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Paul J. Martin - One of the best experts on this subject based on the ideXlab platform.
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The Chronic Graft-versus-Host Disease Failure-Free Survival (cGVHD-FFS) Index
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2019Co-Authors: Joseph Pidala, Paul J. Martin, Barry E. Storer, Jeanne Palmer, Madan Jagasia, Corey Cutler, Betty K. Hamilton, Lynn Onstad, Amin M. Alousi, George ChenAbstract:ABSTRACT In clinical trials of chronic graft-versus-host disease (cGVHD), the need to start a new systemic treatment is considered a treatment Failure. A composite endpoint called “Failure-Free Survival” (FFS), where events are initiation of a new systemic cGVHD treatment, recurrent malignancy, and death, has been suggested as a possible long-term indicator of success. The goal of the current study was to identify changes in cGVHD manifestations from baseline to 6 months that could accurately predict subsequent longer-term FFS, thereby making it possible to assess outcomes earlier than would otherwise be possible. We used data from 2 prospective, multicenter, observational studies to develop the cGVHD-FFS index. The cGVHD-FFS index was calculated at 6 months, a typical timepoint for assessment of the primary endpoint of phase II cGVHD trials. Subsequent FFS was only 45% within the next 2 years. We found that changes in the scores for the eyes, joint/fascia, and mouth ulcers from baseline to 6 months were associated with subsequent FFS, but the prognostic accuracy of these changes was not adequate for use in trials. Biomarker studies might help to identify criteria that improve prediction of long-term clinical outcomes in patients with cGVHD.
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Predictors of Survival, nonrelapse mortality, and Failure-Free Survival in patients treated for chronic graft-versus-host disease.
Blood, 2015Co-Authors: Jeanne Palmer, Yoshihiro Inamoto, Paul J. Martin, Barry E. Storer, Mary E.d. Flowers, Xiaoyu Chai, Joseph Pidala, Iskra Pusic, Mukta Arora, Steven Z. PavleticAbstract:Chronic graft-versus-host disease (GVHD) is a pleotropic syndrome that lacks validated methods of measuring response in clinical trials, although several end points have been proposed. To investigate the prognostic significance of these proposed end points, such as the 2005 National Institutes of Health (NIH) response measures, 2014 NIH response measures, clinician-reported response, and patient-reported response, we tested their ability to predict subsequent overall Survival (OS), nonrelapse mortality (NRM), and Failure-Free Survival (FFS). Patients (n = 575) were enrolled on a prospective chronic GVHD observational trial. At 6 months, clinician-reported response (P = .004) and 2014 NIH-calculated response (P = .001) correlated with subsequent FFS, and clinician-reported response predicted OS (P = .007). Multivariate models were used to identify changes in organ involvement, laboratory values, and patient-reported outcomes that were associated with long-term outcomes. At 6 months, a change in the 2005 NIH 0 to 3 clinician-reported skin score and 0 to 10 patient-reported itching score predicted subsequent FFS. Change in the Lee skin symptom score and Functional Assessment of Cancer Therapy-Bone Marrow Transplant score predicted subsequent OS. Change in the Lee skin symptom score predicted subsequent NRM. This study provides evidence that clinician-reported response and patient-reported outcomes are predictive of long-term Survival. The trial was registered at www.clinicaltrials.gov as #NCT00637689.
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Failure Free Survival in a prospective cohort of patients with chronic graft versus host disease
Haematologica, 2015Co-Authors: Jeanne Palmer, Yoshihiro Inamoto, Paul J. Martin, Xiaoyu Chai, Daniel J. Weisdorf, Joseph Pidala, Madan Jagasia, Steven Z. Pavletic, Corey Cutler, Georgia Boyce VogelsangAbstract:Failure-Free Survival, defined as the absence of relapse, non-relapse mortality or addition of another systemic therapy, has been proposed as a potential endpoint for clinical trials, but its use has only been reported for single-center studies. We measured Failure-Free Survival in a prospective observational cohort of patients (n=575) with both newly diagnosed and existing chronic graft-versus-host disease from nine centers. Failure was observed in 389 (68%) patients during the observation period. The median follow up of all patients was 30.9 months, and the median Failure-Free Survival was 9.8 months (63% at 6 months, 45% at 1 year, and 29% at 2 years). Of the variables measured at enrollment, ten were associated with shorter Failure-Free Survival: higher National Institutes of Health 0-3 skin score, higher National Institutes of Health 0-3 gastrointestinal score, worse range of motion summary score, lower forced vital capacity (%), bronchiolitis obliterans syndrome, worse quality of life, moderate to severe hepatic dysfunction, absence of treatment for gastric acid, female donor for male recipient, and prior grade II-IV acute graft-versus-host disease. Addition of a new systemic treatment, the major cause of Failure, was associated with an increased risk of subsequent non-relapse mortality (hazard ratio=2.06, 95% confidence interval: 1.29-3.32; P<0.003) and decreased Survival (hazard ratio=1.51, 95% confidence interval: 1.04-2.18; P<0.03). These results show that fewer than half of patients on systemic treatment will be Failure-Free survivors at 1 year, and fewer than a third will reach 2 years without experiencing Failure. Better treatments are needed for chronic graft-versus-host disease. Clinicaltrials.gov identifier: NCT00637689.
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Failure-Free Survival in a prospective cohort of patients with chronic graft-versus-host disease
Haematologica, 2015Co-Authors: Jeanne Palmer, Yoshihiro Inamoto, Paul J. Martin, Xiaoyu Chai, Daniel J. Weisdorf, Joseph Pidala, Madan Jagasia, Steven Z. Pavletic, Corey Cutler, Georgia Boyce VogelsangAbstract:Failure-Free Survival, defined as the absence of relapse, non-relapse mortality or addition of another systemic therapy, has been proposed as a potential endpoint for clinical trials, but its use has only been reported for single-center studies. We measured Failure-Free Survival in a prospective observational cohort of patients (n=575) with both newly diagnosed and existing chronic graft-versus-host disease from nine centers. Failure was observed in 389 (68%) patients during the observation period. The median follow up of all patients was 30.9 months, and the median Failure-Free Survival was 9.8 months (63% at 6 months, 45% at 1 year, and 29% at 2 years). Of the variables measured at enrollment, ten were associated with shorter Failure-Free Survival: higher National Institutes of Health 0-3 skin score, higher National Institutes of Health 0-3 gastrointestinal score, worse range of motion summary score, lower forced vital capacity (%), bronchiolitis obliterans syndrome, worse quality of life, moderate to severe hepatic dysfunction, absence of treatment for gastric acid, female donor for male recipient, and prior grade II-IV acute graft-versus-host disease. Addition of a new systemic treatment, the major cause of Failure, was associated with an increased risk of subsequent non-relapse mortality (hazard ratio=2.06, 95% confidence interval: 1.29-3.32; P
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Failure-Free Survival after initial systemic treatment of chronic graft-versus-host disease.
Blood, 2014Co-Authors: Yoshihiro Inamoto, Brenda M. Sandmaier, Sahika Zeynep Aki, Paul A. Carpenter, Stephanie J. Lee, Barry E. Storer, Mary E.d. Flowers, Paul J. MartinAbstract:This study was designed to characterize Failure-Free Survival (FFS) as a novel end point for clinical trials of chronic graft-versus-host disease (GVHD). The study cohort included 400 consecutive patients who received initial systemic treatment of chronic GVHD at our center. FFS was defined by the absence of second-line treatment, nonrelapse mortality, and recurrent malignancy during initial treatment. The FFS rate was 68% at 6 months and 54% at 12 months after initial treatment. Multivariate analysis identified 4 risk factors associated with treatment Failure: time interval
Yan-ming Jiang - One of the best experts on this subject based on the ideXlab platform.
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Induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy with or without adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma: meta-analysis of 1,096 patients from 11 randomized control
Asian Pacific journal of cancer prevention : APJCP, 2013Co-Authors: Zhong-guo Liang, Xiao-dong Zhu, Ai-hua Tan, Yan-ming JiangAbstract:Purpose: To evaluate the efficacy and toxicity of induction chemotherapy followed by concurrent chemoradiotherapy (the treatment group) versus concurrent chemoradiotherapy with or without adjuvant chemotherapy (the control group) for locoregionally advanced nasopharyngeal carcinoma. Methods: The search strategy included Pubmed, Embase, the Cochrane Library, China National Knowledge Internet Web, Chinese Biomedical Database and Wanfang Database. We also searched reference lists of articles and the volumes of abstracts of scientific meetings. All randomized controlled trials were included for a meta-analysis performed with RevMan 5.1.0. The Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) was used to rate the level of evidence. Results: Eleven studies were included. Risk ratios of 0.99 (95%CI 0.72-1.36), 0.37 (95%CI 0.20-0.69), 1.08 (95%CI 0.84-1.38), 0.98 (95%CI 0.75-1.27) were observed for 3 years overall Survival, 3 years progression-Free Survival, 2 years loco-regional Failure-Free Survival and 2 years distant metastasis Failure-Free Survival. There were no treatment-related deaths in either group in the 11 studies. Risk ratios of 1.90 (95%CI 1.24-2.92), 2.67 (95%CI 0.64-11.1), 1.04 (95%CI 0.79-1.37), 0.98 (95%CI 0.27-3.52) were found for grade 3-4 leukopenia, grade 3-4 thrombocytopenia, grade 3-4 mucous membrane, and grade 3-4 hepatic hematologic and gastrointestinal toxicity, the most significant toxicities for patients. Conclusion: Compared with the control group, induction chemotherapy followed by concurrent chemoradiotherapy was well tolerated but could not significantly improve prognosis in terms of overall Survival, loco-regional Failure-Free Survival or distant metastasis Failure-Free Survival.
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Comparison of concurrent chemoradiotherapy followed by adjuvant chemotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a meta-analysis of 793 patients from 5 randomized controlled trials.
Asian Pacific journal of cancer prevention : APJCP, 2012Co-Authors: Zhong-guo Liang, Xiao-dong Zhu, Zhi-rui Zhou, Yan-ming JiangAbstract:Purpose: The main objective of the present study was to evaluate the efficacy and toxicity of concurrent chemoradiotherapy followed by adjuvant chemotherapy compared with concurrent chemoradiotherapy alone in the treatment of locoregionally advanced nasopharyngeal carcinoma. Methods: The search strategy included Pubmed, Embase, the Cochrane Library, China National Knowledge Internet Web, Chinese Biomedical Database and Wanfang Database. We also searched reference lists of articles and the volumes of abstracts of scientific meetings. Randomized controlled trials (RCTs) that compared concurrent chemoradiotherapy followed by adjuvant chemotherapy with concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma were included. Meta-analysis was performed with RevMan 5.1.0. The Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) was used to rate the level of evidence. Results: Five studies were included. Risk ratios of 1.02 (95%CI 0.89-1.15), 0.93 (95%CI 0.72-1.21), 1.07 (95%CI 0.87-1.32), 0.95 (95%CI 0.80-1.13) were observed for 3 years overall Survival, 5 years Failure-Free Survival, 5 years locoregional Failure-Free Survival and 5 years distant metastasis Failure-Free Survival. There were no treatment-related deaths in both groups of five studies. Hematologic and gastrointestinal toxicity were the most significant for patients during adjuvant chemotherapy. The level of evidence was low. Conclusion: Compared with concurrent chemoradiotherapy alone, concurrent chemotherapy followed by adjuvant chemotherapy did not improve prognosis. More toxicity was found during adjuvant chemotherapy.
Yoshihiro Inamoto - One of the best experts on this subject based on the ideXlab platform.
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Predictors of Survival, nonrelapse mortality, and Failure-Free Survival in patients treated for chronic graft-versus-host disease.
Blood, 2015Co-Authors: Jeanne Palmer, Yoshihiro Inamoto, Paul J. Martin, Barry E. Storer, Mary E.d. Flowers, Xiaoyu Chai, Joseph Pidala, Iskra Pusic, Mukta Arora, Steven Z. PavleticAbstract:Chronic graft-versus-host disease (GVHD) is a pleotropic syndrome that lacks validated methods of measuring response in clinical trials, although several end points have been proposed. To investigate the prognostic significance of these proposed end points, such as the 2005 National Institutes of Health (NIH) response measures, 2014 NIH response measures, clinician-reported response, and patient-reported response, we tested their ability to predict subsequent overall Survival (OS), nonrelapse mortality (NRM), and Failure-Free Survival (FFS). Patients (n = 575) were enrolled on a prospective chronic GVHD observational trial. At 6 months, clinician-reported response (P = .004) and 2014 NIH-calculated response (P = .001) correlated with subsequent FFS, and clinician-reported response predicted OS (P = .007). Multivariate models were used to identify changes in organ involvement, laboratory values, and patient-reported outcomes that were associated with long-term outcomes. At 6 months, a change in the 2005 NIH 0 to 3 clinician-reported skin score and 0 to 10 patient-reported itching score predicted subsequent FFS. Change in the Lee skin symptom score and Functional Assessment of Cancer Therapy-Bone Marrow Transplant score predicted subsequent OS. Change in the Lee skin symptom score predicted subsequent NRM. This study provides evidence that clinician-reported response and patient-reported outcomes are predictive of long-term Survival. The trial was registered at www.clinicaltrials.gov as #NCT00637689.
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Failure Free Survival in a prospective cohort of patients with chronic graft versus host disease
Haematologica, 2015Co-Authors: Jeanne Palmer, Yoshihiro Inamoto, Paul J. Martin, Xiaoyu Chai, Daniel J. Weisdorf, Joseph Pidala, Madan Jagasia, Steven Z. Pavletic, Corey Cutler, Georgia Boyce VogelsangAbstract:Failure-Free Survival, defined as the absence of relapse, non-relapse mortality or addition of another systemic therapy, has been proposed as a potential endpoint for clinical trials, but its use has only been reported for single-center studies. We measured Failure-Free Survival in a prospective observational cohort of patients (n=575) with both newly diagnosed and existing chronic graft-versus-host disease from nine centers. Failure was observed in 389 (68%) patients during the observation period. The median follow up of all patients was 30.9 months, and the median Failure-Free Survival was 9.8 months (63% at 6 months, 45% at 1 year, and 29% at 2 years). Of the variables measured at enrollment, ten were associated with shorter Failure-Free Survival: higher National Institutes of Health 0-3 skin score, higher National Institutes of Health 0-3 gastrointestinal score, worse range of motion summary score, lower forced vital capacity (%), bronchiolitis obliterans syndrome, worse quality of life, moderate to severe hepatic dysfunction, absence of treatment for gastric acid, female donor for male recipient, and prior grade II-IV acute graft-versus-host disease. Addition of a new systemic treatment, the major cause of Failure, was associated with an increased risk of subsequent non-relapse mortality (hazard ratio=2.06, 95% confidence interval: 1.29-3.32; P<0.003) and decreased Survival (hazard ratio=1.51, 95% confidence interval: 1.04-2.18; P<0.03). These results show that fewer than half of patients on systemic treatment will be Failure-Free survivors at 1 year, and fewer than a third will reach 2 years without experiencing Failure. Better treatments are needed for chronic graft-versus-host disease. Clinicaltrials.gov identifier: NCT00637689.
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Failure-Free Survival in a prospective cohort of patients with chronic graft-versus-host disease
Haematologica, 2015Co-Authors: Jeanne Palmer, Yoshihiro Inamoto, Paul J. Martin, Xiaoyu Chai, Daniel J. Weisdorf, Joseph Pidala, Madan Jagasia, Steven Z. Pavletic, Corey Cutler, Georgia Boyce VogelsangAbstract:Failure-Free Survival, defined as the absence of relapse, non-relapse mortality or addition of another systemic therapy, has been proposed as a potential endpoint for clinical trials, but its use has only been reported for single-center studies. We measured Failure-Free Survival in a prospective observational cohort of patients (n=575) with both newly diagnosed and existing chronic graft-versus-host disease from nine centers. Failure was observed in 389 (68%) patients during the observation period. The median follow up of all patients was 30.9 months, and the median Failure-Free Survival was 9.8 months (63% at 6 months, 45% at 1 year, and 29% at 2 years). Of the variables measured at enrollment, ten were associated with shorter Failure-Free Survival: higher National Institutes of Health 0-3 skin score, higher National Institutes of Health 0-3 gastrointestinal score, worse range of motion summary score, lower forced vital capacity (%), bronchiolitis obliterans syndrome, worse quality of life, moderate to severe hepatic dysfunction, absence of treatment for gastric acid, female donor for male recipient, and prior grade II-IV acute graft-versus-host disease. Addition of a new systemic treatment, the major cause of Failure, was associated with an increased risk of subsequent non-relapse mortality (hazard ratio=2.06, 95% confidence interval: 1.29-3.32; P
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Failure-Free Survival after initial systemic treatment of chronic graft-versus-host disease.
Blood, 2014Co-Authors: Yoshihiro Inamoto, Brenda M. Sandmaier, Sahika Zeynep Aki, Paul A. Carpenter, Stephanie J. Lee, Barry E. Storer, Mary E.d. Flowers, Paul J. MartinAbstract:This study was designed to characterize Failure-Free Survival (FFS) as a novel end point for clinical trials of chronic graft-versus-host disease (GVHD). The study cohort included 400 consecutive patients who received initial systemic treatment of chronic GVHD at our center. FFS was defined by the absence of second-line treatment, nonrelapse mortality, and recurrent malignancy during initial treatment. The FFS rate was 68% at 6 months and 54% at 12 months after initial treatment. Multivariate analysis identified 4 risk factors associated with treatment Failure: time interval
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Failure-Free Survival After Initial Systemic Treatment Of Chronic GVHD
Blood, 2013Co-Authors: Yoshihiro Inamoto, Paul J. Martin, Brenda M. Sandmaier, Sahika Zeynep Aki, Paul A. Carpenter, Stephanie J. Lee, Barry E. Storer, Mary E.d. FlowersAbstract:Background Failure-Free Survival (FFS) has been proposed as a useful and meaningful endpoint for clinical trials testing second-line systemic treatment of chronic graft-versus-host disease (GVHD) [Blood 2013;121:2340], but this endpoint has not been evaluated in the context of initial systemic treatment. The current study was designed to (1) determine the FFS rate after initial systemic treatment for patients with moderate or severe chronic GVHD according to NIH criteria, (2) elucidate risk factors associated with treatment Failure, and (3) examine whether the dose of prednisone at 6 months after treatment predicts subsequent withdrawal of all immunosuppression after resolution of chronic GVHD. Results of initial treatment were compared to those after second-line treatment. Methods The study cohort included 400 consecutive relapse-Free patients who received initial systemic treatment at our center between 2006 and 2010. FFS was defined as the absence of second-line systemic treatment, nonrelapse mortality and recurrent malignancy during initial treatment. Cox regression models were used to identify risk factors for treatment Failure. Covariates at transplant included patient age, disease risk, conditioning intensity, graft source, donor relation, HLA matching and gender matching. Covariates at initial treatment of chronic GVHD included time from transplantation, involved site, number of involved sites, Karnofsky score, NIH global score, classic vs. overlap subcategory, thrombocytopenia, hyperbilirubinemia, progressive onset, steroid dose before initial treatment, and type and number of agents used for initial treatment. Results The median age of patients was 51 years (range, 0-79), and the median time from transplantation to initial systemic treatment was 6.8 months (range, 2.6-58). The FFS rate after initial systemic treatment was 68% (95% CI, 63-72%) at 6 months ([Figure 1][1]). Treatment change was the predominant category of treatment Failure. Multivariate Cox models identified 3 risk factors associated with treatment Failure ([Table][2]): interval time
Georgia Boyce Vogelsang - One of the best experts on this subject based on the ideXlab platform.
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Failure Free Survival in a prospective cohort of patients with chronic graft versus host disease
Haematologica, 2015Co-Authors: Jeanne Palmer, Yoshihiro Inamoto, Paul J. Martin, Xiaoyu Chai, Daniel J. Weisdorf, Joseph Pidala, Madan Jagasia, Steven Z. Pavletic, Corey Cutler, Georgia Boyce VogelsangAbstract:Failure-Free Survival, defined as the absence of relapse, non-relapse mortality or addition of another systemic therapy, has been proposed as a potential endpoint for clinical trials, but its use has only been reported for single-center studies. We measured Failure-Free Survival in a prospective observational cohort of patients (n=575) with both newly diagnosed and existing chronic graft-versus-host disease from nine centers. Failure was observed in 389 (68%) patients during the observation period. The median follow up of all patients was 30.9 months, and the median Failure-Free Survival was 9.8 months (63% at 6 months, 45% at 1 year, and 29% at 2 years). Of the variables measured at enrollment, ten were associated with shorter Failure-Free Survival: higher National Institutes of Health 0-3 skin score, higher National Institutes of Health 0-3 gastrointestinal score, worse range of motion summary score, lower forced vital capacity (%), bronchiolitis obliterans syndrome, worse quality of life, moderate to severe hepatic dysfunction, absence of treatment for gastric acid, female donor for male recipient, and prior grade II-IV acute graft-versus-host disease. Addition of a new systemic treatment, the major cause of Failure, was associated with an increased risk of subsequent non-relapse mortality (hazard ratio=2.06, 95% confidence interval: 1.29-3.32; P<0.003) and decreased Survival (hazard ratio=1.51, 95% confidence interval: 1.04-2.18; P<0.03). These results show that fewer than half of patients on systemic treatment will be Failure-Free survivors at 1 year, and fewer than a third will reach 2 years without experiencing Failure. Better treatments are needed for chronic graft-versus-host disease. Clinicaltrials.gov identifier: NCT00637689.
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Failure-Free Survival in a prospective cohort of patients with chronic graft-versus-host disease
Haematologica, 2015Co-Authors: Jeanne Palmer, Yoshihiro Inamoto, Paul J. Martin, Xiaoyu Chai, Daniel J. Weisdorf, Joseph Pidala, Madan Jagasia, Steven Z. Pavletic, Corey Cutler, Georgia Boyce VogelsangAbstract:Failure-Free Survival, defined as the absence of relapse, non-relapse mortality or addition of another systemic therapy, has been proposed as a potential endpoint for clinical trials, but its use has only been reported for single-center studies. We measured Failure-Free Survival in a prospective observational cohort of patients (n=575) with both newly diagnosed and existing chronic graft-versus-host disease from nine centers. Failure was observed in 389 (68%) patients during the observation period. The median follow up of all patients was 30.9 months, and the median Failure-Free Survival was 9.8 months (63% at 6 months, 45% at 1 year, and 29% at 2 years). Of the variables measured at enrollment, ten were associated with shorter Failure-Free Survival: higher National Institutes of Health 0-3 skin score, higher National Institutes of Health 0-3 gastrointestinal score, worse range of motion summary score, lower forced vital capacity (%), bronchiolitis obliterans syndrome, worse quality of life, moderate to severe hepatic dysfunction, absence of treatment for gastric acid, female donor for male recipient, and prior grade II-IV acute graft-versus-host disease. Addition of a new systemic treatment, the major cause of Failure, was associated with an increased risk of subsequent non-relapse mortality (hazard ratio=2.06, 95% confidence interval: 1.29-3.32; P
Jeanne Palmer - One of the best experts on this subject based on the ideXlab platform.
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The Chronic Graft-versus-Host Disease Failure-Free Survival (cGVHD-FFS) Index
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2019Co-Authors: Joseph Pidala, Paul J. Martin, Barry E. Storer, Jeanne Palmer, Madan Jagasia, Corey Cutler, Betty K. Hamilton, Lynn Onstad, Amin M. Alousi, George ChenAbstract:ABSTRACT In clinical trials of chronic graft-versus-host disease (cGVHD), the need to start a new systemic treatment is considered a treatment Failure. A composite endpoint called “Failure-Free Survival” (FFS), where events are initiation of a new systemic cGVHD treatment, recurrent malignancy, and death, has been suggested as a possible long-term indicator of success. The goal of the current study was to identify changes in cGVHD manifestations from baseline to 6 months that could accurately predict subsequent longer-term FFS, thereby making it possible to assess outcomes earlier than would otherwise be possible. We used data from 2 prospective, multicenter, observational studies to develop the cGVHD-FFS index. The cGVHD-FFS index was calculated at 6 months, a typical timepoint for assessment of the primary endpoint of phase II cGVHD trials. Subsequent FFS was only 45% within the next 2 years. We found that changes in the scores for the eyes, joint/fascia, and mouth ulcers from baseline to 6 months were associated with subsequent FFS, but the prognostic accuracy of these changes was not adequate for use in trials. Biomarker studies might help to identify criteria that improve prediction of long-term clinical outcomes in patients with cGVHD.
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Predictors of Survival, nonrelapse mortality, and Failure-Free Survival in patients treated for chronic graft-versus-host disease.
Blood, 2015Co-Authors: Jeanne Palmer, Yoshihiro Inamoto, Paul J. Martin, Barry E. Storer, Mary E.d. Flowers, Xiaoyu Chai, Joseph Pidala, Iskra Pusic, Mukta Arora, Steven Z. PavleticAbstract:Chronic graft-versus-host disease (GVHD) is a pleotropic syndrome that lacks validated methods of measuring response in clinical trials, although several end points have been proposed. To investigate the prognostic significance of these proposed end points, such as the 2005 National Institutes of Health (NIH) response measures, 2014 NIH response measures, clinician-reported response, and patient-reported response, we tested their ability to predict subsequent overall Survival (OS), nonrelapse mortality (NRM), and Failure-Free Survival (FFS). Patients (n = 575) were enrolled on a prospective chronic GVHD observational trial. At 6 months, clinician-reported response (P = .004) and 2014 NIH-calculated response (P = .001) correlated with subsequent FFS, and clinician-reported response predicted OS (P = .007). Multivariate models were used to identify changes in organ involvement, laboratory values, and patient-reported outcomes that were associated with long-term outcomes. At 6 months, a change in the 2005 NIH 0 to 3 clinician-reported skin score and 0 to 10 patient-reported itching score predicted subsequent FFS. Change in the Lee skin symptom score and Functional Assessment of Cancer Therapy-Bone Marrow Transplant score predicted subsequent OS. Change in the Lee skin symptom score predicted subsequent NRM. This study provides evidence that clinician-reported response and patient-reported outcomes are predictive of long-term Survival. The trial was registered at www.clinicaltrials.gov as #NCT00637689.
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Failure Free Survival in a prospective cohort of patients with chronic graft versus host disease
Haematologica, 2015Co-Authors: Jeanne Palmer, Yoshihiro Inamoto, Paul J. Martin, Xiaoyu Chai, Daniel J. Weisdorf, Joseph Pidala, Madan Jagasia, Steven Z. Pavletic, Corey Cutler, Georgia Boyce VogelsangAbstract:Failure-Free Survival, defined as the absence of relapse, non-relapse mortality or addition of another systemic therapy, has been proposed as a potential endpoint for clinical trials, but its use has only been reported for single-center studies. We measured Failure-Free Survival in a prospective observational cohort of patients (n=575) with both newly diagnosed and existing chronic graft-versus-host disease from nine centers. Failure was observed in 389 (68%) patients during the observation period. The median follow up of all patients was 30.9 months, and the median Failure-Free Survival was 9.8 months (63% at 6 months, 45% at 1 year, and 29% at 2 years). Of the variables measured at enrollment, ten were associated with shorter Failure-Free Survival: higher National Institutes of Health 0-3 skin score, higher National Institutes of Health 0-3 gastrointestinal score, worse range of motion summary score, lower forced vital capacity (%), bronchiolitis obliterans syndrome, worse quality of life, moderate to severe hepatic dysfunction, absence of treatment for gastric acid, female donor for male recipient, and prior grade II-IV acute graft-versus-host disease. Addition of a new systemic treatment, the major cause of Failure, was associated with an increased risk of subsequent non-relapse mortality (hazard ratio=2.06, 95% confidence interval: 1.29-3.32; P<0.003) and decreased Survival (hazard ratio=1.51, 95% confidence interval: 1.04-2.18; P<0.03). These results show that fewer than half of patients on systemic treatment will be Failure-Free survivors at 1 year, and fewer than a third will reach 2 years without experiencing Failure. Better treatments are needed for chronic graft-versus-host disease. Clinicaltrials.gov identifier: NCT00637689.
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Failure-Free Survival in a prospective cohort of patients with chronic graft-versus-host disease
Haematologica, 2015Co-Authors: Jeanne Palmer, Yoshihiro Inamoto, Paul J. Martin, Xiaoyu Chai, Daniel J. Weisdorf, Joseph Pidala, Madan Jagasia, Steven Z. Pavletic, Corey Cutler, Georgia Boyce VogelsangAbstract:Failure-Free Survival, defined as the absence of relapse, non-relapse mortality or addition of another systemic therapy, has been proposed as a potential endpoint for clinical trials, but its use has only been reported for single-center studies. We measured Failure-Free Survival in a prospective observational cohort of patients (n=575) with both newly diagnosed and existing chronic graft-versus-host disease from nine centers. Failure was observed in 389 (68%) patients during the observation period. The median follow up of all patients was 30.9 months, and the median Failure-Free Survival was 9.8 months (63% at 6 months, 45% at 1 year, and 29% at 2 years). Of the variables measured at enrollment, ten were associated with shorter Failure-Free Survival: higher National Institutes of Health 0-3 skin score, higher National Institutes of Health 0-3 gastrointestinal score, worse range of motion summary score, lower forced vital capacity (%), bronchiolitis obliterans syndrome, worse quality of life, moderate to severe hepatic dysfunction, absence of treatment for gastric acid, female donor for male recipient, and prior grade II-IV acute graft-versus-host disease. Addition of a new systemic treatment, the major cause of Failure, was associated with an increased risk of subsequent non-relapse mortality (hazard ratio=2.06, 95% confidence interval: 1.29-3.32; P
