FIRST ANALYSIS OF THE MULTICENTRE, BLINDED, PLACEBO-CONTROLLED PRE-GVHD CLINICAL-TRIAL FOR PREDICTION AND PRE-EMPTIVE TREATMENT OF ACUTE GVHD IN 210 OF 260 PATIENTS
(Abstract release date: 05/19/16)
EHA Library. Weissinger E. 06/11/16; 135281; S525
Prof. Dr. Eva Weissinger
Contributions
Contributions
Abstract
Abstract: S525
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 17:00 - 17:15
Location: Room H5
Background
The success of allogeneic stem cell transplantation (HSCT) is limited by acute graft-versus-host disease (aGvHD), one of the major and life-limiting complications. A proteomic urine pattern “aGvHD_MS17” capable to predict aGvHD grade II or more has been developed (Weissinger et al, 2007 and 2014). In 2008 a multicenter, randomized, placebo-controlled, double blind clinical trial to evaluate the proteomic-based prediction of aGvHD as well as possibilities of pre-emptive therapy was initiated. Patients after the first allogeneic HSCT could be included in this trial. Ten centers in Germany contributed 267 patients to this trial and 90 were randomized according to the positivity of proteomic urine pattern aGvHD-MS17 to receive either prednisolone or placebo. To date, data of 210 (89 randomized) patients have been analysed for incidence of acute GvHD grade II or more and overall survival for the first year post HSCT.
Aims
The aim of this clinical trial was to evaluate the predicitve potential of aGvHD_MS17 for the development of aGvHD grade II to IV. In additioan we analysed the possibility of 2mg/kg body weigth prednisolon for pre-emtptive therapy of aGvHD diagnosed by the positivity of aGvHD_MS17.
Methods
Urine was collected on days +7, +14, +21,+28, +35, +50 and +80 (all +/-3 days) after allogeneic HSCT frozen, shipped to Hannover and analysed within 72h as described (Weissinger et al., 2007). Positivity of aGvHD_MS17 was achieved, when the dimensionless classification factor (CF) was +0.1 or more. Upon positivity of a sample for aGvHD_MS17, patients were randomized and received either prednisolone (2mg/kg BW for 5 days) or placebo. The majority of the patients had acute leukaemia prior to transplantation (n= 120), were not in CR/CP (n=126; 60%) and were transplanted from matched (n=184; 84%). One hundred fifty one (71%) received reduced intensity conditioning regimens and the majority (84%; n=177) received immunosuppressive antibodies as GVHD-prophylaxis prior to transplantation and a calcineurin-inhibitor (CSA/MTX n=78; CSA/MMF n=93) based GvHD-prophylaxis afterwards.
Results
Prospective and blinded evaluation of aGvHD_MS17 revealed in this first analysis the correct classification of patients developing aGvHD grade II or more with a sensitivity of 71.17% and a specificity of 80%. The best CF (criterion) for the prediction of acute GvHD was at 0.16, which is between the previously published discriminatory CF of 0.2 (Weissinger et al, Blood 2007) and 0.11 (Weissinger et al, Leukemia 2014). The aGvHD-MS17-pattern turns positive about 7 days (range: 1 to 21) prior to the prior to clinical or biopsy based diagnosis of aGvHD. Patients in the aGvHD-MS17-positve group developed aGvHD grades II to IV in 49.5% while 19% of patients with aGvHD-MS17 negative samples developed acute GvHD grade II to IV. Interestingly, aGvHD_MS17 positivity between day +5 to +35 indicated pending aGvHD II-IV very accurately. Pattern-negative patients developed aGvHD II-IV later namely between days +20 and +40. Both groups reach a plateau around day +50. Patients with aGvHD_MS17-positive samples have a 2.76 fold risk of developing severe acute GvHD (p<0.0001). In addition, overall survival is significantly different for patients with samples positive for aGvHD_MS17, 40% of those die within the 1st year after HSCT (day +80 and +250). In contrast, 90% of patients who never had aGvHD_MS17-positive samples survive the first year (p <0.0001).
Conclusion
Our first analysis of the Pre-GvHD-trial implicates that aGvHD_MS17 is highly reproducible in the early prediction of aGvHD development, especially shortly after HSCT (up to day +25). Additionally, univariate analysis suggests that aGvHD_MS17 accurately separates patients with high and low overall survival after allogeneic HSCT.
Session topic: Stem cell transplantation - Clinical 1
Keyword(s): Acute graft-versus-host disease, Allogeneic hematopoietic stem cell transplant, Clinical trial
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 17:00 - 17:15
Location: Room H5
Background
The success of allogeneic stem cell transplantation (HSCT) is limited by acute graft-versus-host disease (aGvHD), one of the major and life-limiting complications. A proteomic urine pattern “aGvHD_MS17” capable to predict aGvHD grade II or more has been developed (Weissinger et al, 2007 and 2014). In 2008 a multicenter, randomized, placebo-controlled, double blind clinical trial to evaluate the proteomic-based prediction of aGvHD as well as possibilities of pre-emptive therapy was initiated. Patients after the first allogeneic HSCT could be included in this trial. Ten centers in Germany contributed 267 patients to this trial and 90 were randomized according to the positivity of proteomic urine pattern aGvHD-MS17 to receive either prednisolone or placebo. To date, data of 210 (89 randomized) patients have been analysed for incidence of acute GvHD grade II or more and overall survival for the first year post HSCT.
Aims
The aim of this clinical trial was to evaluate the predicitve potential of aGvHD_MS17 for the development of aGvHD grade II to IV. In additioan we analysed the possibility of 2mg/kg body weigth prednisolon for pre-emtptive therapy of aGvHD diagnosed by the positivity of aGvHD_MS17.
Methods
Urine was collected on days +7, +14, +21,+28, +35, +50 and +80 (all +/-3 days) after allogeneic HSCT frozen, shipped to Hannover and analysed within 72h as described (Weissinger et al., 2007). Positivity of aGvHD_MS17 was achieved, when the dimensionless classification factor (CF) was +0.1 or more. Upon positivity of a sample for aGvHD_MS17, patients were randomized and received either prednisolone (2mg/kg BW for 5 days) or placebo. The majority of the patients had acute leukaemia prior to transplantation (n= 120), were not in CR/CP (n=126; 60%) and were transplanted from matched (n=184; 84%). One hundred fifty one (71%) received reduced intensity conditioning regimens and the majority (84%; n=177) received immunosuppressive antibodies as GVHD-prophylaxis prior to transplantation and a calcineurin-inhibitor (CSA/MTX n=78; CSA/MMF n=93) based GvHD-prophylaxis afterwards.
Results
Prospective and blinded evaluation of aGvHD_MS17 revealed in this first analysis the correct classification of patients developing aGvHD grade II or more with a sensitivity of 71.17% and a specificity of 80%. The best CF (criterion) for the prediction of acute GvHD was at 0.16, which is between the previously published discriminatory CF of 0.2 (Weissinger et al, Blood 2007) and 0.11 (Weissinger et al, Leukemia 2014). The aGvHD-MS17-pattern turns positive about 7 days (range: 1 to 21) prior to the prior to clinical or biopsy based diagnosis of aGvHD. Patients in the aGvHD-MS17-positve group developed aGvHD grades II to IV in 49.5% while 19% of patients with aGvHD-MS17 negative samples developed acute GvHD grade II to IV. Interestingly, aGvHD_MS17 positivity between day +5 to +35 indicated pending aGvHD II-IV very accurately. Pattern-negative patients developed aGvHD II-IV later namely between days +20 and +40. Both groups reach a plateau around day +50. Patients with aGvHD_MS17-positive samples have a 2.76 fold risk of developing severe acute GvHD (p<0.0001). In addition, overall survival is significantly different for patients with samples positive for aGvHD_MS17, 40% of those die within the 1st year after HSCT (day +80 and +250). In contrast, 90% of patients who never had aGvHD_MS17-positive samples survive the first year (p <0.0001).
Conclusion
Our first analysis of the Pre-GvHD-trial implicates that aGvHD_MS17 is highly reproducible in the early prediction of aGvHD development, especially shortly after HSCT (up to day +25). Additionally, univariate analysis suggests that aGvHD_MS17 accurately separates patients with high and low overall survival after allogeneic HSCT.
Session topic: Stem cell transplantation - Clinical 1
Keyword(s): Acute graft-versus-host disease, Allogeneic hematopoietic stem cell transplant, Clinical trial
Abstract: S525
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 17:00 - 17:15
Location: Room H5
Background
The success of allogeneic stem cell transplantation (HSCT) is limited by acute graft-versus-host disease (aGvHD), one of the major and life-limiting complications. A proteomic urine pattern “aGvHD_MS17” capable to predict aGvHD grade II or more has been developed (Weissinger et al, 2007 and 2014). In 2008 a multicenter, randomized, placebo-controlled, double blind clinical trial to evaluate the proteomic-based prediction of aGvHD as well as possibilities of pre-emptive therapy was initiated. Patients after the first allogeneic HSCT could be included in this trial. Ten centers in Germany contributed 267 patients to this trial and 90 were randomized according to the positivity of proteomic urine pattern aGvHD-MS17 to receive either prednisolone or placebo. To date, data of 210 (89 randomized) patients have been analysed for incidence of acute GvHD grade II or more and overall survival for the first year post HSCT.
Aims
The aim of this clinical trial was to evaluate the predicitve potential of aGvHD_MS17 for the development of aGvHD grade II to IV. In additioan we analysed the possibility of 2mg/kg body weigth prednisolon for pre-emtptive therapy of aGvHD diagnosed by the positivity of aGvHD_MS17.
Methods
Urine was collected on days +7, +14, +21,+28, +35, +50 and +80 (all +/-3 days) after allogeneic HSCT frozen, shipped to Hannover and analysed within 72h as described (Weissinger et al., 2007). Positivity of aGvHD_MS17 was achieved, when the dimensionless classification factor (CF) was +0.1 or more. Upon positivity of a sample for aGvHD_MS17, patients were randomized and received either prednisolone (2mg/kg BW for 5 days) or placebo. The majority of the patients had acute leukaemia prior to transplantation (n= 120), were not in CR/CP (n=126; 60%) and were transplanted from matched (n=184; 84%). One hundred fifty one (71%) received reduced intensity conditioning regimens and the majority (84%; n=177) received immunosuppressive antibodies as GVHD-prophylaxis prior to transplantation and a calcineurin-inhibitor (CSA/MTX n=78; CSA/MMF n=93) based GvHD-prophylaxis afterwards.
Results
Prospective and blinded evaluation of aGvHD_MS17 revealed in this first analysis the correct classification of patients developing aGvHD grade II or more with a sensitivity of 71.17% and a specificity of 80%. The best CF (criterion) for the prediction of acute GvHD was at 0.16, which is between the previously published discriminatory CF of 0.2 (Weissinger et al, Blood 2007) and 0.11 (Weissinger et al, Leukemia 2014). The aGvHD-MS17-pattern turns positive about 7 days (range: 1 to 21) prior to the prior to clinical or biopsy based diagnosis of aGvHD. Patients in the aGvHD-MS17-positve group developed aGvHD grades II to IV in 49.5% while 19% of patients with aGvHD-MS17 negative samples developed acute GvHD grade II to IV. Interestingly, aGvHD_MS17 positivity between day +5 to +35 indicated pending aGvHD II-IV very accurately. Pattern-negative patients developed aGvHD II-IV later namely between days +20 and +40. Both groups reach a plateau around day +50. Patients with aGvHD_MS17-positive samples have a 2.76 fold risk of developing severe acute GvHD (p<0.0001). In addition, overall survival is significantly different for patients with samples positive for aGvHD_MS17, 40% of those die within the 1st year after HSCT (day +80 and +250). In contrast, 90% of patients who never had aGvHD_MS17-positive samples survive the first year (p <0.0001).
Conclusion
Our first analysis of the Pre-GvHD-trial implicates that aGvHD_MS17 is highly reproducible in the early prediction of aGvHD development, especially shortly after HSCT (up to day +25). Additionally, univariate analysis suggests that aGvHD_MS17 accurately separates patients with high and low overall survival after allogeneic HSCT.
Session topic: Stem cell transplantation - Clinical 1
Keyword(s): Acute graft-versus-host disease, Allogeneic hematopoietic stem cell transplant, Clinical trial
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 17:00 - 17:15
Location: Room H5
Background
The success of allogeneic stem cell transplantation (HSCT) is limited by acute graft-versus-host disease (aGvHD), one of the major and life-limiting complications. A proteomic urine pattern “aGvHD_MS17” capable to predict aGvHD grade II or more has been developed (Weissinger et al, 2007 and 2014). In 2008 a multicenter, randomized, placebo-controlled, double blind clinical trial to evaluate the proteomic-based prediction of aGvHD as well as possibilities of pre-emptive therapy was initiated. Patients after the first allogeneic HSCT could be included in this trial. Ten centers in Germany contributed 267 patients to this trial and 90 were randomized according to the positivity of proteomic urine pattern aGvHD-MS17 to receive either prednisolone or placebo. To date, data of 210 (89 randomized) patients have been analysed for incidence of acute GvHD grade II or more and overall survival for the first year post HSCT.
Aims
The aim of this clinical trial was to evaluate the predicitve potential of aGvHD_MS17 for the development of aGvHD grade II to IV. In additioan we analysed the possibility of 2mg/kg body weigth prednisolon for pre-emtptive therapy of aGvHD diagnosed by the positivity of aGvHD_MS17.
Methods
Urine was collected on days +7, +14, +21,+28, +35, +50 and +80 (all +/-3 days) after allogeneic HSCT frozen, shipped to Hannover and analysed within 72h as described (Weissinger et al., 2007). Positivity of aGvHD_MS17 was achieved, when the dimensionless classification factor (CF) was +0.1 or more. Upon positivity of a sample for aGvHD_MS17, patients were randomized and received either prednisolone (2mg/kg BW for 5 days) or placebo. The majority of the patients had acute leukaemia prior to transplantation (n= 120), were not in CR/CP (n=126; 60%) and were transplanted from matched (n=184; 84%). One hundred fifty one (71%) received reduced intensity conditioning regimens and the majority (84%; n=177) received immunosuppressive antibodies as GVHD-prophylaxis prior to transplantation and a calcineurin-inhibitor (CSA/MTX n=78; CSA/MMF n=93) based GvHD-prophylaxis afterwards.
Results
Prospective and blinded evaluation of aGvHD_MS17 revealed in this first analysis the correct classification of patients developing aGvHD grade II or more with a sensitivity of 71.17% and a specificity of 80%. The best CF (criterion) for the prediction of acute GvHD was at 0.16, which is between the previously published discriminatory CF of 0.2 (Weissinger et al, Blood 2007) and 0.11 (Weissinger et al, Leukemia 2014). The aGvHD-MS17-pattern turns positive about 7 days (range: 1 to 21) prior to the prior to clinical or biopsy based diagnosis of aGvHD. Patients in the aGvHD-MS17-positve group developed aGvHD grades II to IV in 49.5% while 19% of patients with aGvHD-MS17 negative samples developed acute GvHD grade II to IV. Interestingly, aGvHD_MS17 positivity between day +5 to +35 indicated pending aGvHD II-IV very accurately. Pattern-negative patients developed aGvHD II-IV later namely between days +20 and +40. Both groups reach a plateau around day +50. Patients with aGvHD_MS17-positive samples have a 2.76 fold risk of developing severe acute GvHD (p<0.0001). In addition, overall survival is significantly different for patients with samples positive for aGvHD_MS17, 40% of those die within the 1st year after HSCT (day +80 and +250). In contrast, 90% of patients who never had aGvHD_MS17-positive samples survive the first year (p <0.0001).
Conclusion
Our first analysis of the Pre-GvHD-trial implicates that aGvHD_MS17 is highly reproducible in the early prediction of aGvHD development, especially shortly after HSCT (up to day +25). Additionally, univariate analysis suggests that aGvHD_MS17 accurately separates patients with high and low overall survival after allogeneic HSCT.
Session topic: Stem cell transplantation - Clinical 1
Keyword(s): Acute graft-versus-host disease, Allogeneic hematopoietic stem cell transplant, Clinical trial
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