Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arsenic trioxide (As2O3) has recently been shown to induce complete remission in acute promyelocytic leukemia (APL). As2O3 reportedly has dose-dependent dual effects on APL cells, triggering apoptosis at relatively high concentrations and inducing differentiation at lower concentrations. However, its effect is still controversial for other AML cells and hematological neoplasms. We studied the in vitro effect of As2O3 on lymphoid lineage cells: lymphoma cell lines, NOL-3, Raji and Daudi, a myeloma cell line, NOP-1, normal peripheral blood lymphocytes (PBL), non-Hodgkin's lymphoma (NHL) cells and chronic lymphocytic leukemia (CLL) cells, and compared it with the effect on APL cell line, NB4, as well as other myeloid cell lines, HL-60 and NKM-1. As2O3 at a concentration of 1 micromol/l markedly inhibited both proliferation and viability of NB4, NOP-1, NOL-3 and NKM-1 cells, but it reduced only viability in normal PBL, CLL cells and NHL cells. As2O3 induced apoptosis and down-regulated bcl-2 expression in NB4, NOP-1 and NKM-1 cells. On the other hand, in HL-60, Raji and Daudi cells, 1 micromol/l As2O3 inhibited only the proliferation weakly, and neither induced apoptosis nor down-regulated bcl-2 expression, but arrested only cell cycle at G1 phase. As2O3 at a low concentration of 0.1 micromol/l had no effect on proliferation and viability of these cells except for NB4. These results showed that As2O3 exerted variable and definite effects on lymphoid cells and indicated that As2O3 might be clinically useful in lymphoid neoplasms such as malignant lymphoma and CLL.
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PMID:The induction of apoptosis and cell cycle arrest by arsenic trioxide in lymphoid neoplasms. 973 86

Donor lymphocyte infusions (DLI) are an effective treatment of leukemia relapse after allogeneic bone marrow transplantation. Undesired side-effects are the development of graft-versus-host disease (GVHD) and the occurrence of pancytopenia in some patients. In a pilot study, we investigated if unmanipulated G-CSF-mobilized peripheral blood stem cells which naturally contain large numbers of T lymphocytes (D-PBSC/LI) would be equally effective or even superior than DLI in generating a graft-versus-leukemia reaction (GVL) but could mitigate or prevent the development of pancytopenia. We treated 12 patients with CML chronic phase (n = 5), CML blast crisis (n = 2), AML (n = 2), ALL (n = 1), CLL (n = 1) and multiple myeloma (n = 1). In five patients with acute leukemia or CML blast crisis D-PBSC/LI followed intensive chemotherapy (group A), in seven patients D-PBSC/LI were given without any prior chemotherapy (group B). In group A two patients were evaluable for hematologic toxicity. Leukopenia <1000/microl lasted for 10 and 19 days, and thrombocytopenia <20,000/microl for 11 and 13 days, respectively. In group B leukopenia <1000/microl and thrombocytopenia <20,000/microl was observed in only one patient. Moderate cytopenia developed in four of five evaluable patients. A complete remission could be achieved in all seven patients with CML who all developed acute and/or chronic GVHD. None of the remaining five patients achieved a complete remission despite acute and/or chronic GVHD in two of them. Four patients died from disease progression, one patient from a secondary lymphoma, and one patient as a result of uncontrolled GVHD. In conclusion, D-PBSC/LI is effective in inducing GVL reaction but it does not prevent pancytopenia in each case. It remains unclear if it mitigates the incidence and severity of pancytopenia.
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PMID:Treatment of relapse after allogeneic bone marrow transplantation with unmanipulated G-CSF-mobilized peripheral blood stem cell preparation. 975 47

From September 1982 to August 1997, 767 bone marrow or peripheral blood stem cell transplants have been performed at the Health Sciences Center in Oklahoma. Five hundred and two (502) autologous transplants (AutoTX) preceded by high-dose myeloablative therapy were performed for breast cancer (BC, 36%), non-Hodgkin's lymphomas (NHL, 24%), Hodgkin's disease (HD, 10%), acute myeloid leukemia (AML, 8%), testicular cancer (TC, 4%), multiple myeloma (MM, 2%) and other malignancies (16%). Two hundred and sixty-five (265) allogeneic marrow transplants (AlloTX) (related, unrelated) were carried out in chronic myeloid leukemia (CML, 30%), AML (23%), acute lymphoid leukemia (ALL, 14%), myelodysplastic syndrome (MDS, 9%), severe aplastic anemia (SAA, 8%), and other diseases (14%). Compared between 1980s to 1990s, 100-day mortality rates have decreased from 28% to 5% for AutoTX and from 40% to 25% for AlloTX. In the AutoTX setting, major changes included the routine use of growth factors post-transplant and the switch from bone marrow to growth factor-mobilized peripheral blood as a source of stem cells over the last five years. In the AlloTX setting, improvements in recognition and control of cytomegalovirus and Candida organisms, the selective use of growth factors and screened blood products, and better selection of unrelated donors using DNA-based techniques of HLA-matching have contributed to reduce early mortality from infection and primary graft failure. The five-year survival outcomes are comparable to those reported in registry data from the International Bone Marrow Transplant Registry (IBMTR) and the National Marrow Donor Program (NMDP).
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PMID:Marrow and stem cell transplantation in Oklahoma: fifteen years of experience and results. 976 68

The aim of this study was to investigate long-term immunity to tetanus toxoid among patients with hematological disease who had been treated with conventional doses of chemotherapy. Altogether 206 patients with different hematological malignancies were included in the study. There were marked differences between the rates of seronegativity against tetanus, varying from 20% to 70% in different groups of study patients. We found that 21 of 80 (36%) patients with AML, 45 of 80 (56%) with ALL, 12 of 22 (54%) with lymphoma, 4 of 13 (31%) with myeloma and 2 of 11 (18%) with CML were not immune to tetanus. In a multivariate logistic regression model increasing age (P = 0.0001), lymphoid malignancy (P = 0.0005) and advanced disease stage (P = 0.0001) were independent risk factors for loss of tetanus immunity in patients with hematological malignancies.
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PMID:Tetanus immunity in patients with hematological malignancies. 977 65

During the period from 1995 to 1997, we studied 19 new cases of therapy-related myelodysplasia (t-MDS) and acute myeloid leukemia (t-AML), extending our series to 180 consecutive cases: 123 patients with t-MDS and 57 patients with t-AML. Cytogenetically unrelated clones were observed in 13 patients: 11 patients with two unrelated clones, one patient with three unrelated clones, and one patient with four unrelated clones. Twelve cases of unrelated clones presented as t-MDS, whereas only one case presented as overt t-AML. Partial or complete deletions of the long arms or monosomy for chromosome 5 or chromosome 7, which are characteristic of t-MDS and t-AML, were observed in both unrelated clones in four patients and in one unrelated clone only in six patients, whereas three patients showed aberrations in both clones that were uncharacteristic of t-MDS or t-AML. Three different interpretations of the origin and significance of cytogenetically unrelated clones in t-MDS and t-AML are presented, although the disease is still considered to be monoclonal. First, patients with different defects of the long arm of chromosome 5 or chromosome 7 in two unrelated clones often seem to have acquired these aberrations as independent events. For this reason, it is possible that they may play an important role in leukemic transformation, for instance, by activating or potentiating the effect of a genetic change that is present in all cells but not disclosed as a visible chromosome abnormality. In cases with involvement of other chromosomes, unrelated clones sometimes develop by cytogenetic change in only a subclone of cells, indicating that they play a role only in tumor progression. Finally, unrelated clones in t-MDS and t-AML may represent two different monoclonal diseases: the primary tumor and t-MDS. This view is supported by the significant excess of unrelated clones observed in t-MDS following multiple myeloma (4 in 13 cases) compared with other diseases (9 in 167 cases; P = 0.02), and by results from a case with a balanced translocation that is highly characteristic of non-Hodgkin's lymphoma in one clone and a t-MDS-associated deletion of the long arm of chromosome 5 in another.
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PMID:Cytogenetically unrelated clones in therapy-related myelodysplasia and acute myeloid leukemia: experience from the Copenhagen series updated to 180 consecutive cases. 982 7

Platelets express the receptor for thrombopoietin. It is possible that thrombopoietin modulates platelet reactivity. We examined the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet activation in vitro using flow cytometry. We compared samples from healthy individuals and from patients with various hematologic diseases (AML, myeloma, postchemotherapy). Citrated whole blood was incubated with PEG-rHuMGDF (10 or 100 ng/ml), then a mild stimulus was added (0.1 U thrombin/ml). Blood from healthy individuals showed a significantly higher degree of platelet activation (CD62p expression), microparticle generation, and aggregate formation after incubation with PEG-rHuMGDF+thrombin versus thrombin alone (p < 0.05). However, this difference could not be shown for platelets from patients with thrombocytopenia or other hematologic diseases. The use of PEG-rHuMGDF should be safe and not cause an additional risk of thromboocclusive disease in these patients.
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PMID:Reactivity of platelets from healthy individuals and from patients with hematologic diseases following incubation with pegylated recombinant human megakaryocyte growth and development factor in vitro. 988 69

Data on 73,070 patients for seven major haematological malignancies diagnosed in Europe between 1985 and 1989 from 39 population-based cancer registries in 17 countries are included in the EUROCARE database. Relative survival was analysed by country and age between 1985 and 1989 and time trends were analysed from 1978-1989 for 13 countries which collaborated in EUROCARE for this entire period. The European weighted age-standardised 5-year relative survival rate was 72% for patients with Hodgkin's disease (HD, ranging from 45 to 76% in 13 countries), 63% for chronic lymphocytic leukaemia (CLL, range 51-79%, 14 countries), 46% for patients with non-Hodgkin's lymphoma (NHL, range 25-63%, 17 countries), 31% for patients with chronic myelocytic leukaemia (CML, range 8-40%, 13 countries), 28% for patients with multiple myeloma (MM, range 18-36%, 14 countries), 25% for patients with acute lymphoblastic leukaemia (ALL, range 19-33%, 7 countries) and 10% for patients with acute myeloblastic leukaemia (AML, range 4-15%, 11 countries). In all countries, relative survival declined with age, most markedly for patients with acute leukaemias. Patients in Northern and Western Europe had better survival rates, particularly in younger patients (15-45 years of age), whilst those in Eastern European countries tended to have poorer rates. Compared with 1978-1979, relative 5-year survival improved in 1987-1989 for most haematological malignancies (relative risk (RR) of death for CLL 0.65, AML 0.75, HD 0.76, ALL 0.79, NHL 0.82), with only CML (RR 0.95) and MM (RR 1.00) showing little or no change. These results suggest that generally and particularly in Eastern Europe there is room for improvement in the diagnosis and treatment of haematological malignancies. The intercountry differences also highlight the importance of socio-economic conditions to health status.
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PMID:Variation in survival of adult patients with haematological malignancies in Europe since 1978. EUROCARE Working Group. 1007 Feb 96

The study purpose was to determine if G-CSF plus dose-intensive cyclophosphamide 5.25 g/m2, etoposide 1.05 g/m2 and cisplatin 105 mg/m2 (DICEP) results in superior autologous blood stem cell mobilization (BSCM) than less intensive chemotherapy. From January 1993 until May 1997, 152 consecutive patients with non-Hodgkin's lymphoma (n = 55), breast cancer (n = 47), Hodgkin's disease (n = 14), multiple myeloma (n = 9), AML (n = 9), or other cancers (n = 18) initially underwent BSCM by one of three methods: Group 1: G-CSF alone x 4 days (n = 30). Group 2: disease-oriented chemotherapy, dosed to avoid blood transfusions, followed by G-CSF starting day 7 or 8, and apheresis day 13 or 14 (n = 82). Group 3: DICEP days 1-3, G-CSF starting day 14, and apheresis planned day 19, 20 or 21 (n = 40). A multivariate analysis was performed to determine which factors independently predicted BSCM. The median peripheral blood CD34+ (PB CD34+) cell count the morning of apheresis linearly correlated with the number of CD34+ cells removed per litre of apheresis that day. The median PB CD34+ cell count and median CD34+ cells x 10(6) removed per litre of apheresis were highest for Group 3, intermediate for Group 2, and lowest for Group 1. By multivariate analysis, mobilization group (3 > 2 > 1), disease other than AML, no prior melphalan or mitomycin-C, and less than two prior chemotherapy regimens predicted better BSCM. Out of 15 Group 3 patients who had infiltrated marrows, 11 had no detectable cancer in marrow and apheresis products after DICEP. These data suggest that DICEP results in superior BSCM than less intensive chemotherapy regimens.
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PMID:Superior autologous blood stem cell mobilization from dose-intensive cyclophosphamide, etoposide, cisplatin plus G-CSF than from less intensive chemotherapy regimens. 1019 94

The p73 gene, a member of the p53 family, is a new candidate tumor suppressor gene. To investigate the possibility of genetic alteration of p73 in leukemia and lymphoma, we examined 55 cell lines and 39 patient samples together with 17 nonhematopoietic cancer cell lines. Gene expression of p73 was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in cell lines (5 of 7 pre B/B-acute lymphoblastic leukemia [ALL], 13 of 21 T-ALL/lymphoblastic lymphomas [LBL], 9 of 10 B-non-Hodgkin's lymphomas [B-NHL], 8 of 9 acute myelogenous leukemias [AML], 2 of 2 T-NHL, 3 of 3 multiple myeloma), and in patient samples (16 of 23 pre B-ALL, 5 of 8 T-ALL/LBL, 5 of 8 B-NHL). PCR-single-strand conformation polymorphism (SSCP) of cDNAs showed no mutation in 43 p73-expressing cell lines within the regions that corresponded to the 5 mutational hotspots of the p53 gene. Neither homologous deletion nor rearrangement of the p73 gene were found by Southern blot analysis in any of the cell lines that lack expression of p73. In contrast to prior published data, analysis of a polymorphic site showed that the p73 gene was expressed biallelically in cell lines and normal peripheral blood. Notably, the p73-negative cell lines were hypermethylated at a CpG island in the 5' untranslated region of the p73 mRNA, and treatment of these cell lines with 5-azacytidine (5-AC), a demethylation reagent, induced p73 expression. Taken together, we found that a sizable proportion (32%) of ALL/B-NHL cell lines and primary tumors had negligible or limited expression of the p73 gene associated with hypermethylation of the gene. These findings suggest that silencing of the p73 gene by hypermethylation may contribute to development and/or progression of lymphoid neoplasms.
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PMID:Loss of p73 gene expression in leukemias/lymphomas due to hypermethylation. 1041 5

The development of refractory disease in acute myeloid or lymphoblastic leukaemias (AML, ALL) and multiple myeloma (MM) is frequently associated with the expression of one or several multidrug resistance (MDR) genes. MDR1, MRP1 and LRP have been identified as important adverse prognostic factors in AML, T-ALL and MM. Recently, it has become possible to reverse clinical multidrug resistance by blocking P-glycoprotein-mediated drug efflux. The potential relevance of these reversal agents of MDR and potential new approaches to treat refractory disease are discussed.
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PMID:Multidrug resistance in haematological malignancies. 1080 91


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