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)

Based on our experience in the field of fetal liver transplantation (FLT) that we have developed since 1976, we initiated, in 1988, in utero FLT into human fetuses, taking advantage of the immunologic tolerance in young fetuses. The transplants have involved fetuses suffering from various diseases at 12-28 weeks postfertilization, with 2 of the 6 cases eventually resulting in abortion. With the 4 other fetuses, a favorable outcome was observed. Three children are more than 4 years old, and they are alive and well, with evidence of engraftment, reconstitution of immunity, and partial correction of beta-thalassemia. In the fourth case, the fetus is alive and well and birth is expected soon. In utero transplantation of stem cells is a therapy with remarkable advantages: (a) tolerance induction due to immune immaturity of the host, (b) lack of graft-versus-host disease (GVHD) due to immaturity of the donor, (c) ideal isolation of the fetus in the maternal uterus, and (d) optimal environment for donor fetal cell development in the vicinity of host fetal cells and growth factors.
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PMID:In utero transplantation of fetal liver stem cells into human fetuses. 872

Bone marrow transplantation was performed on 14 Chinese patients with transfusion dependent thalassaemia major (n = 13) and haemoglobin H disease (n = 1). The donors were HLA identical siblings. The source of haematopoietic stem cells were from bone marrow (n = 13) and umbilical cord blood (n = 1). The pre-transplant conditioning regimens were (1) busulphan 14 mg/kg and cyclophosphamide 200 mg/kg in two patients; (2) busulphan 16 mg/kg, cyclophosphamide 200 mg/kg and anti-thymocyte globulin 110 mg/kg in five patients; (3) busulphan 16 mg/kg, cyclophosphamide 150 mg/kg and anti-thymocyte globulin 110 mg/kg in seven patients. Graft-versus-host disease prophylaxis was cyclosporin A and methotrexate. All patients engrafted and achieved stable haematopoiesis except the one who underwent the umbilical cord blood transplant, who had autologous marrow recovery. One patient who had stable engraftment rejected the marrow graft and developed aplastic anaemia 4 months after BMT. This patient had a second BMT but rejection recurred again. She eventually died of septicaemia. The other 12 patients were transfusion independent and disease free. The majority have gone back to school or work. Disease-free and actuarial survival probability were 85 and 93%, respectively with a median follow-up time of 30 months (13 to 42 months). Our data suggest that BMT from HLA identical siblings for transfusion dependent thalassaemia gives a high chance of cure with acceptable mortality and morbidity, and that a more immunosuppressive pre-transplant conditioning schedule may be required to prevent rejection.
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PMID:A more immunosuppressive pre-transplant conditioning may be required for Chinese patients with thalassaemia. 880 92

Since 1976, we have performed more than 240 fetal tissue transplants (FLTs) to treat 63 patients with severe immunodeficiency disease (IDD), with inborn errors of metabolism (IEM), or with severe aplastic anemia. In both IDD and IEM, FLT into postnatal recipients has demonstrated beneficial effects (67%) of the patients were either cured or improved significantly). In 1988, we developed in utero FLT into human fetuses, taking advantage of the immunological tolerance of young fetuses. The transplants have involved fetuses suffering from various diseases at 12-28 weeks postfertilization with 2 of the 6 cases eventually resulting in abortion. With the 4 other fetuses, a favorable outcome was observed: 3 children are now more than 4 years old, and are alive and well with evidence of engraftment, reconstitution of immunity, and partial correction of beta zero thalassemia. In the fourth case, the fetus is alive and well and birth is expected soon. In utero transplantation of stem cells is a therapy with remarkable advantages: (a) tolerance induction due to the immune immaturity of the host, (b) lack of graft-versus-host disease due to the immaturity of the donor, (c) ideal isolation of the fetus in the maternal uterus, and (d) an optimal environment for donor fetal cell development in the vicinity of host fetal cells and growth factors.
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PMID:Treatment of human fetuses and induction of immunological tolerance in humans by in utero transplantation of stem cells into fetal recipients. 887 6

Langerhans' cell histiocytosis (LCH) is an uncommon disorder of childhood, formerly referred to histiocytosis X. A significant proportion of children with disseminated disease may undergo progression to a fatal outcome despite chemotherapy with single or multiple agents. Only six cases of LCH treated with BMT have been reported in the literature, including two cases of autologous BMT. Of them, only one was less than 14 years of age. We describe a 4-year-old child whose disseminated, refractory Langerhans' cell histiocytosis was not controlled by front-line monotherapy with etoposide, nor by rescue treatment with combined chemotherapy (vinblastine and etoposide) and immunotherapy (steroids and cyclosporine). Due to the high risk of fatal progressive disease, he underwent bone marrow transplantation from his HLA-identical sister who was heterozigous for beta-thalassemia. On day 24 after transplantation marrow reconstitution was evident, with WBC count 2.3 x 10(9)/L, neutrophil count > 0.5 x 10(9)/L, and platelet count 72 x 10(9)/L. Engraftment was demonstrated by PCR DNA analysis. The patient was discharged on day 25. After transplantation he experienced fever for 11 days and developed signs of grade I cutaneous and intestinal graft-versus-host disease, that was treated with methylprednisolone from days 11 to day 68 (1 mg/kg/day for 18 days, then tapered). He became transfusion independent on day 24; the hemoglobin value was 7.5 g/dL on day 54 and has remained > 10 g/dL since day 200. Features of heterozygous beta-thalassemia have been evident since then. Bone marrow aspirate was normal on days 25 and 94. At the time of this writing he remains in excellent condition, disease and treatment free, 25 months after transplantation. Although limited, current experience suggests that bone marrow transplantation has the potential to cure refractory Langerhans' cell histiocytosis.
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PMID:Bone marrow transplantation for refractory Langerhans' cell histiocytosis. 895 63

We analyzed risk factors in 724 patients evaluable for acute graft-versus-host disease (GVHD) and in 614 patients evaluable for chronic GVHD who had received bone marrow transplantation (BMT) from HLA-identical siblings and/or parents for thalassemia and/or microdrepanocytosis, in a single institution. The overall incidence of grade II-IV and III-IV acute GVHD (aGVHD) was 26.9% and 13.5%, respectively. The cumulative incidence of grade II-IV aGVHD in patients treated with cyclosporine (CsA)/methylprednisolone (MP) or CsA/methotrexate (MTX)/MP was 32% and 17%, respectively (P=0.001). In logistic regression analysis, the risk factors associated with the onset of grade II-IV aGVHD in the entire group of patients were: patient age < or = 4 years (P=0.009), male patient sex (P=0.023), GVHD prophylaxis with CsA/MP or MTX/MP (P=0.000), more than twofold elevated alanine aminotransferase (P=0.001), and patient seropositivity for two to three herpes viruses (P=0.007). In patients treated with CsA/MP, splenomegaly > 2 cm (P=0.042) and donor age > or = 17 years (P=0.034) predicted aGVHD. Risk factors for grade III-IV aGVHD were similar to the risk factors identified for grade II-IV aGVHD. Moreover, moderate and severe liver fibrosis or cirrhosis predicted grade III-IV aGVHD (P=0.018). The incidence of chronic GVHD (cGVHD) was 27.3%. The probability of cGVHD at 2 years after BMT in patients with grade 0, I, II, and III-IV aGVHD was 15%, 32%, 53%, and 54%, respectively. Among patients with absent or grade I-IV aGVHD, prior aGVHD (P=0.000), female donor sex (P=0.000), use of alloimmune female donors for male patients (0.009), and GVHD prophylaxis with CsA/MP or MTX/MP (P=0.003) predicted cGVHD. This data should be considered in clinical management and in future investigations for improvement of immunosuppressive prophylaxis in BMT patients with thalassemia.
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PMID:Graft-versus-host disease after bone marrow transplantation for thalassemia: an analysis of incidence and risk factors. 908 26

A 12-year-old girl with beta-thalassemia hemoglobin E disease received a marrow transplant from her HLA-identical elder brother in July 1995. She had previously been treated by repeated blood transfusions. Conditioning included busulfan 16 mg/kg for 2 days and cyclophosphamide 120 mg/kg for 2 days. Cyclosporine was used for graft-versus-host disease prophylaxis. Spiking fevers occurred on days 6 and 11. Plasmodium falciparum parasites, both trophozoites and gametocytes, were found on the peripheral blood smear. Quinine 30 mg/kg three times a day for 7 days followed by a single dose of mefloquine 25 mg/kg was given. The fever subsided within 2 days and parasitemia cleared in 4 days. After transplant, the girl autologously reconstituted and was followed-up over 15 months.
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PMID:Malaria infection after allogeneic bone marrow transplantation in a child with thalassemia. 920 23

Preparative regimens for marrow allografts in thalassemia have two objectives. One is eradication of diseased marrow and the other suppression of host-versus-graft (HVG) reactions so that the allograft survives. A common regimen to accomplish these goals has combined high-dose busulfan with cyclophosphamide. Postgrafting immunosuppression with cyclosporine/methotrexate has been used for GVHD prevention. Some patients may die from regimen-related toxicity. Overall event-free survival is 75%. Occasional patients have become mixed donor/host hematopoietic chimeras and, yet, disease symptoms have abated. This has raised the possibility of developing safer and less toxic transplant programs that result in stable mixed hematopoietic chimerism. We have devised such a program in dogs consisting of a nonlethal dose of total body irradiation (200 cGy) before and a novel combination of mycophenolate mofetil and cyclosporine after transplant. Mixed donor/host chimerism (> or = 50% donor cells in all lineages) has persisted for > 80 weeks, even though immunosuppression was discontinued after five weeks.
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PMID:Current and future preparative regimens for bone marrow transplantation in thalassemia. 966 49

Allogeneic marrow transplantation is curative therapy for thalassemia, but fewer than 30% of patients have an HLA-identical sibling marrow donor. Selection of alternative donors of hematopoietic stem cells (unrelated individuals or HLA-nonidentical family members) has been aided by establishment of world-wide donor registries now exceeding 3.6 million volunteers and by DNA-based HLA typing to more closely match potential donors. Coupled with improved methods to control graft-versus-host disease and prevent fungal and cytomegalovirus infection, remarkable progress has been made in alternative donor transplantation. For patients 50 years of age or younger, with recently diagnosed chronic myelogenous leukemia (CML) in chronic phase, 1- and 5-year survivals after HLA-A, B, DRB1 identical unrelated marrow transplantation in Seattle are 82% and 74%, respectively. These results are essentially identical to outcome in similar patients given HLA-matched sibling allografts. However, the world-wide number of alternative donor transplants for thalassemia remains limited to date: 4 unrelated and 60 HLA-nonidentical related transplants have been reported to the IBMTR since 1969 with actuarial overall survival of 75%. Using the paradigm of CML, it is likely that access to curative therapy of thalassemia will improve with optimal HLA typing and donor selection early in the course of disease.
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PMID:Unrelated and HLA-nonidentical related donor marrow transplantation for thalassemia and leukemia. A combined report from the Seattle Marrow Transplant Team and the International Bone Marrow Transplant Registry. 966 53

A six-year-old boy with homozygous beta-thalassemia in the favorable class 1 risk group received a bone marrow transplant, from his histocompatible sister. He developed grade IV skin and eye graft-versus-host disease (GVHD) following varicella zoster reactivation. Despite the appropriate prophylactic use of cyclosporin A (CsA), methotrexate (MTX), and prompt treatment with high-dose steroids, GVHD progressed resulting in total body epidermal necrolysis. Anti-IL-2 receptor monoclonal antibodies (anti-IL-2R moAb) in combination with steroids were administered to selectively block the activated T cells. After 27 days of daily administration, followed by 17 doses of alternate-day therapy with anti-IL-2R moAb, the severe skin and eye GVHD resolved. The patient, at two years posttransplant, has full engraftment and immune reconstitution without chronic GVHD (cGVHD). In conclusion, we suggest that in the HLA-genoidentical bone marrow transplantation setting, very severe and steroid-resistant GVHD can be controlled through the use of anti-IL-2 receptor antibodies which specifically block the activated IL-2 receptor expressing T cells.
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PMID:Blockade of acute grade IV skin and eye graft-versus-host disease by anti-interleukin-2 receptor monoclonal antibody in genoidentical bone marrow transplantation setting. 967 28

Eurocord Transplant has established a registry for studying results of cord blood transplant. We have analyzed 78 patients who have received a related CBT between October 1988 and December 1996. The median follow-up time was 29 months (1-99). The median age was 5 years (0.2-20), median weight 19 kg (5-50). Forty-six patients had a malignant disease: 32 acute leukemia (AL), six chronic myeloid leukemia (CML), four myelodysplastic syndrome, two neuroblastoma and two non-Hodgkin lymphoma. Thirty-two patients were transplanted for non-malignant diseases including 17 bone marrow failure syndromes (BMFS), three sickle cell anemia, five thalassemia and seven inborn errors. The donor was an HLA-identical sibling in 60 cases and an HLA-mismatched donor in 18 cases. As conditioning, 36 patients received irradiation and 40 patients received associated busulfan-containing regimens. GVHD prophylaxis consisted of CsA alone in 36 cases, CsA associated with prednisone in eight cases, CsA, methotrexate (Mtx) with or without prednisone in 28 cases and CsA with monoclonal antibody or ATG in four cases. The median number of nucleated cells (NC) infused/kg was 3.9 x 10(7) (0.7-15). One-year survival was 63 +/- 6%. Age, weight, HLA identity and negative cytomegalovirus (CMV) serology in the recipient were significant favorable prognostic factors. Among these 78 patients, the incidence of grade > or = II GVHD was 9% in HLA-matched CBT and 50% in mismatched CBT (P < 0.001). Neutrophil engraftment was associated with age <6 years (P = 0.02) and weight <20 kg (P = 0.02). It was 73% in patients receiving <3.7 x 10(7) nucleated cells (NC) infused/kg and 85% in patients receiving more (P = 0.06). Favorable factors for platelets engraftment were age <6 years (P = 0.03), weight <20 kg (P = 0.002) and HLA identity (P < 0.0001). Related cord blood transplantation offers a good alternative to BMT. Theses results are in favor of freezing cord blood in families in whom a transplant might be indicated.
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PMID:Related cord blood transplants: the Eurocord experience from 78 transplants. Eurocord Transplant group. 971 97


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