Thrombocytopenia and hemostatic disorders in chronic graft versus host disease

Pulanić, Dražen; Lozier, Jay N.; Pavletić, Steven Z.

doi:10.1038/bmt.2009.196

Cited by 34 publications

(31 citation statements)

References 108 publications

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“…Of note, in the two retrospective analyses revealing significantly worse OS in patients with severe chronic GVHD compared with mild and moderate one, median follow-up were 46 and 37 months, and thus, longer than in our study. 11,12 Most interestingly, platelet counts below 100 g/l had a significant negative impact on survival after allogeneic HCT as has been reported previously by investigators using the revised Seattle criteria of chronic GVHD [32][33][34][35][36][37][38][39] or reclassifying their chronic GVHD patient cohort according to the NIH consensus criteria. 9 In our study progressive onset type of chronic GVHD was significantly associated with worse survival and increased NRM.…”

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Significantly worse survival of patients with NIH-defined chronic graft-versus-host disease and thrombocytopenia or progressive onset type: results of a prospective study

et al. 2011

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Chronic graft-versus-host disease (GVHD) remains a serious complication after allogeneic hematopoietic stem cell transplantation (HCT). In 2005 the National Institutes of Health (NIH) established new criteria for chronic GVHD based on retrospective data and expert recommendations. We prospectively evaluated the incidence of NIH-defined chronic GVHD and its prognostic impact in 178 consecutive patients. The cumulative incidence of chronic GVHD at 3 years was 64, 48 and 16% for chronic classic GVHD and overlap syndrome. Prior acute GVHD and myeloablative conditioning were significantly associated with increased risk of chronic GVHD. Three-year survival (overall survival (OS)) for late-acute GVHD, chronic classic and overlap chronic GVHD when assigned on day 100 were 69, 83 and 73%. OS was significantly worse for patients with platelet counts below 100 g/l at onset of chronic GVHD (35% versus 86%, Po0.0001) and progressive as compared with de novo and quiescent onset of chronic GVHD (54.5% versus 89.5% versus 84%, P ¼ 0.022 and 0.001). Peak severity of chronic GVHD had no impact on non-relapse mortality (NRM) and OS. Recurrent acute GVHD, platelet counts below 100 g/l at diagnosis of chronic GVHD, progressive onset of chronic GVHD and advanced disease stage prior to HCT were significantly associated with increased NRM. This prospective analysis provides for the first-time data on the incidence rates of NIHdefined chronic GVHD categories and identified risk factors for the occurrence of chronic GVHD. A prognostic value of thrombocytopenia and progressive onset type of chronic GVHD for survival after HCT was observed in NIH-defined chronic GVHD.

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Significantly worse survival of patients with NIH-defined chronic graft-versus-host disease and thrombocytopenia or progressive onset type: results of a prospective study

et al. 2011

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“…Low platelet counts (<100 K/μL) at diagnosis are predictive for higher risk of non-relapse mortality 43-44 and thrombocytopenia in cGVHD patients is among the strongest predictors of poor survival across many studies. 45 Low platelets were not prognostic for survival in this cohort, possibly due to only 7% of patients with platelets <100 K/μL or long time from cGVHD diagnosis to enrollment (median 23 months). In contrast, higher platelet counts were associated with more active and severe disease in this cohort.…”

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confidence: 69%

Clinical laboratory markers of inflammation as determinants of chronic graft-versus-host disease activity and NIH global severity

et al. 2011

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Chronic graft versus host disease (cGVHD) remains a major cause of non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Currently there are no accepted measures of cGVHD activity to aid in clinical management and disease staging. We analyzed clinical markers of inflammation in the sera of patients with established cGVHD and correlated those with definitions of disease activity. 189 adults with cGVHD (33% moderate and 66% severe according to NIH global scoring) were consecutively enrolled onto a cross-sectional prospective cGVHD natural history study. At the time of evaluation, 80% were receiving systemic immunosuppression and failed a median of 4 prior systemic therapies (PST) for their cGVHD. Lower albumin (p<0.0001), higher CRP (C-reactive protein; p=0.043), higher platelets (p=0.030) and higher number of PST (p<0.0001) were associated with active disease defined as clinician's intention to intensify or alter systemic therapy due to the lack of response. Higher platelet count (p=0.021) and higher number of PST (p<0.0001) were associated with more severe diseased defined by NIH global score. This study identified common laboratory indicators of inflammation that can serve as markers of cGVHD activity and severity.

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“…In contrast, lower platelet count has been shown to be among the most consistent and strongest negative prognostic factors for survival across a number of cGVHD studies. (45-49). We have previously reported an association between higher platelet counts and cGVHD activity and severity in the same cGVHD patient cohort reported here, suggesting higher platelet count could be interpreted as a surrogate for cGVHD activity and severity in our cohort.…”

Section: Discussionmentioning

confidence: 99%

Characterization and Risk Factor Analysis of Osteoporosis in a Large Cohort of Patients with Chronic Graft-versus-Host Disease

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Curtis

Steinberg

et al. 2016

Biology of Blood and Marrow Transplantation

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The NIH Chronic Graft-versus-Host Disease (cGVHD) Consensus Project Ancillary and Supportive Care Guidelines recommend annual assessment of bone mineral density (BMD) to monitor bone health. The study of osteoporosis in patients with cGVHD has been limited to small numbers of patients and the guidelines are based on experiences in other chronic diseases and expert opinion. We hypothesized that the prevalence of osteoporosis is high in a cohort of 258 patients with moderate to severe cGVHD due to prolonged exposure to risk factors for osteoporosis after allogeneic hematopoietic stem cell transplantation. We defined osteoporosis using BMD criteria (T-score ≤ -2.5) at three anatomical sites (femoral neck – FN, lumbar spine – LS, total hip – TH) and characterized risk factors through univariate and multivariate analyses. We found that low body weight (FN p<0.0001, LS p=0.0002, TH p<0.0001), malnutrition (FN p=0.0002, LS p=0.03, TH p=0.0076), higher platelet count (FN p=0.0065, TH p=0.0025), higher average NIH organ score (FN p=0.038), higher prednisone dose (LS p=0.032), lower complement component 3 (LS p=0.0073), and physical inactivity (FN p=0.01) were associated with osteoporosis in one or more site. T-scores were significantly lower in the FN than in the other two sites (p<0.0001 for both). The prevalence of osteoporosis and osteopenia was high (17% and 60%, respectively), supporting current recommendations for frequent monitoring of BMD. The association of higher platelet count in cGVHD patients with osteoporosis has not been previously reported and presents a new area of interest in the study of osteoporosis after allogeneic hematopoietic stem cell transplantation.

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Thrombocytopenia and hemostatic disorders in chronic graft versus host disease

Cited by 34 publications

References 108 publications

Significantly worse survival of patients with NIH-defined chronic graft-versus-host disease and thrombocytopenia or progressive onset type: results of a prospective study

Significantly worse survival of patients with NIH-defined chronic graft-versus-host disease and thrombocytopenia or progressive onset type: results of a prospective study

Clinical laboratory markers of inflammation as determinants of chronic graft-versus-host disease activity and NIH global severity

Characterization and Risk Factor Analysis of Osteoporosis in a Large Cohort of Patients with Chronic Graft-versus-Host Disease

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