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BAL has similar symptoms with other types of leukemia, but usually more serious.
Symptoms caused by bone marrow damage
Bruising, spotting: the reason is lack of platelets, it is very common in BAL patients, most of patients die due to the
Anemia: Because the decline of hematopoietic function, need blood transfusion therapy
Persistent fever, infection prolonged healing:
Diffuse hemorrhage: also called Septicemia, which is dangerous and might lead to death.
Symptoms caused by blood cancer cells infiltration into tissues:
Lymphadenopathy
Joint pain
Swelling of the gums
Hepatoslenomegaly
Headache and vomiting: blood cancer infiltration into the wear performance of the central nervous system.
Skin lumps: Because look was slightly green, also known as the "Green tumor."
Pericardial or pleural effusion
Initial symptoms can be nonspecific, particularly in children. Over 50% of children with leukemia had one or more of five features: a liver one can feel (64%), a spleen one can feel (61%), pale complexion (54%), fever (53%), and bruising (52%). Additionally, recurrent infections, feeling tired, arm or leg pain, and enlarged lymph nodes can be prominent features. The B symptoms, such as fever, night sweats, and weight loss, are often present as well.
Central nervous system (CNS) symptoms such cranial neuropathies due to meningeal infiltration are identified in less than 10% of adults and less than 5% of children, particularly mature B-cell ALL (Burkitt leukemia) at presentation.
The signs and symptoms of ALL are variable and include:
- Generalized weakness and feeling tired
- Anemia
- Dizziness
- Headache, vomiting, lethargy, nuchal rigidity, or cranial nerve palsies (CNS involvement)
- Frequent or unexplained fever and infection
- Weight loss and/or loss of appetite
- Excessive and unexplained bruising
- Bone pain, joint pain (caused by the spread of "blast" cells to the surface of the bone or into the joint from the marrow cavity)
- Breathlessness
- Enlarged lymph nodes, liver and/or spleen
- Pitting edema (swelling) in the lower limbs and/or abdomen
- Petechiae, which are tiny red spots or lines in the skin due to low platelet levels
- Testicular enlargement
- Mediastinal mass
Acute biphenotypic leukaemia is an uncommon type of leukemia which arises in multipotent progenitor cells which have the ability differentiating into both myeloid and lymphoid lineages. It is a subtype of "leukemia of ambiguous lineage".
The direct reason lead BAL is still not clear. BAL can be de novo or secondary to previous cytotoxic therapy. Many factors, such as virus, hereditary factors, radiation, might have relationship with BAL.
BAL is hard to treat, usually the chemotherapy is chosen according to the morphology of the blast (ALL or AML). The stem cell transplantation is highly recommended.
About 5% of acute leukaemia cases are BAL. BAL could occur in all the age of the people, but more in adults than in children.
Most signs and symptoms of AML are caused by the replacement of normal blood cells with leukemic cells. A lack of normal white blood cell production makes people more susceptible to infections; while the leukemic cells themselves are derived from white blood cell precursors, they have no infection-fighting capacity. A drop in red blood cell count (anemia) can cause fatigue, paleness, and shortness of breath. A lack of platelets can lead to easy bruising or bleeding with minor trauma.
The early signs of AML are often vague and nonspecific, and may be similar to those of influenza or other common illnesses. Some generalized symptoms include fever, fatigue, weight loss or loss of appetite, shortness of breath, anemia, easy bruising or bleeding, petechiae (flat, pin-head sized spots under the skin caused by bleeding), bone and joint pain, and persistent or frequent infections.
Enlargement of the spleen may occur in AML, but it is typically mild and asymptomatic. Lymph node swelling is rare in AML, in contrast to acute lymphoblastic leukemia. The skin is involved about 10% of the time in the form of leukemia cutis. Rarely, Sweet's syndrome, a paraneoplastic inflammation of the skin, can occur with AML.
Some people with AML may experience swelling of the gums because of infiltration of leukemic cells into the gum tissue. Rarely, the first sign of leukemia may be the development of a solid leukemic mass or tumor outside of the bone marrow, called a chloroma. Occasionally, a person may show no symptoms, and the leukemia may be discovered incidentally during a routine blood test.
The most common symptoms in children are easy bruising, pale skin, fever, and an enlarged spleen or liver.
Damage to the bone marrow, by way of displacing the normal bone marrow cells with higher numbers of immature white blood cells, results in a lack of blood platelets, which are important in the blood clotting process. This means people with leukemia may easily become bruised, bleed excessively, or develop pinprick bleeds (petechiae).
White blood cells, which are involved in fighting pathogens, may be suppressed or dysfunctional. This could cause the patient's immune system to be unable to fight off a simple infection or to start attacking other body cells. Because leukemia prevents the immune system from working normally, some patients experience frequent infection, ranging from infected tonsils, sores in the mouth, or diarrhea to life-threatening pneumonia or opportunistic infections.
Finally, the red blood cell deficiency leads to anemia, which may cause dyspnea and .
Some patients experience other symptoms, such as feeling sick, having fevers, chills, night sweats, feeling fatigued and other flu-like symptoms. Some patients experience nausea or a feeling of fullness due to an enlarged liver and spleen; this can result in unintentional weight loss. Blasts affected by the disease may come together and become swollen in the liver or in the lymph nodes causing pain and leading to nausea.
If the leukemic cells invade the central nervous system, then neurological symptoms (notably headaches) can occur. Uncommon neurological symptoms like migraines, seizures, or coma can occur as a result of brain stem pressure. All symptoms associated with leukemia can be attributed to other diseases. Consequently, leukemia is always diagnosed through medical tests.
The word "leukemia", which means 'white blood', is derived from the characteristic high white blood cell count that presents in most afflicted patients before treatment. The high number of white blood cells are apparent when a blood sample is viewed under a microscope, with the extra white blood cells frequently being immature or dysfunctional. The excessive number of cells can also interfere with the level of other cells, causing further harmful imbalance in the blood count.
Some leukemia patients do not have high white blood cell counts visible during a regular blood count. This less-common condition is called "aleukemia". The bone marrow still contains cancerous white blood cells which disrupt the normal production of blood cells, but they remain in the marrow instead of entering the bloodstream, where they would be visible in a blood test. For an aleukemic patient, the white blood cell counts in the bloodstream can be normal or low. Aleukemia can occur in any of the four major types of leukemia, and is particularly common in hairy cell leukemia.
Although not a malignant neoplasm like other cancers, MPNs are classified within the hematological neoplasms. There are four main myeloproliferative diseases, which can be further categorized by the presence of the Philadelphia chromosome:
In 2008, the World Health Organization listed these diagnoses as types of MPD:
- Chronic myelogenous leukemia (BCR-ABL1–positive)
- Chronic neutrophilic leukemia
- Polycythemia vera
- Primary myelofibrosis
- Essential thrombocythemia
- Chronic eosinophilic leukemia (not otherwise specified)
- Mastocytosis
The myeloproliferative neoplasms (MPNs), previously myeloproliferative diseases (MPDs), are a group of diseases of the bone marrow in which excess cells are produced. They are related to, and may evolve into, myelodysplastic syndrome and acute myeloid leukemia, although the myeloproliferative diseases on the whole have a much better prognosis than these conditions. The concept of myeloproliferative disease was first proposed in 1951 by the hematologist William Dameshek. In the most recent World Health Organization classification of hematologic malignancies, this group of diseases was renamed from "myeloproliferative diseases" to "myeloproliferative neoplasms". This reflects the underlying clonal genetic changes that are a salient feature of this group of disease.
The increased numbers of blood cells may not cause any symptoms, but a number of medical problems or symptoms may occur. The risk of thrombosis is increased in some types of MPN.
Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruising, enlarged lymph nodes, or bone pain. As an acute leukemia, ALL progresses rapidly and is typically fatal within weeks or months if left untreated.
Most cases occur due to an unknown reason. Genetic risk factors may include Down syndrome, Li-Fraumeni syndrome, or neurofibromatosis type 1. Environment risk factors may include significant radiation exposure or prior chemotherapy. Evidence regarding electromagnetic fields or pesticides is unclear. Some hypothesize that an abnormal immune response to a common infection may be a trigger. The underlying mechanism involves multiple genetic mutations that results in rapid cell division. The excessive immature lymphocytes in the bone marrow interfere with the production of new red blood cells, white blood cells, and platelets. Diagnosis is typically based on blood tests and bone marrow examination.
ALL is typically treated initially with chemotherapy aimed at bringing about remission. This is then followed by further chemotherapy typically over a number of years. Additional treatments may include intrathecal chemotherapy or radiation therapy if spread to the brain has occurred. Stem cell transplantation may be used if the disease recurs following standard treatment. Additional treatments such as immunotherapy are being studied.
ALL affected about 876,000 people globally in 2015 and resulted in about 111,000 deaths. It occurs most commonly in children, particularly those between the ages of two and five. In the United States it is the most common cause of cancer and death from cancer among children. ALL is notable for being the first disseminated cancer to be cured. Survival for children increased from under 10% in the 1960s to 90% in 2015. Survival rates remain lower for babies (50%) and adults (35%).
Clinically and pathologically, leukemia is subdivided into a variety of large groups. The first division is between its "acute" and "chronic" forms:
- Acute leukemia is characterized by a rapid increase in the number of immature blood cells. The crowding that results from such cells makes the bone marrow unable to produce healthy blood cells. Immediate treatment is required in acute leukemia because of the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs of the body. Acute forms of leukemia are the most common forms of leukemia in children.
- Chronic leukemia is characterized by the excessive buildup of relatively mature, but still abnormal, white blood cells. Typically taking months or years to progress, the cells are produced at a much higher rate than normal, resulting in many abnormal white blood cells. Whereas acute leukemia must be treated immediately, chronic forms are sometimes monitored for some time before treatment to ensure maximum effectiveness of therapy. Chronic leukemia mostly occurs in older people, but can occur in any age group.
Additionally, the diseases are subdivided according to which kind of blood cell is affected. This divides leukemias into lymphoblastic or "lymphocytic leukemias" and myeloid or "myelogenous leukemias":
- In lymphoblastic or lymphocytic leukemias, the cancerous change takes place in a type of marrow cell that normally goes on to form lymphocytes, which are infection-fighting immune system cells. Most lymphocytic leukemias involve a specific subtype of lymphocyte, the B cell.
- In myeloid or myelogenous leukemias, the cancerous change takes place in a type of marrow cell that normally goes on to form red blood cells, some other types of white cells, and platelets.
Combining these two classifications provides a total of four main categories. Within each of these main categories, there are typically several subcategories. Finally, some rarer types are usually considered to be outside of this classification scheme.
Aggressive NK-cell leukemia (ANKL) is a lymphoid leukemia that is a deficiency NK cells. Not very much is known about this disease due to its rarity, but it is highly aggressive. Most patients will die within 2 years.
"T-cell leukemia" describes several different types of lymphoid leukemias which affect T cells.
The most common T-cell leukemia is precursor T-cell lymphoblastic leukemia. It causes 15% of acute leukemias in childhood, and also 40% of lymphomas in childhood. It is most common in adolescent males. Its morphology is identical to that of "precursor B-cell lymphoblastic leukemia". Cell markers include TdT, CD2, CD7. It often presents as a mediastinal mass because of involvement of the thymus. It is highly associated with NOTCH1 mutations.
Other types include:
- Large granular lymphocytic leukemia
- Adult T-cell leukemia/lymphoma
- T-cell prolymphocytic leukemia
In practice, it can be hard to distinguish T-cell leukemia from T-cell lymphoma, and they are often grouped together.
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cells. Symptoms may include feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection. Occasionally spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly and is typically fatal within weeks or months if left untreated.
Risk factors include smoking, previous chemotherapy or radiation therapy, myelodysplastic syndrome, and exposure to the chemical benzene. The underlying mechanism involves replacement of normal bone marrow with leukemia cells, which results in a drop in red blood cells, platelets, and normal white blood cells. Diagnosis is generally based on bone marrow aspiration and specific blood tests. AML has several subtypes; for which treatments and outcomes may vary.
AML is typically initially treated with chemotherapy aimed at inducing remission. People may than go on to receive additional chemotherapy, radiation therapy, or a stem cell transplant. The specific genetic mutations present within the cancer cells may guide therapy, as well as determine how long that person is likely to survive. Arsenic trioxide may be tried in cases that have recurred following usual treatments.
AML affected about one million people globally in 2015 and resulted in 147,000 deaths. It most commonly occurs in older adults. Males are affected more often than females. AML is curable in about 35% of people under 60 years old and 10% over 60 years old. Older people who are not healthy enough to receive intensive chemotherapy have a typical survival of 5–10 months. It accounts for roughly 1.8% of cancer deaths in the United States.
Most people are diagnosed without symptoms as the result of a routine blood test that shows a high white blood cell count. Less commonly, CLL may present with enlarged lymph nodes without a high white blood cell count or no evidence of the disease in the blood. This is referred to as small lymphocytic lymphoma. In some individuals, the disease comes to light only after the cancerous cells overwhelm the bone marrow resulting in anemia producing tiredness or weakness.
Chronic lymphoid leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on there is typically no symptoms. Latter non-painful lymph nodes swelling, feeling tired, fever, or weight loss for no clear reason may occur. Enlargement of the spleen and anemia may also occur. It typically worsens gradually.
Risk factors include having a family history of the disease. Agent Orange and certain insecticides might also be a risk. CLL results in the build up of B cell lymphocytes in the bone marrow, lymph nodes, and blood. These cells do not function well and crowd out healthy blood cells. It is divided into two main types those with a mutated IGHV gene and those without. Diagnosis is typically based on blood tests finding high numbers of mature lymphocytes and smudge cells.
Management of early disease is generally with watchful waiting. Infections should more readily be treated with antibiotics. In those with significant symptoms chemotherapy or immunotherapy may be used. The medications fludarabine, cyclophosphamide, and rituximab are typically the initial treatment in those who are otherwise healthy.
CLL affected about 904,000 people globally in 2015 and resulted in 60,700 deaths. The disease most common occurs in people over the age of 50. Males are affected more often than females. It is much less common in people from Asia. Five-year survival following diagnosis is approximately 83% in the United States. It represents less than 1% of deaths from cancer.
Leukemia cutis is the infiltration of neoplastic leukocytes or their precursors into the skin resulting in clinically identifiable cutaneous lesions. This condition may be contrasted with leukemids, which are skin lesions that occur with leukemia, but which are not related to leukemic cell infiltration.
Leukemia cutis can occur in most forms of leukemia, including chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, and prolymphocytic leukemia.
Precursor B-cell lymphoblastic leukemia is a form of lymphoid leukemia in which too many B-cell lymphoblasts (immature white blood cells) are found in the blood and bone marrow. It is the most common type of acute lymphoblastic leukemia (ALL). It is sometimes additionally classified as a lymphoma, as designated "leukemia/lymphoma".
It consists of the following subtypes:
- t(9;22)-BCR/ ABL
- t(v;11q23)-MLL rearrangement
- t(1;19)-E2A/PBX1
- t(12;21)-ETV/ CBFα
- t(17;19)-E2A-HLF
Acute leukemia or acute leukaemia is a family of serious medical conditions relating to an original diagnosis of leukemia. In most cases, these can be classified according to the lineage, myeloid or lymphoid, of the malignant cells that grow uncontrolled, but some are mixed and for those such an assignment is not possible.
Forms of acute leukemia include:
- Acute myeloid leukemia
- Acute erythroid leukemia
- Acute lymphoblastic leukemia
- T-cell acute lymphoblastic leukemia
- Adult T-cell leukemia/lymphoma
- (Precursor)T-lymphoblastic leukemia/lymphoma
- "Blast crisis" of chronic myelogenous leukemia
A B-cell leukemia is any of several types of lymphoid leukemia which affect B cells.
Types include (with ICD-O code):
- 9823/3 - B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma
- 9826/3 - Acute lymphoblastic leukemia, mature B-cell type
- 9833/3 - B-cell prolymphocytic leukemia
- 9835/3-9836/3 - Precursor B lymphoblastic leukemia
- 9940/3 - Hairy cell leukemia
Clonal hypereosinophilia, also termed Primary hypereosinophelia or clonal eosinophilia, is a grouping of hematological disorder characterized by the development and growth of a pre-malignant or malignant population of eosinophils, a type of white blood cell, in the bone marrow, blood, and/or other tissues. This population consists of a clone of eosinophils, i.e. a group of genetically identical eosinophils derived from a sufficiently mutated ancestor cell.
The clone of eosinophils bear a mutation in any one of several genes that code for proteins that regulate cell growth. The mutations cause these proteins to be continuously active and thereby to stimulate growth in an uncontrolled and continuous manner. The expanding population of eosinophils, initially formed in the bone marrow may spread to the blood and then enter into and injure various tissues and organs.
Clinically, clonal eosinophilia resembles various types of chronic or acute leukemias, lymphomas, or myeloproliferative hematological malignancies. However, many of the clonal hypereosinophilias are distinguished from these other hematological malignancies by the genetic mutations which underlie their development and, more importantly, by their susceptibility to specific treatment regiments. That is, many types of these disorders are remarkably susceptible to relatively non-toxic drugs.
Richter's syndrome (RS), also known as Richter's transformation, is a transformation which occurs in about 5-10% of B cell chronic lymphocytic leukemia (CLL) and hairy cell leukemia into a fast-growing diffuse large B cell lymphoma, a variety of non-Hodgkin lymphoma which is refractory to treatment and carries a bad prognosis. There is also a less common variant in which the CLL changes into a Hodgkin's lymphoma. Rarely, transformations to a form of myeloid leukemia have been observed. These extraordinarily rare transformations carry a very poor prognosis.
Richter's transformation affects about 5% of CLL patients at some point during their lives.
Symptoms of Richter’s transformation in a CLL patient include fever (without infection), an elevated serum levels of lactate dehydrogenase, and rapidly enlarging lymph nodes. While about 8% of all CLL patients will have elevated levels of serum lactate dehydrogenase (LDH), more than 50% of CLL patients with Richter's transformation will have elevated LDH levels.
Richter's can appear suddenly, even in patients who were in remission.
Hematopoietic stem cells give rise to: 1) myeloid precursor cells that differentiate into red blood cells, mast cells, blood platelet-forming megakaryocytes, or myeloblasts, which latter cells subsequently differentiate into white blood cells viz., neutrophils, basophils, monocytes, and eosinophils; or 2) lymphoid precursor cells which differentiate into T lymphocytes, B lymphocytes, or natural killer cells. Malignant transformation of these stem or precursor cells results in the development of various hematological malignancies. Some of these transformations involve chromosomal translocations or Interstitial deletions that create fusion genes. These fusion genes encode fusion proteins that continuously stimulate cell growth, proliferation, prolonged survival, and/or differentiation. Such mutations occur in hematological stem cells and/or their daughter myeloid precursor and lymphoid precursor cells; commonly involve genes that encode tyrosine kinase proteins; and cause or contribute to the development of hematological malignancies. A classic example of such a disease is chronic myelogenous leukemia, a neoplasm commonly caused by a mutation that creates the "BCR-ABL1" fusion gene (see Philadelphia chromosome). The disease is due to conversion of the tightly regulated tyrosine kinase of ABL1 protein to being unregulated and continuously active in the BCR-ABL1 fusion protein. This Philadelphia chromosome positive form of chronic myelogenous leukemia used to be treated with chemotherapy but nonetheless was regarded as becoming lethal within 18-60 months of diagnosis. With the discovery of the uncontrolled tyrosine kinase activity of this disorder and the use of tyrosine kinase inhibitors. Philadelphia chromosome positive chronic myelogenous eukemia is now successfully treated with maintenance tyrosine kinase inhibiting drugs to achieve its long-term suppression.
Some hematological malignancies exhibit increased numbers of circulating blood eosinophils, increased numbers of bone marrow eosinophils, and/or eosinophil infiltrations into otherwise normal tissues. These malignancies were at first diagnosed as eosinophilia, hypereosinophilia, acute eosinophilic leukemia, chronic eosinophilic leukemia, other myeloid leukemias, myeloproliferative neoplasm, myeloid sarcoma, lymphoid leukemia, or non-Hodgkin lymphomas. Based on their association with eosinophils, unique genetic mutations, and known or potential sensitivity to tyrosine kinase inhibitors or other specific drug therapies, they are now in the process of being classified together under the term clonal hypereosinophilia or clonal eosinophilia. Historically, patients suffering the cited eosinophil-related syndromes were evaluated for causes of their eosinophilia such as those due to allergic disease, parasite or fungal infection, autoimmune disorders, and various well-known hematological malignancies (e.g. Chronic myelogenous leukemia, systemic mastocytosis, etc.) (see causes of eosinophilia). Absent these causes, patients were diagnosed in the World Health Organization's classification as having either 1) Chronic eosinophilic leukemia, not otherwise specified, (CEL-NOS) if blood or bone marrow blast cells exceeded 2% or 5% of total nucleated cells, respectively, and other criteria were met or 2) idiopathic hypereosinophilic syndrome (HES) if there was evidence of eosinophil-induced tissue damage but no criteria indicating chronic eosinophilic leukemia. Discovery of genetic mutations underlining these eosinophilia syndromes lead to their removal from CEL-NOS or HES categories and classification as myeloid and lymphoid neoplasms associated with eosinophilia and abnormalities of "PDGFRA, PDGFRB, FGFR1," and, tentatively, "PCMA-JAK2". Informally, these diseases are also termed clonal hypereosinophilias. New genetic mutations associated with, and possibly contributing to the development of, eosinophilia have been discovered, deemed to be causes of clonal eosinophilia, and, in certain cases, recommended for inclusion in the category of myeloid and lymphoid neoplasms associated with eosinophilia and abnormalities of "PDGFRA, PDGFRB, FGFR1," and, tentatively, "PCMA-JAK2". Many of the genetic causes for clonal eosinophilia are rare but nonetheless merit attention because of their known or potential sensitivity to therapeutic interventions that differ dramatically form the often toxic chemotherapy used to treat more common hematological malignancies.
The T-cell lymphomas are four types of lymphoma that affect T cells. These account for about one in ten cases of non-Hodgkin lymphoma.
They can be associated with Epstein Barr virus and Human T-cell leukemia virus-1.
PTGC is usually characterized by localized lymphadenopathy and is otherwise typically asymptomatic.
Progressive transformation of germinal centres (PTGCs) is a reactive lymph node process of undetermined cause.