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)

The active immunization of bone marrow (BM) donors with myeloma immunoglobulin (Ig) results in an idiotypic T cell response that can be transferred to the recipient. Using a murine model we evaluated the effectiveness, side-effects and underlying mechanisms of this approach. Balb/c (H-2d) mice were given a dose of HOPC-1F myeloma cells secreting the monoclonal IgG2a followed by lethal total body irradiation (7.5 Gy) 2 days later and a subsequent transplantation of 2 x 10(7) allogeneic MHC-matched DBA/2-derived marrow cells. Donors were pre-immunized with three i.p. injections of HOPC(IgG2a) or control Ig given with incomplete Freund's adjuvants (IFA) spaced 1 week apart. In some experiments, donor-spleen cells were additionally transferred 2 h post transplant. Injection of HOPC-myeloma led to death of all animals after a median survival time (MST) of 42 days. A lethal dose of TBI followed by transfer of unmanipulated marrow grafts plus splenocytes resulted in moderate antimyeloma effects with 8% of mice achieving long-term survival. Nearly the same results were obtained after transplantation of BM immunized with the control Ig. In contrast, transplantation of marrow grafts from HOPC(IgG2a) immunized donors exerted a significant GVM effect with 63% long-term survival for more than 180 days. The additional transfer of 2 x 10(7) immune splenocytes derived from the same donor resulted in even stronger anti-myeloma effects (FFR 87%). No increase in the incidence of severe acute GVHD was observed. In vitro data suggest that allogeneic CD8+ idiotype-specific T cells may be the major effector cells. Our results demonstrate that active immunization of the donor with the myeloma-specific Ig can induce powerful graft-versus-myeloma effects after allogeneic BMT.
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PMID:Transfer of idiotypic protein primed allogeneic marrow grafts elicits potent graft-versus-myeloma effects in mice. 1127 75

Allogeneic transplantation of hematopoietic stem cells (HSC) is a curative treatment for hematological malignancies aiming to eradicate the malignant clone using the immunological conflict inherent to donor HSC installation in the recipient. The different possible sources of HSCs (bone marrow, blood, and cord blood) and better knowledge of HLA typing has led to the development of new transplantation techniques and modalities (transplantations after non-myeloablative conditioning, haploidentical transplantations, etc.), which should improve patient survival and extend allograft indications. HSC allografting is subject to immunological reactions stemming from the histocompatibility discrepancy between donor and recipient. For the most part, these are reactions of the graft against the host (graft-versus-host disease: GVHD) and graft rejection (host-versus-graft: HVG). This immunological conflict can also be responsible for recognizing and destroying the recipient's residual tumor cells, which carry specific tumor antigens and/or minor antigens of histocompatibility (graft-versus-leukemia effect, GVL or graft-versus-malignancy effect, GVM). The posttransplantation period can also be riddled with various complications such as veno-occlusive disease, endocrine complications, as well as complications arising from infections and secondary neoplasms because of a more or less substantial and durable immune deficiency. Acute and chronic leukemias are the major indications for HSC allogeneic transplantation, for which the results are variable and closely related to the patient status, the hematological disease, and the transplant procedure. Other hematological diseases are also indications for allogeneic transplantation but are rarer, for which allogeneic transplantation remains nevertheless the only curative treatment, despite an overly high level of toxicity. Improvement in the results of unrelated transplantations, use of peripheral HSC or cord blood cells, development of non-myeloablative conditioning regimens, and techniques of ex vivo manipulation of the graft have allowed HSC allogeneic transplantation indications to be extended. The antitumor efficacy of donor lymphocytes infusion for relapses after transplantation mirrors the GVL effect and is the first stage in a targeted cellular immunotherapy using sensitized lymphocytes or dendritic cells.
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PMID:[Allogeneic hematopoietic stem-cell transplantation for hematological malignancies]. 1160 65

We describe a 51-year-old woman with recurrent follicular lymphoma from the age of 47 despite chemo-radio therapy, who subsequently underwent nonmyeloablative stem cell transplantation with conditioning consisting of fludarabine and low-dose total body irradiation (2 Gy). Myelosuppression was very mild, so the patient required no transfusions. Chimerism analysis from peripheral blood showed that T-cell mixed chimerism continued over 12 months after stem cell transplantation (the percentage of recipient T-cells was approximately 20%). Despite this, the lymphadenopathy disappeared, and the patient developed grade II acute GVHD (graft versus host disease). It has been considered that the establishment of full donor chimerism is required to induce GVHD and GVM (graft versus malignancy) effects. In this case, however, an allo-response was observed despite the persistence of T-cell mixed chimerism.
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PMID:[Persistent T-cell mixed chimerism in a case of malignant lymphoma after nonmyeloablative allogeneic peripheral blood stem cell transplantation]. 1250 89

Progress in allogeneic SCT will depend on several factors including the advances in the conventional treatment of diseases treated currently with allogeneic SCT, the expansion of the donor pool, the selective control of GVHD, the development of more effective and less toxic preparative regimens to eradicate the neoplastic cell population, the characterization of a new generation of hematopoietic growth factors and cytokines and the development of newer and safer techniques for ex-vivo manipulation of stem cells. The use of hematopoietic growth factor-mobilized donor progenitor cells collected from the peripheral blood has been associated with a rapid hematopoietic engraftment without an increase in the incidence of acute GVHD compared to allogeneic BMT, an increased donor acceptance, elimination of the risk of general anesthesia and a decreased cost. The use of nonmyeloablative conditioning regimens prior to SCT represents a novel treatment approach that may lead to reduced toxicity and an extended use of this treatment in older patients and those with co-morbid conditions and in the treatment of malignant and non-malignant disorders. This approach may play a role in inducing tolerance for solid organ transplantation and in utilizing the GVM effect to treat solid tumors that are not fully responsive to myeloablative cytotoxic regimens. The optimal intensity of cytoreduction and immunosuppression is not well defined. GVHD and disease recurrence remain a challenge. Promising results have been reported in patients with refractory hematologic malignancies as well as in metastatic renal cell cancer, but the ultimate role of this treatment modality remains to be defined pending prospective, well designed, randomized trials.
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PMID:Current concepts in allogeneic hematopoietic stem cell transplantation. 1498 67

For many years progress in event free and overall survival in patients diagnosed with multiple myeloma have been modest, however recently newer therapeutic options have become available and, for a small but increasing subset of patients, an "operational cure" can be offered. Although autologous transplantation is associated with a prolongation in event free and overall survival as compared to conventional chemotherapy, there is no plateau in the survival curves. By contrast, the use of allogeneic hematopoietic stem cells provides a tumor-free stem cell source and graft-vs.-myeloma activity leading to a higher frequency of long term survivors in molecular remission. Unfortunately, allogeneic transplantation has been associated with high transplant-related mortality (TRM). Non-myeloablative or reduced intensity conditioning (RIC) regimens, designed to be immunosuppressive rather than myeloablative, in an effort to reduce the toxicity and TRM associated with high dose chemotherapy, but maintaining the GVM effect, have been developed showing up to 90% overall response rate and low TRM. Interestingly, in a significant proportion of patients disease response is preceded by GVHD, suggesting a clear relationship between GVHD and graft vs. myeloma effect. Nevertheless these patients are at risk of developing life threatening complications and, on the contrary, some patients who reach disease control after GVHD and respond to GVHD therapy may finally relapse. Thus, efforts to separate GVM and GVHD are still required in order to improve the outcome of myeloma patients receiving allogeneic transplantation.
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PMID:Graft vs. host disease and graft vs. myeloma effect after non-myeloablative allogeneic transplantation. 1522 29

TCR gamma/delta profiles were analyzed in 13 multiple myeloma patients after allogeneic non-myeloablative transplantation. Results show that both aGVHD and minimal residual disease (MRD) eradication did significantly affect TCR gamma/delta profile. During follow-up, six patients developed an aGVHD episode; in five of them, this event fitted with a modification of the TCR profile. Eleven patients achieved PCR-negativity during follow-up. In the 90% of them, the appearance of a new predominant TCR peak was concomitant to the disappearance of the IgH clone. These results suggest that different T gamma/delta populations would sustain GVM and GVH effects after non-myeloablative allogeneic transplant.
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PMID:Different gamma/delta T clones sustain GVM and GVH effects in multiple myeloma patients after non-myeloablative transplantation. 1624 28