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)

Immune mechanisms superimposed to the myeloablative conditioning regimens exert an additional powerful effect in eradicating leukemia and in achieving immunological control of minimal residual disease. The impact of GVHD-independent GVL has been evaluated to be absent, or near absent, in ALL, about 30% in AML and about 40% in CML. While until little time ago most of the evidence in favor of an immune antileukemia mechanism exerted by allo BMT in CML was indirect, based on the lack of GVL, there is now solid evidence of a positive type, based on the antileukemia effect of donor lymphocyte infusions in patients having relapsed after transplant. There are three lines of indirect clinical evidence for GVL in CML: they include the classical linkage between GVHD and reduced relapse rate, increased relapse rate after identical twin allografts, and increased relapse risk after effective GVHD prophylaxis, with T lymphocyte depletion in the foreground. The eradicating effects of donor lymphocyte infusions in relapsed patients are the ultimate demonstration that allogeneic immune competent cells are capable of recognizing and destroying the Ph-positive clone. However the frequency of irreversible aplasia indicates that donor lymphocytes act in the same way on residual host hematopoiesis, so that a second graft, without repeat conditioning, should be programmed for such cases.
Leuk Lymphoma 1993
PMID:The graft versus leukemia (GVL) effect after allogeneic bone marrow transplantation for chronic myelogenous leukemia (CML). 825

Two hundred and twenty-nine patients with chronic myeloid leukaemia in chronic phase awaiting bone marrow transplantation from an HLA-identical sibling donor were randomized as part of their conditioning, to receive splenic irradiation (SI+, 115 patients), or not (SI-, 114 patients). Both groups were identical in regard to age, sex, donor/recipient sex combination and disease activity. Survival, leukaemia-free survival, incidence of transplant-related mortality, acute and chronic graft versus host disease, incidence of rejection and probability of relapse were not different in either groups at a median follow-up time of 4.5 years (minimum follow-up 2 years). Recovery of peripheral white blood cell counts to 1 x 10(9)/l but not of platelet counts to 50 x 10(9)/l was significantly faster in patients with SI+ (21 vs 24 days). This small benefit does not justify routine splenic irradiation prior to BMT, in CML.
Leuk Lymphoma 1993
PMID:Splenic irradiation before bone marrow transplantation for chronic myeloid leukemia: update of a prospective randomized study. 825 1

Rodents given cyclosporine (CSP) for several weeks after autologous or syngeneic bone marrow transplantation develop a syndrome that mimics allogeneic graft-versus-host disease (GVHD). Autologous GVHD has also been reported after administration of CSP in patients who have received autologous bone marrow transplantation (ABMT) with untreated marrow for lymphoma or acute myeloid leukemia (AML). Our study was designed to determine whether CSP administration is associated with appearance of autologous GVHD in patients with AML receiving ABMT with 4-hydroperoxycyclophosphamide (4HC)-purged marrow and whether there was a dose-dependent effect of CSP on development of the syndrome. Thirty-three patients with AML (18 in first remission [CR1], 10 in CR2, and 5 in CR3) received intravenous CSP, beginning on the day of ABMT, after a preparative regimen of busulfan and cyclophosphamide and ABMT with 4HC-treated marrow. Skin biopsies were obtained weekly after ABMT or on appearance of rash and were graded for GVH changes. In the first phase of this study, groups of patients received CSP dosages of either 1 mg/kg/day (7 patients), 2.5 mg/kg/day (8 patients), or 3.75 mg/kg/day (6 patients) for 28 days. Sixteen of the 21 patients (76%) developed cutaneous histopathologic grade 2 GVHD at a median of 34 days (range, 14-49) after ABMT, and cutaneous manifestation were present at time of positive biopsy in 11 of the 16 patients. There was no apparent difference in frequency, time to onset, or duration of GVHD among the three CSP dosage groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Leuk Lymphoma 1993 Oct
PMID:Cyclosporine-induced graft-versus-host disease after autologous bone marrow transplantation for acute myeloid leukemia. 826 Aug 96

Patients with human T-cell lymphotropic virus I (HTLV-I)-associated leukemia/lymphoma were treated with different forms of IL-2 receptor (IL-2R)-directed therapy that exploit the difference in IL-2R expression between normal and malignant cells. Using unmodified anti-Tac monoclonal antibody, one-third of the patients with adult T-cell leukemia (ATL) treated have undergone a remission, in two cases complete. There was little toxicity observed; however, unmodified monoclonal antibodies are limited by their immunogenicity and their poor effector functions. To address these issues, "humanized" anti-Tac was produced that contains the complementarity-determining regions from the mouse with the remainder of the molecule derived from human IgG1 kappa. This antibody is dramatically less immunogenic than the murine version, has improved pharmacokinetics, and, in contrast to the parent antibody, manifests antibody-dependent cellular cytotoxicity (ADCC). To enhance its effector function, anti-Tac was armed with toxins and alpha- and beta-emitting radionuclides. In a clinical trial of 90Y-anti-Tac in ATL patients, at the doses used (5, 10, and 15 mCi 90Y-anti-Tac per patient), 10 of the 15 patients with ATL treated to date underwent sustained partial or complete remission. Thus, the clinical application of IL-2R-directed therapy represents a new perspective for the prevention of allograft rejection and for the treatment of graft-versus-host disease, select autoimmune disorders, and leukemia/lymphoma.
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PMID:1992 Stohlman Memorial Lecture: targeting the IL-2 receptor. 836 Dec 23

We report a case study of a patient suffering from T-lymphoblastic lymphoma, for whom autologous T-cell-depleted bone marrow transplantation was carried out. Low-dose cyclosporin A (CsA) was administered just after autologous bone marrow transplantation (ABMT) for induction of autologous graft-versus-host disease. Three months later, the lymphoma relapsed with marked monoclonal gammopathy of the immunoglobulin A type, which had not been seen before ABMT. It is suggested that the regrowth of the lymphoma cells was related to the maturation of B cells or the secretion of immunoglobulins from plasma cells, associated with some cytokines produced under the condition of an abnormal immunological circumstance after ABMT plus CsA.
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PMID:Monoclonal gammopathy (IgA: lambda) after autologous T-cell-depleted bone marrow transplantation in a patient with non-Hodgkin's lymphoma. 837 1

Although serial detection of bcr-abl positive cells by PCR appears able to identify distinct patient groups with different risks of relapse following BMT, there remain many unanswered questions regarding the clinical utility and biological significance of PCR detectable cells in this disease. Many of the studies summarized have conflicting results and the influence of various clinical parameters which are known to affect the risk of relapse post-BMT has not yet been consistently associated with the ability to detect bcr-abl positive cells by PCR. These clinical parameters include GVHD, T-cell depletion and intensity of immunosuppression following BMT. Prospective studies with larger patient numbers will be necessary to define the impact of these factors in PCR status and relapse. The answers to all these questions will increase our understanding of the biology of chronic myelogenous leukemia and help provide more effective therapies for the future.
Leuk Lymphoma 1993 May
PMID:Clinical significance of bcr-abl gene rearrangement detected by the polymerase chain reaction after allogeneic bone marrow transplantation in chronic myelogenous leukemia. 837 16

Treatment with ganciclovir was assessed in 13 patients who underwent allogeneic T-lymphocyte depleted bone marrow transplantation (BMT) for a variety of malignant hematological disorders and subsequently developed severe cytomegalovirus (CMV) disease without pneumonia. The manifestations of CMV disease appeared on days 23-105 (median 51) post BMT, and included gastrointestinal symptoms, weight loss, fever, disturbed liver function, leukopenia and thrombocytopenia. Ganciclovir was administered for 14 days, without the addition of intravenous immunoglobulins. Following therapy, the clinical manifestations subsided in most of the patients, while leukopenia, thrombocytopenia and liver dysfunction resolved in about half of the patients. One patient who experienced recurrent CMV disease responded to a second course of ganciclovir. Poor response to ganciclovir treatment was observed in 2 of the 3 patients with grade 4 graft-versus-host disease (GVHD). Our experience suggests that a 2-week course of ganciclovir may be effective in BMT recipients who develop severe CMV-associated disease without lung involvement, especially when there is no concomitant severe GVHD.
Leuk Lymphoma 1993 May
PMID:Ganciclovir for the treatment of disseminated CMV disease without pneumonia in allogeneic T-lymphocyte depleted bone marrow transplantation. 839 30

Immunologic reactions occurring after allogeneic bone marrow transplantation, known as graft-versus-leukemia effect, contribute significantly to the control of minimal residual disease and decreased risk of relapse post-transplant. Graft-versus-leukemia reactions occur with or without graft-versus-host disease and are either mediated through T-cells or are independent of T-cells. The contribution made by graft-versus-leukemia reactions to improvement in overall survival depends upon the underlying type of leukemia, the nature of the marrow graft and the morbidity of any associated graft-versus-host disease. This article reviews the evidence demonstrating graft-versus-leukemia effect in clinical bone marrow transplantation, some approaches to dissociate graft-versus-leukemia from graft-versus-host disease, and attempts to induce graft-versus-leukemia reactions in the setting of autologous bone marrow transplantation by immunotherapy.
Leuk Lymphoma 1993 Aug
PMID:Graft-versus-leukemia reactions in clinical bone marrow transplantation. 840 Nov 79

When allogeneic BMT is used for the treatment of leukemia, depletion of T cells from the donor BM to avoid GVHD may be accompanied by persistence of host cells and post-transplant relapse. In this report, a murine model of MHC-compatible BMT was used to show that delayed infusion of immunocompetent donor cells early after T cell-deficient BMT eliminated residual host cells and provided an antileukemic effect without causing lethal GVHD. AKR (H-2k) recipient mice were pre-conditioned with 9 Gy total body irradiation (LD50) and transplanted with 10(7) BM cells from MHC-matched B10.BR donors. These mice did not develop GVHD and became stable, long-term mixed (donor-host) T cell chimeras. In this model, mixed or incomplete donor T cell chimerism was associated with decreased GVL reactivity. AKR hosts that were transplanted with B10.BR bone marrow admixed with 3 x 10(7) B10.BR spleen cells (as a source of T cells) became complete donor T cell chimeras, but they developed severe and lethal GVHD. However, when the infusion of donor spleen cells was delayed until 21 days after BMT, few mice exhibited any clinical signs of GVHD, and > 95% of the mice became long-term survivors. The infused spleen cells eliminated residual host T cells by 21 days after infusion, and most chimeras were able to resist a supralethal challenge with AKR leukemia/lymphoma cells. Thus, post-transplant adoptive immunotherapy with normal mononuclear cells from the marrow donor may be an effective way to eliminate residual disease or treat leukemia relapse after BMT without causing significant GVHD.
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PMID:Delayed infusion of normal donor cells after MHC-matched bone marrow transplantation provides an antileukemia reaction without graft-versus-host disease. 848 80

Interleukin-1 receptor type 1 (IL-1R), IL-2 receptor alpha subunit (IL-2R) and IL-6 receptor alpha subunit (IL-6R) mRNA expression in peripheral blood mononuclear cells (PBMC) in 17 patients who underwent allogeneic bone marrow transplantation (allo BMT) and 2 patients who underwent autologous transplantation were analyzed using a semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). There were several exceptions in some cases and IL-1R expression was found to vary in a rather wide range, however, the expression of IL-2R and IL-6R mRNA tended to increase during the development of graft-versus-host disease (GVHD). In particular, IL-2R mRNA expression was increased in four patients with GVHD and graft failure. In contrast, IL-2R and IL-6R mRNA expression was not increased in autologous (auto) BMT and auto peripheral blood stem cell transplantation (PBSCT) patients. These findings suggest that IL-2R and maybe IL-6R mRNA expression in PBMC play an important role in the development of an allo response and GVHD. Therefore, the analysis of cytokine receptor mRNA expression in PBMC after allo BMT may provide important information concerning the immune response and the cytokine network system in marrow transplants.
Leuk Lymphoma 1995 Oct
PMID:Cytokine receptor gene expression in peripheral blood mononuclear cells during graft-versus-host disease after allogeneic bone marrow transplantation. 853 20


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