Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between 1989 and 1998 93 patients with malignant lymphoma were treated, in our centre, with high-dose chemotherapy and autologous stem cell transplantation. Diagnosis according to the REAL-classification were: 38 patients with high-grade lymphoma (diffuse large B-cell lymphoma (DLCL) (n = 26), anaplastic T-cell (n = 5), lymfoblastic (n = 3) and others (n = 4)), 31 patients with low-grade lymphoma (follicular (n = 18), mantle cell (n = 4), B-CLL (n = 3) and others (n = 6)) and, finally, 24 patients with Hodgkin's disease. The source of stem cells was bone marrow (14 patients), peripheral blood stem cells (64 patients) or a combination of both sources (15 patients). There was no early ( < 100 days) transplant-related mortality. One patient died 11 months post-transplant in unexplained liver failure and all other causes of death were related to relapse of lymphoma. So far, no case of myelodysplastic syndromes or secondary acute leukacmia's has occurred. Overall survival (OS) and progression-free survival (PFS) are: (a) DLCL (26 patients, 4-year probability) OS 40%. PFS 33%; (b) follicular (18 patients, 3-year probability) OS 79%, PFS 52%; (c) Hodgkin's lymphoma (24 patients, 5-year probability) OS 65%, PFS 55%. Out of 52 evaluable patients, 34 (65%) have reached remission inversion. The most important findings are no early transplantation-related mortality, remission inversion in a majority of patients, and so far no cases of secondary myelodysplastic syndromes (MDS) acute myelogenous leukaemias (AML). Concerning OS and PFS, our results seem to be in accordance with other centres.
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PMID:Remission inversion and no transplant-related mortality--a single centre experience of autologous stem cell transplantation in malignant lymphoma. 1114 44

A nondifferentiating mouse myeloid leukemia cell line produces differentiation-inhibiting factors. One of these factors was purified as a homologue of nm23. The nm23 gene was isolated as a metastasis-suppressor gene that exhibits low expression in high-level metastatic cancer cells. The nm23 gene was overexpressed in acute myelogenous leukemia (AML) cells and a higher level of nm23-H1 expression was correlated with a poor prognosis in AML. Multivariate analysis of putative prognostic factors revealed that elevated nm23-H1 mRNA levels significantly contributed to the prognosis of patients with AML. The overexpression of nm23-H1 was also observed in various hematological neoplasms. To use nm23 overexpression to determine the prognosis for lymphoma, we established an enzyme-linked immunosorbent assay (ELISA) technique to determine the serum level of nm23-H1 protein. This assay is far simpler than that used to determine nm23 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). Using this system, we measured nm23-H1 protein levels in many hematological malignancies. Serum nm23-HI levels were significantly higher in patients with all of the hematological neoplasms tested (AML, chronic myelogenous leukemia, acute lymphoblastic leukemia, (ALL) myelodysplastic syndrome (MDS) and malignant lymphomas) than in normal controls. An elevated serum nm23-H1 protein concentration predicted a poor outcome for AML and non-Hodgkin's lymphoma. Especially in diffuse large B-cell lymphoma (DLBCL), seram nm23-H1 protein levels were an important prognostic factor in planning an appropriate treatment strategy for DLBCL. The serum nm23-H I protein levels probably depend on the total mass of malignant cells overexpressing nm23-H1.
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PMID:Serum nm23-H1 protein as a prognostic factor in hematological malignancies. 1215 76

The cyclin-dependent kinase inhibitor p57(KIP2) is thought to be a potential tumor suppressor gene (TSG). The present study examines this possibility. We found that the expression of p57(KIP2) gene is absent in various hematological cell lines. Exposing cell lines to the DNA demethylating agent 5-aza-2'-deoxycytidine restored p57(KIP2) gene expression. Bisulfite sequencing analysis of its promoter region showed that p57(KIP2) DNA was completely methylated in cell lines that did not express the p57(KIP2) gene. Thus, DNA methylation of its promoter might lead to inactivation of the p57(KIP2) gene. DNA methylation of this region is thought to be an aberrant alteration, since DNA was not methylated in normal peripheral blood mononuclear cells or in reactive lymphadenitis. Methylation-specific polymerase chain reaction analysis found frequent DNA methylation of the p57(KIP2) gene in primary diffuse large B-cell lymphoma (54.9%) and in follicular lymphoma (44.0%), but methylation was infrequent in myelodysplastic syndrome and adult T-cell leukemia (3.0% and 2.0%, respectively). These findings directly indicate that the profile of the p57(KIP2) gene corresponds to that of a TSG.
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PMID:Aberrant DNA methylation of p57(KIP2) gene in the promoter region in lymphoid malignancies of B-cell phenotype. 1223 71

Bone marrow involvement is infrequent at presentation in cases of diffuse large B-cell lymphoma. We report four adult patients with diffuse large B-cell lymphoma in whom bone marrow involvement with hematologic manifestations was the predominant clinical feature at presentation. Three patients presented with a leukoerythroblastic blood picture and one with pancytopenia. In each case, the unusual hematologic manifestations, with bone marrow replacement and the presence of immature forms in the peripheral blood, led to consideration of alternative hematologic diagnoses, including acute granulocytic leukemia in three cases and a myelodysplastic syndrome in one. The correct diagnoses were established by immunohistochemistry on formalin-fixed, paraffin-embedded bone marrow for two cases and by flow cytometry on aspirated bone marrow or peripheral blood lymphocytes for the other two. Diffuse large B-cell lymphoma should be considered in the differential diagnosis of unusual hematologic presentations, particularly in the elderly.
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PMID:Primary bone marrow B-cell lymphoma: report of four cases. 1263 6

Radioimmunotherapy (RIT) is a novel treatment modality that combines the benefits of radiotherapy and immunotherapy, enabling multiple sites of disseminated disease to be treated simultaneously and effectively, while minimizing toxicity to normal tissues. 90Y-ibritumomab tiuxetan consists of the anti-CD20 monoclonal antibody (MAb) ibritumomab covalently linked to tiuxetan for chelation of 90Y for therapy. Early work established that a dose of 14.8 MBq/kg (0.4 mCi/kg) is safe and effective in patients with < 25% bone marrow involvement and adequate marrow reserves, as is a dose of 11.1 MBq/kg (0.3 mCi/kg) in patients with mild thrombocytopenia (platelet counts 100 x 10(9)-150 x 10(9)/l). To date, 5 clinical trials using 90Y-ibritumomab tiuxetan have been reported, one of which assessed the efficacy in rituximab-refractory patients with follicular non-Hodgkin's lymphoma (NHL) histology. Within the 54 follicular lymphoma patients, an overall response (OR) rate of 74% and a complete response (CR) rate of 15% were achieved, despite patients having received a median of 4 prior therapies and 73% having tumors > or = 5 cm in diameter. In addition, a major phase III randomized trial directly compared 90Y-ibritumomab tiuxetan with the unlabeled anti-CD20 MAb rituximab. Results from the randomized trial demonstrated that OR and CR rates were significantly higher with 90Y-ibritumomab tiuxetan, compared with rituximab (OR rate 80% vs. 56%, P = 0.002; CR rate 30% vs. 16%, P = 0.004). Time to progression (TTP) was 11.2 vs. 10.1 months (P = 0.173). Treatment was generally well tolerated; the primary toxicity associated with 90Y-ibritumomab tiuxetan therapy is reversible myelosuppression, which correlates with the degree of bone marrow involvement at baseline. In an integrated analysis of safety data from 5 90Y-ibritumomab tiuxetan studies, only 7% of patients were hospitalized due to infection during the treatment period. In addition, 90Y-ibritumomab tiuxetan therapy was not shown to increase the risk of developing secondary malignancies (myelodysplastic syndrome/acute myeloid leukemia), or preclude subsequent therapy upon relapse. Current investigations are focussing on the potential role of 90Y-ibritumomab tiuxetan earlier in the treatment algorithm, including as single-agent therapy for relapsed diffuse large B-cell lymphoma patients not eligible for transplantation, and consolidation treatment for low-grade NHL patients after first-line, alkylating agent-based therapy.
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PMID:Radioimmunotherapy for NHL: experience of 90Y-ibritumomab tiuxetan in clinical practice. 1515 41

We conducted a phase II study to evaluate the efficacy and safety of cladribine (2-chlorodeoxyadenosine [2-CdA]) for patients with refractory or relapsed indolent B-cell lymphoma or mycosis fungoides. Forty-five patients were enrolled, and 43 patients, including 34 with follicular lymphoma, were eligible. 2-CdA was given by continuous intravenous infusion at a dose of 0.09 mg/kg daily for 7 consecutive days, and this schedule was repeated every 4 weeks up to a maximum of 6 cycles. The overall and complete response rates were 58.1% (25/43; 90% confidence interval, 44.5%-70.9%) and 14.0% (6/43), respectively. The disease progression-free proportions of all 43 eligible and all 25 responding patients at 2 years were 30.3% and 48.1%, respectively. Neutropenia and thrombocytopenia of grade 3 or 4 were observed in 53.3% and 37.8% of patients, respectively, with prolonged cytopenia observed in patients with increased numbers of treatment cycles. Nonhematologic toxicities of grade 3 or greater included diarrhea, arrhythmia, malaise, and gastrointestinal bleeding in 1 patient each, an increase in glutamic-pyruvic transaminase level in 2 patients, and infection in 5 patients. Two treatment-related deaths were observed. Four patients developed myelodysplastic syndrome (MDS) at 13 months to 2 years after completion of the 2-CdA treatments. 2-CdA is an active agent with acceptable toxicity for refractory or relapsed indolent lymphoma; however, prolonged myelosuppression and the potential development of MDS should be carefully monitored.
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PMID:Durable response but prolonged cytopenia after cladribine treatment in relapsed patients with indolent non-Hodgkin's lymphomas: results of a Japanese phase II study. 1554 Sep 3

Hematopoietic and immune function tend to deteriorate in the elderly. The incidence of hematologic diseases in the elderly is increasing as the percentage of elderly people in the whole population increases. Acute leukemia, myelodysplastic syndrome, malignant lymphoma, multiple myeloma, and myelodysplastic syndromes are commonly seen in the elderly. Malignant lymphomas are frequently seen in the elderly, and many elderly patients have poor performance status, and because they are more likely to suffer from impaired cardiac, respiratory, hepatic and renal function, as well as glucose intolerance, they are also more likely to suffer side effects due to chemotherapy. Particularly in patients aged over 80 years, to avoid side effects it is essential to adjust dosage and route of administration of chemotherapy. Although age is a significant negative prognostic factor for non-Hodgkin's lymphoma, it is possible for patients to enter complete remission with improvement of host-side factors. The clinical application of Rituximab is expected to improve chemotherapy outcomes in elderly B-cell lymphoma. The median age at the time of initial diagnosis of multiple myeloma (MM) is 60-70 years, and age is a negative prognostic factor. Clinically, higher rates of infection and heavy comorbidity are characteristic of this condition in the elderly. Although the incidence of bony lesions in elderly patients with MM is not different from the non-elderly, they do have a higher incidence of bone pain and pathologic fractures compared with the non-elderly patients. As the response to chemotherapy is good in the elderly, it is worth trying chemotherapy for MM. Polycythemia vera must be treated in the elderly, because chemotherapy decreases the incidence of thrombosis.
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PMID:[Malignant lymphoma, multiple myeloma and myeloproliferative diseases in the elderly]. 1565 67

Serum levels of hepatocyte growth factor (HGF), a potent angiogenic factor, increase during various haematological malignancies. In this study, we examined serum HGF in 59 patients with non-Hodgkin's lymphoma (NHL). Serum HGF levels in NHL patients were increased, as were levels in patients with multiple myeloma, chronic myeloproliferative disorders, and myelodysplastic syndrome. Some 29 patients with T-cell lymphoma, including 20 with adult T-cell leukemia/lymphoma, exhibited a significant increase in serum HGF, as did 23 with B-cell lymphoma. The levels of serum HGF correlated with increased neutrophil counts (r=0.487, p<0.0001), and also paralleled a neutrophil increase in NHL patients who received granulocyte-colony stimulating factor (G-CSF) at the nadir of neutrophil count following chemotherapy. Additionally, in in vitro experiments, HGF secretion from polymorphonuclear neutrophils and its expression in bone marrow myeloid cells were stimulated by G-CSF. Although HGF has been thought to be involved in the pathogenesis of NHL through its angiogenic activities, these results suggest that HGF production by neutrophils and myeloid lineage cells may also contribute to an increase in serum HGF in NHL patients.
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PMID:Possible involvement of neutrophils in a serum level increase of hepatocyte growth factor in non-Hodgkin's lymphoma. 1570 13

According to several reports, the 10 year incidence of secondary acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) after systemic chemotherapy is approximately 1.5%. The cumulative risk increases by 0.25--1% for the first 8 years after treatment. We have reported only 6 cases of hematological malignancies (0.3%) after breast cancer chemotherapy in our institute. We detected 2 cases of secondary AML and 1 case of MDS, 19, 52 and 12 months, respectively, after systemic chemotherapy for breast cancer. Published data on the occurrence of secondary hematological malignancies other than AML or MDS in this setting are scarce. We encountered diffuse large B-cell lymphoma, angioimmunoblastic lymphoma and mantle cell lymphoma as secondary hematological malignancies after systemic chemotherapy for breast cancer.
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PMID:Secondary hematological malignancies after breast cancer chemotherapy. 1608 60

We identified a reciprocal translocation between chromosomes 3 and 8, with breakpoints at bands 3q26 and 8q24, in five patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The t(3;8)(q26;q24) was the sole cytogenetic aberration in two patients, was associated with trisomy 13 in one patient, and occurred with monosomy 7 in two patients. In three patients, the AML or MDS developed 36, 52, and 57 months following chemotherapy for soft tissue sarcoma, mantle cell lymphoma, and diffuse large B-cell lymphoma, respectively; in these three patients, the neoplasms were considered to be therapy-related. All five patients displayed marked trilineage dysplasia and variable degrees of cytopenias, with marked thrombocytosis noted in one patient and a normal platelet count in another patient. All patients were treated with combination chemotherapy; at writing, four were still alive and one had died during a follow-up period ranging from 1 to 16 months. We conclude that the t(3;8)(q26;q24) is a recurrent translocation associated with therapy-related MDS/AML or de novo AML, and is frequently associated with monosomy 7.
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PMID:Translocation (3;8)(q26;q24): a recurrent chromosomal abnormality in myelodysplastic syndrome and acute myeloid leukemia. 1661 15


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