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

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.

Download Full-text

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.

Download Full-text

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

Blood ◽

10.1182/blood.v77.8.1821.bloodjournal7781821 ◽

1991 ◽

Vol 77 (8) ◽

pp. 1821-1828 ◽

Cited By ~ 1

Author(s):

PJ Martin ◽

G Schoch ◽

L Fisher ◽

V Byers ◽

FR Appelbaum ◽

...

Keyword(s):

Treatment Failure ◽

Graft Versus Host Disease ◽

Immunosuppressive Agents ◽

Complete Response ◽

Initial Therapy ◽

Secondary Treatment ◽

Glucocorticoid Treatment ◽

Host Disease ◽

Graft Versus Host ◽

Acute Graft

We have reviewed results of secondary therapy in 427 patients with acute graft-versus-host disease (GVHD) who did not have a durable satisfactory response after primary treatment. At the beginning of secondary treatment, 320 patients (75%) had rash, 252 (59%) had liver dysfunction, and 228 (53%) had gut dysfunction. Secondary treatment was with glucocorticoids (n = 249), cyclosporine (n = 80), antithymocyte globulin (n = 114), or monoclonal antibody (n = 19) either singly (n = 390) or in combination (n = 37). Parameters of GVHD severity were recorded weekly, and responses were determined according to values at the initiation of tertiary treatment or, for patients without such treatment, using values on day 29 of secondary treatment or the last recorded values before death, whichever occurred first. Minimal criteria for improvement or deterioration 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 or resolution of GVHD in the respective organ was seen in 45% of patients with skin disease, 25% of patients with evaluable liver disease, and in 35% of patients with evaluable gut disease. Overall complete or partial responses were seen in 40% of patients. The highest complete response rate with secondary therapy (23%) was seen when GVHD recurred during the taper phase of primary glucocorticoid treatment and was managed by increasing the dose of glucocorticoids. Multivariate analyses were performed to identify patient, disease, or treatment factors associated with likelihood of complete response or overall improvement. A similar analysis was performed to identify covariates associated with time to treatment failure (defined as initiation of tertiary therapy or death not due to relapse of malignancy). Severe dysfunction in the skin, liver, and gut at the beginning of treatment was associated both with a decreased likelihood of complete response and an increased treatment failure rate. The times to treatment failure and the proportions of patients in various response categories were similar for primary and secondary treatment, suggesting that the potential efficacy of new immunosuppressive agents for treatment of acute GVHD can be assessed meaningfully in patients who have not responded adequately to initial therapy.

Download Full-text

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

Blood ◽

10.1182/blood.v77.8.1821.1821 ◽

1991 ◽

Vol 77 (8) ◽

pp. 1821-1828 ◽

Cited By ~ 163

Author(s):

PJ Martin ◽

G Schoch ◽

L Fisher ◽

V Byers ◽

FR Appelbaum ◽

...

Keyword(s):

Treatment Failure ◽

Graft Versus Host Disease ◽

Immunosuppressive Agents ◽

Complete Response ◽

Initial Therapy ◽

Secondary Treatment ◽

Glucocorticoid Treatment ◽

Host Disease ◽

Graft Versus Host ◽

Acute Graft

Abstract We have reviewed results of secondary therapy in 427 patients with acute graft-versus-host disease (GVHD) who did not have a durable satisfactory response after primary treatment. At the beginning of secondary treatment, 320 patients (75%) had rash, 252 (59%) had liver dysfunction, and 228 (53%) had gut dysfunction. Secondary treatment was with glucocorticoids (n = 249), cyclosporine (n = 80), antithymocyte globulin (n = 114), or monoclonal antibody (n = 19) either singly (n = 390) or in combination (n = 37). Parameters of GVHD severity were recorded weekly, and responses were determined according to values at the initiation of tertiary treatment or, for patients without such treatment, using values on day 29 of secondary treatment or the last recorded values before death, whichever occurred first. Minimal criteria for improvement or deterioration 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 or resolution of GVHD in the respective organ was seen in 45% of patients with skin disease, 25% of patients with evaluable liver disease, and in 35% of patients with evaluable gut disease. Overall complete or partial responses were seen in 40% of patients. The highest complete response rate with secondary therapy (23%) was seen when GVHD recurred during the taper phase of primary glucocorticoid treatment and was managed by increasing the dose of glucocorticoids. Multivariate analyses were performed to identify patient, disease, or treatment factors associated with likelihood of complete response or overall improvement. A similar analysis was performed to identify covariates associated with time to treatment failure (defined as initiation of tertiary therapy or death not due to relapse of malignancy). Severe dysfunction in the skin, liver, and gut at the beginning of treatment was associated both with a decreased likelihood of complete response and an increased treatment failure rate. The times to treatment failure and the proportions of patients in various response categories were similar for primary and secondary treatment, suggesting that the potential efficacy of new immunosuppressive agents for treatment of acute GVHD can be assessed meaningfully in patients who have not responded adequately to initial therapy.

Download Full-text

Initial treatment of acute graft-versus-host disease with a murine monoclonal antibody directed to the human α/β T cell receptor

Cancer Immunology Immunotherapy ◽

10.1007/bf01741342 ◽

1991 ◽

Vol 34 (2) ◽

pp. 97-102 ◽

Cited By ~ 4

Author(s):

Dietrich W. Beelen ◽

Hans Grosse-Wilde ◽

Ursula Ryschka ◽

Klaus Quabeck ◽

Herbert G. Sayer ◽

...

Keyword(s):

Monoclonal Antibody ◽

T Cell ◽

T Cell Receptor ◽

Graft Versus Host Disease ◽

Initial Treatment ◽

Cell Receptor ◽

Murine Monoclonal Antibody ◽

Host Disease ◽

Graft Versus Host ◽

Acute Graft

Download Full-text

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

Bone Marrow Transplantation ◽

10.1038/s41409-020-01049-0 ◽

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

Download Full-text

Phase II Trial of Natalizumab (Tysabri®) with Corticosteroids as Initial Treatment of Gastrointestinal Acute Graft Versus Host Disease

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2017.12.649 ◽

2018 ◽

Vol 24 (3) ◽

pp. S81 ◽

Cited By ~ 1

Author(s):

Natasha Kekre ◽

Haesook T. Kim ◽

Vincent T. Ho ◽

Yikun Guo ◽

Umair Mahmood ◽

...

Keyword(s):

Phase Ii ◽

Graft Versus Host Disease ◽

Initial Treatment ◽

Phase Ii Trial ◽

Host Disease ◽

Graft Versus Host ◽

Acute Graft

Download Full-text

How I treat acute graft-versus-host disease of the gastrointestinal tract and the liver

Blood ◽

10.1182/blood-2015-10-612747 ◽

2016 ◽

Vol 127 (12) ◽

pp. 1544-1550 ◽

Cited By ~ 33

Author(s):

George B. McDonald

Keyword(s):

Graft Versus Host Disease ◽

Acute Gvhd ◽

Prolonged Exposure ◽

Initial Therapy ◽

Therapy Algorithm ◽

Host Disease ◽

Graft Versus Host ◽

Clinical Responses ◽

Proximate Causes ◽

Acute Graft

AbstractTreatment of acute graft-versus-host disease (GVHD) has evolved from a one-size-fits-all approach to a more nuanced strategy based on predicted outcomes. Lower and time-limited doses of immune suppression for patients predicted to have low-risk GVHD are safe and effective. In more severe GVHD, prolonged exposure to immunosuppressive therapies, failure to achieve tolerance, and inadequate clinical responses are the proximate causes of GVHD-related deaths. This article presents acute GVHD-related scenarios representing, respectively, certainty of diagnosis, multiple causes of symptoms, jaundice, an initial therapy algorithm, secondary therapy, and defining futility of treatment.

Download Full-text

Etanercept, mycophenolate, denileukin, or pentostatin plus corticosteroids for acute graft-versus-host disease: a randomized phase 2 trial from the Blood and Marrow Transplant Clinical Trials Network

Blood ◽

10.1182/blood-2009-03-212290 ◽

2009 ◽

Vol 114 (3) ◽

pp. 511-517 ◽

Cited By ~ 155

Author(s):

Amin M. Alousi ◽

Daniel J. Weisdorf ◽

Brent R. Logan ◽

Javier Bolaños-Meade ◽

Shelly Carter ◽

...

Keyword(s):

Graft Versus Host Disease ◽

Hematopoietic Cell Transplantation ◽

Complete Response ◽

Marrow Transplant ◽

Initial Therapy ◽

Phase 2 ◽

Host Disease ◽

Graft Versus Host ◽

Phase 2 Trial ◽

Acute Graft

Abstract Acute graft-versus-host disease (aGVHD) is the primary limitation of allogeneic hematopoietic cell transplantation. Corticosteroids remain the standard initial therapy, yet only 25% to 41% of patients completely respond. This randomized, 4-arm, phase 2 trial was designed to identify the most promising agent(s) for initial therapy for aGVHD. Patients were randomized to receive methylprednisolone 2 mg/kg per day plus etanercept, mycophenolate mofetil (MMF), denileukin diftitox (denileukin), or pentostatin. Patients (n = 180) were randomized; their median age was 50 years (range, 7.5-70 years). Myeloablative conditioning represented 66% of transplants. Grafts were peripheral blood (61%), bone marrow (25%), or umbilical cord blood (14%); 53% were from unrelated donors. Patients who received MMF for prophylaxis (24%) were randomized to a non-MMF arm. At randomization, aGVHD was grade I to II (68%), III to IV (32%), and (53%) had visceral organ involvement. Day 28 complete response rates were etanercept 26%, MMF 60%, denileukin 53%, and pentostatin 38%. Corresponding 9-month overall survival was 47%, 64%, 49%, and 47%, respectively. Cumulative incidences of severe infections were as follows: etanercept 48%, MMF 44%, denileukin 62%, and pentostatin 57%. Efficacy and toxicity data suggest the use of MMF plus corticosteroids is the most promising regimen to compare against corticosteroids alone in a definitive phase 3 trial. This study is registered at http://www.clinicaltrials.gov as NCT00224874.

Download Full-text