Leukemia myelogenous

For example, exposure to the air toxin benzene catr increase the risk of getting myelogenous leukemia or aplastic anemia, while exposure to ground-level ozone can cause a 15 to 20 percent decrease in lung capacity in some healthy adults. 

The plasma half-life of 6-MP after intravenous bolus injection is 21 min in children and is twofold greater in adults. After oral intake peak levels are attained within 2 h. 6-MP is used for the treatment of ALL and has shown certain activity in chronic myelogenous leukemia. The major side effects involve myelosuppression, nausea, vomiting, and hepatic injury. 

Thioguanine is used primarily as part of induction chemotherapy regimens for acute myelogenous leukemia (AML). 

Cytarabine is used in the chemotherapy of acute myelogenous leukemia, usually in combination with anthracyclines, thioguanine, or both. It is less useful in acute lymphoblastic leukemia and lymphomas and has marginal activity against other tumors. Myelosuppres-sion is a major toxicity, as is severe bone marrow hypoplasia nausea and mucositis may also occur. 

In chronic myelogenous leukemia (CML) as well as in a subset of acute lymphoblastic leukemia (ALL) Bcr-Abl, a fusion protein of c-Abl and the breakpoint cluster region (bcr), is expressed in the cytosol of leukemic cells. This fusion protein forms homo-oligomeric complexes that display elevated kinase activity and is the causative molecular abnormality in CML and certain ALL. The transforming effect of Bcr-Abl is mediated by numerous downstream signaling pathways, including protein kinase C (PKC), Ras-Raf-ERK MAPK, JAK-STAT (see below), and PI3-kinase pathways. 

Acute lymphatic leukemia, acute or chronic myelogenous leukemia... 

A detailed study of the 0-linked oligosaccharides present on the surface of normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells has been completed. Structures were elucidated by f.a.b.-m.s. after permethylation, and methylation analysis before and after specific exo-glycosidase treatments. Some of the components were shown by f.a.b.-m.s. to be poly(N-acetyllactosaminyl) oligosaccharides, for example, 29. 

Acute myelogenous leukemia has been observed in 0.07% of MS patients treated with mitoxantrone.46 This form of acute leukemia appears within 2 to 4 years of initiating mitoxantrone and is generally responsive to standard antileukemic therapy. 

Mercaptopurine (6-MP) is an oral purine analog that is converted to a ribonucleotide to inhibit purine synthesis. Mercaptopurine is converted into thiopurine nucleotides, which are catabolized by thiopurine S-methyltransferase (TPMT), which is subject to genetic polymorphisms and may cause severe myelosuppression. TPMT status may be assessed prior to therapy to reduce drug-induced morbidity and the costs of hospitalizations for neutropenic events. Mercaptopurine is poorly absorbed, with a time to peak concentration of 1 to 2 hours after an oral dose. The half-life is 21 minutes in pediatric patients and 47 minutes in adults. Mercaptopurine is used in the treatment of acute lymphocytic leukemia and chronic myelogenous leukemia. Significant side effects include myelosuppression, mild nausea, skin rash, and cholestasis. When allopurinol is used in combination with 6-MP, the dose of 6-MP must be reduced by 66% to 75% of the usual dose because allopurinol blocks the metabolism of 6-MP. 

Topotecan inhibits topoisomerase I to cause single-strand breaks in DNA. The pharmacokinetics of topotecan can be described by a two-compartment model, with a terminal half-life of 80 to 180 minutes, with renal clearance accounting for approximately 70% of the clearance.19 Topotecan has shown clinical activity in the treatment of ovarian and lung cancer, myelodysplastic syndromes, and acute myelogenous leukemia. The intravenous infusion may be daily for 5 days or once weekly. Side effects include myelosuppression, mucositis, and diarrhea. 

Idarubicin inhibits both DNA and RNA polymerase, as well as topoisomerase II. The pharmacokinetics of idarubicin can best be described by a three-compartment model, with an a half-life of 13 minutes, a (3 half-life of 2.4 hours, and a terminal half-life of 16 hours.22 Idarubicin is metabolized to an active metabolite, idarubicinol, which has a half-life of 41 to 69 hours. Idarubicin and idarubicinol are eliminated by the liver and through the bile. Idarubicin has shown clinical activity in the treatment of acute leukemias, chronic myelogenous leukemia, and myelodysplastic syndromes. Idarubicin causes cardiomyopathy at cumulative doses of greater than 150 mg/m2 and produces cumulative cardiotoxic effects with other anthracyclines. Idarubicin is a vesicant and causes red-orange urine, mucositis, mild to moderate nausea and vomiting, and bone marrow suppression. 

The oncologist prescribes the normal doses of idarubicin 12 mg/m2 IV daily for 3 days and cytarabine 100 mg/m2 per day by continuous infusion for 7 days to treat her acute myelogenous leukemia. Her baseline laboratory measurements are significant for an elevated WBC count, a creatinine concentration of 2.5 mg/dL (221 pmol/L), and a bilirubin level of 1.6 mg/dL (27 pmol/L). 

Acute leukemias are classified according to their cell of origin. Acute lymphocytic leukemia (ALL) arises from the lymphoid line. Acute nonlymphocytic leukemia (ANLL) or acute myelogenous leukemia (AML) arises from the myeloid line. 

The current induction therapy for acute myelogenous leukemia (AML) usually consists of a combination of cytara-bine and daunorubicin, with the frequent addition of a steroid and/or an antimetabolite such as 6-thioguanine. The risk of infection is so high during this period that patients receive antibiotic and fungal prophylaxis. 

For all newly diagnosed patients with leukemia, an aspirate of the liquid marrow and a bone marrow core biopsy are obtained.5 Morphologic and cytochemical analysis of these samples distinguishes three subtypes of ALL (LI, L2, and L3) and eight subtypes of AML (M0-M7) as classified by the French-American-British (FAB) scheme. See Tables 92-2 and 92-3 for the FAB classification of acute myelogenous leukemia and acute lymphocytic leukemia. 

TABLE 92-2. Morphologic (FAB) Classification of Acute Myelogenous Leukemia... 

Explain the role of the Philadelphia chromosome in the pathophysiology of chronic myelogenous leukemia (CML). 

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