Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Paroxysmal nocturnal haemoglobinuria (PNH) terminating in acute leukaemia (AL) is an infrequent condition. In several cases, flow cytometric analysis of glycosylphosphatidylinositol anchored membrane proteins such as DAF and CD59/MACIF has suggested the leukaemic cells to be derived from the PNH clone, thereby implicating PNH as a potential preleukaemic disease. In the present paper, we review the data for one patient treated in our hospital and 20 cases reported in the literature from 1969 to 1993. The sex ratio is 1 female/2 males, mean age at diagnosis of PNH was 46 years and the mean interval between the diagnoses of PNH and AL was 53 months. AL type was AML M6 in 8 patients, other types of AML in 12 and ALL in one, with a mean survival of 7.1 months following diagnosis of AL. In all cases analyzed, the PNH phenotype of erythrocytes disappeared with progression of AL, whereas reappearance of this phenotype with complete remission of AL was inconstant. PNH would thus appear to be a potential preleukemic disease. When this disorder terminates in AL, the type is often AML M6, although ALL is also possible. The prognosis of AL in PNH is poor as for other secondary leukaemias. Apart from marrow aplasia, leukaemic transformation is another life threatening complication of PNH which may justify allogeneic bone marrow transplantation (allo-BMT) and potential leukaemic transformation can therefore be an additional argument in favour of allo-BMT when pancytopenia develops in PNH patients.
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PMID:Acute leukaemia in paroxysmal nocturnal haemoglobinuria. Case report and review of the literature. 897 94

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disease of hematopoiesis due to a mutation in the PIG-A gene. Affected patients may demonstrate hemolysis or venous thrombosis, and may develop MDS or aplastic anemia. Successful results may be obtained after conditioning and transplantation from syngeneic or genotypically matched sibling donors. Experience with transplantation from matched unrelated donors (MUD) is limited to eight patients, with only one survivor. We report three patients who underwent successful MUD BMT for PNH. All three patients had severe aplastic anemia (SAA) and PNH at the time of BMT. Unrelated donors were six-antigen HLA-matched (n = 2) or HLA-A mismatched (n = 1). Conditioning consisted of cytarabine, cyclophosphamide, TBI, and ATG. Grafts were T cell-depleted by anti-CD6/CD8 antibodies + complement. Further GVHD prophylaxis consisted of cyclosporine. Patients received 0.7-1.1 x 10(8) nucleated cells/kg and 1.1-2.1 x 10(6) CD34(+) cells/kg. Neutrophil engraftment occurred at 16-21 days. One patient developed grade 1 acute GVHD. Although all three patients experienced significant transplant-related complications, they ultimately resolved and all patients are alive and well 30-62 months after BMT. T cell-depleted MUD BMT is an effective treatment option for PNH-related MDS and SAA.
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PMID:Successful unrelated donor bone marrow transplantation for paroxysmal nocturnal hemoglobinuria. 1131 87

A patient with paroxysmal nocturnal hemoglobinuria (PNH) received a syngeneic peripheral blood stem cell transplant (PBSCT) with high-dose cyclophosphamide (CY) conditioning. He had a reasonable engraftment and complete hematologic recovery. However, at 12 months after PBSCT, he became symptomatic and peripheral blood cells were almost entirely composed of glycosylphosphatidylinositol-anchored proteins deficient cells. This case suggests that high-dose CY may not exert a significant effect on PNH clones in the long term, although it had been effective in allogeneic BMT. In view of the possible autoimmune basis, it seems to be necessary to include other immunosuppressive therapy including ALG in addition to CY.
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PMID:Conditioning with high-dose cyclophosphamide may not be sufficient to provide a long-term remission of paroxysmal nocturnal hemoglobinuria following syngeneic peripheral blood stem cell transplantation. 1175 56

Androgens widely used in the treatment of bone marrow failure syndromes can in rare cases cause hepatic peliosis, a pathological entity characterized by multiple blood-filled cavities in the liver parenchyma. Bone marrow failure syndromes per se are associated with a low coagulation status, which is further magnified by bone marrow transplantation for aplastic anaemia due to deep thrombocytopenia. Both these conditions can cause bleeding; their combination is especially dangerous. We describe two cases of aplastic anaemia due to paroxysmal nocturnal hemoglobinuria and Fanconi syndrome, in which patients developed peliosis hepatis after prolonged treatment with androgens. One patient developed severe subcapsular bleeding, successfully treated with catheterization of the right hepatic artery and embolization of the bleeding site. The second patient bridged over deep post-transplant aplasia with high frequency platelet transfusions, and demonstrated an uncomplicated post-BMT course. We suggest avoiding or interrupting treatment with androgens in patients preparing for BMT.
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PMID:Peliosis hepatis following treatment with androgen-steroids in patients with bone marrow failure syndromes. 1802 86

We evaluated the safety and efficacy of high-dose, posttransplantation cyclophosphamide (Cy) to prevent graft rejection and graft-versus-host disease (GVHD) after outpatient nonmyeloablative conditioning and T cell-replete bone marrow transplantation from partially HLA-mismatched (haploidentical) related donors. Patients with advanced hematologic malignancies (n = 67) or paroxysmal nocturnal hemoglobinuria (n = 1) received Cy 50 mg/kg i.v. on day 3 (n = 28) or on days 3 and 4 (n = 40) after transplantation. The median times to neutrophil (>500/microL) and platelet recovery (>20,000/microL) were 15 and 24 days, respectively. Graft failure occurred in 9 of 66 (13%) evaluable patients, and was fatal in 1. The cumulative incidences of grades II-IV and grades III-IV acute (aGVHD) by day 200 were 34% and 6%, respectively. There was a trend toward a lower risk of extensive chronic GVHD (cGVHD) among recipients of 2 versus 1 dose of posttransplantation Cy (P = .05), the only difference between these groups. The cumulative incidences of nonrelapse mortality (NRM) and relapse at 1 year were 15% and 51%, respectively. Actuarial overall survival (OS) and event-free survival (EFS) at 2 years after transplantation were 36% and 26%, respectively. Patients with lymphoid malignancies had an improved EFS compared to those with myelogenous malignancies (P = .02). Nonmyeloablative HLA-haploidentical BMT with posttransplantation Cy is associated with acceptable rates of fatal graft failure and severe aGVHD or cGVHD.
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PMID:HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. 1848 89

This study was purposed to investigate the expansion and hematopoietic reconstitution capability of CD34(+)CD59(+) cells from patients with paroxysmal nocturnal hemoglobinuria (PNH) by using BALB/c nude mice so as to provide experimental basis for clinical anto-BMT or auto-PBHSCT in patients with PNH. CD34(+)CD59(+) cells were selected from the bone marrow mononuclear cells in normal persons and PNH patients by immunomagnetic positive double sorting and were engrafted sublethally irradiated BALB/c nude mice. The human CD45(+) cells in bone marrow, spleen and peripheral blood of recipient mice were detected by flow cytometry and DNA assay. The results showed that the CD34(+)CD59(+) cells in PNH patient group and normal person group could expanded ex vivo, but ex vivo expansion capability of CD34(+)CD59(+) cells in PNH patient group at day 7 seemed inferior to that in normal control. While CD34(+)CD59(+) cells of PNH patients and normal persons were transfused into recipient mice, the human CD45(+) cells could be detected in bone marrow, spleen and peripheral blood at 6 weeks after transfusion, but there was no statistical difference in counts of CD45 cells between 2 groups. It is concluded that CD34(+)CD59(+) cells from PNH patients may keep characteristics of normal hematopoietic stem cells, and possess ability to expand ex vivo and support hemopoiesis.
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PMID:[Ex vivo expansion of CD34(+)CD59(+) cells from patients with paroxysmal nocturnal hemoglobinuria and their hematopoietic reconstitution capability in irradiated nude mice]. 1854 29

PNH is the most common clonal hematopoietic disorder arising in patients with aAA. PNH is caused by mutations in PIGA, a gene that encodes the catalytic subunit of an enzyme involved in the biosynthesis of GPI anchors, transmembrane glycolipids required for cell surface expression of many proteins. PNH clones likely arise as immune escape mechanisms in aAA by preventing CD1D-restricted T-cell recognition of GPI anchors and GPI-linked autoantigens. Though many patients with aAA treated with IST will develop subclinical PNH clones, only a subset will develop PNH disease, characterized by increased thrombosis, intravascular hemolysis, and potential for severe organ dysfunction. In contrast to IST, allogeneic HSCT for patients with aAA is thought to cure bone marrow aplasia and prevent hematopoietic clonal evolution to PNH. Herein, we present a phenomenon of host-derived PNH disease arising in a patient with aAA many years following MSD-BMT, highlighting the importance of monitoring for this clonal disease in aAA patients with stable mixed donor/recipient chimerism after HSCT. We also provide a literature review for similar occurrences of PNH arising after HSCT.
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PMID:Development of hemolytic paroxysmal nocturnal hemoglobinuria without graft loss following hematopoietic stem cell transplantation for acquired aplastic anemia. 3090 Mar 67