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

Blood ◽  
1991 ◽  
Vol 77 (8) ◽  
pp. 1821-1828 ◽  
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.

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

Blood ◽  
1991 ◽  
Vol 77 (8) ◽  
pp. 1821-1828 ◽  
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.

scholarly journals 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 ◽  
2009 ◽  
Vol 114 (3) ◽  
pp. 511-517 ◽  
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.

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

Blood ◽  
1990 ◽  
Vol 76 (8) ◽  
pp. 1464-1472 ◽  
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

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.

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

Blood ◽  
1990 ◽  
Vol 76 (8) ◽  
pp. 1464-1472 ◽  
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.

scholarly journals Treatment of corticosteroid resistant acute graft-versus-host disease by in vivo administration of anti-interleukin-2 receptor monoclonal antibody (B-B10) [see comments]

Blood ◽  
1990 ◽  
Vol 75 (4) ◽  
pp. 1017-1023 ◽  
Author(s):  
P Herve ◽  
J Wijdenes ◽  
JP Bergerat ◽  
P Bordigoni ◽  
N Milpied ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Complete Response ◽  
Host Disease ◽  
Graft Versus Host ◽  
In Vivo Administration ◽  
Acute Graft ◽  
Receptor Monoclonal Antibody

Abstract In a multicenter pilot study, 32 patients showing steroid-resistant acute graft-versus-host disease (GVHD) were treated by in vivo administration of anti-interleukin-2 (IL-2) receptor monoclonal antibody (MoAb B-B10). Twenty-three patients received marrow from HLA- matched related donors, four from matched unrelated donors and five from partially matched related donors. The overall grade of GVHD was II in 16 patients, III in two, and IV in five. Five milligrams of B-B10 MoAb was infused in bolus daily for 10 days and then every second day for a further 10 days in an attempt to reduce GVHD recurrence. No clinical side effects were noted during the B-B10 treatment period. A complete response (CR) acute GVHD was achieved in 21 patients (65.6%). Six patients (18.7%) showed partial improvement (PR) and 5 patients (15.6%) no response (NR). A significant factor associated with GVHD response was the delay between the onset of the GVHD and the first day of B-B10 infusion. The earlier B-B10 was introduced, the greater the probability of CR (P = .03). There was no correlation between the serum B-B10 level and GVHD response (P = .69). There was, however, a significant correlation between the clinical response and the B-B10 kinetics as a function of time: serum B-B10 levels attained a plateau level more rapidly in the CR group than in the PR/NR group. Among the 26 complete and partial evaluable responders, GVHD recurred in 10 cases (38.4%). Host anti-B-B10 MoAb immune response occurred in only one (7.1%) of the 14 patients analyzed. Fourteen of the 32 patients (43.7%) are currently alive between 2 and 14 months after GVHD treatment with B- B10 was completed.

Sirolimus Yields High Response Rates in Hematopoietic Allograft Recipients with Steroid-Refractory Acute Graft-Versus-Host Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2235-2235
Author(s):  
Joseph A. Pidala ◽  
Daanish Hoda ◽  
Norma Salgado-Vila ◽  
Jongphil Kim ◽  
Janelle Perkins ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Immunosuppressive Agents ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Host Disease ◽  
Graft Versus Host ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Maximum Decrease ◽  
Steroid Refractory ◽  
Acute Graft

Abstract Abstract 2235 Poster Board II-212 Acute graft-versus-host disease (aGVHD) remains the major cause of morbidity and mortality in allogeneic hematopoietic cell transplant recipients. There is no consensus in regards to the best therapy for patients who fail to respond to, or do not tolerate, systemic glucocorticoids. We evaluate the efficacy of sirolimus in 34 pts, median age of 49 (23-67) years, with steroid-refractory (N=31) or steroid-intolerant (N=3) aGVHD. The diagnosis of aGVHD was established at a median of 34 (7-1042) days after transplantation, and confirmed by biopsy in all cases. Initial treatment of aGVHD consisted of prednisone up to 2 mg/kg. Sirolimus was initiated at a median of 9 (1-255) days after glucocorticoid initiation. A loading dose of sirolimus was administered to 19 (56%) of 34 pts, median 6 (3-8) mg, followed by maintenance therapy of 1-2 mg per day with doses adjusted to target therapeutic trough levels between 4 and 12 ng/ml; therapeutic levels were achieved in all cases. The overall response rate was 76%. Fifteen (44%) of the 34 pts achieved a CR after sirolimus initiation and without requiring additional immune suppressive agents. CR was achieved in 11/31 (42%) steroid-refractory patients, and in 2/3 (67%) steroid-intolerant patients. The median overall survival (OS) after initiation of sirolimus was 5.6 months, and one year OS was 44% (95% C.I. 27%-60%). Maximum decrease in dose of steroids over 12 weeks following sirolimus was a median of 50% (range 0-100%). Fourteen (42%) of 33 pts reached a dose < 20 mg of prednisone at a median of 4 months (95% CI: 3.5-13.5) after initiation of sirolimus. Seven (21%) of 34 pts were free from steroids after a median of 20 months (95% CI: 9.2-20.0) after initiation of sirolimus. Two pts were shown to be successfully liberated from all immunosuppressive agents without recurrent GVHD at 2.7 and 7.1 months after initiation of sirolimus, respectively. These data indicate the sirolimus is effective in controlling steroid-refractory aGVHD. Further studies are needed to determine the most appropriate timing for sirolimus after transplantation, whether prophylaxis, primary or secondary GVHD therapy. Disclosures: Off Label Use: Sirolimus for graft-versus-host disease.

scholarly journals Predicting Complete Response to Itacitinib and Corticosteroids in Acute Graft Versus Host Disease

2020 ◽  
Vol 26 (3) ◽  
pp. S185
Author(s):  
Michael Pratta ◽  
Hao Liu ◽  
Sherry Owens ◽  
Ying Yan ◽  
Michael Arbushites ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Complete Response ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

scholarly journals Children and Adults with Refractory Acute Graft-versus-Host Disease Respond to Treatment with the Mesenchymal Stromal Cell Preparation “MSC-FFM”—Outcome Report of 92 Patients

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1577 ◽  
Author(s):  
Halvard Bonig ◽  
Zyrafete Kuçi ◽  
Selim Kuçi ◽  
Shahrzad Bakhtiar ◽  
Oliver Basu ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Mononuclear Cells ◽  
Opportunistic Infections ◽  
Immunosuppressive Agents ◽  
Survival Rates ◽  
Third Party ◽  
Efficient Treatment ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

(1) Background: Refractory acute graft-versus-host disease (R-aGvHD) remains a leading cause of death after allogeneic stem cell transplantation. Survival rates of 15% after four years are currently achieved; deaths are only in part due to aGvHD itself, but mostly due to adverse effects of R-aGvHD treatment with immunosuppressive agents as these predispose patients to opportunistic infections and loss of graft-versus-leukemia surveillance resulting in relapse. Mesenchymal stromal cells (MSC) from different tissues and those generated by various protocols have been proposed as a remedy for R-aGvHD but the enthusiasm raised by initial reports has not been ubiquitously reproduced. (2) Methods: We previously reported on a unique MSC product, which was generated from pooled bone marrow mononuclear cells of multiple third-party donors. The products showed dose-to-dose equipotency and greater immunosuppressive capacity than individually expanded MSCs from the same donors. This product, MSC-FFM, has entered clinical routine in Germany where it is licensed with a national hospital exemption authorization. We previously reported satisfying initial clinical outcomes, which we are now updating. The data were collected in our post-approval pharmacovigilance program, i.e., this is not a clinical study and the data is high-level and non-monitored. (3) Results: Follow-up for 92 recipients of MSC-FFM was reported, 88 with GvHD ≥°III, one-third only steroid-refractory and two-thirds therapy resistant (refractory to steroids plus ≥2 additional lines of treatment). A median of three doses of MSC-FFM was administered without apparent toxicity. Overall response rates were 82% and 81% at the first and last evaluation, respectively. At six months, the estimated overall survival was 64%, while the cumulative incidence of death from underlying disease was 3%. (4) Conclusions: MSC-FFM promises to be a safe and efficient treatment for severe R-aGvHD.

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

Blood ◽  
2016 ◽  
Vol 127 (12) ◽  
pp. 1544-1550 ◽  
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.

Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 83-89 ◽  
Author(s):  
D. Przepiorka ◽  
N. A. Kernan ◽  
C. Ippoliti ◽  
E. B. Papadopoulos ◽  
S. Giralt ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Complete Response ◽  
Competitive Inhibitor ◽  
Controlled Study ◽  
Activated Lymphocytes ◽  
Host Disease ◽  
Graft Versus Host ◽  
Interleukin 2 Receptor ◽  
Acute Graft

Abstract Daclizumab, a humanized monoclonal IgG1 directed against the  chain of the interleukin-2 receptor (IL-2R), is a competitive inhibitor of IL-2 on activated lymphocytes. To test the hypothesis that specific inhibition of activated lymphocytes in patients with ongoing acute graft-versus-host disease (GVHD) might ameliorate the process, we treated 43 patients with advanced or steroid-refractory GVHD with daclizumab. The first cohort of 24 patients was treated with daclizumab 1 mg/kg on days 1, 8, 15, 22, and 29. On day 43, the complete response (CR) rate was 29% (95% confidence interval [CI], 13%-51%). Survival on day 120 was 29% (95% CI, 13%-51%). A second cohort of 19 patients was treated with daclizumab 1 mg/kg on days 1, 4, 8, 15, and 22. For these patients, the CR rate on day 43 was 47% (95% CI, 24%-71%), and survival on day 120 was 53% (95% CI, 29%-76%). There were no infusion-related reactions and no serious side effects related to daclizumab. Following treatment, there was a reduction in serum concentrations of soluble IL-2R and peripheral blood CD3 + 25+ lymphocytes, but these changes were not predictive of response. Daclizumab has substantial activity for the treatment of acute GVHD, and the second regimen evaluated is recommended for a controlled study. (Blood, 2000; 95:83-89)

Sign in / Sign up

Export Citation Format

Share Document