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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)

Functional studies of helper and cytotoxic T cells in families with recombinant HLA haplotypes have played a crucial role in the early studies of the HLA chromosomal region. It has been shown that for the generation of CTLs directed against HLA-A or -B antigen differences an additional difference in the HLA-D region between responder and stimulator cells was a prerequisite. We have re-examined in a sensitive limiting dilution assay the possibility of generating CTL against HLA class I antigens in responder-stimulator pairs with a negative MLC reaction of two recombinant families (differing in one or two HLA class I antigens but identical in class II antigens) and two pairs of unrelated individuals. In all cases we could detect low but definitely measurable CTL activity (8-15 CTL precursors in 10(6) PBMCs) directed against the mismatched class I HLA antigen(s). We conclude that mismatches in class I HLA antigens in MLC nonreactive responder-stimulator pairs can induce generation of allospecific CTLs. This has implications in allogeneic bone marrow transplantation with HLA-matched unrelated donors; i.e., in the case of an HLA-A,B,DR matched donor a low donor CTLpf against the recipient may be an indication of a serologically not-detected class I HLA "subtype" incompatibility which might cause graft-versus-host disease.
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PMID:Estimates of cytotoxic T-lymphocyte precursor frequencies against HLA class I antigens in responder-stimulator pairs with a negative mixed lymphocyte culture reaction. 884 34

A 6-year-old boy with CML in blastic crisis was transplanted with BM and PBSC from his HLA-mismatched MLC-positive mother following CD34-positive selection. Preconditioning for transplant was with thiotepa, cyclophosphamide, rabbit anti-human thymocyte globulin, and TBI followed by infusion of 2.6 x 10(6)/kg of CD34-positive BM and PBSC. Engraftment was confirmed by FISH analysis, and GVHD was not observed. On day 50, he relapsed and died despite three transfusions of donor lymphocytes without GVHD prophylaxis. CD34-positive cell selection for HLA-mismatched transplantation may prevent severe acute GVHD.
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PMID:Allogeneic bone marrow and peripheral stem cell transplantation from a haplo-identical mother and CD34 positive selection for CML. 886 62

In order to determine the influence of anxiety on the development of BMT complications and survival, we analysed data on 35 consecutive patients undergoing BMT in our Centre between June 1992 and December 1994. All patients received bone marrow from HLA-identical MLC non-responsive siblings. For GVHD prophylaxis, all patients received cyclosporin (CsA) and short methotrexate (MTX). The diagnosis and severity of acute GVHD were defined according to the Seattle Transplant Team criteria. The patients were tested with the Spielberger STAI test as a measure of anxiety as a state (STAI-S) and as a trait (STAI-T). The STAI-S/1 and STAI-T/1 were performed during the first week of isolation (day -5 to day -3 prior BMT) and STAI-S/2 and STAI-T/2 at the end of the discharge from laminar air flow units (day +35 to day +40 post-transplant). During isolation all patients had daily psychiatric support. Out of 35 patients, 31 (89%) fulfilled the STAI-S and STAI-T during the first week and at discharge from laminar air flow isolation. The level of anxiety at the beginning of isolation as measured by STAI-S/1 and STAI-T/1 tests had been significantly higher in patients who subsequently developed acute grade II-IV GVHD as compared to patients with GVHD grade 0-I (P < 0.001), irrespective of age, sex or stage of the disease prior to BMT. In those patients who died, the STAI-S/1, STAI-T/1 and STAI-T/2 tests had been almost identical to those of surviving patients, while STAI-S/2 had been significantly higher (P = 0.034). These data clearly indicate an association between the level of anxiety and the risk for BMT complications, but this should be confirmed in further controlled clinical trials.
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PMID:Anxiety as a possible predictor of acute GVHD. 887 22

The utility of the MLC assay as a test of HLA-D region matching and predictor of graft-versus-host disease (GvHD) was evaluated in 435 patients receiving marrow grafts from unrelated donors. Donors and recipients were phenotyped for HLA-A, B and DR antigens by serology, tested in MLC, and retrospectively genotyped for DRB1, B3, B4, B5, DQB1 and DPB1 alleles by PCR/SSOP. Of the 244 HLA-A, B, DR-identical donor-recipient pairs with valuable MLC and DRB1 typing results available, 208 were matched for HLA-A, B and DRB1, while 36 were matched for HLA-A and B and mismatched for a DRB1 allele. Donor anti-recipient relative responses (RR) in MLC, corresponding to the GvHD vector in marrow transplantation, ranged from 7.2 to 100%, with a median of 4.0%. A comparison of reactivity in MLC between pairs matched versus mismatched for DRB1 alleles showed a significant overlap in the distribution of RRs. Using optimally-defined RR cutoffs of 4 and 16%, no correlation between MLC results and risk of developing clinically significant grades III-IV GvHD (p=0.6 and 0.5, respectively) was found when the contribution of DRB1 mismatch was accounted for. Matching for DRB1 alleles, in contrast, was a better predictor of clinically significant GvHD, with DRB1-matched transplant recipients less likely to develop grades III-IV GvHD than DRB1-mismatched recipients (p=0.14). Among the 208 patients and donors matched for DRB1 alleles, the MLC, although reactive (RR > 4.0%) in 45% of cases, did not predict GvHD. Overall, these results underscore the limitations in using the MLC to predict DRB1 matching or risk of clinically significant GvHD among patients receiving unrelated marrow grafts. The availability of DRB1 allele matching by sequence-specific oligonucleotide probes (SSOP) or by direct sequencing provides a method for donor matching that is rapid, precise and superior to the MLC for predicting clinically relevant outcome.
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PMID:Evaluation of the mixed lymphocyte culture (MLC) assay as a method for selecting unrelated donors for marrow transplantation. 892 10

Dendritic cells (DC), as professional antigen-presenting cells, play a major role in stimulating naive T cell responses in vivo and in vitro, and may exacerbate or modulate T lymphocyte-mediated reactions, such as interactions between a hematopoietic graft and the recipient, eg GVHD and graft-versus-leukemia. Here, we describe a two-stage cell culture system for expansion of functionally active human DC from CD34+ marrow precursors. Optimal outgrowth was achieved by initially culturing CD34+ cells for 5 days in medium containing GM-CSF, MGF and TNF-alpha. Substitution of CD40L and IL-4 for TNF-alpha during a subsequent 5-day subculture increased DC content, such that by 10 days the cultures contained approximately 40% DC as determined by immunophenotype and morphology. An increase in DC purity to 84% at 10 days was achieved by immunomagnetic separation for CD1a+ cells from 5-day cultures and subculturing these cells in medium with IL-4 and CD40L. Reversing the sequence of growth factors during culture and subculture decreased the yield and purity of DC. Expression of CD80 and CD86 was enhanced by adding CD40L and IL-4, and the DC showed stimulatory activity in MLC. In conclusion, we have described a simple two-stage culture system to generate functional DC from CD34+ marrow precursors.
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PMID:In vitro expansion and characterization of dendritic cells derived from human bone marrow CD34+ cells. 893 57

A 13-yr-old boy was diagnosed as T cell lymphoma. After the second remission, he underwent BMT from an HLA-identical, MLC negative sibling donor. After BMT, he developed grade II acute GVHD. GVHD was improved by pulsed steroid therapy using prednisolone. About 12 months after BMT, he developed bronchiolitis obliterans, sicca syndrome, and leukoderma, which were related to chronic GVHD. Pulsed steroid therapy was carried out twice, and his condition improved. Twenty-seven months after BMT, he developed nephrotic syndrome. A renal biopsy was performed, and the diagnosis was histologically membranous nephropathy and focal glomerular sclerosis. The response to steroids was not satisfactory. After 5 weeks, dipyridamole was added, but proteinuria persisted. Proteinuria disappeared 8 weeks after the addition of cyclosporine. The second biopsy after 5 months of treatment revealed an improvement in the renal lesions. The patient showed a low T4 to T8 ratio of T-lymphocytes at the onset of nephrotic syndrome. However after treatment with cyclosporine, the ratio gradually increased. These findings suggested the nephrotic syndrome in this patient was related to renal involvement in the course of chronic GVHD.
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PMID:[Nephrotic syndrome related to chronic graft versus host disease after allogeneic bone marrow transplantation in a patient with malignant lymphoma]. 899 26

We studied the outcome of BMT in 38 consecutive CML patients in CP1 who received transplants depleted of lymphocytes using counterflow centrifugation. In all patients the conditioning regimen was intensified by the addition of anthracyclines. Donors were HLA, MLC-identical siblings. Six patients (16%) died within 6 months. All 37 patients with a follow-up of more than 0.5 months engrafted and only one (3%) suffered from acute GVHD > or = grade 3. Chronic GVHD was evaluable in 33 patients and was extensive in six (18%). The projected 5-year probabilities of hematologic, cytogenetic and molecular relapse were 30% (95% confidence interval (CI), 10-49%), 35% (95% CI, 14-56%), and 34% (95% CI, 13-55%), respectively. The projected 5-year probability of survival was 68% (95% CI, 50-86%). Projected at 5 years, probabilities of leukemia-free survival (LFS) in hematologic, cytogenetic and molecular remission were 55% (95% CI, 37-73%), 51% (95% CI, 32-69%), and 51% (95% CI, 32-70%), respectively. All patients with relapse but one who relapsed in blastic phase were treated with retransplantation (n = 1) or with the infusion of lymphocytes (n = 6). Six patients regained second hematologic remission and five entered second cytogenetic and molecular remission. Including these patients, the probability of survival in first or second hematologic remission at the end of follow-up was 68% (95% CI, 50-86%). The probabilities of survival in first or second cytogenetic and molecular remission at the end of follow-up were both 61% (95% CI, 42-80%). We advocate revaluation of T cell depletion of donor marrow for patients with CML-CP1, especially for those at high risk of developing GVHD.
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PMID:Survival in first or second remission after lymphocyte-depleted transplantation for Philadelphia chromosome-positive CML in first chronic phase. 920 14

Thirty-five children with poor-prognosis disease underwent allogeneic bone marrow transplantation (BMT) from related donors other than HLA identical siblings (parents in 18 cases, non-identical siblings in 14, and other relatives in 3). Phenotypically identical donors were involved in 12 cases, donors with one mismatched locus in 17, and donors with two or more mismatched loci in 6. Thirty-two of the children received total-body irradiation as part of their conditioning regimen, followed by unpurged marrow-cell infusions (averaging 4.09 x 10(8) cells/kg). Methotrexate and cyclosporin were administered for graft-versus-host disease (GVHD) prophylaxis; 15 of the children also received antithymocyte globulin (ATG) infusions. The effective graft rate for the group was 84. 8%; of 5 patients who experienced rejections, 4 had non-malignant diseases. The incidence of grade II-IV acute GVHD was 48.4%, significantly higher than that for groups that received allogeneic BMT from matched sibling donors. Three children (8.8%) died of severe GVHD. The incidence of acute GVHD in phenotypically matched patients was the same as that in the one-locus mismatched cases. MLC reactivity affected the incidence of acute GVHD (60.0% MLC-positive, 28.6% negative). ATG reduced the severity of acute GVHD. The event-free survival rate was 40.8 +/- 8.5% for the entire group (N = 35; 32.9 +/- 10.5% for the 22 children with malignancies, and 53.8 +/- 13.8% for the 13 with non-malignant diseases). Despite the risk of severe GVHD, allogeneic BMT from related donors other than HLA-identical siblings seems to be an effective treatment for patients with poor-prognosis diseases.
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PMID:[Allogeneic bone marrow transplantation in children from related donors other than HLA-identical siblings]. 979 95

Myasthenia gravis and polymyositis are each a rare manifestation of immune dysregulation in chronic graft-versus-host disease (cGVHD). We report a 4-year-old boy with idiopathic acquired aplastic anemia who developed myasthenia gravis 22 months and polymyositis 69 months after an allogeneic BMT (5/6 matched, MLC-nonreactive). The occurrence of both syndromes in one patient is unique. Autoimmune dysfunction may be associated with the development of cGVHD as demonstrated by the high incidence of prior aplastic anemia in BMT patients presenting with myasthenia gravis and polymyositis. Recognition of these neurologic manifestations is important in the diagnosis and treatment of cGVHD.
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PMID:Myasthenia gravis and polymyositis as manifestations of chronic graft-versus-host-disease. 1010 May 85

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease symptomized by failure to generate superoxide and recurrent bacterial and fungal infections. Allogeneic bone marrow transplantation (BMT) is one of the therapeutic options available. However, it presents considerable risk to the recipient, especially if the patient is already at an advanced stage of disease, after repeated bacterial and fungal infections and organ damage. We present a case report of a 6-year-old child with long-standing CGD, severe clubbing, and jeopardized pulmonary function after multiple bacterial pulmonary infectious episodes, who had failed treatment with sulphamethazole trimethoprim, multiple antibiotic courses, itraconazole, as well as steroid and interferon-y therapy. He underwent allogeneic peripheral blood stem cell transplantation (alloPBSCT) from his HLA-matched MLC non-reactive sister following non-myeloablative conditioning. His ANC did not fall below 0.2 x 10(9)/l, his lowest WBC was 0.6 x 10(9)/l, and his platelets did not fall below 28 x 10(9)/l. He had normal engraftment, with no mucositis or organ toxicity. Neither parenteral nutrition nor platelet infusions were necessary. Partial donor chimerism following alloPBSCT was converted to full donor chimerism and superoxide production reverted to normal after donor lymphocyte infusions (DLI) from his HLA-matched sister. Twenty four months post transplant the patient is well, with stable and durable engraftment, 100% donor chimerism, normal superoxide production, no GVHD, and stabilization of his pulmonary condition. We suggest that alloPBSCT preceded by non-myeloablative conditioning and followed by DLI may constitute a successful mode of therapy for patients suffering from advanced CGD with recurrent infectious episodes resulting in organ dysfunction, enabling them to achieve full donor chimerism and normal superoxide production with minimal risk of transplant-related toxicity and GVHD.
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PMID:Donor lymphocyte infusion post-non-myeloablative allogeneic peripheral blood stem cell transplantation for chronic granulomatous disease. 1045 77


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