Concise Review: Acute Graft-Versus-Host Disease: Immunobiology, Prevention, and Treatment

Sung, Anthony D.; Chao, Nelson J.

doi:10.5966/sctm.2012-0115

Cited by 109 publications

(98 citation statements)

References 97 publications

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“…5,7,8 aGVHD and cGVHD are major causes of nonrelapse morbidity and mortality, affecting 40-60% patients post allo-SCT for malignant conditions. 27, 28 We observed an incidence of grade II-IV aGVHD in 17% and cGVHD in 11% of patients. Although the sample size is small, these results are comparable to those seen in children and adolescents with SCD after MAC and lower than the incidence in those with malignant conditons.…”

Section: Discussionmentioning

confidence: 92%

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Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease

Bhatia

Jin

Baker

et al. 2014

Bone Marrow Transplant

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BU and CY (BU/CY; 200 mg/kg) before HLA-matched sibling allo-SCT in children with sickle cell disease (SCD) is associated with 85% EFS but is limited by the acute and late effects of BU/CY myeloablative conditioning. Alternatives include reduced toxicity but more immunosuppressive conditioning. We investigated in a prospective single institutional study, the safety and efficacy of a reduced-toxicity conditioning (RTC) regimen of BU 12.8-16 mg/kg, fludarabine 180 mg/m 2 , alemtuzumab 54 mg/m 2 (BFA) before HLA-matched sibling donor transplantation in pediatric recipients with symptomatic SCD. Eighteen patients, median age 8.9 years (2.3-20.2), M/F 15/3, 15 sibling BM and 3 sibling cord blood (CB) were transplanted. Mean whole blood and erythroid donor chimerism was 91% and 88%, at days +100 and +365, respectively. Probability of grade II-IV acute GVHD was 17%. Two-year EFS and OS were both 100%. Neurological, pulmonary and cardiovascular function were stable or improved at 2 years. BFA RTC and HLA-matched sibling BM and CB allo-SCT in pediatric recipients result in excellent EFS, long-term donor chimerism, low incidence of GVHD and stable/improved organ function.Bone Marrow Transplantation (2014) 49, 913-920;

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Section: Discussionmentioning

confidence: 92%

“…Although the sample size is small, these results are comparable to those seen in children and adolescents with SCD after MAC and lower than the incidence in those with malignant conditons. 5,7,8,[27][28][29][30][31] Methods to decrease GVHD are paramount, especially since many of the patients in this cohort had less severe disease.…”

Section: Discussionmentioning

confidence: 99%

Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease

Bhatia

Jin

Baker

et al. 2014

Bone Marrow Transplant

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“…1,2 Acute GVHD can be difficult to treat, especially if refractory to frontline steroid therapy, and mortality is high. Risk factors for acute GVHD include recipient age, donor and recipient HLA matching, and intensity of preparative regimen, none of which can be easily modified to reduce risk.…”

Section: Introductionmentioning

confidence: 99%

Lower levels of vitamin A are associated with increased gastrointestinal graft-versus-host disease in children

Lounder

Khandelwal

Dandoy

et al. 2017

Blood

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• Vitamin A levels below the median at day 30 posttransplant are associated with increased cumulative incidence of GI GVHD in children.• Potential mechanisms include increased intestinal permeability and increased lymphocyte homing to the intestine.Vitamin A promotes development of mucosal tolerance and enhances differentiation of regulatory T cells. Vitamin A deficiency impairs epithelial integrity, increasing intestinal permeability. We hypothesized that higher vitamin A levels would reduce the risk of graftversus-host disease (GVHD) through reduced gastrointestinal (GI) permeability, reduced mucosal injury, and reduced lymphocyte homing to the gut. We tested this hypothesis in a cohort study of 114 consecutive patients undergoing allogeneic stem cell transplant. Free vitamin A levels were measured in plasma at day 30 posttransplant. GI GVHD was increased in patients with vitamin A levels below the median (38% vs 12.4% at 100 days, P 5 .0008), as was treatment-related mortality (17.7% vs 7.4% at 1 year, P 5 .03). Bloodstream infections were increased in patients with vitamin A levels below the median (24% vs 8% at 1 year, P 5 .03), supporting our hypothesis of increased intestinal permeability. The GI mucosal intestinal fatty acid-binding protein was decreased after transplant, confirming mucosal injury, but was not correlated with vitamin A levels, indicating that vitamin A did not protect against mucosal injury. Expression of the gut homing receptor CCR9 on T-effector memory cells 30 days after transplant was increased in children with vitamin A levels below the median (r 5 20.34, P 5 .03). Taken together, these data support our hypothesis that low levels of vitamin A actively promote GI GVHD and are not simply a marker of poor nutritional status or a sicker patient. Vitamin A supplementation might improve transplant outcomes. (Blood. 2017;129(20):2801-2807

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“…Inflammation, including the production of chemokines and cytokines, in GVH target organs is another important factor in the development of GVHD (48,49). In the current study comparing MAST and RIST, MAST should have produced stronger inflammation in GVH target organs than RIST, which may have enhanced clinical GVHD in MAST.…”

Section: Discussionmentioning

confidence: 76%

Host Foxp3+CD4+ Regulatory T Cells Act as a Negative Regulator of Dendritic Cells in the Peritransplantation Period

Inoue

Ikegame

Kaida

et al. 2016

The Journal of Immunology

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Host Foxp3+CD4+ regulatory T cells (Tregs) have been shown to suppress graft-versus-host disease (GVHD) in experimental bone marrow transplantation (BMT) models; however, the detailed mechanism is unknown. To address this issue, we established a murine MHC-haploidentical BMT model (BDF1 (H-2b/d) → B6C3F1 (H-2b/k)), in which transplantation following conditioning with high-dose (13 Gy) or low-dose (5 Gy) total body irradiation corresponds to myeloablative stem cell transplantation (MAST) or reduced-intensity stem cell transplantation (RIST) BMT. All MAST recipients died of GVHD within 70 d, whereas RIST recipients developed almost no GVHD and survived for at least 3 mo. In this BMT model, we investigated the kinetics of immune cells in the mesenteric lymph nodes because GVHD was most prominent in the intestines. Host Tregs that survived after total body irradiation could proliferate transiently by day 4. Comparing the kinetics of immune cells among MAST, RIST, and anti-CD25 mAb-treated RIST, we found that the transiently surviving host Tregs were fully functional, closely contacted with host dendritic cells (DCs), and significantly restrained the maturation (CD80 and CD86 expression) of DCs in a dose-dependent manner. There was a positive correlation between the ratio of DCs to host Tregs and the extent of maturation of DCs. Host Tregs suppressed alloresponse mainly by contact inhibition. Host Tregs are already active in lymph nodes before transplantation and restrain the maturation of host DCs, thereby dampening the ability of DCs to activate allogeneic donor T cells and consequently reducing the magnitude of graft-versus-host reaction. Thus, host Tregs are negative regulators of host DCs that act in the peritransplantation period.

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Concise Review: Acute Graft-Versus-Host Disease: Immunobiology, Prevention, and Treatment

Cited by 109 publications

References 97 publications

Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease

Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease

Lower levels of vitamin A are associated with increased gastrointestinal graft-versus-host disease in children

Host Foxp3+CD4+ Regulatory T Cells Act as a Negative Regulator of Dendritic Cells in the Peritransplantation Period

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