Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early trials of allogeneic marrow transplantation for homozygous thalassemia were disappointing in patients older than 16, with four of six patients dying early of graft-versus-host disease-related complications, one patient dying at 9 months of infection due to graft failure, and one dying at 6 years of recurrent thalassemia. Three classes of risk could be identified in analyses of results of transplantation in younger patients using the criteria of degree of hepatomegaly, the presence or absence of portal fibrosis, and a history of adequate or inadequate chelation therapy. Patients for whom all three criteria were adverse constituted a very high risk group (class 3) for marrow transplantation. On the basis of these analyses, a conditioning regimen was designed that yielded superior results for class 3 patients under 17 years of age. Most patients older than 16 years presenting for transplantation have disease characteristics that place them in class 3 and, because of the improved results with the new class 3 regimen in younger patients, a study was designed to treat patients older than 16 years using treatment regimens assigned on the basis of disease class. Twenty patients were treated using this protocol and, with a minimum follow-up of 9 months, there have been three early deaths, one patient has recurrent thalassemia, and 16 patients are alive disease-free. The actuarial probabilities of survival, disease-free survival, and rejection are 0.85, 0.80, and 0.05, respectively, with a survival plateau extending from 6 months to 3 years. Marrow transplantation is a reasonable option for adults with progressive thalassemia who have suitable donors.
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PMID:Bone marrow transplantation in adult thalassemia. 152 Aug 85

Over the past 20 years allogeneic bone marrow transplantation has been increasingly utilized in the treatment of acute and chronic leukemias, aplastic anemia, severe forms of thalassemia, immunodeficiency syndromes and metabolic disorders due to a lack of specific enzymes in the monocyte-macrophage system. Despite the overall success of this approach and besides the so-called classic complications arising from the toxicity of the conditioning regimen, occurrence of GVH disease and interstitial pneumonitis, there are other less common complications which have been reported mainly by teams transplanting on a large number of patients. With only a limited experience, concerning 60 patients with transplants between May 1987 and May 1991, we have seen some unusual complications such as toxoplasma encephalitis, myasthenia gravis and aseptic bone necrosis, which may give rise to difficult diagnostic and therapeutic decisions.
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PMID:[Unusual complications of bone marrow transplantation. Experience at the BMT Unit of the Francisco Gentil Portuguese Institute of Oncology, Lisbon Center]. 180 30

Graft-versus-host disease (GVHD) is an immunologically mediated disease occurring most frequently after allogeneic bone marrow transplantation. The aim of this study was to evaluate the contribution of immunohistochemistry in the diagnosis of cutaneous GVHD. Patients transplanted for either leukemia or beta-thalassemia were included in the study. Skin lesions of acute and chronic GVHD were examined both by direct immunofluorescence to detect immunoglobulin deposits and by an avidin-biotin-peroxidase complex technique to evaluate the inflammatory cell infiltrate. Epidermal and dermal fluorescent bodies (IgG and IgM) were frequently found in both acute and chronic GVHD. Most of the infiltrating cells were CD3+ T lymphocytes, with CD8+ cells representing the major cell population invading the epidermis both in acute GVHD and in chronic lichenoid GVHD. A small proportion of the dermal cells were CD14+ macrophages; no B cells were detected. HLA-DR, but not HLA-DQ antigens, were variably expressed by keratinocytes in all cases of acute GVHD and in chronic lichenoid GVHD. KL-1, a monoclonal antikeratin antibody specific for the 56.5 KD acidic polypeptide usually present in suprabasal keratinocytes, stained all epidermal layers, including the basal layer. Langerhans cells were dramatically reduced in number in the epidermis of both acute and chronic lichenoid GVHD. It is concluded that immunohistologic analysis may be supportive in the diagnosis of acute and early chronic lichenoid cutaneous GVHD.
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PMID:Immunohistochemistry of cutaneous graft-versus-host disease after allogeneic bone marrow transplantation. 193 60

We review the first 100 patients receiving a bone marrow transplant as definitive therapy for their underlying disease. These patients were treated between May 1975 and June 1988. Median age was 8 years (range, 1 month to 43 years). Initially, patients were given transplants late in their disease but, as the programme progressed, patients were given transplants earlier and while in remission from their disease. The types of disease considered for treatment by bone marrow transplantation (BMT) expanded from leukaemia, and aplastic anaemia to include neuroblastoma, thalassaemia and immune deficiency. Initially matched donors were used but the source of marrow broadened to include mismatched family members, matched unrelated donors and autologous marrow. Problems after BMT were rejection (11%), acute graft-versus-host disease (GVHD) (45%), interstitial pneumonitis (22%) and relapse (36%). Recurrence of disease was the cause of half the deaths. GVHD was less frequent with the use of methotrexate and cyclosporin, T-cell depleted marrow or matched donors. Interstitial pneumonitis was more commonly associated with the use of mismatched donors and the development of GHVD. Relapse was less likely when BMT was undertaken in the first remission. At least one long-term side effect was seen in all patients treated with total body irradiation whereas no patient treated without irradiation had long-term side effects. The rate of disease free survival of patients at 24 months was 56% for matched, 48% for closely matched, 46% for autologous and 29% for mismatched transplants. For matched transplants mortality within the first 6 months after transplantation decreased from 28% before 1984 to 5% since 1984. Fifty-one patients have survived to June 1989, 49 of them disease free, for periods ranging from 12 to 123 months (median 29 months).
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PMID:Bone marrow transplantation: a review of a programme and its first 100 patients. 223 31

Forty-three patients with hematopoietic disease were treated with intensive chemotherapy and radiotherapy, followed by allogeneic bone marrow transplantation (BMT) from 28 HLA-identical and 10 one to two antigen haploidentical sibling donors and autologous BMT (5 cases). Of these cases, there were 21 with acute nonlymphocytic leukemia (ANLL), 5 with acute lymphocytic leukemia (ALL), 6 with chronic myelocytic leukemia (CML), 2 with Hodgkin's disease (HD), 8 with severe-form aplastic anemia (SAA) and 1 with thalassemia. Complications of BMT were evaluated including acute graft-versus-host disease (GVHD), interstitial pneumonia (IP), veno-occlusive liver disease (VOD), abnormalities of liver function (LF), and alteration of hepatitis B virus (HBV) markers. In thirty-three patients who were followed up for more than 3 months, we found that the incidence of moderate to severe acute GVHD (9.1%) and IP (two cases, 4.7%) were low. No VOD occurred in our series. During the follow-up period, 27 out of 35 patients (77%) had high alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, even up to 1000 U/liter; however, only one patient succumbed to a hepatitis-related complication. Previous hepatic damage from HBV infection before BMT does not appear to increase the risk of posttransplant morbidity and mortality.
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PMID:Complications of bone marrow transplantation in Chinese. 232 72

An increasing number of diseases may be treated successfully by allogeneic bone marrow transplantation (BMT). Initially used for the treatment of immunodeficiency where a cell series or product is replaced, it has now become routine treatment for many forms of leukemia where the transplant provides the rescue after lethal marrow ablation. Recently, diseases such as thalassemia and other inherited metabolic diseases have also been treated by BMT. Formerly the problems of BMT were mainly concerned with graft versus host disease (GVHD) in HLA-matched transplants with HLA-mismatched ones not being possible as GVHD was usually fatal. Since the development of techniques for T cell removal the incidence of GVHD has greatly diminished. T cell removal has also allowed HLA haploidentical mismatched grafts to be performed successfully for immunodeficiency, but there is still a high graft rejection rate in leukemia. This also occurs to a lesser extent with HLA-matched grafts in leukemia. Furthermore, in certain forms of leukemia, particularly chronic granulocytic leukemia, the relapse rate after T cell-depleted BMT is much higher. Trials of better forms of bone marrow conditioning of the recipient are being attempted in order to prevent graft rejection and leukemia relapse. These include total lymphoid irradiation, heavier irradiation and chemotherapeutic regimens, or the use of in vivo monoclonal antibodies such as CAMPATH 1G or anti-LFA-1 (CD11a). In the future, positive selection of stem cells combined with hemopoietic growth factors may allow engraftment without graft versus host disease. This should become the method of choice for autologous transplantation for malignancy. Two monoclonal antibodies directed against the human progenitor cell antigen 1 (HPCA-1) (CD34) have been used for autologous positive stem cell selection in primates and these cells gave full hemopoietic reconstitution in the animals following lethal total body irradiation.
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PMID:Recent advances in bone marrow transplantation. 256 39

Fourteen thalassemia patients (aged 1.6-13.5 years; median age of 6 years) underwent allogeneic bone marrow transplantation (BMT) between March 1984 and May 1987. The preconditioning regimens consisted of oral busulfan, intravenous cyclophosphamide, with or without irradiation. Two of the patients, who received maternal transplants, failed to engraft but experienced autologous recovery. Of the 12 patients who received sibling marrow, two experienced autologous recovery and one developed marrow chimerism. Five patients died of complications of bone marrow transplantation: two died of intracranial hemorrhage, two died of sepsis, and one succumbed to acute graft-versus-host disease associated with cytomegalovirus infection. Six patients engrafted and have been followed for 1-4 years (median of 2.6 years) without intoward events. The overall survival rate was 64% (nine out of 14) with follow-up of 1-4 years. These results demonstrate that bone marrow transplantation can cure thalassemia but infection, graft-versus-host disease, and hemorrhage were major causes of morbidity and mortality in this group of patients. Other factors of importance include the unfavorable influence of engraftment of prior multiple transfusions and sex-mismatched transplantation. In patients who fail to engraft, autologous recovery usually occurs within 2 months of transplantation.
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PMID:Allogeneic bone marrow transplantation for thalassemia in Taiwan: factors associated with graft failure. 261 76

Bone marrow transplantation represents the technical application of basic immunologic principles to the treatment of a variety of neoplastic and allied disorders that originate in the bone marrow. The results have improved during the past 15 years, being most striking for the treatment of the acute and chronic leukemias. The promise of autologous bone marrow transplantation for the treatment of leukemias and solid tumors is awaiting the perfection of techniques for the effective removal of residual neoplastic cells as well as more effective therapy. The use of this technique at its present stage of development for the treatment of benign hematologic disorders, which cause severe morbidity (ie, thalassemia or sickle cell anemia), is controversial, raises serious ethical issues, and cannot be recommended routinely at this time. Complications of bone marrow transplantation such as graft rejection, graft-versus-host disease, and opportunistic infections are discussed.
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PMID:Bone marrow transplantation: a review. 266 96

30 patients with homozygous beta-thalassaemia aged 6 months to 7 years received allogeneic marrow transplants following busulphan (Bu) and cyclophosphamide (Cy). Post-transplant immunosuppression was with methotrexate (MTX) or MTX and Cy. The first 6 patients received 16 mg/kg Bu and 200 mg/kg Cy. 3 died of transplant-related complications and 3 survived without thalassaemia 701-762 days after transplantation. The subsequent 24 patients received 14 mg/kg Bu and 200 mg/kg Cy. 1 died on day 28 without engraftment and 23 survived 64-624 days after transplantation. 19 of the 23 surviving patients are without thalassaemia while 4 patients with initial engraftment became thalassaemic again in 32-46 days and survived 253-624 days after transplantation. The latest death was 50 days after transplantation. The probability of developing grade 2 or greater acute graft versus host disease (GVHD) in patients with sustained engraftment was 23%. 5 patients had chronic GVHD which is still active and causing disability in 3 patients 358, 456, and 477 days after transplantation. The actuarial survival was 86% and the actuarial disease-free survival was 73%.
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PMID:Marrow transplantation for thalassaemia following busulphan and cyclophosphamide. 286 12

The use of busulphan and cyclophosphamide permitted engraftment in 44 of 49 children receiving 'displacement' bone marrow transplants. Three patients who received T-cell-depleted marrow cells from HLA-haploidentical donors failed to engraft and other graft failures were due to inadequate induction dosage. Our standard schedule comprises busulphan 80 mg/m2/day x 4 days (adjusted if necessary to a minimum of 4 mg/kg/day or a maximum of 5 mg/kg/day) followed by cyclophosphamide 2 g/m2/day x 4 days but reduced so as not to exceed 75 mg/kg/day, a maximum dose preferred for patients with full marrows (e.g. those with thalassaemia major). Of 21 recipients of mixed lymphocyte culture (MLC)-negative donor marrow cells with full engraftment at 100 days, there were three late rejections. Of patients transplanted with marrow from MLC-positive donors, one had late rejection after cyclosporin A toxicity had necessitated withdrawal of the drug at day + 146 but six other patients, whose cyclosporin A was stopped routinely 1 year, remain well with full grafts. Ten patients died as a result of graft-versus-host disease. We are therefore exploring new approaches to T-cell depletion and storing autologous marrow for use in the event of graft failure. If necessary, a second transplant with busulphan and cyclophosphamide is best performed at 3 months after full recovery of the host. We conclude that elective transplants can be performed successfully in children with normal immune function without the need for irradiation.
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PMID:Engraftment rates related to busulphan and cyclophosphamide dosages for displacement bone marrow transplants in fifty children. 297 9


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