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)

Autologous hematopoietic stem cell transplantation (autoSCT) is an effective treatment for patients with various hematologic malignancies. Despite the significant improvement in the overall outcome, disease progression after transplantation remains the major cause of treatment failure. With longer follow-up, therapy-related myelodysplasia/acute myelogenous leukemia is becoming an important cause of treatment failure. The prognosis for these 2 groups of patients is very poor. Allogeneic hematopoietic stem cell transplantation (alloSCT) is a potential curative treatment for these patients. However, the outcome with conventional myeloablative alloSCT after failed autoSCT is typically poor because of high transplant-related mortality. In an attempt to reduce the treatment-related toxicity, we studied a reduced-intensity conditioning regimen followed by alloSCT for patients with progressive disease or therapy-related myelodysplasia/acute myelogenous leukemia after autoSCT. This report describes the outcomes of 28 patients with hematologic malignancies who received a reduced-intensity alloSCT after having treatment failure with a conventional autoSCT. Fourteen patients received a hematopoietic stem cell transplant from a related donor and 14 from an unrelated donor. The conditioning regimen consisted of low-dose (2 Gy) total body irradiation with or without fludarabine in 4 patients and the combination of melphalan (140 mg/m(2)) and fludarabine in 24. Cyclosporine and mycophenolate mofetil were used for posttransplantation immunosuppressive therapy, as well as graft-versus-host disease (GVHD) prophylaxis, in all patients. All patients engrafted and had >90% donor chimerism on day 100 after SCT. Currently, 13 patients (46%) are alive and disease free, 7 patients (25%) developed disease progression after alloSCT, and 8 (32%) died of nonrelapse causes. Day 100 mortality and nonrelapse mortality were 25% and 21%, respectively. With a median follow-up of 24 months for surviving patients, the 2-year probabilities of overall survival, event-free survival, and relapse rates were 56.5%, 41%, and 41.9%, respectively. Six patients (21%) developed grade III to IV acute GVHD. Among 21 evaluable patients, 15 (67%) developed chronic GVHD. We conclude that (1) reduced-intensity alloSCT is feasible and has an acceptable toxicity profile in patients who have previously received autoSCT and that (2) although follow-up was short, a durable remission may be achieved in some patients who would otherwise be expected to have a poor outcome.
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PMID:Reduced-intensity allogeneic stem cell transplantation for patients whose prior autologous stem cell transplantation for hematologic malignancy failed. 1456 61

An X-linked severe combined immunodeficient (SCID) patient received a nonirradiated erythrocyte transfusion and developed transfusion-associated graft-versus-host disease (TAGVHD), which was controllable with high-dose corticosteroids. Haplo-identical SCT was performed, after a myeloablative conditioning regimen. At day +26, he developed GVHD. Chimerism studies revealed DNA of the erythrocyte transfusion donor (ETD) and recipient only. Because of early nonengraftment and the presence of alloreactive T cells of ETD origin, the patient was treated with an immunosuppressive conditioning regimen followed by a second SCT from the same donor. While tapering immunosuppression, he again developed mild GVHD, and DNA of ETD and bone marrow donor origin were both present. On cyclosporin, the ETD-DNA signal finally disappeared. High-resolution HLA typing revealed haplo-identity between BMD, ETD and the patient, which might have contributed to the relative mild course of the TAGVHD.
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PMID:Nonlethal transfusion associated graft-versus-host disease in a severe combined immunodeficient patient. 1459 91

Cytotoxic T lymphocytes (CTLs) are important effector cells of graft-versus-host disease (GVHD) and vascular endothelial cells are target cells of allospecific CTL. A combined assessment of T-cell activation and endothelial injury should result in a specific and sensitive test for GVHD. We examined circulating T lymphocytes for effector molecules involved in CTL-mediated endothelial injury. We analyzed CD4 and CD8 T lymphocytes of 24 long-term survivors of allogeneic stem cell transplantation with or without GVHD, and nine healthy, age-matched controls for signs of CTL activation and endothelial injury. IFN-gamma transcript levels in CD8 T cells were significantly elevated in SCT recipients with GVHD compared to patients without GVHD (767 CD3epsilon units/T cell (376-2050) vs 211 CD3epsilon units/T cell (159-274), P=0.01). Fas ligand transcript levels in CD4 T cells were significantly elevated in SCT recipients without GVHD compared to patients with GVHD (20 CD3epsilon units/T cell (0-78) vs 0 CD3epsilon units/T cell (0-0), P=0.01). Von Willebrand factor plasma levels were high in patients with GVHD, but normal in patients without GVHD (209 (186-254) vs 120 (100-141), P=0.0005). This assessment of T-cell activation and endothelial injury results in a sensitive and specific test to identify patients with active chronic GVHD.
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PMID:Combining altered levels of effector transcripts in circulating T cells with a marker of endothelial injury is specific for active graft-versus-host disease. 1462 79

Agnogenic myeloid metaplasia (AMM) is a clonal hematopoietic stem cell disorder characterized by bone marrow fibrosis, extramedullary hemopoiesis, splenomegaly and a leukoerythroblastic blood picture. Current standard therapies using hydroxyurea, interferon, androgens or corticosteroids have not shown to prolong survival of patients with AMM. In this study, we performed a curative approach using an HLA-matched sibling as a donor for allogeneic peripheral blood stem cell transplantation (PBSCT) for a 45-year-old woman with AMM. Busulfan and cyclophosphamide were given as a conditioning regimen from day -7 to day -2 with cyclosporinA and methotrexate as post-transplant immunosuppressive therapy. Donor PBSCs were mobilized by G-CSF at 16 microg/kg/day for five days and transplantation was performed on March 2-3, 2000. The patient rapidly engrafted within 2 weeks after PBSC infusion without evidence of graft versus host disease. Her blood counts and bone marrow 2 years after transplantation were normal with full donor pattern by molecular analysis. In conclusion, marrow fibrosis can be reverted to normal by allogeneic PBSCT. Allogeneic PBSCT should thus be offered to AMM patients if an HLA-matched sibling is available. This report represents the first SCT for AMM in Thailand.
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PMID:Reversal of marrow fibrosis in agnogenic myeloid metaplasia by allogeneic peripheral blood stem cell transplantation. 1462 30

We performed a retrospective analysis of outcome in 45 patients with multiple myeloma receiving unrelated donor stem cell transplants (UD-SCT) in the UK between 1993 and 2002; 17 received myeloablative conditioning regimens and 28 received reduced intensity conditioning (RIC) protocols. Forty patients received pretransplant CAMPATH serotherapy. Forty-two of 45 patients had detectable disease at transplant, but 33 of 45 were chemoresponsive. Sixty per cent of patients had received a previous autograft. Myeloid engraftment was seen in 95% of recipients and was significantly faster in recipients receiving peripheral blood stem cells (P = 0.07) and RIC (P = 0.001). The incidence of severe (grade 3/4) acute graft versus host disease (aGvHD) was 5% (2/40). The 100-d non-relapse mortality was 18% (5/38) following RIC and 53% (9/17) following myeloablative regimens. Twenty-nine per cent of patients achieved a complete remission, 61% a partial remission, giving a 90% overall response rate. At median follow-up (513 d), overall survival was 40%: 54% in the RIC group (median follow-up: 489 d) and 18% in the myeloablative group (median follow-up: 560 d). In recipients of UD-SCT, RIC protocols that incorporated CAMPATH were associated with faster myeloid engraftment, less severe aGvHD and lower 100-d non-relapse mortality than myeloablative regimens, without a corresponding rise in relapse rate during the period of observation.
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PMID:The outcome of unrelated donor stem cell transplantation for patients with multiple myeloma. 1463 80

Allogeneic stem cell transplantation (allo-SCT) is a well-established treatment modality for children with severe aplastic anemia (SAA). Treatment failures are rare and mostly caused by graft rejection. Increasing mixed chimerism represents a stage at the very beginning of graft rejection, where immunological intervention might be an effective prophylactic approach. To substantiate this, we: (1) monitored peripheral blood cells from children with SAA after allo-SCT and performed pre-emptive immunotherapy in patients with increasing MC. In all, 23/34 courses of 32 children with SAA after allo-SCT showed a complete chimerism (CC) throughout and 10/34 developed different types of mixed chimerism (MC). Altogether, 4/10 with MC spontaneously developed decreasing MC, 2/10 courses persisted with low proportions of autologous cells below 30% (stable-MC), 4/10 developed increasing MC and one patient showed an autologous recovery. All patients with CC, decreasing MC or stable MC remained in continuous complete remission (CCR). In all, 2/4 patients with increasing MC developed graft rejection. Based on these observations, 2/4 new patients with increasing MC received low-dose DLIs prophylactically, and remained in CCR without any GVHD. These results substantiate that low-dose DLI in children with SAA and increasing MC can prevent graft rejection with a calculable risk to induce severe GVHD.
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PMID:Clinical relevance of serial quantitative analysis of hematopoietic chimerism after allogeneic stem cell transplantation in children for severe aplastic anemia. 1464 53

To evaluate the feasibility of reduced intensity stem cell transplantation (RIST) with bone marrow from a matched unrelated donor (MUD), we retrospectively investigated 20 patients with hematological disorders who received RIST in the Tokyo SCT consortium from January 2000 to October 2002. The preparative regimens were fludarabine-based (150-180 mg/m(2), n=18) or cladribine-based (0.77 mg/kg, n=2). To enhance engraftment, antithymocyte globulin (ATG) and 4 or 8 Gy total body irradiation (TBI) were added to these regimens in nine and 11 patients, respectively. GVHD prophylaxis was cyclosporine with or without methotrexate. In all, 19 achieved primary engraftment. Three developed graft failure (one primary, two secondary), and five died of treatment-related mortality within 100 days of transplant. Seven of the 19 patients who achieved initial engraftment developed grade II-IV acute GVHD, and seven of 13 patients who survived >100 days developed chronic GVHD. At a median follow-up of 5.5 months, estimated 1-year overall survival was 35%. Compared with a TBI-containing regimen, an ATG-containing regimen was associated with a high risk of graft failure (30 vs 0%, P=0.0737). This study supports the feasibility of RIST from MUD; however, procedure-related toxicities remain significant in its application to patients.
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PMID:Feasibility of reduced intensity hematopoietic stem cell transplantation from an HLA-matched unrelated donor. 1475 17

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

Graft-versus-lymphoma (GVL) effect has been described in patients with malignant lymphoma after allogeneic stem cell transplantation (alloSCT). The effect of interferon-alpha (IFN-alpha) on the GVL effect still remains unclear. Here we report on a 29-year-old woman with refractory diffuse large B-cell lymphoma (DLBL). Her clinical findings included multiple masses in the liver, stomach, bilateral kidneys, thyroid, vertebral bones and a bulky mediastinal mass. Since the patient did not respond to various combination chemotherapies and further developed superior vena cava syndrome, allogeneic peripheral blood stem cell transplantation (PBSCT) from a HLA-identical brother was carried out after a myeloablative TBI/CY-based conditioning regimen. DLIs have been also performed every 4 weeks since day +14. As a result, the lymphoma masses showed a partial response. In order to enhance the GVL effect, IFN-alpha was further given at a maximum of 3 MU four times per week. Although the patient only experienced graft-versus-host disease of the skin (grade II) even after both DLIs and IFN, complete clinical remission was observed. 200 days after transplantation, the patient is still disease-free and in good condition. This report suggests the curative potential of IFN-alpha combined with DLI after allogeneic SCT in refractory DLBL.
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PMID:[Remission induction of refractory diffuse large B-cell lymphoma with allogeneic peripheral blood stem cell transplantation followed by interferon-alpha and donor lymphocyte infusion]. 1504 25

Graft rejection is a major cause of treatment failure after T-cell-depleted stem cell transplantation (TCD-SCT) and remains a therapeutic challenge. Donor leukocyte infusions (DLIs) have an efficient graft versus host effect, which has been successfully used to treat recipient relapses. We hypothesized that this effect could be exploited to counteract the host versus graft reactions responsible for graft rejection. We report two adult patients with haematological malignancies who underwent sex-mismatched TCD-SCT from HLA-identical sibling donors. Peripheral blood (PB) counts and bone marrow (BM) cellularity were studied on a serial basis. Sequential chimaerism and minimal residual disease analysis were performed by FISH on PB and BM samples as well as on leukocyte lineages (T and B lymphocytes and myeloid cells) purified from PB using immunomagnetic technology. Both patients were diagnosed with incipient graft rejection 2-3 months after engraftment, based on persistently decreasing PB counts and BM cellularity together with the observation of decreasing mixed chimaerism (increasing percentage of recipient cells), mostly in whole PB and T lymphocytes. Both patients were successfully treated with a single DLI (1 x 10(7) CD3+ cells/kg), thereafter achieving normal PB counts and BM cellularity as well as complete chimaerism. Interestingly, the only side effect observed was mild graft versus host disease that did not require treatment. In conclusion, provided that an early diagnosis is made, the graft versus host lymphohaemopoietic effect harboured by immunocompetent donor cells can be successfully used for the treatment of incipient graft rejection.
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PMID:Successful treatment of incipient graft rejection with donor leukocyte infusions, further proof of a graft versus host lymphohaemopoietic effect. 1506 92


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