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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

We report severe aplastic anemia of neonatal onset diagnosed in six girls between 1985 and 1995 in a single center. Initial blood cell counts (mean age 3.8 days old, 1 to 15 days) showed thrombocytopenia (six of six), anemia (four of six), and neutropenia (two of six). Neutrophil counts gradually decreased below 0.5 x 10(9)/L, and severe aplastic anemia occurred in three patients by 3 months of age and in all patients by 1 year of age. Lymphocyte number and functions were normal. In all children bone marrow biopsy showed hypocellularity for age and absence of fibrosis, blasts, lymphocytic infiltrates, and cytologic abnormalities. Blood and medullary cytogenetic studies were normal. A search for known constitutional, viral, or toxic causes was negative. Immunosuppressive therapy failed to restore hematopoiesis (three of six). Five children received a bone marrow transplantation at an average age of 9 months (range 2.7 to 29 months). One child is alive and well after a human leukocyte antigen-identical bone marrow transplantation, whereas the other four died. Both congenital onset and the high rate of familial involvement suggest that this condition may be inherited.
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PMID:Severe aplastic anemia of neonatal onset: a single-center retrospective study of six children. 958 Jul 48

Patients with hematologic malignancy or severe aplastic anemia after myeloablative chemo- and radiotherapy were given granulocyte colony-stimulating factor (G-CSF)-mobilized, cryopreserved allogeneic peripheral blood stem cells (PBSCs) from 15 healthy donors who were either human leukocyte antigen (HLA)-matched siblings (n = 13) or haploidentical offspring (2). Polymerase chain reaction-amplified short tandem repeat genotyping was used for early confirmation of donor engraftment after PBSC transplantation (PBSCT). A standard cyclosporine A/methotrexate combination was used to prevent acute graft-versus-host disease (GVHD). All donors, including one in the third trimester of pregnancy, tolerated G-CSF administration and 3-day PBSC harvesting procedures well. Engraftment was prompt for all patients; it was verified using a panel of 12 human polymorphic short tandem repeat loci from bone marrow as early as 7 days posttransplantation. This status was maintained until relapse, when mixed chimerism was detected using the polymerase chain reaction. A minimum resurgence of recipient cells to 1% of the population was required to detect chimerism. The median times to recovery of the absolute neutrophil count to greater than 0.5 x 10(9)/L and the sustained platelet count to greater than 20 x 10(9)/L without transfusion were 10 and 12 days after PBSCT, respectively. Six patients experienced acute GVHD, Grade I in two patients and Grade II in four, including two HLA-haploidentical recipients. Chronic GVHD was noticed in three of the 11 patients who were followed for at least 100 days after PBSCT. Ten patients were still alive at the latest follow-up and have been disease free for a median of 278 days (range 60-671). Five patients died from causes other than graft failure: three from leukemia relapse and two from transplant-related complications. The results confirm that G-CSF can be safely administered to healthy donors and that engraftment after allogeneic PBSCT is fast and durable. Complete chimerism can be detected early by genomic analysis. PBSCT may offer an alternative to bone marrow transplantation.
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PMID:Allogeneic peripheral blood stem cell transplantation and early detection of donor engraftment by polymerase chain reaction. 958 76

In this review we examine the clinical outcomes of patients who have received both bone marrow transplantation (BMT) and solid organ transplantation (SOT) and discuss the possible immunologic consequences of the dual transplants. We collected cases through a comprehensive literature search (MEDLINE database, English literature only) covering the years 1990 through 1997 and correspondence with the International Bone Marrow Transplant Registry. Our study selected case reports of patients who have undergone both bone marrow and solid organ transplants; cases in which bone marrow transplantation was undertaken as an adjunct ot induce or augment donor-specific tolerance in a recipient to the transplanted organ were excluded. Clinical characteristics included patient's demographic information, underlying disorders for each transplant, source of donor organ or tissue, time between transplants, and immunosuppressive regimens used to prevent graft-versus-host disease (GVHD) or graft rejection. Clinical outcomes included patient survival, complications of transplantation, and donor-specific tolerance that was experienced in many cases. Twenty-one cases of SOT after BMT and 7 cases of BMT after SOT were reviewed. Solid organ transplantations included lung, liver, cardiac, and kidney for a variety of BMT-related complications including GVHD, hepatic veno-occlusive disease, chronic renal failure, end-stage pulmonary disease, and severe cardiomyopathy. Bone marrow transplants were performed following SOT for aplastic anemia and hematologic malignancies. Clinical outcomes for patients who received both BMT and SOT were variable and depended on transplant indication and degree of histocompatibility. Prior bone marrow transplantation may tolerize for a subsequent organ transplant from the same donor. Conversely, severe GVHD may follow BMT from human leukocyte antigen (HLA)-matched donors following SOT. The favorable survival in this high-risk group of patients may represent a literature review bias (that is, an undetermined number of unsuccessful cases may not have been reported). Nonetheless, dual transplantation is clearly feasible in selected cases.
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PMID:Outcomes of recipients of both bone marrow and solid organ transplants. A review. 977 24

Allogeneic marrow transplantation offers curative therapy for patients with aplastic anemia. We analyzed retrospective results in 141 patients with severe aplastic anemia who received transplants between 1988 and 1995 from an unrelated volunteer donor identified through the National Marrow Donor Program (NMDP). All patients had failed one or more courses of immunosuppressive therapy. Of the patients, 121 (86%) received a radiation-containing conditioning regimen, and 20 (14%) were given chemotherapy only. Based on serologic human leukocyte antigen (HLA) typing (class I and II), 105 patients (74%) received HLA-matched marrow, and 36 (26%) received marrow mismatched for at least one HLA-A, -B, or -DR antigen. Allele-level (molecular) typing for HLA-DRB1 was available in 108 donor-recipient pairs; 77 patients received DRB -matched and 31 DRB1-mismatched transplants. All but 13% of patients were given a cyclosporine-containing regimen for graft-vs.-host disease (GVHD) prophylaxis, and 45 patients (32%) received marrow that was T cell-depleted. Among 131 evaluable patients, 116 (89%) achieved sustained engraftment and 15 (11%) did not. Among patients with engraftment, acute GVHD of grades II-IV developed in 60 patients (52%) and extensive chronic GVHD in 24 patients at risk (31%). Currently, 51 patients (36%) are surviving at 11-94 months (median 36) after transplantation. All but five have Karnofsky scores > or =80. Patients who received a serologically matched transplant fared somewhat better than did patients given a serologically mismatched transplant p = 0.03). Patients with donors matched by both serology and allele-level DRB1 typing had significantly better survival than DRB1-mismatched patients with 56 vs. 15% surviving at 3 years p = 0.001). Outcome in patients transplanted within 3 years of diagnosis was superior to that among patients transplanted with greater delay. Major causes of death were graft failure, GVHD, and infections. These data suggest that unrelated marrow transplantation offers successful therapy for a proportion of patients who have failed immunosuppressive therapy.
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PMID:Marrow transplantation from unrelated donors for patients with severe aplastic anemia who have failed immunosuppressive therapy. 1046 4

Bone marrow transplantation is an effective therapy for aplastic anemia. Infusion of allogeneic hematopoietic stem cells after high-dose immune suppression restores normal hematopoiesis in most patients and long-term follow-up has confirmed the durability of donor hematopoiesis. However, success of this approach is limited by transplant-related complications, such as graft failure, graft-versus-host disease, and various organ toxicities. Long-term survival rates range from less than 40% to more than 90% in reported series. These rates have improved over the past 20 years due to significant reductions in graft-versus-host disease, interstitial pneumonitis, and early transplant-related mortality. Most long-term survivors have excellent performance status. Late effects such as cataracts, thyroid disorders, joint problems, and therapy-related cancers are observed, especially in patients who received radiation for pretransplant conditioning. Results are best in young patients transplanted with bone marrow from a human leukocyte antigen (HLA)-identical sibling; early transplantation is appropriate in this group. For older patients or those without an HLA-identical related donor, transplants are better reserved for those who fail to respond to immunosuppressive therapy.
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PMID:Current status of allogeneic bone marrow transplantation in acquired aplastic anemia. 1067 9

Bone marrow transplantation (BMT) from a human leukocyte antigen (HLA)-matched sibling is the treatment of choice in children and young adults with severe aplastic anemia (SAA). However, because only 30% of patients have a suitable donor, more aggressive nontransplant immunosuppressive regimens have been used, with reasonable results. The use of mismatched family member and unrelated donors, initially fraught with problems of nonengraftment and severe graft-versus-host disease (GVHD), has improved markedly over the past 10 years. The establishment of donor registries, more precise HLA typing methods, and better supportive care are significant factors in the improved outcomes. The challenge for the future is to assemble the optimal combination of donor selection, conditioning regimen, and GVHD prophylaxis to enhance disease-free survival. These better outcomes should encourage the treating physician to consider stem-cell transplant at an earlier stage of disease.
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PMID:Alternative-donor hematopoietic stem-cell transplantation for severe aplastic anemia. 1067 10

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

The objective of this study was to analyse human leukocyte antigen (HLA) and disease association in common blood diseases [chronic myelogenous leukemia (CML), acute nonlymphocytic leukemia (ANLL), thalassemia and severe aplastic anemia] in Thais. The subjects were patients from the Hematological Clinic, Departments of Medicine and Pediatrics, Ramathibodi Hospital who were referred for HLA typing for bone marrow transplantation (BMT) at the Histocompatibility Laboratory from March 1988 to September 1997. A total of 129 patients had complete HLA-ABC typing. The patients included 45 CML, 40 ANLL, 26 thalassemia (Thal) and 18 severe aplastic anemia (SAA). Of these, 88 patients were typed for HLA class II. The HLA class I (ABC) and II (DR, DQ) typings were performed by microlymphocytotoxicity test. It was found that HLA class I was associated with CML, ANLL and Thal, whereas, HLA class II was associated with SAA. HLA-B8 and HLA-B18 were increased in CML with R.R. values of 12.2 and 3.9, respectively, whereas, HLA-B18 was increased in ANLL with R.R. value of 4.5. In addition, HLA-DR2 and DR3 were increased in SAA with R.R. values of 3.8 and 4.8, respectively. For Thal, HLA-A2 and B46 were increased in Thal in Central Thais with R.R. values of 3.3 and 6.1, respectively, whereas, HLA-B13 was increased in Thal in Northern Thais with R.R. value of 8.5. On the other hand, HLA-B7 was absent in CML. HLA-Cw7 was decreased in CML and SAA, whereas, HLA-DR6 was decreased in ANLL and SAA. Furthermore, HLA-Cw6 was also decreased in CML, whereas, HLA-A33 and Bw4 were decreased in SAA. Although the sample size of each disease was small, the increase of HLA-DR2 was observed in SAA in Thais which was similar to other studies in different ethnic groups. These preliminary data may be useful for further study in HLA and blood disease association.
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PMID:Preliminary study of HLA-ABCDR antigens in CML, ANLL, thalassemia and severe aplastic anemia in Thais. 1086 19

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


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