What is Chronic Leukemia?

Chronic leukemia is a group of hematological malignancies with relatively insidious onset, slow progression, peripheral blood and / or bone marrow with increased juvenile cells but relatively well differentiated. The natural course is longer than that of acute leukemia. Leukemia cells have a certain ability to differentiate and mature. Bone marrow and peripheral blood are mainly abnormal mature cells.

Basic Information

Visiting department: Department of Hematology
Common causes: Related to genetic changes, genetic abnormalities, and changes in the bone marrow microenvironment.

Common symptoms: General weakness, low fever, discomfort, and liver and spleen.
Contagious: no

Classification of chronic leukemia

According to the cell type, it is divided into chronic myeloid leukemia and chronic lymphocytic leukemia.
1. Chronic myeloid leukemia Chronic myeloid leukemia includes chronic myelogenous leukemia (CML), chronic myelogenous leukemia (CMML), atypical chronic myelogenous leukemia (aCML), juvenile myeloid leukemia, and chronic Granulocytic leukemia and so on.
2. Chronic Lymphocytic Leukemia Chronic lymphocytic leukemia (CLL) is generally limited to neoplastic B-cell disease, while the previous T-cell CLL is now referred to as T naive lymphocytic leukemia.
Clinically, chronic myelogenous leukemia and chronic lymphocytic leukemia are the two most common.

Causes of chronic leukemia

1. The C-ABL proto-oncogene on chromosome 9 of patients with chronic myelogenous leukemia CML is transferred to chromosome 22, which is connected to the breakpoint concentration region (BCR) of the chromosome 22 stump, that is t (9; 22) (q34 Q11), forming a BCR-ABL fusion gene. The p210BCR-ABL protein encoded by it has extremely strong tyrosine kinase activity, which causes a series of signaling proteins to undergo continuous phosphorylation, which affects cell proliferation, differentiation, apoptosis and adhesion, leading to CML.
2. Monoclonal B lymphocytosis (MBL) existed in almost all CLLs before the onset of chronic lymphocytic leukemia. It is speculated that B lymphocytes responded abnormally to antigen stimulation and produced memory B cell clones with a CLL phenotype. Due to other genetic abnormalities or changes in the bone marrow microenvironment, B cell clones were further affected, eventually leading to the progression of MBL to CLL.

Clinical manifestations of chronic leukemia

(1) Chronic myelogenous leukemia can occur in all age groups, most common in middle age, and more men than women.
1. Early general symptoms may include fatigue, fatigue, low fever, and abdominal discomfort.
2. Hepatosplenomegaly and splenomegaly are found in 90% of patients. The degree of splenomegaly is closely related to the condition, course of disease, and especially the number of white blood cells. Liver is seen in 40% to 50% of patients.
3. Accelerated / rapid phase manifestations such as fever, weakness, bone pain, progressive enlargement of the spleen, infiltration of other extramedullary organs, exacerbation or bleeding of the unexplained disease, and failure of the original effective drug, prompting entry Period or sudden change period. The sudden change period is the terminal stage of CML, most of which are acute granulosis, followed by acute gonorrhea.
(2) Chronic lymphocytic leukemia is more common in elderly patients, has a slow onset, and has no conscious symptoms in the early stages. It is often due to abnormal blood tests or lymph nodes or splenomegaly.
1. Generally, early symptoms include fatigue, fatigue, and discomfort, and weight loss, fever, and night sweats appear as the disease progresses. In the later stage, due to impaired hematopoietic function, anemia and thrombocytopenia occur. Due to the decline of immune function, infection is easy to occur. Richter transformation can occur in the terminal stage, that is, into other types of lymphatic tumors.
2. Large lymph nodes, hepatosplenomegaly 60% to 80% of patients with enlarged lymph nodes, neck, supraclavicular parts are common. The enlarged lymph nodes are hard, non-adhesive, tender, and mobile. They can fuse as the disease progresses, forming large, fixed masses. CT scans revealed large hilar, retroperitoneal, and mesenteric lymph nodes. 50% to 70% of patients had mild to moderate splenomegaly and mild hepatomegaly. Splenic infarction is rare.
3. Autoimmune manifestations: Partially advanced or after chemotherapy, 4% to 25% of patients have autoimmune hemolytic anemia, 2% have idiopathic thrombocytopenic purpura, and <1% of patients have pure red blood cell aplastic anemia.

Chronic leukemia test

1. Chronic myelogenous leukemia (1) The white blood cell count in the chronic phase of blood routine is significantly increased, higher than 20 × 109 / L in the early stage, and up to 100 × 109 / L in the later stage. , Late promyelocytic and rod-shaped neutrophils; eosinophils, basophils increased; anemia may occur; platelets are normal or increased in early stages, and gradually decrease in late stages.
(2) Bone marrow smear cytology showed obvious or extremely active bone marrow hyperplasia, mainly myeloid cells, especially neutral mesophile, late myelin, and rod-shaped nucleus granulocytes; promyelocytic cells were less than 10%, Burst phase 20%, or blast + early immature cells 50%.
(3) Chromosome examination Ph chromosome is an important sign of CML. If the Ph chromosome is negative and CML is clinically suspected, the BCR-ABL fusion gene can be found by fluorescence in situ hybridization.
(4) BCR-ABL fusion gene was positive in molecular biology examination.
2. Chronic lymphocytic leukemia (1) Blood routine Peripheral blood B lymphocytes 5 × 109 / L, and last at least 3 months.
(2) Bone marrow smear cytology showed that the bone marrow hyperplasia was significantly active or extremely active, mainly mature lymphocytes, and red blood cells, granulocytes, and megakaryocytes were reduced.
(3) Immune phenotype Tumorous B lymphocytes are monoclonal, expressing only one of or light chain, positive for CD5, CD19, CD23, CD27, CD43; weakly positive for SmIg, CD20; FMC7, CD22, CD79b Weak positive or negative; CD10 negative.
(3) Routine karyotype analysis of chromosome and gene examination 40% to 50% of CLL patients with chromosomal abnormalities, 13q- is the most common, simple 13q- has a better prognosis; followed by 11q-, +12, 17p-, the prognosis is poor; with complex The prognosis for chromosomal abnormalities is the worst.
(4) Lymph node biopsy showed typical diffuse small lymphocyte infiltration, and the cell morphology was consistent with lymphocytes in blood.

Chronic leukemia diagnosis

1. Chronic myelogenous leukemia. According to the splenomegaly, typical peripheral white blood cell counts are increased, mainly late granulocytes and rod-shaped nucleus cells. The absolute counts of eosinophils and basophils increase, NAP scores decrease, and Ph chromosomes And / or a positive BCR-ABL gene can be diagnosed.
2. Chronic lymphocytic leukemia (1) Lymphocytes 5 × 109 / L for at least 3 months, with CLL immunophenotypic characteristics; or (2) Although peripheral blood lymphocytes <5 × 109 / L, there are CLL can be diagnosed by hemocytopenia caused by typical bone marrow infiltration and typical CLL immunophenotypic characteristics (CD5, CD19, CD23 positive, FMC7 negative, weak SmIg expression, CD22 / CD79b weak expression or negative, etc.).

Chronic leukemia treatment

(I) Chronic myelogenous leukemia 1. Targeted therapy The first-line first-line treatment regimen for newly diagnosed patients with chronic phase of CML is imatinib, and the efficacy evaluation is performed regularly.
2. Chemotherapy with hydroxyurea can reduce the number of white blood cells, and other busulan, homoharringtonine, and cytarabine are less used.
Interferon alpha
Slow onset, for patients who cannot be treated with imatinib for various reasons.
4. Allogeneic hematopoietic stem cell transplantation Allogeneic hematopoietic stem cell transplantation is the only method that is expected to cure CML. High-risk CML patients can choose hematopoietic stem cell transplantation.
(B) Most CLL of chronic lymphocytic leukemia is a chronic, inert process, without treatment in the early stage, and regularly observed. Treat after indications for treatment appear.
1. Chemotherapy Chemotherapy commonly used drugs are chlorambucil, fludarabine, bendamustine, cyclophosphamide and so on.
2. Immunotherapy includes rituximab and alendumab.
3. Targeted drugs targeting B-cell receptor signaling pathways include Ibrutinib, a new type of oral tyrosine kinase inhibitor, which can improve the survival of elderly patients and significantly improve the disease-free survival of 17p-patients. Idelaisib is a phosphatidylinositol 3 kinase (PI3K) inhibitor.
4. Radiotherapy is only used to relieve the symptoms of oppression due to lymphadenopathy, painful bone disease, and painful splenomegaly who cannot perform splenectomy, and it should be used in combination with other treatments.
5. Hematopoietic stem cell transplantation Hematopoietic stem cell transplantation can be considered for young patients who can tolerate strong treatment and have high risk factors.

Chronic leukemia prognosis

Chronic myelogenous leukemia has a natural course of 3 to 5 years. Imatinib and other tyrosine kinase inhibitors have significantly improved the survival of CML patients, and patients with chronic stage are expected to prolong their median survival to 20 years after imatinib treatment.
Although the development of chronic lymphocytic leukemia is slow, it is difficult to cure, and the duration varies from 6 months to more than 10 years.

Chronic leukemia care

1. Pay attention to rest and avoid fatigue during general nursing treatment. Those with significant spleen may cause discomfort in the left upper abdomen. Eat a high-protein, high-vitamin diet and drink more than 1500 ml of water daily.
2. Observation of the disease Regularly check blood picture, blood uric acid and urine sediment. Note whether the patient has hematuria or low back pain. Once hematuria occurs, report it to the doctor immediately and check renal function. Pay attention to observe if there is no known cause of fever, bone pain, anemia, exacerbation of bleeding, and rapid enlargement of the spleen. If there is a change, it should be treated in time.
3. Medication care: Give chemotherapeutic drugs according to the doctor's orders and observe the adverse reactions of the drugs.