Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to determine the relationship between bone marrow (bm) endosteal cells (EDC) and hemopoietic progenitors, we have analyzed the immunophenotype of EDC using various antibodies (Ab) against mesenchymal antigens. The Ab were applied on paraffin sections of normal bm (iliac crest, n=17; talus, n=1; phalanx, n=1), myeloregenerative bm (after chemotherapy), and hematologic disorders (acute myeloid leukemia (AML), n=8; chronic myeloid leukemia (CML), n=6; myelodysplastic syndromes (MDS), n=14; severe aplastic anemia (SAA), n=4; essential thrombocythemia (ET), n=2; idiopathic (primary) osteomyelo-fibrosis (IMF), n=1; polycythemia vera (PV), n=1). In normal bm, EDC were found to react with Ab against vimentin, tenascin, alpha-smooth muscle actin, osteocalcin, CD51, and CD56, but did not react with Ab against CD3, CD15, CD20, CD34, CD45, CD68, or CD117. An identical phenotype of EDC was found in AML, MDS, SAA, ET, IMF, PV, myeloregenerative bm, and peripheral bones lacking active hemopoiesis (talus, phalanx). In patients with CML, EDC reacted with Ab to CD51, but did not react with Ab to CD56. Based on their unique antigen profile, EDC were enriched from normal bm by enzyme digestion and cell sorting. However, these enriched cells (CD56+, CD45-, CD34-) did not give rise to hemopoietic cells under the culture conditions used, i.e. in the presence of the growth factors IGF-1, bFGF, SCF, IL-3, and GM-CSF Together, our data do not support the hypothesis that EDC are totipotent mesenchymal progenitors giving rise to hemopoietic cells.
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PMID:Immunophenotypic characterization of human bone marrow endosteal cells. 1039 6

Cyclosporin A (CsA) is used to prevent rejection in transplantation and to treat autoimmune and hematologic diseases such as aplastic anemia. However, the tumor growth-promoting effect of CsA remains controversial. We report the case of a 24-year-old man who developed acute lymphoblastic leukemia of precursor-T-cell origin after 75 months of treatment with CsA for aplastic anemia. The surface antigen phenotype of his leukemic cells was CD2+, CD3+, CD5+, CD7+, CD4-, CD8-, CD10-, CD20-, CD34-, CD41-, and CD56-. Southern blot analysis revealed a monoclonal rearrangement of T-cell receptor-Jgamma nongermline fragments in HindIII digestion.
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PMID:T-Cell type acute lymphoblastic leukemia following cyclosporin A therapy for aplastic anemia. 1137 36

Post-transplant lymphoproliferative disorder (PTLD) constitutes a serious complication of allogeneic bone marrow transplantation. We describe a case of PTLD in a twenty-six year-old male treated with bone marrow transplantation for aplastic anemia of unknown cause. The patient received unmanipulated marrow graft from his HLA-matched brother. Fifty-one days post transplant he developed progressive enlargement of cervical lymph nodes, followed by hepatosplenomegaly and generalized lymphadenopathy. Polymorphic PTLD was diagnosed basing on the lymph node histopathology, positive EBV detection, flow cytometry and IgH rearrangement studies proving monoclonality (capillary electrophoresis with ABI PRISM 310 Genetic Analyzer). There was no response to anti-CD20 antibody, cessation of immunosuppression, donor lymphocyte infusion and cytostatic therapy. The patient died on the 65th day of multiple organ failure. We discuss the diagnostics and management of PTLD in the setting of bone marrow transplantation.
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PMID:Fatal post-transplant lymphoproliferative disorder following allogeneic bone marrow transplantation for aplastic anemia. 1201 24

Post-transplantation lymphoproliferative disorder (PTLD) is usually an aberrant proliferation of EBV-infected B cells. We report the case of a 31-year-old man with severe aplastic anemia who suffered PTLD 42 days post-BMT from an unrelated donor. At the onset of PTLD, peripheral blood lymphocytes were comprised of 40% CD20(+) cells, 3% CD4(+) cells, and 56% CD8(+) cells. A highly sensitive in situ hybridization (ISH) method was used to detect EBV-encoded small non-polyadenylated RNA 1 (EBER-1) in 33.9% of sorted CD20(+) cells, 4.4% of CD4(+) cells, and 1.4% of CD8(+) cells. Each T-cell fraction contained less than 0.034% of contaminated EBV-infected B cells. Clonal proliferation of both B and T cells was demonstrated by Southern blotting. The patient did not respond to donor leukocyte infusion and died due to deterioration of PTLD. At autopsy, examination of multiple organs revealed B-cell (rather than T-cell) infiltration. This case clearly indicates that EBV can simultaneously infect B and T cells and can induce clonal proliferation of both lymphocyte subsets in severely immunocompromised patients.
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PMID:Epstein-Barr virus (EBV)-associated post-transplantation lymphoproliferative disorder simultaneously affecting both B and T cells after allogeneic bone marrow transplantation. 1266 36

Fibrodysplasia ossificans progressiva (FOP) is a severe, progressive disease of the musculoskeletal system. Muscles, tendons and other connective tissues ossify after minor trauma, and patients often become encased in a second immobile skeleton. There is no known cure or treatment for FOP. It has been found that lymphocytes from FOP patients elaborate excess levels of bone morphogenic protein-4 (BMP-4). Given this, it has been suggested that allogenic bone marrow transplantation (BMT) possibly could be a cure for FOP, and drawn attention to a previously unappreciated case of an FOP patient who had successful BMT for aplastic anemia with apparent short- and medium-term arresting of the FOP disease process. However, BMT has non-trivial associated morbidity and mortality. Here, it is noted that if B cells are found to be the lymphocytes responsible for excess BMP-4 production in FOP, use of Rituximab, a monoclonal anti-CD20 antibody which effectively targets B cells, could be a less permanent and less risky treatment alternative for FOP.
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PMID:Consideration of Rituximab for fibrodysplasia ossificans progressiva. 1528 57

An otherwise healthy 73-year-old female was admitted to our department in 1997 because of easy bruising and a platelet count of 12 x 10(9)/L. The patient was taking no medications. Bone marrow examination revealed erythroid hyperplasia, megakaryocytic hypoplasia, and no sign of malignancy. Chromosome analysis showed a normal karyotype. There was serological evidence of previous infection with parvovirus B19. No antibodies to HBV, HCV, CMV, or EBV were found. ANA and cardiolipin antibodies were not detected. Treatment with prednisolone was without effect, but 3 weeks after i.v. gamma-globulin therapy, the platelet count was normal, 233 x 10(9)/L. Two years later, the patient was readmitted with a platelet count of 11 x 10(9)/L. At this time, treatment with corticosteroids, azathioprine, and gamma-globulin had only a temporary effect, and further therapy was stopped because of side effects. During the next 3 years, the patient developed transfusion-dependent anemia, and her white blood cell count decreased to 1.8 x 10(9)/L. A new bone marrow examination showed aplastic anemia with bone marrow cellularity about 10%. After an intracerebral hemorrhage, the patient accepted treatment with rituximab and received 4 weekly doses of 375 mg/m2. This therapy was followed by an increase in the platelet count to 232 x 10(9)/L, white blood cell count to 6.8 x 10(9)/L, and no more need for blood transfusions. A bone marrow examination 5 months after treatment with rituximab showed hyperplastic myelopoiesis, normoblastic erythropoiesis, and slightly reduced megakaryopoiesis. The use of anti-CD20 monoclonal antibody in aplastic anemia warrants further investigation.
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PMID:Aplastic anemia successfully treated with rituximab. 1631 56

We report a case of Epstein-Barr virus (EBV)-associated lymphoproliferative disease (LPD) following unrelated bone marrow transplantation (UBMT) for severe aplastic anemia treated with a conditioning regimen that included anti-thymocyte globulin (ATG). The patient showed signs of EBV reactivation as early as 34 days after UBMT. Our weekly schedule for EBV monitoring failed to trace rapid changes in EBV viral load and the patient eventually developed EBV-LPD. However, early intervention with monoclonal antibody against CD20, rituximab, stopped the further progression of EBV-LPD. As several recent reports have suggested, the safety and efficacy of rituximab treatment for EBV-LPD is supported by our limited experience with post transplant EBV-LPD.
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PMID:Rapidly progressive Epstein-Barr virus-associated lymphoproliferative disorder unpredictable by weekly viral load monitoring. 2046 79

A 1-yr-old Japanese male infant developed hepatitis-associated aplastic anemia (AA), and anti-thymocyte globulin (ATG) plus cyclosporine A (CsA) was administered without any appreciable effects. Laboratory examination of the patient's serum obtained before therapy revealed various autoantibodies, such as PA-IgG, anti-platelets, anti-single-stranded DNA (ssDNA), and anti-double-stranded DNA (dsDNA) antibodies (Abs) in addition to anti-DRS-1 Abs and anti-moesin Abs, both of which are known to be detectable in approximately 40% of all patients presenting with AA. He was therefore treated with 17.5 mg/kg/d rituximab 5.5 months after ATG/CsA therapy. The same rituximab therapy was repeated three times once a month thereafter. His neutrophil counts started to increase 50 d after the first rituximab therapy and he achieved a complete remission at 16 months after the last rituximab administration. All of the autoantibodies including anti-ssDNA, dsDNA, DRS-1, and moesin became undetectable when he attained the remission. Anti-CD20 monoclonal antibody therapy may be effective in a subset of patients with AA characterized by the presence of autoantibodies.
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PMID:Aplastic anemia successfully treated with rituximab: the possible role of aplastic anemia-associated autoantibodies as a marker for response. 2141 30

Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV-PTLD) is a life-threatening complication following allogeneic hematopoietic stem cell transplantation (HSCT). Monitoring of EBV DNA in high-risk patients with subsequent pre-emptive rituximab treatment is highly effective, and can prevent EBV-associated disease following HSCT. Here, we report a 10-year-old girl with aplastic anemia who developed CD20 negative EBV-PTLD after unrelated bone marrow transplantation that was refractory to rituximab treatment. Similar to other types of lymphoma, the absence of CD20 antigen is likely to be characteristic of rituximab-refractory EBV-PTLD.
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PMID:CD20-negative Epstein-Barr virus-associated post-transplant lymphoproliferative disease refractory to rituximab in a patient with severe aplastic anemia. 2155 14

Paroxysmal nocturnal hemoglobinuria is caused by expansion of a hematopoietic stem cell clone with an acquired somatic mutation in the PIG-A gene. This mutation aborts the synthesis and expression of the glycosylphosphatidylinositol anchor proteins CD55 and CD59 on the surface of blood cells, thereby making them more susceptible to complement-mediated damage. A spectrum of disorders occurs in PNH ranging from hemolytic anemia and thrombosis to myelodysplasia, aplastic anemia and, myeloid leukemias. Aplastic anemia is one of the most serious and life-threatening complications of PNH, and a PNH clone is found in almost a third of the cases of aplastic anemia. While allogeneic bone marrow transplantation and T cell immune suppression are effective treatments for aplastic anemia in PNH, these therapies have significant limitations. We report here the first case, to our knowledge, of PNH associated with aplastic anemia treated with the anti-CD20 monoclonal antibody rituximab, which was associated with a significant reduction in the size of the PNH clone and recovery of hematopoiesis. We suggest that this less toxic therapy may have a significant role to play in treatment of PNH associated with aplastic anemia.
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PMID:Response of paroxysmal nocturnal hemoglobinuria clone with aplastic anemia to rituximab. 2293 17


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