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

The authors report 2 cases of hepatocellular tumour in children treated with anabolic androgens for aplastic anemia. In both cases, the presentation was by a picture of acute abdomen due to hemoperitoneum caused by tumour rupture. In the first case, there was multiple hepatic adenomas necessitating right hepatic lobectomy. The second infant had a single tumour of segment IV treated by simple excision of the tumour. It was a hepatocellular-carcinoma. Follow-up for one year after the initial operation showed no signs of recurrence in both infants. The review of the literature permitted us to find 48 other cases of hepatocellular tumour secondary to androgen therapy. In order of frequency, the hepatocellular-carcinoma is the most frequent and it is usually single; followed by the adenoma which is usually multiple. The other types of tumours are rare: focal nodular hyperplasia, angiosarcoma and cholangiocarcinoma. The hepatocellular-carcinoma and adenoma have some characteristic features: spontaneous regression may occur after withdrawing of androgens; the risk of rupture is important; their evolution is almost always favorable despite of a severe histopathological picture; the alpha-foeto-protein is nearly always negative; and the metastasis are exceptional. The hepatocellular-carcinomas associated with androgen therapy are probably just adenomas with marked dysplasia, but their long term malignant potential remain unknown. Except in case of rupture, surgical intervention should be postponed until the effect of discontinuing the hormonal therapy is assessed, because of the potential for spontaneous regression. The administration of antineoplastic chemotherapeutic agents should be reserved for the tumours showing evidence of malignancy.
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PMID:[Tumors of the liver secondary to androgen therapy. Apropos of 2 cases in children]. 304 Feb 81

Aplastic anaemia is a haematological syndrome in which pancytopenia is due to a depletion, damage of inhibition of hemopoietic stem cells. The pathogenetic factors are still unclear: damage or inhibition of hemopoietic stem cells may be direct or indirect mediated through changes in the cellular humoral environment; evidence is accumulating that in some cases these processes are of autoimmune nature. The prognostic evaluation is based on hematological parameters at diagnosis: severe aplastic anemia (SAA) is defined by the following criteria: neutrophils less than 0.5 X 10(9)/l; reticulocytes less than 0.5 X 10(9)/l and platelets less than 20 X 10(9)/l. Survival rates in children with SAA are poor; the probability of survival at 1 year from diagnosis being 10%. In this form treatment is based on supportive therapy (transfusion and prevention of infections) and on a specific therapy: immunosuppression and/or BMT. BMT is reserved to patient with an HLA identical sibling donor and may be curative in 70-80% of cases. To date the use of antilymphocytoglobulin in SAA has also given satisfactory results with a favorable response in 50-60% of cases.
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PMID:[Bone marrow aplasia]. 352 46

The current use of allogeneic bone marrow transplantation in various hematologic diseases is reviewed. Bone marrow transplantation (BMT) involves infusion of bone marrow from a suitable donor into a properly conditioned recipient. Most BMT is allogeneic, in which the donor is genetically dissimilar but shares some common tissue antigens with the recipient. Almost all patients undergoing allogeneic BMT must be "prepared" with high-dose cyclophosphamide to prevent graft rejection. Most patients with hematologic malignancy also receive total body irradiation to eradicate malignant cells located in areas inaccessible to the systemic circulation. Bone marrow transplantation is the treatment of choice for severe aplastic anemia. In acute myelogenous leukemia, the best results are observed in young patients undergoing BMT in first remission. In acute lymphoblastic leukemia, BMT is usually reserved for patients in second or subsequent remission. Early results are promising in patients with chronic myelogenous leukemia who receive BMT before the accelerated phase or blast crisis of this disease. Allogeneic BMT offers an opportunity for cure in some patients with relapses of Hodgkin's disease or those with certain subtypes of non-Hodgkin's lymphoma. Other diseases for which BMT has been used include severe combined immune deficiency disease, Fanconi's anemia, and multiple myeloma. Complications of BMT include graft failure or rejection, acute and chronic graft-versus-host disease, and infectious complications; late complications, such as restrictive and obstructive pulmonary disease, cataracts, sterility, and secondary malignancies, may also occur. Bone marrow transplantation has become an important treatment for many hematologic diseases, but it will probably remain a treatment reserved for only a few highly specialized centers. If morbidity and mortality caused by transplant-related complications can be reduced, BMT may be offered to older patients and those without HLA-identical sibling donors.
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PMID:Allogeneic bone marrow transplantation in the treatment of hematologic diseases. 388 73

Severe aplastic anemia (SAA) in children has been previously treated with high dose methyl prednisolone (HDMP) with favorable results. We reviewed our experience with intravenous HDMP. Seven children with a diagnosis of SAA confirmed on bone marrow biopsy were treated with 300 mg/kg total dose of intravenous HDMP over a 4 week period. Patients were closely monitored for response and side effects. HDMP was well tolerated except for hyperglycemia in one case. Six of the seven patients showed no response to HDMP. This observation is in stark contrast with previous trials on use of HDMP in SAA. It is concluded that HDMP should be reserved only for patients with milder bone marrow hypoplasia.
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PMID:Treatment of aplastic anemia in children with high dose methyl prednisolone. 898 42

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

The true etiology of severe aplastic anemia is unknown; however, autoimmune activation of T-lymphocytes is one of the potential causes. Stem cell transplantation is regarded as a first line therapy if a fully matched sibling is available. Immunosuppressive therapy is reserved for those who have no matched sibling available for transplant, or for those individuals who fall outside the age range eligible for stem cell transplantation. This case describes a child with a hepatitis-associated severe aplastic anemia for whom a fully matched sibling was available but a transplant was postponed due to active hepatitis. While awaiting bone marrow transplantation, the child acquired a life-threatening aspergillosis infection treated with amphotericin B, granulocyte infusions, and surgical resection of the involved lung. A decision was made to proceed with immunosuppressive therapy while waiting for successful treatment of the fungal infection. Following administration of equine anti-thymocyte globulin (ATG), high dose granulocyte colony stimulating factor (G-CSF), cyclosporine, and steroids, the child had partial hematopoietic reconstitution and is now followed in our clinic. This case demonstrates the extraordinary multidisciplinary care required during the early phases of treating severe aplastic anemia. With such care, recovery is a possibility.
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PMID:Severe aplastic anemia associated with hepatitis and complicated by pulmonary aspergillosis: response to immune suppression and antifungal therapy. 1219 7

Patients with severe aplastic anemia who do not have a human leukocyte antigen (HLA)-identical sibling generally receive immunosuppressive therapy as a first-line therapy, with allogeneic transplantation being reserved for those who do not have an adequate sustained response. Barriers to the use of unrelated-donor transplantation for aplastic anemia include identifying a suitable alternative donor, and risks of graft failure, regimen-related toxicity, and graft-versus-host disease (GVHD). Despite the more than 14 million adults registered with donor registries worldwide, only approximately 50% of patients of Caucasian descent will have an available and fully HLA-matched unrelated adult donor; the rate is substantially lower for non-Caucasians. While umbilical cord blood allows transplantation with greater donor-recipient HLA disparity (without excessive risk of GVHD), risks of graft failure and transplant-related mortality are higher than after transplantation of adult donor grafts. Among patients with a suitable donor, recent changes in pre-transplant conditioning regimens have lowered the risks of organ toxicity and graft failure. Although advances in donor HLA typing and selection practices and improved GVHD prophylaxis have lowered the risk, GVHD remains an important obstacle to long-term symptom-free survival. Despite these limitations, unrelated-donor transplantation offers the best chance of long-term survival for many patients in whom current immunosuppression strategies are not effective. Wider applicability of alternative-donor transplantation for aplastic anemia will require better approaches to prevent graft failure and GVHD and to expand the pool of unrelated-donor grafts. This includes exploring strategies to effectively use alternative grafts such as umbilical cord blood.
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PMID:Alternative donor transplantation for aplastic anemia. 2123 69

Clinical and experimental evidence suggests an immune-mediated pathophysiology in subjects with lower-risk myelodysplastic syndromes (MDS) in whom immunosuppressive therapy may be effective. The novel immunosuppressive strategy of cyclosporine A (CsA) alternately combined with levamisole (LMS; CsA + LMS regimen) can dramatically improve the response rate and survival in aplastic anemia from those of our previous study. Herein, we retrospectively analyzed the data of 89 lower-risk MDS patients who received the CsA + LMS regimen. A total of 63 patients (70.8%) achieved either complete remission or hematological improvement at 4 months. Overall, 51, 41 and 19 patients had erythroid, platelet and neutrophil responses, respectively. Following the CsA + LMS regimen, 6 patients progressed to more advanced MDS at a median interval of 5 months (range, 3-42 months). The estimated 24-month progression-free survival was 82.2% (95% CI, 72.84-91.56) for all patients. Within the median follow-up of 18.5 months (range, 7.0-61.0), 6 patients died. In conclusion, the CsA + LMS regimen alleviated cytopenias and improved survival and freedom from evolution, suggesting that it could be reserved as an alternative choice for lower-risk MDS.
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PMID:Cyclosporine Combined with Levamisole for Lower-Risk Myelodysplastic Syndromes. 2592 50

The improved success of HLA-matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) for severe aplastic anemia (SAA) in recent decades has had an impact on the indications for and timing of this treatment modality. In the absence of a matched sibling donor (MSD), historically MUD HSCT was reserved as an option after failure to respond to at least 2 courses of immunosuppressive therapy (IST) in adults with SAA, but with improved outcomes over time, it is now considered following failure to respond to 1 course of IST. Recent national and international studies and guidelines now recommend upfront MUD HSCT as an option for children for whom an MUD is readily available, because outcomes are similar to those for MSD HSCT. Fludarabine-based conditioning and the use of in vivo T cell depletion with antithymocyte globulin or alemtuzumab has been associated with a reported overall survival (OS) of >85% in adult patients undergoing MUD HSCT. However, the recent introduction of eltrombopag for patients with SAA has transformed the treatment landscape, and there is currently much interest in its use with IST as upfront treatment, which showed a high response rate in an early-phase study. The risks of HSCT, especially graft-versus-host disease (GVHD), need to be carefully balanced against the concerns of IST, namely relapse and later clonal evolution to myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML). In the absence of a current prospective randomized trial comparing these 2 approaches, in this review we examine the evidence supporting consideration of early MUD HSCT in adults with SAA who would have been considered for MSD HSCT but who lack a MSD and for whom an MUD is readily available, especially using an irradiation-free conditioning regimen, with a low risk of GVHD, as another treatment option. This option may be offered to patients to provide them with an informed choice, with the aim of curing disease rather than achieving freedom from disease, relapse-free survival, or OS. Furthermore, understanding the immune signature for the response to IST and the immunologic responses to somatic mutations and clonal progression to MDS/AML may help define the future indications for upfront HSCT and a more precise medical approach to therapy.
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PMID:The Case for Upfront HLA-Matched Unrelated Donor Hematopoietic Stem Cell Transplantation as a Curative Option for Adult Acquired Severe Aplastic Anemia. 3112 54

Treatment options for newly diagnosed aplastic anemia (AA) patient includes upfront allogeneic hematopoietic stem cell transplant (HSCT) or immunosuppressive therapy (IST). With recent advances in supportive care, conditioning regimens and post-transplant immunosuppression the overall survival for HSCT approaches 70-90%. Transplant eligibility needs to be assessed considering age, comorbidities, donor availability and probability of response to immunosuppressive therapy (IST). Upfront HSCT should be offered to children and young adults with matched related donor (MRD). Upfront HSCT may also be offered to children and young adults with rapidly available matched unrelated donor (MUD) who require urgent HSCT. Bone marrow (BM) graft source and cyclosporine (CsA) plus methotrexate (MTX) as graft versus host disease (GVHD) prophylaxis are preferable when using anti-thymocyte globulin (ATG) based conditioning regimens. Alemtuzumab is an acceptable alternative to ATG and is used with CsA alone and with either BM or peripheral blood stem cells (PBSC). Cyclophosphamide (CY) plus ATG conditioning is preferable for patients receiving MRD transplant, while Fludarabine (Flu) based conditioning is reserved for older adults, those with risk factors of graft failure and those receiving MUD HSCT. For haploidentical transplant, use of low dose radiotherapy and post-transplant cyclophosphamide has resulted in a marked reduction in graft failure and GVHD.
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PMID:Allogeneic hematopoietic stem cell transplantation in aplastic anemia: current indications and transplant strategies. 3318 12


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