Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred and nine consecutive patients with de novo acute nonlymphocytic leukemia aged over 56 years were admitted with the intention of administering high-dose cytosine arabinoside (HD Ara-C) intensification. After remission induction, the patients were consolidated with a course of daunorubicin (30 mg/m2/day, days 1-3) and Ara-C (100 mg/m2/day, days 1-7), followed by the intensification (Ara-C, 2 g/m2/12 h, days 1-4). The planned induction course was not started in 13 patients because of cardiac failure or unsatisfactory general status. Remission was achieved in 55% (53/96) of the patients. Twenty-seven patients (28%) had refractory disease, seven died early during induction therapy, five died of hemorrhage and three of infection during the hypoplasia that followed induction treatment. Thirty-nine patients started consolidation and 32 had the planned intensification. In these last patients the 3-year leukemia-free survival (LFS) probability was 29% (SE, 8%). No patient died as a consequence of intensification. The relapse rate of the intensified patients did not differ from the relapse rate of those patients who did not receive the planned intensification (p = 0.12). The only pretreatment variables significantly associated with a better LFS were younger age (p = 0.02) and a low WBC at diagnosis (p = 0.04). For the whole patient group, the 3-year survival probability was 15% (SE, 4%). This study shows that elderly patients can tolerate HD Ara-C. The patients completing consolidation-intensification have a currently acceptable LFS. To what extent HD Ara-C contributed to the length of the remissions remains unclear.
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PMID:High-dose cytosine arabinoside intensification for acute nonlymphocytic leukemia in patients over 56 years of age. 158 6

A 14-year-old girl with acute promyelocytic leukemia (APL) developed cardiomyopathy following chemotherapy for remission induction and subsequent consolidation consisting of cumulative doses of 644 mg/m2 of daunorubicin and 31 mg/m2 of mitoxantrone. Six months after the first complete remission, when relapse of APL was recognized an allogeneic bone marrow transplantation (BMT) from her HLA-identical brother was performed. A preconditioning regimen, consisting of cytarabine (Ara-C, 2 g/m2/day x 3 days and 4 g/m2/day x 3 days), total body irradiation (TBI, 1200 cGy) and etoposide (VP-16, 50 mg/kg) caused moderate gastrointestinal symptoms and transient hemorrhagic cystitis, but did not worsen her cardiac function. Both continuous intravenous administration of heparin to control DIC and continuous low dose dopamine infusion to prevent cardiac failure achieved their purpose. The patient is leukemia-free and has no symptoms related to cardiomyopathy at the eight month after BMT. A preconditioning regimen (Ara-C, TBI and VP-16) appeared to be suitable for BMT to a patient with anthracycline-induced cardiomyopathy.
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PMID:[A successful allogeneic bone marrow transplantation for acute promyelocytic leukemia with anthracycline-induced cardiomyopathy at relapse]. 160 7

Cytosine arabinoside (ara-C) is one of the most active compounds in the treatment of acute leukemias. In the majority of current protocols ara-C is combined with other cytotoxic agents in an attempt to increase antileukemic activity. The present study investigated the impact of etoposide, teniposide, amsacrine, mitoxantrone, anthracyclines, and asparaginase on the cellular accumulation of ara-C and its intracellular metabolism in order to provide a better rationale for combination therapy. Intracellular accumulation and phosphorylation of ara-C were determined in peripheral blast cells from twenty patients with acute leukemias after exposure to 1 and 10 mumol/l ara-C alone and after preincubation with 1 and 10 micrograms/ml etoposide, 10 and 100 micrograms/ml teniposide, 10 mumol/l amsacrine, 500 ng/ml mitoxantrone (or daunorubicin or doxorubicin) or 10 mumol/l asparaginase. Ara-C accumulation at 10 mumol/l was decreased by 1 microgram/ml etoposide (67 +/- 18% of control), 10 micrograms/ml etoposide (30 +/- 22%), 10 micrograms/ml teniposide (12 +/- 23%), 100 micrograms/ml teniposide (10 +/- 18%), and amsacrine (51 +/- 21%). Intracellular ara-CTP formation was determined at an extracellular concentration of 10 mumol/l and preincubation with these drugs. The intracellular formation of ara-CTP was decreased by 1 microgram/ml etoposide (77 +/- 15% of control), 10 micrograms/ml etoposide (32 +/- 22%), 10 micrograms/ml teniposide (10 +/- 9%), 100 micrograms/ml teniposide (0 +/- 0%), but not by amsacrine. These data indicate that prior exposure to etoposide and teniposide influence ara-C metabolism and possibly cytotoxicity, and thus should not immediately precede ara-C administration in clinical trials.
Leukemia 1992 Jun
PMID:Intracellular cytosine arabinoside accumulation and cytosine arabinoside triphosphate formation in leukemic blast cells is inhibited by etoposide and teniposide. 160 95

A decrease of endogenous acetyl-ser-asp-lys-pro (AcSDKP) levels in murine plasma was observed after Ara-C treatment. This decrease preceded the entry of pluripotent hemopoietic stem cells (CFU-S) into the cell cycle. This suggests a correlation between CFU-S kinetics and levels of endogenous AcSDKP. The subsequent increase of AcSDKP levels seem to indicate a feedback mechanism which should permit the reestablishment of homeostasis in the stem cells. Therefore, the expulsion of the physiological brake may be the response to a signal (stimulatory factors) to start dividing and the retention of the physiological brake may the mechanism for a return to normal values of cell proliferation.
Leukemia 1992 Jun
PMID:Correlation of endogenous acetyl-ser-asp-lys-pro plasma levels in mice and the kinetics of pluripotent hemopoietic stem cells entry into the cycle after cytosine arabinoside treatment: fundamental and clinical aspects. 160 98

The antiviral activities of antileukemic drugs 1-beta-D-arabinofuranosylcytosine (Cytarabine; Ara-C), 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine (Ancitabine; Cyclo-C), and N4-behenoyl-1-beta-D-arabinofuranosylcytosine (Enocitabine; BH-AC) were evaluated in vitro against human cytomegalovirus (HCMV) in comparison with those of five other antiviral drugs. Both Ara-C and Cyclo-C showed the strongest inhibitory effect to HCMV. BH-AC inhibited the replication of HCMV and depicted almost as the same dose-response curve as Ganciclovir (DHPG). In the presence of Ara-C, Cyclo-C, or BH-AC, triphosphate forms of the nucleoside analogs were detected in the HCMV-infected cells, and synthesis of HCMV DNA was strongly suppressed. Thus, Ara-C, Cyclo-C, and BH-AC were not only antileukemic, but also antiviral in vitro. However, Ara-C and Cyclo-C may not be suitable as anti-HCMV agents, because they are cytotoxic or excreted rapidly in the urine in vivo [Van Voris, 1984; Hirayama et al., 1974]. Because of lower toxicity and longer retention in vivo, BH-AC may be expected as an anti-HCMV agent in patients with leukemia, in addition to serving as an antileukemic drug.
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PMID:Antiviral effect of antileukemic drugs N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC) and 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine (cyclo-C) against human cytomegalovirus. 169 58

The retrospective analysis has concerned 323 patients with acute nonlymphocytic leukaemia (ANLL). The comparable patients groups were treated since 1981 according to protocols used by the Polish Acute Leukaemia Group (induction; modified TAD or Adriamycin plus Ara-C, maintenance; rotatingly changed polychemotherapy for 3 years). The prognostic value for achieving complete remission (CR) and survival of 67 pre-treatment factors (42 quantitative and 25 qualitative) was evaluated. The most important 9 parameters were scored according to the prognostic value as follows: age, proportion of blasts in bone marrow, blast count in peripheral blood, morphological subtype, percentage of granulocytes in bone marrow, proportion of blasts with CD-15 antigen, thrombocyte count, spleen/liver enlargement, protein concentration in cerebro-spinal fluid. The scoring system has been elaborated allowing selection of ANLL patients to standard risk group and a high risk group.
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PMID:The evaluation of prognostic factors for achieving complete remission and survival in ANLL of adults. The proposition of a prognostic scale. 170 8

Significant advances in the treatment and prevention of meningeal leukaemia have been made in the past 3 decades. This progress has resulted from the development of innovative approaches to treatment as well as a better understanding of the pharmacokinetics and pharmacodynamics of the commonly used antileukaemic agents. Intrathecal therapy, via the intralumbar or intraventricular route, is a form of regional therapy that results in the delivery of very high drug concentrations to the principle target tumour site (the meninges) using a relatively small drug dose, thereby minimising both systemic drug exposure and systemic toxicity. The dosage and schedules, clinical pharmacology and toxicities of the commonly used intrathecal agents, methotrexate and cytarabine (cytosine arabinoside; Ara-C) are discussed in detail. Another approach which has been used to overcome the poor penetration of antileukaemic drugs into the CNS has been the use of high-dose systemic therapy. This strategy has been successfully applied in the treatment of meningeal leukaemia using both high-dose methotrexate and high-dose cytarabine. The clinical pharmacology, toxicities, and potential limitations of this approach are outlined. Finally, new agents that are currently undergoing clinical evaluation and future directions for research are also discussed.
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PMID:Current pharmacological treatment approaches to central nervous system leukaemia. 171 5

In the present study we demonstrate that Aza-dC in combination with Amsacrine has major antileukaemic properties in patients who have not already received extensive Ara-C therapy. Eight out of 11 patients in their first relapse of acute leukaemia achieved complete remission. Cross resistance between Ara-C and Aza-dC was revealed by the lack of antileukaemic activity in five patients with with Ara-C resistant leukaemia. Combination therapy with Aza-dC/Ams-acrine induced a considerable period of a granulocytopenia (28-35 days), while the toxic effect on erythro- and megakaryopoiesis was comparable to that reported for high dose Ara-C/Amsacrine chemotherapy. Remarkable is the long disappearance time for leukaemic blast cells in bone marrow, i.e. 3-5 weeks in some cases. Analysis of cell membrane markers showed a loss of the early differentiation antigens CD34 and CD33 from leukaemic bone marrow cells after 7 days of Aza-dC treatment, which is suggestive of leukaemic cell differentiation. In the small group of patients tested for DNA hypomethylation no association existed between the degree of hypomethylation and clinical response. Non-haematologic side effects were considerable in patients receiving the highest dosages of Aza-dC and consisted of severe, although usually reversible, gastrointestinal and neurological complications. In comparison with Ara-C, Aza-dC causes less nausea and vomiting and is therefore better tolerated.
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PMID:The antileukaemic activity of 5-Aza-2 deoxycytidine (Aza-dC) in patients with relapsed and resistant leukaemia. 171 50

Cytosine arabinoside (ara-C) is a component of many protocols for the treatment of CNS (central nervous system) leukemia and lymphoma in humans and dogs. It is also used for the prophylaxis of CNS metastasis in acute lymphoblastic leukemia. Although ara-C enters the cerebrospinal fluid (CSF) of human cancer patients after i.v. administration, it is unclear whether a similar CNS distribution occurs in humans whose blood-brain barrier has not been compromised by invasive disease. No information on the penetration of ara-C into the CSF in dogs is available. We studied the plasma and CSF pharmacokinetics of 600 mg/m2 ara-C in ten healthy male dogs after its administration as a rapid i.v. bolus (six dogs) or as a 12-h i.v. infusion (four dogs). Ara-C concentration in blood and CSF samples was determined by high-performance liquid chromatography (HPLC). After an i.v. bolus of ara-C, the mean plasma distribution half-life was 7.1 +/- 4.5 min and the mean elimination half-life was 69 +/- 28 min. The mean plasma clearance was 227 +/- 125 ml min-1 m-2. The peak concentration of ara-C in the CSF was 29 +/- 11 microM, which occurred at 57 +/- 13 min after the ara-C bolus. The CSF elimination half-life was 113 +/- 26 min. During a 12-h infusion of ara-C (50 mg m-2 h-1), the plasma steady-state concentration was 14.1 +/- 4.2 microM, the CSF steady-state concentration was 8.3 +/- 1.1 microM, and the CSF: plasma ratio was 0.62 +/- 0.14. The plasma elimination half-life was 64 +/- 19 min and the plasma clearance was 214 +/- 69 ml min-1 m-2. The CSF elimination half-life was 165 +/- 28 min. No clinically significant toxicity was observed over a 21-day period following drug administration in either of the treatment groups. Our data indicate that ara-C crosses the blood-brain barrier in normal dogs and that i.v. administration of this drug has potential as a treatment modality for neoplasia involving the CNS.
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PMID:Plasma and cerebrospinal fluid pharmacokinetics of cytosine arabinoside in dogs. 174 43

The occurrence of hypoplastic acute leukemia is widely recognized as an atypical leukemia, and is defined as hypocellular marrow with more than 30% blasts and none or few blasts in the circulating blood. The pathogenesis of hypoplastic acute leukemia is still unknown. Clinically, it usually follows a less progressive course and has a high prevalence rate among the elderly. The treatment and prognosis remains unclear. We present a case of hypoplastic acute leukemia, which responded well to low dose Ara-C. The 67 year-old female patient had symptoms of bruising easily and dizziness for about 3 years. Initial investigation revealed pancytopenia in the circulating blood and hypocellularity (10%) with blast cells (60%) in the bone marrow. Besides supportive treatment with blood transfusions and antibiotics, chemotherapy of low dose Ara-C 10 mg/m2 was administrated for 14 days by subcutaneous injection. Bone marrow examination revealed an increase of cellularity and a decrease of blast cells following chemotherapy. Anemia and thrombocytopenia also simultaneously improved. Such results may suggest induction of differentiation effect of low dose Ara-C in hypoplastic leukemia.
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PMID:Remission of hypoplastic acute leukemia by low dose Ara-C: one case report. 181 Oct 73


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