Hematopoietic stem cell transplantation(HSCT)is widely performed as a treatment for malignant blood disorders,such as leukemia.To achieve good clinical outcomes in HSCT,it is necessary to minimize the unfavorable effe...Hematopoietic stem cell transplantation(HSCT)is widely performed as a treatment for malignant blood disorders,such as leukemia.To achieve good clinical outcomes in HSCT,it is necessary to minimize the unfavorable effects of acute graft-vs-host disease(GVHD)and induce the more tolerable,chronic form of the disease.For better management of GVHD,sensitive and specific biomarkers that predict the severity and prognosis of the disease have been intensively investigated using proteomics,transcriptomics,genomics,cytomics,and tandem mass spectrometry methods.Here,I will briefly review the current understanding of GVHD biomarkers and future prospects.展开更多
AIM: To investigate appropriate therapeutic strategies for graft-vs-host disease (GVHD) following liver transplantation. METHODS: Four patients who developed GVHD after liver transplantation in West China Hospital wer...AIM: To investigate appropriate therapeutic strategies for graft-vs-host disease (GVHD) following liver transplantation. METHODS: Four patients who developed GVHD after liver transplantation in West China Hospital were included in this study. Therapeutic strategies with augmentation or withdrawal of immunosuppressants combined with supportive therapy were investigated in these patients. In addition, a literature review of patients who developed GVHD after liver transplantation was performed. RESULTS: Although a transient response to initial treatment was detected, all four patients died of complications from GVHD: one from sepsis with multiple organ failure, one from gastrointestinal bleeding, and the other two from sepsis with gastrointestinal bleeding. Few consensuses for the treatment of GVHD after liver transplantation have been reached.CONCLUSION: New and effective treatments are re-quired for GVHD after liver transplantation to improve the prognosis of patients with this diagnosis.展开更多
Hematopoietic stem cell transplantation has become a curative choice of many hematopoietic malignancy,but graft-vs-host disease(GVHD)has limited the survival quality and overall survival of hematopoietic stem cell tra...Hematopoietic stem cell transplantation has become a curative choice of many hematopoietic malignancy,but graft-vs-host disease(GVHD)has limited the survival quality and overall survival of hematopoietic stem cell transplantation.Understanding of the immune cells’reaction in pathophysiology of GVHD has improved,but a review on the role of macrophages in GVHD is still absent.Studies have observed that macrophage infiltration is associated with GVHD occurrence and development.In this review,we summarize and analyze the role of macrophages in GVHD based on pathophysiology of acute and chronic GVHD,focusing on the macrophage recruitment and infiltration,macrophage polarization,macrophage secretion,and especially interaction of macrophages with other immune cells.We could conclude that macrophage recruitment and infiltration contribute to both acute and chronic GVHD.Based on distinguishing pathology of acute and chronic GVHD,macrophages tend to show a higher M1/M2 ratio in acute GVHD and a lower M1/M2 ratio in chronic GVHD.However,the influence of dominant cytokines in GVHD is controversial and inconsistent with macrophage polarization.In addition,interaction of macrophages with alloreactive T cells plays an important role in acute GVHD.Meanwhile,the interaction among macrophages,B cells,fibroblasts,and CD4+T cells participates in chronic GVHD development.展开更多
Chronic graft-vs-host disease(c GVHD) is the leading cause of long-term morbidity and mortality following allogeneic hematopoietic stem cell transplantation. It presents as a chronic inflammatory and sclerotic autoimm...Chronic graft-vs-host disease(c GVHD) is the leading cause of long-term morbidity and mortality following allogeneic hematopoietic stem cell transplantation. It presents as a chronic inflammatory and sclerotic autoimmune-like condition that most frequently affects the skin, oral mucosa, liver, eyes and gastrointestinal tract. Both clinical and animal studies have shown that multiple T cell subsets including Th1, Th2, Th17, T follicular helper cells and regulatory T-cells play some role in cG VHD development and progression; B cells also play an important role in the disease including the production of antibodies to HY and nuclear antigens that can cause serious tissue damage. An array of cytokines and chemokines produced by different types of immune cells also mediate tissue inflammation and damage of cG VHD target tissues such as the skin and oral cavity. Many of these same immune regulators have been studied as candidate cG VHD biomarkers. Recent studies suggest that some of these biomarkers may be useful for determining disease prognosis and planning long-term clinical followup of cG VHD patients.展开更多
BACKGROUND Graft-vs-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation.Some patients have steroid-refractory(SR) GVHD.AIM To evaluate the effect and safety of ru...BACKGROUND Graft-vs-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation.Some patients have steroid-refractory(SR) GVHD.AIM To evaluate the effect and safety of ruxolitinib add-on in the treatment of patients with SR acute (a) and chronic (c) GVHD.METHODS We retrospectively analyzed 38 patients administered ruxolitinib add-on to standard immunosuppressive therapy for SR-aGVHD or SR-cGVHD following allogeneic hematopoietic stem cell transplantation.Ruxolitinib was administered5-10 mg/d depending on disease severity,patient status,and the use of antifungal drugs.Overall response rate,time to best response,malignancy relapse rate,infection rate,and treatment-related adverse events were assessed.RESULTS The analysis included 10 patients with SR-aGVHD (gradeⅢ/Ⅳ,n=9) and 28patients with SR-cGVHD (moderate/severe,n=24).For the SR-aGVHD and SRcGVHD groups,respectively:Median number of previous GVHD therapies was 2(range:1-3) and 2 (1-4);median follow-up was 2.5 (1.5-4) and 5 (1.5-10) mo;median time to best response was 1 (0.5-2.5) and 3 (1-9.5) mo;and overall response rate was 100%(complete response:80%) and 82.1%(complete response:10.7%) with a response observed in all GVHD-affected organs.The malignancy relapse rates for the SR-aGVHD and SR-cGVHD groups were 10.0%and 10.7%,respectively.Reactivation rates for cytomegalovirus,Epstein-Barr virus,and varicella-zoster virus,respectively,were 30.0%,10.0%,and 0%for the SR-aGVHD group and 0%,14.3%,and 7.1%for the SR-cGVHD group.CONCLUSION Ruxolitinib add-on was effective and safe as salvage therapy for SR-GVHD.展开更多
BACKGROUND Acute gastrointestinal(GI)graft-vs-host disease(aGVHD)is the most complication of hematopoietic stem cell transplant(HSCT)in patients with hematologic malignancy.Limited data exists on endoscopic evaluation...BACKGROUND Acute gastrointestinal(GI)graft-vs-host disease(aGVHD)is the most complication of hematopoietic stem cell transplant(HSCT)in patients with hematologic malignancy.Limited data exists on endoscopic evaluation of GVHD in post-HSCT patients with differing GI symptoms.Further,the diagnostic value of gross endoscopic findings as well as the safety of endoscopy in this commonly thrombocytopenic and neutropenic patient population remains unclear.AIM To understand the diagnostic value of symptoms and gross endoscopic findings as well as safety of endoscopy in aGVHD patients.METHODS We analyzed 195 endoscopies performed at City of Hope in patients who underwent allogeneic HSCT less than 100 d prior for hematologic malignancy and were subsequently evaluated for aGVHD via endoscopy.The yield,sensitivity,and specificity of diagnosing aGVHD were calculated for upper and lower endoscopy,various GI tract locations,and presenting symptoms.RESULTS Combined esophagogastroduodenoscopy(EGD)and flexible sigmoidoscopy(FS)demonstrated a greater diagnostic yield for aGVHD(83.1%)compared to EGD(66.7%)or FS(77.2%)alone with any presenting symptom.The upper and lower GI tract demonstrated similar yields regardless of whether patients presented with diarrhea(95.7%vs 99.1%)or nausea/vomiting(97.5%vs 96.8%).Normalappearing mucosa was generally as specific(91.3%)as abnormal mucosa(58.7%-97.8%)for the presence of aGVHD.Adverse events such as bleeding(1.0%),infection(1.0%),and perforation(0.5%)only occurred in a small proportion of patients,with no significant differences in those with underlying thrombocytopenia(P=1.000)and neutropenia(P=0.425).CONCLUSION Combined EGD and FS with biopsies of normal and inflamed mucosa demonstrated the greatest diagnostic yield regardless of presenting symptom and appears to be safe in this population of patients.展开更多
We report a case of a 56-year-old woman with a history of allogenic bone marrow transplantation for two years,complaining with dysphagia and weight loss. Upper endoscopy revealed esophageal stenosis and extensive muco...We report a case of a 56-year-old woman with a history of allogenic bone marrow transplantation for two years,complaining with dysphagia and weight loss. Upper endoscopy revealed esophageal stenosis and extensive mucosa sloughing. Biopsies confirmed the diagnosis of graft-vs-host disease(GVHD). Balloon dilation,corticosteroids and cyclosporin resulted in marked clinical improvement. Gastrointestinal tract is involved in the majority of patients with chronic GVHD. Esophageal manifestations are rare and include vesiculobullous disease,ulceration,esophageal webs,casts or strictures. Sloughing esophagitis along with severe stenosis requiring endoscopic dilation has never been reported in this context.展开更多
基金Supported by partly a Grant-in-Aid for Scientific Research(KAKENHI)Grant,No.15K09639.
文摘Hematopoietic stem cell transplantation(HSCT)is widely performed as a treatment for malignant blood disorders,such as leukemia.To achieve good clinical outcomes in HSCT,it is necessary to minimize the unfavorable effects of acute graft-vs-host disease(GVHD)and induce the more tolerable,chronic form of the disease.For better management of GVHD,sensitive and specific biomarkers that predict the severity and prognosis of the disease have been intensively investigated using proteomics,transcriptomics,genomics,cytomics,and tandem mass spectrometry methods.Here,I will briefly review the current understanding of GVHD biomarkers and future prospects.
文摘AIM: To investigate appropriate therapeutic strategies for graft-vs-host disease (GVHD) following liver transplantation. METHODS: Four patients who developed GVHD after liver transplantation in West China Hospital were included in this study. Therapeutic strategies with augmentation or withdrawal of immunosuppressants combined with supportive therapy were investigated in these patients. In addition, a literature review of patients who developed GVHD after liver transplantation was performed. RESULTS: Although a transient response to initial treatment was detected, all four patients died of complications from GVHD: one from sepsis with multiple organ failure, one from gastrointestinal bleeding, and the other two from sepsis with gastrointestinal bleeding. Few consensuses for the treatment of GVHD after liver transplantation have been reached.CONCLUSION: New and effective treatments are re-quired for GVHD after liver transplantation to improve the prognosis of patients with this diagnosis.
基金Supported by Youth Project of National Natural Science Foundation,No. 81200400National Social Science Foundation,No. 14CFX031+2 种基金TopNotch Innovative Talents Project and Fujian Project,No. 2016Y9025,No. 2016J06018 and No. 2017I0004Fujian Medical University Teaching Reform Project,No.Y17005Fujian Provincial Health and Family Planning Commission Youth Research Project,No. 2017-1-6
文摘Hematopoietic stem cell transplantation has become a curative choice of many hematopoietic malignancy,but graft-vs-host disease(GVHD)has limited the survival quality and overall survival of hematopoietic stem cell transplantation.Understanding of the immune cells’reaction in pathophysiology of GVHD has improved,but a review on the role of macrophages in GVHD is still absent.Studies have observed that macrophage infiltration is associated with GVHD occurrence and development.In this review,we summarize and analyze the role of macrophages in GVHD based on pathophysiology of acute and chronic GVHD,focusing on the macrophage recruitment and infiltration,macrophage polarization,macrophage secretion,and especially interaction of macrophages with other immune cells.We could conclude that macrophage recruitment and infiltration contribute to both acute and chronic GVHD.Based on distinguishing pathology of acute and chronic GVHD,macrophages tend to show a higher M1/M2 ratio in acute GVHD and a lower M1/M2 ratio in chronic GVHD.However,the influence of dominant cytokines in GVHD is controversial and inconsistent with macrophage polarization.In addition,interaction of macrophages with alloreactive T cells plays an important role in acute GVHD.Meanwhile,the interaction among macrophages,B cells,fibroblasts,and CD4+T cells participates in chronic GVHD development.
文摘Chronic graft-vs-host disease(c GVHD) is the leading cause of long-term morbidity and mortality following allogeneic hematopoietic stem cell transplantation. It presents as a chronic inflammatory and sclerotic autoimmune-like condition that most frequently affects the skin, oral mucosa, liver, eyes and gastrointestinal tract. Both clinical and animal studies have shown that multiple T cell subsets including Th1, Th2, Th17, T follicular helper cells and regulatory T-cells play some role in cG VHD development and progression; B cells also play an important role in the disease including the production of antibodies to HY and nuclear antigens that can cause serious tissue damage. An array of cytokines and chemokines produced by different types of immune cells also mediate tissue inflammation and damage of cG VHD target tissues such as the skin and oral cavity. Many of these same immune regulators have been studied as candidate cG VHD biomarkers. Recent studies suggest that some of these biomarkers may be useful for determining disease prognosis and planning long-term clinical followup of cG VHD patients.
文摘BACKGROUND Graft-vs-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation.Some patients have steroid-refractory(SR) GVHD.AIM To evaluate the effect and safety of ruxolitinib add-on in the treatment of patients with SR acute (a) and chronic (c) GVHD.METHODS We retrospectively analyzed 38 patients administered ruxolitinib add-on to standard immunosuppressive therapy for SR-aGVHD or SR-cGVHD following allogeneic hematopoietic stem cell transplantation.Ruxolitinib was administered5-10 mg/d depending on disease severity,patient status,and the use of antifungal drugs.Overall response rate,time to best response,malignancy relapse rate,infection rate,and treatment-related adverse events were assessed.RESULTS The analysis included 10 patients with SR-aGVHD (gradeⅢ/Ⅳ,n=9) and 28patients with SR-cGVHD (moderate/severe,n=24).For the SR-aGVHD and SRcGVHD groups,respectively:Median number of previous GVHD therapies was 2(range:1-3) and 2 (1-4);median follow-up was 2.5 (1.5-4) and 5 (1.5-10) mo;median time to best response was 1 (0.5-2.5) and 3 (1-9.5) mo;and overall response rate was 100%(complete response:80%) and 82.1%(complete response:10.7%) with a response observed in all GVHD-affected organs.The malignancy relapse rates for the SR-aGVHD and SR-cGVHD groups were 10.0%and 10.7%,respectively.Reactivation rates for cytomegalovirus,Epstein-Barr virus,and varicella-zoster virus,respectively,were 30.0%,10.0%,and 0%for the SR-aGVHD group and 0%,14.3%,and 7.1%for the SR-cGVHD group.CONCLUSION Ruxolitinib add-on was effective and safe as salvage therapy for SR-GVHD.
文摘BACKGROUND Acute gastrointestinal(GI)graft-vs-host disease(aGVHD)is the most complication of hematopoietic stem cell transplant(HSCT)in patients with hematologic malignancy.Limited data exists on endoscopic evaluation of GVHD in post-HSCT patients with differing GI symptoms.Further,the diagnostic value of gross endoscopic findings as well as the safety of endoscopy in this commonly thrombocytopenic and neutropenic patient population remains unclear.AIM To understand the diagnostic value of symptoms and gross endoscopic findings as well as safety of endoscopy in aGVHD patients.METHODS We analyzed 195 endoscopies performed at City of Hope in patients who underwent allogeneic HSCT less than 100 d prior for hematologic malignancy and were subsequently evaluated for aGVHD via endoscopy.The yield,sensitivity,and specificity of diagnosing aGVHD were calculated for upper and lower endoscopy,various GI tract locations,and presenting symptoms.RESULTS Combined esophagogastroduodenoscopy(EGD)and flexible sigmoidoscopy(FS)demonstrated a greater diagnostic yield for aGVHD(83.1%)compared to EGD(66.7%)or FS(77.2%)alone with any presenting symptom.The upper and lower GI tract demonstrated similar yields regardless of whether patients presented with diarrhea(95.7%vs 99.1%)or nausea/vomiting(97.5%vs 96.8%).Normalappearing mucosa was generally as specific(91.3%)as abnormal mucosa(58.7%-97.8%)for the presence of aGVHD.Adverse events such as bleeding(1.0%),infection(1.0%),and perforation(0.5%)only occurred in a small proportion of patients,with no significant differences in those with underlying thrombocytopenia(P=1.000)and neutropenia(P=0.425).CONCLUSION Combined EGD and FS with biopsies of normal and inflamed mucosa demonstrated the greatest diagnostic yield regardless of presenting symptom and appears to be safe in this population of patients.
文摘We report a case of a 56-year-old woman with a history of allogenic bone marrow transplantation for two years,complaining with dysphagia and weight loss. Upper endoscopy revealed esophageal stenosis and extensive mucosa sloughing. Biopsies confirmed the diagnosis of graft-vs-host disease(GVHD). Balloon dilation,corticosteroids and cyclosporin resulted in marked clinical improvement. Gastrointestinal tract is involved in the majority of patients with chronic GVHD. Esophageal manifestations are rare and include vesiculobullous disease,ulceration,esophageal webs,casts or strictures. Sloughing esophagitis along with severe stenosis requiring endoscopic dilation has never been reported in this context.
