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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a patient with anaplastic large-cell lymphoma (ALCL) who has been given immunosuppressive therapy for Evans syndrome for 10 years. He was admitted with spike fever, intra-abdominal lymphadenopathy, and multiple liver masses. Examination of biopsy specimens obtained by para-aortic lymph nodes and liver masses resulted in a diagnosis of ALCL. Immunohistochemically, these cells were reactive to anti-CD30 antibody but were not of B- or T-lineage. Bone marrow aspiration demonstrated the invasion of giant neoplastic cells and trilineage myelodysplasia. Because the patient showed severe inflammatory symptoms, we examined serum levels of various cytokines. Pretreatment levels of IL-6 and VEGF in this patient were significantly elevated compared to those of normal controls. He was treated with combination chemotherapy (ABVD regimen), achieving complete remission. Myelodysplasia and serum IL-6 and VEGF also normalized after treatment. We assumed that ALCL resulted from long-term immunosuppressive therapy and that the up-regulation of IL-6 and VEGF played a role in pathogenesis of this type of lymphoma.
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PMID:Anaplastic large-cell lymphoma which showed severe inflammatory status and myelodysplasia with increased VEGF and IL-6 serum levels after long-term immunosuppressive therapy. 1142 93

The Myelodysplastic Syndromes (MDS) represent a group of potentially acute myeloid leukemic disorders. There exists a delicate balance between increased apoptosis and proliferation of the leukemic hematopoietic stem cell that permits many patients to survive for years. When the balance shifts towards proliferation AML develops with a poor outcome for most but not all patients. I will review the latest proposals from the W.H.O. in classification, including pediatric MDS, prognostic factors and response criteria. Then I will present a strategy for the management of low risk patients with supportive care or low intensity treatment (cytokines, Immune modulation, anti-VEGF agents) and finally chemotherapy and intensive therapy with auto and allo BMT.
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PMID:The myelodysplastic syndromes: morphology, risk assessment, and clinical management (2002). 1243 Sep 30

The last decade has witnessed a multistep evolution in the understanding of the natural history, clinical manifestations, and some of the molecular mechanisms that underlie the ineffective hematopoiesis and leukemic transformation in the myelodysplastic syndrome (MDS). The international prognostic scoring system, FAB, and WHO classifications have helped define specific subgroups with their characteristic cytogenetic, molecular and immunological abnormalities. Until recently the mainstay of the treatment has been entirely supportive with blood and platelet transfusions. What is increasingly manifest now is the considerable excitement generated by the emergence of novel therapeutic strategies based on painstaking research findings from the laboratories. In Section I, Dr. Alan List reviews the therapeutic strategies with the specific emphasis on the relevance of molecular mechanism of apoptosis and targeted therapies using small molecules. Of particular interest is the excitement surrounding the clinical benefit obtained from potent immunomodulatory derivative (IMiD) of thalidomide CC5013. The review provides an update of the role of small molecule inhibitors of VEGF receptor tyrosine kinase, arsenic trioxide, oral matrix metalloprotease inhibitors, farnesyl transferase inhibitors, and imatinib mesylate in the treatment of MDS subgroups. In Section II, Dr. Steven Gore describes the results of clinical trials of inhibitors of DNA methylation such as 5 azacytidine (5 AC) and 5-aza 2-deoxycytidine (Decitabine). The review also provides an update on the rationale and results obtained from the combination therapy using histone deacetylases (HDAC) and DNA methyltransferase inhibitors in the treatment of MDS. In Section III, Professor Ghulam Mufti and Dr. Aloysius Ho describe the role of bone marrow transplantation with particular emphasis on recent results from reduced-intensity conditioned transplants, exploiting the graft versus leukemia effect without significant early treatment-related mortality. The section provides an update on the results obtained from the manipulation of the host's immune system with immunosuppressive agents such as ALG and/or cyclosporine A.
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PMID:Myelodysplastic syndrome. 1463 82

Angiogenesis is defined as the formation of new capillaries from prexisting blood vessels and plays an important role in the progression of solid tumors and hematologic malignancies. Markers of angiogenesis correlate with clinical characteristics in leukemia and non-Hodgkin's-lymphoma, serving as predictors of poor prognosis. Antiangiogenic effects of chemotherapeutics as well as of novel drugs such as farnesyltransferase inhibitors and tyrosine kinase inhibitors such as Gleevec might contribute to their therapeutic potential. Thalidomide which has antiangiogenic effects and direct cytotoxic effects was found to be effective in multiple myeloma and is considered as an established treatment modality for patients with refractory or relapsed multiple myeloma. Thalidomide has a significant therapeutic effect in myelodysplastic syndrome (MDS) by improving cytopenia and achieving independence of transfusion therapy in a subset of patients. Preliminary data indicate activity of specific VEGF receptor tyrosine kinase (RTK) inhibitors in multiple myeloma (MM) and acute myeloid leukemia (AML). The positive correlation between increased levels of angiogenic cytokines and clinical response to VEGF-RTK inhibitors and thalidomide indicates the relevance of detecting angiogenesis markers to identify best candidate patients for specific approaches. Including antiangiogenic drugs into treatment protocols for hematologic malignancies is an important task for future clinical studies.
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PMID:Antiangiogenic therapy in hematologic malignancies. 1507 37

This meeting was convened by Richard T. Silver, M.D. and co-chaired by Jerry L. Spivak, M.D. It was held from 16 to 18 October 2003 in New York City, New York, USA. Thirty-nine invited speakers from nine different countries participated in the conference. There were more than 350 attendees. There were formal presentations and discussions on biology, clinical aspects, and management of patients with these diverse bone marrow stem cell disorders linked by a variable progression to acute myeloid leukemia. Of considerable interest, a clinical symposium exclusively for patients was held the day preceding the meeting at which John Bennett, Tiziano Barbui, Richard Silver, Jerry Spivak, and Ayalew Tefferi spoke on various topics pertaining to these diseases. This proved to be highly informative to the patients who reported that they enjoyed the program immensely. This was sponsored by the Cancer Research & Treatment Fund, Inc. Representatives of the Myelodysplasia Foundation were also present. This meeting report provides a summary of five different sections prepared by one or more of the session chairs. The keynote address was given by Shahin Rafii (Cornell Medical Center). Most appropriately, this talk focused on the expression and activation of angiogenic factors which play a crucial role in the progression of both myeloproliferative disorders and myelodysplastic syndromes (MDS). Among the known factors, vascular endothelial growth tyrosine kinase receptors (VEGF-R1, R2, and R3) support proliferation, survival, and mobility. Rafii's team has demonstrated that these receptors are expressed on subsets of primary hematopoietic cells as well as leukemic cells. Some leukemic cells express both VEGF-A and VEGF-R2, resulting in the generation of an autocrine loop that supports survival and within the osteoblastic zone translocating these cells to the vascular enriched niche for receipt of molecular instructions required for proliferation and differentiation. A pathologic correlation can be seen in some patients with the identification of abnormal localization of immature precursors (ALIP) in the central portions of the medullary cavity. Misplaced megakaryocytes can release pro-fibrotic factors, including platelet derived growth factors and transforming growth factor-beta. Collectively, these data suggest that chronic disregulation of angiogenic factors alter the microenvironment dislocating marrow stem cells that force both proliferation and differentiation in varying degrees, contributing to these hematological disorders.
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PMID:The second international congress on myeloproliferative and myelodysplastic syndromes. 1523 76

Treatment of myelodysplastic syndrome (MDS) has been hampered by the lack of understanding of the molecular and biological abnormalities associated with this disease. Biological abnormalities may lead to typical phenotypic changes in more differentiated cells. Recent developments in the natural history and underlying molecular mechanisms of MDS and acute myeloid leukemia (AML) have identified new molecular therapeutic targets. Several new classes of drugs have shown promise in early clinical trials and may alter the standard of care of these patients. Among these new drugs are farnesyltransferase inhibitors, receptor tyrosine kinase inhibitors, protein kinase C inhibitors, and VEGF inhibitors. These agents have been tested in patients with solid tumors and hematological malignancies such as AML and MDS. Most of the studies in MDS are in early stages of development, where doses are being determined based on the experience in refractory or relapsed AML or solid tumors. Future therapies in MDS will attempt to resolve cytopenias, eliminate malignant clones and allow differentiation by attacking specific mechanisms of the disease.
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PMID:Inhibitors of signaling in myelodysplastic syndrome. 1549 98

Stromal cells from a child with constitutional trisomy 8 who developed myelodysplastic syndrome (MDS) were found to produce abnormal levels of various cytokines, including VEGF, and supported the growth of leukemic cells in co-culture assays. This study shows that the geldanamycin derivative 17-AAG effectively reduces the VEGF expression by MDS stromal cells. In co-culture experiments this agent also blocks the ability of the MDS stromal cells to stimulate the growth of leukemic cells. These data provide important initial evidence for the effect of 17-AAG on the marrow microenvironment and its potential use in the treatment of MDS and leukemia.
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PMID:The geldanamycin derivative 17-AAG decreases VEGF secretion and leukemia growth support by trisomy 8 myelodysplastic syndrome bone marrow stromal cells. 1580 96

We treated with thalidomide seven patients with primary MDS and observed reduction of the transfusion requirement in three cases and reduction of bone marrow blasts in one case. The apoptotic rate of bone marrow cells diminished significantly from a mean of 43.8% to a mean of 17.5%, whereas the proliferative activity did not change. Plasma TNF-alpha, bFGF, IL-1beta levels decreased variably, whereas VEGF levels tended to increase. Matrix metalloproteinases 2 and 9 expression decreased in bone marrow cells of responders. A reduction of CD4 cells and an increase of NK cells was observed in the peripheral blood. Thus, thalidomide may produce a fairly good hematological improvement in erythroid series in MDS, with complex biological mechanisms.
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PMID:Thalidomide treatment reduces apoptosis levels in bone marrow cells from patients with myelodysplastic syndromes. 1586 3

AG-013736 is an oral anti-angiogenesis agent with activity against a variety of receptor tyrosine kinases, including VEGFR-1, VEGFR-2, VEGFR-3, c-kit, and PDGFR-beta. A phase 2 study was conducted in patients with poor prognosis AML or MDS. Twelve patients (six AML; six MDS) were treated with AG-013736 at a dose of 10mg orally daily for a median of 56 days (range, 1-248 days). Median age was 80 years (range, 58-88 years). Grade 3 or 4 drug-related toxicities included hypertension (42%), mucositis (8%) and deep venous thrombosis (8%). No objective responses occurred; two patients with MDS had stable disease for 8.3 and 6.2 months, respectively. Bone marrow expression of VEGFR-1 and VEGFR-2 was observed in 11% and 0% of patients, respectively. Sustained decreases in soluble VEGFR-2 plasma levels with concomitant elevation in plasma VEGF and placental growth factor levels were obtained during the course of therapy with AG-013736. AG-01736 had minimal biologic or clinical activity in this elderly patient population.
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PMID:The anti-angiogenesis agent, AG-013736, has minimal activity in elderly patients with poor prognosis acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). 1633 90

To determine the possible roles of survivin in the pathogenesis of myelodysplastic syndrome (MDS) and to explore the relationship between apoptosis and angiogenesis in MDS, the expressions of survivin, Bcl-2 and VEGF were detected in the BM cells of de novo patients with MDS, patients with AML and individuals of control by immunochemical staining and their relationship was analyzed. The results showed that the expression rate and integral of all the three proteins in the low-risk group of MDS, high-risk group of MDS and de novo acute myeloid leukemia patients gradually increased, in addition to expression of Bcl-2 in low-risk group of MDS and control group. The significant differences were observed in every two groups and there were positive relations between the every two proteins. It is concluded that survivin, Bcl-2 and VEGF are all involved in the pathogenesis of MDS, and related with the progression of this disease, the deregulated apoptosis and angiogenesis may be involved in the pathogenesis of MDS through interaction among three proteins mentioned above.
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PMID:[Expressions of survivin, Bcl-2 and VEGF in patients with myelodysplastic syndrome and their relationship]. 1663 95


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