leukaemia



OVERVIEW

Definition

Leukemia (leukemia) is a group of heterogeneous malignant clonal diseases originating from hematopoietic stem cells and is a malignant tumor of the hematopoietic system.

Due to the proliferation of abnormal blood cells (i.e. leukemia cells) in the bone marrow and other hematopoietic tissues, infiltration of various tissues, so that the normal hematopoietic function is inhibited, the production of normal blood cells is reduced, and the corresponding clinical manifestations.

Disease type

Classified according to the course of the disease and the degree of cell differentiation

Acute Leukemia

Chronic Leukemia

Classification according to morphology and cytochemistry of leukemia cells

Acute leukemia is further classified into acute lymphoblastic leukemia and acute myeloid leukemia.

Chronic leukemia is classified into chronic myeloid leukemia and chronic lymphocytic leukemia.

Rare and Special Types of Leukemia

Adult acute lymphoblastic leukemia is a malignant proliferative disease of the lymphatic system and is one of the most common adult acute leukemias.

The disease originates in the bone marrow, with early antigenic markers on the surface of leukemic cells in the form of B cells or T cells.

At the time of diagnosis, normal cells in the bone marrow are replaced by a large number of leukemic cells, known as primitive lymphocytes, while normal hematopoiesis is suppressed.

The presence of primitive lymphocytes with impaired differentiation and maturation, which do not have normal lymphocyte function, and the suppression of normal granulocytes make the patient susceptible to complications such as infections and an increased risk of death.

Acute myeloid leukemia is the most common type of adult leukemia, accounting for about 80% of acute leukemias over the age of 20.

Acute myeloid leukemia can occur at any age, but is predominantly found in the elderly.

Acute myeloid leukemia can be primary or secondary when first diagnosed.

Chronic myeloid leukemia, with a slow onset, is characterized by a significant increase in the number of late granulocytes in the peripheral blood with impaired maturation, basophilia, and marked splenomegaly, even with the development of a giant spleen.

The natural course of the disease includes chronic, accelerated and acute phases.

Ph chromosome and BCR/ABL fusion gene are the hallmark changes.

Chronic lymphocytic leukemia is a mature B-cell tumor characterized by the abnormal proliferation and progressive accumulation of monoclonal small B lymphocytes (immunophenotype usually CD5+/CD23+) in the peripheral blood, bone marrow, lymph nodes, liver, and spleen.

Clinical manifestations include peripheral blood lymphocytosis and enlargement of the liver, spleen and lymph nodes.

Advanced stage may manifest as bone marrow failure.

Morbidity

Incidence rate

The incidence rate of leukemia in China is (3-5)/100,000 people.

In 2015, the number of new leukemia patients in China was about 75,300.

Mortality rate

The mortality rate of leukemia in men is the 6th highest among the mortality rate of malignant tumors, and the mortality rate of leukemia in women is the 7th highest among the mortality rate of malignant tumors.

In 2015, about 534,000 patients died of leukemia nationwide.

Classification ratio

Acute leukemia is more common than chronic leukemia in China.

Acute myeloid leukemia is the most common, followed by acute lymphoblastic leukemia (about 15%) and chronic myeloid leukemia (about 15%).

Population

Of the acute leukemias, acute myeloid leukemia is most common in adults and acute lymphoblastic leukemia is most common in children.

The incidence of acute myeloid leukemia and chronic myeloid leukemia increases gradually with age.

Causes

Causes

The exact cause of leukemia is unknown and may be related to the following factors.

Infection

A variety of retroviruses such as avian leukemia virus (ALV), murine leukemia virus (MLV), feline leukemia virus (FeLV), gibbon ape leukemia virus (GaLV), and reticuloendothelial tissue proliferating virus (REV) can cause leukemia.

In the Burkitt’s lymphoma/leukemia endemic areas of equatorial Africa, leukemia causation is associated with EBV (Epstein-Barr virus) infection.

Human T-cellophilic virus type I (HTLV-I) is a causative factor in adult T-cell lymphoma/leukemia.

Radiation Factors

Ionizing radiation such as X-rays and gamma rays are leukemogenic, with a higher incidence in areas exposed to higher doses of radiation.

The probability of leukemia is significantly higher in patients requiring radiation therapy for malignant tumors and certain benign diseases (e.g., seronegative ankylosing spondylitis, etc.) than in the general population.

In the past, the prevalence of leukemia was relatively high among medical personnel engaged in radiological diagnosis and treatment, but with improved protective measures, the prevalence of leukemia in this group has been more or less the same as that in the general population.

Chemical factors

Leukemia caused by chemical factors is more common in acute myeloid leukemia.

Benzene: the incidence of leukemia in benzene-exposed individuals is 2 to 4.5 times that of the normal population.

Antineoplastic drug alkylating agents: The risk of leukemia is significantly higher in those who apply antineoplastic drug alkylating agents (nitrogen mustard, nitrogen mustard phenylbutyrate, cyclophosphamide, melphalan, carmustine, lomustine, etc.) or topoisomerase II inhibitors.

Etanercept: Some acute promyelocytic leukemias (APL) are associated with treatment with etanercept.

Smoking: not strongly associated with leukemia causation, but one study showed that smoking increased the incidence of t(8;21) acute myeloid leukemia.

Alcohol: alcohol consumption during pregnancy may also increase the risk of acute myeloid leukemia in infants and children after birth.

Genetic factors

Although leukemia is not a hereditary disease, the occurrence of leukemia in one of the monozygotic twins within 6 years of age gives the other a 25% chance of developing leukemia.

The prevalence of leukemia in first-degree relatives (parents, children, siblings) of leukemia patients is three times higher than in the general population.

Patients and family members with congenital or genetic disorders such as Down syndrome and Fanconi anemia are susceptible to acute myeloid leukemia.

The incidence of acute leukemia in patients with Down syndrome is 10 times higher than in the normal population, and the incidence of acute myeloid leukemia type M7 is 500 times higher than in the normal population.

Other Blood Disorders

Certain blood disorders may eventually develop into leukemia, such as myelodysplastic syndromes (MDS), lymphoma, multiple myeloma, and paroxysmal sleep hemoglobinuria (PNH).

Pathogenesis

The “second strike” theory

Mutations in ras, myc and other genes in hematopoietic cells lead to the generation of clonally abnormal hematopoietic cells. Clonally abnormal hematopoietic cells have a proliferative and/or survival advantage and are often impaired in apoptosis.

Genetic alterations such as the formation of fusion genes like PML/RARA may result in blocked or disrupted hematopoietic cell differentiation.

Leukemia stem cells

Leukemia is a malignancy that originates in a single cell in the body.

The malignant transformation occurs at the hematopoietic stem/progenitor cell stage, resulting in the formation of leukemic stem cells that have the ability to self-renew and the advantage of proliferation and survival.

As leukemic stem cells continue to self-renew and proliferate while suffering from apoptosis and differentiation defects, leukemia eventually develops.

Symptoms

The onset of leukemia varies in urgency. Clinical manifestations are mainly related to the inhibition of normal hematopoiesis and infiltration of leukemia cells, and are mostly non-specific.

Symptoms of acute leukemia

The onset of acute leukemia varies. In the case of acute onset, there may be a sudden onset of high fever, similar to a “cold”, or there may be severe bleeding. Those with a slow onset of the disease often have a pale complexion and purpura (ecchymosis due to subcutaneous bleeding), and are often detected when they visit the doctor because of heavy menstruation or bleeding that is difficult to stop after a tooth is extracted.

Common Symptoms

Pallor of the skin and mucous membranes, fatigue, etc. may be present.

Half of the patients have severe anemia at the time of presentation, especially those with leukemia secondary to myelodysplastic syndromes.

Some patients may have no anemia due to the short course of the disease.

Half of the patients have fever as an early manifestation.

It may be low-grade fever, and the body temperature may be 39-40℃, or above 40℃, accompanied by chills and sweating.

Although leukemia itself can be febrile, high fever often suggests secondary infection.

Infections can occur in multiple sites, with oral, gingival, and pharyngeal isthmus infections being the most common, and localized mucosal ulceration or necrosis can occur.

Pulmonary infections, perianal infections, and perianal abscesses are also common, and in severe cases, bloodstream infections may be present.

Nearly 40% of people with bleeding as an early manifestation.

A large number of leukemia cells stagnation and infiltration in blood vessels, thrombocytopenia, coagulation abnormalities are the main reasons for bleeding.

Bleeding can occur in all parts of the body, and the common ones are skin petechiae, ecchymosis, nosebleed, gum bleeding, and menorrhagia.

Bleeding from the fundus of the eye can lead to visual impairment.

In severe cases, widespread bleeding throughout the body occurs due to complications of coagulation abnormalities.

Intracranial hemorrhage may result in headache, vomiting, inconsistent pupil size on both sides, and even coma and death.

Infiltration symptoms

Lymph node enlargement is more common. In some patients, mediastinal lymph node enlargement can be found by examination.

Liver and spleen are mostly mild to moderate, and giant spleen is rare.

Pressure pain in the lower part of the sternum is often present. Joint and bone pain may occur, especially in children.

When bone marrow necrosis occurs, severe bone pain may occur.

Some patients may have granulocytic sarcoma, or chloroma, which often involves the periosteum and most often occurs in the orbit, causing protruding eyes, double vision, or blindness.

Gums may be hyperplastic and swollen.

The skin may appear blue-gray maculopapular rash, with localized skin elevation, hardening, and purplish-blue nodules.

It is the most common site of extramedullary infiltration in leukemia.

Most chemotherapeutic drugs are difficult to pass the blood-brain barrier and cannot effectively kill leukemia cells hidden in the central nervous system, thus causing central nervous system leukemia (CNSL).

In mild cases, it manifests as headache and dizziness; in severe cases, there is vomiting, neck stiffness, and even convulsions and coma.

Most often, there is painless enlargement of one testicle and no enlargement of the other.

Leukemia can infiltrate other tissues and organs, and the lungs, heart, digestive tract and genitourinary system can be involved.

Symptoms of chronic leukemia

Symptoms of chronic myeloid leukemia

The natural course of chronic myeloid leukemia is divided into chronic phase (CP), accelerated phase (AP) and acute phase (BP/BC).

It usually lasts for 1 to 4 years, and patients have symptoms of hypermetabolism such as malaise, low-grade fever, excessive sweating or night sweating, and weight loss.

Splenomegaly is often the most prominent sign, and if splenic infarction occurs, significant splenic region (left lower abdomen) pressure may be present.

When there is a significant increase in white blood cells, there may be congestion and hemorrhage in the fundus.

In the accelerated phase of the disease, there is often fever, weakness, progressive weight loss, bone pain, and gradual development of anemia and hemorrhage; the accelerated phase can last from a few months to several years.

When acute myeloid leukemia enters the acute phase, the prognosis is poor and patients often die within months.

Symptoms of chronic lymphocytic leukemia

Chronic lymphocytic leukemia has a slow onset, mostly without conscious symptoms, and is mostly found during physical examination or medical checkups for other diseases.

Symptomatic patients may show weakness and fatigue in the early stage, followed by loss of appetite, emaciation, low-grade fever, night sweats and so on.

60% to 80% of patients have enlarged lymph nodes, mostly in the head and neck, clavicle and other places. More than half of the patients have mild to moderate splenomegaly, mild hepatomegaly and other symptoms.

In the advanced stage, patients may have anemia, thrombocytopenia and granulocytopenia, and are often susceptible to complications of infection.

Consultation

Department of Medicine

Department of Hematology

When symptoms such as fever, anemia, bleeding, bone pain, hepatomegaly, splenomegaly, enlarged lymph nodes, fatigue, night sweats and weight loss occur, it is recommended to consult a doctor promptly.

Leukemia Clinic

If you are diagnosed with leukemia, you can also go to the Leukemia Treatment Center of a hospital specializing in hematology.

Preparation

Preparing for the consultation: registration, preparation of documents, and frequently asked questions.

Tips for medical treatment

The doctor will usually conduct a physical examination. It is recommended that you choose loose-fitting clothes to complete the examination.

Leukemia, with no specific symptoms in the early stage, is easy to be overlooked, so people with family history of leukemia should have regular cancer checkups.

Certain blood diseases may eventually develop into leukemia, such as myelodysplastic syndromes (MDS), lymphoma, multiple myeloma, paroxysmal sleep hemoglobinuria (PNH), etc. It is recommended to follow the doctor’s instructions for regular follow-up.

Checklist for medical preparation

Particular attention should be paid to the time of onset of symptoms, special manifestations, etc.

Are there any signs of anemia such as pale skin and mucous membranes, weakness, etc.?

Is there any unexplained fever?

Are there any recent skin bruises, nosebleeds, bleeding gums, etc.?

Do women have excessive menstruation?

Are there patients with leukemia and other malignant tumors in the family?

Is there a history of radiation therapy?

Are there any concomitant diseases such as myelodysplastic syndromes, paroxysmal sleep hemoglobinuria (PNH), etc.?

Are there any drug or food allergies?

Test results in the last six months, which can be brought to the doctor’s office

Specialized tests: Tumor marker reports, blood tests (blood smears, etc.), bone marrow image tests.

Imaging tests: ultrasound, CT, magnetic resonance imaging (MRI) and other imaging reports.

Laboratory tests: blood routine, urine routine, biochemical test reports, etc.

Other tests: PET-CT, etc.

Diagnosis

Leukemia is mainly determined based on clinical manifestations, signs and laboratory tests.

The most important thing for clear diagnosis is laboratory examination, which mainly includes bone marrow morphology and histochemical staining, bone marrow immunological examination, cytogenetics, molecular biology examination and so on.

Diagnosis is based on

Medical History

A detailed medical history helps the doctor to make a correct diagnosis and guide the treatment.

The following information generally needs to be given to the doctor:

Fever: whether it is regular, what is the highest body temperature, whether it is accompanied by chills and sweating, etc.

Bleeding: whether there are frequent nosebleeds, bleeding gums or bleeding that does not stop easily after tooth extraction, and whether women have excessive menstruation.

Family history: whether there are patients with leukemia or other malignant tumors in the immediate family.

Clinical manifestations

Acute leukemia in children and adolescents tends to have a rapid onset. Common first symptoms include fever, progressive anemia, significant bleeding tendency or bone and joint pain.

The slow onset of the disease is common in the elderly and some young patients, and the condition is gradually aggravated.

In a few patients, convulsions, blindness, toothache, swollen gums, pericardial effusion, and paraplegia of both lower limbs are the first symptoms.

Examination may reveal the presence of enlarged liver, spleen and lymph nodes, sternal pressure pain, pale or bleeding skin and mucous membranes.

Laboratory tests

Laboratory tests are important for the diagnosis of leukemia. Different types of leukemia may have different tests, but the main ones are as follows.

Blood picture

White blood cells: most patients have an increase in white blood cells, called leukocytoclastic leukemia. There is also a normal or reduced white blood cell count, called leukocytoclastic leukemia.

Blood smear classification: varying numbers of primitive and naïve cells can be seen, but it is difficult to find primitive cells on the blood smear in cases of leukocytoclastic leukemia.

Anemia: patients often have varying degrees of normocytic anemia, and juvenile red blood cells can be found in a few patients with varying sizes of red blood cells on blood film.

Platelets: platelets are often extremely reduced in advanced leukemia.

Bone Marrow Imaging

Bone marrow picture is a mandatory test, which is the main basis for the diagnosis of leukemia and helps to classify the leukemia.

In most acute leukemia, the bone marrow image shows significant proliferation of nucleated cells, mainly primitive cells; in a few cases, the bone marrow image is hypoproliferative, which is called hypoproliferative acute leukemia.

Chronic leukemia may show extremely active bone marrow hyperplasia with predominantly granulocytes. Megakaryocytes are normal or increased and decreased in advanced stages.

Cytochemistry

Used primarily to help identify various types of leukemia, the usual specimens are peripheral blood or bone marrow.

The main items include myeloperoxidase (MPO), glycogen staining (PAS), and non-specific esterase (NSE).

Immunophenotyping

Immunophenotyping is currently an important tool for leukemia disease diagnosis, prognostic stratification and efficacy monitoring.

Most of the tests are currently performed using flow cytometry.

This is done by testing the patient’s bone marrow or peripheral blood samples with a variety of specific antibodies to examine the characteristic antigenic expression patterns of leukemia cells, thereby identifying the source of the leukemia cells and determining their unique phenotype.

Cytogenetic and molecular biology tests

Leukemia is often associated with specific cytogenetic (chromosomal karyotype) and molecular biological alterations (e.g., fusion genes, gene mutations).

The specimens commonly used for this test are peripheral blood or bone marrow, and it is primarily used for typing and assessing prognosis.

Blood biochemical tests

Uric acid: patients may present with increased serum uric acid concentrations, especially during chemotherapy. Uric acid excretion is increased and even uric acid crystals appear.

Coagulation: Patients may develop coagulation abnormalities when disseminated intravascular coagulation (DIC) occurs.

Lactate dehydrogenase: serum lactate dehydrogenase (LDH) may be increased.

Tumor Staging

Among leukemias, chronic lymphocytic leukemia has exclusive staging criteria.

The most widely accepted methods of staging chronic lymphocytic leukemia are Rai staging and Binet staging.

Rai Staging

Based on the peripheral blood lymphocyte count (ALC) and comorbid symptoms, Rai staging is divided into three risk strata: low, intermediate, and high risk, ranging from stage 0 to stage IV.

Binet staging

Binet staging is mainly based on the extent of the involved lymph nodes, which is evaluated in five regions, including the neck, axilla, groin, liver, and spleen, and is categorized into three stages, A, B, and C.

Differential Diagnosis

There are numerous subtypes of leukemia, and in addition to differentiating the subtypes from each other, it is also necessary to differentiate them from the following diseases.

Megaloblastic anemia

Similarities: symptoms such as anemia, bleeding, and infection may be present.

Differences: Patients with megaloblastic anemia do not have an increase in primitive cells in the bone marrow, and the glycogen staining reaction of young red blood cells is often negative.

Myelodysplastic syndrome

Similarities: primitive and naïve cells in the peripheral blood, hypoplasia and chromosomal abnormalities.

Differences: In myelodysplastic syndromes, less than 20% of the bone marrow is composed of primitive cells.

Leukemia-like reaction

Similarities: The clinical presentation of leukemia-like reactions is highly similar to that of leukemia.

Differences: Leukemia-like reaction is often complicated by severe infections, malignant tumors and other underlying diseases, and has the clinical manifestations of the corresponding underlying diseases; platelets and hemoglobin are mostly normal. Leukocytes return to normal after the underlying disease is controlled.

Other causes of splenomegaly

Similarities: schistosomiasis, chronic malaria, black fever, cirrhosis, hypersplenism, etc. all have splenomegaly.

Differences: other causes of splenomegaly have their own clinical characteristics of the original disease, and the blood and bone marrow images do not have the typical changes of leukemia; Ph chromosome and BCR-ABL fusion gene are negative.

Pancytopenia caused by other diseases

Similarity: EBV infection, whooping cough, infectious lymphocytosis, rubella and other viral infections can also manifest as pancytopenia.

Differences: These diseases are short-lived, benign, and do not increase the number of primitive naïve cells in the bone marrow. Leukemia has a long course and is associated with an increase in the number of primitive naive cells in the bone marrow.

Treatment

Principles of treatment

Doctors will stratify the prognostic risk according to the patient’s specific typing results and clinical features, and select and design the optimal, complete and systematic treatment plan according to the patient’s wishes and financial ability.

Considering the need for treatment and to minimize the pain of repeated puncture, the doctor will usually recommend the retention of a deep vein catheter.

Those who are suitable for allogeneic hematopoietic stem cell transplantation should have blood drawn for human leukocyte antigen (HLA) matching.

General Treatment

Emergency treatment of hyperleukocytemia

When peripheral blood leukocytes are >100×109/L, urgent hydration must be given to prevent complications such as hyperuricemia, acidosis, electrolyte disorders, and coagulation abnormalities.

Short-term pretreatment before chemotherapy can be used, and the commonly used drugs are dexamethasone with hydroxyurea.

Prevention of infection

Patients with leukemia are often accompanied by granulocytopenia or lack of granulocytes, which is prone to infection.

Strict bedside isolation should be carried out, and antibiotic treatment should be applied for prevention if necessary.

Component blood transfusion support

Severe anemia will cause severe hypoxia, weakness, dizziness, chest tightness and shortness of breath after activity, and even fainting. Oxygen intake and transfusion of concentrated red blood cells can be administered.

Patients with abnormal coagulation function can be transfused with plasma to supplement coagulation factors and improve bleeding symptoms.

Blood product infusion treatment

Patients with abnormal coagulation function, especially those with acute promyelocytic leukemia, can be infused with blood products such as fibrinogen and prothrombinogen complex to supplement the required coagulation factors and improve the bleeding symptoms.

Prevention of hyperuricemia nephropathy

Leukemia patients should drink more water during chemotherapy and alkalinize the urine appropriately.

When patients have oliguria, anuria and renal insufficiency, they should be treated as acute renal failure.

Supplementary nutrition

Leukemia is a serious consumptive disease, especially when chemotherapy and radiotherapy cause patients’ gastrointestinal mucous membrane damage and functional disorders.

Attention should be paid to supplemental nutrition to maintain water and electrolyte balance. Doctors usually give patients high-protein, high-calorie, easy-to-digest food, and supplement nutrition via vein when necessary.

Treatment of different types of leukemia

The treatment of leukemia needs to be individualized according to the specific type of leukemia and the patient’s own condition.

Treatment of Acute Lymphoblastic Leukemia

The choice of treatment regimen for acute lymphoblastic leukemia needs to take into account multiple factors, such as the patient’s age, subtype of acute lymphoblastic leukemia, microscopic residual disease (MRD) after treatment, the availability of stem cell donors and targeted therapeutic agents.

VP regimen

Effectiveness: The VP regimen results in complete remission (CR) in 50% of adults with acute lymphoblastic leukemia, with a CR period of 3 to 8 months.

Treatment after remission is generally divided into two stages: intensive consolidation and maintenance therapy.

Intensive consolidation therapy: chemotherapy and hematopoietic stem cell transplantation (HSCT) are the two main modalities. Currently, most of the chemotherapy adopts the intermittent repetition of the original induction regimen, and other intensive regimens are given at regular intervals.

Maintenance therapy: Oral 6-mercaptopurine (6-MP) and methotrexate (MTX) with intermittent VP chemotherapy is a commonly used and effective maintenance therapy.

Targeted therapy: Ph+ALL-induced remission chemotherapy can be combined with tyrosine kinase inhibitors (TKIs, such as imatinib or dasatinib) for targeted therapy, and the combination of allogeneic hematopoietic stem cell transplantation can lead to a further improvement in survival time and quality of life.

The main control measures for CNS leukemia are:

Craniospinal irradiation.

Intrathecal chemotherapy such as MTX, cytarabine (Ara-C), glucocorticoids and/or high-dose systemic chemotherapy such as high-dose methotrexate (HDMTX), Ara-C.

In patients with testicular leukemia, bilateral irradiation and systemic chemotherapy are indicated even if there is only unilateral testicular leukemia.

Hematopoietic stem cell transplantation involves the intravenous infusion of normal human hematopoietic stem cells into a pretreated (chemotherapy/radiotherapy) patient to rebuild the patient’s hematopoietic and immune functions for the treatment of certain diseases.

Hematopoietic stem cell transplantation can be categorized into autologous HSCT, homozygous HSCT between identical twins, and allogeneic HSCT according to donor genetics.

Hematopoietic stem cell transplantation is essential for curing adult acute lymphoblastic leukemia. Allogeneic HSCT leads to long-term survival in 40% to 65% of patients.

Treatment of Acute Myeloid Leukemia

The treatment strategy for acute myeloid leukemia is similar to that of acute lymphoblastic leukemia, and also includes induction of remission therapy and post-remission therapy, except that the specific regimens and medications are different.

Acute myeloid leukemia (non-acute promyelocytic leukemia)

Acute promyelocytic leukemia (APL): mostly all-trans retinoic acid (ATRA) and/or arsenic ± anthracyclines.

Acute myeloid leukemia (non-acute promyelocytic leukemia): do cerebrospinal fluid examination and intrathecal prophylaxis at least once for CNS leukemia screening.

Acute promyelocytic leukemia

The following regimens are available depending on the patient’s condition:

Combination chemotherapy regimens consisting of newer drugs without cross-resistance.

Combination regimens consisting of medium- and high-dose cytarabine.

Hematopoietic stem cell transplantation.

Clinical trials: e.g., drug resistance reversal agents, new targeted agents (e.g., FLT3 inhibitors, etc.), biologic therapies, etc.

Chronic myeloid leukemia treatment

The treatment of chronic myeloid leukemia should focus on the early chronic phase, avoiding disease transformation and striving for remission at the cytogenetic and molecular biology levels, with a poor prognosis once the disease enters the accelerated or acute phase (collectively referred to as the progressive phase).

Molecular targeted therapy is a therapeutic method to inhibit the growth of tumor cells at the molecular level or even eliminate the tumor by using molecular targeted drugs to specifically block the biological function of the target molecule as the target of tumor tissues or cells with specificity (or relative specificity).

Currently, the commonly used targeted drugs for chronic myeloid leukemia are the amino acid kinase inhibitors (TKI).

First-generation TKIs, such as imatinib mesylate (IM), treat patients with chronic myeloid leukemia with a complete cytogenetic remission rate of 92% and a 10-year overall survival (0S) of up to 84%.

Second-generation TKIs: e.g., nilotinib, dasatinib, are more effective in treating chronic myeloid leukemia, and are gradually becoming optional drugs in the first-line treatment regimen for CML.

Interferon (IFN-α) was the drug of choice before the advent of molecularly targeted drugs for patients who were not candidates for acetate kinase inhibitors (TKIs) and hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation is a curative treatment for chronic myeloid leukemia, but is not used as a first-line agent in the chronic phase.

Allogeneic HSCT is used only in patients with chronic myeloid leukemia who are at very low risk for transplantation and are resistant and intolerant to amine kinase inhibitors (TKIs) and in the progressive phase.

Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia is an inert leukemia and not all patients require immediate treatment after diagnosis.

Premature treatment does not prolong survival, and it is currently believed that patients with early stage (Rai 0 to II or Binet A) do not need treatment, and regular follow-up is sufficient.

The presence of one of the following conditions indicates that the disease is active and the doctor will usually recommend starting treatment:

≥10% weight loss within 6 months for no other reason, extreme fatigue, non-infectious fever (over 38°C) for >2 weeks, and night sweats.

The lower border of the spleen is >10 cm from the subcostal margin or progressive splenomegaly and pain in the splenic region is present.

Lymph nodes are progressively enlarged or >10 cm in diameter.

Progressive peripheral blood lymphocytosis with >50% increase over 2 months or doubling time <6 months.

Presence of autoimmune hematopenia, with ineffective glucocorticoid therapy.

Progressive bone marrow failure with progressive exacerbation of anemia and/or thrombocytopenia.

Chemotherapy: Commonly used chemotherapeutic agents are alkylating agents (e.g., nitrogen mustard phenylbutyrate), purine analogs (e.g., fludarabine), and glucocorticoids.

Immunotherapy: the commonly used drug is rituximab, which has a significant therapeutic effect on CD20-expressing chronic lymphocytic leukemia cells. However, rituximab is cleared too quickly in patients with chronic lymphocytic leukemia, and higher doses or densities are needed to be effective.

Chemoimmunotherapy: Rituximab combined with chemotherapeutic agents can produce synergistic anti-tumor effects and improve the overall response rate and survival rate of patients treated.

Molecular Targeted Therapy

Hematopoietic stem cell transplantation

Treatment Related Nursing

Chemotherapy Care

When the body experiences a decrease in white blood cells, infections are more likely to occur.

During chemotherapy, keep warm and rest, avoid catching cold, and reduce close contact with people to reduce the risk of infection.

Eat small meals and eat easily digestible, light foods.

If necessary, consult your doctor if you need to take anti-emetic drugs.

For fever below 38℃, no antipyretic drugs can be used, drink plenty of warm boiled water and pay attention to rest.

If the temperature exceeds 38℃ and there is obvious headache or general discomfort, you should go to the hospital for follow-up.

This kind of weakness is often related to anemia, which requires sufficient rest and enhanced nutrition. Consuming enough calories and proteins can help relieve your discomfort.

If necessary, ask your doctor if you need to take any medication to correct your anemia.

Hair loss may occur during radiotherapy and will grow back after the treatment is over, so don’t worry too much.

Radiotherapy care

Before radiotherapy, patients need to remove metal objects from their bodies. And wear loose, soft cotton clothes.

After radiotherapy, the skin will be dry and itchy. Avoid strong heat or cold stimulation of the skin at the radiotherapy site, do not use hot water bags, and avoid direct sunlight. When molting and crusting occur, do not tear off the skin with your hands.

When cleaning the skin at the radiotherapy site, use a soft towel, the action should be gentle, avoid using irritating substances, such as soap, alcohol, etc..

Nursing care of intrathecal injection of chemotherapy drugs

Body position: generally take the head low holding the knee side lying position.

Lying down: 4 to 6 hours after the needle is removed from the pillow lying down.

Observation: pay attention to observe whether there is headache, vomiting, fever and other symptoms of chemical meningitis and other neurological damage.

Nursing care of oral ulcers

Leukemia cells are easy to infiltrate the oral mucosa, patients applying methotrexate chemotherapy are more likely to have oral ulcers, attention should be paid to oral care to reduce the probability of infection on the ulcer surface and promote ulcer healing.

In general, saline, compound borax gargle (Dobei liquid) and other alternating gargles can be used.

Each gargle time is 15-20 minutes, at least 3 times a day.

Ulcer patch, topical recombinant human epidermal growth factor derivatives (goldin peptide), tin analogs, neomycin, gentamycin glycerin, etc. can be used.

After gargling with mouthwash after three meals and before bedtime, apply the medicine to the ulcer. In order to ensure the normal effect of the drug, you can not eat or drink until 2~3 hours after applying the drug.

Prevention of bleeding during myelosuppression

Keep the nasal mucosa moist and use liquid paraffin drops three times a day. Don’t blow your nose hard, don’t pick your teeth with toothpicks, and simply gargle for bleeding gums.

Avoid extrusion and trauma during activities, and apply localized pressure for 10 to 20 minutes after various punctures.

Keep the bowel movement unobstructed, observe the color of urine and stool, and notify the nurse if any abnormality is found.

Clothes should be loose, soft and comfortable, cut nails diligently and do not scratch the skin.

Avoid eating hard, spicy, bony and thorny food.

Prognosis

Prognostic factors

The prognosis of leukemia is related to the specific typing of leukemia, the status of genetic testing, the patient’s age, and the effectiveness of treatment.

Survival Assessment

Survival of leukemia patients can be roughly predicted by using 5-year survival rate and median survival period, etc.

5-year survival rate: it refers to the percentage of patients whose tumors survive for more than 5 years after various comprehensive treatments. the probability of recurrence after 5 years is very low, and can generally be regarded as clinical cure.

Median Survival: The survival time of patients with the same disease is ranked in descending order, and the survival time located in the middle of the total number of patients (e.g., the 50th out of 99) is the median survival time.

Special Reminders

Statistics such as 5-year survival rate and median survival are for clinical research only and do not represent the specific survival of an individual. The individual survival of a patient needs to be determined by a combination of factors, and it is recommended to consult with the physician.

Prognosis of acute leukemia

Without specific treatment, the average survival period of acute leukemia is 3 months, or even a few days after diagnosis.

With modern treatments, many patients have achieved remission, improved quality of life, and even long-term survival.

Conventional prognostic factors

Older patients with higher white blood cell counts have a poor prognosis.

Patients with M3 have the best prognosis if early death can be avoided, and most can be cured.

Leukemia secondary to radiation, chemotherapy, or myelodysplastic syndromes (MDS), relapses and primary and secondary multidrug resistance, and those who require prolonged chemotherapy for remission have a poor prognosis.

Those with combined extramedullary leukemia also have a poorer prognosis.

Chromosome-related factors

Normal chromosomal acute myeloid leukemia with isolated NPM1 mutations has a better prognosis.

Patients with t(8;21), t(15;17), or inv(16) have a better prognosis. However, those with concomitant KIT gene mutations have a poorer prognosis.

Patients with acute lymphoblastic leukemia who have t(9;22), t(4;11), or leukocytosis (leukocytes >100×109/L in patients with T-ALL and leukocytes >30×109 in patients with B-ALL) have a poor prognosis.

Tip.

Consult a hematologist for other prognostic factors.

Prognosis of chronic leukemia

Prognosis of chronic myeloid leukemia

Most patients with chronic myeloid leukemia have long-term survival with tyrosine kinase inhibitor (TKI) therapy.

Allogeneic hematopoietic stem cell transplantation can result in a 5-year survival rate of 70% for patients with chronic myeloid leukemia who are resistant to second-generation TKIs, have the T315I mutation, and have accelerated and acute stages of the disease.

At the patient’s initial visit, the general practitioner will assess the risk of the condition by using the Sokal Prognostic Score formula.

Low-risk group: <0.8.

Intermediate-risk group: 0.8 to 1.2.

High-risk group: >1.2.

[Conclusion] Statistically, the prognosis of the low-risk group is relatively good, and the prognosis of the high-risk group is relatively poor.

Ph chromosome is also known as Philadelphia chromosome, named because it was first discovered in Philadelphia.

Ph chromosome is seen in about 95% of patients with chronic myeloid leukemia and is considered an important diagnostic marker for chronic myeloid leukemia.

A small number of patients are Ph negative, and the prognosis for these patients is poor.

Prognosis of chronic lymphocytic leukemia

Chronic lymphocytic leukemia is a highly heterogeneous disease, ranging from lifelong treatment-free to rapid short-term disease progression.

The duration of chronic lymphocytic leukemia can be more than 10 or even 30 years, but the median survival is 3 to 4 years.

Chronic lymphocytic leukemia may also undergo clinical transformation (Richter’s syndrome).

Daily

Life Management

Mindfulness and Emotional Adjustment

A good mood and mindset cannot be replaced by medication.

After diagnosis, the patient may develop a sense of fear and may be afraid of pain, abandonment and death. Family members should pay attention to listen to the patient’s heart, improve the patient’s mental ability and relieve anxiety symptoms.

Encourage the patient so that he/she can face the surgery and other treatments positively with a good mindset.

During the period between treatments and after the treatment, encourage the patient to do work and household chores as much as he/she can, so as to reintegrate into the society.

Living

Keep the living environment clean, with sufficient ventilation, sufficient sunlight and suitable temperature. Sterilize the room regularly to avoid infection.

Maintain good hygiene to prevent accidental bodily injury. Rinse your mouth with saline solution and use a soft-bristled toothbrush after meals and before going to bed.

Maintain a positive and optimistic state of mind, reduce tension and anxiety, and avoid excessive activity and trauma for those who are prone to bleeding.

Dietary regulation

Balanced dietary structure, diversified food types and rich nutrition.

Pickled, fried and deep-fried food should be avoided.

Eat more vitamin-rich vegetables and fruits, such as broccoli, tomatoes, celery, lettuce, kiwi, apples and bananas.

Eat more protein-rich foods, such as eggs, milk, lean meat and fish.

It is recommended not to eat foods that stimulate the secretion of stomach acid, such as foods that are too sweet and spicy.

Rest and Exercise

Pay attention to rest, avoid staying up late or straining, and ensure sufficient sleep and rest to reduce physical exertion and promote recovery.

When the condition improves, you can start with low intensity exercise such as walking and gradually resume normal activities.

Review and Follow-up

After treatment of leukemia, you need to have regular review under the guidance of your doctor, and consult the doctor at any time if you have any discomfort.

Review items

Frequency of review: Strictly follow the doctor’s instructions.

Prevention

The exact cause and pathogenesis of leukemia are still unknown, so there is no standard prevention method. However, avoiding the causative factors of leukemia in daily life can help reduce the risk of leukemia.

Minimize exposure to ionizing radiation, and take precautions if you must be exposed.

Avoid exposure to benzene-containing materials, such as chemicals, glues and paints used in construction.

Pay attention to choosing environmentally friendly decoration materials, and fully ventilate the new house for 3 to 6 months before moving in.

Pay attention to dietary hygiene and do not abuse drugs.

Smoking increases the risk of acute myeloid leukemia and should be stopped.

People with family history of leukemia and history of blood diseases should have regular medical checkups.

Maintain normal body weight, increase physical exercise, ensure sufficient sleep and enhance their immunity.