Chronic leukemia

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. 

Cancers Multiple myeloma Non-Hodgkin s lymphoma Hodgkin s disease Acute myeloid leukemia Neuroblastoma Germ cell tumors Acute myeloid leukemia Acute lymphoblastic leukemia Chronic myeloid leukemia Myelodysplastic syndrome Myeloproliferative disorders Non-Hodgkin s lymphoma Hodgkin s disease Chronic lymphocytic leukemia Multiple myeloma... 

Kinases Abl kinase Mouse cDNA Cancer, acute lymphocytic leukemia, chronic myelocytic leukemia, chronic neutrophilic leukemia Regulation of cytoskeletal organization and movement... 

Fludarabine (Fludara ) is a 2-fluorocytarabine (Figure 8.5) that inhibits DNA biosynthesis via inhibition of DNA polymerase a and of RNDR. It is used clinically for the treatment of leukemia (chronic lymphocytic leukaemia—CLL). 

In June 1999, phase I clinical trials of OTI-010 were initiated in cancer patients receivingchemotherapy and HSC transplantation for the treatment of high-risk hematological malignancies (including acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia and non-Hodgkin s lymphoma). The multicenter studies, conducted in seven US and European cancer centers, showed OTI-010 to be safe and efficacious, with 52% of patients ( 40 patients) responding positively to the therapy [327297], [495015]. 

Uracil mustard Generic Chronic lymphocytic leukemia chronic myelocytic leukemia non-Hodgkin lymphomas Blood disorders [anemia, leukopenia, thrombocytopenia] Gl distress [nausea, vomiting, diarrhea, loss of appetite]... 

Types of Hormones Adrenocorticosteroids Prednisone Prednisolone Others Primary Antineoplastic Indications(s) Acute lymphoblastic leukemia chronic lymphocytic leukemia Hodgkin disease Common Adverse Effects Adrenocortical suppression general catabolic effect on supporting tissues [see Chapter 29]... 

Melphalan is an antineoplastic drug, listed also as a Class I immunosuppressive agent (effective only when given prior to the immune stimulus) [1]. It is used for the treatment of multiple myeloma, ovarian carcinoma, tumors of the testes, chronic granulocytic leukemia, chronic lymphocytic leukemia, seminoma, Ewing s sarcoma, reticulum cell sarcoma, and thymoma [1,2]. Its use as an adjuvant to surgery in the management of primary breast cancer was one of the first illustrations of the therapeutic potential of combined modalities of treatment [3]. 

DAC (decitabine) II myelomonocytic leukemia Chronic myelogenous MDACC NCI/MDACC... 

Genasense (oblimersen Antisense Phase 3 in combination Inhibitor of B-cell leukemia/ Chronic lymphocytic... 

In recent times arsenic and arsenicals have been considered obsolete in medicine, because of their limited therapeutic value, multisystem toxicity, and apparent carcinogenic properties (SED-8, 502) (SED-9, 368). However, arsenic compounds have been used to treat various types of leukemia (1-3), including acute pro-myelocytic leukemia, chronic myelogenous leukemia, and multiple myeloma (4). Arsenic trioxide is effective in acute promyelocytic leukemia, achieving a complete... 

Malignant diseases hairy cell leukemia, chronic myelogenous leukemia, cutaneous T cell lymphoma, follicular lymphoma, multiple myeloma, Kaposi s sarcoma, diffuse melanoma, renal cell carcinoma, carcinoid tumors Viral diseases condylomata acuminata, chronic active hepatitis B and C... 

N-RAS Acute myelogenous leukemia Chronic myelogenous leukemia... 

Indications Leukemia (chronic myeloid), acute lymphoblastic leukemia... 

Secondary gout develops as a complication of hyperuricemia caused by another disorder (e.g., leukemia, chronic nephritis, polycythemia). This type of hyperuricemia usually is associated with abnormally rapid turnover of nucleic acids. The rare cases of gout in adolescents and children are usually of this type. 

The third observation that supported a central role for DNA in cancer came from the study of chromosomes in human leukemia cells. Karyotyping is a cytological technique used to characterize the gross structure of chromosomes in mitotic cells. Researchers noticed that in cells from one type of leukemia, chronic myelogenous leukemia, there was almost always a chromosome rearrangement between chromosomes 9 and 22. This reciprocal translocation led to identification of a small 22 9 chromosome which came to be called the Philadelphia chromosome because it was discovered at the Wistar Institute in Philadelphia. Importantly, the karyotype of nonleukemic cells from patients with this form of leukemia is normal. 

The prototype molecularly targeted therapeutic agent is imatinib, an inhibitor of the Bcr-Abl tyrosine kinase. This oncogenic kinase is produced by translocation of the Bcr locus on chromosome 9 to the c-Abl tyrosine kinase on chromosome 11, termed the Philadelphia chromosome because of its discovery in 1960 at the University of Pennsylvania School of Medicine by Peter Nowell and David Hungerford from the Institute for Cancer Research [9]. It was later demonstrated in 1973 by Janet Rowley that the Philadelphia translocation was responsible for a specific form of leukemia, chronic myelogenous leukemia (CML) [10], In 2001, imatinib was approved for treatment of CML patients, and produced remarkable results with more than 92% patients achieving 14-month progression-free survival on imatinib as a monotherapy. 

Hairy cell leukemia chronic lymphocytic leukemia small cell non-Hodgkin s lymphoma... 

Acute myelocytic or lymphocytic leukemia Chronic lymphocytic leukemia... 

Cyclophosphamide is effective against acute leukemia, chronic lymphocytic leukemia and multiple myeloma. In combination with other chemotherapeutic agents it is found to cause radical cure in acute lymphoplastic leukemia in children and also in Burkitt s lymphoma. It has a positive advantage over other alkylating agents because of its activity both parenterally and orally besides its tolerance over prolonged periods in divided doses. 

Adrenocortico -steroids Inhibit DMA and protein synthesis as well as mitosis. Used for acute lymphocytic leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, multiple myeloma, breast cancer, and lymphoma. 

B. After chronic exposure, hematologic disorders such as pancytopenia, aplastic anemia, acute myelogenous leukemia, and its variants may occur. Causality is suspected for chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myeloma, Hodgkin s disease, and paroxysmal nocturnal hemoglobinuria. There is unproven association between benzene exposure and acute lymphoblastic leukemia, myelofibrosis, and lymphomas. Chromosomal abnormalities have been reported, although no effects on fertility have been described in women after occupational exposure. 

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