scholarly journals The role of HLA-DPB1 disparity in the development of acute graft-versus- host disease following unrelated donor marrow transplantation

Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1923-1932 ◽  
Author(s):  
EW Petersdorf ◽  
AG Smith ◽  
EM Mickelson ◽  
GM Longton ◽  
C Anasetti ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Group A ◽  
Group B ◽  
Acute Graft

Abstract The role of HLA-DPB1 disparity in the development of acute graft-versus- host disease (GVHD) following unrelated donor (URD) marrow transplantation is unknown. We studied 129 patients who underwent marrow transplantation from HLA-A, -B, -DRB, and -DQB matched URDs to determine whether matching for HLA-DPB1 alleles significantly decreased the risk of developing acute GVHD. HLA-DPB1 alleles were determined by sequence-specific oligonucleotide hybridization and by the number of patient DPB1 alleles not shared by the donor scored. The Kaplan-Meier probability of developing grades II to IV acute GVHD was determined for patients incompatible for zero (group A), one (group B), or two (group C) DPB1 alleles. Of the 129 pairs, there was no recipient DPB1 incompatibility in 28 (22%), one DPB1 mismatch in 72 (56%), and two DPB1 mismatches in 29 (22%). The probability of grades II to IV acute GVHD was 0.69 (0.50, 0.86) for group A, 0.83 (0.73, 0.91) for group B, and 0.72 (0.56, 0.87) for group C (P = .63). These results indicate that matching patients and unrelated donors for HLA-A, -B, -DRB, and - DQB does not predict for matching at DPB1. However, recipient incompatibility for DPB1 alleles does not detectably influence the risk of acute GVHD. Therefore, HLA-DP disparity should not be used as an exclusion criterion for donor selection in unrelated marrow transplantation.

scholarly journals The role of HLA-DPB1 disparity in the development of acute graft-versus- host disease following unrelated donor marrow transplantation

Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1923-1932 ◽  
Author(s):  
EW Petersdorf ◽  
AG Smith ◽  
EM Mickelson ◽  
GM Longton ◽  
C Anasetti ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Group A ◽  
Group B ◽  
Acute Graft

The role of HLA-DPB1 disparity in the development of acute graft-versus- host disease (GVHD) following unrelated donor (URD) marrow transplantation is unknown. We studied 129 patients who underwent marrow transplantation from HLA-A, -B, -DRB, and -DQB matched URDs to determine whether matching for HLA-DPB1 alleles significantly decreased the risk of developing acute GVHD. HLA-DPB1 alleles were determined by sequence-specific oligonucleotide hybridization and by the number of patient DPB1 alleles not shared by the donor scored. The Kaplan-Meier probability of developing grades II to IV acute GVHD was determined for patients incompatible for zero (group A), one (group B), or two (group C) DPB1 alleles. Of the 129 pairs, there was no recipient DPB1 incompatibility in 28 (22%), one DPB1 mismatch in 72 (56%), and two DPB1 mismatches in 29 (22%). The probability of grades II to IV acute GVHD was 0.69 (0.50, 0.86) for group A, 0.83 (0.73, 0.91) for group B, and 0.72 (0.56, 0.87) for group C (P = .63). These results indicate that matching patients and unrelated donors for HLA-A, -B, -DRB, and - DQB does not predict for matching at DPB1. However, recipient incompatibility for DPB1 alleles does not detectably influence the risk of acute GVHD. Therefore, HLA-DP disparity should not be used as an exclusion criterion for donor selection in unrelated marrow transplantation.

scholarly journals Tacrolimus and minidose methotrexate for prevention of acute graft- versus-host disease after matched unrelated donor marrow transplantation

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4383-4389 ◽  
Author(s):  
D Przepiorka ◽  
C Ippoliti ◽  
I Khouri ◽  
M Woo ◽  
R Mehra ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Advanced Disease ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Unrelated Donors ◽  
Acute Graft

Abstract Thirty adults with leukemia or lymphoma undergoing marrow transplantation from HLA-compatible unrelated donors received tacrolimus (FK506), a new immunosuppressive macrolide lactone, and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 36 years (range 21 to 49 years). Twenty-four patients had advanced disease, and 11 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/d intravenously (i.v.) by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued through day 180 posttransplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6, and 11. All patients engrafted. Grades 2–4 GVHD occurred in 34% (95% CI, 17% to 52%), and grades 3–4 GVHD in 17% (95% CI, 3% to 31%). Mild renal toxicity was common before day 100; 63% of patients had a doubling of creatinine, and 52% had a peak creatinine greater than 2 mg/dL, but only one patient was dialyzed. The median last i.v. dose of tacrolimus was 53% of the scheduled dose, and the median oral dose on day 100 was 41% of that scheduled. Overall survival at 1 year was 47% (95% CI, 27% to 66%). We conclude that tacrolimus can be combined safely with minidose methotrexate, and the combination has substantial activity in preventing acute GVHD after unrelated donor marrow transplantation.

scholarly journals Tacrolimus and minidose methotrexate for prevention of acute graft- versus-host disease after matched unrelated donor marrow transplantation

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4383-4389 ◽  
Author(s):  
D Przepiorka ◽  
C Ippoliti ◽  
I Khouri ◽  
M Woo ◽  
R Mehra ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Advanced Disease ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Unrelated Donors ◽  
Acute Graft

Thirty adults with leukemia or lymphoma undergoing marrow transplantation from HLA-compatible unrelated donors received tacrolimus (FK506), a new immunosuppressive macrolide lactone, and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 36 years (range 21 to 49 years). Twenty-four patients had advanced disease, and 11 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/d intravenously (i.v.) by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued through day 180 posttransplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6, and 11. All patients engrafted. Grades 2–4 GVHD occurred in 34% (95% CI, 17% to 52%), and grades 3–4 GVHD in 17% (95% CI, 3% to 31%). Mild renal toxicity was common before day 100; 63% of patients had a doubling of creatinine, and 52% had a peak creatinine greater than 2 mg/dL, but only one patient was dialyzed. The median last i.v. dose of tacrolimus was 53% of the scheduled dose, and the median oral dose on day 100 was 41% of that scheduled. Overall survival at 1 year was 47% (95% CI, 27% to 66%). We conclude that tacrolimus can be combined safely with minidose methotrexate, and the combination has substantial activity in preventing acute GVHD after unrelated donor marrow transplantation.

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.

The role of HLA-DPB1 disparity in the development of acute graft-versus-host disease (GVHD) following unrelated marrow transplantation

1992 ◽  
Vol 34 (1) ◽  
pp. 56 ◽  
Author(s):  
E.W. Petersdorf ◽  
A.G. Smith ◽  
E.M. Mickelson ◽  
G.M. Longton ◽  
C. Anasetti ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

High-producer interleukin-2 genotype increases risk for acute graft-versus-host disease after unrelated donor bone marrow transplantation

2003 ◽  
Vol 76 (12) ◽  
pp. 1758-1762 ◽  
Author(s):  
Margaret L. MacMillan ◽  
Gretchen A. Radloff ◽  
William R. Kiffmeyer ◽  
Todd E. DeFor ◽  
Daniel J. Weisdorf ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Interleukin 2 ◽  
Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Donor Bone Marrow ◽  
Acute Graft

Effect of HLA-DRB1 and DQB1 allele disparity on the development of acute graft versus host disease following unrelated donor marrow transplantation

1994 ◽  
Vol 40 ◽  
pp. 3
Author(s):  
Effie W. Petersdorf ◽  
Claudio Anasetti ◽  
Paul J. Martin ◽  
Anajane G. Smith ◽  
Gary Longton ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Dqb1 Allele ◽  
Acute Graft

Pre-Engraftment Serum C-Reactive Protein (CRP) Value as a Predictor of Acute Graft-Versus-Host Disease and Non-Relapse Mortality.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1968-1968
Author(s):  
Shigeo Fuji ◽  
Sung-Won Kim ◽  
Takahiro Fukuda ◽  
Shin-ichiro Mori ◽  
Satoshi Yamasaki ◽  
...  
Keyword(s):  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Unrelated Donor ◽  
Primary Role ◽  
Host Disease ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Grade Ii ◽  
Acute Graft

Abstract Background: In a mouse model, it has been shown that inflammatory cytokines play a primary role in the development of acute graft-versus-host disease (GVHD). Here, we evaluated whether the pre-engraftment CRP value, which is used as a surrogate marker of inflammation, could predict post-transplant complications including GVHD. Methods: The medical records of 224 adult patients (median age, 47 years; range, 18–68 y), who underwent conventional (CST, n=105) or reduced-intensity (RIST, n=119) allogeneic stem cell transplantation between January 2002 and July 2006 were reviewed retrospectively. Their diagnosis included AML (n=94), ALL (n=23), NHL (n=62), MDS (n=27) and others (n=18). Stem cell sources included bone marrow (n=108), peripheral blood stem cells (n=98) and cord blood cells (n=18). Patients were categorized according to the maximum CRP value during the pre-engraftment neutropenic period: the “low CRP” group (CRP < 15 mg/dL) included 157 patients and the “high CRP” group (CRP≥15 mg/dL) included 67 patients. We assessed the occurrence of acute GVHD, non-relapse mortality (NRM) and overall survival. Results: The incidence of documented infections during neutropenia was higher in the high CRP group (34% vs 17%, P=0.004). The CRP value was significantly lower after RIST than after CST (P=0.017) or after related than after unrelated transplantation (P<0.001). A multiple logistic regression analysis showed that male sex, unrelated donor and HLA-mismatched donor were associated with high CRP values. The high CRP group developed significantly more grade II-IV acute GVHD, grade III-IV acute GVHD and NRM as shown in Figure 1 and 2. A multivariate analysis showed that a high CRP level was associated with an increased risk of grade II-IV acute GVHD, poor OS and high NRM. Conclusion: The present findings suggest that the CRP value may reflect the net degree of tissue damage due to the conditioning regimen, inflammation, infection and allogeneic immune reactions, all of which lead to subsequent acute GVHD and NRM. Future clinical studies to evaluate the feasibility of earlier intervention and adjustment of GVHD prophylaxis based on monitoring of the early CRP value are warranted. Fig 1 grade II-IV acute GVHD Fig 1. grade II-IV acute GVHD Fig 2 non-relapse mortality Fig 2. non-relapse mortality

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