Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

Unrelated cord blood (UCB) is being used as a source of alternative hematopoietic stem cells for transplantation with increasing frequency. From November 1994 to February 1999, 30 UCB transplant procedures were performed for both malignant and nonmalignant diseases in 27 children, aged 0.4 to 17.1 years. Patients received either HLA-matched (n = 3) or 1- or 2-antigen-mismatched (n = 27) UCB following 1 of 2 standardized preparative and graft-versus-host disease regimens (hyperfractionated total body irradiation, cyclophosphamide, and antithymocyte globulin [ATG] with cyclosporine A and methotrexate; or busulfan, melphalan, and ATG with cyclosporine A and prednisone). The median time to neutrophil and platelet engraftment was 27 days (12-60 days) and 75 days (33-158 days) posttransplantation, respectively. No correlation was noted between neutrophil and platelet engraftment and nucleated cells per kilogram, CD34(+) cells per kilogram infused, or cytomegalovirus status of recipient. The cumulative probability of acute grade 2 or greater graft-versus-host disease (GVHD) was 37.2%, and of grade 3 or greater GVHD was 8.8%. No patients developed chronic GVHD. CD4, CD19, and natural killer cell recovery was achieved at a median of 12, 6, and 2 months, respectively. CD8 recovery was delayed at a median of 9 months. Normal mitogen response was achieved at 6 to 9 months. The probability of survival, disease-free survival, and event-free survival at 1 year was 52.3% (34.1%-70.5%), 54.7% (34.5%-74.9 %) and 49.6% (29.9%-69.4%), respectively. This series of 30 UCB transplants suggests that although CD8 cell recovery is delayed, the pattern of immune reconstitution with UCB is similar to that reported for other stem cell sources. (Blood. 2000;96:2703-2711)
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PMID:Analysis of engraftment, graft-versus-host disease, and immune recovery following unrelated donor cord blood transplantation. 1102 1

Both rejection and graft-versus-host-disease may occur after fully allogeneic small bowel transplantation. In this study, we established unidirectional models of rejection and GVHD in rats and evaluated the efficacy of 15-deoxyspergualin (DSG). When F1 small bowel was transplanted into LEW rats (rejection model) the graft was acutely rejected. The administration of DSG (5 mg/kg per day for 10 days) significantly prolonged the survival, but was efficacious only when used prophylactically. When a unidirectional GVHD model (F1 --> LEW SBTx) was examined, the administration of DSG from day 0 after grafting greatly suppressed GVHD, resulting in more than 300 days survival. However, only cutaneous GVHD, but not fatal GVHD, was suppressed when the start of administration was postponed until day 4 after grafting. From in vitro studies, DSG inhibited natural killer cell activities to K-562 and skin epidermal cells. The response was well correlated with in vivo GVHD course. These results suggest that DSG is an effective immunosuppressant for both rejection and GVHD when used prophylactically. DSG exerted the effect more stongly against cutaneous GVHD than fatal GVHD by inhibiting natural killer systems.
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PMID:The effect of deoxyspergualin (DSG) on rejection and graft-versus-host disease (GVHD) after small bowel transplantation. 1127 Dec 78

T cells with natural killer cell phenotype and function (NKT cells) have been described in both human and murine tissues. In this study, culture conditions were developed that resulted in the expansion of CD8(+) NKT cells from bone marrow, thymus, and spleen by the timed addition of interferon-gamma (IFN-gamma), interleukin 2 (IL-2), and anti-CD3 monoclonal antibody. After 14 to 21 days in culture, dramatic expansion of CD3(+), CD8(+), alphabetaT-cell receptor(+) T cells resulted with approximately 20% to 50% of the cells also expressing the NK markers NK1.1 and DX5. The CD8(+) NKT cells demonstrated lytic activity against several tumor target cells with more than 90% lysis by day 14 to day 21 of culture. Cytotoxicity was observed against both syngeneic and allogeneic tumor cell targets with the greatest lytic activity by the cells expressing either NK1.1 or DX5. The expanded CD8(+) NKT cells produce T(H)1-type cytokines with high levels of IFN-gamma and tumor necrosis factor alpha. Expansion of the CD8(+) NKT cells was independent of CD1d. Ly49 molecules were expressed on only a minority of cells. A single injection of expanded CD8(+) NKT cells was capable of protecting syngeneic animals from an otherwise lethal dose of Bcl1 leukemia cells. Expanded CD8(+) NKT cells produced far less graft-versus-host disease (GVHD) than splenocytes across major histocompatibility barriers, even when 10 times the number of CD8(+) NKT cells as compared to splenocytes were injected. This reduction in GVHD was related to IFN-gamma production since cells expanded from IFN-gamma knock-out animals caused acute lethal GVHD, whereas cells expanded from animals defective in fas ligand, fas, IL-2, and perforin did not. These data indicate that CD8(+) NKT cells expanded in this fashion could be useful for preserving graft-versus-leukemia activity without causing GVHD.
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PMID:Expansion of cytolytic CD8(+) natural killer T cells with limited capacity for graft-versus-host disease induction due to interferon gamma production. 1134 13

Until a decade ago, hematopoietic stem cell transplantation from related donor mismatched at two or three HLA-A, -B or DR loci was largely unsuccessful in leukemia patients because of severe graft-versus-host disease in unmanipulated bone marrow transplants and graft failure in extensively T-cell-depleted transplants. The breakthrough came with the use of a megadose of T-cell-depleted hematopoietic progenitor cells. Donor-vs-recipient natural killer cell alloreactivity also plays a role in facilitating engraftment and in preventing relapse of acute myeloid leukemia. Event-free survival and transplant-related mortality for high risk acute leukemia patients treated at less advanced stages of disease compare favourably with reports from unrelated matched transplants.
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PMID:Hematopoietic stem cell transplantation from full-haplotype mismatched donors. 1235 53

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that exhibits specific tumoricidal activity against a variety of tumors. It is expressed on different cells of the immune system and plays a role in natural killer cell-mediated tumor surveillance. In allogeneic hematopoietic-cell transplantation, the reactivity of the donor T cell against malignant cells is essential for the graft-versus-tumor (GVT) effect. Cytolytic activity of T cells is primarily mediated through the Fas-Fas ligand and perforin-granzyme pathways. However, T cells deficient for both Fas ligand and perforin can still exert GVT activity in vivo in mouse models. To uncover a potential role for TRAIL in donor T cell-mediated GVT activity, we compared donor T cells from TRAIL-deficient and wild-type mice in clinically relevant mouse bone-marrow transplantation models. We found that alloreactive T cells can express TRAIL, but the absence of TRAIL had no effect on their proliferative and cytokine response to alloantigens. TRAIL-deficient T cells showed significantly lower GVT activity than did TRAIL-expressing T cells, but no important differences in graft-versus-host disease, a major complication of allogeneic hematopoietic cell transplantation, were observed. These data suggest that strategies to enhance TRAIL-mediated GVT activity could decrease relapse rates of malignancies after hematopoietic cell transplantation without exacerbation of graft-versus-host disease.
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PMID:T cells require TRAIL for optimal graft-versus-tumor activity. 1242 60

We describe herein a case of nephrotic syndrome (NS) following allogeneic bone marrow transplantation (allo-BMT) for natural killer cell leukemia/lymphoma. Histologic studies defined the diagnosis as crescentic glomerulonephritis with massive immunoglobulin A (IgA) deposition, which has never been reported in NS cases following allo-BMT. Most of the massive infiltrated cells in the interstice were CD3(+)CD4(-)CD8(+) T cells derived from the donor. We observed mesangial deposition of Haemophilus parainfluenza outer membrane (OMHP) antigen and decreased glycosylation of the IgA1 hinge in the recipient's samples is consistent with the recently reported pathogenesis of IgA nephropathy. Further, the titer of IgA antibody against the donor serum was as high as other IgA nephropathy cases. These findings suggest that NS and crescentic glomerulonephritis in this case occurred as one of the forms of chronic graft-versus-host disease (GVHD), and that IgA deposition was associated with H parainfluenza and decreased glycosylation of the IgA1 hinge.
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PMID:Nephrotic syndrome with crescent formation and massive IgA deposition following allogeneic bone marrow transplantation for natural killer cell leukemia/lymphoma. 1254 67

We investigated whether a novel chemotherapy-alone conditioning regimen would permit durable engraftment of standard doses of CD34+ purified stem cell grafts from full-haplotype mismatched related donors. We also examined the role of infusing limited doses of donor leukocytes for prevention of leukemia relapse. Our conditioning regimen consisted of thiotepa, fludarabine, rabbit antithymocyte globulin, melphalan, cyclosporin, and prednisolone. Since October 1998, 14 patients with high-risk leukemia were treated; 13 donor-patient pairs shared 3 of 6 HLA antigens, and 1 pair shared 5 of 6 HLA antigens. A median of 5.4 x 10(6) CD34+ cells per kilogram, 1.62 x 10(4) CD3+ cells per kilogram, and 9.32 x 10(4) CD19+ cells per kilogram were infused. T-cell depletion was the only graft-versus-host disease (GVHD) prophylaxis. All patients had prompt engraftment, and no late graft rejections were observed. All surviving patients received at least 1 infusion of donor whole blood containing 5, 7, 10, 25, or 50 x 10(3) CD3+ cells per kilogram between days 25 and 95 after transplantation, after which 8 developed acute GVHD (3 grade I, 2 grade II, 2 grade III, and 1 grade IV) and 2 developed a bronchiolitis obliterans-like syndrome. After attaining complete remission, 5 patients relapsed and died with active leukemia. The estimated relapse-related mortality at 4 years is 38.1%. As of June 15, 2003, 6 of 14 patients have survived a median of 43.5 months after transplantation with 100% donor cells. All 6 surviving patients developed acute GVHD and had a natural killer cell mismatch with their donors in the direction of graft versus host. The estimated overall survival and event-free survival for the 14 patients at 4 years is 41.7% +/- 13.5%.
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PMID:Haploidentical stem cell transplantation with purified CD34 cells after a chemotherapy-alone conditioning regimen. 1456 59

To evaluate the development of the neonatal immune system, we measured T lymphocyte response to Con A, intracellular IL-2, IL-4, IFN-gamma and IL-10 production, and natural killer cell (NKC) activity in 12 very preterm, 12 preterm and 20 term neonates, 10 children and 10 adults. Immunoproliferation to Con A was significantly lower in cord blood than in children or adults. The percentage of CD4+ lymphocytes was significantly higher in newborns while CD8+ cells were higher at older ages, with a resulting gradual decline of the CD4+/CD8+ ratio. The percentage of IL-2-producing CD4+ and CD8+ cells was higher in all newborn groups than in children and adults, while the percentage of IL-4-producing cells was higher for CD8+ and lower for CD4+ cells in cord blood than in children and adults. Neonates had substantially lower percentages of CD4+ and CD8+ IFN-gamma-producing cells. A significant negative correlation was observed between gestational age and IFN-gamma-CD4+-, IL-2-CD8+-, and IL-10- CD4+-producing cells. In addition, a positive correlation was found between gestational age and IL-10-CD8+-producing cells. Percentages of CD4+/CD45RA+ cells were higher and CD4+/CD45RO+ percentages were lower in newborns than in children and adults. NKC activity in infants was significantly correlated with gestational age and significantly impaired compared to children and adults. On the whole, these results suggest a gradual development of immunity during gestation and show significant immaturity of cellular immune response at birth. The reduction of NKC activity, the lower proliferative response of T cells, the reduced cytotoxic response and a dysregulated cytokine production may contribute to the neonatal increased risk of infection and to the low incidence of graft-versus-host disease after cord blood transplantation.
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PMID:Age-related changes in intracellular TH1/TH2 cytokine production, immunoproliferative T lymphocyte response and natural killer cell activity in newborns, children and adults. 1459 40

In order to monitor the immunological status of patients after allogeneic hematopoietic stem cell transplantation(HSCT), granzyme B(GrB), perforin(PRF) and Fas ligand(L) antigens and mRNAs were measured by flow cytometry and real time RT-PCR, respectively. Cytoplasmic antigens were detected in whole blood after fixation and pretreatment with saponin. Real time PCR was carried out using extracted RNA from buffy coat. We measured these substances in a cytotoxic T cell clone, a natural killer cell line, and peripheral blood collected from 11 patients after HSCT. Although changes in antigen levels were not detected, increased levels of GrB and Fas L mRNAs were quantitatively measured in CTLs and NK cells stimulated by IL-2 combined with IL-12. Increased levels of GrB and/or PRF antigens were detected in four of five patients with chronic GVHD. Increased mRNA levels were also observed in one or more of GrB, PRF or Fas L in four of five patients with cGVHD, although there was a discrepancy between antigen and mRNA positivity. Four of six patients without cGVHD were positive for apoptosis-inducing factors, either by antigen detection or RT-PCR. One of these four had relapsing leukemia, and another had herpes zoster infection, while the reasons for positive results in the other two patients are not clear. Although changes in antigen levels did not parallel those in mRNA, measurement of these parameters may assist in predicting GVHD, GVL and infections following HSCT.
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PMID:[Levels of granzyme B, perforin and Fas ligand antigens and mRNAs in patients following allogeneic hematopoietic stem cell transplantation]. 1474 38

We describe the case of a 48-year-old man with acute myeloid leukemia complicated with pulmonary infection that was successfully treated by nonmyeloablative allogeneic peripheral blood stem cell transplantation with conditioning by low-dose total body irradiation and fludarabine. The disease was diagnosed immunophenotypically as myeloid/natural killer cell precursor acute leukemia. After two courses of induction therapy, complete remission was achieved. However, the patient developed pneumonia from prolonged severe neutropenia. Nonmyeloablative allogeneic transplantation was performed because of the active pulmonary infection and the patient's poor performance status. Myelosuppression after transplantation was mild, and the pulmonary infiltration was well controlled during the course of treatment. At the time of this report the patient was an outpatient in our clinic, and on day 500, his disease was in remission with well-controlled chronic graft-versus-host disease. Nonmyeloablative transplantation may provide a new therapeutic strategy for treating patients with active infection who cannot tolerate conventional transplantation with high-dose chemoradiotherapy.
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PMID:Successful treatment with nonmyeloablative allogeneic hematopoietic stem cell transplantation in a patient with acute myeloid leukemia complicated with pulmonary infection. 1497 85


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