scholarly journals Predictive factors for acute graft-versus-host disease in patients transplanted with HLA-identical bone marrow

Blood ◽  
1984 ◽  
Vol 63 (6) ◽  
pp. 1265-1270 ◽  
Author(s):  
DS Bross ◽  
PJ Tutschka ◽  
ER Farmer ◽  
WE Beschorner ◽  
HG Braine ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia ◽  
Host Disease ◽  
Graft Versus Host ◽  
Predictive Parameters ◽  
Clinically Significant ◽  
Mismatched Donor ◽  
Acute Graft

Abstract To identify predictive parameters for incidence and severity of acute graft-versus-host disease (GVHD), 136 patients, transplanted with histocompatible marrow as therapy for aplastic anemia and hematologic malignancies, were examined using univariate and multivariate analyses. The risk of GVHD increased in patients with acute lymphocytic leukemia (p less than 0.05), in sex-mismatched donor-recipient pairs (p less than 0.01), and in patients older than 23.7 yr (p less than 0.05). No other commonly observed factors appeared to have any relationship to GVHD except the presence of certain alleles. The presence of a Cw4 allele or of the Bw21 specificities B49 and B50 were associated with significantly increased risks of GVHD (p less than 0.05), whereas the presence of Aw19 (or the related specificities A29, Aw30, Aw31 , Aw32, Aw33 ) was associated with a significantly decreased risk (p less than 0.01). Using these factors, a regression equation can be constructed that estimates the risk of a given patient to develop clinically significant acute GVHD.

scholarly journals Predictive factors for acute graft-versus-host disease in patients transplanted with HLA-identical bone marrow

Blood ◽  
1984 ◽  
Vol 63 (6) ◽  
pp. 1265-1270
Author(s):  
DS Bross ◽  
PJ Tutschka ◽  
ER Farmer ◽  
WE Beschorner ◽  
HG Braine ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia ◽  
Host Disease ◽  
Graft Versus Host ◽  
Predictive Parameters ◽  
Clinically Significant ◽  
Mismatched Donor ◽  
Acute Graft

To identify predictive parameters for incidence and severity of acute graft-versus-host disease (GVHD), 136 patients, transplanted with histocompatible marrow as therapy for aplastic anemia and hematologic malignancies, were examined using univariate and multivariate analyses. The risk of GVHD increased in patients with acute lymphocytic leukemia (p less than 0.05), in sex-mismatched donor-recipient pairs (p less than 0.01), and in patients older than 23.7 yr (p less than 0.05). No other commonly observed factors appeared to have any relationship to GVHD except the presence of certain alleles. The presence of a Cw4 allele or of the Bw21 specificities B49 and B50 were associated with significantly increased risks of GVHD (p less than 0.05), whereas the presence of Aw19 (or the related specificities A29, Aw30, Aw31 , Aw32, Aw33 ) was associated with a significantly decreased risk (p less than 0.01). Using these factors, a regression equation can be constructed that estimates the risk of a given patient to develop clinically significant acute GVHD.

scholarly journals Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia [published erratum appears in Blood 1989 Aug 15;74(3):1180]

Blood ◽  
1989 ◽  
Vol 73 (6) ◽  
pp. 1720-1728 ◽  
Author(s):  
KM Sullivan ◽  
PL Weiden ◽  
R Storb ◽  
RP Witherspoon ◽  
A Fefer ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Blast Crisis ◽  
Chronic Gvhd ◽  
Chronic Phase ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Host Disease ◽  
Graft Versus Host

Abstract To assess the influence of graft-versus-host disease (GVHD) on recurrent leukemia and survival after allogeneic marrow transplantation, we studied 1,202 patients with acute nonlymphocytic leukemia (ANL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML) given unmodified marrow grafts from HLA- identical siblings. Proportional hazards regression models using acute GVHD and chronic GVHD as time-dependent covariates demonstrated a significant association of GVHD with a decreased relative risk (RR, 0.33 to 0.42) of relapse in patients with ANL, ALL, and CML transplanted in advanced disease. Among patients developing either acute or chronic GVHD, treatment failure (that is, mortality or relapse) was decreased in patients with ALL transplanted in relapse (RR = 0.70, P less than .033) and CML in blast crisis (RR = 0.37, P less than .009). This effect was independent of age, sex, preparative regimen, GVHD prophylaxis, or length of follow-up. Five-year actuarial estimates were derived for the subset of 657 patients who survived in remission 150 days after transplant and were at risk for development of chronic GVHD. Among patients with ANL in first remission or CML in chronic phase, GVHD had an adverse effect on survival and no apparent influence on relapse. Among patients with ANL and ALL transplanted in relapse, the probability of relapse after day 150 was 74% without [corrected] GVHD, 45% with acute and chronic GVHD, 35% with [corrected] only acute GVHD, and 34% with only chronic GVHD (P less than .001). Actuarial survival in these four GVHD groups was 25%, 34%, 59%, and 62%, respectively (P less than .009). Among patients with CML in acceleration or blast crisis, the probability of relapse after day 150 was 65% without GVHD and 36% with acute and/or chronic GVHD (P less than .017). We conclude that acute and chronic GVHD were associated with a durable antileukemic effect and improved survival in patients transplanted in advanced stages of ALL and CML.

scholarly journals Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate [see comments]

Blood ◽  
1992 ◽  
Vol 80 (7) ◽  
pp. 1838-1845 ◽  
Author(s):  
RA Nash ◽  
MS Pepe ◽  
R Storb ◽  
G Longton ◽  
M Pettinger ◽  
...  
Keyword(s):  
Risk Factors ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Malignant Disease ◽  
Acute Gvhd ◽  
Host Disease ◽  
Cox Regression Analysis ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Acute Graft

Abstract Previous studies of risk factors for acute graft-versus-host disease (GVHD) involved patients receiving predominantly single-agent prophylaxis. Therefore, a retrospective analysis was performed on 446 patients, from a single institution, who received transplants of marrow from HLA-identical siblings and the combination of cyclosporine (CSP) and methotrexate (MTX) to determine risk factors for acute GVHD associated with this more effective form of GVHD prophylaxis. The incidences of Grades II-IV and Grades III-IV (severe) acute GVHD were 35% and 16%, respectively. Increased clinical grades of acute GVHD in patients without advanced malignant disease were associated with a decreased survival. In a multivariate Cox regression analysis, risk factors associated with the onset of Grades II-IV acute GVHD were sex mismatch and donor parity (P = .001), increased dose of total body irradiation (TBI) (P = .001), and reduction to less than 80% of the scheduled dose of MTX (P = .02) or CSP (P = .02). The multivariate analysis indicated a relative risk of 1.37 for acute GVHD in a group defined as having advanced malignant disease at transplant; however, this difference failed to reach conventional levels of statistical significance (P = .07). Reduction of MTX and CSP occurred in up to 36% and 44% of patients, respectively, primarily because of renal or hepatic dysfunction. The periods of increased risk for the onset of acute GVHD were up to 1 week after a reduction of MTX and 2 weeks after a reduction in CSP. When only patients who developed Grades II-IV acute GVHD were considered, the more severe acute GVHD of Grades III-IV was associated with increased patient age of 40 years or greater (P = .05) and dose reductions of CSP (P = .008). Serologic status of patient and donor for cytomegalovirus (CMV), HLA antigens in the A and B loci, and isolation in a laminar air flow room during marrow transplantation, all previously identified as risk factors for acute GVHD, were not confirmed as risk factors in this study population. The toxicity of MTX and CSP and the development of acute GVHD from inadequate immunosuppression because of dose reduction warrants further trials with potentially less toxic immunosuppressive agents. Risk factors for acute GVHD should be considered in clinical management and in the design of clinical trials.

Mesenchymal Stem Cells for Treatment of Severe Acute Graft-Versus-Host Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5304-5304 ◽  
Author(s):  
Katarina Le Blanc ◽  
Francesco Frassoni ◽  
Lynne Ball ◽  
Edoardo Lanino ◽  
Berit Sundberg ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Third Party ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Abstract Mesenchymal stem cells (MSC) from adult bone marrow have the capacity to differentiate into several mesenchymal tissues and inhibit T-cell alloreactivity in vitro. Within the EBMT MSC expansion consortium we have used MSC to treat grades III–IV acute graft-versus-host disease (GvHD) in 40 patients. The MSC dose was median 1.0 (range 0.4–9) 10^6 cells/kg body weight of the recipient. No side-effects were seen after MSC infusions. Nineteen patients received one dose, 19 patients received two doses, two patients received three and five doses respectively. MSC donors were in five cases HLA-identical sibling donors, 19 haploidentical donors and 41 third-party HLA-mismatched donors. Among the 40 patients treated for severe acute GvHD, 19 had complete responses, nine showed improvement, seven patients did not respond, four had stable disease and one patient was not evaluated due to short follow-up. Twenty-one patients are alive between six weeks up to 3.5 years after transplantation. Nine of these patients have extensive chronic GvHD. One patient with ALL has recurrent leukaemia and one patient has denovo AML of recipient origin. We conclude that MSC have immunomodulatory and tissue repairing effects and should be further explored as treatment of severe acute GvHD in prospective randomized trials.

Acute Graft Versus Host Disease after Donor Lymphocyte Infusion: A Single Center Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5807-5807
Author(s):  
Fiona C. He ◽  
Daniel J. Weisdorf ◽  
Erica D. Warlick ◽  
Jeffrey S. Miller ◽  
Shernan G. Holtan ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Conflicts Of Interest ◽  
Significant Risk ◽  
Donor Lymphocyte Infusion ◽  
Myelogenous Leukemia ◽  
Host Disease ◽  
Graft Versus Host ◽  
Grade Ii ◽  
Acute Graft

Abstract Donor lymphocyte infusion (DLI) is an option for relapsed hematologic malignancies following allogeneic hematopoietic cell transplantation (HCT). We analyzed the incidence and manifestations of acute graft versus host disease (GVHD) in patients with malignant and non-malignant conditions treated with DLI. At the University of Minnesota, we gave 171 DLI to 120 patients from 1995-2013. The cumulative incidence of grade II-IV acute GVHD was 31.6% (CI 25-42%,n = 40); grade III-IV 23.3% (CI 16-32%,n = 29). GVHD after DLI (n = 46) included involvement of skin in 70% (n = 32), lower gastrointestinal (GI) 65% (n = 30), upper GI 43% (n = 20), and liver 35% (n = 16). Patients receiving chemotherapy prior to DLI (chemo-DLI) had more frequent acute GVHD and GI GVHD. Significant risk factors for grade II-IV acute GVHD included: age > 40, chemo-DLI, malignant disease, and time from HCT to DLI < 200 days. Response to treatment of acute GVHD at 8 weeks was complete in 40% and complete/partial in 52%. Patients developing GVHD had frequent disease response. In chronic myelogenous leukemia (CML) patients, responses were excellent (80%) with or without GVHD. The CR rate was 34% for non-CML malignancies; only 9% achieved CR without acute GVHD. Non-malignant diseases showed poor prognosis following acute GVHD and good prognosis without. Overall survival at 2 years for CML patients was similar (83% vs 79%, p = 0.89) with or without grade II-IV acute GVHD, but in non-CML malignancies survival was better in absence of acute GVHD (41% vs 22%, p = 0.04). We observed frequent, yet therapy-responsive acute GVHD following DLI. DLI often induced remission in CML, but less so for non-CML malignancies without chemo-DLI, particularly in absence of acute GVHD. Improvements in DLI efficacy and GVHD management are still needed. Disclosures No relevant conflicts of interest to declare.

scholarly journals Association of Serum Interleukin-7 Levels With the Development of Acute Graft-Versus-Host Disease

2008 ◽  
Vol 26 (35) ◽  
pp. 5735-5741 ◽  
Author(s):  
Robert M. Dean ◽  
Terry Fry ◽  
Crystal Mackall ◽  
Seth M. Steinberg ◽  
Fran Hakim ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Critical Role ◽  
Human Leukocyte ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Interleukin 7 ◽  
Acute Graft

Purpose Morbidity from acute graft-versus-host disease (GVHD) limits the success of allogeneic hematopoietic stem-cell transplantation (HSCT) to treat malignancy. Interleukin-7 (IL-7), the principal homeostatic cytokine for T cells, is required for acute GVHD in murine models. In contrast to inflammatory cytokines (eg, IL-2, tumor necrosis factor α), IL-7 has not been studied extensively in the clinical transplant setting relative to its relationship with acute GVHD. Patients and Methods We evaluated the association of serum IL-7 levels with acute GVHD in 31 patients who were uniformly treated in a prospective clinical trial with reduced-intensity allogeneic HSCT from human leukocyte antigen–identical siblings. GVHD prophylaxis consisted of cyclosporine and methotrexate. Serum IL-7 levels and lymphocyte populations were determined at enrollment, the day of transplantation before the allograft infusion, and at specified intervals through 12 months post-transplantation. Results As expected, IL-7 levels were inversely correlated with T-cell populations (P < .00001). Acute GVHD was significantly associated with higher IL-7 levels at day +7 (P = .01) and day +14 (P = .00003) post-transplantation as well as with the allograft CD34+ cell dose (P = .01). IL-7 levels at day +14 also correlated with the severity of acute GVHD (P < .0001). In logistic regression models, these factors were highly sensitive (up to 86%) and specific (100%) for classifying whether patients developed acute GVHD. Conclusion These data support preclinical observations that IL-7 plays a critical role in inducing acute GVHD and provide a rational basis for novel approaches to prevent and treat acute GVHD through modulation of the IL-7 pathway.

scholarly journals Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria

Blood ◽  
2011 ◽  
Vol 117 (11) ◽  
pp. 3214-3219 ◽  
Author(s):  
Mary E. D. Flowers ◽  
Yoshihiro Inamoto ◽  
Paul A. Carpenter ◽  
Stephanie J. Lee ◽  
Hans-Peter Kiem ◽  
...  
Keyword(s):  
Risk Factors ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Human Leukocyte ◽  
National Institutes Of Health ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Abstract Risk factors for grades 2-4 acute graft-versus-host disease (GVHD) and for chronic GVHD as defined by National Institutes of Health consensus criteria were evaluated and compared in 2941 recipients of first allogeneic hematopoietic cell transplantation at our center. In multivariate analyses, the profiles of risk factors for acute and chronic GVHD were similar, with some notable differences. Recipient human leukocyte antigen (HLA) mismatching and the use of unrelated donors had a greater effect on the risk of acute GVHD than on chronic GVHD, whereas the use of female donors for male recipients had a greater effect on the risk of chronic GVHD than on acute GVHD. Total body irradiation was strongly associated with acute GVHD, but had no statistically significant association with chronic GVHD, whereas grafting with mobilized blood cells was strongly associated with chronic GVHD but not with acute GVHD. Older patient age was associated with chronic GVHD, but had no effect on acute GVHD. For all risk factors associated with chronic GVHD, point estimates and confidence intervals were not significantly changed after adjustment for prior acute GVHD. These results suggest that the mechanisms involved in acute and chronic GVHD are not entirely congruent and that chronic GVHD is not simply the end stage of acute GVHD.

scholarly journals Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia [published erratum appears in Blood 1989 Aug 15;74(3):1180]

Blood ◽  
1989 ◽  
Vol 73 (6) ◽  
pp. 1720-1728 ◽  
Author(s):  
KM Sullivan ◽  
PL Weiden ◽  
R Storb ◽  
RP Witherspoon ◽  
A Fefer ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Blast Crisis ◽  
Chronic Gvhd ◽  
Chronic Phase ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Host Disease ◽  
Graft Versus Host

To assess the influence of graft-versus-host disease (GVHD) on recurrent leukemia and survival after allogeneic marrow transplantation, we studied 1,202 patients with acute nonlymphocytic leukemia (ANL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML) given unmodified marrow grafts from HLA- identical siblings. Proportional hazards regression models using acute GVHD and chronic GVHD as time-dependent covariates demonstrated a significant association of GVHD with a decreased relative risk (RR, 0.33 to 0.42) of relapse in patients with ANL, ALL, and CML transplanted in advanced disease. Among patients developing either acute or chronic GVHD, treatment failure (that is, mortality or relapse) was decreased in patients with ALL transplanted in relapse (RR = 0.70, P less than .033) and CML in blast crisis (RR = 0.37, P less than .009). This effect was independent of age, sex, preparative regimen, GVHD prophylaxis, or length of follow-up. Five-year actuarial estimates were derived for the subset of 657 patients who survived in remission 150 days after transplant and were at risk for development of chronic GVHD. Among patients with ANL in first remission or CML in chronic phase, GVHD had an adverse effect on survival and no apparent influence on relapse. Among patients with ANL and ALL transplanted in relapse, the probability of relapse after day 150 was 74% without [corrected] GVHD, 45% with acute and chronic GVHD, 35% with [corrected] only acute GVHD, and 34% with only chronic GVHD (P less than .001). Actuarial survival in these four GVHD groups was 25%, 34%, 59%, and 62%, respectively (P less than .009). Among patients with CML in acceleration or blast crisis, the probability of relapse after day 150 was 65% without GVHD and 36% with acute and/or chronic GVHD (P less than .017). We conclude that acute and chronic GVHD were associated with a durable antileukemic effect and improved survival in patients transplanted in advanced stages of ALL and CML.

Association between Regimen Related Toxicity and Acute-Graft-Versus-Host Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5017-5017
Author(s):  
Edward A. Copelan
Keyword(s):  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Tissue Injury ◽  
Critical Factor ◽  
Allogeneic Transplantation ◽  
Host Disease ◽  
Graft Versus Host ◽  
Grade Ii ◽  
Grade 3 ◽  
Acute Graft

Abstract Tissue injury resulting from preparative therapy for transplantation is integral to the development of acute graft-versus-host disease (GVHD) according to current theory. If toxicity to normal tissues is a critical factor in the pathophysiology of GVHD, greater degrees of regimen related toxicities should be associated with a higher incidence and greater severity of GVHD. We analyzed 438 patients who underwent allogeneic transplantation from related (n=360) or unrelated (78) donors and who survived > 100 days following transplantation. Patients had received preparative regimens of BuCy (n=340) or BuCyVP16 (n=98). Median age was 36 (range 4–66). There were 263 males and 175 females. This cohort survived a median of 35 months (range 3 months to 20 years). Sixty-eight of these patients had developed (Bearman) grade 3-4 regimen related toxicities. These patients had a 50% incidence of acute GVHD > grade II and a 26% incidence of developing GVHD ≤ grade II, compared to significantly lower incidences of 33% (P=.01) and 14% (P=.02) respectively in the group experiencing < grade 3 regimen related toxicity. Exclusion of patients whose GVHD prophylactic regimens were significantly altered because of toxicity did not significantly influence these results. This data suggest that patients who develop severe regimen related toxicity are significantly more likely to develop severe acute GVHD, supporting a potential pathophysiologic role for tissue injury in the development of acute GVHD.

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