Acute lymphoblastic leukemia overview: Difference between revisions
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{{Acute lymphoblastic leukemia}} | {{Acute lymphoblastic leukemia}} | ||
{{CMG}} {{AE}} {{RT}} | {{CMG}} {{AE}} {{RT}} {{CLG}} | ||
==Overview== | ==Overview== | ||
'''Acute lymphoblastic leukemia''' is a form of [[leukemia]] | '''Acute lymphoblastic leukemia''' is a form of [[leukemia]] or [[hematological malignancy|cancer of the white blood cells]]. Acute refers to the undifferentiated, immature state of the circulating [[lymphocytes]] ("blasts") and to the rapid progression of disease, which can be fatal in weeks to months if left untreated. May be classified according to the [[World Health Organization]] (WHO). [[Genetic mutations]] involved in the [[pathogenesis]] of acute lymphoblastic leukemia are related with [[chromosomal translocation]]s. [[Genes]] involved in the [[pathogenesis]] include [[Philadelphia chromosome|t(9;22)(q34;q11.2) ''BCR-ABL1'']], t(v;11q23);, t(12;21)(p13;q22) ''TEL-AML1'', t(5;14)(q31;q32)''IL3-IGH'' and t(1;19)(q23;p13.3) ''TCF3-PBX1''. Acute lymphoblastic leukemia must be differentiated from other diseases such as [[acute myelogenous leukemia]], [[hairy cell leukemia]] and [[malignant lymphoma]]. In 2015 according with the National cancer institute the [[incidence]] of acute lymphocytic leukemia is 1.9 per 100,000 individuals and the case fatality rate of 2.3 per 100,000 individuals in the United States. Common risk factors in the development of the disease are [[down syndrome]], [[ataxia telangiectasia]], [[bloom syndrome]], [[X-linked agammaglobulinemia]], [[fanconi's anemia]] and [[severe combined immunodeficiency]]. The most common [[symptoms]] include [[generalized weakness]], [[fatigue (physical)|fatigue]] and [[fever]]. Common [[physical examination]] findings include [[lymphadenopathy]], [[hepatomegaly]] and [[pallor]]. Laboratory findings include [[eosinophilia]], [[lymphocytosis]], [[Red blood cell|red cell]] production reduced and [[thrombocytopenia]]. [[CT scan]]ning findings can show invasion of other [[organs]] commonly the [[lung]], [[liver]], [[spleen]], [[lymph nodes]], [[brain]], [[kidneys]] and [[reproductive organs]]. [[Chemotherapy]] is indicated for acute lymphocytic leukemia and can be divided in several phases: Induction chemotherapy, consolidation therapy, [[CNS]] [[prophylaxis]] and maintenance treatments with [[Chemotherapeutic agent|chemotherapeutic drugs]] such as [[prednisone]] plus [[vincristine]] plus [[cyclophosphamide]] plus [[doxorubicin]] or [[methotrexate]] plus 6-MP. [[Radiation therapy]] is used on [[painful]] [[Bone|bony]] areas in severe disease or as part of the preparations for a [[bone marrow transplant]] (total body [[irradiation]]). | ||
Acute lymphoblastic leukemia must be differentiated from other diseases such as [[acute myelogenous leukemia]], [[hairy cell leukemia]] and [[malignant lymphoma]] | |||
Common risk factors in the development of | |||
Laboratory findings | |||
==Historical Perspective== | ==Historical Perspective== | ||
Leukemia was first described in 1827 by a | Leukemia was first described in 1827 by a French physician named [[Alfred-Armand-Louis-Marie Velpeau]]. | ||
==Classification== | ==Classification== | ||
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==Pathophysiology== | ==Pathophysiology== | ||
Generally cancer is caused by damage to [[Deoxyribonucleic Acid|DNA]] that leads to uncontrolled cellular growth causing the development of acute lymphoblastic leukemia. Genetic mutations involved in the pathogenesis of acute lymphoblastic leukemia are related with [[chromosomal translocation]]s. Genes involved in the pathogenesis of acute | Generally, [[cancer]] is caused by damage to [[Deoxyribonucleic Acid|DNA]] that leads to uncontrolled [[cellular]] [[growth]] causing the development of acute lymphoblastic leukemia. [[Genetic mutations]] involved in the [[pathogenesis]] of acute lymphoblastic leukemia are related with [[chromosomal translocation]]s. [[Genes]] involved in the [[pathogenesis]] of acute lymphoblastic leukemia include t(9;22)(q34;q11.2) ''BCR-ABL1'', t(v;11q23);, t(12;21)(p13;q22) ''TEL-AML1'', t(5;14)(q31;q32)''IL3-IGH'' and t(1;19)(q23;p13.3) ''TCF3-PBX1''. | ||
==Differentiating Acute lymphoblastic leukemia from other Diseases== | ==Differentiating Acute lymphoblastic leukemia from other Diseases== | ||
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==Screening== | ==Screening== | ||
According to the National cancer institute screening for acute lymphoblastic leukemia is not recommended. | According to the National cancer institute [[Screening (medicine)|screening]] for acute lymphoblastic leukemia is not recommended. | ||
==Natural History, Complications, and Prognosis== | ==Natural History, Complications, and Prognosis== | ||
Prognosis has improved from a 0% to 20-75% survival rate largely due to the continuous development of [[clinical trial]]s and improvements in [[bone marrow transplant]]ation (BMT) and [[stem cell transplantation]] (SCT) technology. The prognosis for acute | [[Prognosis]] has improved from a 0% to 20-75% survival rate largely due to the continuous development of [[clinical trial]]s and improvements in [[bone marrow transplant]]ation (BMT) and [[stem cell transplantation]] (SCT) technology. The [[prognosis]] for acute lymphoblastic leukemia differs between individuals depending on a wide variety of factors such as gender, ethnicity, age, [[blood cell count]], dissemination and [[genetic]] involvement. | ||
==Diagnosis== | ==Diagnosis== | ||
=== Diagnostic Study of Choice === | |||
The diagnostic study of choice for acute lymphoblastic lymphoma is [[bone marrow biopsy]]. | |||
===History and Symptoms=== | ===History and Symptoms=== | ||
Symptoms of acute lymphoblastic leukemia include | [[Symptoms]] of acute lymphoblastic leukemia include [[generalized weakness]] and [[fatigue (physical)|fatigue]], frequent or unexplained [[fever]] and [[infection]]s, [[weight loss]] and/or loss of appetite, excessive [[bruising]], [[hemorrhage|bleeding]] from wounds, [[nosebleed]]s, [[petechiae]], [[bone pain]], [[joint pain]]s and [[dyspnea]]. | ||
===Physical Examination=== | ===Physical Examination=== | ||
Common physical examination findings of acute lymphoblastic leukemia include [[lymphadenopathy]], [[hepatomegaly]], [[stridor]], [[splenomegaly]], [[pallor]], [[petechiae]], [[bruising]], [[papilledema]], | Common [[physical examination]] findings of acute lymphoblastic leukemia include [[lymphadenopathy]], [[hepatomegaly]], [[stridor]], [[splenomegaly]], [[pallor]], [[petechiae]], [[bruising]], [[papilledema]], [[nuchal rigidity]], [[cranial nerve palsy]] and [[testicular]] enlargement. | ||
===Laboratory Findings=== | ===Laboratory Findings=== | ||
Laboratory findings consistent with the diagnosis of acute lymphoblastic leukemia include [[eosinophilia]], [[lymphocytosis]], red cell production reduced, [[thrombocytopenia]]. Chemistry panels with altered levels of [[uric acid]], [[creatinine]], [[blood urea nitrogen]], [[potassium]], [[phosphate]], [[calcium]], [[bilirubin]], [[hepatic transaminases]] and [[ferritin]]. A [[lumbar puncture|spinal tap]] will tell if the spinal column and [[central nervous system|brain]] has been invaded. | |||
=== | === Electrocardiogram === | ||
There are no [[ECG]] findings associated with acute lymphoblastic leukemia. | |||
===X Ray=== | ===Chest X-Ray=== | ||
On [[Chest X-ray|chest x-ray]] acute lymphoblastic leukemia is characterized by [[swollen lymph node]]s. | |||
=== | ===Bone X-Ray=== | ||
On [[x-ray]], acute lymphoblastic leukemia is characterized by [[periosteal reaction]]. | |||
=== | === Echocardiography and Ultrasound === | ||
Additional imaging studies that can be useful in acute lymphoblastic leukemia include [[echocardiogram]] and [[ultrasound]]. [[Echocardiogram]] is useful for assessing [[cardiac]] function in patients receiving [[anthracycline]] [[chemotherapy]]. [[Ultrasound]] is useful for assessing for [[deep vein thrombosis]] which is a common complication of acute lymphoblastic leukemia. [[Ultrasound]] can also assess for [[spleen]] size. | |||
== | ===CT=== | ||
Acute lymphoblastic leukemia [[CT scan]]ning findings can show invasion of other [[organs]] commonly the [[lung]], [[liver]], [[spleen]], [[lymph nodes]], [[brain]], [[kidneys]] and [[reproductive organs]]. | |||
=== MRI === | |||
[[MRI]] of the [[brain]] may be useful in patients who present with [[Neurological|neurologic]] [[symptoms]], which is common in acute lymphoblastic leukemia. [[MRI]] may reveal [[Glial cell|glial cel]]<nowiki/>l [[hyperplasia]], [[leukoencephalopathy]] and [[meningitis]]. | |||
===Other Diagnostic Studies=== | |||
Other diagnostic studies about acute lymphoblastic leukemia can be made made by [[cytogenetics]], Bone marrow [[biopsy]], [[flow cytometry]], [[RT-PCR]] and [[FISH]]. | |||
=== Other Imaging Findings === | |||
[[Positron emission tomography|18F-FDG PET/CT]] may be helpful in the [[diagnosis]] of acute lymphoblastic leukemia. Findings on an [[PET scan|18F-FDG PET/CT]] suggestive of acute lymphoblastic leukemia include heterogenous uptake in [[lymph nodes]] and high [[Metabolism|metabolic activity]]. | |||
== Treatment == | |||
[[Category:Disease]] | |||
[[Category:Autoimmune diseases]] | |||
[[Category:Hematology]] | |||
[[Category:Rare diseases]] | |||
[[Category:Dermatology]] | |||
[[Category:Up-To-Date]] | |||
[[Category:Oncology]] | |||
[[Category:Medicine]] | |||
[[Category:Hematology]] | |||
[[Category:Immunology]] | |||
===Medical Therapy=== | |||
[[Chemotherapy]] is indicated for acute lymphocytic leukemia and can be divided in several phases: induction [[chemotherapy]], consolidation therapy, [[CNS]] [[prophylaxis]] and maintenance treatments with [[Chemotherapeutic agent|chemotherapeutic]] drugs such as [[prednisone]] plus [[Vincristine]] plus [[cyclophosphamide]] plus [[doxorubicin]] or [[methotrexate]] plus [[Mercaptopurine|6-MP]]. [[Radiation therapy]] is used on painful [[Bone|bony]] areas in severe disease or as part of the preparations for a [[bone marrow transplant]]. Drugs approved for acute lymphoblastic leukemia include: [[Methotrexate]], [[nelarabine]], [[blinatumomab]], [[cyclophosphamide]], [[clofarabine]], [[cytarabine]], [[dasatinib]], [[doxorubicin hydrochloride]], [[mercaptopurine]], [[pegaspargase]], [[prednisone]]. A therapy that was recently approved by the [[Food and Drug Administration]] is chimeric antigen receptor T (CAR-T) cell therapy in the form of [[tisagenlecleucel]], which is used in patients with B cell acute lymphoblastic leukemia. | |||
=== Surgery === | |||
[[Surgery|Surgical intervention]] is not recommended for the management of acute lymphoblastic leukemia. | |||
=== Primary Prevention === | |||
There is no established method for [[primary prevention]] of acute lymphoblastic leukemia. | |||
=== Secondary Prevention === | |||
There is no established method for [[secondary prevention]] of acute lymphoblastic leukemia. | |||
==References== | ==References== | ||
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{{WH}} | {{WH}} | ||
{{WS}} | {{WS}} | ||
Latest revision as of 15:28, 16 April 2019
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Acute lymphoblastic leukemia Microchapters |
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Differentiating Acute lymphoblastic leukemia from other Diseases |
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Diagnosis |
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Treatment |
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Risk calculators and risk factors for Acute lymphoblastic leukemia overview |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2] Carlos A Lopez, M.D. [3]
Overview
Acute lymphoblastic leukemia is a form of leukemia or cancer of the white blood cells. Acute refers to the undifferentiated, immature state of the circulating lymphocytes ("blasts") and to the rapid progression of disease, which can be fatal in weeks to months if left untreated. May be classified according to the World Health Organization (WHO). Genetic mutations involved in the pathogenesis of acute lymphoblastic leukemia are related with chromosomal translocations. Genes involved in the pathogenesis include t(9;22)(q34;q11.2) BCR-ABL1, t(v;11q23);, t(12;21)(p13;q22) TEL-AML1, t(5;14)(q31;q32)IL3-IGH and t(1;19)(q23;p13.3) TCF3-PBX1. Acute lymphoblastic leukemia must be differentiated from other diseases such as acute myelogenous leukemia, hairy cell leukemia and malignant lymphoma. In 2015 according with the National cancer institute the incidence of acute lymphocytic leukemia is 1.9 per 100,000 individuals and the case fatality rate of 2.3 per 100,000 individuals in the United States. Common risk factors in the development of the disease are down syndrome, ataxia telangiectasia, bloom syndrome, X-linked agammaglobulinemia, fanconi's anemia and severe combined immunodeficiency. The most common symptoms include generalized weakness, fatigue and fever. Common physical examination findings include lymphadenopathy, hepatomegaly and pallor. Laboratory findings include eosinophilia, lymphocytosis, red cell production reduced and thrombocytopenia. CT scanning findings can show invasion of other organs commonly the lung, liver, spleen, lymph nodes, brain, kidneys and reproductive organs. Chemotherapy is indicated for acute lymphocytic leukemia and can be divided in several phases: Induction chemotherapy, consolidation therapy, CNS prophylaxis and maintenance treatments with chemotherapeutic drugs such as prednisone plus vincristine plus cyclophosphamide plus doxorubicin or methotrexate plus 6-MP. Radiation therapy is used on painful bony areas in severe disease or as part of the preparations for a bone marrow transplant (total body irradiation).
Historical Perspective
Leukemia was first described in 1827 by a French physician named Alfred-Armand-Louis-Marie Velpeau.
Classification
Acute lymphoblastic leukemia may be classified according to the French-American-British (FAB) classification and World Health Organization (WHO). The French-American-British (FAB) classification is divided into 3 groups: ALL-L1: small uniform cells, ALL-L2: large varied cells, ALL-L3: large varied cells with vacuoles (bubble-like features). World Health Organization (WHO) classification is divided into 3 groups: B lymphoblastic leukemia/lymphoma, B lymphoblastic leukemia/lymphoma (Not organ specific), B lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities.
Pathophysiology
Generally, cancer is caused by damage to DNA that leads to uncontrolled cellular growth causing the development of acute lymphoblastic leukemia. Genetic mutations involved in the pathogenesis of acute lymphoblastic leukemia are related with chromosomal translocations. Genes involved in the pathogenesis of acute lymphoblastic leukemia include t(9;22)(q34;q11.2) BCR-ABL1, t(v;11q23);, t(12;21)(p13;q22) TEL-AML1, t(5;14)(q31;q32)IL3-IGH and t(1;19)(q23;p13.3) TCF3-PBX1.
Differentiating Acute lymphoblastic leukemia from other Diseases
Acute lymphoblastic leukemia must be differentiated from other diseases such as acute myelogenous leukemia, hairy cell leukemia and malignant lymphoma.
Epidemiology and Demographics
In 2011, the incidence of acute lymphocytic leukemia was estimated to be 1.77 cases per 100,000 individuals and the prevalence of 17.4 per 100,000 individuals in the United States. In 2015 according with the National cancer institute the incidence of acute lymphocytic leukemia is 1.9 per 100,000 individuals and the case fatality rate of 2.3 per 100,000 individuals in the United States. Males are more commonly affected with acute lymphoblastic leukemia than females.
Risk Factors
Common risk factors in the development of acute lymphoblastic leukemia are down syndrome, ataxia telangiectasia, bloom syndrome, X-linked agammaglobulinemia, fanconi's anemia and severe combined immunodeficiency.
Screening
According to the National cancer institute screening for acute lymphoblastic leukemia is not recommended.
Natural History, Complications, and Prognosis
Prognosis has improved from a 0% to 20-75% survival rate largely due to the continuous development of clinical trials and improvements in bone marrow transplantation (BMT) and stem cell transplantation (SCT) technology. The prognosis for acute lymphoblastic leukemia differs between individuals depending on a wide variety of factors such as gender, ethnicity, age, blood cell count, dissemination and genetic involvement.
Diagnosis
Diagnostic Study of Choice
The diagnostic study of choice for acute lymphoblastic lymphoma is bone marrow biopsy.
History and Symptoms
Symptoms of acute lymphoblastic leukemia include generalized weakness and fatigue, frequent or unexplained fever and infections, weight loss and/or loss of appetite, excessive bruising, bleeding from wounds, nosebleeds, petechiae, bone pain, joint pains and dyspnea.
Physical Examination
Common physical examination findings of acute lymphoblastic leukemia include lymphadenopathy, hepatomegaly, stridor, splenomegaly, pallor, petechiae, bruising, papilledema, nuchal rigidity, cranial nerve palsy and testicular enlargement.
Laboratory Findings
Laboratory findings consistent with the diagnosis of acute lymphoblastic leukemia include eosinophilia, lymphocytosis, red cell production reduced, thrombocytopenia. Chemistry panels with altered levels of uric acid, creatinine, blood urea nitrogen, potassium, phosphate, calcium, bilirubin, hepatic transaminases and ferritin. A spinal tap will tell if the spinal column and brain has been invaded.
Electrocardiogram
There are no ECG findings associated with acute lymphoblastic leukemia.
Chest X-Ray
On chest x-ray acute lymphoblastic leukemia is characterized by swollen lymph nodes.
Bone X-Ray
On x-ray, acute lymphoblastic leukemia is characterized by periosteal reaction.
Echocardiography and Ultrasound
Additional imaging studies that can be useful in acute lymphoblastic leukemia include echocardiogram and ultrasound. Echocardiogram is useful for assessing cardiac function in patients receiving anthracycline chemotherapy. Ultrasound is useful for assessing for deep vein thrombosis which is a common complication of acute lymphoblastic leukemia. Ultrasound can also assess for spleen size.
CT
Acute lymphoblastic leukemia CT scanning findings can show invasion of other organs commonly the lung, liver, spleen, lymph nodes, brain, kidneys and reproductive organs.
MRI
MRI of the brain may be useful in patients who present with neurologic symptoms, which is common in acute lymphoblastic leukemia. MRI may reveal glial cell hyperplasia, leukoencephalopathy and meningitis.
Other Diagnostic Studies
Other diagnostic studies about acute lymphoblastic leukemia can be made made by cytogenetics, Bone marrow biopsy, flow cytometry, RT-PCR and FISH.
Other Imaging Findings
18F-FDG PET/CT may be helpful in the diagnosis of acute lymphoblastic leukemia. Findings on an 18F-FDG PET/CT suggestive of acute lymphoblastic leukemia include heterogenous uptake in lymph nodes and high metabolic activity.
Treatment
Medical Therapy
Chemotherapy is indicated for acute lymphocytic leukemia and can be divided in several phases: induction chemotherapy, consolidation therapy, CNS prophylaxis and maintenance treatments with chemotherapeutic drugs such as prednisone plus Vincristine plus cyclophosphamide plus doxorubicin or methotrexate plus 6-MP. Radiation therapy is used on painful bony areas in severe disease or as part of the preparations for a bone marrow transplant. Drugs approved for acute lymphoblastic leukemia include: Methotrexate, nelarabine, blinatumomab, cyclophosphamide, clofarabine, cytarabine, dasatinib, doxorubicin hydrochloride, mercaptopurine, pegaspargase, prednisone. A therapy that was recently approved by the Food and Drug Administration is chimeric antigen receptor T (CAR-T) cell therapy in the form of tisagenlecleucel, which is used in patients with B cell acute lymphoblastic leukemia.
Surgery
Surgical intervention is not recommended for the management of acute lymphoblastic leukemia.
Primary Prevention
There is no established method for primary prevention of acute lymphoblastic leukemia.
Secondary Prevention
There is no established method for secondary prevention of acute lymphoblastic leukemia.