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)

Based on in vitro evidence of time-dependent synergistic kill of HL-60 leukemia cells exposed to Ara-C and mitoxantrone, 44 patients with relapsed or refractory AML and 3 with blastic CML were treated with a timed sequence of both drugs. There were 25 females and 22 males, with a median age of 53 (range 21-75). Of 31 patients with relapsed AML, 24 had one prior remission, 6 had two and 1 had three. Of these, 15 had failed a second reinduction attempt. Thirteen patients were primarily refractory to induction with Ara-C plus daunorubicin. Each dose of Ara-C, 500 mg/m2, was followed after 6 hr by mitoxantrone, 5 mg/m2, and the sequence was repeated four to six times (44-68 hr) in different cohorts of patients. All but two patients (one with blastic CML and one in relapse and refractory) are evaluable for response and toxicity. Of 16 patients in relapse without prior reinduction 7 achieved CR and 3 PR (62% response rate); there were 3 CR in the 14 patients who were in relapse and refractory (21% response rate) and 4 CR and 1 PR (35% response rate) in the 14 patients with primary anthracycline resistance. Five of seven patients previously exposed to mitoxantrone achieved CR. Response lasted from 2 to 42 months, with two patients alive and in continuing remission at 34 and 42 months. Average marrow recovery was seen after 25 days and time to remission was 30 days. Six patients died in induction (four from sepsis and two from the tumor lysis syndrome) and 21 had progressive disease. Chemotherapy was well tolerated with minor nausea and vomiting in 13 patients, moderate in 20, and severe in 2. Most patients did not have evidence of drug-induced mucositis: it was minor in 9 and moderate in 2. Renal dysfunction was attributable to the use of nephrotoxic antibiotics. Hepatic dysfunction was reversible and was minor in 10 patients, moderate in 13, and severe in 3. Sequential, timed administration of intermediate-dose Ara-C and mitoxantrone is an active and well-tolerated antileukemic regimen.
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PMID:Sequential intermediate-dose cytosine arabinoside and mitoxantrone for patients with relapsed and refractory acute myelocytic leukemia. 220 4

We analysed probability of disease free survival (DFS) and remaining in remission (POR) in evaluable patients with hematological malignancies undergoing allogeneic bone marrow transplantation by Nagoya BMT groups between 1976 and August 1989 according to conditioning regimens retrospectively. Patients were divided into good risk patients with acute leukemia in first remission or CML in chronic phase and high risk patients with advanced disease. The results are as follows: 1. DSF and POR in good risk patients was 45% and 68% at 7 1/2 years for thirty nine patients treated by CY + TBI, 63% and 78% at 5 2/3 years for thirty nine patients treated by CA + CY + TBI, 84% and 84% at 2 years for sixteen patients treated by preconditioning regimens without TBI respectively. 2. DFS and POR in high risk patients was 21% and 45% at 6 years for twenty nine patients treated by CY + TBI, 23% and 48% at 4 5/6 years for forty patients treated by CA + CY + TBI, 64% and 74% at 2 years for eight patients treated by preconditioning regimens without TBI respectively. 3. There were no statistical differences among these conditioning regimens in good and high risk patients. These results show that more effective and stronger preconditioning regimens are needed especially for high risk patients for prevention of posttransplant leukemia relapses.
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PMID:[Comparison among three preconditioning regimens for allogeneic bone marrow transplantation in hematological malignancies]. 220 18

Alterations in neoplastic cell behaviour responsible for increased production of terminally-differentiated granulocytes during long-term culture of bone marrow in different categories of acute leukaemia and myelodysplasia have been investigated. An increase in neutrophils associated with transition to a morphological picture identical to normal control cultures occurred in 15 of 25 studies on acute leukaemia in contrast to one of six studies on myelodysplastic disorders. An abnormal neoplastic karyotype was employed as a marker for monitoring the course of the neoplastic cell population in 11 studies in which there was progression towards a normal pattern of differentiation. An increase in differentiation was shown by this means to represent increased maturation of cells of the neoplastic process in one study on a myelodysplastic disorder, demonstrating domination of proliferative activity in culture by all of the myelodysplastic disorders examined. Transition towards normal differentiation in nine studies on acute leukaemia, however, correlated with partial or complete replacement of the acute leukaemic cells by normal haemopoietic series in de novo acute leukaemia, and by Ph positive cells in blast crisis of CML. Conversion to morphologically and cytogenetically normal cell populations in five studies on de novo acute leukaemia occurred in four cases which failed to respond to remission-induction therapy, suggesting the selective toxic effect capable of purging acute leukaemic cells from bone marrow operated by a mechanism which lacked cross-resistance to currently-employed cytotoxic agents.
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PMID:Contrasting patterns of neoplastic cell behaviour in long-term culture of bone marrow from patients with acute leukaemia and myelodysplastic disorders. A survey of responses in 31 cases with cytogenetic determination of neoplastic status of cultured cells in 17 studies. 220 99

DNA aneuploidy (DA) was examined in adult leukemia using flow cytometry, and the method and the clinical implication of DA as a tumor marker were evaluated. The method was simple, rapid, objective, quantitative and further did not need any mitotic cells, so was proved to be very useful for screening of DA. While, DA was detected in 50 (27%) out of 185 adult cases with various types of leukemia. The frequencies of DA in the subtypes of leukemia were 55% in ATL, 26% in ALL, 17% in ANLL, 26% in CML-BC and 6% in CLL, respectively. When compared with other subtypes, the frequency in ATL was significantly higher (p less than 0.01), which suggested a special entity of this disease. In general, however, the frequency of DA in leukemia was rather low, which indicated the difficulty in application of DA by itself in diagnosis of leukemia. While, in cases with DA, DA was very useful as a tumor marker in monitoring the clinical course, for example, in the detection of early relapse or recruitment of leukemic cells. Furthermore, DA was found to be a good prognostic factor which indicates a poor prognosis in cases with ANLL and CML-BC.
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PMID:[Analysis of DNA aneuploidy as a tumor marker]. 221 64

We studied the activity of serum adenosine deaminase (ADA) and its isozyme in 36 leukemic patients (16 ANLL, 11 ALL, and 9 CML) and 8 MDS. Isozyme was measured by erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) inhibitory assay. This assay was simple and reliable. The appearance rate of abnormally high ADA value were 81.24% for ANLL, 100% for ALL, 77.8% for CML and 37.5% for MDS. The ADA level became high when MDS turned into overt leukemia. In isozyme pattern, there was a clear difference between ANLL and ALL. The isozyme I/II ratio was significantly higher (p less than 0.001) in ALL than ANLL. Lymphoblastic crisis of CML also had a high isozyme I/II ratio. There was a correlation between isozyme I and absolute number of peripheral blasts in ALL (r = 0.768). When observed time sequentially, ADA and isozyme changed correlatively with the number of blasts counts. Serum ADA and its isozyme are useful parameters both for leukemic diagnosis and treatment.
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PMID:[Serum adenosine deaminase and its isozyme activity in leukemia and MDS]. 223 54

We previously administered ara-C at a dose rate of 250 mg/m2/hr for 36-72 hr to patients with leukemia. Gastrointestinal toxicity was dose-limiting. This regimen was modified to an every other day schedule, administering 24-hr periods of high dose continuous infusion ara-C, each followed by a 24-hr rest period. Sixteen patients with relapsed/refractory acute myeloid leukemia (AML) (N = 4), secondary AML (N = 2), relapsed/refractory acute lymphoblastic leukemia (N = 7), or CML in blast crisis (N = 3) received this regimen of three 24-hr infusions with two intercurrent 24-hr rest periods. Grade 3 gastrointestinal toxicity was encountered in 57% of the courses, and hypoplasia was achieved in all patients. Three of the patients died while hypoplastic, two with septicemia and another with intracranial hemorrhage. There were five responding patients (2 CRs, 3 PRs). Median steady-state plasma ara-C levels were 24 microM, 22 microM, and 20 microM during the first, second, and third 24-hr infusions, respectively. Ara-C levels ranged from 4-118 microM during the infusions and were always below 4.5 microM during the rest periods. A significant level of ara-C incorporation into DNA was detected in each of the five patients studied, thus demonstrating that (ara-C)DNA formation is detectable in blasts from patients receiving high dose continuous infusion ara-C therapy. These findings suggest that alternate day continuous infusion ara-C may be useful in the treatment of acute leukemia and CML in blast crisis.
Leukemia 1990 Dec
PMID:A phase I study of intermittent continuous infusion high dose cytosine arabinoside for acute leukemia. 224 7

Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate), a derivative of cytosine arabinoside, on hematological malignancies was conducted by multi-institutional cooperative group. YNK01 was administered orally at dose of 100-300 mg/body/day for more than 2 weeks. The number of registered and evaluated patients were 211 and 156, respectively. Of 23 patients with acute myelogeneous leukemia (AML), 2 complete response (CR), one partial response (PR) were observed (CR + PR: 13.0%). Hypoplastic leukemia (1/4: 25%), acute unclassified leukemia (1/1: 100%). Of 45 patients with MDS, 2CRs, 6 good response (GR) and 5PRs were observed (CR + PR: 28.9%). AML developing after a prior history of MDS (5/17: 29.4%), CML-BC (2/9: 22.2%). Of 19 patients with CML, 9 achieved CR, 3 achieved PR (63.2%). Of 11 patients with polycythemia vera, 4 achieved CR, 5 achieved PR (81.8%). Of 6 patients with essential thrombocytosis, 2 achieved CR, one achieved PR (50%). The major adverse effects included gastrointestinal toxicities such as nausea, vomiting, anorexia, diarrhea, and elevation of GOT and GPT which were tolerable and reversible. This study indicates that YNK01 is a useful agent against acute leukemia and MDS, especially RAEB, RAEB in T, CMMoL.
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PMID:[Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate) on hematological malignancies]. 226 Aug 76

The diagnosis and classification of leukaemia started with simple morphological examination and now embraces use of special stains, cytochemistry and immunophenotyping. Genetic studies have progressed from karyotyping to detection of genetic changes within genes. The methods described in this chapter are still at an early stage of development and, so far, have provided relatively little in the way of an extension of available diagnostic information. Sometimes the methods provide extensions to existing techniques, for example by the detection of bcr rearrangements in patients who have CML or ALL but do not have a detectable Philadelphia chromosome. Another example is retrospective diagnosis of gene rearrangements using DNA from slide preparations. However, it should be noted that it has only very recently been shown that there is likely to be a causal relationship between the Ph chromosome and leukaemia. Daley et al (1990) induced CML in mice by bone marrow transplantation of cells infected with a retrovirus encoding P210bcr/abl and Heisterkamp et al (1990) produced mice transgenic for a BCR/ABL P190 DNA construct and showed that the progeny died of acute leukaemia (mostly ALL). We have not summarized studies of the incidence of activated oncogenes such as RAS in leukaemia and myelodysplasia. Such oncogenes appear to be involved in many tumours and may well indicate either a predisposition to cancer or a particular stage of malignancy, but their analysis does not at present help in making a diagnosis. It is likely that, as we understand more about the nature of the malignant process, we shall be able to use genetic techniques to enhance considerably both diagnostic and prognostic precision.
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PMID:Molecular biology and leukaemia diagnosis. 227 97

Cytogenetic analyses were performed on 12 adult patients with abnormal megakaryoblastic proliferation which was detected by ultrastructural cytochemical study (platelet peroxidase) and platelet-megakaryocytes-specific monoclonal antibodies (TP-80, Plt1, AN51, and KOR-77). The patients consisted of two patients with myelodysplastic syndromes (MDS), three with acute megakaryoblastic leukemia (AMKL), six with megakaryoblastic transformation in Philadelphia-positive chronic myelogenous leukemia (CML-meg-BC), and one case of chronic myeloproliferative disorder (CMPD). Among them, an inversion of the long arm of chromosome 3 [inv(3)(q21q26)] was found in one AMKL patient with a normal platelet count. Chromosome change at band 3q26 was also found in one MDS patient without thrombocythemia. Furthermore, the long arm of chromosome 13, where rearrangements in myelofibrosis are clustered (13q12----q22) was seen in one MDS patient. Trisomoy of chromosome 19 was found in one AMKL patient and three CML-meg-BC patients. These findings indicate that cytogenetic abnormalities involving 3q26, 13q, and trisomy 19 are associated with hematologic neoplasia with megakaryocytic lineage in adult patients, although these abnormalities were not related to the survival of the patients. During the period of this study, two acute myelogenous leukemia patients (AML-M2 and AML-M5b) with chromosome rearrangements at band 3q21 and thrombocythemia were found, indicating that chromosome abnormality at band 3q21 is related to quantitative platelet dysfunction, whereas that at 3q26 is related to hematologic malignancies with a proliferation of megakaryocytic lineage.
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PMID:Cytogenetic findings in adult acute leukemia and myeloproliferative disorders with an involvement of megakaryocyte lineage. 229 63

The antitumour agent from Ixora javanica flowers shows broad activity against transplantable solid tumours (DLA) in mice by inhibiting the growth of tumour and arresting the growth of already formed tumours; with lesser activity against Ascites tumours. In vitro cytotoxic studies showed 50% cytotoxicity to Dalton's lymphoma (DLA) and Ehrlich Ascites tumour cells at a concentration of 12 micrograms and 65 micrograms, respectively, with no activity against normal lymphocytes but preferential activity for lymphocytes derived from leukemia patients (ALL) (CML), and K 562 suspension cell culture. Tritiated thymidine incorporation studies indicated the mechanism of action of the agent at the site of DNA synthesis. The purified fractions contained Ferulic acid, Pyrocatacheuic acid and caffeic acid.
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PMID:Antitumour principles from Ixora javanica. 230 4


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