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)

Hairy cell leukemia (HCL) is an uncommon chronic lymphoproliferative disorder, its treatment requires continuous update. Splenectomy as first line therapy has few indications; recombinant alfa interferon (IFN) leads to a high overall response rate but there are few bone marrow remissions; deoxycoformycin (dCF) or pentostatin leads to a higher complete bone marrow response rate than with IFN but follow-up biopsies show persistence of hairy cells; 2-chlorodeoxyadenosine (2-CdA) is a purine analog that after a single seven day intravenous infusion leads to a complete response rate. 2-CDA will probably become the drug of choice for first line therapy for HCL.
Leukemia 1992 Nov
PMID:Hairy cell leukemia 1992. 127 27

The treatment of hairy cell leukemia (HCL) requires continuing update. The role for splenectomy is extremely limited. Alfa-interferon therapy has been available and utilized for five years; there have been few complete remissions. The experience with Pentostatin has resulted in a majority of clinical complete remissions after several months of therapy, but persistence of a small percentage of hairy cells in the bone marrow. The most recent therapeutic agent, 2-chloro-deoxyadenosine (2-CDA) is given for seven days and results in a complete remission in the great majority of patients with no evidence of persistent bone marrow disease. If this trend persists, 2-CDA will become first line therapy for HCL as it may cure the disease.
Leukemia 1992
PMID:The treatment of hairy cell leukemia: an update. 134 62

To evaluate its toxicity and clinical efficacy in children with relapsed or refractory leukemia, we performed a phase I trial of 2-chloro-2'-deoxy-adenosine (2-chlorodeoxyadenosine; 2-CDA) given as a continuous 5-day infusion at doses of 3 to 10.7 mg/m2/d. In this study of 31 children with acute leukemia, the only dose-limiting toxicity was myelosuppression. At the highest dose level, three of seven patients developed fatal systemic bacterial or fungal infections. At dose levels above 6.2 mg/m2/d, significant oncolytic responses occurred in all patients. In addition, there was a significant correlation between both the responsiveness by cell type and dose of 2-CDA, such that more oncolytic responses were noted in acute myeloid leukemia (AML) patients than acute lymphoblastic leukemia (ALL) patients (P = .02). Although this was a phase I trial in heavily pretreated patients with refractory disease, two AML patients treated at 5.2 and 10.7 mg/m2/d, respectively, had complete hematologic responses, and one patient treated at 10.7 mg/m2/d had a partial response. In addition, there was a dose-response relationship in all patients with improved cytoreduction of peripheral blast cells at higher doses of 2-CDA. In vitro evaluation of 2-CDA uptake and anabolism by leukemic blast cells from 22 patients demonstrated that 2-chloro-2'-deoxyadenosine (Cld-AMP) and 2-chloro-2'-deoxyadenosine 5'-striphosphate (CldATP) reached concentrations close to steady-state levels within 1 hour. Intracellular nucleotide disappearance rates were high with half-lives of 1.29 and 2.47 hours for CldAMP and CldATP, respectively. This suggests that continuous infusion is necessary to maintain the desired plasma concentration. The results of this study confirm the antileukemic activity of 2-CDA and the lack of prohibitive nonhematologic toxicity. Phase II trials in patients with AML and ALL are warranted.
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PMID:A phase I clinical trial of 2-chlorodeoxyadenosine in pediatric patients with acute leukemia. 167 75

We describe a prospective study comparing four different assays for PAIgG. Platelets from patients with a variety of thrombocytopenic disorders were collected into ACD, washed, and the PAIgG then measured using three assays for surface PAIgG. These included: (a) a direct binding assay using 125I-monoclonal anti-IgG (MoAb); (b) a direct binding assay using 125I-staphylococcal protein A (SPA); and (c) a two-stage assay. PAIgG also was measured using an assay for 'total' PAIgG following platelet lysis. The mean +/- SD number of molecules of IgG per platelet on washed platelets from 29 healthy, non-thrombocytopenic controls was: 86 +/- 80 (125I-MoAb); 94 +/- 96 (125I-SPA); 3520 +/- 1890 (two-stage surface assay); and 10,850 +/- 3720 (total PAIgG). A total of 62 different patients with idiopathic thrombocytopenic purpura or thrombocytopenia complicating systematic lupus erythematosus, and 73 different patients with 'non-immune' thrombocytopenia, were tested using each of the four assays. These 'non-immune' thrombocytopenic patients included patients with carcinoma, septicaemia, pre-eclampsia, chronic leukaemia, thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome, acute leukaemia and myelodysplasia. All four assays gave similar results for both the immune and non-immune thrombocytopenic patients. The sensitivity of the assays for the most severely thrombocytopenic patients with immune thrombocytopenia was: MoAb 60%; SPA 88%; two-stage 82%; and 'total' PAIgG 88%. The specificity of the four assays in the non-immune thrombocytopenic patients was 57% 'total' PAIgG; 63% two-stage surface; 25% SPA; 38% MoAb.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A prospective comparison of four techniques for measuring platelet-associated IgG. 291 34

In this article, the clinical effects of rH-TNF on various cancer patients and the mechanism of self-induction of defense against rH-TNF cytotoxicity in tumor cells and the counter measures against this are reviewed. 1) Clinical effects of rH-TNF Intratumoral administration of rH-TNF was performed in 7 patients and clinical efficacy (PR + MR) was observed in 3/7 (42.9%). Also a reduction of leukemia cells in peripheral blood was observed in all 4 leukemia patients following intravenous (i.v.) administration of rH-TNF. Furthermore, in 2 multiple myeloma patients, the myeloma protein and plasma cells in bone marrow were reduced by i.v. administration of rH-TNF. 2) Self-induction of defense against rH-TNF cytotoxicity Investigation of the effect of TNF on RNA and protein synthesis by tumorigenic and normal cell lines showed that their synthesis in tumor cells was increased at 12 h and peaked at 24 h of incubation with TNF, while that in normal diploid fibroblast (HEL) cells was apparently unaffected by the presence of TNF. Artificial inhibition of either RNA or protein synthesis by L-M cells, upon addition of Act D or CHI increased the cytotoxic effect of TNF, thus suggesting that the elevated RNA and protein synthesis is related not to the cytotoxic reaction itself but rather to a defense mechanism. Similar incubation of HEL cells with TNF in the presence of either inhibitor resulted in the occurrence of cytotoxicity not observed with TNF alone, thus suggesting the existence of a defense mechanism in normal, TNF-resistant cells which is absent or greatly weakened in tumor cells. 3) Combination therapy of rH-TNF with various anticancer drugs. A synergistic increase in the cytotoxic effects of rH-TNF and anti-cancer drugs was demonstrated in vitro The cytotoxicity of rH-TNF against L-M cells in combination with MMC, ADM, Ara-C, ACD, DM, CDDP, VCR and 5-FU was 4 to 347 times as high as that of rH-TNF alone. These results suggest that combination therapy including rH-TNF and anti-cancer drugs may be of value in the treatment of malignancy in human patients.
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PMID:[Anti-tumor effect of human recombinant TNF]. 329 72

Young cats (3-6 mo old) were challenged with oncogenic Snyder-Theilen feline sarcoma virus (FeSV) after vaccination with live or killed FL74 cat lymphoma cells. Compared with controls immunized with normal cat fibroblasts, the FL74-vaccinated cats exhibited increased resistance to FeSV-induced progressive primary and disseminated secondary tumors. Maximum protection was achieved by vaccination with live FL74 cells or with a low dose of freeze-thawed cells, but tumor cells inactivated by glutaraldehyde or paraformaldehyde were also effective. Infectious helper feline leukemia virus (FeLV) was detected in the blood of all cats after FeSV challenge, but the duration and magnitude of this viremia were reduced in animals that had been previously vaccinated with live, freeze-thawed, or paraformaldehyde-fixed cells. Although immunized cats were resistant to FeSV-induced tumors and FeLV viremia, no evidence was obtained to suggest that vaccination with dead cells induced detectable circulating antibody prior to challenge with oncogenic virus. After FeSV challenge, complement-dependent antibody to feline oncornavirus-associated cell membrane antigen (CDA-FOCMA) appeared at high titer in cats that were destined either to survive tumor-free or to develop small, localized, and eventually regressing tumors. Cats immunized with live FL74 cells developed CDA-FOCMA prior to challenge, and antibody appeared in these cats following an episode of transient FeLV viremia induced by virus replicating from the injected tumor cells. Therefore, apparently, a state of transient or persistent FeLV viremia regularly preceded detection of CDA-FOCMA activity. Several individually derived feline lymphoma cell lines were used as targets for CDA-FOCMA, and the results suggested that lytic activity is directed to multiple antigen determinants expressed differently by individual feline lymphomas.
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PMID:Protection of cats against progressive fibrosarcomas and persistent leukemia virus infection by vaccination with feline leukemia cells. 625 14

Mature T-cell lymphoproliferative disorders comprise a heterogenous group of diseases for which there is no standard therapy. These disorders are uncommon, and are usually treated similarly to their B-cell counterparts, but with less success. Nucleoside analogues have proven effective in indolent B-cell disorders but have been less well explored in T-cell malignancies. We treated 22 patients with mature T-cell lymphoproliferative diseases with 2-chlorodeoxyadenosine (2-CDA) administered as a continuous infusion at a daily dose of 4 mg/m2 over 7 days. Nineteen of the patients had received prior therapy with a median number of prior regimens of three. Eleven patients had leukemia or large granular lymphocytosis, eight patients had mycosis fungoides, and three had T-cell lymphoma. Nine patients (41%) responded to 2-CDA. Four of the patients had responses that were complete remissions, and three of these four patients remain in remission at 23, 24, and 23 months. The only important toxic effects were fever or infection, seen during 38% of courses. In conclusion, 2-CDA appears to be an effective therapy in T-cell lymphoproliferative disorders and deserves wider evaluation in this subset of patients.
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PMID:2-Chlorodeoxyadenosine therapy in patients with T-cell lymphoproliferative disorders. 791 41

The influence of 2-chlorodeoxyadenosine (2-CDA) administered alone and in combination with cyclophosphamide (CY) or methotrexate (MTX) on the survival time of mice bearing L1210 or P388 leukemia was investigated. 2-CDA given alone significantly prolonged survival time of mice bearing L1210 leukemia and caused only a slight prolongation of survival time in mice bearing P388 leukemia. Survival times of mice bearing both kinds of leukemia, receiving combined therapy of 2-CDA and MTX were not significantly prolonged as compared with mice treated with these agents separately. The groups of mice with both leukemia L1210 and P388 treated with 2-CDA and CY lived significantly longer as compared with the control group and with mice receiving only single cytostatic.
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PMID:Synergistic action of 2-chlorodeoxyadenosine and cyclophosphamide on murine leukemias L1210 and P388. 810 59

The cytostatic drug acetyldinaline [ACD, CI-994, 4-acetylamine-N-(2-aminophenyl)-benzamide] shows an extreme antileukemic effect in the Brown Norway (BN) rate model for acute myelocytic leukemia (BNML) with only minor toxicity for normal pluripotent hemopoietic stem cells. So far, the mode of action is unknown. A resistant subline (BNML/ACD-R) was developed in vivo in the BNML model. Leukemic rats received repeated oral administrations of ACD. When the leukemia relapsed after initial remission-induction with ACD, the cells were transferred to new recipients which were again treated. In total, the animals received 247 oral administrations of ACD (33 x 2 mg/kg per day and 214 x 5 mg/kg per day) before full resistance was reached. The cell line was transferred 17 times in total. Treatment of the final resistant cell line with therapeutically highly active doses of 23.7 mg/kg per day and 11.85 mg/kg per day ACD for 5 days, that resulted in an increase of life span (ILS) of 57 and 18 days, respectively, when applied to the sensitive parent BNML line (BNML/S), resulted in only 10 and 3 days ILS, respectively. These results indicate that a significant degree of resistance has been achieved, which can be overcome partially by increasing the dose of ACD. Whether the development of a resistant subpopulation of the BNML is a result of acquired resistance or whether a naturally resistant subpopulation has been selected out after prolonged treatment with ACD remains to be established. The currently available resistant subline BNML/ACD-R now offers the possibility for further studies on the mechanism of action of ACD.
Leukemia 1993 Aug
PMID:In vivo development of an acetyldinaline resistant subline of the BN rat acute myelocytic leukemia (BNML). 835 Jun 29

In vitro studies suggest that nucleoside analogs have an antileukemic effect against chronic myelogenous leukemia (CML). We investigated the antileukemia effect of deoxycoformycin (DCF) and fludarabine in patients with CML. Four patients with Philadelphia chromosome (Ph)-positive CML were treated with DCF at 4 mg/m2 every week for 4 weeks, then every other week for four doses, and then every month as maintenance. Two patients were in late chronic phase and two in accelerated phase. All had previously failed therapy with interferon-alpha (IFN-A). Nine patients were treated with fludarabine 30 mg/m2/day for 5 days every 28 days. Three had Ph-positive CML, and six Ph-negative disease. Five patients were in accelerated phase and four in late chronic phase. Three patients treated with DCF had normalization of WBC counts while on the weekly schedule but progressed when changed to every other week. The fourth patient had no objective response. There were no cytogenetic responses. DCF was well tolerated with only mild nausea and vomiting in all patients. Patients treated with fludarabine received a median of two courses (range 1-4). In two patients (both Ph-positive), disease progressed to blastic phase upon recovery. Two other patients died of hemorrhagic complications secondary to thrombocytopenia. In all other cases fludarabine produced a transient reduction of WBC counts, but counts recovered to levels equal to or greater than the pre-treatment values. There were no cytogenetic responses. These results, together with previous experience with 2-CDA producing only hematologic responses, suggest that nucleoside analogs may not have a significant role in the management of CML.
Leukemia 1997 Jun
PMID:Treatment of chronic myelogenous leukemia with nucleoside analogs deoxycoformycin and fludarabine. 917 28


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