Acute lymphoblastic leukemia overview

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Overview

Historical Perspective

Classification

Pathophysiology

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Differentiating Acute lymphoblastic leukemia from other Diseases

Epidemiology and Demographics

Risk Factors

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Natural History, Complications and Prognosis

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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 generalised 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 limphoblastic 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

History and Symptoms

Symptoms of acute lymphoblastic leukemia include generalised 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, nuchar rigidity, craneal nerve palsy and in males 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.

Chest X Ray

On Chest x ray acute lymphoblastic leukemia is characterized by swollen lymph nodes.

X Ray

On x ray, acute lymphoblastic leukemia is characterized by periosteal reaction.

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.

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.

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 (total body irradiation).

References


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