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)

Mafosfamide (ASTA-Z 7557) is a chemotherapeutic agent currently used for purging human bone marrow cells prior to autologous bone marrow transplantation. Adoptive cell-mediated immunotherapy has been shown to have a positive effect on the control of minimal residual disease and reinduction of remission post-bone marrow transplantation. Large granular lymphocytes and natural killer (NK) cells are believed to play a role in this effect. In the present work, we assessed the effect of ASTA-Z on the cytotoxic and proliferative capabilities of large granular lymphocytes (LGLs). The ASTA-Z significantly inhibited peripheral blood and bone marrow-derived LGL proliferation and cytotoxic capabilities, while this effect was less pronounced post-IL-2 treatment. We conclude that ASTA-Z purging may significantly impair the NK cell-mediated graft versus leukemia effect and therefore should be preceded by IL-2 therapy.
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PMID:ASTA-Z 7557 impairs human natural killer (NK) cell activity. 862 16

From 1980 through 1994, we identified 47 adult patients with acquired pure red cell aplasia (median age, 64 years; range, 22 to 84 years). Associated clinical disorders included T-cell large granular lymphocytic (LGL) leukemia, thymoma, chronic lymphocytic leukemia, and non-Hodgkin's lymphoma. Review of bone marrow findings in 40 patients showed absence of erythroid precursors in 14 patients and rare pronormoblasts in 26. None had morphologic evidence of myelodysplasia. T-cell receptor gene rearrangement studies with Southern blot technique in 14 patients showed clonal rearrangements in nine. Karyotypic analyses performed in 28 patients showed clonal abnormalities in four. Overall, 28 of 47 patients (60%) responded to immunosuppressive therapy, but none were the patients with cytogenetic abnormalities. There was a trend toward superior response to immunosuppressive agents in the patients with T-cell LGL leukemia. Cyclophosphamide, with or without corticosteroids, was the most useful treatment agent. Cyclosporine A was effective for refractory disease. Neither the presence of an associated clinical disorder nor the existence of detectable erythroid precursors affected overall survival. We conclude that (1) T-cell LGL leukemia is the disorder most commonly associated with pure red cell aplasia, (2) the presence of clonal cytogenetic abnormality predicts poor response to immunosuppressive therapy, and (3) oral cyclophosphamide and cyclosporine A are effective treatment regimens.
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PMID:Pure red cell aplasia: association with large granular lymphocyte leukemia and the prognostic value of cytogenetic abnormalities. 887 28

The effects of adenosine (ADO) analogs on cells of the human promyelocytic HL-60 line were examined. ADO A(3) receptor agonists, N(6)-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (IB-MECA, 30-60 microM) and 2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (CI-IB-MECA, 10-30 microM) induced apoptotic cell death. In contrast, neither an A(1)/A(2) antagonist (XAC) nor other selective ADO receptor agonists (CPA, NECA and CGS21680) induced apoptosis at concentrations of <30 microM. Both IB-MECA and CI-IB-MECA significantly induced Ca(2+) release from intracellular Ca(2+) pools followed by Ca(2+) influx, suggesting the presence of phospholipase C-coupled ADO A(3) receptors on HL-60 cells. This was further supported by the presence of mRNA of ADO A3 receptor in the cells. These results suggest that activation of ADO A(3) receptors is responsible for the ADO-induced apoptosis in HL-60 cells and could be of potential therapeutic value in the treatment of leukemia.
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PMID:Induction of apoptosis in HL-60 human promyelocytic leukemia cells by adenosine A(3) receptor agonists. 864 77

Graft versus host disease (GVHD) is one of the obstacles encountered in allogeneic bone marrow transplantation (alloBMT) and has a direct impact on the transplant outcome and survival. In this report, we summarized the incidence of acute and chronic GVHD among 71 HLA matched and 9 HLA mismatched sibling alloBMTs performed for various hematological malignancies, mainly leukemias seen at Ibn-i Sina Hospital. Fifty-five were male and 25 were female Turkish patients. Median age was 29 (12-48). Cyclophosphamide(CY)+total body irradiation (TBI)(12), CY+total lymphatic irradiation (TLI)(6), busulfan (BU)+CY(58) and ALG/ATG+CY(4) were the regimens used for conditioning. Cyclosporin A (CsA)+short term methotrexate were given for GVHD prophylaxis except for two syngeneic transplants who both received only CsA. In 22 of the patients ABO and in 30 patients sex mismatched bone marrow was given. Thirty-one (38.8%) patients showed acute GVHD (grade I-II: 22, grade III-IV: 9) and 8 (11.6%) showed chronic GVHD. In HLA matched and mismatched patients acute GVHD incidence were 33.7% and 44.4% respectively. All of the HLA mismatched patients that showed acute GVHD were in advanced stage. Of the patients with acute GVHD, 28 (96.5%) disclosed skin, 22 (75.9%) hepatic and 14 (48.3%) gut involvement. In the chronic form three patients had mild limited, two limited, two moderate and one advanced GVHD. Seven of the patients were lost due to GVHD. To determine the graft versus leukemia effect of alloBMT, we compared the disease free survival (DFS) of the 68 leukemia patients. Although the patients who had grade I-II acute GVHD showed a better DFS than the patients who did not have acute GVHD, it did not reach to a significance (15.9 vs 13.6 months: p = 0.43).
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PMID:Incidence of graft vs host disease in allogeneic bone marrow transplantation in a single center study from Turkey. 926 89

To compare the pathogenicity of HTLV-I derived from patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) and that from patients with adult T-cell leukemia (ATL), neonatal WKA rats were inoculated with either an HTLV-I-infected T-cell line (Fuk line) newly established from a HAM/TSP patient or MT-2 derived from a patient with ATL. Of 38 rats, 34 developed mesenchymal tumors (89%) only after 14 months of age, irrespective of the cell lines used. The rats inoculated with the Fuk line developed severe arthritis (27%) and anti-type II collagen antibody (64%), and less frequently, paraparesis (7%). Those inoculated with MT-2 developed paraparesis (23%), but not arthritis. Cyclophosphamide (CY) administration to induce immunosuppression in the Fuk line-inoculated rats increased the frequency of paraparesis (70%), but decreased the frequency of tumors (20%). HTLV-I proviral DNA was found in the spinal cord, sciatic nerves, tumors, and joints, whereas pX mRNA was detected in the sciatic nerves and tumors, but not in the spinal cord and joints. As a result, HTLV-I is considered to facilitate development of both chronic inflammatory arthropathy associated with autoimmunity and mesenchymal tumors in rats by experimental infection, and its pathogenicity is likely to be greatly influenced by the host immune state.
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PMID:Induction of chronic inflammatory arthropathy and mesenchymal tumors in rats infected with HTLV-I. 942 Mar 18

In an effort to develop more effective therapy for patients with refractory or relapsed acute myelogenous leukemia (R-AML) we combined three drugs with proven activity in AML, that are not typically used in induction regimens, with cytosine arabinoside (ara-C). Twenty-five patients (3 primary refractory, 22 relapsed) were treated. Patients received 3 days of "CECA" therapy as follows: cyclophosphamide (CTX) 1 g/m2 i.v. over 2 hrs., etoposide (VP-16) 200 mg/m2 i.v. over 3 hr, carboplatin (CBP) 150 mg/m2 i.v. over 24 hours and ara-C 1 g/m2 over 2 hr. Peripheral circulating blasts cleared in 24 cases (96%), and marrow aplasia was achieved in 19 (76%). There were 3 complete remissions (CR), 1 patient died before day 14, 5 died aplastic 14 or more days from the start of therapy, 5 had primary resistant disease, and 10 had secondary resistance i.e., leukemia reappearing after developing aplasia and 1 was lost to follow up 6 weeks into therapy. Two of the patients achieving CR received allogeneic BMT in CR (at 18 and 22 weeks): one died of fungal infection on day 50 and the other, who had CNS involvement at relapse, is alive 24 months post transplant. Toxicity was tolerable: one patient each developed grade III diarrhea and mucositis, another had grade III cardiac toxicity, a fourth developed a grade IV bilirubin elevation. Single, 2, and 3 or more infectious episodes occurred in 10, 5 and 4 patients respectively. This regimen showed definite anti-leukemic activity: the 3 patients achieving CR were among 23 patients with a 1%, 10% or 20% expectation for second CR attainment. The CECA regimen should be investigated in better prognosis salvage groups.
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PMID:CECA-cyclophosphamide, etoposide, carboplatin and cytosine arabinoside--a new salvage regimen for relapsed or refractory acute myelogenous leukemia. 951 8

This study was performed to analyze the effect of Bleomycin, Adriamycin, Cyclophosphamide, Vincristine, Deacadron, Etoposide (BACOD-E) chemotherapy for patients with non-Hodgkin's lymphoma. Seventy patients with non-Hodgkin's lymphoma (stage I: 15, stage II: 23, stage III: 20, and stage IV: 12) were treated at the Department of Radiology, Chiba University Hospital, between 1987 and 1995. The response rates for treatment were CR: 63%, PR: 35%, and PD: 2%. The overall disease-free 5-year survival rate was 54%, and those for each stage were as follows: stage I: 78%, stage II: 55%, stage III: 51%, and stage IV: 28%. There were no significant differences between patients with and without B symptoms, or those with and without elevated LDH levels. Treatment associated deaths occurred in six patients. Two patients died due to side effects of chemotherapy during treatment, and one patient due to leukemia 2 years and 5 months after treatment. One patient died due to radiation pneumonitis, one patient due to heart failure, and one patient due to an unknown reason one month after treatment. This chemotherapy may be useful for patients with advanced disease or unfavorable prognostic factors such as B symptoms or elevated LDH. Moreover, the addition of radiation therapy may prolong survival.
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PMID:[Bleomycin, adriamycin, cyclophosphamide, vincristine, deacadron, etoposide (BACOD-E) chemotherapy for the treatment of non-Hodgkin's lymphoma: long-term survival rate and complications]. 971 Oct 76

The combination of a cyclophosphamide (CTX)-based chemotherapy regimen and interleukin-2 (IL-2) has been shown to provide synergistic effects against malignancy in animal models. We therefore conducted a phase I-II trial combining CTX-based combination chemotherapy or CTX alone with high-dose IL-2 in patients with advanced and refractory malignant disease. Fifteen patients with hemato-oncological malignancies (malignant lymphoma 8, multiple myeloma 3, solid tumor 2, leukemia 2) were enrolled in the study. Continuous high-dose IL-2 infusion was shown to be safely administered, starting as soon as recovery of white blood cell count. All patients developed rebound lymphocytosis 24-48 h after termination of IL-2 infusion. Although grade IV toxicity was observed in 5 patients (7 episodes), all side effects completely subsided. Triple chemotherapy (CTX, etoposide and Ara-C) seemed rather toxic (in this group of heavily treated patients) while CTX alone was well tolerated. Four out of 13 (31%) evaluable patients had partial response and another patient (7%) had stabilization of disease progression lasting 2-8 months. Our conclusion is that the combination of CTX and continuous infusion of IL-2 is feasible and should be investigated in patients with various malignant neoplasms.
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PMID:Continuous interleukin-2 infusion combined with cyclophosphamide- based combination chemotherapy in the treatment of hemato-oncological malignancies. Results of a phase I-II study. 979 34

We succeeded in establishing a human myelogenous leukemia model in severe combined immunodeficient (SCID) mice by transplanting 2 x 10(7) ML-2 cells intraperitoneally (i.p.) with cyclophosphamide (CTX) pretreatment. Two months after transplantation, 9 of 10 mice developed leukemia and leukemia cells were detected in the peripheral blood (PB) and bone marrow (BM). The main findings at autopsy were peritoneal and pleural effusions and large tumor masses involving the peritoneal organs. However, successful transplantation required injection of a large number of cells. We therefore established a new cell line, ML-2S, from the PB of a mouse with ML-2 leukemia. Although only 2 x 10(6) ML-2S cells were inoculated, ML-2S induced the same pattern of leukemic dissemination reminiscent of the parent ML-2 cells. Compared to ML-2, progression of ML-2S was slow, suggesting that ML-2S is suitable as a leukemia model to study treatment. Furthermore, we confirmed that ML-2S cells are of human origin using isoenzyme analysis and also that ML-2S and ML-2 cells have the same phenotypic character by cell surface marker analysis.
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PMID:Establishment of an in vivo human myeloid leukemia model in the SCID mouse. 1021 30

The H2 complex has an important role in determining susceptibility to viral and chemical leukemogenesis in inbred mice. This also applies to transplantable leukemias, within the syngeneic system. In this respect H2K is sensitive, H2d is relatively sensitive, and H2b is absolutely resistant to leukemia induction and transplantation. In our present study we investigated the effect of Cyclophosphamide, (a known chemical leukemogen) on onco/suppressor gene expression in CBA/Ca mice, very shortly after treatment with chemical carcinogen without any manifestation of tumour/leukemia symptoms. Here we describe, in a "short-term" experiment, the gene expression of Ha-ras, c-myc and p53 which was similar to the leukemia induction in a "long-term" experiment. H2K showed marked elevation in terms of onco/suppressor gene expression. H2b expression was modest and H2d turned out to be more or less silent. The results obtained from a short term gene expression investigation shows similarity to those obtained earlier from long term leukemia inducing experiments.
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PMID:Different H2 haplotypes have a strong influence on oncogene action. 1036 72


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