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)

Nonablative hematopoietic cell transplantation (HCT) is becoming a preferred treatment for those recipients in whom the potential toxicity risk of standard ablative allogeneic therapy may be unacceptable. Graft-versus-malignancy effects may be generated against epithelial malignancies which are similar to the graft-versus-leukemia activity that is well documented in human hematological malignancies. Renal cell carcinoma has been shown to be responsive to immunotherapy with recombinant human cytokines and may be an ideal model for exploring this novel therapy. Clinical investigations have demonstrated regression of metastatic renal cell carcinoma occurs in some patients following nonablative allogeneic HCT. However, graft-versus-host disease remains a significant toxicity of nonablative transplantation, and further investigations are warranted to further evaluate this promising approach and to improve its safety.
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PMID:Nonablative hematopoietic cell transplantation for the treatment of metastatic renal cell carcinoma. 1247 72

We evaluated the feasibility and efficacy of a reduced-intensity conditioning (RIC) regimen of fludarabine and melphalan to achieve rapid complete donor chimerism after allogeneic stem cell transplantation (SCT) in patients with metastatic solid tumors. Between January 1999 and January 2003, 8 patients with metastatic breast cancer (BC) and 15 with metastatic renal cell carcinoma (RCC) underwent allogeneic SCT after an RIC regimen of 5 days of fludarabine and 2 days of melphalan. Filgrastim-mobilized stem cells from HLA-identical related or unrelated donors were infused. Prophylaxis for graft-versus-host disease (GVHD) consisted of tacrolimus and methotrexate. All 22 evaluable patients had 100% donor chimerism at day 30 and at all measurement times thereafter. One patient died 19 days after SCT. Nine patients (39%) had grades II to IV acute GVHD and 10 patients (43%) had chronic GVHD. Five patients (22%) died of nonrelapse treatment-related complications. Treatment-related disease response was seen in 10 patients (45%), with 3 complete responses, 2 partial responses, and 5 minor responses. Fludarabine-melphalan is a feasible and effective RIC regimen for allogeneic SCT in metastatic BC and RCC. It induces rapid complete donor chimerism without the need for donor lymphocyte infusion. Tumor regression associated with GVHD is consistent with graft-versus-tumor effect.
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PMID:Rapid induction of complete donor chimerism by the use of a reduced-intensity conditioning regimen composed of fludarabine and melphalan in allogeneic stem cell transplantation for metastatic solid tumors. 1288 8

Reduced-intensity hematopoietic stem cell transplantation (RIST) is a new approach of stem cell transplantation, which has shown promising features as reported in multiple phase I and II studies. Elderly patients, who are not eligible for conventional myeloablative hematopoietic stem cell transplantation (HSCT), are now treatable with RIST. It has also reduced regimen-related toxicity and provided better prognosis in short-term follow-up than that of conventional HSCT. Favorable results have been reported particularly in hematological malignancies, such as chronic myelocytic leukemia and malignant lymphoma. Among solid tumors, metastatic renal cell carcinoma was found to respond well to RIST. Clinical studies are currently being conducted to evaluate the efficacy of RIST in other types of solid tumors. However, the mechanism of graft-versus-host disease and graft-versus-tumor remains unclear. More knowledge on the mechanism is crucial to enhance antitumor effect and to further improve the prognosis.
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PMID:Development of reduced-intensity hematopoietic stem cell transplantation in the National Cancer Center Hospital, Japan. 1292 7

We investigate the feasibility of CD34-selected peripheral blood stem cell (PBSC) transplantation followed by pre-emptive CD8-depleted donor lymphocyte infusions (DLI) after a minimal conditioning regimen. Six patients with advanced hematological malignancies ineligible for a conventional myeloablative transplant (n=5) or metastatic renal cell carcinoma (n=1), and with an HLA-identical (n=4) or alternative (n=2) donor were included. The nonmyeloablative conditioning regimen consisted in 2 Gy TBI alone (n=4), 2 Gy TBI and fludarabine (RCC patient, n=1) or cyclophosphamide and fludarabine (patient who had previously received 12 Gy TBI, n=1). Post transplant immunosuppression was carried out with cyclosporin (CyA) and mycophenolate mofetil (MMF). Initial engraftment was achieved in all patients. One out of six patients (17%) experienced grade > or =2 acute GVHD only after abrupt cyclosporin discontinuation and alpha interferon therapy for life-threatening tumor progression. T-cell chimerism was 23% (19-30) on day 28, 32% (10-35) on day 100, 78% (49-95) on day 180 and 99.5% (99-100) on day 365. Three out of four patients who had measurable disease before the transplant experienced a complete response. We conclude that CD34-selected NMSCT followed by CD8-depleted DLI is feasible and preserves engraftment and apparently also the graft-versus-leukemia (GVL) effect. Further studies are needed to confirm this encouraging preliminary report.
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PMID:Low T-cell chimerism is not followed by graft rejection after nonmyeloablative stem cell transplantation (NMSCT) with CD34-selected PBSC. 1452 Apr 30

Allogeneic hematopoietic stem-cell transplantation can induce curative graft-versus-leukemia reactions in patients with hematological malignancies. There is also evidence of such an effect in patients with solid tumors. We report two patients with metastatic renal cell carcinoma who underwent RIST. In both patients, disease progression was observed 6 months after transplantation. However, one patient had transient symptoms of tumor progression after the occurrence of acute graft-versus-host disease, consistent with graft-versus-tumor effects.
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PMID:Reduced-intensity stem cell transplantation in two cases of metastatic renal cell carcinoma. 1463 87

Nonmyeloablative allogeneic stem cell transplantation (NST) is thought to be an immunologic therapy in which donor T cells mediate a graft-versus-tumor effect. We recently reported the clinical outcome of a phase II trial of NST in metastatic renal cell carcinoma (RCC). However, the immune response correlates of clinical activity remain unknown. We now describe the analysis of T-cell subsets and T-cell cytokine-producing potential for those patients evaluable for immune monitoring. The incidence of graft-versus-host disease (GVHD) correlated with clinical outcome, with all responders exhibiting chronic GVHD. Following initial tapering of immunosuppression, an increase in the total numbers of CD8+ T cells but not CD4+ T cells was observed among responders compared to nonresponders. In addition, a greater ratio of CD8+ to CD4+ T cells producing IFN-gamma and IL-2 was seen in clinical responders at the time when clinical responses were first detected (day 180 after transplantation). Our results support the hypothesis that the antitumor effects of NST may be mediated by IFN-gamma-producing CD8+ T cells, and indicate that isolation of putative tumor antigen-specific T cells, ideally, should be pursued around day +180.
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PMID:Clinical responses following nonmyeloablative allogeneic stem cell transplantation for renal cell carcinoma are associated with expansion of CD8+ IFN-gamma-producing T cells. 1471 41

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

We describe a patient who had received reduced-intensity stem cell transplantation (RIST) for metastatic renal cell carcinoma (RCC). A 37-year-old man developed rapid progression of RCC during steroid therapy for immune-mediated thrombocytopenia and graft-versus-host disease (GVHD). After discontinuation of corticosteroid, RCC achieved long stable disease with the presence of chronic GVHD, despite low dose of prednisolone. This case suggests the impact of immunosuppression on progression of metastatic RCC after RIST.
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PMID:Balance between acute graft-versus-host disease and graft-versus-tumor effect after reduced-intensity transplantation for metastatic renal cell carcinoma. 1516 16

Seven out of 29 patients with metastatic renal cell carcinoma (RCC) considered eligible for allogeneic stem cell transplantation underwent nonmyeloablative stem cell transplantation (NST) from HLA-identical donors. Conditioning comprised cyclophosphamide, fludarabine and antithymocyte globulin. Prolonged mixed chimerism (MC) after engraftment converted to complete donor chimerism (CC) after infusion of donor lymphocytes and/or graft-versus-host disease (GvHD) in six patients. Five patients developed severe GvHD. Two of seven patients had a delayed tumor response after conversion to CC. After a median follow-up of 10 months (4-24 months), 5/7 patients are alive, one in very good partial remission (PR), one with stable and three with progressive disease. One of the seven patients died from sepsis in PR and 1/7 died from rapid tumor progression after sustained MC. None of the 22 nontransplanted patients responded to further therapies. Survival after 1 year was 59% in transplanted and 66% in nontransplanted patients (n.s.). A pooled data analysis from the literature suggests a graft-versus-tumor effect after transplant in patients with metastatic RCC, which becomes effective after chimerism conversion. Available data demonstrate high nonrelapse mortality in these patients. NST in RCC still has to be regarded as an investigational approach requiring careful patients' selection and longer follow-up within clinical studies.
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PMID:Nonmyeloablative stem cell transplantation in metastatic renal cell carcinoma: delayed graft-versus-tumor effect is associated with chimerism conversion but transplantation has high toxicity. 1522 Sep 55

Reduced intensity stem cell transplantation (RIST) is a new approach of stem cell transplantation, which has shown promising features as reported in multiple phase I and II studies. Elderly patients, who are not eligible for conventional myeloablative hematopoietic stem cell transplantation (HSCT), are now treatable with RIST. It has also reduced regimen-related toxicity and provided better prognosis in short-term follow-up than conventional HSCT. Among solid tumors, metastatic renal cell carcinoma was found to respond well to RIST. Clinical studies are currently being conducted to evaluate the efficacy of RIST in other types of solid tumors. However, the mechanism of graft-versus-host disease (GVHD) and graft-versus-tumor (GVT) effects remains unclear. More knowledge on the mechanism is crucial to enhance the antitumor effect and to improve the prognosis further.
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PMID:Reduced-intensity hematopoietic stem cell transplantation (RIST) for solid malignancies. 1564 May


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