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)

We present the case of a 60-year-old woman with drug-induced aplastic anaemia with a healthy monozygotic twin. Proof of monozygosity was confirmed by studies using the hypervariable minisatellite probe to obtain identical DNA fingerprints in donor and recipient. In vitro co-culture studies performed showed no evidence of a recipient-derived cellular or humoral inhibitor of donor haemopoiesis. Despite this, there was no engraftment following simple marrow infusion without preconditioning. A second syngeneic transplant following high dose cyclophosphamide therapy produced trilineage engraftment but severe thrombocytopenia developed at 3 months, followed later by pancytopenia with generalized marrow failure. Following a third syngeneic transplant with cyclophosphamide and total lymphoid irradiation there was good initial engraftment but graft failure occurred at 14 weeks. A fourth transplant using Campath 1G as preconditioning resulted in no engraftment and the patient died of septicaemia 8 weeks following her fourth transplant. We suggest that the cause of the recurrent aplastic anaemia in this case was a defect of marrow stroma as neither an inhibitor of donor haemopoiesis nor an intrinsic defect of donor stem cell growth could be demonstrated in vitro.
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PMID:Recurrent graft failure following syngeneic bone marrow transplantation for aplastic anaemia. 279 Mar 37

5 patients underwent bone marrow transplantation for severe aplastic anemia (2) and acute leukemia (ALL) in first remission (3). Graft versus host disease prophylaxis was performed by depleting T lymphocytes in the donor bone marrow with the rat monoclonal Campath-1 and autologous complement. In addition, patients received cyclosporin A. Engraftment occurred normally in all 5 patients but 1 patient (SAA) had a late graft failure. Two patients suffered mild degrees of GvHD. All patients are currently in complete remission, one having undergone a second transplantation.
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PMID:[Transplantation of allogeneic bone marrow treated in vitro with Campath-1 monoclonal antibody]. 390 87

CD52 is a phosphatidylinositolglycan (PIG)-anchored glycoprotein (PIG-AP) expressed on normal T and B lymphocytes, monocytes, and the majority of B-cell non-Hodgkin lymphomas. We observed the emergence of CD52- T cells in 3 patients after intravenous treatment with the humanized anti-CD52 monoclonal antibody Campath-1H for refractory B-cell lymphoma and could identify the underlaying mechanism. In addition to the absence of CD52, the PIG-AP CD48 and CD59 were not detectable on the CD52- T cells in 2 patients. PIG-AP-deficient T-cell clones from both patients were established. Analysis of the mRNA of the PIG-A gene showed an abnormal size in the T-cell clones from 1 of these patients, suggesting that a mutation in the PIG-A gene was the cause of the expression defect of PIG-AP. An escape from an immune attack directed against PIG-AP+ hematopoiesis has been hypothesized as the cause of the occurrence of PIG-AP-deficient cells in paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia. Our results support the hypothesis that an attack against the PIG-AP CD52 might lead to the expansion of a PIG-anchor-deficient cell population with the phenotypic and molecular characteristics of PNH cells.
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PMID:Emergence of CD52-, phosphatidylinositolglycan-anchor-deficient T lymphocytes after in vivo application of Campath-1H for refractory B-cell non-Hodgkin lymphoma. 763 56

Campath-1G is an immunosuppressive monoclonal antibody directed against human lymphocytes. Its effectiveness in preventing graft-versus-host disease (GVHD) by simple opsonisation of bone marrow T-cells has been studied in 36 consecutive allografts: in 17 for leukaemia, one for essential thrombocytosis and four for myeloma this was the sole means of GVHD prophylaxis. A further eight patients with aplastic anaemia received 3 months post-transplantation cyclosporin A (CsA) for this purpose whereas in the ninth and tenth the preparative regimen has been modified with this immunosuppressive agent now discontinued. Nucleated cells were harvested and after quantitative recovery of the mononuclear population on the Cobe 2997 separator they were exposed to 20 mg Campath-1G for 30 min at room temperature and then infused. Following standard conditioning, which included total lymphoid irradiation, the median days to reach 0.5 and 1.0 x 10(9)/l neutrophils were respectively 18 (range 9-34) and 28 (range 10-59); to 25 and 100 x 10(9)/l platelets the corresponding times were 17 days (range 5-32 days) and 27 days (range 13-127 days). In all, the day 14 trephine biopsy showed engraftment. At median follow-up of 20 months (range 5-44 months) only one patient has developed possible grade I cutaneous GVHD that responded promptly to corticosteroids: no chronic GVHD or CMV pneumonitis has been encountered. Of those with haematological malignancy transplanted in remission only two with acute leukaemia have relapsed. In aplastic anaemia graft loss initially occurred but this has been overcome by adding Campath-1G in vivo and omitting CsA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:T cell depletion by exposure to Campath-1G in vitro prevents graft-versus-host disease. 1045 57

Allogeneic BMT for severe aplastic anemia is associated with a significant rate of graft rejection, especially in patients who have been previously transfused. We report a child with aplastic anemia who rejected donor marrow twice despite adequate immunosuppression as part of the conditioning therapy but engrafted successfully following combined administration of three modalities of immunosuppression: antithymocyte globulin, total lymphoid irradiation and the monoclonal antibody Campath-1G. Restriction fragment length polymorphism studies > 1 year after BMT show full donor hematopoiesis with no evidence of autologous recovery.
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PMID:Total lymphoid irradiation, anti-lymphocyte globulin and Campath 1-G for immunosuppression prior to bone marrow transplantation for aplastic anemia after repeated graft rejection. 801 59

We report on 24 patients with leukemia (19 pts), congenital disorders (4 pts) or severe aplastic anemia (1 pt) who received bone marrow transplantation from unrelated volunteer donors in 8 Italian Institutions. All the donor/recipient pairs were serologically HLA-A,B,DR matched; MLR was non reactive in 21 out of 24 cases. Preparative regimens were in accord with standards for diagnosis and disease status and included TBI in 15 patients, busulfan in 8, cyclophosphamide alone in one patient with SAA. GvHD prophylaxis consisted of cyclosporine/methotrexate in the majority of cases; 6 patients received additional immunotherapy with anti-lymphocyte globulin and 1 patient in vivo Campath-1G. The bone marrow was T-cell depleted in 2 cases. Acute GvHD grade II-IV occurred in 87% of patients (gr.III-IV: 57%) and was the main cause of death in 8 cases. Six patients (25%) survive with a median follow-up of 9 months, (16% actuarial survival at 3 years). A trend in favour of a better outcome has been found for age < 20 yrs at BMT (33% vs 22%), intensified GvHD prophylaxis (33% vs 22%) and transplants performed in more recent years (31% vs 18%).
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PMID:Bone marrow transplantation from unrelated donors: the Italian experience. GITMO, AIEOP and IBMDR. 844 60

We have evaluated the effect of in vivo Campath-1G on engraftment and GVHD in 23 patients with severe aplastic anaemia transplanted from HLA-identical sibling donors. In 14 patients Campath 1g was given pre-transplant for up to 9 days in an attempt to overcome graft rejection (group 1). In nine patients Campath-1G was given pre-transplant, but also continued post-transplant until day +5 to reduce GVHD (group 2). There were three patients with late graft failure in group I following initial neutrophil engraftment, and four cases of grade II+ GVHD. In group II, two patients had early graft failure (no take), and there were no cases of acute GVHD out of seven evaluable patients. One patient in group I developed chronic GVHD of the liver, and two patients (one in each group) had transient localised chronic GVHD. PCR of short tandem repeats was used to evaluate chimaeric status in 13 patients. Of 11 patients with initial neutrophil engraftment, only one had 100% donor haemopoiesis at all times. The remaining patients had either transient mixed chimaerism or persistence of recipient (< 20%) cells. We conclude that in vivo Campath-1G is associated with a high incidence of mixed chimaerism which tips the balance away from GVHD but towards graft rejection.
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PMID:Campath-1G in vivo confers a low incidence of graft-versus-host disease associated with a high incidence of mixed chimaerism after bone marrow transplantation for severe aplastic anaemia using HLA-identical sibling donors. 873 4

We have analyzed the factors associated with engraftment in 216 recipients of T-cell depleted allogeneic HLA identical sibling marrow transplants using Campath 1 monoclonal antihuman lymphocyte (CD52) antibodies. The patient population consisted of 168 patients with hematologic malignancies, 26 with severe aplastic anemia (SAA), and 22 with hemoglobinopathies, half of whom received marrow treated in vitro with Campath-1M (IgM) and half received marrow with Campath-1G (IgG2b isotype). Patients with durable engraftment had fast hematopoietic recovery: SAA patients reached ANC > 0.5 x 10(6)/L on Day 14; those with leukemia attained ANC > 0.5 x 10(6)/L on Days 18, 17, and 15 for ANLL, ALL and CML respectively, while patients with thalasemia reached ANC > 0.5 x 10(6)/L on Day 21. Overall, 24 patients (17 with leukemia, 4 with SAA, and 3 with thalassemia) suffered graft failure: 10 patients (all grafted with Campath-1M) rejected their grafts, while 14 others (9 grafted with Campath-1M, and 5 with 1G isotype) never engrafted (p = 0.009). Multivariate analysis revealed that neither pretransplant protocol, nor stage of disease or type of antibody used, donor sex and ABO match had any impact on engraftment. The variables favorably associated with engraftment were older age (p = 0.030, RR = 1.016) and CFU-GM number (p = 0.013, RR = 1.001). Patients with ANLL or SAA had a better chance to engraft (p = 0.027, RR = 1.400; and p = 0.003, RR = 2.677, respectively) compared to patients with thalassemia (p = 0.001, RR = 0.551). A higher concentration of Campath-1 antibody in vitro and in vivo adversely affected engraftment. Our data show that satisfactory engraftment can be achieved in patients transplanted with Campath-1 treated marrow allografts. However, despite the measures undertaken to prevent rejection, graft failure still poses a problem. Further pretransplant immunosuppression and perhaps more selective T-cell depletion may reduce the increased graft failure in these patients.
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PMID:Engraftment of marrow allografts treated with Campath-1 monoclonal antibodies. 1039 Jan 97

The increasing success of human leucocyte antigen (HLA)-matched sibling donor (MSD) transplants and combination immunosuppressive treatments have dramatically improved the prognosis of severe aplastic anaemia (SAA) in children and young adults. For patients who lack a MSD there is a significant minority who fail immunosuppressive therapy or suffer from a severe constitutional aplastic anaemia in which immunosuppression would be ineffective. Alternative donor bone marrow transplantation (AD-BMT) has only had limited success in this context. We report the successful outcome of AD-BMT in eight consecutive patients aged 7 months to 15 years, six of whom had acquired aplastic anaemia who had previously failed to respond to immunosuppression, and two of whom had a severe (non-Fanconi) constitutional aplastic anaemia. All eight patients had received multiple red cell and platelet transfusions. We used a new combination of agents for pretransplant conditioning aiming to maximize immunosuppression and minimize toxicity, consisting of Campath-1G or -1H, cyclophosphamide and low-dose total body irradiation (LD TBI) or fludarabine. Toxicity was minimal and all eight children are alive, well and free of disease at a median follow-up of 32 months. We suggest that this approach could facilitate the successful treatment of children with SAA in whom immunosuppressive therapy has failed or is not appropriate.
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PMID:Improved outcome of alternative donor bone marrow transplantation in children with severe aplastic anaemia using a conditioning regimen containing low-dose total body irradiation, cyclophosphamide and Campath. 1155 1

We report the outcome of nine unrelated bone marrow transplants performed for acquired severe aplastic anaemia at a single centre. Six patients received transplants from fully matched donors. Three donor/recipient pairs were mismatched, two at a single allele on high resolution typing. Pre-transplant conditioning consisted of cyclophosphamide and in vivo Campath-1 monoclonal antibody. One patient also received total body irradiation (TBI), and another patient with a coexisting paroxysmal nocturnal haemoglobinuria (PNH) clone received additional busulphan. Cyclosporin A was given for 12 months as prophylaxis against graft-versus-host disease (GVHD). Six of nine patients are alive and transfusion independent with a mean follow-up of 24 months (range: 1.5-94). All six patients who received fully matched transplants are alive; the three who received mismatched grafts died. Four long-term survivors developed autologous haematological recovery following rejection of their grafts. Acute GVHD grade II+ occurred in two patients. We highlight the importance of high-resolution HLA typing, including Cw matching in reducing the incidence of graft rejection and GVHD, resulting in improved survival in our patient group. This study also shows that autologous recovery with long-term survival can occur following non-irradiation conditioning regimens.
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PMID:Autologous recovery following non-myeloablative unrelated donor bone marrow transplantation for severe aplastic anaemia. 1218 7


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