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)

Since January 1988, 91 children with ANLL have been treated with a polychemotherapy regimen containing Mitoxantrone (MTZ), excluding other anthracyclines. Induction consisted of Ara-C, MTZ, and VP 16. Consolidation lasted 6 weeks with Vincristine, MTZ, Ara-C and 6-thioguanine (6TG), and was followed by 2 intensification courses combining High-dose Ara-C with respectively MTZ or VP 16. Maintenance therapy associated 6TG, Ara-C and MTZ up to a cumulative dose of 150 mg/m2. 91 patients are evaluable: 70 (76.9%) achieved complete remission, 59 (64.8%) after induction alone. There were 7 early deaths, 5 deaths in complete remission, and 17 relapses. Major toxic side effects were observed during the consolidation phase, mainly infectious complications, and the median duration of neutropenia was 82 days in this phase, leading to decrease the MTZ dose from 10 to 8 mg/m2. The event-free survival at three years is 38%. Cardiac toxicity is presently absent in children without previous cardiopathy.
Leukemia 1992
PMID:Mitoxantrone and high dose Ara-C for the treatment of ANLL in childhood: a pilot study of the EORTC CLCG (EORTC 58 872). 157 44

Vincristine overdose (7.5 mg/m2) was accidentally administered to 3 children with acute lymphoblastic leukemia. Treatment included double-volume exchange transfusion, phenobarbital administered prophylactically, and folinic acid rescue 18 mg every 3 hours for 16 doses. Vincristine levels were also assayed and showed a dramatic decline in postexchange levels in the 2 patients who survived and an almost unchanged value in the patient who succumbed. Early signs of toxicity in the 2 survivors were peripheral neuropathy (day 4), bone marrow toxicity (day 5), gastrointestinal toxicity (days 6 and 7), and hypertension (days 7 and 8). Marrow aplasia lasted for 4 and 10 days, peripheral neuropathy for 15 and 42 days, gastrointestinal toxicity for 3 and 5 days, and hypertension for 5 and 14 days. The 2 children were discharged on days 13 and 16 and cytostatic therapy was restarted on days 18 and 25. Both are alive without evidence of leukemia. The third patient developed liver and marrow toxicity on day 3 and died on day 9. Postmortem examination showed leukemia infiltration of the liver and spleen.
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PMID:Vincristine overdose: experience with 3 patients. 186 39

Preliminary clinical observations have suggested that low cellular glucocorticoid receptor (GR) levels might have been connected with multidrug resistance in children with acute myeloblastic leukaemia (AML). To test this possibility, we have developed glucocorticoid resistant subclones of two recently established human myeloid leukaemic cell lines. The cause of glucocorticoid resistance was GR negativity in these subclones. GR positive parent cell lines or GR negative subclones were incubated for 1 h in the presence of Adriamycin, Cytosine-arabinosid, Etoposide or Vincristine, respectively. After short-term (1 h) incubation in suspension cultures cells were washed and plated in clonogenic agar cultures. Each anticancer drug was more potent against both GR positive parent cell lines than against the GR negative subclones. The results of this study suggest that the absence of GRs is a useful marker of multidrug resistance in childhood AML.
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PMID:Decreased sensitivity of cytostatic drugs in glucocorticoid receptor-free acute myeloid leukaemia cells. Clinical and experimental observations. 186 89

Pentoxifylline (PTX) is a methylxanthine used clinically in the treatment of intermittent claudication. It is an active hemorheological agent used for the treatment of defective microcirculation. The use of the anticancer agent vincristine is limited by its toxicity to normal body tissues. The data presented in the present paper show that it is possible to achieve greater cell-kill by using vincristine in combination with pentoxifylline. The effect of pentoxifylline alone and in combination with vincristine was studied using membrane filtration technique in P388 leukemia (P388) and its subline P388/DOX resistant to doxorubicin and cross-resistant to vincristine. Pentoxifylline (100 mumol/l) had minimal inhibitory effect on DNA biosynthesis in P388 leukemia cells. Vincristine, at the concentration employed in this study did not show significant inhibition of DNA biosynthesis confirming multidrug resistant nature of P388/DOX cells. Pentoxifylline had a dose-sparing effect, wherein it enhanced the antiproliferative activity of vincristine at a clinically achievable concentration. The studies on reversibility of inhibition of DNA biosynthesis in P388/DOX cells pretreated with vincristine and pentoxifylline showed the irreversible nature of the effect of combination of vincristine and pentoxifylline. This observation warrants the possible use of pentoxifylline as an adjuvant in cancer chemotherapy.
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PMID:Inhibition of DNA biosynthesis by vincristine and pentoxifylline in murine P388 leukemia cells resistant to doxorubicin. 227 81

S 12363 is a new vinca alkaloid derivative obtained by grafting an optically active alpha-aminophosphonate at the C23 position of O4-deacetyl vinblastine. This compound was as potent as Vincristine (VCR), and less potent than Vinblastine (VLB), in inhibiting in vitro tubulin polymerization. However, S 12363 was found to be 7 to 553 and 12 to 74-fold more cytotoxic than VCR and VLB, respectively, when tested on a panel of 2 murine and 6 human tumor cell lines using the Microculture Tetrazolium Assay. S 12362, which differs only by the configuration of the asymmetric carbon atom of the side chain, was 18 to 59-fold less cytotoxic. At equitoxic doses, all these compounds induced a "G2 + M" phase accumulation of L1210 cells, suggesting a similar mechanism of action. S 12363, administered i.p. or i.v., was at least as active as reference compounds on two murine transplantable tumors (P388 leukemia and B16 melanoma) while the optimal dosage was 20-fold lower: 0.15-0.20 mg/kg versus 2-5 mg/kg, respectively. S 12362 was practically inactive at 1-3 mg/kg. The hematological toxicity of S 12363 (0.1 mg/kg) was similar to that of VLB (4 mg/kg). The exceptionally high potency of S 12363 did not appear to be due to a better interaction with tubulin, its intracellular target, but rather to some properties conferred by the alpha-aminophosphonic acid, such as a facilitated uptake and/or a better cellular retention.
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PMID:Pharmacological properties of a new alpha-aminophosphonic acid derivative of vinblastine. 233 19

Synergistic antitumor effects between Vincristine (VCR) and allograft responses have been found in mice bearing allogeneic retrovirus-induced leukemia. In this model VCR depressed weakly allograft reactivity if given before but not after antigen administration. In a parallel human tumor model in vitro using HTLV-1 induced MT-2 leukemia, additive but not synergistic immuno-chemotherapeutic effects were obtained with allogeneic mononuclear cells (MNC) combined with VCR at 0.1 but not at 1 micrograms/ml. In this case natural immunity (NI) rather than antigen-dependent immunity (ADI) was involved in the combined effects of VCR + MNC. In the in vitro model pretreatment of effector cells with 1 or 0.1 micrograms/ml of VCR depressed natural cell-mediated cytotoxicity (NCMC). However when the drug was added to the effector + target cells during the 4 h cytotoxicity assay, 1 but not 0.1 micrograms/ml of the drug was capable of depressing NCMC function. These results would provide valuable information for developing in vitro immuno-chemotherapy studies in human tumor systems, including those characterized by the presence of tumor-associated oncogenic retroviruses, capable of depressing both NI and ADI functions.
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PMID:Role of vincristine in immunochemotherapy of leukemia in mouse or human models. 235 91

Sixteen elderly patients affected by acute non lymphoblastic leukaemia (ANLL) with a preexisting severe internal disease were treated with a low systemic toxicity drugs combination: OAP (Vincristine, Cytarabine and Prednisone). Complete remission was achieved in 5 patients (31%) after 2 OAP courses. The mean duration of remission was 18 weeks. Six patients were resistant to the therapy. Six patients died during the treatment: 5 in induction phase and 1 in consolidation phase. Even though the duration of remission was short we retain that OAP combination may be still considered a good therapeutical approach in elderly ANLL patients with associated severe internal disease.
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PMID:OAP combination in the treatment of elderly leukaemic patients with preexisting severe internal disease. 247 96

Forty-five patients with acute lymphoblastic leukemia of standard risk who were treated with the same protocol of therapy are presented. Induction therapy consisted of Vincristine (5 doses), L-asparaginase (10 doses) and prednisone. Complete remission was attained in 43 cases (95%). Two different methods of CNS prophylaxis were used; radiotherapy of the skull (18 Gy) associated with intrathecal methotrexate and intermediate dose intravenous methotrexate (1 g/M, 12 dose) with simultaneously intrathecal methotrexate. With a mean follow-up time of 28 months in group A and 35 Mo in group B, 82% and 75% respectively remain in continuous complete remission (p: NS). One case of meningeal leukemia was detected in each group. There patients in group A (13.6%) and four in group B (20%) suffered a bone marrow relapse. Actuarial survival rate at 36 months were 76 among the patients in group A and 83% in group B. Our results indicate that the two methods of CNS prophylaxis are both effective and in this series we have not observed any decrease in the bone marrow relapse rate when intermediate dose methotrexate was used.
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PMID:[Acute lymphoblastic leukemia of standard risk: preliminary results obtained with protocol LL-IV-81]. 348 21

Electrolyte imbalance in leukemia can be due to either organ infiltration and cell death or to a side effect of cytostatic drugs. From the wide variety of these disturbances seen in acute leukemias in childhood, the excess of potassium is most dangerous. Further electrolyte changes, which are however less evident, are hyperphosphataemia, hyperphosphaturia, and hypocalcaemia. The destruction of a large amount of cells during aggressive induction therapy can boost the electrolyte imbalance and therefore lead to renal failure. Such situations are demonstrated in two cases. Following Vincristine and Cyclophosphamide administration, electrolyte changes such as acute or prolonged decrease of sodium in the serum and urinary loss of sodium are seen frequently. Based on the data from 20 patients with acute lymphoblastic leukemias we describe the dynamics of this process. These changes are probably caused by the syndrome of inadequate ADH-secretion. The clinical importance of these findings are discussed and procedures for improving therapy are set out.
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PMID:[Electrolyte changes in acute leukemia in childhood]. 385 51

The aim is to examine experimentally whether injections of LPS in combination with Daunomycin are effective on a rat myelomonocytic leukemia. Effects of Lipopolysaccharide (LPS), one of the major differentiation-inducing agents in the mouse myeloid leukemia cell line M1, were investigated on the cells of a rat myelomonocytic leukemia cell line c-WRT-7 in vitro and in vivo. It was shown that sensitive cells of c-WRT-7 cells changed remarkably into macrophage-like cells, which lost the growth potential by LPS-treatment, whereas such change and growth inhibition in insensitive cells of c-WRT-7 were not so remarkable by LPS-treatment. Although the sensitive cells were extremely malignant in vivo, the sensitive cells treated with LPS in vitro lost the transplantability into the syngeneic rats. The sensitive cells by injections of LPS developed morphologically into macrophage-like cells in diffusion chamber i.p. in syngeneic rat. Injections of LPS inhibited the progression of leukemia in 60% of the rats which had been inoculated with the sensitive cells, whereas the leukemia-development was inhibited in only 20% of the rats which had been inoculated with the insensitive cells and i.p. treated with LPS. Daunomycin, Aclacinomycin A and Vincristine induced phagocytic activities in c-WRT-7 cells, whereas Actinomycin D and Cycloheximide showed no such effects. Daunomycin in combination with LPS increased the number of phagocytic cells, whereas cycloheximide inhibited the LPS induced phagocytosis. Injections of LPS in combination with Daunomycin inhibited doubtlessly the leukemia-development in rats which had been i.p. inoculated with the sensitive cells, compared to the injections of LPS or Daunomycin alone. In conclusion, it is suggested that the effects of LPS and Daunomycin on the inhibition of the leukemia-development could be associated in part with their differentiation-inducing activities.
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PMID:[Experimental studies on the therapy of rat myelomonocytic leukemia with lipopolysaccharide (LPS) and daunomycin (DM)]. 386 74


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