Manifestations and Treatment of Acute Graft‐versus‐Host Disease

Cutler, Corey; Antin, Joseph H.

doi:10.1002/9781118416426.ch83

Cited by 12 publications

(7 citation statements)

References 265 publications

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“…1 Even though GVHD is an iatrogenic illness, its pathogenesis is not completely understood, and deaths from GVHD are a continuing obstacle to successful transplantation. 2 Here, I summarize my approach to acute GVHD of the gut and liver (Table 1) through illustrative cases.…”

Section: Introductionmentioning

confidence: 99%

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

McDonald

2016

Blood

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Treatment 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.

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Section: Introductionmentioning

confidence: 99%

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

McDonald

2016

Blood

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“…GVHD can be divided into acute and chronic ones. Acute GVHD (aGVHD) is characterized by severe infiltration of lymphocytes and other mononuclear cells and tissue cell apoptosis [18, 19]. Chronic GVHD (cGVHD) usually follows aGVHD and has overlapping target organs with aGVHD, but some cGVHD can occur with little prior aGVHD, and has prototypical target organs such as the salivary gland [20–22].…”

Section: Introductionmentioning

confidence: 99%

Administration of Anti-CD20 mAb Is Highly Effective in Preventing but Ineffective in Treating Chronic Graft-Versus-Host Disease While Preserving Strong Graft-Versus-Leukemia Effects

Johnston

Racine

et al. 2014

Biology of Blood and Marrow Transplantation

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Chronic graft-versus-host disease (cGVHD) is an autoimmune-like syndrome, and donor B cells play important roles in augmenting its pathogenesis. B cell-depleting anti-CD20 mAb has been administered before or after cGVHD onset for preventing or treating cGVHD in clinic. Although administration before onset appeared to be more effective, the effect is variable and sometimes minimal. Here, we used two mouse cGVHD models to evaluate the preventive and therapeutic effect of anti-CD20 mAb. With the model of DBA/2 donor to MHC-matched BALB/c recipient, one intravenous injection of anti-CD20 mAb (40 mg/kg) the following day or on day 7 after HCT when serum autoantibodies were undetectable effectively prevented induction of cGVHD and preserved strong graft-versus-leukemia (GVL) effect. The separation of GVL effect from GVHD was associated with a significant reduction of donor CD4+ T cell proliferation and expansion, and protection of host thymic medullary epithelial cells. Anti-CD20 mAb administration also prevented expansion of donor T cells and induction of cGVHD in another mouse model of C57BL/6 donor to MHC-mismatched BALB/c recipients. In contrast, administration of anti-CD20 mAb after GVHD onset was not able to effectively deplete donor B cells or ameliorate cGVHD in either model. These results indicate that administration of anti-CD20 mAb prior to signs of cGVHD can prevent induction of autoimmune-like cGVHD while preserving GVL effect; there is little effect if administered after cGVHD onset. This provides new insights into clinical prevention and therapy of cGVHD with B cell-depleting reagents.

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“…1 GVHD can occur after HLA-matched transplantation when the donor cells recognize polymorphic peptides (“minor histocompatibility antigens”) presented by the recipient’s HLA. 2 In HLA-mismatched transplantation, direct recognition of the recipient’s mismatched HLA by the donor’s cells provides a potent stimulus for graft-versus-host allorecognition 3–7 ; recognition of the donor’s mismatched HLA by the recipient’s immune system leads to graft rejection.…”

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confidence: 99%

High HLA-DP Expression and Graft-versus-Host Disease

et al. 2015

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Background Transplantation of hematopoietic cells from unrelated donors can cure blood disorders but carries a significant risk of acute graft-versus-host disease (GVHD). The risk is higher when the recipient and donor are HLA-DPB1–mismatched, but the mechanisms leading to GVHD are unknown. The HLA-DPB1 regulatory region variant rs9277534 is associated with HLA-DPB1 expression. We tested the hypothesis that the GVHD risk correlates with the rs9277534 allele linked to the mismatched HLA-DPB1 in the recipient. Methods We genotyped rs9277534 in 3505 persons to define rs9277534-DPB1 haplotypes. Among 1441 recipients of transplants from HLA-A,B,C,DRB1,DQB1–matched unrelated donors with only one HLA-DPB1 mismatch, linkage of the rs9277534 A and G alleles to the mismatched HLA-DPB1 was determined. HLA-DPB1 expression was assessed by means of a quantitative polymerase-chain-reaction assay. The risk of acute GVHD among recipients whose mismatched HLA-DPB1 allele was linked to rs9277534G (high expression) was compared with the risk among recipients whose mismatched HLA-DPB1 allele was linked to rs9277534A (low expression). Results The mean HLA-DPB1 expression was lower with rs9277534A than with rs9277534G. Among recipients of transplants from donors with rs9277534A-linked HLA-DPB1, the risk of acute GVHD was higher for recipients with rs9277534G-linked HLA-DPB1 mismatches than for recipients with rs9277534A-linked HLA-DPB1 mismatches (hazard ratio, 1.54; 95% confidence interval [CI], 1.25 to 1.89; P<0.001), as was the risk of death due to causes other than disease recurrence (hazard ratio, 1.25; 95% CI, 1.00 to 1.57; P = 0.05). Conclusions The risk of GVHD associated with HLA-DPB1 mismatching was influenced by the HLA-DPB1 rs9277534 expression marker. Among recipients of HLA-DPB1–mismatched transplants from donors with the low-expression allele, recipients with the high-expression allele had a high risk of GVHD. (Funded by the National Institutes of Health and others.)

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Manifestations and Treatment of Acute Graft‐versus‐Host Disease

Cited by 12 publications

References 265 publications

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

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

Administration of Anti-CD20 mAb Is Highly Effective in Preventing but Ineffective in Treating Chronic Graft-Versus-Host Disease While Preserving Strong Graft-Versus-Leukemia Effects

High HLA-DP Expression and Graft-versus-Host Disease

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