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)

A 12-year-old girl with nonmetastatic osteogenic sarcoma received treatment with doxorubicin, methotrexate, cisplatin, cyclophosphamide, bleomycin, and dactinomycin. She developed unexplained persistent pancytopenia after completion of chemotherapy. Twenty-three months after the initial diagnosis of osteosarcoma an evaluation revealed a bone marrow pattern consistent with the diagnosis of refractory anemia with excess blasts, and karyotype analysis showed characteristic findings of therapy-related myelodysplasia (loss of chromosomes 5 and 7, as well as 12p and 17p deletions). Bone marrow transplantation from an human leukocyte antigen (HLA)-compatible sibling donor was performed 26 months after the diagnosis of the primary malignancy. Although it is unproven that the alkylating agents administered to this patient were responsible for the myelodysplastic syndrome, careful follow-up of osteosarcoma patients who receive alkylating agents is warranted.
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PMID:Secondary myelodysplastic syndrome complicating therapy for osteogenic sarcoma. 171 91

The translocation (6;9)(p23;q34) is a rare cytogenetic aberration found in patients with acute myeloid leukemia (AML). The clinical, morphologic, and immunophenotypic findings of eight t(6;9) acute leukemias are described. The patients included six men and two women with a mean age of 38.5 years. The leukemias were classified in the French-American-British (FAB) system as AML FAB M2 in four cases and as FAB M4 in four cases. Underlying myelodysplasia was evident in six cases. Bone marrow basophilia was found at presentation in six of the seven cases studied. In two cases with basophilia, darkly stained granules were also present in many eosinophils. In one case, initial basophilia was absent, but was present at relapse, as were eosinophils containing darkly stained granules. Iron stains were available in five cases; four showed increased incorporation and three had ringed sideroblasts. All cases studied by flow cytometry (six at presentation and three at relapse) expressed CD13, CD33, and human leukocyte antigen-DR. At presentation, five cases were CD34 negative. In one case at presentation, a subset of blasts (18%) weakly expressed CD34. Three cases studied at relapse were positive for CD34. Two of seven cases studied were terminal deoxynucleotidyl transferase positive. The t(6;9)(p23;q34) was the only cytogenetic abnormality in five cases. Trisomy 8 was found in two cases, and ring 12 was present in one case. Three patients are living with refractory leukemia 6 weeks to 6 months after initial diagnosis, and three patients died of complications of allogeneic bone marrow transplantation. Only one patient is alive without evidence of disease 3 years after bone marrow transplantation. t(6;9) leukemia is an unusual type of AML that is associated with poor prognosis, early age of onset, basophilia, myelodysplasia with frequent ringed sideroblasts, and a CD34-negative initial phenotype.
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PMID:Acute myeloid leukemia with t(6;9) (p23;q34): association with myelodysplasia, basophilia, and initial CD34 negative immunophenotype. 912 11

Allogeneic peripheral blood stem cell (PBSC) transplant has recently been introduced for the treatment of hematological malignancies. As the data were limited mainly to adult patients, this study aimed to assess the feasibility and safety of this procedure in pediatric patients and donors. Eleven children aged 2-16 years received allogeneic PBSC transplant for acute lymphoblastic leukemia (n = 4), acute myeloid leukemia (n = 1), myelodysplastic syndrome (n = 1), severe aplastic anemia (n = 3), and thalassemia (n = 2). Nine donors were human leukocyte antigen (HLA)-identical siblings and the other two were one antigen mismatched family members. Eight donors were younger than 18 years old (10 months to 17 years). Donors were primed with granulocyte colony-stimulating factor (G-CSF) at 10-16 micrograms/kg for 4-5 days. Aphereses were performed on 1 or 2 consecutive days, and the patients received a mean of 14.4 x 10(8)/kg nucleated cells, 6.9 x 10(6)/kg CD34 cells, and 6.9 x 10(8)/kg T cells. All patients achieved neutrophil counts of > 0.5 x 10(9)/l at a median of 16 days. Nine patients achieved platelet counts of > 20 x 10(9)/l at a median of 13 days. Grade II acute graft vs. host disease (GVHD) occurred in only one patient. Chronic GVHD was not observed in the seven patients with follow-up of more than 3 months. Eight patients remained in continuous complete remission after transplant ranged from 2 to 26 months. Allogeneic PBSC transplant appears safe in pediatric patients and donors, and it seems not to be associated with increase of acute GVHD or chronic GVHD.
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PMID:Allogeneic peripheral blood stem cell transplant in children. 943 21

Sodium phenylacetate (PA) and sodium phenylbutyrate (PB) are aromatic fatty acids that can effect differentiation in a variety of cell lines at doses that may be clinically attainable. We have studied the impact of these two agents on lineage- and differentiation stage-specific antigen expression, proliferation, apoptosis, and clonogenic cell survival in primary cultures of bone marrow samples from patients with myeloid neoplasms at presentation and in remission and from normal volunteers. PB inhibited the proliferation of primary acute myeloid leukemia cells in suspension culture with an ID50 of 6.6 mM, similar to its ED50 in cell lines. At higher doses (>/=5 mM), PB also induced apoptosis. PB inhibited clonogenic leukemia cell growth with a median ID50 of less than 2 mM; however, colony-forming units-granulocyte/macrophage from patients with myelodysplasia and normal volunteers were inhibited with a similar ID50. In contrast to PB, its metabolite PA had no significant effect on either acute myeloid leukemia proliferation or apoptosis. Expression of the monocytic marker CD14 was increased in monocytic and myelomonocytic leukemias in response to PB, and to a lesser extent, PA. Surprisingly, both agents appeared to increase expression of the progenitor cell antigen CD34, as well as the DR locus of the human leukocyte antigen. These data indicate that PB, but not its metabolite PA, has significant cytostatic and differentiating activity against primary neoplastic myeloid cells at doses that may be achievable clinically.
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PMID:Impact of the putative differentiating agents sodium phenylbutyrate and sodium phenylacetate on proliferation, differentiation, and apoptosis of primary neoplastic myeloid cells. 981 60

Allogeneic stem cell transplantation (allo-SCT) is the only treatment with curative potential for patients with myelodysplastic syndrome (MDS). From June 1986 to April 1997, we treated 12 patients with primary MDS (5 men, 7 women, median age, 36.5 years) by allo-SCT. All patients had one or more of the following poor prognostic factors: intermediate-2 or high-risk categories according to the International Prognostic Scoring System; disease progression during follow-up; heavy transfusion requirements and recurrent infections. The median duration from diagnosis of MDS to allo-SCT was 6 months. The preconditioning regimen included total body irradiation combined with either high-dose cytarabine (n = 6), high-dose cyclophosphamide (n = 4), or other regimens (n = 2). Ten patients received bone marrow transplantations and two patients received peripheral blood stem cell transplantations. Prophylaxis for graft-versus-host disease (GVHD) consisted of standard cyclosporin and short-course methotrexate. Acute GVHD of grade 2 or above occurred in 10 patients, while chronic GVHD occurred in seven of the nine patients who survived longer than 6 months after allo-SCT. With a median follow-up of 50 months, all nine patients with human leukocyte antigen (HLA)-matched sibling donors survived. One patient had a relapse 6 months after transplantation and achieved complete remission again with low-dose cytarabine therapy. The three patients receiving allo-SCT from unrelated or HLA-mismatched donors died of grade 3 to 4 acute GVHD and infection within 5 months after transplantation. The estimated disease-free survival at 4 years was 67% (95% confidence interval, 40-93%), and the overall survival was 75% (95% confidence interval, 50-99%). Our data suggest that allo-SCT should be considered early in the clinical course for young MDS patients with a poor prognosis and a matched sibling donor.
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PMID:Allogeneic stem cell transplantation for patients with high-risk myelodysplastic syndrome. 1036 33

Aregeneratoric anemia (AA) occurs rarely after ABO-incompatible allogeneic peripheral blood stem cell transplantation (alloPBSCT), and its management is generally difficult. Here, we present a 31-year-old white man with myelodysplastic syndrome who developed AA after receiving stem cells from his human leukocyte antigen (HLA) identical, but ABO-incompatible sibling. Because his anti-A antibody titers were high, therapy with conventional doses of erythropoietin and prednisolone failed to treat the AA. Following 8 cycles of plasma exchange and higher doses of erythropoietin and prednisolone as well as danazol administration, anti-A titers decreased, and his anemia improved significantly. In conclusion, to treat and obtain a low titer of antibodies in a patient with AA following an ABO-incompatible alloPBSCT, higher doses of erythopoietin and corticosteroids associated with plasma exchange have to be used.
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PMID:Treatment of aregeneratoric anemia following an ABO-incompatible allogeneic peripheral blood stem cell transplantation: a case report. 1042 29

Severe aplastic anemia (SAA) has a poor prognosis in the absence of treatment. Current accepted therapeutic strategies include allogeneic stem-cell transplantation and immunosuppression, both resulting in long-term survival in the majority of patients. Although human leukocyte antigen (HLA)-matched sibling stem-cell transplantation is highly effective, the 25% probability of finding a suitable sibling donor within a family renders this approach available to only a minority of patients. Transplantation using HLA-matched, unrelated donors carries a high risk of treatment failure along with considerable toxicity. While combined immunosuppression with both antithymocyte globulin (ATG) and cyclosporine A (CSA) produces hematologic improvement in most patients, relapse is common. Late evolution of aplastic anemia to other serious hematologic disorders, including paroxysmal nocturnal hemoglobinuria (PNH), myelodysplasia, and acute leukemia, is also a significant problem following treatment with ATG/CSA. Recently, results of immunosuppression in SAA with another potent immunosuppressive agent, cyclophosphamide, were reported in a small number of patients. The overall response rate was similar to that seen with ATG/CSA, but relapse and late clonal disease were not observed during a long period of follow-up. A larger randomized trial comparing sustained hematologic response rates to either conventional immunosuppression with ATG/CSA or high-dose cyclophosphamide and CSA is now underway; secondary end points include response duration, event-free survival, and overall survival. Additionally, a number of protocols designed to test the efficacy of alternative immunosuppressive or immunomodulatory agents are being developed.
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PMID:Cyclophosphamide and other new agents for the treatment of severe aplastic anemia. 1067 15

A prospective multicenter trial of 119 children 1 to 18 years of age with newly diagnosed aplastic anemia (AA) was conducted, comparing treatment using antithymocyte globulin (ATG), cyclosporine (CyA), and danazol (DAN) with or without rhG-CSF (400 microg/m(2), day on days 1-90). All children with very severe AA received rhG-CSF (VSAA group, n = 50). The other children were randomized to receive ATG, CyA, DAN, and rhG-CSF (G-CSF+ group, n = 35) or ATG, CyA, and DAN without rhG-CSF (G-CSF- group, n = 34). After 6 months, the hematologic response rate was 71%, 55%, and 77% in the VSAA group, G-CSF+ group, and G-CSF- group, respectively. There was no difference in the incidence of febrile episodes and documented infections between the G-CSF+ and G-CSF- groups. Bone marrow transplantation (BMT) was attempted in 22 patients in whom initial immunosuppressive therapy (IST; n = 18) failed or in whom a relapse occurred after an initial response (n = 4). Nineteen of the 22 patients are alive and well after a median follow-up of 18 months (range, 3 to 66 months) since BMT. The probability of survival at 4 years was 83% +/- 7% in the VSAA group, 91% +/- 5% in the G-CSF+ group, and 93% +/- 6% in the G-CSF- group. Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) developed in one patient in each of the three groups; the overall risk for MDS/AML was 3% +/- 2% at 4 years. Because the results of IST were encouraging, it is suggested that children with AA receive IST as first-line therapy if there is no human leukocyte antigen-matched sibling donor.
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PMID:Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia. 1097 46

Rejection of a graft after human leukocyte antigen (HLA)-identical stem cell transplantation (SCT) can be caused by recipient's immunocompetent T lymphocytes recognizing minor histocompatibility antigens on donor stem cells. During rejection of a male stem cell graft by a female recipient, 2 male (H-Y)-specific cytotoxic T lymphocyte (CTL) clones were isolated from peripheral blood. One CTL clone recognized an HLA-A2-restricted H-Y antigen, encoded by the SMCY gene. Another CTL clone recognized an HLA-B60-restricted H-Y antigen. In this study UTY was identified as the gene coding for the HLA-B60-restricted H-Y antigen. The UTY-derived H-Y antigen was characterized as a 10-amino acid residue peptide, RESEEESVSL. Although the epitope differed by 3 amino acids from its X-homologue, UTX, only 2 polymorphisms were essential for recognition by the CTL clone HLA-B60 HY. These results illustrate that CTLs against several H-Y antigens derived from different proteins can contribute simultaneously to graft rejection after HLA-identical, sex-mismatched SCT. Moreover, RESEEESVSL-specific T cells could be isolated from a female HLA-B60+ patient with myelodysplastic syndrome who has been treated with multiple blood transfusions, but not from control healthy HLA-B60+ female donors. This may indicate that RESEEESVSL-reactive T cells are more common in sensitized patients.
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PMID:UTY gene codes for an HLA-B60-restricted human male-specific minor histocompatibility antigen involved in stem cell graft rejection: characterization of the critical polymorphic amino acid residues for T-cell recognition. 1104 93

To clarify the role of dose escalation of donor leukocyte infusion (DLI) in the treatment of relapsed leukemia after allogeneic bone marrow transplant (BMT), data from 100 patients were collected from 46 facilities in Japan and analyzed with respect to indications and infused cell dose. Complete remission (CR) was achieved in 11 of 12 (91%) patients with relapsed chronic myelogenous leukemia (CML) in the chronic phase, 3 of 11 (27%) with CML in the acute phase, 8 of 21 (38%) with acute myelogenous leukemia (AML), 6 of 23 (25%) with acute lymphoblastic leukemia (ALL), and 5 of 11 (45%) with myelodysplastic syndrome (MDS). The probability of remaining in CR at 3 years was 82% in CML patients in the chronic phase, but 0% in those with CML in the acute phase, 7% in those with AML, 0% with ALL, and 33% with MDS. Acute graft-versus-host disease (GVHD) (> or = 2) developed in 31 of 89 (34%) patients with human leukocyte antigen identical related donors and was fatal for 7 (7%). A leukocyte dose of 1 x 10(7)/kg of recipient body weight with CML in the chronic phase, 3 x 10(7)/kg of recipient body weight with MDS, and 1 x 10(8)/kg of recipient body weight with acute leukemia appeared to be optimal as an initial dose of DLI. However, the minimal dose of leukocyte developing fatal GVHD was 7 x 10(7)/kg of recipient body weight. These suggest that a relatively small dose of DLI ranging from 1 x 10(7)/kg to 5 x 10(7)/kg of recipient body weight should be administered initially then the infused escalating dose 2 or 3 months later in patients with CML in the chronic phase and MDS. However, a large number of leukocytes around 1 x 10(8)/kg are needed to induce graft versus leukemia effects in patients with acute leukemia despite a 7% fatality in GVHD.
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PMID:Donor leukocyte infusion for Japanese patients with relapsed leukemia after allogeneic bone marrow transplantation: indications and dose escalation. 1125 9


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