GAcute lymphoblastic leukemia (ALL) is a malignant (clonal) di

Sh hease of the bone marrow in which early lymphoid precursors proliferate and replace the normal hematopoietic cells of the marrow. ALL may be *;tdistinguished from other malignant lymphoid disorders by the immunophenotype of the cells, which is similar to B- or T-precursor cells. Immunochemistry, cytochemistry, and cytogenetic markers may also aid in categorizing the malignant lymphoid clone. Pathophysiology The malignant cells of acute lymphoblastic leukemia (ALL) are lymphoid precursor cells (ie, lymphoblasts) that are arrested in an early stage of development. This arrest is caused by an abnormal expression of genes, often as a result of chromosomal translocations. The lymphoblasts replace the normal marrow elements, resulting in a marked decrease in the production of normal blood cells. Consequently, anemia, thrombocytopenia, and neutropenia occur to varying degrees. The lymphoblasts also proliferate in organs other than the marrow, particularly the liver, spleen, and lymph nodes. Etiology Less is known about the etiology of acute lymphoblastic leukemia (ALL) in adults compared with acute myelogenous leukemia (AML). Most adults with ALL have no identifiable risk factors. Although most leukemias occurring after exposure to radiation are AML rather than ALL, an increased prevalence of ALL was noted in survivors of the Hiroshima atomic bomb but not in those who survived the Nagasaki atomic bomb. Rare patients have an antecedent hematologic disorder (AHD) such asmyelodysplastic syndrome (MDS) that evolves to ALL. However, most patients with MDS that evolves to acute leukemia develop AML rather than ALL. Increasingly, cases of ALL with abnormalities of chromosome band 11q23 following treatment with topoisomerase II inhibitors for another malignancy have been described. However, most patients who develop secondary acute leukemia after chemotherapy for another cancer develop AML rather than ALL. Prognosis Only 20-40% of adults with acute lymphoblastic leukemia (ALL) are cured with current treatment regimens. Patients with acute lymphoblastic leukemia (ALL) are divided into 3 prognostic groups: good risk, intermediate risk, and poor risk. Good risk includes the following: No adverse cytogenetics Age younger than 30 years White blood cell (WBC) count of less than 30,000/L Complete remission within 4 weeks Intermediate risk includes those whose condition does not meet the criteria for either good risk or poor risk. Poor risk includes the following: Adverse cytogenetics [(t9;22), (4;11)] Age older than 60 years Precursor B-cell WBCs with WBC count greater than 100,000/L Failure to achieve complete remission within 4 weeks Patient education Although activity may occur as tolerated, patients with ALL may not participate in strenuous activities such as lifting or exercise. In addition, a neutropenic diet is recommended in these individuals, as follows: No fresh fruits or vegetables may be eaten. All foods must be cooked. Meats are to be cooked until well done.

Acute myelogenous leukemia (AML) is a malignant disease of the

bone marrow in which hematopoietic precursors are arrested in an early stage of development. Most AML subtypes are distinguished from other related blood disorders by the presence of more than 20% blasts in the bone marrow.

The underlying pathophysiology in AML consists of a maturational arrest of bone marrow cells in the earliest stages of development. (See Pathophysiology.) Several factors have been implicated in the causation of AML, including antecedent hematologic disorders, familial syndromes, environmental exposures, and drug exposures. However, most patients who present with de novo AML have no identifiable risk factor. (See Etiology.) Patients with AML present with symptoms resulting from bone marrow failure, symptoms resulting from organ infiltration with leukemic cells, or both. The time course is variable. (See Clinical.) Workup for AML includes blood tests, bone marrow aspiration and biopsy (the definitive diagnostic tests), analysis of genetic abnormalities, and diagnostic imaging. (See Workup.) Current standard chemotherapy regimens cure only a minority of patients with AML. As a result, all patients should be evaluated for entry into well-designed clinical trials. If a clinical trial is not available, the patient can be treated with standard therapy. (See Treatment.) For consolidation chemotherapy or for the management of toxic effects of chemotherapy, readmission is required. Pathophysiology The underlying pathophysiology in AML consists of a maturational arrest of bone marrow cells in the earliest stages of development. The mechanism of this arrest is under study, but in many cases, it involves the activation of abnormal genes through chromosomal translocations and other genetic abnormalities.[1, 2] This developmental arrest results in 2 disease processes. First, the production of normal blood cells markedly decreases, which results in varying degrees of anemia, thrombocytopenia, and neutropenia. Second, the rapid proliferation of these cells, along with a reduction in their ability to undergo programmed cell death (apoptosis), results in their accumulation in the bone marrow, the blood, and, frequently, the spleen and liver. Etiology Several factors have been implicated in the causation of AML, including antecedent hematologic disorders, familial syndromes, environmental exposures, and drug exposures. However, most patients who present with de 855+*novo AML have no identifiable risk factor. antecedent hematologic disorders myelodysplastic syndrome (MDS).. aplastic anemia, myelofibrosis, paroxysmal nocturnal hemoglobinuria, and polycythemia vera. congenital disorders Bloom syndrome, Down syndrome, congenital neutropenia, Fanconi anemia, andneurofibromatosis. Usually, these patients develop AML during childhood; rarely, some may present in young adulthood. familial syndromes Germline mutations in the gene AML1 (RUNX1, CBFA2) occur in the familial platelet disorder with predisposition for AML, an autosomal dominant disorder characterized by moderate thrombocytopenia, a defect in platelet function, and propensity to develop AML.[5] Mutation of CEBPA (the gene encoding CCAAT/enhancer binding protein alpha, a granulocytic differentiation factor and member of the bZIP family) was described in a family with 3 members affected by AML.[6] environmental exposures radiation exposure and leukemia. - therapeutic irradiation for ankylosing spondylitis were at increased risk of leukemia. Survivors of the atomic bomb explosions in Japan were at a markedly increased risk for the development of leukemia. Persons who smoke have a small but statistically significant (odds ratio, 1.5) increased risk of developing AML. Exposure to benzene is associated with aplastic anemia and pancytopenia. These patients often develop AML. Many of these patients demonstrate M6 morphology. Drug exposures Patients with previous exposure to chemotherapeutic agents can be divided into 2 groups: (1) those with previous exposure to alkylating agents and (2) those with exposure to topoisomerase-II inhibitors. Complications Death may occur in patients with AML as a consequence of uncontrolled infection or hemorrhage. This may happen even after use of appropriate blood product and antibiotic support.

The most common complication in AML patients is failure of the leukemia to respond to chemotherapy. The prognosis for these patients is poor because their disease usually does not respond to other chemotherapy regimens