ACUTE GRAFT VERSUS HOST DISEASE GRADE I : FINAL ANALYSIS OF A GITMO RANDOMIZED TRIAL OF PREDNISOLONE VS NO TREATMENT
(Abstract release date: 05/19/16)
EHA Library. Bacigalupo A. 06/11/16; 135278; S522
Andrea Bacigalupo
Contributions
Contributions
Abstract
Abstract: S522
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:15 - 16:30
Location: Room H5
Background
Management of patients with grade I acute graft versus host disease (GvHD) (a skin rash covering less than 15% of the body surface), is a matter of individual preference: some would treat with steroids, most clinicians would probably not treat. We hypothesized that treatment of grade I GvHD would significantly reduce the proportion of patients progressing to grade II GvHD.
Aims
To test whether steroid treatment of acute GvHD grade I, protects patients from progressing to grade II GvHD.
Methods
Nine Centers of the Italian Group for Bone Marrow Transplantation (GITMO), randomized 171 patients with acute grade I skin GvHD, to an observation arm (n=85) or to a treatment arm (n=86)- prednisolone 1 mg/kg/day for 5 days and then taper and discontinue on day +30. Patients in the observation arm, could be treated when GvHD grade II developed, at whatever interval from randomization. The primary end point of the study was progression to acute GvHD grade II. Secondary end points were: transplant related mortality (TRM), survival, infections and chronic GvHD.The two groups were balanced for diagnosis (p=0.9), disease phase (p=0.4) and donor type (p=0.4) The median age for the observation arm, was borderline higher than the treatment arm (46 vs 38 years, p=0.08).
Results
The cumulative incidence of progression to acute GvHD grade II, was 50% in the observation and 35% in the treatment arm (p=0.02). This difference was 58% vs 35%, (p=0.05) for HLA identical siblings (n=70) and 45% vs 36% for alternative donors (n=101) (p=0.3). Grade III-IV GvHD was diagnosed in 11 observation vs 12 treatment patients (13% vs 14%, p=0.8); the incidence was comparable in the two arms, also when stratified in HLA identical siblings (17% vs 18%) or alternative donor grafts (10% vs 11%). Moderate/severe chronic GvHD was comparable in the two groups (17% vs19%). Patients in the observation arm had less bacterial infections (11 vs 23, p=0.05) less CMV reactivation episodes (66 vs 95, p=0.01), and comparable fungal infections (6 vs 8, p=0.4). Severe adverse events (SAE) were recorded less frequently in the observation arm (n=18) than in the treatment arm (n=31)(p=0.1). Cumulative incidence of transplant related mortality (TRM) was 20% (observation) vs 26% (treatment) (p=0.2). Relapse related death (RRD) was 25% vs 21%. Actuarial 1 year survival was 86% (observation) vs 82% (treatment) (p=0.3). Main causes of death in observation/treatment arms, were as follows : acute GvHD 7% -12%; chronic GvHD 4%> 2%; infection, 6%> 11%; and leukemia relapse 21% -17%.
Conclusion
In conclusion, steroid treatment of grade I GvHD prevents progression to grade II GvHD, however, it does not protect patients against GvHD grade III-IV, nor against chronic GvHD, and exposes patients to a higher risk of infections. For this reason there is no beneficial effect on TRM, relapse related death and survival. Based on this prospective trial, patients with grade I GvHD should be left untreated, untill GvHD resolves spontaneously or progresses to grade II.
Session topic: Stem cell transplantation - Clinical 1
Keyword(s): Acute graft-versus-host disease, Leukemia, Transplant-related mortality
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:15 - 16:30
Location: Room H5
Background
Management of patients with grade I acute graft versus host disease (GvHD) (a skin rash covering less than 15% of the body surface), is a matter of individual preference: some would treat with steroids, most clinicians would probably not treat. We hypothesized that treatment of grade I GvHD would significantly reduce the proportion of patients progressing to grade II GvHD.
Aims
To test whether steroid treatment of acute GvHD grade I, protects patients from progressing to grade II GvHD.
Methods
Nine Centers of the Italian Group for Bone Marrow Transplantation (GITMO), randomized 171 patients with acute grade I skin GvHD, to an observation arm (n=85) or to a treatment arm (n=86)- prednisolone 1 mg/kg/day for 5 days and then taper and discontinue on day +30. Patients in the observation arm, could be treated when GvHD grade II developed, at whatever interval from randomization. The primary end point of the study was progression to acute GvHD grade II. Secondary end points were: transplant related mortality (TRM), survival, infections and chronic GvHD.The two groups were balanced for diagnosis (p=0.9), disease phase (p=0.4) and donor type (p=0.4) The median age for the observation arm, was borderline higher than the treatment arm (46 vs 38 years, p=0.08).
Results
The cumulative incidence of progression to acute GvHD grade II, was 50% in the observation and 35% in the treatment arm (p=0.02). This difference was 58% vs 35%, (p=0.05) for HLA identical siblings (n=70) and 45% vs 36% for alternative donors (n=101) (p=0.3). Grade III-IV GvHD was diagnosed in 11 observation vs 12 treatment patients (13% vs 14%, p=0.8); the incidence was comparable in the two arms, also when stratified in HLA identical siblings (17% vs 18%) or alternative donor grafts (10% vs 11%). Moderate/severe chronic GvHD was comparable in the two groups (17% vs19%). Patients in the observation arm had less bacterial infections (11 vs 23, p=0.05) less CMV reactivation episodes (66 vs 95, p=0.01), and comparable fungal infections (6 vs 8, p=0.4). Severe adverse events (SAE) were recorded less frequently in the observation arm (n=18) than in the treatment arm (n=31)(p=0.1). Cumulative incidence of transplant related mortality (TRM) was 20% (observation) vs 26% (treatment) (p=0.2). Relapse related death (RRD) was 25% vs 21%. Actuarial 1 year survival was 86% (observation) vs 82% (treatment) (p=0.3). Main causes of death in observation/treatment arms, were as follows : acute GvHD 7% -12%; chronic GvHD 4%> 2%; infection, 6%> 11%; and leukemia relapse 21% -17%.
Conclusion
In conclusion, steroid treatment of grade I GvHD prevents progression to grade II GvHD, however, it does not protect patients against GvHD grade III-IV, nor against chronic GvHD, and exposes patients to a higher risk of infections. For this reason there is no beneficial effect on TRM, relapse related death and survival. Based on this prospective trial, patients with grade I GvHD should be left untreated, untill GvHD resolves spontaneously or progresses to grade II.
Session topic: Stem cell transplantation - Clinical 1
Keyword(s): Acute graft-versus-host disease, Leukemia, Transplant-related mortality
Abstract: S522
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:15 - 16:30
Location: Room H5
Background
Management of patients with grade I acute graft versus host disease (GvHD) (a skin rash covering less than 15% of the body surface), is a matter of individual preference: some would treat with steroids, most clinicians would probably not treat. We hypothesized that treatment of grade I GvHD would significantly reduce the proportion of patients progressing to grade II GvHD.
Aims
To test whether steroid treatment of acute GvHD grade I, protects patients from progressing to grade II GvHD.
Methods
Nine Centers of the Italian Group for Bone Marrow Transplantation (GITMO), randomized 171 patients with acute grade I skin GvHD, to an observation arm (n=85) or to a treatment arm (n=86)- prednisolone 1 mg/kg/day for 5 days and then taper and discontinue on day +30. Patients in the observation arm, could be treated when GvHD grade II developed, at whatever interval from randomization. The primary end point of the study was progression to acute GvHD grade II. Secondary end points were: transplant related mortality (TRM), survival, infections and chronic GvHD.The two groups were balanced for diagnosis (p=0.9), disease phase (p=0.4) and donor type (p=0.4) The median age for the observation arm, was borderline higher than the treatment arm (46 vs 38 years, p=0.08).
Results
The cumulative incidence of progression to acute GvHD grade II, was 50% in the observation and 35% in the treatment arm (p=0.02). This difference was 58% vs 35%, (p=0.05) for HLA identical siblings (n=70) and 45% vs 36% for alternative donors (n=101) (p=0.3). Grade III-IV GvHD was diagnosed in 11 observation vs 12 treatment patients (13% vs 14%, p=0.8); the incidence was comparable in the two arms, also when stratified in HLA identical siblings (17% vs 18%) or alternative donor grafts (10% vs 11%). Moderate/severe chronic GvHD was comparable in the two groups (17% vs19%). Patients in the observation arm had less bacterial infections (11 vs 23, p=0.05) less CMV reactivation episodes (66 vs 95, p=0.01), and comparable fungal infections (6 vs 8, p=0.4). Severe adverse events (SAE) were recorded less frequently in the observation arm (n=18) than in the treatment arm (n=31)(p=0.1). Cumulative incidence of transplant related mortality (TRM) was 20% (observation) vs 26% (treatment) (p=0.2). Relapse related death (RRD) was 25% vs 21%. Actuarial 1 year survival was 86% (observation) vs 82% (treatment) (p=0.3). Main causes of death in observation/treatment arms, were as follows : acute GvHD 7% -12%; chronic GvHD 4%> 2%; infection, 6%> 11%; and leukemia relapse 21% -17%.
Conclusion
In conclusion, steroid treatment of grade I GvHD prevents progression to grade II GvHD, however, it does not protect patients against GvHD grade III-IV, nor against chronic GvHD, and exposes patients to a higher risk of infections. For this reason there is no beneficial effect on TRM, relapse related death and survival. Based on this prospective trial, patients with grade I GvHD should be left untreated, untill GvHD resolves spontaneously or progresses to grade II.
Session topic: Stem cell transplantation - Clinical 1
Keyword(s): Acute graft-versus-host disease, Leukemia, Transplant-related mortality
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:15 - 16:30
Location: Room H5
Background
Management of patients with grade I acute graft versus host disease (GvHD) (a skin rash covering less than 15% of the body surface), is a matter of individual preference: some would treat with steroids, most clinicians would probably not treat. We hypothesized that treatment of grade I GvHD would significantly reduce the proportion of patients progressing to grade II GvHD.
Aims
To test whether steroid treatment of acute GvHD grade I, protects patients from progressing to grade II GvHD.
Methods
Nine Centers of the Italian Group for Bone Marrow Transplantation (GITMO), randomized 171 patients with acute grade I skin GvHD, to an observation arm (n=85) or to a treatment arm (n=86)- prednisolone 1 mg/kg/day for 5 days and then taper and discontinue on day +30. Patients in the observation arm, could be treated when GvHD grade II developed, at whatever interval from randomization. The primary end point of the study was progression to acute GvHD grade II. Secondary end points were: transplant related mortality (TRM), survival, infections and chronic GvHD.The two groups were balanced for diagnosis (p=0.9), disease phase (p=0.4) and donor type (p=0.4) The median age for the observation arm, was borderline higher than the treatment arm (46 vs 38 years, p=0.08).
Results
The cumulative incidence of progression to acute GvHD grade II, was 50% in the observation and 35% in the treatment arm (p=0.02). This difference was 58% vs 35%, (p=0.05) for HLA identical siblings (n=70) and 45% vs 36% for alternative donors (n=101) (p=0.3). Grade III-IV GvHD was diagnosed in 11 observation vs 12 treatment patients (13% vs 14%, p=0.8); the incidence was comparable in the two arms, also when stratified in HLA identical siblings (17% vs 18%) or alternative donor grafts (10% vs 11%). Moderate/severe chronic GvHD was comparable in the two groups (17% vs19%). Patients in the observation arm had less bacterial infections (11 vs 23, p=0.05) less CMV reactivation episodes (66 vs 95, p=0.01), and comparable fungal infections (6 vs 8, p=0.4). Severe adverse events (SAE) were recorded less frequently in the observation arm (n=18) than in the treatment arm (n=31)(p=0.1). Cumulative incidence of transplant related mortality (TRM) was 20% (observation) vs 26% (treatment) (p=0.2). Relapse related death (RRD) was 25% vs 21%. Actuarial 1 year survival was 86% (observation) vs 82% (treatment) (p=0.3). Main causes of death in observation/treatment arms, were as follows : acute GvHD 7% -12%; chronic GvHD 4%> 2%; infection, 6%> 11%; and leukemia relapse 21% -17%.
Conclusion
In conclusion, steroid treatment of grade I GvHD prevents progression to grade II GvHD, however, it does not protect patients against GvHD grade III-IV, nor against chronic GvHD, and exposes patients to a higher risk of infections. For this reason there is no beneficial effect on TRM, relapse related death and survival. Based on this prospective trial, patients with grade I GvHD should be left untreated, untill GvHD resolves spontaneously or progresses to grade II.
Session topic: Stem cell transplantation - Clinical 1
Keyword(s): Acute graft-versus-host disease, Leukemia, Transplant-related mortality
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