The influence of a partially HLA-matched blood transfusion on the disease activity of rheumatoid arthritis.
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OBJECTIVE: Based on the immunosuppressive effects of blood transfusions in organ transplantation, we determined the effect of a blood transfusion on disease activity of rheumatoid arthritis (RA). METHOD: In this double-blind pilot study, 40 patients with active RA were randomly assigned to receive a HLA-DRB1-matched blood transfusion (n = 30) or placebo (n = 10). Disease activity was scored according to the American College of Rheumatology response criteria during 6 months of follow-up. RESULTS: After 1 month and 6 months, respectively, 6 and 16% of patients fulfilled the response criteria in the blood transfusion group compared to none and 30%, respectively, in the placebo group. Following correction for the increase in haemoglobin levels, a majority of the response parameters in the blood transfusion group showed significant improvement compared to the placebo group. CONCLUSION: A DRB1-matched blood transfusion shows improvement of symptoms in several RA patients. Additional studies are required to identify blood transfusion regimens that enhance the potential for therapeutic responses. (+info)
Differential immune responses to alpha-gal epitopes on xenografts and allografts: implications for accommodation in xenotransplantation.
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Xenograft recipients produce large amounts of high-affinity anti-Gal IgG in response to Galalpha1-3Galbeta1- 4GlcNAc-R (alpha-gal) epitopes on the graft. In contrast, ABO-mismatched allograft recipients undergo "accommodation," a state of very weak immune response to ABO antigens. These differences in anti-carbohydrate immune response were studied in alpha1,3galactosyltransferase knock-out mice. Pig kidney membranes administered to these mice elicited extensive production of anti-Gal IgG, whereas allogeneic kidney membranes expressing alpha-gal epitopes elicited only a weak anti-Gal IgM response. Anti-Gal IgG response to xenograft membranes depended on helper T cell activation and was inhibited by anti-CD40L antibody. These T cells were activated by xenopeptides and not by alpha-gal epitopes. Moreover, allogeneic cell membranes manipulated to express xenoproteins also induced anti-Gal IgG response. Xenoglycoproteins with alpha-gal epitopes are processed by anti-Gal B cells. Xenopeptides presented by these cells activate a large repertoire of helper T cells required for the differentiation of anti-Gal B cells into cells secreting anti-Gal IgG. Alloglycoproteins with alpha- gal epitopes have very few immunogenic peptides and fail to activate helper T cells. Similarly, ineffective helper T-cell activation prevents a strong immune response to blood group antigens in ABO-mismatched allograft recipients, thus enabling the development of accommodation. (+info)
Allogeneic bone marrow transplantation for children with acute leukemia: cytoreduction with fractionated total body irradiation, high-dose etoposide and cyclophosphamide.
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Marrow-ablative chemo-radiotherapy followed by hematopoietic stem cell rescue from an allogeneic source improves outcomes for children with high-risk acute leukemia. The first effective pre-transplant preparative regimens consisted of high-dose cyclophosphamide (CY) and total body irradiation (TBI). Subsequent attempts have been made to improve leukemia-free survival, by adding other chemotherapy agents to these agents. In previous clinical studies of total body irradiation, etoposide, cyclophosphamide (TBI-VP-16-Cy) in adult allogeneic bone marrow transplantation, there has been a high incidence of severe regimen-related toxicity. In this study, we investigated the safety and efficacy of this combination in 41 children who received TBI (12-14 Gy), VP-16 (30 mg/kg), and CY (60 mg/kg x 2) and then either matched sibling or alternative donor transplants for acute leukemia. There was only one case of fatal regimen-related toxicity. The estimated 3-year event-free survival for patients with early or intermediate stage disease was 68% (53-88%). The estimated event-free survival of patients with advanced disease was 17% (5-59%). TBI-VP16-CY is safe in pediatric transplantation, and it has good efficacy for transplant recipients with less advanced disease. Bone Marrow Transplantation (2000) 25, 489-494. (+info)
Allogeneic peripheral blood hematopoietic stem cell transplantation: guidelines for red blood cell immuno-hematological assessment and transfusion practice.Societe Francaise de Greffe de Moelle.
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Allogeneic peripheral blood hematopoietic stem cell transplantation (PBSCT) is presently being evaluated in a French randomized study comparing peripheral blood vs bone marrow. Cases of potentially lethal acute hemolysis have recently been reported after allogeneic PBSCT in the presence of a 'minor' ABO incompatibility. Patients were frequently transfused with recipient-compatible and donor-incompatible RBC and usually did not receive methotrexate in addition to cyclosporin A for graft-versus-host disease (GVHD) prophylaxis. In order to homogenize immuno-hematological (IH) assessment and transfusion practices within our protocol, we made proposals to 25 allo-transplant French centers on the following aspects: pre-inclusion IH assessment, IH exclusion criteria, transfusion rules, post-transplant IH surveillance and treatment of hemolysis. Analysis of responses to our proposals led to the elaboration of guidelines which were approved and implemented by the French Bone Marrow Transplantation Society (SFGM). Pre-inclusion IH testing includes mandatory detection and titration of anti-RBC allo-Ab, as well as titration of anti-A and anti-B Ab. The presence in the donor of an anti-A (group A or AB recipients), anti-B (group B or AB recipients) Ab with a titer >1/32 or the presence of allo-Ab against Rh, Kell, Fya, Fyb, Jka, Jkb, Ss Ag present on recipient RBC is an exclusion criterion for the protocol. ABO and RhD compatibility of RBC blood products with both HSC donor and recipient is mandatory. A similar compatibility is also required for Rh (other than D) and Kell Ag. If not possible, compatibility of RBC blood products with the HSC donor is mandatory. Lastly, guidelines regarding post-transplantation IH follow-up as well as acute hemolysis treatment have been elaborated. The implementation of these guidelines should contribute to enhancing the quality of transfusion practice after PBSCT. Such an approach will be applied to other aspects of transfusion medicine in the setting of HSC transplantation. Bone Marrow Transplantation(2000) 25, 507-512. (+info)
Detection of an anti-RhD antibody 2 years after sensitization in a patient who had undergone an allogeneic BMT.
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We describe an HLA matched bone marrow transplantation with minor ABO incompatibility and RhD mismatch (donor RhD negative and recipient RhD positive). GVHD appeared on day +96 and therapy with steroid and cyclosporin was started. When GVHD disappeared and immunosuppressive therapy was stopped (2 years after BMT), an anti-RhD antibody was detected in the patient's serum. The delayed appearance of this antibody may have been associated with the prolonged immunosuppression that was required for treatment of the patient's GVHD. (+info)
One antigen mismatched related donor bone marrow transplant in a patient with acute lymphoblastic leukaemia and beta-thalassaemia major: potential cure of both marrow disorders.
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We report a case of a 34-year-old man with T-ALL and beta-thalassaemia major who underwent a one antigen mismatched related donor bone marrow transplant. Five months post transplant chimeric studies revealed full donor haemopoiesis and the patient remains leukaemia and thalassaemia free at 12 months post transplant. Cumulative risk factors contributing to the increased transplant-related mortality in patients with two different marrow disorders are discussed. (+info)
Blood utilisation in elective general surgery cases: requirements, ordering and transfusion practices.
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AIMS: For elective surgeries, over ordering of blood is a common practice. This can be decreased by simple means of changing the blood cross matching and ordering schedule depending upon the type of surgery performed. The principle aim of the study was to improve the efficacy of ordering system for maximum utilisation of blood and formulation of maximum surgical blood order schedule (MSBOS) for procedures where a complete cross-match appears mandatory. MATERIAL AND METHODS: We evaluated blood ordering and transfusion practices in 500 elective general surgical procedures at our institute. With the help of different indices such as cross-match to transfusion ratio (C/T ratio), transfusion probability (% T) and transfusion index (TI), blood ordering pattern was changed in the next 150 patients. RESULTS: Out of 1145 units of blood crossmatched for the first 500 patients only 265 were transfused with non-utilisation of 76.86% of ordered blood. With the help of the indices the wastage was reduced in next 150 patients, i.e. from 76.86% to 25.26% and improved the utilisation of blood, i.e. from 23.14% to 74.74%. CONCLUSIONS: Change of blood ordering patterns with use of MSBOS can avoid the over ordering of blood. (+info)
Tacrolimus (FK 506) induced thrombotic thrombocytopenic purpura after ABO mismatched second liver transplantation: salvage with plasmapheresis and prostacyclin.
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We report the course of thrombotic thrombocytopenic purpura (TTP) in a patient receiving tacrolimus (FK506) immunosuppression for an ABO mismatched second liver graft. A Chinese woman with fulminant hepatitis-B reactivation failed a living-related orthotopic liver transplantation (OLT) due to portal vein thrombosis. An ABO mismatched cadaveric OLT (group A to O) was performed, with peri-operative plasmapheresis to reduce anti-A hemagglutinin titers. On day 30, she developed fever, hemolysis, thrombocytopenia and neurologic dulling. Prominent microangiopathic features in peripheral blood film, and characteristic brain lesions on magnetic resonance imaging confirmed TTP. She responded initially to intensive plasmapheresis with cryosupernatant replacement, and withdrawal of FK506. An attempted reintroduction of FK506 for threatened rejection led to TTP exacerbation. This was controlled with prolonged plasmapheresis and a ten-day infusion of prostacyclin. Immunosuppression was changed to mycophenolate mofetil. By day 53, the peripheral film and lactate dehydrogenase level had returned to baseline and plasmapheresis was stopped. (+info)