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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two consecutive patients with acute myeloid leukaemia (AML) developed severe probable graft-versus-host disease (GVHD) following transfusion of blood products from normal donors. In one patient the AML had arisen de novo, while in the other it occurred four years after the patient developed non-Hodgkin's lymphoma (NHL) and was treated with radiotherapy and combination cytotoxic chemotherapy. Both patients received anti-leukaemic treatment with doxorubicin and cytosine arabinoside and intensive haematological supportive care with transfusions of red cell, white cell and platelet concentrates obtained from normal donors. Clinically the GVHD in each patient was manifest by a severe erythematous rash, intractable diarrhoea and abnormalities in the liver function tests. On pathological examination the skin in each case showed the typical changes of GVHD. Both patients died. There have been few previous reports of GVHD occurring after accidental engraftment of immunosuppressed patients undergoing therapy for acute leukaemia. Our experience suggests that it may occur more often than has hitherto been recognised. At present there is controversy concerning the possible anti-leukaemic effects of granulocyte transfusions. Until the relative importance of the benefits and deleterious effects of cells with the potential for engraftment is determined by further studies, we recommend the routine irradiation of all cellular blood products intended for administration to acute leukaemia patients undergoing intensive cytoreductive chemotherapy.
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PMID:Graft-versus-host disease in consecutive patients with acute myeloid leukaemia treated with blood cells from normal donors. 694 43

Complement-mediated cytolysis has been used to remove T-lymphocytes from suspensions of human peripheral blood and bone marrow. Selective T-cell removal was investigated by three monoclonal antibodies. OKT3, MBG6 and OKT11A. All three removed greater than 90% of T-cells but combinations were necessary to kill greater than 99% of T-cells in vitro. The macrophage-granulocyte and erythroid colony forming cells of the bone marrow were spared. The method can be applied on bulk BM samples during clinical BM transplantation and will be useful to establish whether the virtually complete removal of T-lymphocytes totally prevents transplant associated graft-versus-host disease in man.
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PMID:Elimination of T-lymphocytes from human bone marrow with monoclonal T-antibodies and cytolytic complement. 697 74

Granulocyte chemotaxis and iodination were studied in 87 allogeneic marrow transplant recipients and in 25 normal individuals. Chemotactic responses of marrow transplant recipients as a group were depressed during the first 4 months after transplantation and normal in patients studied as long-term survivors (days 175--2202 post-transplantation). Patients with moderate to severe acute or chronic graft-versus-host disease (GVHD) or infections had lower chemotactic responses than those without. Granulocyte iodination and the ability of patient serum to support iodination were normal. Thus, depressed granulocyte chemotaxis recovered slowly with time following allogeneic marrow transplantation. Both acute and chronic GVHD, however, were associated with impairment of granulocyte chemotaxis, a defect which may contribute to the high risk of infection among allogeneic marrow graft recipients with GVHD.
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PMID:Granulocyte function in human allogenic marrow graft recipients. 701 34

Twenty-five patients with major ABO blood group incompatibility between donor and recipient underwent allogeneic bone marrow transplantation using erythrocyte depletion of the bone marrow infusate prior to administration. Over 95% of the original erythrocyte content of the marrows was removed, while retaining 75% of the mononuclear cell content and 57% of the granulocyte-monocyte colony-forming units. Recipients, well hydrated and premedicated with corticosteroids, diphenhydramine, and mannitol, tolerated infusions well. The frequency of engraftment, rate of recovery of peripheral blood leukocytes, granulocytes, and platelets, and the incidence of graft-versus-host disease was similar to that observed following ABO blood group compatible bone marrow transplantation. Erythroid development following ABO blood group incompatible transplantation was significantly impaired until hemagglutinins fell to 1:4 or lower, at which time recovery of erythrocytes was detected in the peripheral blood. The erythrocyte hypoplasia associated with incompatible hemagglutinins was temporary. Erythrocyte purging is a safe and effective technique to perform bone marrow transplantation across major ABO blood group incompatibilities.
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PMID:Bone marrow transplantation with major ABO blood group incompatibility using erythrocyte depletion of marrow prior to infusion. 704 47

Graft loss secondary to chronic rejection remains a major source of morbidity and mortality in solid organ transplantation. Mixed chimerism has been suggested as one potential approach to overcome this limitation. Until now, whether long-term tolerance for primarily vascularized allografts can be achieved with mixed chimerism has not been adequately assessed due to technical limitations in the mouse and the inability to establish a reliable model of mixed chimerism in the rat. We now report that stable multilineage mixed hematopoietic chimerism can be achieved following the transplantation of a mixture of T cell-depleted syngeneic and allogeneic bone marrow cells into myeloablated rat recipients using a number of MHC plus minor antigen-disparate donor and recipient strain combinations (F344+WF-->F344, F344+ACI-->F344, WF+F344-->WF, and WF+ACI-->WF). Ninety-one percent of animals engrafted with a level of lymphoid chimerism ranging between 12% and 93% (73.3 +/- 4.8%). Peripheral blood lymphocyte chimerism remained stable for up to 13 months after reconstitution. Multilineage chimerism for lymphoid (T and B cells) and myeloid (granulocyte and macrophage) lineages was present, which suggests that engraftment of the pluripotent rat stem cell had occurred. There was no clinical or histologic evidence of graft-versus-host disease. Donor-specific skin (mean survival time [MST] > or = 177 days) and primarily vascularized cardiac (MST > or = 213 days) grafts were accepted without evidence for acute or chronic rejection. In contrast, MHC-disparate third-party skin (MST = 14 days) and cardiac grafts (MST = 13 days) were rapidly rejected. The tolerance was systemic, since donor-specific tolerance was present in vitro as assessed by the mixed lymphocyte proliferation assay. These data suggest that mixed chimerism prevents graft loss secondary to chronic rejection in skin as well as primarily vascularized grafts. Furthermore, a rat model for mixed allogeneic chimerism may provide insight into the mechanisms involved in tolerance induction for a variety of allografts (lungs, small bowel, limb, etc.) not readily transplantable in mouse recipients.
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PMID:Mixed allogeneic chimerism in the rat. Donor-specific transplantation tolerance without chronic rejection for primarily vascularized cardiac allografts. 749 3

The pathophysiologic role of nitric oxide (NO) in graft-versus-host disease (GVHD) was investigated in a murine bone marrow (BM) transplantation model where donor and recipient were H-2-matched but differed at multiple minor histocompatibility antigens. Host AKR/J (H-2K) mice received lethal total body irradiation as pretransplant conditioning followed by transplantation of donor B10.BR (H-2K) BM cells with or without spleen cells as a source of GVH-reactive T cells. NO production, as assessed by serum nitrate and nitrite levels, was increased for up to 3 weeks posttransplant in animals undergoing both moderate and severe GVHD. Administration of NG-methyl-L-arginine (L-NMA), an inhibitor of nitric oxide synthase, to animals undergoing GVHD resulted in effective suppression of NO production when compared with saline-treated GVHD control animals. Suppression of NO production by L-NMA in GVHD animals was associated with enhanced weight loss early posttransplant and decreased overall survival. Histologic analysis of tissues from L-NMA-treated and saline-treated GVHD animals showed that early weight loss was not because of an exacerbation of GVHD, indicating that NO did not appear to play an immunosuppressive role in this experimental model. L-NMA-treated animals with enhanced weight loss were observed to have splenic atrophy, decreased extramedullary hematopoiesis, and a reduction in BM cellularity when compared with GVHD control mice that were weight-matched before transplant. Analysis of T-cell chimerism in the spleen showed that L-NMA treatment impaired donor T-cell repopulation. In vitro colony-forming unit (CFU) assays were performed to further assess the role of NO on BM progenitor cell growth. L-NMA added directly into culture had no effect on CFU-granulocyte/macrophage (CFU-GM) formation in normal murine BM. In contrast, total CFU-GM from L-NMA-treated animals were significantly reduced when compared with GVHD controls or BM control animals who did not develop GVHD. Collectively, these data indicate that inhibition of NO impairs hematopoietic reconstitution and support the premise that NO appears to play a novel role in the facilitation of alloengraftment posttransplant.
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PMID:Inhibition of nitric oxide production is associated with enhanced weight loss, decreased survival, and impaired alloengraftment in mice undergoing graft-versus-host disease after bone marrow transplantation. 752 27

Human dendritic cells (DC) generated from CD34+ hematopoietic progenitors cultured in the presence of granulocyte macrophage colony stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-alpha are related to Langerhans cells (DLC) and have been shown to induce a strong proliferation of allogeneic CD4+ T cells. The present study shows that recombinant human IL-10 (h-IL-10) inhibits the primary and secondary proliferative responses of both CD4+ and CD8+ T cells induced by allogeneic CD1a+ DLC. The alloreaction induced by DLC generated after 5-18 days of culture of CD34+ HPC was equally inhibited by h-IL-10, thus indicating that DLC were sensitive to h-IL-10 at all stages of differentiation. This is further indicated by the h-IL-10-induced inhibition of the T cell alloreaction mediated by interdigitating DC freshly isolated from tonsils. h-IL-10 specifically acted on DLC as it did not affect the proliferation induced by Epstein-Barr virus lymphoblastoid cell lines (EBV-LCL) nor that induced by immobilized anti-CD3. The inhibitory effect of h-IL-10 was not due to the production of suppressive factors by the DLC, as the addition of DLC and IL-10 did not inhibit EBV-LCL-induced T cell proliferation. Rather, the inhibition of cytokine production (IL-2, GM-CSF, TNF, IFN-gamma) observed after 24 h of co-culture may explain the inhibition of T cell DNA synthesis detected 3 days later. The h-IL-10-induced inhibition of human DC mediated alloreaction advocates considering the use of h-IL-10 in the prevention of transplant rejection and graft versus host disease, phenomena initiated by DC.
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PMID:Interleukin 10 inhibits T cell alloreaction induced by human dendritic cells. 752 90

Immunotherapy can be defined as treatment directed at augmenting host immune defence mechanisms. Non-antimicrobial therapies and immunoprophylaxis in bone marrow transplantation (BMT) can be subdivided into three broad categories: passive immunotherapy with intravenous immunoglobulin (IVIG); cytokine therapy; and anti-endotoxin-directed treatments. Most studies using IVIG in BMT are prophylactic and suffer from variability in study design, type of IVIG and dosing regimens. Various effects on viral and bacterial infections and graft-versus-host disease (GVHD) have been reported but few if any have shown benefit in terms of improved patient survival. Moreover the immunomodulatory effect of immunoglobulin G preparations is frequently overlooked. With the exception of cytomegalovirus (CMV) pneumonitis, there is little evidence of benefit in the treatment of established infections and the relative benefits of hyperimmune preparations are poorly established. The development of haemopoietic growth factors has led to the widespread use of cytokines in BMT. The benefits of these agents both in the prevention of fever and infection and as adjuvants to standard antimicrobial therapy in established infection (e.g. invasive mycoses) are rapidly becoming apparent. Both human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and granulocyte colony-stimulating factor (rhG-CSF) have been shown to accelerate granulocyte recovery following BMT and reduce fever days, antibiotic usage and hospitalization. RhGM-CSF appears superior in these respects. The roles of interleukin 1 (IL1), IL3, IL6 and interferons are also under evaluation. As with the much publicised studies using anti-endotoxin antibodies as therapy in sepsis, there is little evidence of benefit in the few studies performed in BMT patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunotherapy and immunoprophylaxis in bone marrow transplantation. 756 Sep 54

Growing attention has been focused on cord blood as a source of transplantable hematopoietic stem cells. However, clinical experience is rather limited. In this study we describe a child with advanced acute lymphoblastic leukemia who received an HLA-haploidentical cord blood transplant. The patient was transplanted in third complete remission after conditioning with fractionated total body irradiation, thiotepa and cyclophosphamide. Forty-one milliliters of cryopreserved umbilical cord blood, containing 0.15 x 10(8) nucleated cells/kg and 0.25 x 10(4) CFU-GM/kg, were infused. Cyclosporine and prednisone were administered for graft-versus-host disease (GVHD) prophylaxis. The patient received G-CSF from day +1 to day +35, but no improvement in granulocyte counts was observed. Therefore, administration of GM-CSF was started on day +36 to day +59, which resulted in a significant increase in white blood cells and granulocyte counts. Sustained myeloid engraftment was evidenced by a granulocyte count > 0.5 x 10(9)/l by day +41. The presence of donor-derived cells could be documented in the peripheral blood and bone marrow of the patient by cytogenetic analysis, HLA phenotyping and DNA studies. Forty-one days after transplant, clonogenic bone marrow assays showed the presence of low frequencies of primitive hematopoietic progenitor cells (BFU-E = 19/10(5) and CFU-GM = 8/10(5)). The chimerism was complete and no host-derived cells could be detected. However, the engraftment was restricted to the myeloid lineage whereas lymphoid and megakaryocytic engraftments were inadequate. The immunophenotype of the patient's peripheral blood showed the presence of T lymphocytes expressing an immature phenotype (CD2+ CD3-) at day +21.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HLA-haploidentical umbilical cord blood stem cell transplantation in a child with advanced leukemia: clinical outcome and analysis of hematopoietic recovery. 758 Nov 41

Transfusion of blood and blood components may be fraught with serious immunologically mediated side effects. Acute hemolytic reactions are still the most common cause of fatal transfusion sequelae. The incidence of alloimmunization against erythrocyte antigens as studied in long-term transfused patients with thalassemia depends on the age at the beginning of transfusion therapy. HLA alloimmunization is often associated with refractoriness to platelet transfusions and febrile transfusion reactions. Neonatal alloimmune thrombocytopenia and post-transfusion purpura are elicited by platelet-specific antibodies reacting with determinants on platelet glycoproteins IIb/IIIa, Ib/IX, and Ia/IIa. Another serious complication of transfusion therapy, transfusion-related acute lung injury, is caused by granulocyte-specific alloantigens in donor plasma. Graft-versus-host disease is a rare but dangerous complication of blood transfusion which mainly affects patients with impaired T-cell-related immunity.
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PMID:[Risk of immunization to blood cells and diagnostic and therapeutic implications]. 769 63


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