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)

We describe previously transfused patients with sickle cell disease (n = 6) and thalassemia (n = 1) who received nonmyeloablative hematopoietic stem cell transplantation (HCT) to induce stable (full or partial) donor engraftment. Patients were 3 to 20 years (median, 9 years) old. All 7 received pretransplantation fludarabine and 200 cGy of total body irradiation; 2 patients also received horse antithymocyte globulin. Patients received bone marrow (n = 6) or peripheral blood stem cells (n = 1) from HLA-identical siblings, followed by a combination of mycophenolate mofetil and cyclosporine or tacrolimus for postgrafting immunosuppression. After nonmyeloablative HCT, absolute neutrophil counts were <0.5 x 10(9)/L and <0.2 x 10(9)/L for a median of 5 days (range, 0-13 days) and 0 days (range 0-13 days), respectively. A median of 0 (range, 0-9) platelet transfusions were administered. No grade IV nonhematologic toxicities were observed. One patient experienced grade II acute graft-versus-host disease. Two months after transplantation, 6 of 7 patients had evidence of donor chimerism (range, 25%-85%). Independent of red blood cell transfusions, these 6 patients initially had increased total hemoglobin and hemoglobin A concentrations and a reduction of reticulocytosis and transfusion requirements. There were no complications attributable to sickle cell disease during the interval of transient mixed chimerism. However, after posttransplantation immunosuppression was tapered, there was loss of the donor graft, and all patients experienced autologous hematopoietic recovery and disease recurrence. One patient did not engraft. The duration of transient mixed chimerism ranged from 97 to 441 days after transplantation in patients 4 and 6, respectively, and persisted until immunosuppressive drugs were discontinued after transplantation. In summary, the nonmyeloablative HCT regimens described here produced minimal toxicity and resulted in transient donor engraftment in 6 of 7 patients with hemoglobinopathies. Although complications from the underlying hemoglobinopathies did not occur during the period of mixed chimerism, these results suggest that stable (full or partial) donor engraftment after nonmyeloablative HCT is more difficult to achieve among immunocompetent pediatric patients with hemoglobinopathies than among adults with hematologic malignancies, perhaps in part because recipients may have been sensitized to minor histocompatibility antigens of their donor by preceding blood transfusions.
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PMID:Results of minimally toxic nonmyeloablative transplantation in patients with sickle cell anemia and beta-thalassemia. 1293 Nov 21

Cyclosporin A is an essential drug for graft versus host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplantation. Cyclosporin A-associated neurotoxicity is common but poorly understood. The authors herein report on 3 patients receiving transplants for thalassemia. GvHD prophylaxis included cyclosporin A, prednisolone, and methotrexate. All patients developed a status epilepticus with cortical signal alterations located mainly in occipital regions on T2-weighted magnetic resonance imaging. Complete disappearance of the neurologic symptoms and radiographic findings was observed without discontinuing cyclosporin A therapy. Especially, pediatric thalassemics receiving busulfan/cyclophosphamide as preparative regimen seem to be significantly prone to cyclosporin A-associated seizures.
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PMID:Cyclosporin A-associated status epilepticus related to hematopoietic stem cell transplantation for thalassemia. 1463 24

To determine the outcome of children with homozygous beta-thalassemia (beta/beta) and severe beta-thalassemia/hemoglobin E disease (beta/E) who underwent allogeneic peripheral blood stem cell transplantation (PBSCT). The authors conducted a cohort study of allogeneic PBSCT in beta/beta and beta/E patients who had 6/6 or 5/6 HLA-matched sibling donors. All patients received a conditioning regimen including busulfan and cyclophosphamide, except one who received busul-fan and cyclophosphamide plus antithymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A and methotrexate for eight patients and cyclosporine and mycophenolate mofetil for one patient. Donors received G-CSF for 4 days before leukapheresis collections. There were five beta/beta and four beta/E patients in this study. The median age was 9 years (range 1.5-10 years). The median CD34+ cell count was 7.4 x 10(6) cells/kg recipient body weight. All patients achieved neutrophil and platelet engraftment with a median time of 15 days and 21 days respectively. Acute GVHD grade 2 to 4 appeared in four patients (grade 2, n = 3; grade 4, n = 1). Three patients developed chronic GVHD (limited, n = 2; extensive, n = 1). All patients were alive with a median follow-up time of 23 months (range 7-52 months). Neither graft failure nor graft rejection was observed. Allogeneic PBSCT is feasible for children with beta/beta and beta/E, although the incidence of GVHD was apparently high compared with bone marrow transplant study in Thais.
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PMID:Allogeneic peripheral blood stem cell transplantation in children with homozygous beta-thalassemia and severe beta-thalassemia/hemoglobin E disease. 1508 53

To evaluate factors affecting outcome of sibling umbilical cord blood transplantation in Chinese children with thalassemia. The authors conducted a retrospective review of all patients undergoing such transplants in a single institution. Nine children with thalassemia major were diagnosed at a median age of 12 months. They received irregular blood transfusions and suboptimal iron chelation therapy before transplant. Sibling cord blood transplant was performed at a median of 5.5 years (range 3.5-10 years). Six donors were HLA-identical; three were one- to three-antigen mismatched. The mean number of nucleated cells infused was 6.6 x 10(7)/kg (range 3.4-12.7); the mean number of CD34+ cells infused was 3.8 x 10(5)kg (range 0.6-11.7). Seven patients had engraftment of donor cells. The median number of days to achieve a neutrophil count of > 0.5 x 10(9)/L was 19 days (range 10-25); the median number of days to achieve a platelet count of > 20 x 10(9)/L was 33 days (range 19-63). Of the six patients who received HLA-identical transplants, one developed grade 2 and two developed grade 1 acute graft-versus-host disease. Two of the three patients receiving mismatched cord blood did not achieve engraftment, and the other one engrafted but developed grade 4 acute graft-versus-host disease. Two patients subsequently developed secondary graft rejection and had autologous marrow regeneration before day 60 posttransplantation. With a median follow-up of 49 months (range 38-64), eight patients survived but only four were transfusion-independent. Umbilical cord blood transplant appears to have a higher chance of nonengraftment and secondary rejection. A more intensive immunosuppressive conditioning regimen may be required.
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PMID:Umbilical cord blood transplantation in Chinese children with beta-thalassemia. 1512 11

We report the results of allogeneic bone marrow transplantation in 26 female and 37 male patients with beta-thalassaemia major (age range: 2-17 years), performed at Namazi Hospital over the period 1992-99. In all cases, standard conditioning and immunosuppressive regimens were employed. Currently, 50 patients remain thalassaemia-free, 9 of whom have developed chronic graft-versus-host disease. There were 8 deaths among the 13 unsuccessful transplant cases: 4 due to acute uncontrollable graft-versus-host disease, and 4 to non-transplant-related causes such as hypoglycaemia, hypersensitivity reactions and advanced disease. We conclude that allogeneic bone marrow transplantation is an effective therapy for the treatment of beta-thalassaemia major, particularly for patients classified as classes I and II.
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PMID:Bone marrow transplantation in thalassaemia patients in Shiraz, Islamic Republic of Iran. 1533 87

Patients with sickle cell disease (N = 3) and thalassemia (N = 1) with high-risk features received hematopoietic stem cell transplantations (HCT) to induce stable (full or partial) donor engraftment. Patients were 9-30 years of age. Fludarabine, rabbit anti-thymocyte globulin (ATG), and 200 cGy total body irradiation were administered pre-transplant. Patients received bone marrow (N = 3) or peripheral blood stem cells (N = 1) from HLA-identical siblings, followed by mycophenolate mofetil and cyclosporine for post-grafting immunosuppression. Significant lymphopenia, but only moderate neutropenia and thrombocytopenia developed post transplant. No grade IV nonhematological toxicities or acute graft-versus-host disease (GVHD) were observed. At 3 months after transplantation, three of four patients had evidence of donor myeloid chimerism (range, 15-100%). However, after post transplant immunosuppression was discontinued, graft rejection occurred in all but one patient. This patient is now doing well 27 months post transplant with full donor engraftment. One patient died after a second transplant, and another patient experienced a stroke as her graft was being rejected. These results suggest that stable donor engraftment after nonmyeloablative HCT is difficult to achieve among immunocompetent patients with hemoglobinopathies and that new approaches will need to be developed before wider application of this transplantation method for hemoglobinopathies.
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PMID:Hematopoietic stem cell transplantation for multiply transfused patients with sickle cell disease and thalassemia after low-dose total body irradiation, fludarabine, and rabbit anti-thymocyte globulin. 1553 1

We retrospectively evaluated the association between risk factors and acute graft-versus-host disease (aGVHD) among 182 beta thalassemia patients who received 73 peripheral blood stem cell (PBSC) or 109 bone marrow transplants from HLA-identical siblings between 1991 and 2003. The relationship between the severity of aGVHD was examined for the following factors: HLA antigens, age, sex, ABO mismatch, sex mismatch (between recipient and donor), thalassemia class, graft source, transplant cell dose, CD3+ cell dose, conditioning regimen, GVHD prophylaxis, neutrophil engraftment duration, and blood product transfusions using univariate and multivariate analyses. Overall 61 (34%) patients developed clinical grade III or grade IV aGVHD. Univariate analysis confirmed an increased risk of severe aGVHD, which was associated with HLA-A11, HLA-A26, and PBSCT (P=.04, .03, and .03, respectively). The risk of aGVHD was reduced in the presence of HLA-A3 (P=.03). Multivariate analysis confirmed the increased risk of aGVHD associated with HLA-A11 (P=.04), HLA-A26 (P=.01), and a short-period neutrophil recovery (P=.009). In this study HLA-A11, HLA-A26, PBSCT, and a short neutrophil engraftment period were probable risk factors and HLA-A3 a probable protective factor associated with severe aGVHD. These data may provide useful guidelines to choose strategies for treatment and prevention.
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PMID:Are HLA antigens a risk factor for acute GVHD in thalassemic patients receiving HLA-identical stem cell transplantation? 1568 26

We compared the effects of cyclosporin A (CsA) alone as graft-versus-host disease (GVHD) prophylaxis vs cyclosporine with short-course methotrexate (MTX) in patients with thalassemia. In all, 140 patients were enrolled in this study. The first group, of 50 patients, received CsA alone at 3 mg/kg i.v. from day -2 to +5 followed by 12.5 mg/kg p.o., which was tapered according to the patient's condition. The other group, of 90 patients, received the combination of CsA+MTX in which CsA was used with the above-mentioned dose and MTX was on 10 mg/m(2) day +1 and 6 mg/m(2) on days +3 and +6. Incidence of acute GVHD grade II-IV in the CsA group was 78% and in the CsA+MTX group was 52.2%, which was statistically significant (P=<0.001). There were no significant differences in the incidence of chronic GVHD between the two groups. The mean neutrophil engraftment to 0.5 x 10(9)/l was 14 and 23 days for CsA group and CsA+MTX group, respectively (P=<0.001). There were no significant differences for platelet recovery between the two groups. Graft failure in the CsA and CsA+MTX groups was seven (14%) and nine (10%) patients, respectively (P=0.58). Overall survival in the CsA and CsA+MTX groups was 77 and 85%, respectively. Disease-free survival in the CsA and CsA+MTX groups were 58 and 80%, respectively.
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PMID:Cyclosporin A and mini short-term methotrexate vs cyclosporin A as graft-versus-host disease prophylaxis in patients with beta thalassemia major undergoing allogeneic blood and marrow transplantation. 1582 73

We report here the first successful transplant of unrelated umbilical cord blood (UCB) for a child with beta-thalassemia major in Taiwan. A total of 2.48 x 10(5)/kg CD34 cells were infused into a 3(1/2)-year-old girl following conditioning with a pre-transplant cytoreductive/immunosuppressive regimen of busulfan and cyclophosphamide. The absolute neutrophil count first exceeded 0.5 x 10(9)/l on day 17, and the patient became red cell- and platelet-independent on days 34 and 49, respectively. Engraftment of donor hematopoietic populations was documented by cytogenetic analysis, hemoglobin electrophoresis, Southern blot analysis for thalassemia markers, and molecular analysis of short tandem repeats sequences. The patient was ex-thalassemic for more than 15 months post transplant. From this experience, it is postulated that UCB will indeed allow us to expand the available donor pool for recipients with an HLA DRB1 mismatched at one locus and reduce the risk of graft-versus-host disease.
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PMID:Successful unrelated cord blood transplantation in a child with beta-thalassemia major. 1584 Jul 63

Children and adolescents with homozygous beta-thalassemia can be cured by transplantation of normal stem cells after eradication of the thalassemic hematopoietic system. In an attempt to achieve durable engraftment and to minimize regimen-related toxicity (RRT), we have initiated a fludarabine-based pilot protocol not containing cyclophosphamide. Between 1999 and 2004, five children with beta-thalassemia major were enrolled. Median age at transplantation was 11.5 years (range 4-14 years). Three patients received conditioning with fludarabine (30 mg/m2/day x 6), oral busulfan (3.5 mg/kg/day x 4), and ATG rabbit Fresenius (10 mg/kg/day x 4). Two children received intravenous busulfan instead of oral busulfan at a dose of 2 x 1.4 mg/kg/day x 4 days. All children were transplanted with a fresh bone marrow graft from an HLA-identical sibling. Mean cell doses given were 3.7 x 10(8) nucleated cells/kg BW (range 2.4-6.2 x 10(8)/kg). Overall, 5/5 patients achieved donor engraftment and are alive and well. No GVHD exceeding grade I was observed, and 2/5 children maintained donor chimerism at 100%. One patient maintains mixed hematopoietic donor chimerism being between 94 and 97% nearly 5 years after transplant.
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PMID:Complete substitution of cyclophosphamide by fludarabine and ATG in a busulfan-based preparative regimen for children and adolescents with beta-thalassemia. 1599 11


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