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)

Anemia is a frequent complication in hematologic malignancies. In advanced stages of chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and myeloma, anemia usually develops in parallel with marrow involvement. However, anemia may occur in the absence of overt infiltration of bone marrow by malignant cells. When all other causes of anemia (such as chronic bleeding, vitamin deficiency, hemolysis, and pure red blood cell aplasia) are eliminated, anemia can be related to "anemia of chronic disorders." Myelodysplastic syndromes are characterized by cytopenias. Anemia is very frequent, and nearly 90% of patients present with anemia during the evolution of the disease. In this disorder, erythroid progenitors are defective for their proliferation and maturation, as shown by in vitro culture techniques. Moreover, these patients often have a high endogenous serum erythropoietin level. The rationale for treating these patients with epoetin alfa is the possibility of overcoming the defective proliferation by pharmacologic doses of epoetin alfa. The response rate was rather low with epoetin alfa alone. Combinations with earlier-acting cytokines, such as recombinant human granulocyte colony-stimulating factor, have been tested in an attempt to improve response rates.
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PMID:Update on the role of epoetin alfa in hematologic malignancies and myelodysplastic syndromes. 967 24

First used successfully to correct the anemia associated with chronic renal failure, epoetin alfa has been shown to be highly effective in many patients with either hematologic or nonhematologic malignancies. Multiple studies have demonstrated effective response rates, with increases in hemoglobin concentration and reduction or elimination of transfusion requirements in up to 75% or 80% in such patients. Nevertheless, as clinical experience has grown, several issues have arisen. First, not all cancer patients respond to epoetin alfa and, consequently, it is important to identify those patients most likely to respond to make early clinical decisions regarding dose adjustment or drug withdrawal. Second, experience in patients with renal failure has revealed a state of "functional iron deficiency" and, thus, highlighted the importance of iron supplementation to optimize the response to epoetin alfa. Does "functional iron deficiency" complicate epoetin alfa therapy of patients with the anemia of cancer, and could such patients benefit from iron supplementation? Finally, some hematologic malignancies, especially myelodysplastic syndromes, can be resistant to epoetin alfa monotherapy. Can the effective response rates in such patients be improved by combining epoetin alfa therapy with the administration of other hematopoietic growth factors? Epoetin alfa has made substantial contributions to the care of patients with cancer and, with time, additional uses for this very valuable drug will become apparent.
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PMID:Epoetin alfa: into the new millennium. 967 36

Supportive care in hematologic malignancies includes a wide range of topics. We have selected the following issues for a review of recently published developments: new insights into the benefits and risks of established hematopoietic growth factors (HGF), such as granulocyte- or granulocyte-macrophage colony-stimulating factor (G-CSF, GM-CSF); the emerging role of newly introduced HGFs such as keratinocyte-growth factor (KGF) and thrombopoietin; the prophylactic and therapeutic use of amifostine, a cytoprotective agent; the role of hematopoietic growth factors and the demethylating agent decitabine in myelodysplastic syndromes (MDS); infectious complications of anticancer therapy; and, recent improvements in and complications of transfusional therapy, including the renewed interest in granulocyte transfusions.
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PMID:Supportive care in hematologic malignancies. 974 34

Shwachman-Diamond syndrome is an autosomal recessive disorder characterized by exocrine pancreatic dysfunction, bony metaphyseal dysostosis, various degrees of cytopenia, and a striking tendency to develop myelodysplastic syndrome and acute myeloblastic leukemia. Isochromosome 7 [i(7q)] is a rare non-random cytogenetic abnormality of myeloid cells in hematological malignancy. We report two cases of Shwachman-Diamond syndrome in which patients developed myelodysplastic syndrome and i(7q), detected by G-banding karyotype analysis and fluorescence in situ hybridization. Three other children have been previously reported to have myelodysplastic syndrome in association with i(7q); two of them had Shwachman-Diamond syndrome. Isochromosome 7q may be a fairly specific marker of myeloid malignant transformation in this syndrome and play a role in its pathogenesis.
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PMID:Malignant myeloid transformation with isochromosome 7q in Shwachman-Diamond syndrome. 976 4

Radioimmunotherapy offers an exciting new therapeutic modalities for patients with recurrent hematologic malignancies or resistant to conventional chemotherapy. Clinical trials involving hematologic malignancies have produced more impressive results than these involving solid tumors. In recurrent non Hodgkin's lymphoma Seattle trials have demonstrated objective responses in 90% of patients, complete responses in 85% of patients, a progression free survival of 62%, and an overall survival of 93% with a median follow-up of 2 years. In recurrent acute myelogenous leukemia, or myelodysplasia treated with radiolabeled antibodies, total body irradiation, and high dose chemotherapy 67% of patients remain disease free with a median follow-up of 33 months.
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PMID:[Radioimmunotherapy of lymphomas and leukemias]. 976 96

A newly formed National Comprehensive Cancer Network (NCCN) panel on bone marrow transplantation has the task of ensuring the incorporation of allogeneic and autologous transplantation into all disease guidelines where significant evidence exists to warrant their inclusion. The panel is further charged with ensuring that there is consistency among guidelines regarding the use of marrow transplantation. A preliminary review of existing NCCN guidelines found that marrow transplantation was appropriately included for the treatment of the common hematologic malignancies of adults, including acute myeloid leukemia, chronic myeloid leukemia, myelodysplasia, multiple myeloma, Hodgkin's disease, and the malignant lymphomas. Frequent refinements regarding lymphomas will be necessary, particularly in rapidly evolving areas, such as multiple myeloma and myelodysplasia, and conditions with changing definitions, such as malignant disease. The increasing volume of data supporting the use of autologous bone marrow transplantation in advanced primary and responding metastatic breast cancers needs to be reflected in the breast cancer guideline if it is to remain credible. Well-designed and well-conducted clinical trials are the most appropriate setting for all bone marrow transplantations and patient referral to these trials remains the standard of care in all settings.
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PMID:Roundtable discussion: Incorporating bone marrow transplantation into NCCN guidelines. 1002 22

We have identified a membrane-bound form of M-CSF (m-M-CSF) from an established human leukemic J6-1 cell line. To further understand its biological significance, we studied the expression of this membrane-associated growth factor in the lymph nodes of lymphoma patients and bone marrow smears from patients with hematologic diseases by immunohistochemical staining using anti-M-CSF MAb. We detected a high incidence of m-M-CSF expression in 75% (9/12) of the lymph node sections from patients with Hodgkin's Disease (HD). The antigens were detected primarily in large clusters of mononuclear Hodgkin's cells and the extracellular matrix (EM) surrounding them. In one HD patient with abundant multinucleated Reed-Sternberg (R-S) cells, all of them were intensely stained with anti-M-CSF MAb. In non-Hodgkin's lymphomas (NHL), the incidence (17.6 %) of m-M-CSF expression was lower (3/17). Yet, no m-M-CSF antigens were detected in the lymph nodes from six cases of non-hematologic malignancies and other diseases. A high response also was detected in bone marrow smears obtained from patients with hematologic malignancies, which include myeloid leukemias (32.5%), lymphomas with bone marrow metastasis (50%) and myelodysplastic syndromes (MDS) (37.5 %). By comparison, only 6.8 % of bone marrow smears from non-malignant hematologic diseases and 2.7% of lymphoid leukemias showed positive staining with anti-M-CSF MAb. Our results showed that high expression of m-M-CSF antigens is linked to some types of lymphomas, especially HD. and myeloid leukemias, and may play a role in the development of these hematologic malignancies.
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PMID:Expression of membrane-associated macrophage colony-stimulating factor (M-CSF) in Hodgkin's disease and other hematologic malignancies. 1003 31

A 73-year-old man was admitted for investigation of pancytopenia. His physical examination was unremarkable and the bone marrow aspirate was compatible with myelodysplastic syndrome (RAEB). Cytogenetic analysis of the bone marrow revealed a trisomy 21. The patient received transfusions of packed red cells, and his condition remained stable for the next 7 months. He was then admitted with a chest infection and was treated with broad-spectrum antibiotics with satisfactory response. During his hospitalization there was a gradual increase in his complete blood count values, which persisted, resulting in a normal peripheral blood after 3 months. A bone marrow aspirate performed at that time revealed normal findings with no karyotypic abnormalities, indicating a spontaneous remission. The patient remained stable for the next 6 months; then he recurred with 20% blasts in his bone marrow and reappearance of trisomy 21 in 42% of the metaphases examined. Several hematologic malignancies with spontaneous remissions have been described to date, but they have generally been short and recurrence is the rule, as in the case described. The role of endogenous cytokines in triggering these spontaneous remissions is under question, as the exact mechanism is unknown.
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PMID:Spontaneous remission in myelodysplastic syndrome. 1008 25

The phosphorylated thiol amine, amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA), is a cytoprotective agent for cisplatin-based chemotherapy. Recent investigations have given rise to new potential applications of amifostine in hematologic malignancies. Amifostine appears to exert a sustained mitogenic effect in primitive hematopoietic progenitors that results in a significant increase in colony-forming capacity. Amifostine also retards cell loss and delays commitment to apoptosis initiated by cytokine deprivation, suggesting that amifostine has trophic effects similar to the hematopoietic cytokines. The abilities to prolong progenitor survival and to delay apoptosis under conditions of cellular stress make amifostine an attractive agent for investigation in bone marrow failure states. Amifostine promotes more effective hematopoiesis in patients with myelodysplastic syndrome, although additional investigation is needed to further define the optimal dose and schedule of administration. Furthermore, amifostine may selectively enhance the cytotoxicity of chemotherapeutic agents in leukemia progenitors. When the sensitivity of leukemic and normal progenitors to mafosfamide was evaluated with and without amifostine pretreatment, amifostine effectively protected normal myeloid and erythroid progenitors while increasing leukemic cell kill. Thus, amifostine represents a unique agent with promising potential for therapeutic application in hematologic malignancies. Further investigation is needed to define its role in clinical practice.
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PMID:Use of amifostine in hematologic malignancies, myelodysplastic syndrome, and acute leukemia. 1034 62

Abnormalities of chromosome band 13q14 occur in hematologic malignancies of all lineages and at all stages of differentiation. Unlike other chromosomal translocations, which are usually specific for a given lineage, the chromosomal translocation t(12;13)(p12;q14) has been observed in both B-cell and T-cell precursor acute lymphoblastic leukemia (BCP-, TCP-ALL), in differentiated and undifferentiated acute myeloblastic leukemia (AML), and in chronic myeloid leukemia (CML) at progression to blast crisis. The nature of these translocations and their pathologic consequences remain unknown. To begin to define the gene(s) involved on chromosome 13, we have performed fluorescence in situ hybridization (FISH) using a panel of YACs from the region, on a series of 10 cases of acute leukemia with t(12;13)(p12;q14) and 1 case each with "variant" translocations including t(12;13)(q21;q14), t(10;13)(q24;q14) and t(9;13)(p21;q14). In 8/13 cases/cell lines, the 13q14 break fell within a single 1.4 Mb CEPH MegaYAC. This YAC fell immediately telomeric of the forkhead (FKHR) gene, which is disrupted in the t(2;13)(q35;q14) seen in pediatric alveolar rhabdomyosarcoma. Seven of the 8 cases with breaks in this YAC were AML. In 4/13 cases, the 13q14 break fell within a 1.7-Mb YAC located about 3 Mb telomeric of the retinoblastoma (RB1) gene: all 4 cases were ALL. One case of myelodysplastic syndrome exhibited a break within 13q12, adjacent to the BRCA2 gene. These data indicate the presence of myeloid- and lymphoid-specific breakpoint cluster regions within chromosome band 13q14 in acute leukemia.
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PMID:Myeloid- and lymphoid-specific breakpoint cluster regions in chromosome band 13q14 in acute leukemia. 1037 68


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