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)

Thrombotic microangiopathy (TMA) may occur after allogeneic hematopoietic stem cell transplantation (HSCT) and is related in part to calcineurin inhibitor toxicity. We observed a higher-than-expected rate of TMA when calcineurin inhibitors were combined with sirolimus. To determine the incidence of and risk factors for TMA after HSCT, we performed a retrospective cohort analysis of myeloablative allogeneic HSCT recipients between 1997 and 2003. TMA diagnosis required the simultaneous occurrence of (1) creatinine increase >2 mg/dL or >50% above baseline, (2) schistocytosis, (3) increased lactate dehydrogenase, and (4) no evidence of disseminated intravascular coagulopathy. A total of 111 sirolimus-exposed subjects were compared with 216 nonexposed subjects after HSCT. TMA occurred in 10.8% of the sirolimus group and 4.2% in the nonsirolimus group (odds ratio, 2.79; P=.03). Sirolimus exposure was associated with TMA earlier than in nonsirolimus patients (25 versus 58 days; P=.04). Only the use of sirolimus (exact odds ratio, 3.49; P=.02) and grade II to IV acute graft-versus-host disease (exact odds ratio, 6.60; P=.0002) were associated with TMA in regression analyses. Treatment of TMA varied among affected individuals. Renal recovery was complete in 92% of sirolimus-treated patients. Overall survival after TMA diagnosis was better for sirolimus subjects than for nonsirolimus subjects (58.3% versus 11.1%; P=.02). Sirolimus seems to potentiate the effects of calcineurin inhibitors on TMA after HSCT. TMA associated with sirolimus seems reversible and has a favorable prognosis when compared with TMA associated with calcineurin inhibitors alone. A careful monitoring strategy for TMA should be used with a sirolimus-containing graft-versus-host disease prophylaxis regimen.
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PMID:Sirolimus and thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation. 1598 55

Differentiating thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) from other complications following allogeneic hematopoietic cell transplantation (HPCT) requires objective, reliable markers. To this purpose, we assessed the clinical usefulness of sequential quantified analysis of fragmented red blood cells (FRC) with the Sysmex XE-2100 automated hematology analyzer. The correlation between manual and automated counting was significant (r = 0.917; P < .0001). Of 25 cases, the peak FRC percentage (FRC%) exceeded 1.3% after allogeneic HPCT in 11 cases, and lactate dehydrogenase levels were elevated in 5 of these 11 cases. Two patients received diagnoses of TTP-HUS following allogeneic HPCT, and both had initial diagnoses of acute graft-versus-host disease. In both cases, the sharp increase in the FRC% to >3% simultaneously with clinical exacerbation was helpful for differentiating TTP-HUS following allogeneic HPCT from other complications. We conclude that FRC% data sequentially obtained by an automated count seem to be useful as an objective marker of TTP-HUS following allogeneic HPCT.
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PMID:Usefulness of sequential automated analysis of fragmented red blood cells for the differential diagnosis of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome following allogeneic hematopoietic cell transplantation. 1602 37

Thrombotic microangiopathy (TMA) is a significant complication after hematopoietic stem-cell transplantation (HSCT); however, there is little information on it following reduced-intensity cord blood transplantation (RI-CBT). We reviewed the medical records of 123 adult patients who received RI-CBT at Toranomon Hospital between January 2002 and August 2004. TMA was diagnosed in seven patients based on intestinal biopsy (n = 6) or autopsy results (n = 1). While these patients showed some clinical symptoms such as diarrhea and/or abdominal pain, mental status alterations or neurological disorders were not observed in any of them. Laboratory results were mostly normal at the onset of TMA; >2% fragmented erythrocytes (n = 1), <10 mg/dl haptoglobin (n = 1), and >200 IU/dl lactic dehydrogenase (LD) (n = 4). On endoscopic examination, TMA lesions, consisting of ulcers, erosions, and diffuse exfoliation, were distributed spottily from terminal ileum to rectum. Intestinal graft-versus-host disease (GVHD) and cytomegalovirus (CMV) colitis were confirmed in five and four patients, respectively. With therapeutic measures including supportive care (n = 4), fresh frozen plasma (n = 1), and a reduction of immunosuppressive agents (n = 1), TMA improved in four patients. The present study demonstrates that intestinal TMA is a significant complication after RI-CBT. Since conventional diagnostic criteria can overlook TMA, its diagnosis requires careful examination of the gastrointestinal tract using endoscopy with biopsy.
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PMID:Intestinal thrombotic microangiopathy following reduced-intensity umbilical cord blood transplantation. 1602 50

Sixty three patients aged 27-66 years (median 52) were allografted from HLA-matched sibling (n=47), 10 of 10 allele-matched unrelated (n=19), or one-antigen/allele-mismatched (n=7) donors aged 24-69 years (median 46) after a conditioning regimen comprising 100 mg/m(2) melphalan. Cyclophosphamide (50 mg/kg) was also administered to patients who had not been autografted previously. Cyclosporine or tacrolimus, and mycophenolate mofetil were administered to prevent graft-versus-host disease (GVHD). The 2-year cumulative incidences of relapse and TRM were 55 and 24% respectively, and 2-year probabilities of overall survival (OS) and disease-free survival (DFS) were 36 and 21%, respectively. Poor performance status, donor age >45 years and elevated lactate dehydrogenase (LDH) increased the risk of treatment-related mortality (TRM), refractory disease and donor age >45 years increased the risk of relapse, and OS and DFS were adversely influenced by refractory disease, poor performance status, increased LDH, and donor age >45 years. Our data suggest that younger donor age is associated with better outcome after sub-myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) for hematologic malignancies due to lower TRM and relapse. This finding raises the question of whether a young 10-allele-matched unrelated donor is superior to an older matched sibling donor in patients where the clinical situation permits a choice between such donors.
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PMID:Does younger donor age affect the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies beneficially? 1675 89

The goal of this study was to investigate the association of natural killer (NK) cell recovery with clinical outcomes after unmanipulated haploidentical blood and marrow transplantation. We sequentially monitored the reconstitution kinetics of circulating NK cells, CD56(bright) and CD56(dim), in 43 patients by flow cytometry, and the functionality recovery of cytokine or cytotoxicity of NK cells by flow cytometry or lactate dehydrogenase release assay after transplantation. Reconstitution of NK cells was rapid but accompanied by skewing of cell subsets mainly in CD56(bright), which recovered earlier. Linear regression analysis demonstrated that dose of CD34(+) cells in the allografts was inversely correlated with the ratio of T/NK cells (beta = -0.506, P = .003) and CD56(dim)/CD56(bright) cell (beta = -.403, P = .018) by day 14 after hematopoietic stem cell transplantation (HSCT), and the dose of CD3(+) T cells in the allografts was also inversely correlated with the ratio CD56(dim)/CD56(bright) cells by day 14 after HSCT (beta = -0.474, P = .005). Moreover, the dose of CD56(dim) NK cells in the allograft was positively associated with the day 14 CD56(brigh) NK cells (beta = 0.494, P = .032) and inversely correlated with the day 14 ratio of CD56(dim)/CD56(bright) cells (beta = -0.617, P = .005). Compared with nonacute graft-versus-host disease (GVHD) patients, patients with acute GVHD (aGVHD) had a higher level of NK subsets during week 2 posttransplantation. Cox regression analysis revealed that the patients with more CD56(bright) NK cells in the recovery stage had a higher survival rate (hazard risk [HR], 0.406; P = .017) and the patients with a higher ratio of T/NK (>1.0) had a higher chance of getting aGVHD (HR, 3.436; P = .059) and chronic GVHD (HR, 3.925; P = .028). Our results suggest that the recovery of NK cells is and can be used as an indicator to predicate the clinical outcomes after unmanipulated haploidentical transplantation.
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PMID:Effects of the NK cell recovery on outcomes of unmanipulated haploidentical blood and marrow transplantation for patients with hematologic malignancies. 1827 99

Allogeneic stem cell transplantation (SCT) with reduced-intensity conditioning (RIC) has the potential to lead to long-term remissions for patients with lymphoma. However, the role of RIC SCT in the treatment of lymphoma is still unclear. Specifically, the relative benefit of RIC SCT across lymphoma histologies and the prognostic factors in this population are incompletely defined. We retrospectively analyzed the outcomes of 87 patients with advanced lymphoma who underwent RIC SCT at the Dana-Farber Cancer Institute over a 6-year period with a homogeneous conditioning regimen consisting of fludarabine and low-dose busulfan. Thirty-six patients had Hodgkin disease (HD) and 51 had non-Hodgkin lymphoma (NHL). Sixty-eight percent had undergone prior autologous transplantation. The 1-year cumulative incidence of nonrelapse mortality was 13%, and the 3-year cumulative incidence of progression was 49%. The incidence of grade 3-4 acute GVHD was 11%. The 2-year cumulative incidence of chronic GVHD was 68%, and its development was associated with a decreased risk of progression and an improved progression-free survival (PFS). Three-year overall survival (OS) was 56% for patients with HD, 81% for indolent NHL, 42% for aggressive NHL, and 40% for mantle cell lymphoma. The corresponding figures for 3-year PFS were 22%, 59%, 22%, and 30%, respectively. Multivariate analysis identified elevated pretransplantation lactate dehydrogenase (LDH) as an adverse factor for PFS, while indolent NHL histology was favorable. For OS, advanced age and elevated pretransplantation LDH were adverse factors, whereas indolent NHL histology was favorable. Low early donor chimerism was not predictive of poor outcome in univariate or multivariate analyses. Moreover, progression was not associated with loss of chimerism. These results emphasize the importance of lymphoma histology for patients undergoing RIC SCT, as well as the lack of relevance of donor chimerism for outcome in this patient population.
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PMID:Allogeneic transplantation with reduced-intensity conditioning for Hodgkin and non-Hodgkin lymphoma: importance of histology for outcome. 1834 84

Each year in the US, more than 10 000 patients benefit from allogeneic haematopoietic stem cell transplantation (HSCT), a modality that offers an excellent chance of eradicating malignancy but confers a higher risk of treatment-related mortality. An uncommon but devastating consequence of HSCT is transplantation-associated thrombotic microangiopathy (TA-TMA). The incidence of TA-TMA ranges from 0.5% to 76%, with a mortality rate of 60-90% despite treatment. Although there appears to be a consistent treatment approach to idiopathic thrombotic thrombocytopenic purpura (TTP) using plasma exchange, corticosteroids and rituximab, the treatment strategies for TA-TMA are perplexing, in part, because the literature regarding this complex condition does not provide true consensus for incidence, aetiology, diagnostic criteria, classification and optimal therapy. The classic definition of idiopathic TTP includes schistocytes on the peripheral blood smear, thrombocytopenia and increased serum lactate dehydrogenase. Classic idiopathic TTP has been attributed to deficient activity of the metalloproteinase responsible for cleaving ultra-large von Willebrand factor multimers. This protease is a member of the 'a disintegrin and metalloprotease with thrombospondin type 1 motif' family and is subsequently named ADAMTS-13. Severely deficient ADAMTS-13 activity (<5% of normal) is associated with idiopathic TTP in 33-100% of patients. In constrast to the pathophysiology of idiopathic TTP, patients with TA-TMA have >5% ADAMTS-13 serum activity. These data may explain why plasma exchange, a standard treatment modality for idiopathic TTP that restores ADAMTS-13 activity, is not effective in TA-TMA. TA-TMA has a multifactorial aetiology of endothelial damage induced by intensive conditioning therapy, irradiation, immunosuppressants, infection and graft-versus-host disease. Treatment consists of substituting calcineurin inhibitors with an alternative immunosuppressive agent that possesses another mode of action. One candidate may be daclizumab, especially in those with mild to moderate TMA. Rituximab therapy or the addition of defibrotide may also be beneficial. In general, plasma exchange is not recommended.
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PMID:Thrombotic microangiopathy in haematopoietic stem cell transplantation: diagnosis and treatment. 1922 75

Low CD34 + cell doses increase allograft-related mortality and very high doses increase the risk of graft-versus-host disease. The optimum CD34 + cell dose remains undefined. The effect of the CD34 + cell dose based on ideal weight was analyzed in 130 patients with hematologic malignancies undergoing reduced-intensity allogeneic blood cell transplantation in the context of factors known to affect the outcome: chemosensitivity, donor age, lactate dehydrogenase (LDH), human leukocyte antigen (HLA) match, performance status, and platelet count. The survival of patients receiving >8 x 10(6)/kg CD34 + cells was not significantly different from those receiving <6. The outcome of those receiving 6-8 x 10(6)/kg CD34 + cells was significantly better than the rest. This superiority was confirmed in multivariable analysis. Among patients receiving <or=8 x 10(6)/kg CD34 + cells, an increasing number of infused cells was associated with higher overall survival in a continuous fashion (Risk ratio (RR) 0.8759; p = 0.045). Cell dose based on actual weight did not correlate with survival. The number of CD34 + cells infused, a potentially modifiable factor, affects survival after reduced-intensity allogeneic transplantation. We recommend a CD34 + cell dose of 6-8 x 10(6) per kg ideal body weight to optimize outcome. The possible adverse effect of higher cell doses (>8) needs further confirmation.
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PMID:Optimizing the CD34 + cell dose for reduced-intensity allogeneic hematopoietic stem cell transplantation. 1967 77

Previous reports have suggested that a high serum cyclosporine A (CsA) level could result in a lower incidence of acute-graft-versus-host disease (aGVHD). An elevated serum lactate dehydrogenase (LDH) level has been reported to be an adverse predictor of outcome in stem cell transplantation (SCT) for acute myeloid leukemia. In this study, we retrospectively analyzed the records of 24 patients who received allogeneic SCT from an HLA-matched sibling donor for acute and chronic myelogenous leukemia. Univariate analysis showed that two factors (the serum CsA level at the third week after SCT and the LDH level at the third week after SCT) were significantly associated with the incidence of aGVHD among several variables (age, sex, stem cell source, cell dose, C-reactive protein, absolute lymphocyte count, conditioning regimens, and time to engraftment). A higher serum level of CsA and lower serum LDH level at the third week after SCT were associated with a lower incidence of aGVHD (P=0.015, 0.030). In multivariate analysis, the serum CsA level (hazard ratio [HR], 0.12; 95% confidence interval [CI], 0.022-0.652, P=0.0014) and serum LDH level (HR, 6.59; 95% CI, 1.197-36.316, P=0.030) at the third week after SCT were found to be independent factors that were significantly associated with the development of aGVHD. We conclude that a high CsA level and low LDH level might predict a low cumulative incidence of aGVHD after allogeneic transplantation from a matched sibling donor.
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PMID:Influence of lactate dehydrogenase and cyclosporine A level on the incidence of acute graft-versus-host disease after allogeneic stem cell transplantation. 1965 32

Factors predictive of response to plasma exchange (PE) in treatment of transplantation-associated thrombotic microangiopathy (TA-TMA) are generally poorly understood. To determine any clinical or laboratory factors predictive of response to PE in treatment of TA-TMA, we retrospectively reviewed all 11 cases of TA-TMA treated with PE at out institution between December 2001 and March 2008. Response to PE was correlated with associated clinical conditions, grade of TA-TMA, TA-TMA index and lactate dehydrogenase (LDH) level at diagnosis. Overall response to PE was 27%, with three complete responses (CRs) and eight non-responses (NRs) seen. Response to PE was significantly associated with the absence of acute GVHD at TA-TMA diagnosis, with three CR in four patients without active acute GVHD, and NR in seven patients with acute GVHD (P=0.024). There was no significant association seen between response to PE grade of TA-TMA (P=0.179), TA-TMA index (P=0.25) or LDH measurements (P=0.31). Our experience in use of therapeutic PE for management of TA-TMA suggests that PE may indeed be effective in the treatment of this disorder, depending on the clinical circumstance in which it develops. PE is potentially efficacious in the absence of active acute GVHD, and ineffective when acute GVHD is manifest.
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PMID:Transplantation-associated thrombotic microangiopathy: effect of concomitant GVHD on efficacy of therapeutic plasma exchange. 1976 87


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