Response endpoints and failure-free survival after initial treatment for acute graft-versus-host disease

We have reviewed results of therapy in 740 patients with grades II-IV acute graft-versus-host disease (GVHD) after allogeneic marrow transplantation. At the beginning of therapy, 597 patients (81%) had rash, 369 (50%) had liver dysfunction and 396 (54%) had gut dysfunction. Initial treatment was with glucocorticoids (n = 531), cyclosporine (n = 170), antithymocyte globulin (ATG) (n = 156) or monoclonal antibody (n = 3) either singly (n = 633) or in combination (n = 107). Parameters of GVHD severity in each organ were recorded weekly, and evaluation of response was made using values at the initiation of secondary treatment or, for patients without such treatment, using values on day 29 of primary treatment or the last recorded value before death, whichever occurred first. Minimal criteria for improvement or progression were defined for each organ, but no attempt was made to define liver or gut outcome if another complication such as venocclusive disease or infectious enteritis was present. Improvement rates were 43% for skin disease, 35% for evaluable liver disease and 50% for evaluable gut disease. Overall complete or partial responses were seen in 44% of patients. Multivariate analyses were carried out to identify patient, disease or treatment factors associated with likelihood of overall improvement and likelihood of response in at least one organ. A similar analysis was also carried out to identify covariates associated with time to treatment failure (defined as initiation of secondary therapy or death not due to relapse of malignancy). In all three models, GVHD prophylaxis using cyclosporine combined with methotrexate was associated with favorable GVHD treatment outcome compared to prophylaxis with either agent alone, and treatment with glucocorticoids or cyclosporine was more successful than treatment with ATG. Other factors associated with unfavorable outcome in the model of time to treatment failure and also entered in one of the response models were recipient HLA disparity with the donor, presence of a liver complication other than GVHD, and early onset of GVHD. Results of this analysis indicate that glucocorticoids represent the best initial therapy available for treatment of acute GVHD, although much room for improvement remains.

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Correction: Phase II trial of natalizumab with corticosteroids as initial treatment of gastrointestinal acute graft-versus-host disease

Bone Marrow Transplantation ◽

10.1038/s41409-020-01083-y ◽

2020 ◽

Author(s):

Natasha Kekre ◽

Haesook T. Kim ◽

Julia Hofer ◽

Vincent T. Ho ◽

John Koreth ◽

...

Keyword(s):

Phase Ii ◽

Graft Versus Host Disease ◽

Initial Treatment ◽

Phase Ii Trial ◽

Host Disease ◽

Graft Versus Host ◽

Acute Graft ◽

Correction Phase

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Initial therapy of acute graft-versus-host disease with low-dose prednisone does not compromise patient outcomes

Blood ◽

10.1182/blood-2008-07-168401 ◽

2009 ◽

Vol 113 (13) ◽

pp. 2888-2894 ◽

Cited By ~ 80

Author(s):

Marco Mielcarek ◽

Barry E. Storer ◽

Michael Boeckh ◽

Paul A. Carpenter ◽

George B. McDonald ◽

...

Keyword(s):

Graft Versus Host Disease ◽

Initial Treatment ◽

Low Dose ◽

Standard Dose ◽

Equivalent Dose ◽

Host Disease ◽

Graft Versus Host ◽

Number Of Patients ◽

Dose Prednisone ◽

Acute Graft

Abstract We hypothesized that initial treatment of acute graft-versus-host disease (GVHD) with low-dose glucocorticoids (prednisone-equivalent dose of 1 mg/kg per day) instead of standard-dose glucocorticoids (prednisone-equivalent dose of 2 mg/kg per day) does not compromise major transplantation outcomes. We retrospectively analyzed outcomes among 733 patients who received transplants between 2000 and 2005 according to initial treatment with low-dose (n = 347) versus standard-dose (n = 386) systemic glucocorticoids. The mean cumulative prednisone-equivalent doses at day 100 after starting treatment were 44 and 87 mg/kg for patients given low-dose and standard-dose glucocorticoids, respectively. Adjusted outcomes between the groups given low-dose versus standard-dose glucocorticoids were not statistically significantly different: overall mortality (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.9-1.4), relapse (HR, 1.22; 95% CI, 0.9-1.7), nonrelapse mortality (HR, 1.06; 95% CI, 0.8-1.5). The small number of patients with grades III/IV acute GVHD at onset precluded definitive conclusions for this subgroup. In multivariate analysis, the risks of invasive fungal infections (HR, 0.59; 95% CI, 0.3-1.0) and the duration of hospitalization (odds ratio, 0.62; 95% CI, 0.4-0.9) were reduced in the low-dose prednisone group. We conclude that initial treatment with low-dose glucocorticoids for patients with grades I-II GVHD did not compromise disease control or mortality and was associated with decreased toxicity.

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A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment

Blood ◽

10.1182/blood.v76.8.1464.1464 ◽

1990 ◽

Vol 76 (8) ◽

pp. 1464-1472 ◽

Cited By ~ 363

Author(s):

PJ Martin ◽

G Schoch ◽

L Fisher ◽

V Byers ◽

C Anasetti ◽

...

Keyword(s):

Treatment Failure ◽

Graft Versus Host Disease ◽

Initial Treatment ◽

Initial Therapy ◽

Time To Treatment ◽

Host Disease ◽

Graft Versus Host ◽

Factors Associated ◽

Time To Treatment Failure ◽

Acute Graft

Abstract We have reviewed results of therapy in 740 patients with grades II-IV acute graft-versus-host disease (GVHD) after allogeneic marrow transplantation. At the beginning of therapy, 597 patients (81%) had rash, 369 (50%) had liver dysfunction and 396 (54%) had gut dysfunction. Initial treatment was with glucocorticoids (n = 531), cyclosporine (n = 170), antithymocyte globulin (ATG) (n = 156) or monoclonal antibody (n = 3) either singly (n = 633) or in combination (n = 107). Parameters of GVHD severity in each organ were recorded weekly, and evaluation of response was made using values at the initiation of secondary treatment or, for patients without such treatment, using values on day 29 of primary treatment or the last recorded value before death, whichever occurred first. Minimal criteria for improvement or progression were defined for each organ, but no attempt was made to define liver or gut outcome if another complication such as venocclusive disease or infectious enteritis was present. Improvement rates were 43% for skin disease, 35% for evaluable liver disease and 50% for evaluable gut disease. Overall complete or partial responses were seen in 44% of patients. Multivariate analyses were carried out to identify patient, disease or treatment factors associated with likelihood of overall improvement and likelihood of response in at least one organ. A similar analysis was also carried out to identify covariates associated with time to treatment failure (defined as initiation of secondary therapy or death not due to relapse of malignancy). In all three models, GVHD prophylaxis using cyclosporine combined with methotrexate was associated with favorable GVHD treatment outcome compared to prophylaxis with either agent alone, and treatment with glucocorticoids or cyclosporine was more successful than treatment with ATG. Other factors associated with unfavorable outcome in the model of time to treatment failure and also entered in one of the response models were recipient HLA disparity with the donor, presence of a liver complication other than GVHD, and early onset of GVHD. Results of this analysis indicate that glucocorticoids represent the best initial therapy available for treatment of acute GVHD, although much room for improvement remains.

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