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)

Allogeneic BMT is the treatment of choice for patients with MDS or sAML, offering a good chance of long-term disease-free survival if the transplant is performed in an early stage of disease or if the patient receives the transplant in complete remission after polychemotherapy. The transplant is limited to a minority of relatively young patients (aged below 55 years) with an HLA-identical sibling. Allogeneic BMT may also be considered when a closely- or fully-matched unrelated donor has been identified for a young and fit patient. All patients, including those without an excess of blasts, should be conditioned with bone marrow ablative therapy rather than an immune suppressive regime, such as cyclophosphamide alone. For the majority of patients there is no standard therapy other than appropriate supportive care. Relatively young patients below the age of 60 years with poor risk features can be considered for treatment with combination chemotherapy. Maintaining remission after remission-induction chemotherapy is a difficult issue. Patients not eligible for allogeneic BMT could be treated with post-remission chemotherapy or autologous BMT in the framework of prospective studies. Older patients can be considered for treatment with haematopoietic growth factors alone or in combination with differentiating agents such as low-dose Ara-C. This treatment should be delivered within the context of carefully designed and conducted trials.
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PMID:New treatment approaches for myelodysplastic syndrome and secondary leukaemias. 807 47

A 5-year-old girl was diagnosed as having idiopathic thrombocytopenic purpura (ITP) based on symptoms of nasal bleeding and purpura. The platelet count was 35,000/microliters without anemia or leukopenia. Micromegakaryocytes were observed in normocellular bone marrow without dyserythropoiesis or dysgranulopoiesis. She had periosteal fibroma of the rib and atopic dermatitis with elevated serum IgE. Prednisolone and azathioprine were administered but with no response. The cumulative dose of azathioprine was 20 g for 28 months. Nine years after the diagnosis of ITP, she was admitted because of dyspnea and anemia. The white cell count was 26,900/microliters with 17% monocytes. The hemoglobin was 3.9 g/dl and the platelet count was 9,000/microliters. Dyserythropoiesis, dysgranulopoiesis and micromegakaryocytes were observed in hypercellular bone marrow. The chromosome analysis demonstrated 47, XX, +21. She was diagnosed as having chronic myelomonocytic leukemia (CMMoL) and received bone marrow transplantation (BMT) from an HLA-identical sibling conditioned with high-dose busulfan and melphalan. After 17 months of remission, the disease recurred with an abnormal karyotype of 47, XX, +21, 7q+. Despite a second BMT conditioned with high-dose etoposide, cyclophosphamide and total body irradiation, she died of the disease. Refractory thrombocytopenia as a subgroup of myelodysplastic syndrome, rather than ITP, might have preceded the development of CMMoL, with the possibility of azathioprine-induced leukemia.
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PMID:[Chronic myelomonocytic leukemia developed 9 years after the diagnosis of idiopathic thrombocytopenic purpura in a child]. 807 97

Case 1: A 26-year-old female was admitted because of leukocytosis with 43.6% myeloblasts and 33.6% monocytes, and trilineage myelodysplasia (T-MDS) was detected on bone marrow (BM) smear. She was diagnosed as having acute myeloid leukemia (AML) (M4) with T-MDS and was treated with the Japan Adult Leukemia Study Group (JALSG) AML87 protocol. After completion of chemotherapy, leukemic myeloblasts remained minimally and myelodysplastic changes were still detected on BM smear. She underwent allo-BMT from an HLA-identical sibling. The conditioning regimen consisted of busulfan and cyclophosphamide. Cyclosporine A and short term methotrexate were administered prophylactically for graft-versus-host disease (GVHD). She developed slight veno-occlusive disease and pancytopenia, which improved soon. She is surviving free of disease for 37 months from BMT. Case 2: A 41-year-old male was diagnosed as having T-MDS AML (M2) and achieved complete remission with the AML89 protocol, but relapsed soon. He underwent allo-BMT from an HLA-identical sibling. The conditioning regimen and prophylaxis against GVHD were the same as in case 1. He developed mild acute GVHD, pleural effusion and later mild chronic GVHD. These improved soon. He is surviving free of disease for 21 months from BMT. Some reports suggest that intensive chemotherapy can induce CR in 40%-70% of patients with T-MDS AML, but most of them tend to relapse and rarely survive long. We consider that the best strategy for treatment of T-MDS AML is allo-BMT at present, if suitable donors are available.
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PMID:[Allogeneic bone marrow transplantation for two patients with acute myeloid leukemia with trilineage myelodysplasia (T-MDS)]. 813 16

As typical disorders of the elderly, myelodysplastic syndromes (MDSs) are relatively unusual in childhood. Nevertheless, up to 17% of cases of pediatric acute myeloid leukemia may have a preleukemic phase. In young patients, the goal of treatment is eradication of the preleukemic malignant clone and reconstitution of normal hematopoiesis. Allogeneic bone marrow transplantation (BMT) has proved to be capable of this, but the optimal conditioning treatment to achieve eradication remains to be defined. Between May 1989 and June 1993, eight consecutive pediatric patients with MDS received a marrow transplant from an HLA-identical, mixed lymphocyte culture (MLC) non-reactive sibling. Diagnosis at time of presentation was refractory anemia with excess of blasts (RAEB) in two patients, RAEB in transformation (RAEB-t) in three, and juvenile chronic myelogenous leukemia (JCML, the pediatric counterpart of adult chronic myelomonocytic leukemia) in the remaining three children. Conditioning regimen consisted of busulfan, cyclophosphamide and melphalan, three alkylating agents potentially capable of killing also dormant preleukemic stem cells. The preparative regimen was very well tolerated, and all patients engrafted promptly. Six out of eight patients (75%) are alive and well with a median observation time of 20 months (range 8-34 months). Serial karyotype monitoring and molecular analyses have demonstrated a full chimerism of donor cells and the complete disappearance of trisomy 8 detected before transplant in three cases. All surviving patients have a Karnofsky score of 100%. One boy, affected by RAEB-t with monosomy 7 resistant to treatment with low-dose ara-C, relapsed 11 months after BMT, evolved in AML and died from progressive leukemia. Another patient with RAEB died on day +95 after BMT due to interstitial pneumonia of unclear etiology. This study confirms that allogeneic BMT is the treatment of choice in pediatric patients with MDS, and suggests that the employed conditioning regimen is a safe and effective means for eradicating the preleukemic malignant clone. Particularly noteworthy is that the three children with JCML obtained a complete remission and one of them is now a long-term survivor.
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PMID:Busulfan, cyclophosphamide and melphalan as conditioning regimen for bone marrow transplantation in children with myelodysplastic syndromes. 818 40

To evaluate the efficacy of cyclosporine (CYA) regimens in preventing moderate to severe acute graft-versus-host disease (GVHD), 25 patients received immunosuppressive therapy consisting of either CYA and methylprednisolone or CYA and methotrexate (MTX) and the incidence and severity of acute GVHD was compared. These patients had leukemia or myelodysplastic syndrome (MDS) and received bone marrow transplants (BMT) from genotypically HLA-identical siblings. The incidence of grade I-IV acute GVHD in patients on the CYA/methylprednisolone regimen was 64% (7 of 11) compared with 50% (7 of 14) in those on the CYA/MTX regimen. Five of 11 patients with the CYA/methylprednisolone regimen developed moderate to severe acute GVHD (grade II-IV), fatal in 3 cases. No patient on the CYA/MTX regimen developed moderate to severe acute GVHD. Engraftment was faster in the CYA/methylprednisolone group than in the CYA/MTX group. The incidence of toxicity observed soon after BMT was comparable between groups. The CYA/MTX regimen may be superior to the CYA/methylprednisolone regimen for preventing moderate to severe acute GVHD.
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PMID:Cyclosporine combined with methylprednisolone or methotrexate in prophylaxis of moderate to severe acute graft-versus-host disease. 829 53

We treated 93 patients with myelodysplastic syndrome using cyclophosphamide and either total body irradiation (n = 88) or busulfan (n = 5) followed by marrow transplantation. Sixty-five marrow donors were genotypically HLA-identical siblings and 28 were other family members or unrelated donors. Before transplantation all patients had either severe neutropenia or thrombocytopenia or had greater than 5% blasts in the marrow or peripheral blood. The probabilities of disease-free survival, relapse, and non-relapse mortality at 4 years were 41%, 28%, and 43%, respectively. Multivariate analysis revealed that younger age and shorter disease duration were significantly associated with improved disease-free survival and decreased non-relapse mortality. Relapse was seen only in patients with excess blasts at the time of transplantation (51% at 4 years). Patients younger than age 40 and without excess blasts had a 4-year disease-free survival of 62%. This study confirms that allogeneic marrow transplantation can cure some patients with myelodysplasia. Because of the favorable outcome in younger patients without excess blasts, we recommend that transplantation be considered early for patients younger than age 40, before disease progression or development of life-threatening cytopenias. For older patients and those with excess blasts, changes in the transplant procedure will be necessary to improve outcome.
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PMID:Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome. 832 21

To help elucidate the mechanism responsible for graft failure (GF) following a T-cell depleted bone marrow transplant (BMT) from an unrelated donor, five patients (2 chronic myelogenous leukemia, 1 acute undifferentiated leukemia, 2 myelodysplastic syndrome) who experienced this complication were studied. All patients were HLA class I identical with their donors as determined by serology and one-dimensional isoelectric focusing (IEF); two were serologically matched with their donors for HLA class II antigens, whereas three donor-recipient pairs were serologically mismatched for one HLA-DR antigen. All patients received total body irradiation (fractionated, 1,500 rads), VP-16 (750 mg/m2), and cyclophosphamide (120 mg/kg) pre-BMT and antithymocyte globulin (15 mg/kg every other day) and methylprednisolone (2 mg/kg) post-BMT. Three patients experienced primary nonengraftment and two experienced secondary GF. Peripheral blood mononuclear cells obtained from the patients at the time of GF were studied to examine their functional and phenotypic characteristics. Emerging cells were of host origin and were found to be specifically cytotoxic to donor target cells and suppressive to the in vitro growth of donor BM, especially in the cases of primary nonengraftment. Peripheral blood mononuclear cells from these patients were expanded to form T-cell lines (TcLs). The cytotoxic activities of TcLs were tested in the presence of blocking MoAbs directed against various HLA determinants in an attempt to determine if HLA antigens expressed on donor cells were the target for cytotoxicity. The observed cytotoxic activity was blocked by antibodies to HLA-B, -C (1 patient), HLA-DR (1 patient), and HLA-DQ (1 patient). In two cases, antidonor cytotoxicity could not be blocked by MoAb directed against HLA-A, -B, -C, or -DR. Phenotypic characterization of four successfully maintained TcLs showed 100% CD3+ cells with 100% CD4+ (3 patients) or 50% CD4+/50% CD8+ (1 patient). In two of the three patients with 100% CD4+ cells, antidonor cytotoxicity was blocked by an anti-HLA class II MoAb. In contrast to our previous findings in cases of GF following T-cell-depleted HLA nonidentical family member BMT in which host T cells were CD8+ and cytotoxicity was directed against HLA class I antigens, our present study indicates host T cells emerging at the time of GF following BMT from an HLA class I IEF-identical unrelated donor can be of the CD4+ subset and seem to be capable of recognizing antigenic disparities in the HLA class II region.
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PMID:Characterization of cells emerging at the time of graft failure after bone marrow transplantation from an unrelated marrow donor. 833 33

Apheresis was applied in 17 patients with hypoplastic anemia, myelodysplastic syndrome, chronic renal failure and other diseases sensitized to HLA. Apheresis was done for removal of anti-HLA antibodies and prevention of nonhemolytic transfusion reactions. Multiple massive apheresis led to a marked decrease in the antibody level. After the first or second apheresis with removal of 700.0-2000.0 ml of plasma weekly half of the patients showed increasing titres of lymphocytotoxic antibodies.
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PMID:[The phenomenon of the enhancement of the formation of lymphocytotoxic alloimmune antibodies during the use of plasmapheresis]. 840 Jan 87

We report the case of a 14-year-old boy with myelodysplastic syndrome (MDS/RAEB) which developed following Fanconi anemia. The patient received BMT from an HLA-identical sister. Based on the in vitro CY-sensitivity test, 100 mg/kg of CY was administered for conditioning combined with 6 Gy TBI. Mucosal symptoms such as stomatitis, diarrhea and hematuria were severe, but manageable, and engraftment was successful. The patient has maintained normal trilineage hematopoiesis with > 90% Karnofsky score for 30 months with disappearance of a clonal chromosomal abnormality (47,XY, +i(lq)) which was detected before BMT.
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PMID:Successful allogeneic bone marrow transplantation in a case with myelodysplastic syndrome which developed following Fanconi anemia. 852 82

Clonal chromosome and/or hematological abnormalities typically observed in myelodysplastic syndromes (MDS) have been described with increased frequency after autologous bone marrow transplantation (BMT) for lymphoma. We report the case of a woman with chronic myelogenous leukemia (CML) allografted with her HLA-identical sibling who, 5 years after the transplant and under immunosuppressive treatment for chronic graft host disease (GVHD), suffered a cytogenetic relapse associated with a 5q- deletion in the host metaphases. These findings suggest that myelodysplastic changes, possibly related to the chemo-radiotherapy conditioning regimen, may also present after allogeneic BMT.
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PMID:5q- in a case of chronic myelogenous leukemia relapsed after allogeneic bone marrow transplantation. 856 86


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