Leukemia is a group of malignant clonal diseases of hematopoietic stem cells. Clonal leukemia cells accumulate in the bone marrow and other hematopoietic tissues due to mechanisms such as uncontrolled proliferation, impaired differentiation, and impaired apoptosis, and infiltrate other non-hematopoietic tissues and organs, while inhibiting normal hematopoietic function. Clinical manifestations include varying degrees of anemia, bleeding, infectious fever, and enlargement of the liver, spleen, lymph nodes, and skeletal pain. The incidence of leukemia is reported to be the sixth highest among various tumors in various regions of China.
Causes of leukemia
1. Viral factors
The leukemogenic effect of RNA viruses in animals such as rats, cats, chickens and cattle has been confirmed, and most of the leukemias caused by such viruses are of T-cell type.
2. Chemical factors
Some chemicals have a leukemogenic effect. The incidence of leukemia is higher in people exposed to benzene and its derivatives than in the general population. Leukemia has also been reported to be induced by nitrosamines, pautaxone and its derivatives, chloramphenicol, etc. Certain antitumor cytotoxic drugs, such as nitrogen mustard, cyclophosphamide, methylbenzylhydrazine, VP16, VM26, etc., have leukemogenic effects.
3. Radiation factors
There is evidence that various types of ionizing radiation can cause human leukemia. The occurrence of leukemia depends on the dose of radiation absorbed by the body, and leukemia can be induced by moderate or high doses of radiation to the whole body or part of the torso. It is still uncertain whether small doses of radiation can cause leukemia. The incidence of leukemia is significantly increased in those who are frequently exposed to radioactive materials (e.g., cobalt-60). High-dose radiation diagnosis and treatment can increase the incidence of leukemia.
4. Genetic factors
The incidence of leukemia is higher in people with chromosomal aberrations than in normal people.
Classification of leukemia conditions
Leukemia can be classified into acute and chronic leukemia according to the urgency of the onset of the disease. In acute leukemia, cell differentiation is stagnant at an early stage, with primitive and early juvenile cells predominating, and the disease progresses rapidly and lasts for several months. Chronic leukemia cells are better differentiated, with predominantly naive or mature cells, and the disease develops slowly and lasts for several years. The disease is classified according to the cell lineage of the lesion, including the granulocytic, monocytic, erythrocytic and megakaryocytic lineages of the myeloid lineage and the T and B cell lineages of the lymphoid lineage. Clinically, leukemia is often classified as lymphocytic leukemia, myeloid leukemia, mixed cell leukemia, etc.
Clinical manifestations of leukemia
Most acute leukemias in children and adolescents have an acute onset. Common first symptoms include fever, progressive anemia, significant bleeding tendency or bone and joint pain. The slow onset of acute leukemia is mostly seen in elderly and some young patients, and the disease progresses gradually. In addition, a few patients may have convulsions, blindness, toothache, gum swelling, pericardial effusion, and bilateral lower limb paraplegia as the first symptoms.
1. Fever
It is one of the most common symptoms of leukemia, manifesting as fever and febrile pattern of different degrees. The main cause of fever is infection, among which pharyngitis, stomatitis and perianal infection are the most common, and pneumonia, tonsillitis, gingivitis and perianal abscess are also more common. Ear inflammation, enteritis, carbuncle, pyelonephritis, etc. can also be seen, and sepsis and septicemia can occur in severe cases. Fever can also be a symptom of acute leukemia itself, without any signs of infection.
2. Infection
Bacteria are the most common pathogens. In the later stages of the disease, the likelihood of fungal infections gradually increases due to prolonged below-normal granulocytes and the use of broad-spectrum antibiotics. Viral infections are rare but dangerous and should be noted.
3. Bleeding
Bleeding can occur throughout the body, with skin, gum, and nasal bleeding being the most common, as well as retinal and ear bleeding and internal bleeding in the skull, gastrointestinal tract, and whistle. Excessive menstruation is also common in women and can be the first symptom.
4. Anemia
It can appear at an early stage. In a few cases, myelodysplastic syndrome (MDS) may first appear months or years before the diagnosis, and then develop into leukemia later. Patients often have symptoms such as weakness, pallor, palpitations, shortness of breath, and edema of the lower extremities. Anemia is seen in all types of leukemia and is more common in older patients.
5. Bone and joint pain
Leukemic infiltration of bone and periosteum causes bone pain, which may be diffuse in the limbs or back or confined to the joints, often resulting in difficulty moving. More than 1/3 of patients have sternal pressure pain, a sign that contributes to the diagnosis of the disease.
6. Central nervous system leukemia (CNSL)
CNSL is a serious complication of acute leukemia, commonly seen in M4 and M5 in ALL and AML, but other types can also be seen. It is a blind spot and a difficult area for modern acute leukemia treatment because of the difficulty of crossing the blood-brain barrier with commonly used chemotherapeutic drugs. The infiltration site mostly occurs in the arachnoid and dura mater, followed by the brain parenchyma, choroid or cranial nerves. In severe cases, there are typical manifestations of increased intracranial pressure such as headache, vomiting, strong collar, optic papilla edema, and even convulsions and coma, which may resemble intracranial hemorrhage, while mild cases only complain of mild headache and dizziness. The involvement of cranial nerves (mainly the VI and VII pairs of cranial nerves) may lead to visual impairment and facial palsy, etc.
7. Hepatosplenomegaly and lymph node enlargement
The incidence of hepatosplenomegaly is higher in ALL than in AML, and splenomegaly is more common and more pronounced in chronic than in acute leukemia. Lymph node enlargement is also more common in ALL than AML, and can involve superficial or deep lymph nodes such as mediastinum, mesentery, retroperitoneum, etc.
8. Infiltration of other tissues and organs
Cutaneous infiltrates are less common in ALL than in AML, but testicular infiltrates are more common. Testicular leukemia is also frequently seen in ALL in remission, manifested by painless enlargement of the testes unilaterally or bilaterally, with a firm texture without tenderness, and is second only to CNSL as a source of extramedullary recurrence of leukemia. Leukemic infiltration can also involve various tissues and organs such as lung, pleura, kidney, digestive tract, heart, brain, uterus, ovary, breast, parotid and eye, and show dysfunction of corresponding organs.
9. Symptoms of chronic granulocytic leukemia
The onset of the disease is slow, and there are often no conscious symptoms in the early stage, and the diagnosis is only confirmed by abnormal blood picture or splenomegaly during health checkups or visits to the doctor for other diseases. As the disease progresses, signs of hypermetabolism such as fatigue, low fever, excessive sweating or night sweats, and weight loss may appear. Symptoms such as left upper abdominal cramping and fullness after eating due to splenomegaly may also appear. The most prominent feature on examination is splenomegaly, which often reaches the level of the umbilicus by the time the patient is seen. The disease can be stable for 1 to 4 years, and then enters an accelerated phase with rapid onset of anemia and more symptoms, and then quickly enters an acute phase, which can become AML or ALL.
Treatment of leukemia
Because of the complexity of leukemia typing and prognostic stratification, there is no one-size-fits-all treatment and treatment plans need to be developed in conjunction with careful typing and prognostic stratification. Currently, the following types of treatments are available: chemotherapy, radiation therapy, targeted therapy, immunotherapy, and stem cell transplantation. Through reasonable and comprehensive treatment, the prognosis of leukemia has been greatly improved, and a significant number of patients can be cured or stabilized in the long term.
1. AML treatment (non-M3)
Combination chemotherapy, known as “induction chemotherapy”, is usually required first, and is commonly used with the DA (3+7) regimen. After induction therapy, if remission is achieved, further intensive consolidation chemotherapy or stem cell transplantation can be arranged depending on the prognosis stratification. After consolidation therapy, maintenance therapy is usually not administered at this time and can be discontinued for observation and regular follow-up.
2.M3 treatment
Due to the success of targeted therapy and apoptosis-inducing therapy, PML-RARα-positive acute promyelocytic leukemia (M3) has become the type with the best prognosis in the entire AML. A growing number of studies have shown that all-trans retinoic acid combined with arsenic therapy can cure the vast majority of M3 patients. Treatment needs to be strictly adhered to, and the length of late maintenance therapy is largely determined by the residual fusion gene.
3. ALL treatment
Induction chemotherapy is usually administered first, and there are differences between the common regimens for adults and children, but recent studies have suggested that adult patients treated with pediatric regimens may have better outcomes than traditional adult regimens. Adherence to consolidation and maintenance therapy is required after remission. Stem cell transplantation is available for high-risk patients with conditions. Combination tyrosine kinase inhibitors are recommended for patients with combined Ph1 chromosome positivity.
4. Treatment of chronic granulocytic leukemia
Treatment with tyrosine kinase inhibitors (e.g. imatinib) is preferred in the chronic phase, and early and adequate treatment is recommended; delayed use and irregular use can easily lead to drug resistance. Therefore, if you decide to use imatinib, first, do not delay, and second, be sure to adhere to long-term (near-lifetime) dosing, and never reduce or stop dosing while taking it, as this can easily lead to drug resistance. The accelerated, acute phase usually requires targeted therapy (imatinib plus dose or use of second-generation drugs) first, and then the opportunity to arrange for allogeneic transplantation is selected at the earliest opportunity.
5. Chronic lymphocyte therapy
Early stage asymptomatic patients usually do not require treatment, while in advanced stages multiple chemotherapy regimens are available, such as liucovorin monotherapy, fludarabine, cyclophosphamide combined with melphalan, etc. Newer drugs such as bendamustine and anti-CD52 monoclonal antibody are also effective. In recent years, targeted therapy with BCR pathway inhibitors may be found to have significant effects. Allograft therapy can be considered for refractory patients with conditions.
6. Treatment of central nervous system leukemia
Although types such as M4 and M5 in ALL and AML are commonly combined with CNSL, all other acute leukemias can also occur. Some refractory patients may require whole-cranial cremaster radiotherapy.
This proves that both children and adults must be aware of their health condition, go to the hospital for a comprehensive checkup on a regular basis, and keep an eye on their health condition, so that they will regret if it becomes serious.