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)

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 total of 39 patients with thalassaemia major who received multiple blood transfusions were followed up clinically and serologically for 3 successive years (1993, 1994, 1995). They were screened for hepatitis B surface antigen (HBsAg), and antibodies to hepatitis B core (HBc-total), hepatitis C virus (HCV), human immunodeficiency virus I and II (HIV-I/II) and cytomegalovirus (CMV-total). In spite of transfusing HBsAg screened (by third generation ELISA) blood from voluntary non-remunerated donors, there was a significant increase of HBsAg positivity (P < 0.001) from 17.9 per cent (1993) to 35.9 per cent (1994) to 69.2 per cent (1995). This was probably due to the prevalence of undetectable HBV infection in the population. Anti HBc was present in 17 (43.6%), 14 (35.9%) and 16 (41%) patients in consecutive years. An increase in the units of blood transfused was observed every year. Blood units were not screened for anti HCV antibodies but a gradual increase in positivity [9 (23%), 12 (30.7%) and 14 (35.9%) patients] was seen in consecutive years. Anti-HIV antibodies were found in a 16 yr old male who was included in the study without any clinical evidence of AIDS. Anti CMV antibody was found in 30 (76.9%), 32 (82%) and 29 (74.3%) patients without any apparent clinical infection. Some patients showed change of antibody pattern (from negative to positive or vice versa) and a few patients showed inconsistent results probably due to immune modulation. Recruitment of 'repeat' non-remunerated voluntary blood donors may reduce the risk of high HBV transmission.
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PMID:Serological monitoring of thalassaemia major patients for transfusion associated viral infections. 970 94

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

Human parvovirus B19 gene expression from the viral p6 promoter (B19p6) is restricted to primary human hematopoietic cells undergoing erythroid differentiation. We have demonstrated that expression from this promoter does not occur in established human erythroid cell lines in the context of a recombinant parvovirus genome (Ponnazhagan et al. J Virol 69:8096-8101, 1995). However, abundant expression from this promoter can be readily detected in primary human bone marrow cells (Wang et al. Proc Natl Acad Sci USA 92:12416-12420, 1995; Ponnazhagan et al. J Gen Virol 77:1111-1122, 1996). In the present studies, we investigated the pattern of expression from the B19p6 promoter in primary human bone marrow-derived CD34+ HPC undergoing differentiation into myeloid and erythroid lineages. CD34+ cells were transduced with recombinant adeno-associated virus 2 (AAV) vectors containing the beta-galactosidase (lacZ) gene under the control of the following promoters/enhancers: the cytomegalovirus promoter (vCMVp-lacZ), B19p6 promoter (vB19p6-lacZ), B19p6 promoter with an upstream erythroid cell-specific enhancer element (HS-2) from the locus control region (LCR) from the human beta-globin gene cluster (vHS2-B19p6-lacZ), and the human beta-globin gene promoter with the HS-2 enhancer (vHS2-beta p-lacZ). Transgene expression was evaluated either 48 h after infection or following erythroid differentiation in vitro for 3 weeks. Whereas high-level expression from the CMV promoter 48 h after infection diminished with time, low-level expression from the B19p6 and the beta-globin promoters increased significantly following erythroid differentiation. Furthermore, in HPC assays, there was no significant difference in the level of expression from the CMV promoter in myeloid or erythroid cell-derived colonies. Expression from the B19p6 and the beta-globin promoters, on the other hand, was restricted to erythroid cell colonies. These data further corroborate that the B19p6 promoter is erythroid cell-specific and suggest that the recombinant AAV-B19 hybrid vectors may prove useful in gene therapy of human hemoglobinopathies in general and sickle cell anemia and beta-thalassemia in particular.
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PMID:Adeno-associated virus 2-mediated transduction and erythroid lineage-restricted expression from parvovirus B19p6 promoter in primary human hematopoietic progenitor cells. 1064 62

Regular blood transfusions for patients with thalassemia have improved their overall survival although these transfusions carry a definite risk of the transmission of certain viruses. Infection with hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV) leads to complications which contribute to the morbidity and mortality of patients with thalassemia. We analyzed the blood samples taken from 85 transfusion dependent thalassemics receiving treatment at the day care center in Hospital Universiti Kebangsaan Malaysia and found that the seroprevalence rates for HBV, HCV and CMV were 2.4%, 22.4% and 91.8% respectively. None of the patients tested positive for HIV. Those positive for HBV and HCV will require further tests and treatment if chronic hepatitis is confirmed.
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PMID:Seroprevalence of hepatitis B, hepatitis C, CMV and HIV in multiply transfused thalassemia patients: results from a thalassemia day care center in Malaysia. 1077 66

Over the past decade, safety of blood has increased tremendously because of better donor screening as well as testing of the units for transmissible diseases. Component therapy has allowed more effective and economic use of blood. Whole blood is rarely used; instead, packed red cells, platelets, and fresh frozen plasma (FFP) are the most common components used. These products are further refined using irradiation and microaggregate filters and in the case of FFP, viral inactivation. Irradiation prevents transfusion-associated graft versus host disease, whereas microaggregate filters remove leukocytes, decreasing the rates of alloimmunization, febrile nonhemolytic (FNH) reactions, and cytomegalovirus (CMV) transmission. Autologous donation in older children probably provides the safest blood as far as transmissible diseases are concerned. More families request a directed donation and solicit physician help in deciding as well as making arrangements for autologous and/or directed donations. Transfusions of blood and blood components in children are often challenging and require a knowledge of physiologic changes in hemoglobin and blood volumes during different ages. The unique needs of neonates, immunocompromised patients, and patients with congenital hemolytic anemia (sickle cell, thalassemia) mandate that the pediatrician have an appropriate knowledge of transfusion volumes and choice of blood product as well as indications for transfusion.
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PMID:Pediatric transfusion therapy: practical considerations. 1079 77

Between July 2001 and June 2007, 48 consecutive patients with beta-thalassaemia major received allogeneic haematopoietic stem cell transplants (allo HSCT) from human-leukocyte-antigen-matched siblings at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, using standard conditioning regimens. The median age of the patient cohort was 4 years (range, 1-14 years). Thirty-one patients were in risk class I, 11 in class II and six patients were in class III. Engraftment was achieved in all patients. Survival was calculated from the date of transplant to death or last follow-up. Major post-transplant complications encountered were acute graft versus host disease (Ac GvHD) (grades II-IV), 35.4%; chronic GvHD, 8.3%; haemorrhagic cystitis, 12.5%; veno-occlusive disease (VOD) of the liver, 6.2%; bacterial infections, 37.5%; fungal infections, 19%; cytomegalovirus (CMV) infection, 6.2%; herpes infection, 6.2%; and tuberculosis in 2% of patients. Graft rejection was observed in five patients. Three patients received second transplants. Mortality was observed in 20.8% of patients. Major fatal complications included GvHD, VOD, intracranial haemorrhage, septicaema, CMV disease and disseminated tuberculosis. Overall survival and disease-free survival were 79% and 75%, respectively, at 6 years post-HSCT.
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PMID:Bone marrow transplant cure for beta-thalassaemia major: initial experience from a developing country. 1845 5

Seventeen children (mean age: 7.2 years) with genetic defects involving hematopoietic cell production or function, underwent 19 allogeneic stem cell transplantations from HLA identical siblings. Twelve children were suffering from thalassemia major; 2 from Diamond Blackfan anemia; 2 from Fanconi anemia and 1 from congenital dyserythropoietic anemia. The disease free survival was 77% with a mean follow up of 36 months. The major complications were graft versus host disease, veno-occlusive disease, CMV infection and hemorrhage. One case each of thalassaemia major and Fanconi anemia rejected the graft after 1 year and 11 months, respectively. Both patients were successfully transplanted second time from the same donor with some modification in the conditioning regimen and stem cell source.
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PMID:Hematopoietic stem cell transplantation in children with genetic defects. 1921 90

Various risk factors play roles in hemorrhagic cystitis (HC) presentation and grading in hematopoietic stem cell transplant (HSCT) patients. We retrospectively sought to study these risk factors among the clinical and laboratory records of 283 patients transplanted between 1995 and 2007. Most patients underwent a myeloablative conditioning regimen, but some, a nonmyeloablative regimen. The collected results were analyzed using version 16 of SPSS soft ware. HC was observed in 120 patients (42.4%). The most cases of early onset of HC were detected among donor-recipient gender mismatches (P = .086). Significant correlations were detected between late onset of HC with use of bone marrow as a source of stem cells (P = .001), as well as with class II or III of thalassemia as an underlying disease in HSCT recipients (P = .019). Treatment with cyclophosphamide with busulfan or with antithymocyte globulin (ATG) as the transplant conditioning regimen increased the risk of late-onset HC (P = .001 or P = .073, respectively). A significant relationship was diagnosed between lower grades and late onset of HC with anti-human cytomegalovirus gancyclovir or intravenous immunoglobulin (IVIg) therapy (P = .002). The results of this study showed that significant correlations to the incidence and severity of HC clinical symptoms in HSCT patients among allogeneic transplantations, donor-recipient gender mismatches, bone marrow as a stem cell source, class II and III of thalassemia, use of busulfan plus cyclophosphamide plus ATG in the conditioning regimen, graft-versus-host disease (GVHD) symptoms, use of prednisolone and cyclosporine as prophylaxis treatment of GVHD, and gancyclovir and IVIg as antiviral drugs.
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PMID:The role of different risk factors in clinical presentation of hemorrhagic cystitis in hematopoietic stem cell transplant recipients. 1976 68

Fetomaternal microchimerism suggests immunological tolerance between mother and fetus. Thus, we performed primary hematopoietic stem cell transplantation from a mismatched mother to thalassemic patient without an human leukocyte antigen-identical donor. Twenty-two patients with thalassemia major were conditioned with 60 mg/kg hydroxyurea and 3 mg/kg azathioprine from day -59 to -11; 30 mg/m(2) fludarabine from day -17 to -11; 14 mg/kg busulfan starting on day -10; and 200 mg/kg cyclophosphamide, 10 mg/kg thiotepa, and 12.5 mg/kg antithymocyte globulin daily from day -5 to -2. Fourteen patients received CD34(+)-mobilized peripheral blood and bone marrow progenitor cells; 8 patients received marrow graft-selected peripheral blood stem cells CD34(+) and bone marrow CD3/CD19-depleted cells. T-cell dose was adjusted to 2 x 10(5)/kg by fresh marrow cell addback at the time of transplantation. Both groups received cyclosporine for graft-versus-host disease prophylaxis for 2 months after transplantation. Two patients died (cerebral Epstein-Barr virus lymphoma or cytomegalovirus pneumonia), 6 patients reject their grafts, and 14 showed full chimerism with functioning grafts at a median follow-up of 40 months. None of the 14 patients who showed full chimerism developed acute or chronic graft-versus-host disease. These results suggest that maternal haploidentical hematopoietic stem cell transplantation is feasible in patients with thalassemia who lack a matched related donor.
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PMID:Purified T-depleted, CD34+ peripheral blood and bone marrow cell transplantation from haploidentical mother to child with thalassemia. 2015 Apr 20


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