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)

Reduced-intensity conditioning (RIC) regimens are increasingly used for allogeneic stem cell transplantation (allo-SCT). RIC has been shown to allow engraftment with minimal early transplantation-related mortality (TRM). However, in the context of RIC, predictive factors for acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively) and their effect on outcome remain unknown. In this report, we analyzed the outcome of 101 high-risk patients (70 hematologic and 31 nonhematologic malignancies) who received an HLA-identical sibling allo-SCT after RIC, including fludarabine, busulfan, and antithymocyte globulin (ATG). The cumulative incidence of grade II-IV aGVHD was 36% (95% confidence interval [CI], 27%-45%), whereas the cumulative incidence of cGVHD at 2 years was 43% (95% CI, 33%-53%). In multivariate analysis, the incidence of aGVHD was significantly associated with the ATG dose infused during conditioning (P =.0005), whereas peripheral blood as stem cell source was the only predictive factor for the development of cGVHD (P =.0007). The 1-year cumulative incidences of disease progression or relapse in patients with (n = 69) and without (n = 31) GVHD (whatever its form or grade) were 30% (95% CI, 19%-41%) and 55% (95% CI, 37%-72%), respectively (P =.02), suggesting that a potent graft-versus-tumor (GVT) effect can be achieved in high-risk patients following RIC. Moreover, the GVT effect was closely associated with GVHD without an increased risk of TRM (cumulative incidence of TRM, 18% [95% CI, 10%-25%]). Collectively, these results provide a framework for the refinement of RIC approaches designed to enhance the GVT effect with an acceptable risk of GVHD.
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PMID:Graft-versus-host disease following allogeneic transplantation from HLA-identical sibling with antithymocyte globulin-based reduced-intensity preparative regimen. 1264 33

Allogeneic stem cell transplantation (allo-SCT) after reduced-intensity conditioning was evaluated in 22 patients (median age 53, range 36-66 years) with multiple myeloma with progression after an autologous SCT. Seven patients received a transplant from a human leucocyte antigen (HLA)-identical sibling and 15 patients (68%) from an unrelated donor [including 3/22 (14%) from a HLA-mismatched unrelated donor]. Graft-versus-host disease (GVHD) prophylaxis consisted of serotherapy with antithymocyte globulin (ATG) and cyclosporine (CSA) (n = 12) or CSA plus mycophenolate mofetil (n = 10). Despite of heavy pretreatment, the transplant-related mortality (TRM) for all grafted patients was acceptable at 5/22 patients (23%). Seven of 21 patients (33%) that were evaluated developed grade II GVHD and one (5%) patient developed grade III/IV acute GVHD. Seven patients developed chronic GVHD (cGVHD), but only one was extensive. Eleven patients died of progressive disease within a median of 7 months (2-19 months) post transplant. Thirteen of all 22 patients (59%) achieved a partial or complete remission with six of these 13 patients (46%) remaining event free at a median of 24 months (range 8-36 months) post allografting. Estimated 2 year overall and event-free survival was, respectively, 25.5% and 22.0% for the whole patient group, and 62.5% and 57.1% for patients with chemosensitive disease. Chemorefractory disease prior to allogeneic stem cell transplantation (P = 0.0182) and absence of cGVHD (P = 0.069) were associated with shorter event-free survival. Thus long-term disease control can be achieved, but is restricted to patients responding to prior salvage chemotherapy.
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PMID:Follow-up of patients with progressive multiple myeloma undergoing allografts after reduced-intensity conditioning. 1271 63

In an attempt to capture graft-versus-tumor effects without graft-versus-host disease (GVHD), the authors initiated a trial of nonmyeloablative allogeneic bone marrow transplantation (BMT) in patients with advanced hematologic malignancies, with the majority of patients having chemotherapy-refractory disease. Forty-two patients received an HLA-matched related donor BMT after a cyclophosphamide and antithymocyte globulin-based conditioning that also included thymic irradiation for patients who had not received prior mediastinal radiotherapy. Prophylactic donor leukocyte infusion (pDLI) at a dose of 1 x 10(7) CD3(+) cells per kilogram were given beginning 5 weeks post-BMT to 16 patients with mixed chimerism (MC) but without GVHD, whereas 26 patients did not receive pDLI, either because of GVHD or early relapse. Twelve of 16 patients (75%) receiving pDLI had T cell chimerism at the time of pDLI >/=40%. These patients, by day 100 post-BMT, either converted to full donor chimerism (FDC) (n = 10) or had an increase in or stable donor chimerism (n = 2) after pDLI. Four of 4 patients whose T cell chimerism was </=20% at the time of pDLI, lost the graft. In contrast, only 5 of 18 evaluable patients (28%) not receiving a pDLI converted to FDC by day 100 post-BMT, 7 maintained MC, and 10 of an evaluable 22 lost the graft. Patients who had undergone a previous autologous stem cell transplant had a higher rate of conversion to FDC (69% v 31%) and higher incidence of GVHD (69% v 34%) compared with those who did not have a previous autologous SCT. Eleven of 16 patients (69%) who received a pDLI achieved a remission with 50% 1-year progression-free survival rate and 44% 3-year overall survival rate. Nineteen of 42 patients (45%) had >/=grade II acute GVHD, including 12 after BMT and 7 after pDLI. Approximately one third of patients, after having initial MC, eventually lost their donor graft. The authors conclude that (1) pDLI has the potential to convert MC to FDC; (2) sustained remissions can be achieved in patients with chemorefractory hematologic malignancies who receive a pDLI, albeit with a significant risk of acute GVHD; and (3) the degree of donor T cell chimerism at the time of pDLI is predictive of the fate of MC, ie, donor T cell chimerism >/=40% or </=20% at the time of pDLI correlates with conversion of MC or loss of the graft, respectively.
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PMID:Impact of prophylactic donor leukocyte infusions on mixed chimerism, graft-versus-host disease, and antitumor response in patients with advanced hematologic malignancies treated with nonmyeloablative conditioning and allogeneic bone marrow transplantation. 1276 82

Late-onset noninfectious pulmonary complications (LONIPCs) occurring beyond 3 months after allogeneic stem cell transplantation (allo-SCT) have become recognized as life-threatening complications, and they reduce the recipient's quality of life. However, the pathogenesis and optimal treatment for LONIPCs are still unclear. In this study, we retrospectively analyzed the incidence and outcome of LONIPCs among allo-SCT recipients. Between October 1993 and September 2001, 96 patients underwent allo-SCT and 76 patients who survived and were free of disease for more than 3 months after SCT were enrolled. Among the 76 patients, 18 patients (23.7%) developed LONIPCs at a median interval of 227 days after allo-SCT (range, 91-1105 days). The patients with LONIPCs were subclassified into those with bronchiolitis obliterans (BO) (6 patients), with interstitial pneumonia (IP) (11 patients), or with both BO and IP (1 patient). The presence of extensive chronic graft-versus-host disease (GVHD) was significantly associated with the development of LONIPCs (P =.0008). Liver or skin involvement in chronic GVHD was not associated, but sicca syndrome was significantly associated with the development of LONIPCs (P <.0001). Most of the IP patients (58.3%) responded well to immunosuppressive treatment, while BO patients did not respond to the therapy. Eight of the 18 patients with LONIPCs died. The major cause of death was respiratory failure (62.5%). The relapse rate of primary malignant disease in the LONIPC patients was significantly lower than that of non-LONIPC patients (1 of 17 [5.9%] versus 16 of 52 [30.8%]; P =.0387). These results indicate that the development of LONIPCs was strongly associated with chronic GVHD and especially with sicca syndrome and the graft-versus-leukemia (GVL) effect.
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PMID:Late-onset noninfectious pulmonary complications after allogeneic stem cell transplantation are significantly associated with chronic graft-versus-host disease and with the graft-versus-leukemia effect. 1290 47

HLA disparity is a major risk factor for graft rejection and GVHD. We report a patient with CML (accelerated phase) who underwent allogeneic SCT from a mismatched unrelated donor and developed acute GVHD. With immunosuppression, GVHD symptoms improved but graft rejection occurred. After a second conditioning regimen, the patient received a second graft from a haploidentical related donor. Engraftment occurred, but the patient died from GVHD and pulmonary aspergillosis. Chimeric analysis revealed that all leukocytes were of donor 2 origin apart from CD3+ T cells, which were 100% donor 1 type. Thus, in spite of intensified immunosuppression and successful transplantation of a second graft, T cells from the first donor persisted and induced severe acute GVHD.
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PMID:Severe acute graft-versus-host disease after T-cell depleted allogeneic stem cell graft from a second donor caused by persisting T-cells from the first donor. 1294 98

A number of reduced-intensity conditioning(RIC) regimens, which mainly consisted of potent immunosuppressive agents but not of myeloablative agents, has been explored in order to achieve successful engraftment and subsequent graft-versus-leukemia/tumor effect. Because of the decreased regimen-related toxicity, RIC regimens have replaced myeloablative regimens, particularly for those who are not eligible for high dose chemoradiotherapy due to advanced age or organ dysfunction. However, allogeneic stem cell transplantation(allo-SCT) using RIC regimens sometimes end up with mixed chimerism and may require donor-lymphocyte infusion to achieve complete chimera. Furthermore, strong immunosuppressive agents used in RIC regimens might contribute to the delayed immune recovery after allo-SCT, which might subsequently increase the incidence of infections. These findings suggest that the hematopoietic and immune reconstitution after allo-SCT using RIC regimens is different from that using conventional regimen. In this article, hematopoietic reconstitution, phenotypic analysis of lymphocytes, infections, and graft-versus-host disease after allo-SCT using RIC regimens are discussed, comparing with those using conventional regimens.
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PMID:[Immune reconstitution after allogeneic stem cell transplantation using nonmyeloablative or reduced-intensity conditioning regimen]. 1451 21

Allogeneic hematopoietic stem-cell transplantation(allo-SCT) is a potentially curative treatment for patients with chronic myeloid leukemia(CML). However, a major obstacle to this approach is a considerably high risk for transplantation-related mortality(TRM) mostly associated with toxic conditioning and graft-versus-host disease(GVHD). Clinical observations that the infusions of allogeneic T-cells can successfully induce remissions in the majority of patients with CML in relapse after allo-SCT lead the way to the exploitation of non-myeloablative or reduced-intensity conditioning for the initial allografting. Current results of reduced-intensity transplants for CML in chronic phase are encouraging, although the incidence of graft rejection and intractable GVHD still remains a great challenge. To enhance graft-versus-leukemia without exacerbating GVHD, further efforts are required to develop cellular immunotherapy more selectively targeting malignant but not normal host cells.
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PMID:[Reduced-intensity hematopoietic stem cell transplantation and donor lymphocyte infusions for chronic myeloid leukemia]. 1451 26

Allogeneic stem cell transplantation (allo-SCT) is an effective and potentially curative treatment for some cases of multiple myeloma (MM). The curative efficacy of allo-SCT may be largely attributed to its immunological activity, the graft-versus-myeloma (GVM) effect. To evaluate the kinetics of residual myeloma cells, we analyzed the follow-up bone marrow samples of three MM patients by means of a real-time molecular assay. We identified a consistent correlation between onset of graft-versus-host disease and disease response. These data suggest that real-time molecular follow-up can be used to monitor the GVM effect and that it can be employed in the clinical setting to tailor post transplant immunomodulation.
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PMID:Detection of minimal residual disease by real-time PCR can be used as a surrogate marker to evaluate the graft-versus-myeloma effect after allogeneic stem cell transplantation. 1452 Apr 23

Allogeneic SCT is the most effective method to achieve cure in patients with MPD and MDS. This approach is associated with significant risk of morbidity (eg, GVHD) and TRM, although the incidence and severity vary based on donor and recipient characteristics. For young patients with HLA-matched donors, SCT is the preferred therapy. Efforts to improve outcome for older patients and for patients with alternative donors have led to decreased treatment-associated complications with associated better long-term DFS.
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PMID:Allogeneic hematopoietic stem cell transplantation for myeloproliferative disorders and myelodysplastic syndromes. 1456 Jul 85

The aim of this study was to identify the risk factors for acute graft-versus-host disease (aGVHD) in children transplanted from a matched-sibling donor (MSD) or an unrelated donor (UD). In all, 87 children consecutively underwent allogeneic bone marrow transplantation (BMT) from MSD (n=36), and UD (n=51). GVHD prophylaxis included CsA alone (n=33) or with MTX (n=51). ATG was added in UD-BMT and thalassemic recipients. CsA whole-blood concentrations were measured by EMIT and the dosing regimen was monitored by Bayesian pharmacokinetic modelling. Trough blood concentration (TBC) during the first 2 weeks post transplantation was lower in children who developed grade II-IV aGVHD than those developing no GVHD or only grade I (57+/-9 vs 94+/-8 ng/ml, P=0.007), whereas peak blood concentration and area under concentration curve vs time were similar in both groups. TBC <85 ng/ml and 'use of MTX' were associated with aGVHD in MSD-SCT (P=0.003 and 0.007, respectively) as well as in UD-SCT (P=0.006 and 0.003). Donor age >or=8 years was significant only in MSD-BMT. Our results have shown the significant decisive role of pharmacological factors such as CSA TBC or use of MTX in the occurrence of GVHD in MSD as well as in UD paediatric BMT.
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PMID:Clinical and pharmacological risk factors for acute graft-versus-host disease after paediatric bone marrow transplantation from matched-sibling or unrelated donors. 1456 88


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