survival. However, rapid disease progression or poor control can lead to death.
Clinical classification
Leukemia is divided into two categories: acute and chronic according to the degree of differentiation and maturity of leukemia cells and the natural course of the disease.
1. Acute leukemia (AL)
Cell differentiation is arrested at an early stage, mostly in the form of primitive cells and early immature cells. The disease progresses rapidly, with a natural course of only a few months. AL can be divided into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) based on the primary cell lineage affected.
2. Chronic leukemia (CL)
Cell differentiation is arrested at a late stage, with the majority being mature immature and mature cells. The disease progresses slowly, with a natural course of several years. Based on the primary cell lineage affected, CL can be divided into chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), and rarer types of leukemia, such as hairy cell leukemia and prolymphocytic leukemia.
Epidemiology
Contagious
The disease is not contagious.
Incidence
The incidence of leukemia in my country is 3 to 4 per 100,000 people. Acute leukemia is more common than chronic leukemia, with acute myeloid leukemia being the most common, followed by acute lymphocytic leukemia and chronic myeloid leukemia.
mortality rate
Among the mortality rates caused by malignant tumors, leukemia ranks 6th (male) and 8th (female), and ranks first among children and adults under 35 years old.
Incidence trend
The incidence of chronic myeloid leukemia and chronic lymphocytic leukemia increases with age.
High-risk population
1. People who are exposed to ionizing radiation such as radiation for a long time.
2. People with familial leukemia.
3. Patients with immunodeficiency diseases.
4. Among acute leukemias, acute myeloid leukemia is more common in adults, while acute lymphocytic leukemia is more common in children.
Causes
Overview
The etiology of leukemia is not fully understood, but may be related to biological, physical, chemical, genetic factors, or other blood disorders. These factors lead to increased self-renewal, uncontrolled proliferation, impaired differentiation, and blocked apoptosis of leukemic cells, causing them to stagnate at various stages of development. Leukemic cells proliferate and accumulate in the bone marrow and other hematopoietic tissues, inhibiting normal hematopoiesis and infiltrating other organs and tissues, thereby triggering corresponding symptoms.
Basic cause
1. Biological factors
The main causes are viral infection and immune dysfunction. Adult T-cell leukemia can be caused by human T-lymphotropic virus type 1. After infecting the body, the virus integrates and becomes latent within host cells as an endogenous virus. Under certain physical and chemical factors, it can be activated and expressed, inducing leukemia. Alternatively, it can be transmitted laterally from the outside world as an exogenous virus, directly causing disease. Some individuals with immune dysfunction, such as those with certain autoimmune diseases, have an increased risk of leukemia.
2. Physical factors
Including ionizing radiation such as X-rays and gamma rays. Studies have shown that large-area and high-dose irradiation can cause bone marrow suppression and decreased body immunity, DNA mutation, breakage and recombination, leading to the occurrence of leukemia.
3. Chemical factors
Long-term exposure to benzene and organic solvents containing benzene is related to the occurrence of leukemia. Ethylidene benzoate has extremely strong chromosomal aberration-inducing and leukemogenic effects. Alkylating agents and topoisomerase I inhibitors in anti-tumor drugs can also cause leukemia.
4. Genetic factors
Familial leukemia accounts for approximately 0.7% of all leukemias. In monozygotic twins, if one twin develops leukemia, the other has a 1/5 risk, 12 times higher than in dizygotic twins. Down syndrome, characterized by trisomy of chromosome 21, has a leukemia incidence of 50 per 100,000, 20 times higher than in the general population. Patients with congenital aplastic anemia, Bloom syndrome, ataxia-telangiectasia, and congenital immunoglobulin deficiency also have a higher incidence of leukemia.
5. Other blood diseases
Certain blood diseases may eventually develop into leukemia, such as myelodysplastic syndrome, lymphoma, multiple myeloma, paroxysmal nocturnal hemoglobinuria, etc.
symptom
Overview
The symptoms of leukemia often vary depending on the type. Most acute leukemias have a different onset. Acute ones may have a sudden high fever, similar to a “cold”, or severe bleeding; slow ones often have pale complexion, purpura on the skin, heavy menstruation or difficult to stop bleeding after tooth extraction, and are discovered when seeking medical treatment; chronic leukemia usually progresses slowly, and patients may have no obvious abnormalities in the early stages, and the corresponding symptoms will not appear until the disease progresses to the later stages.
Typical symptoms
1. Acute leukemia
(1) Manifestations of suppression of normal bone marrow hematopoietic function
① Anemia: Some patients may not have anemia due to a short course of illness. Half of the patients already have severe anemia when they seek medical attention, especially those with secondary myelodysplastic syndrome.
② Fever: Fever is an early symptom in half of patients. It can range from low-grade to as high as 39-40°C or higher, often accompanied by chills and sweating. While the disease itself can cause fever, high fever often indicates a secondary infection, most commonly occurring in stomatitis, gingivitis, and pharyngitis, often with ulcers or necrosis. Pulmonary infection, perianal inflammation, and perianal abscesses are also common, and in severe cases, bloodstream infection may occur. Immunocompromised patients may also develop viral infections.
③ Bleeding: Approximately 40% of patients experience early bleeding, which can occur throughout the body, with common manifestations including petechiae or ecchymoses on the skin, nosebleeds, gum bleeding, and menorrhagia. Fundus hemorrhage can cause visual impairment. A few patients may also develop coagulation abnormalities, leading to widespread systemic bleeding. Intracranial hemorrhage can cause headaches, vomiting, pupil asymmetry, and even coma and death.
(2) Manifestations of leukemia cell proliferation and infiltration
① Lymph nodes and liver and spleen: Lymph node enlargement is more common in ALL, while liver and spleen enlargement is mostly mild to moderate, and splenomegaly is rare.
② Bones and joints: Local tenderness below the sternum is common. Joint and bone pain may occur, especially in children. Bone marrow necrosis may cause severe bone pain.
③ Eyes: Some AML may be accompanied by granulocytic sarcoma, also known as green tumor, which often involves the periosteum, most commonly in the orbital area, and can cause proptosis, diplopia or blindness.
④ Oral cavity and skin: Gingival hyperplasia and swelling are common. Blue-gray maculopapular rashes may appear on the skin, with localized skin swelling, hardening, and purple-blue nodules.
⑤ Central nervous system: It is the most common extramedullary infiltration site of leukemia. Most chemotherapy drugs have difficulty passing through the blood-brain barrier and cannot effectively kill leukemia cells hidden in the central nervous system, thus causing central nervous system leukemia (CNSL). ALL is the most common, especially in children. Mild cases manifest as headache and dizziness, while severe cases may have vomiting, neck stiffness, and even convulsions and coma.
⑥ Testicles: Painless enlargement of one testicle is common. Although the other testicle is not enlarged, biopsy often reveals leukemic cell infiltration. This condition occurs in young children and young adults after chemotherapy-induced remission of ALL and is the second most common site of extramedullary recurrence after CNSL.
⑦Others: In addition to the above, leukemia can also infiltrate other tissues and organs such as the lungs, heart, digestive tract, and urinary and reproductive systems, and cause dysfunction of the corresponding organs.
2. Chronic leukemia
(1) Chronic myeloid leukemia
① Chronic phase (CP): Generally lasts 1 to 4 years. Patients often experience fatigue, low-grade fever, excessive sweating or night sweats, and weight loss. Most patients also have splenomegaly, and a few have hepatomegaly. When the white blood cell count (WBC) level is significantly elevated, fundus congestion and bleeding may occur. Extremely elevated levels can cause leukostasis, resulting in symptoms such as difficulty breathing, dizziness, and slurred speech.
② Accelerated phase (AP): This can last from several months to several years. Symptoms include fever, weakness, progressive weight loss, bone pain, gradual onset of anemia and bleeding, and persistent or progressive spleen enlargement.
③ Blastic crisis (BC): It is the terminal stage of chronic myeloid leukemia, and its clinical symptoms are similar to AL.
(2) Chronic lymphocytic leukemia
① Early stage: The onset is slow, and there are usually no subjective symptoms. Most patients are discovered during physical examinations or when they go to the doctor for other diseases. Those with symptoms may show fatigue, tiredness, weight loss, low fever, night sweats, etc. in the early stage. Most have swollen lymph nodes in the head and neck, supraclavicular, axilla, groin, etc., which are generally painless, tough, and have no adhesions. As the disease progresses, they may gradually increase in size or fuse. In severe cases, they may compress the trachea, superior vena cava, bile duct or ureter and cause corresponding symptoms. More than half of the patients have mild to moderate hepatosplenomegaly, and sternal tenderness is rare;
② Late stage: Anemia may occur and infection is likely to occur.
complication
1. Infection
Leukemia patients are often susceptible to infection by various viruses and bacteria due to decreased body resistance. Severe infections may be accompanied by sepsis, which is one of the main causes of death in patients.
2. Bleeding
When leukemia cells proliferate malignantly and coagulation disorders occur, patients may experience bleeding in various parts of the body, and severe intracranial hemorrhage may lead to death.
examine
Scheduled inspection
If you experience fever, pale complexion, night sweats, fatigue, continuous bleeding, skin bruises, enlarged lymph nodes or liver and spleen, bone and joint pain, exophthalmos, or visual impairment, please seek medical attention promptly. The doctor will first ask some basic questions and then perform a physical examination on the patient. If necessary, the doctor will recommend laboratory tests such as blood tests, bone marrow puncture, cytochemistry tests, immunology tests, cytogenetic tests, molecular biology tests, blood biochemistry tests, neutrophil alkaline phosphatase (NAP) assays, etc., in order to understand the progression of the disease.
Physical examination
The doctor will conduct physical examinations such as inspection, palpation, and auscultation on the patient to gain a preliminary understanding of the condition.
1. Visual examination
First, observe whether the patient’s mental state is good, whether he has symptoms such as pale face, bulging eyes, bleeding, skin bruises, and petechiae. Then ask the patient to raise his head and open his mouth to check whether there are abnormal manifestations such as bleeding from the mouth, nose, and gums, and gingival hyperplasia.
2. Palpation
First, the patient’s skin, lymph nodes, and bone joints are palpated to check for nodules, tenderness, and swelling. The patient is then asked to lie on the examination bed and the abdomen is palpated to confirm whether there is hepatosplenomegaly and the degree of enlargement. If the patient is a male, the doctor will also check for testicular swelling and involvement.
3. Auscultation
During the abdominal examination, doctors listen to the abdomen for an abnormal friction sound from the spleen.
Laboratory tests
1. Blood test
It can help doctors understand the degree of reduction of various blood cells and has reference value for diagnosis.
(1) AL: Most patients have an increase in leukocytosis, but some have normal or decreased leukocytosis. Blood smears show varying numbers of primitive and immature cells, often with varying degrees of anemia, and platelet counts are decreased to varying degrees, which can assist in diagnosis.
(2) CL: AML patients may have a significant increase in white blood cell count, often greater than 20×10 9 /L; blood smears show a significant increase in granulocytes, with the majority being neutrophils, late neutrophils, and band-shaped granulocytes. Platelet counts may be normal, increased, or decreased. Eosinophils and basophils increase, with AP basophils greater than 20%. In the chronic phase of CP, primitive cells are less than 10%, AP greater than 10%, and BC greater than 20%. CLL is characterized by a persistent increase in lymphocytes, with B cells greater than 5×10 9 /L. Most leukemic cells are morphologically similar to mature small lymphocytes, with scant cytoplasm and clumped nuclear chromatin. Blood smears show broken cells, a few cells have abnormal morphology, large, immature cell bodies, and deep notched nuclei. Occasionally, primitive lymphocytes are seen. The neutrophil ratio decreases. As the disease progresses, thrombocytopenia and anemia may occur.
2. Bone marrow puncture
(1) AL: Bone marrow puncture is the main basis for the diagnosis of acute leukemia and is a must-do examination. Most patients have significant proliferation of nucleated cells, mainly primitive cells, and a few have hypoplasia. The FAB classification defines the diagnostic standard for AL as primitive cells greater than 30% of bone marrow nucleated cells, while the WHO classification lowers the standard to 20%.
(2) CL: Bone marrow hyperplasia is obvious or extremely active, with granulocytes as the main component. The granulocyte-erythroid ratio is significantly increased, with a significant increase in neutrophils, late neutrophils and band-shaped granulocytes, and an increase in eosinophils and basophils. Erythrocytes are relatively decreased. Megakaryocytes are normal or increased, and decrease in the late stage. Gaucher-like cells are occasionally seen. CP primitive cells are less than 10%, AP greater than 10%. BC greater than 20% or extramedullary primitive cell infiltration occurs; CLL nucleated cell proliferation is obviously active or extremely active, with lymphocytes greater than 40%, mainly mature lymphocytes. The proliferation of erythroid, granulocyte and megakaryocyte cells is suppressed and can be significantly reduced in the late stage. When accompanied by hemolysis, immature red blood cells can proliferate compensatorily.
3. Immunological examination
Flow cytometry is often used for detection. It can determine the source of leukemia cells based on the series of related antigens expressed by the cells, which is of certain significance for diagnosis.
4. Cytochemical examination
It is of great significance for distinguishing various types of leukemia.
5. Cytogenetic and molecular biology examinations
Leukemia is often accompanied by specific cytogenetic and molecular changes, which serve as important diagnostic indicators. Most CML patients present with the presence of a Ph chromosome in their leukemic cells during CP. During AP, other chromosomal abnormalities may be present in Ph chromosome-positive cells, including the BCR-ABL fusion gene. Interphase fluorescence in situ hybridization (FISH) can detect chromosomal abnormalities in >80% of CLL patients, with 50%-60% harboring somatic mutations in the immunoglobulin heavy chain variable region (IgHV) gene. Most CLL cells without IgHV mutations highly express CD38 and ZAP70.
6. Blood biochemistry test
During chemotherapy, patients’ serum uric acid concentrations increase. Disseminated intravascular coagulation (DIC) can lead to abnormal coagulation patterns and elevated serum lactate dehydrogenase (LDH). When patients develop CNSL, they may experience increased cerebrospinal fluid pressure, increased white blood cell count, increased protein, and decreased glucose. This is crucial for assessing the extent of liver and spleen damage, as well as for diagnosis and treatment.
7. Neutrophil alkaline phosphatase (NAP) assay
NAP activity is decreased or negative in CML patients. It can recover when treatment is effective, decrease again when the disease relapses, and increase slightly when bacterial infection is present. It can be used to assist in disease diagnosis and observe treatment efficacy.
diagnosis
Diagnostic principles
The doctor will first ask about the patient’s basic information, such as family history, medical history, history of exposure to radiation and chemical drugs, and then combine the patient’s clinical manifestations and physical signs, and refer to a series of examinations such as blood examination, bone marrow puncture examination, cytochemistry examination, immunology examination, cytogenetic examination, molecular biology examination, blood biochemistry examination, neutrophil alkaline phosphatase (NAP) determination, etc., to make a clear diagnosis.
Differential diagnosis
1. Differential diagnosis of acute leukemia
(1) Myelodysplastic syndrome
In addition to dysplasia, the RAEB type of the disease has primitive and immature cells in the peripheral blood, pancytopenia, and chromosomal abnormalities, making it easy to confuse with leukemia. However, if the bone marrow contains less than 20% primitive cells, it can be quickly identified.
(2) White blood cell abnormalities caused by certain infections
For example, in infectious mononucleosis, atypical lymphocytes appear in the blood, but their morphology differs from that of blasts. Serum heterophil antibody titers gradually increase, and the disease course is short and may resolve spontaneously. In viral infections such as pertussis, infectious lymphocytosis, and rubella, the number of lymphocytes in the blood increases, but their morphology is normal, and the disease course is benign. Bone marrow blasts do not increase.
(3) Megaloblastic anemia
Megaloblastic anemia can sometimes be confused with erythroleukemia. However, megaloblastic anemia does not increase in bone marrow blasts, and the PAS reaction of immature erythrocytes is often negative. Treatment with folic acid and vitamin B12 is effective.
(4) Recovery period of acute granulocytosis
During the recovery phase of agranulocytosis caused by drugs or certain infections, the number of promyelocytes and myelocytes in the bone marrow increases, but the cause is often clear, platelets are normal, and there are no Auer bodies or chromosomal abnormalities in the promyelocytes and myelocytes. Bone marrow granulocyte maturation returns to normal within a short period of time.
2. Differential diagnosis of chronic leukemia
(1) Differential diagnosis of CML
① Other causes of splenomegaly: Schistosomiasis, chronic malaria, kala-azar, cirrhosis, and hypersplenism can all cause splenomegaly. However, each condition has its own underlying clinical characteristics, and blood and bone marrow examinations lack the typical changes of chronic myeloid leukemia. Ph chromosomes and BCR-ABL fusion genes are also negative.
② Leukemoid reaction: This reaction often occurs concurrently with underlying diseases such as severe infection and malignancy, and presents with clinical manifestations of the corresponding primary disease. Toxic granules and vacuoles are often present in the granulocyte cytoplasm, while eosinophils and basophils are not increased. The NAP reaction is strongly positive. The Ph chromosome and BCR-ABL fusion gene are negative. Platelets and hemoglobin are usually normal. Once the primary disease is controlled, the white blood cell count returns to normal.
③ Myelofibrosis: Patients with primary myelofibrosis have significantly enlarged spleens, increased leukocytosis, and the presence of immature granulocytes in the blood, making them easily confused with chronic myeloid leukemia. However, the peripheral blood leukocyte count in myelofibrosis is generally lower than that in CML, often not exceeding 30 × 10 9 /L, and NAP is positive. In addition, immature red blood cells may persist in the peripheral blood, with abnormal morphology, often with a teardrop shape. Ph chromosomes and the BCR-ABL fusion gene are negative. Patients may harbor mutations in the JAK2V617F, CALR, and MPL genes. Multiple bone marrow aspirations from multiple sites are performed, and bone marrow biopsies are positive for reticular fiber staining.
(2) Differential diagnosis of CCL
① Reactive lymphocytosis caused by viral infection: Lymphocytosis is polyclonal and transient, and the lymphocyte count can gradually return to normal as the infection is controlled.
② Other B-cell chronic lymphoproliferative diseases: Other B-cell chronic lymphoproliferative diseases that invade the bone marrow are easily confused with CLL. In addition to having a history of primary disease, the former are different from CLL in cell morphology, lymph node and bone marrow pathology, immunophenotypic characteristics and cytogenetics.
Prolymphocytic leukemia (PLL): Common in elderly patients, it presents with elevated white blood cell counts, significant splenomegaly, and minimal lymphadenopathy. Peripheral blood and bone marrow smears show numerous immature lymphocytes with nucleoli. PLL cells highly express FMC7, CD22, and Smlg and are CD5 negative. CLL with an immature lymphocyte count greater than 10% but less than 55% is termed CLL with prolymphocytosis.
④ Hairy cell leukemia: Most cases present with pancytopenia and splenomegaly. Lymphadenopathy is uncommon, making it easy to differentiate. However, a few patients may have elevated white blood cell counts of up to (10-30) × 109 / L. “Hairy cells” (HCLs) with ciliated cytoplasmic protrusions can be seen in the peripheral blood and bone marrow. They stain positive for tartrate-resistant acid phosphatase, are CD5 negative, and highly express CD25, CD11c, CD103, and CD123, as well as harbor the characteristic BRAFV600E mutation.
treat
Treatment principles
Doctors will design a personalized treatment plan based on the patient’s disease type and clinical characteristics. This plan primarily includes general treatment, medication, and chemotherapy. Suitable patients may also undergo allogeneic hematopoietic stem cell transplantation to completely cure the disease.
General treatment
1. General treatment of acute leukemia
(1) Treatment of hyperleukocytosis: When the number of white blood cells in the circulating blood is greater than 100×10 9 /L, the patient may develop leukostasis, which manifests as dyspnea, hypoxemia, slow reaction, slurred speech, intracranial hemorrhage, etc. The doctor will immediately use a blood cell separator to remove the excessive white blood cells, and at the same time provide hydration and chemotherapy, and give the corresponding chemotherapy plan according to the type; or use dexamethasone, hydroxyurea and other drugs for short-term pretreatment before chemotherapy, and then combine chemotherapy, and also prevent complications such as hyperuricemia, acidosis, electrolyte imbalance, and coagulation abnormalities induced by leukemia cell lysis.
(2) Prevention and treatment of infection: Patients often experience granulocytopenia or agranulocytosis, which can last for a long time, especially after chemotherapy or radiotherapy. Doctors will give G-CSF to shorten the granulocytosis period. This is suitable for ALL, elderly patients, patients undergoing intensive chemotherapy, or AML with infection. If fever is present, bacterial culture and drug sensitivity testing will be performed on the patient, and antibiotic treatment will be promptly initiated.
(3) Component transfusion support
Severe anemia can be treated with oxygen and concentrated red blood cell transfusions to maintain Hb levels above 80g/L. To avoid ineffective transfusions and fever caused by allogeneic immune responses and to prevent transfusion-related graft-versus-host disease, the cellular blood is irradiated with 25-30Gγ before transfusion to inactivate lymphocytes. During transfusion, a filter is used to remove white blood cells from the blood components. If leukocytosis occurs, blood transfusion is not performed immediately to avoid further increasing blood viscosity. When a patient’s platelet count is too low and bleeding occurs, doctors may transfuse apheresis platelet suspension.
(4) Prevention and treatment of hyperuricemia nephropathy: Due to the massive destruction of leukemia cells, the uric acid concentration in serum and urine increases and blocks the renal tubules, often causing hyperuricemia nephropathy. At this time, it is necessary to drink plenty of water. The doctor will perform 24-hour continuous intravenous rehydration to maintain the patient’s normal urine. Allopurinol can be given during chemotherapy to inhibit uric acid synthesis (contraindicated for those with allergies). When the patient experiences oliguria, anuria, or renal insufficiency, the doctor will treat the patient according to the symptoms of acute renal failure.
(5) Maintain nutrition: Leukemia is a serious wasting disease. Especially when chemotherapy and radiotherapy cause gastrointestinal mucosal inflammation and functional disorders in patients, nutritional supplements are needed, and if necessary, they can be given intravenously to maintain water and electrolyte balance.
2. General treatment of chronic leukemia
(1) The treatment of patients with chronic myeloid leukemia mainly focuses on CP. During the initial treatment, doctors choose leukocyte separation or use drugs such as hydroxyurea, allopurinol, and imatinib.
(2) Chronic lymphocytic leukemia is an indolent leukemia. Early-stage patients do not require treatment and only require regular checkups. If any of the following conditions occur, it indicates that the disease is active and treatment is recommended.
① Weight loss greater than 10%, extreme fatigue, non-infectious fever (over 38°C) for more than 2 weeks, and night sweats within 6 months without other reasons.
② Enlarged spleen (subcostal margin greater than 10 cm) or progressive splenomegaly and pain in the splenic area.
③ Lymph nodes are progressively enlarged or their diameter is greater than 10 cm.
④ Progressive peripheral blood lymphocytosis, an increase of more than 50% within 2 months, or a doubling time of less than 6 months.
⑤ Autoimmune cytopenia occurs and glucocorticoid treatment is ineffective.
⑥ Progressive bone marrow failure, progressive worsening of anemia and/or thrombocytopenia.
Drug treatment
1. Targeted drugs
During treatment with tyrosine kinase inhibitors (TKIs), hematological toxicities such as leukopenia, thrombocytopenia, and anemia, as well as non-hematological toxicities such as edema, headache, rash, and increased bilirubin may occur. Therefore, doctors monitor the efficacy at 3, 6, 12, and 18 months after the start of treatment. Patients who fail treatment will be tested for ABL kinase region gene mutations, and the drug will be changed or hematopoietic stem cell transplantation will be considered based on the mutation form and response to the drug.
(1) First-generation tyrosine kinase inhibitors: Imatinib mesylate is commonly used, which can effectively inhibit the proliferation of BCR-ABL positive cells. However, arbitrarily reducing or stopping the drug can easily cause mutations in the BCR-ABL kinase region, leading to secondary drug resistance.
(2) Second-generation tyrosine kinase inhibitors: such as nilotinib and dasatinib, can achieve faster and deeper molecular responses and gradually become optional drugs for the first-line treatment of CML.
2. Interferon
Interferon was the drug of choice for treating CML before the advent of molecularly targeted therapies. It is currently commonly used in patients ineligible for TKIs and allo-HSCT. It is typically administered subcutaneously or intramuscularly, often in combination with low-dose cytarabine (Ara-C). Its main side effects include flu-like symptoms such as fatigue, fever, headache, loss of appetite, musculoskeletal pain, weight loss, and abnormal liver function, which can cause mild to moderate cytopenias. Prophylactic use of acetaminophen and other medications can alleviate flu-like symptoms.
3. Immunotherapy
(1) Chimeric antigen receptor T (CAR-T) cell therapy: It is a new anti-tumor immunotherapy technology with specific killing efficacy and controllable side effects. It is an alternative method of killing tumors besides chemotherapy and radiotherapy. It has been used in clinical refractory recurrent cases and is expected to become a first-line treatment.
(2) Rituximab: used for the treatment of CLL, it is a human-mouse chimeric anti-CD20 monoclonal antibody that has a significant therapeutic effect on CLL cells expressing CD20 and can also be combined with other drugs for chemotherapy.
Related drugs
Dexamethasone, hydroxyurea, allopurinol, imatinib, imatinib mesylate, nilotinib, dasatinib, interferon, cytarabine (Ara-C), acetaminophen, chlorambucil, cyclophosphamide (CTX), bendamustine, fludarabine (Flu), cladribine, pentostatin, rituximab, vincristine (VCR), prednisone (P), daunorubicin, asparaginase (L-ASP), pegaspargase (PEG-Asp), methotrexate (MTX), 6-mercaptopurine (6-MP), idarucizumab, homoharringtonine (HHT), aclarubicin (Acla), all-trans retinoic acid (ATRA), arsenic trioxide, busulfan
Surgical treatment
Patients who meet the conditions can undergo allogeneic hematopoietic stem cell transplantation, which is currently the only possible way to cure the disease.
Chemoradiotherapy
Chemotherapy and radiotherapy are important methods for treating leukemia. Radiotherapy uses high-energy beams of radiation to kill cancer cells, while chemotherapy uses chemotherapy drugs to kill tumor cells or inhibit their growth and proliferation.
1. Chemotherapy for acute leukemia
The first stage of AL treatment is to use combined chemotherapy for induction remission treatment, so that patients can quickly achieve complete remission (CR), and then enter the second stage of post-remission treatment. The main methods are chemotherapy and HSCT, and the level of minimal residual disease (MRD) is regularly monitored. Patients with persistently negative MRD can expect to achieve long-term disease-free survival or even be cured.
(1) ALL
① Induction remission therapy: Commonly used regimens include the VP regimen of vincristine (VCR) and prednisone (P), the DVP regimen of VP plus anthracyclines (such as daunorubicin, DNR), and the DVLP regimen of DVP plus asparaginase (L-ASP) or pegaspargase (PEG-Asp). Other drugs can also be added to DVLP, including cyclophosphamide (CTX) or cytarabine (Ara-C).
② Post-remission treatment: The main drugs include high-dose methotrexate (MTX), Ara-C, 6-mercaptopurine (6-MP) and L-ASP.
(2) AML
① Induction remission therapy: The most commonly used regimens are IA (I stands for IDA, i.e., idarubicin) and DA (D stands for DNR). There are also regimens composed of anthracyclines such as homoharringtonine (HHT) and aclarubicin (Acla), HAD, HAA regimens, all-trans retinoic acid (ATRA) + anthracyclines, and ATRA + anthracyclines + arsenic agents (arsenic trioxide, ATO) regimens.
② Treatment after remission: mainly includes ATRA, arsenic, Ara-C and other drugs.
2. Radiotherapy for acute leukemia
(1) Prevention and treatment of CNSL
Throughout the entire treatment process, including craniospinal irradiation and intrathecal chemotherapy.
(2) Testicular leukemia
Bilateral testicular irradiation is required.
3. Chemotherapy for chronic leukemia
(1) Hydroxyurea: It is a drug that specifically inhibits DNA synthesis in the cycle, with a rapid onset and short duration of action. During treatment, the doctor will monitor the patient’s blood count to adjust the dosage. It has fewer side effects and can more steadily control the white blood cell count, but does not change cytogenetic abnormalities. It is currently mostly used for early control of blood counts or patients who cannot tolerate imatinib mesylate.
(2) Alkylating agents: Commonly used agents include chlorambucil, cyclophosphamide, busulfan, and bendamustine. Currently, they are mostly used for older CLL patients who cannot tolerate other chemotherapy drugs or have complications. They have anti-metabolic and alkylating properties. As a single agent, they have shown high response rates and CR rates in both newly diagnosed and relapsed refractory CLL patients. Overdose or low-dose use in sensitive patients can cause severe bone marrow suppression and slow recovery. They are now rarely used.
(3) Purine analogs: Commonly used are fludarabine (Flu), cladribine, and pentostatin, which are effective for patients resistant to alkylating agents. Combining them with alkylating agents, such as cyclophosphamide (FC regimen), is superior to using them alone.
(4) Glucocorticoids: Mainly used for the treatment of combined autoimmune cytopenia and generally not used alone.
(5) Others: cytarabine, homoharringtonine, rubin, arsenic, etc.
4. Radiotherapy for chronic leukemia
When a patient has an enlarged spleen, swollen lymph nodes, and obvious compression symptoms, the doctor may consider local radiotherapy to relieve pain.
Treatment cycle
Individual differences may exist due to factors such as the severity of the disease, treatment plan, treatment timing, age and physical condition.
Treatment costs
The specific costs are related to the selected hospital, individual treatment plan, medical insurance policy, etc.
Prognosis
General prognosis
Without specialized treatment, the average survival for acute leukemia is only three months, with some patients dying within days of diagnosis. While less severe, chronic leukemia also carries a risk of death if not promptly sought medical attention. With advances in treatment technology, many leukemia patients can achieve symptom relief or alleviation through proactive and effective treatment, ensuring long-term survival.
Hazards
1. Leukemia patients have low immunity and are easily infected by various viruses and bacteria. When combined with sepsis, it will seriously threaten the patient’s life.
2. Patients may experience bleeding in various parts of the body, such as bleeding gums, nosebleeds, etc., which may lead to death if intracranial hemorrhage occurs.
3. Patients may experience fatigue, repeated fever, weight loss, etc., which will seriously affect their quality of life.
4. This disease is a malignant disease and patients who progress rapidly may die within a short period of time.
Self-healing
It generally cannot heal on its own and requires active treatment in the hospital.
Curative
After timely and active treatment, the patient’s symptoms may be relieved or alleviated, and some patients can be cured through allogeneic hematopoietic stem cell transplantation.
Cure rate
The cure rate for leukemia is low, and there is currently no large data sample research.
Lifecycle
Without special treatment, the average survival time of patients with acute leukemia is only 3 months, and in some cases, they die within a few days after diagnosis. Patients with chronic leukemia can survive for a long time after active treatment.
daily
Overview
Patients need to face their condition, understand the disease, alleviate negative emotions, build confidence in treatment, and receive postoperative care and medication under the guidance of a doctor. They should also get adequate rest, exercise moderately, eat a balanced diet, ventilate and disinfect their living room regularly, and undergo regular checkups so that the doctor can adjust the treatment plan in a timely manner.
Psychological care
1. Psychological characteristics
(1) After being diagnosed with leukemia, the patient is shocked at first, then doubts the diagnosis, and even has a lucky mentality, thinking that he has always been healthy and it is impossible for him to get sick. He does not admit the fact that he is sick and resists treatment.
(2) After accepting reality, patients will feel that they have lost hope in life, thus experiencing negative emotions such as anxiety and fear.
(3) Patients often consider giving up treatment due to the severe physical discomfort and heavy financial burden caused by the disease.
(4) Hair loss caused by chemotherapy can make patients extremely self-deprecating and unwilling to go out or see people.
2. Nursing measures
(1) First, patients should face their own diseases, listen to the doctor’s advice and cooperate with treatment.
(2) Actively learn about leukemia-related knowledge and effective treatment cases, build confidence in defeating the disease, and consult a psychologist if necessary.
(3) Family members should understand, care for, and guide patients to relieve their psychological burden.
(4) When going out, you can use wigs, hats, etc. to cover your head.
Medication care
1. Care for drug leakage
Certain chemotherapy drugs, such as daunorubicin, doxorubicin, and vincristine, are highly irritating to local tissues. Leakage of the drug can cause pain, redness, swelling, and even necrosis. Therefore, family members should closely monitor the patient during the infusion and notify medical staff immediately if leakage is detected.
2. Gastrointestinal reaction care
Many chemotherapy drugs can cause nausea, vomiting, and loss of appetite. Patients often experience significant weight loss and decreased immunity after chemotherapy. Therefore, family members should keep the ward quiet, tidy, and well-ventilated during chemotherapy. If a patient vomits, they should promptly remove vomitus, assist with rinsing their mouth, and provide comfort and companionship.
3. Nursing for liver and kidney function damage
Purine, methotrexate, and L-asparaginase can damage liver function. Patients should observe the color of their skin and urine during medication use and report any abnormalities to their doctor promptly.
4. Glucocorticoid care
The use may cause moon face and mood changes. Family members should pay more attention to the children and not laugh at or ridicule them.
5. Nursing of uric acid nephropathy
Drink plenty of water during medication to facilitate the dilution and excretion of uric acid and chemotherapy drug degradation products, and take allopurinol tablets orally as prescribed by your doctor to inhibit the formation of uric acid.
Postoperative care
1. Fever care
If the patient has a fever, family members can give him a warm water bath and use an ice pillow. Avoid using acetaminophen and alcohol baths to avoid lowering the white blood cell count and increasing bleeding tendency.
2. Isolation care
Family members must wear masks and hats when coming into contact with patients, pay attention to personal hygiene, and limit the number of visitors and the number of visits.
3. Infection prevention care
(1) Oral care: Keep the oral cavity clean and rinse with chlorhexidine before going to bed, before meals, and after meals. If there is a fungal infection in the oral cavity, you can apply sodium bicarbonate + nystatin to the oral cavity as prescribed by the doctor.
(2) Anal care: Maintain smooth bowel movements and prevent anal fissures. Take a sitz bath with Refununo powder three times a week. Wash the anus with warm water after defecation to avoid infection.
(3) Skin care: Keep your skin clean, change clothes frequently, cut your nails frequently, and wash your hands frequently.
(4) Observe for early signs of infection: Family members should observe whether the patient has swollen and painful gums, red and sore throat, skin damage, redness and swelling, and any abnormalities around the anus or vulva. If any signs of infection are found, the doctor should be informed immediately.
Life Management
1. Ensure adequate rest, avoid staying up late and overwork to prevent affecting the body’s recovery.
2. Keeping the living room clean and tidy, ventilating and disinfecting frequently will help with recovery from illness.
3. When the temperature drops, add or remove clothes appropriately to prevent upper respiratory tract infections.
4. Do appropriate exercise, such as walking, aerobics, etc., to enhance the body’s immunity.
5. Strengthen self-protection, avoid going to public places and crowded places, and reduce the risk of accidental injury.
5. Follow the doctor’s instructions and take the medication regularly. Do not stop taking the medication or change the dosage without permission. Also, have regular physical examinations and follow-up checks to understand your condition.
Disease monitoring
If the patient shows signs of confusion, convulsions, coma, etc., the doctor should be informed immediately.
Follow-up Instructions
Follow your doctor’s instructions for regular follow-up visits so that your doctor can adjust your treatment plan.
diet
Dietary adjustment
A reasonable and balanced diet can promote the body’s recovery as soon as possible. Maintain a regular diet, mainly eat high-calorie, high-protein, high-vitamin, and iron-containing foods, drink plenty of water, eat small meals frequently, and avoid eating spicy and irritating foods.
Dietary recommendations
1. High calories
The patient’s basal metabolic rate increases, and the body’s need for various nutrients increases. Therefore, high-calorie food must be provided to leukemia patients as much as possible.
2. High protein
Supplementing with high-quality protein can maintain the functions of various tissues and organs. In particular, you should choose some animal proteins and bean proteins with good quality and high digestion and absorption rates, such as eggs, milk, fish, shrimp, lean meat, animal blood, animal offal, tofu, tofu pudding, bean curd sticks, soy milk, etc., to supplement the body’s needs for protein.
3. High in vitamins
Vitamin C can enhance the body’s local matrix resistance and systemic immune function. It can be found in rapeseed, tomatoes, Chinese cabbage, leeks, shepherd’s purse, hawthorn, citrus, fresh dates, kiwi, sea buckthorn, and lemon. Vitamin A can stimulate the body’s immune system, mobilize the body’s anti-cancer efforts, and resist the invasion of pathogens. It can be found in carrots, pumpkin, egg yolks, cod liver oil, bell peppers, and spinach.
4. Water
Sufficient water should be added to maintain electrolyte balance, such as potassium, sodium, chloride, and calcium. Inorganic salts such as juice, milk, porridge, soup, and watermelon juice, pear juice, tomato juice, milk, and honey should be consumed.
5. Iron-rich foods
Patients may have symptoms such as anemia and bleeding, so they should regularly eat foods rich in iron and that have the functions of nourishing blood, producing blood, and activating blood circulation, such as animal liver, turtle, peas, black beans, green vegetables, dates, brown sugar, black fungus, sesame paste, egg yolk, etc.
6. Eat small, frequent meals
Patients often experience adverse reactions during chemotherapy, such as nausea, vomiting, diarrhea and other symptoms. At this time, they can adopt the method of eating small meals frequently, or add some small, high-calorie, nutritious foods in addition to three meals, such as cakes, chocolate, bread, quail eggs, yogurt, kiwi, fresh vegetables, fruit juice, etc.
Dietary taboos
1. Avoid spicy and irritating foods.
2. Avoid smoking and drinking.
prevention
Preventive measures
Avoid exposure to certain chemicals and high levels of radiation in daily life.
Medical Guide
Emergency (120) indications
1. Sudden confusion, convulsions, and coma.
2. Heavy bleeding or hemoptysis occurs.
3. Other emergency situations occur.
All of the above require prompt emergency treatment and call the emergency number if necessary.
Outpatient indications
1. Pale complexion, fatigue, palpitations, and loss of appetite.
2. Fever of unknown cause occurs.
3. Repeated bleeding from gums and nose, and increased menstrual flow in women.
4. Bruises and petechiae appear on the skin.
5. Pain and tenderness in bones and joints.
6. Painless swelling of the male testicles.
7. Enlargement of the liver, spleen and lymph nodes.
8. Continuous weight loss for unknown reasons.
All of the above require prompt medical consultation.
Treatment department
It is generally recommended to go to the hematology department for treatment. Young children can go to the pediatric department for consultation. Those with severe symptoms should go to the emergency department immediately.
Medical preparation
1. Make an appointment in advance and bring your ID card, medical insurance card, medical card, etc.
2. The doctor may perform a physical examination on your abdomen. Wear loose clothing that easily exposes your abdomen for easier examination.
3. If you have taken any medicine recently, you can record the name, usage and dosage to facilitate communication with your doctor.
4. If you have had medical treatment recently, please bring relevant medical records, examination reports, laboratory test results, etc.
5. Family members may accompany the patient to the clinic and should be prepared with questions they wish to ask.
Questions your doctor may ask
1. What symptoms do you have? When did they start? How long have they lasted?
2. Have you ever had similar symptoms before? Have you received treatment?
3. Do you usually catch colds and fevers easily?
4. Do you feel tired and exhausted easily recently?
5. Have your parents, siblings, or friends ever experienced similar symptoms?
6. Have you taken any medication on your own? Did the symptoms improve after taking the medication?
7. Have you been treated in other hospitals? How was the result?
What questions can patients ask?
1. Is there a clear diagnosis now? Do I have leukemia?
2. What are the causes of my disease?
3. Is my condition serious? Is my life in danger in the short term?
4. What tests do I need to undergo? Will the tests cause any harm to my body?
5. Do I need long-term chemotherapy?
6. How long does treatment take? Is it curable?
7. What should I pay attention to in my daily life?
8. Do I need a follow-up examination? How long will it take?