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)

The number of treatment modalities for patients with myelodysplastic syndromes (MDS) has increased, but curative options are still limited. For the majority of patients with low risk there is no standard therapy other than appropriate supportive care. In selected patients anabolic steroids, differentiation inducers such as cis-retinoic acid (RA), interferon alpha or gamma have been claimed to be active. Application of growth factors such as granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), and interleukin 3 (IL-3) improves neutrophil count and diminishes frequency of infectious complications, but responses are incomplete and of short duration. Preliminary results of erythropoietin (Epo) applied in therapeutical doses are disappointing, giving an improvement in 15-20% patients. Epo in large doses produces greater and sustained responses, but this treatment is too expensive. Low-dose cytosine arabinoside (Ara-C) induces a response rate in 25-30% patients, however, no survival advantage has been obtained. Addition of RA or GM-CSF produces response rates comparable to Ara-C alone, but also with no prolongation in survival. Bone marrow transplantation (BMT) offers a good chance of long-term disease-free survival if is performed in an early stage of the disease or in complete remission, however, it is limited to patients below 55 years with an HLA-identical donor. Relatively young, high risk patients not eligible for allogeneic BMT should be considered for treatment with intensive polychemotherapy.
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PMID:[Current approaches of treatment for myelodysplastic syndrome (MDS)]. 857 34

FK506 (Tacrolimus) is an immunosuppressive drug that blocks the activation of antigen-specific T lymphocytes, a major component in the pathogenesis of graft-versus-host disease (GVHD). This study was designed to obtain first estimates of the safety and efficacy of FK506 monotherapy in the prevention of GVHD following HLA-identical sibling marrow transplantation. Additionally, a subset of patients was studied to define the pharmacokinetic profile of FK506. Twenty-seven adult patients with leukemia or myelodysplasia received FK506 starting the day before transplant at a dose of 0.04 mg/kg/d by continuous intravenous infusion. When clinically possible, FK506 was given orally in two divided doses starting at five times the daily intravenous dose. FK506 doses were adjusted to target a steady state or trough blood level between 10 to 30 ng/mL. These patients were followed for 6 months posttransplant. All patients had sustained marrow engraftment. Frequently noted adverse events included reversible renal dysfunction, diarrhea, fever, nausea, vomiting, and headache. Most patients required FK506 dose reductions associated with elevated serum creatinine. Two (7%) patients relapsed, one of whom died of the disease within the 6-month study period. A second patient died due to pulmonary mucor. Whole blood pharmacokinetic parameters indicated a half-life of 18.2 +/- 12.1 hours; volume of distribution of 1.67 +/- 1.02 L/kg; clearance of 71 +/- 34 mL/h/kg; and bioavailability of 32 +/- 24%. Eleven of 27 (41%) patients developed grade II to IV acute GVHD, including 10 grade II and one grade III. Six of 24 (25%) evaluable patients developed chronic GVHD. These data indicate that FK506 monotherapy has activity in preventing GVHD. Further studies of FK506 with lower doses to improve tolerability and in combination with other immunosuppressants to augment efficacy are warranted.
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PMID:FK506 (Tacrolimus) monotherapy for prevention of graft-versus-host disease after histocompatible sibling allogenic bone marrow transplantation. 860 72

Allogeneic marrow transplantation using related marrow donors for myelodysplasia (MDS) and acute myeloid leukaemia (AML) arising from MDS results in 35-56% actuarial disease-free survival. Because the use of unrelated donors has not been well-characterized, we report on the outcome of 52 patients with MDS or MDS-related AML consecutively treated between 1987 and 1993 with unrelated donor marrow transplantation. The median age was 33 (range 1-53) years. 33 patients received chemotherapy and total body irradiation and the remainder busulfan and cyclophosphamide. The donors were phenotypically identical at the HLA-A, B and Dw/DRB1 loci in 34 cases and mismatched for one HLA locus in 17 cases and two loci in one case. Marrow was non-T-cell depleted and methotrexate with cyclosporine or FK506 was used for postgrafting immunosuppression. The 2-year disease-free survival, relapse, and non-relapse mortality rates were 38%, 28% and 48%, respectively. One patient who relapsed survives disease-free after withdrawal of immunosuppressive therapy. 16/19 survivors have a performance status of 90-100%. Patients with MDS in transformation or with AML had a significantly higher risk of relapse than patients with less advanced disease (P = 0.0014). Increased non-relapse mortality was significantly associated with higher age, longer disease duration before transplant, lower neutrophil count on admission and, unexpectedly, being seronegative for cytomegalovirus. We conclude that the outcome with transplantation using unrelated donors is similar to reported results using related donors and that a meaningful proportion of eligible patients with an otherwise incurable disease may be cured with this treatment. However, mortality from the transplant procedure is high and future studies should focus on reducing toxicity.
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PMID:Unrelated donor marrow transplantation for myelodysplasia (MDS) and MDS-related acute myeloid leukaemia. 861 76

We undertook an analysis of 2,150 recipients of bone marrow transplant (BMT) at the University of Minnesota to determine the incidence of post-BMT malignant neoplasms (MNs). Fifty-one patients developed 53 MNs, compared with 4.3 expected from general population rates (standardized incidence ratio [SIR], 11.6, 95% confidence interval [CI], 8.2-14.5). These included 22 occurrences of B-cell lymphoproliferative disorder (BLPD), 17 solid nonhematopoietic tumors, 10 myelodysplastic syndromes (MDS), 1 acute myelogenous leukemia (AML), 2 non-Hodgkin's lymphoma (NHL), and 1 Hodgkin's disease (HD). The estimated actuarial incidence of any post-BMT malignancy was 9.9% +/- 2.3% at 13 years posttransplant. The cumulative probability of BLPD plateaued at 1.6% +/- 0.3% by 4 years from transplant and factors independently associated with increased risk included in vitro T-cell depletion of marrow (relative risk (RR) = 11.9, P < .001), HLA mismatch (RR = 8.9, P < .001), use of antithymocyte globulin (ATG) for graft versus host disease (GVHD) prophylaxis (RR = 5.9, P < .001) or in the preparative regimen (RR = 3.1, P = .03) and primary immunodeficiency (RR = 2.5, P = .06). The cumulative probability of developing solid malignancy was 5.6% +/- 2.2% at 13 years from BMT. Malignant melanomas were the most common (SIR, 10.3, 95% CI 1.9 to 25.4). The actuarial incidence of MDS/AML plateaued at 2.1% +/- 0.8% at 9 years and was seen most often in older patients receiving autologous peripheral blood stem cells for HD or NHL. These data document that BMT recipients are at an increased risk of later malignancy, which may add significant morbidity and mortality to the transplant process. Methods for screening and identification of individuals at increased risk need to be addressed in future studies.
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PMID:Malignant neoplasms following bone marrow transplantation. 861 87

We describe two women; one (patient 1) with the diagnosis of acute myeloblastic leukemia (AML), the second (patient 2) with myelodysplastic syndrome (MDS). Both patients underwent allogeneic bone marrow transplantation (BMT), from their HLA-matched brothers. Cytogenetic analysis after the BMT revealed a chromosomal mosaicism in both patients, with the karyotype 46,XX/45,X with no sign of the Y chromosome. The origin of the clone with monosomy X was determined using cytogenetic analysis including heteromorphism and segregation of DNA polymorphic markers. The results led us to the conclusion that in both patients the origin of the 45,X clone was that of the donors. Patient 1 had MDS-like syndrome after the BMT and was stabilized in the chimeric state; to date she is doing well. Patient II also had MDS. However, in her case, it was her primary disease. The graft in patient II was rejected and she died 6 months after BMT.
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PMID:Predominant 45,X,--Y karyotype in donor cells after allogeneic BMT: cytogenetic and molecular analysis. 861 77

Transplantation of hematopoietic precursor cells is an established therapy today in the treatment of hematological malignancies. Cells from different sources [bone marrow, peripheral blood, cord blood] and from different donor types [autologous, syngeneic or allogeneic] are used for transplantation. The aim of autologous transplantation is to apply intensive high-dose chemo-radiotherapy and to shorten the duration of aplasia. Allogeneic cells, in addition, are free of potentially contaminating precursor cells and provide a graft-versus-leukemia effect. For all patients, transplantation should be considered at diagnosis as an integral part of treatment strategy and, depending on risk factors, be performed early in the course of disease. Preferred time for patients with high-risk acute leukemias is first complete remission, second complete remission for standard or low-risk acute leukemias. For chronic myeloid leukemia, allogeneic transplantation should be performed within one year of diagnosis, preferably still in first chronic phase. Autologous transplantation can be considered in a protocol setting. For patients with myelodysplastic syndromes of the FAB subtype refractory anemia or refractory anemia with sideroblasts, allogeneic transplantation is the treatment of choice as initial therapy. For patients with refractory anemia and excess of blasts with or without transformation, remission induction should be attempted before transplantation. Autologous transplantation is the preferred treatment strategy for patients with Hodgkin's and non-Hodgkin's lymphoma, for high-risk patients in first complete remission, for other patients in chemotherapy-sensitive first relapse. For patients with myeloma, transplantation should be considered after first line therapy. Age is the main individual patient's risk factor, transplant-related mortality immediately increases in parallel to increasing age. Autologous transplants are limited to patients below 60 to 65 years, allogeneic HLA-identical sibling transplants to patients below 50 to 55 years, and unrelated transplants to patients below 40 to 45 years. Prerequisites for transplant are availability of a donor, access to a transplant bed, informed consent of patient and donor, as well as financial guarantee. Indications for the different hematological malignancies and the major risk factors are discussed.
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PMID:[Indications for bone marrow and peripheral stem cell transplantation in malignant hematological diseases]. 862 66

Myelodysplastic syndromes [MDS] are clonal disorders of hematopoietic stem cells leading to a deregulation of proliferation and differentiation of the bone marrow cells. Clinically the patients present with symptoms and signs of anemia, thrombocytopenia, and neutropenia. About a third of the patients will develop acute myeloid leukemia. Supportive care is the mainstay of therapy in these mostly elderly patients. G-CSF should only be given in cases of neutropenia and infection, but not prophylactically. Selected patients with severe or transfusion-dependent anemia will respond to treatment with erythropoietin. In advanced MDS aggressive chemotherapy should be considered, while in patients below 50 years of age and an HLA-identical sibling donor allogeneic bone marrow transplantation is the treatment of choice.
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PMID:[Myeloproliferative syndromes]. 862 70

The option of bone marrow transplantation (BMT) significantly improved prognosis of adult patients with hematologic malignancies aged less than 50 years. Allogeneic BMT using the marrow of an HLA-identical family member still provides the most effective method of BMT. Conventional indications for this form of BMT are chronic myeloid leukemia (CML), acute leukemias presenting with adverse risk factors, myelodysplastic syndromes and severe aplastic anemia. If performed early in the disease course (e.g. during the chronic phase of CML or first remission of acute leukemia and MDS) allogeneic BMT cures 50 to 60% of patients. About 20% die of therapy related complications, e.g. graft versus host disease (GvHD), fatal infections or venoocclusive disease of the liver (VOD) and about 20% of patients succumb to relapse of their hematologic disorder. 80% presenting with severe aplastic anemia can be cured, if allogeneic BMT is performed soon after diagnosis without previous immunosuppressive therapy and blood transfusions. BMT with the marrow of a matched unrelated donor or autologous BMT are increasingly used as alternative procedures. A rate of lethal complications as high as 50% hinders rapid extension of BMT with unrelated donors. Therefore, this form of BMT should be restricted to young patients with leukemias, who cannot achieve long-term remission with conventional chemotherapy (in case of acute leukemias) or alpha-interferon (in case of CML). Reconstitution of hematopoiesis is more rapid after peripheral blood stem cell transplantation (PBSCT) compared with autologous BMT. Therefore, PBSCT will replace autologous BMT in most cases. Most favourable results of PBSCT have been reported in patients with malignant lymphomas after relapse or inferior response to primary induction therapy. Due to the higher relapse rate autologous BMT is inferior to allogeneic BMT in leukemia patients. Trials are required to clarify the potential role of myeloablative therapy with stem cell support in the treatment of patients with solid tumors. Many of the preliminary results already published are unsatisfactory and data of larger trials are still lacking. Therefore, BMT or PBSCT cannot be recommended generally for the therapy of patients with solid tumors.
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PMID:[Indications, technique and risks in bone marrow transplantation in adulthood]. 864 1

A cytogenetically normal man with severe aplastic anemia was treated with granulocyte colonystimulating factor (G-CSF), erythropoietin (EPO), cyclosporin A, anti-thymocyte globulin, and interleukin-6 (IL-6), which resulted in a gradual improvement in his neutrophil count and hemoglobin level. After 2 years of the therapy, monosomy 7 was detected during cytogenetic analysis of his bone marrow, which evolved during a period of 5 months into acute myeloblastic leukemia. An in vitro proliferation assay of cytokine responses showed that leukemic blasts were sensitive only to G-CSF, and not to EPO or IL-6. Although allogeneic bone marrow transplantation from an HLA-matched unrelated donor was carried out in the non-remission stage, the patient died of systemic fungal infection on day 25, without any evidence of hematological engraftment. As long-term use of cytokines and immunomo-suppressants in patients with severe aplastic anemia may induce or hasten the onset of a malignant transformation, careful attention must be paid to clonal evolution. Due to the poor prognosis of secondary myelodysplasia and leukemia, allogeneic bone marrow transplantation for such patients must be carried out early in the course of the disease.
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PMID:Transformation of severe aplastic anemia into acute myeloblastic leukemia with monosomy 7. 864 49

Between December 1981 and March 1994, 24 patients with a myelodysplastic syndrome (MDS) underwent allogeneic bone marrow transplantation (BMT) for RA with trilineage dysplasia (n = 4), CMML (n = 1), RAEB (n = 4), RAEBt (n = 9) and AML following MDS (n = 6). Fifteen patients (two RAEB, seven RAEBt and six sAML) received chemotherapy before BMT resulting in complete remission in 10 patients (six RAEBt and four sAML) at the time of BMT. Sixteen marrow donors were genotypically HLA-identical siblings. Remaining donors were other family members (five) or unrelated donors (three). The status of the underlying disease at the time of conditioning was the major factor determining long-term survival. The disease-freed survival of RA patients and patients presenting with RAEB, RAEBt and AML but transplanted in complete remission, was respectively 50 and 60%. On the contrary, none of the nine high-risk MDS patients transplanted with persistent disease, survived. Outcome after transplantation with alternative donors was inferior with one long-term survivor, mainly related to the high incidence of severe acute GVHD and its accompanying infectious complications. Six patients relapsed resulting in an actuarial probability of relapse of 28%. Twelve patients died of transplant-related complications leading to a non-relapse mortality at 5 years of 50%. At present eight patients are alive and disease-free 20 to 132 months post-transplantation resulting in an actuarial 5-year disease-free survival of 40.7%. Our results suggest that allogeneic bone marrow transplantation is a feasible treatment option for patients with MDS. However, improvement in GVHD prophylaxis and supportive care to reduce transplant-treated mortality and improved relapse prevention are imperative.
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PMID:Treatment of patients with myelodysplastic syndromes with allogeneic bone marrow transplantation from genotypically HLA-identical sibling and alternative donors. 873 92


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