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World Journal of Clinical Cases 2023年第29期11卷 7200-7206页

作者： Jin Yan Ting Jin Li Wang School of Medicine Jianghan UniversityWuhan 430056Hubei ProvinceChina Department of Hematology The Central Hospital of WuhanWuhan 430014Hubei ProvinceChina

BACKGROUND Immunosuppressive therapy and matched sibling donor hematopoietic stem cell transplantation(MSD-HSCT)are the preferred treatments for aplastic anemia(AA).CASE SUMMARY In this report,we describe a 43-year-old male patient with severe AA who carried BRIP1(also known as FANCJ),TINF2,and TCIRG1 mutations.Screening of the family pedigree revealed the same TINF2 mutation in his mother and older brother,with his older brother also carrying the BRIP1 variant and demonstrating normal telomere length and hematopoietic function.The patient was successfully treated with oral cyclosporine A,eltrombopag,and acetylcysteine,achieving remission 4 years after receiving MSD-HSCT from his older brother.CONCLUSION This case provides a valuable clinical reference for individuals with suspected pathogenic gene mutations,normal telomere length,and hematopoietic function,highlighting them as potential donors for patients with AA.

关键词： Aplastic anemia hematopoietic stem cell transplantation BRIP1 gene TINF2 gene Telomere length Case report

Measles,mumps,and rubella revaccination in children after completion of chemotherapy and hematopoietic stem cell transplantation:a single-center prospective efficacy and safety analysis

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World Journal of Pediatrics 2023年第11期19卷 1062-1070页

作者： Min Wang Qing Yuan Peng-Fei Deng Yi Fei Hua Zhang Fen Zhou Wen-Juan Chen Qing Cao Jing Chen Yi-Jin Gao Department of Hematology and Oncology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityNo.1678 Dongfang RoadPudong DistrictShanghai200127China Center for Diseases Control and Prevention Fudan University Pudong Institute of Preventive MedicineShanghai200136China Department of Infectious Diseases Shanghai Children’s Medical CenterShanghai Jiao Tong University School of MedicineShanghaiChina

Background Chemotherapy and hematopoietic stem cell transplantation(HSCT)can damage the immune system,and may result in a loss of protection from infectious diseases.This study aimed to evaluate the impact of these treatments on the decrease in antibody titers of the measles,mumps,and rubella(MMR)vaccine and seroconversion post-revaccination of MMR.Methods After completion of treatment for primary diseases,participants received an MMR revaccination.Antibody titers for MMR before revaccination were analyzed for all 110 children.After revaccination,68 participants received a follow-up evaluation of antibody titer and adverse reaction.Results Multivariable analysis showed that therapeutic schedules were the only factor correlated with lack of antibody titers for measles after completing treatment(P=0.008),while for mumps and rubella,no statistically significant difference was observed.Importantly,our study clearly demonstrated positive seroconversion rates for measles(97.5%),mumps(81.0%),and rubella(93.2%),with antibody levels rising across the board and peaking at around 6 months following revaccination.However,6 months after revaccination,a downtrend of antibody titer levels was observed,which is comparatively earlier than the waning immunity observed in healthy children.Furthermore,we found MMR revaccination to be safe,with only a single adverse reaction(local pain at the injection site)reported.Conclusions MMR revaccination is immunogenic for the population.We suggest periodic monitoring of antibody titers,in addition to a booster vaccination,although the optimal timing of booster vaccination remains to be investigated further.

关键词： Adjuvant Chemotherapy Children hematopoietic stem cell transplantation Immunogenicity Mumps-measles-rubella.Vaccine

Current status and prospects of hematopoietic stem cell transplantation in China

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Chinese Medical Journal 2022年第12期135卷 1394-1403页

作者： Xiaoqi Wang Ruihao Huang Xiaohui Zhang Xi Zhang Medical Center of Hematology Xinqiao HospitalState Key Laboratory of TraumaBurn and Combined InjuryArmy Medical UniversityChongqing 400037China Peking University People’s Hospital&Peking University Institute of Hematology National Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China

hematopoietic stem cell transplantation(HSCT)is a highly effective and unique medical procedure for the treatment of most hematological malignancies.The first allogeneic transplantation was performed by E.Donnall Thomas in 1957.Since then,the field has evolved and expanded worldwide.The first successful allogenic HSCT(allo-HSCT)in China was conducted in 1981.Although the development of allo-HSCT in China lagged,China has since made considerable contributions to the process of HSCT worldwide,with more than 10,000 HSCTs performed annually.In particular,haploid HSCT(haplo-HSCT)technology represented in the Beijing Protocol has demonstrated similar efficacy to human leukocyte antigen-matched HSCT and has gradually become the pre-dominant choice for allo-HSCT in China.Currently,the number of haplo-HSCT procedures exceeds 5000 per year,and the Beijing Protocol has been greatly improved by implementing updated individualized strategies for controlling complications,relapse,and infection management.In addition,innovative haplo-HSCT technologies developed by different medical transplantation centers,such as Soochow,Zhejiang,Fujian,Chongqing,and Anhui,have emerged,providing inspiration for the refinement of global practice.This review will focus on the current activity in this field and highlight important trends that are vital in China’s allo-HSCT process,examining the current viewpoint and future directions.

关键词： hematopoietic stem cell transplantation Haploidentical China

Risk stratification system for skin and soft tissue infections after allogeneic hematopoietic stem cell transplantation:PAH risk score

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Frontiers of Medicine 2022年第6期16卷 957-968页

作者： Shan Chong Yun He Yejun Wu Peng Zhao Xiaolu Zhu Fengrong Wang Yuanyuan Zhang Xiaodong Mo Wei Han Jingzhi Wang Yu Wang Huan Chen Yuhong Chen Xiangyu Zhao Yingjun Chang Lanping Xu Kaiyan Liu Xiaojun Huang Xiaohui Zhang Peking University People’s Hospital Peking University Institute of HematologyBeijing100044China Collaborative Innovation Center of Hematology Peking UniversityBeijing100044China Beijing Key Laboratory of hematopoietic stem cell transplantation Beijing100044China National Clinical Research Center for Hematologic Disease Beijing100044China

Skin and soft tissue infections(SSTIs)refer to infections involving the skin,subcutaneous tissue,fascia,and muscle.In transplant populations with hematological malignancies,an immunocompromised status and the routine use of immunosuppressants increase the risk of SSTIs greatly.However,to date,the profiles and clinical outcomes of SSTIs in hematopoietic stem cell transplantation(HSCT)patients remain unclear.This study included 228 patients(3.67%)who developed SSTIs within 180 days after allogeneic HSCT from January 2004 to December 2019 in Peking University People’s Hospital.The overall annual survival rate was 71.5%.We compared the differences between survivors and non-survivors a year after transplant and found that primary platelet graft failure(PPGF),comorbidities of acute kidney injury(AKI),and hospital-acquired pneumonia(HAP)were independent risk factors for death in the study population.A PPGF-AKI-HAP risk stratification system was established with a mortality risk score of 1×PPGF+1×AKI+1×HAP.The areas under the curves of internal and external validation were 0.833(95%CI 0.760–0.906)and 0.826(95%CI 0.715–0.937),respectively.The calibration plot revealed the high consistency of the estimated risks,and decision curve analysis showed considerable net benefits for patients.

关键词： skin and soft tissue infections hematopoietic stem cell transplantation risk stratification system mortality

The Viral Load of Epstein-Barr Virus in Blood of Children after hematopoietic stem cell transplantation

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Biomedical and Environmental Sciences 2022年第9期35卷 804-810页

作者： WANG Wen Jun FENG Shun Qiao HE Feng DU Hai Jun FENG Miao WANG Rui Fang MEI Guo Yong LIU Mi LIU Rong YAO Hai Lan HAN Jun State Key Laboratory of Infectious Disease Prevention and Control National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Department of Hematology Children’s Hospital of Capital Institute of PediatricsBeijing 100020China Department of Biochemistry&Immunology Capital Institute of PediatricsBeijing 100020China

Objective To detect the Epstein-Barr virus(EBV)viral load of children after hematopoietic stem cell transplantation(HSCT)using chip digital PCR(cdPCR).Methods The sensitivity of cdPCR was determined using EBV plasmids and the EBV B95-8 strain.The specificity of EBV cdPCR was evaluated using the EBV B95-8 strain and other herpesviruses(herpes simplex virus 1,herpes simplex virus 2,varicella zoster virus,human cytomegalovirus,human herpesvirus 6,and human herpesvirus 7).From May 2019 to September 2020,64 serum samples of children following HSCT were collected.EBV infection and the viral load of serum samples were detected by cdPCR.The epidemiological characteristics of EBV infections were analyzed in HSCT patients.Results The limit of detection of EBV cdPCR was 110 copies/mL,and the limit of detection of EBV quantitative PCR was 327 copies/mL for the pUC57-BALF5 plasmid.The result of EBV cdPCR was up to 121 copies/mL in the EBV B95-8 strain,and both were more sensitive than that of quantitative PCR.Using cdPCR,the incidence of EBV infection was 18.75%in 64 children after HSCT.The minimum EBV viral load was 140 copies/mL,and the maximum viral load was 3,209 copies/mL using cdPCR.The average hospital stay of children with EBV infection(184±91 days)was longer than that of children without EBV infection(125±79 days),P=0.026.Conclusion EBV cdPCR had good sensitivity and specificity.The incidence of EBV infection was 18.75%in 64 children after HSCT from May 2019 to September 2020.EBV cdPCR could therefore be a novel method to detect EBV viral load in children after HSCT.

关键词： Chip digital PCR Epstein-Barr virus hematopoietic stem cell transplantation Quantitative PCR

Allogeneic hematopoietic stem cell transplantation with the modified myeloablative conditioning regimen for children with chronic active Epstein–Barr virus infection

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Pediatric Investigation 2022年第4期6卷 250-259页

作者： Yanhui Luo Ang Wei Bin Wang Guanghua Zhu Rui Zhang Chenguang Jia Yan Yan Xuan Zhou Jun Yang Maoquan Qin Tianyou Wang Department of stem cell transplantation Beijing Key Laboratory of Pediatric Hematology OncologyNational Key Discipline of Pediatrics(Capital Medical University)Key Laboratory of Major Diseases in ChildrenMinistry of EducationBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina

Importance:Allogeneic hematopoietic stem cell transplantation(alloHSCT)is considered the only effective treatment for chronic active Epstein–Barr virus infection(CAEBV).The clinical efficacy and safety of allo-HSCT with different conditioning regimens in children with CAEBV remain unclear.Objective:To evaluate the effectiveness and safety of allo-HSCT with the modified myeloablative conditioning(MAC)regimen for children with CAEBV and also the factors affecting the outcomes.Methods:We retrospectively analyzed children with CAEBV who underwent allo-HSCT with the modified MAC regimen at Beijing Children’s Hospital,Capital Medical University from October 2016 to June 2021.Data related to the clinical manifestations,engraftment,and outcome were extracted from the medical records.Results:The cohort comprised 41 patients(24 males,17 females)with a median transplantation age of 92.6(60.4,120.7)months and a median follow-up time of 28.2(15.3,40.2)months.Four patients(9.8%)died,among which three died from primary disease relapse,and one died from grade IV acute graft-versus-host diseases(aGVHD)after stopping treatment.The 3-year overall survival(OS)and 3-year event-free survival(EFS)rates were 88.8%±5.4%and 85.0%±5.7%,respectively.The 3-year OS and EFS did not significantly differ between the patients with hemophagocytic lymphohistiocytosis(HLH)and the patient without HLH(87.7%±6.8%vs.91.7%±8.0%,P=0.790;85.0%±6.9%vs.84.6%±10.0%,P=0.921),or among the patients with complete remission,partial remission,and activity disease before HSCT(all P>0.05).Multivariate analysis showed that grade III–IV aGVHD was a risk factor for mortality(Hazards ratio:11.65,95%confidence interval:1.00,136.06;P=0.050).Interpretation:Allo-HSCT with the modified MAC regimen is safe and effective for pediatric CAEBV.This treatment benefits patients with HLH or active disease.Patients with Grade III–IV aGVHD may be associated with worse outcomes.

关键词： Myeloablative conditioning Chronic active Epstein-Barr virus infection hematopoietic stem cell transplantation Children

Sarcopenia and gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation

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中国癌症研究:英文版 2023年第4期35卷 386-398页

作者： Boshi Wang Wei Hu Xue Zhang Yanchao Cao Lin Shao Xiaodong Xu Peng Liu Department of Clinical Nutrition Peking University People’s HospitalBeijing 100044China Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing 100044China

Objective: The aim of this study was to investigate the prevalence of sarcopenia(SP) and its relationship with gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation(HSCT).Methods: A total of 108 patients with various hematological disorders were selected from Peking University People’s Hospital. SP was screened and diagnosed based on the 2019 Asian Sarcopenia Diagnosis Strategy. Physical measurements and fecal samples were collected, and 16S rRNA gene sequencing was conducted. Alpha and beta diversity analyses were performed to evaluate gut microbiota composition and diversity.Results: After HSCT, significant decreases in calf circumference and body mass index(BMI) were observed,accompanied by a decline in physical function. Gut microbiota analyses revealed significant differences in the relative abundance of Enterococcus, Bacteroides, Blautia and Dorea species before and after HSCT(P<0.05). Before HSCT, sarcopenic patients had lower Dorea levels and higher Phascolarctobacterium levels than non-sarcopenia patients(P<0.01). After HSCT, no significant differences in species abundance were observed. Alpha diversity analysis showed significant differences in species diversity among the groups, with the highest diversity in the postHSCT 90-day group and the lowest in the post-HSCT 30-day group. Beta diversity analysis revealed significant differences in species composition between pre-and post-HSCT time points but not between SP groups. Linear discriminant analysis effect size(LEfSe) identified Alistipes, Rikenellaceae, Alistipes putredinis, Prevotellaceae defectiva and Blautia coccoides as biomarkers for the pre-HSCT sarcopenia group. Functional predictions showed significant differences in anaerobic, biofilm-forming and oxidative stress-tolerant functions among the groups(P<0.05).Conclusions: This study demonstrated a significant decline in physical function after HSCT and identified potential gut microbiota biomarkers and functional alterations a

关键词： Sarcopenia hematological diseases hematopoietic stem cell transplantation gut microbiota 16S rRNA gene sequencing

Early diagnostic value of liver stiffness measurement in hepatic sinusoidal obstruction syndrome induced by hematopoietic stem cell transplantation

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World Journal of Clinical Cases 2022年第26期10卷 9241-9253页

作者： You-Wen Tan Yi-Chun Shi Department of Hepatology The Third Hospital of Zhenjiang Affiliated Jiangsu UniversityZhenjiang 212003Jiangsu ProvinceChina

hematopoietic stem cell transplantation(HSCT)-sinusoidal obstruction syndrome(SOS),also known as veno-occlusive disease,is a clinical syndrome characterized by symptoms,such as right upper quadrant pain,jaundice,fluid retention,and hepatomegaly,and is caused by pre-treatment-related hepatotoxicity during the early stages after HSCT.Clinical diagnosis of HSCT-SOS is based on the revised Seattle or Baltimore standards.The revised standard by the European Society for Bone Marrow transplantation in 2016 has good practicability and can be used in combination with these two standards.Eight studies have shown the value of liver stiffness measurement(LSM)in the early diagnosis of HSCT-SOS.Four studies investigated LSM specificity and sensitivity for the early diagnosis of HSCT-SOS.LSM can distinguish SOS from other post-HSCT complications,enabling a clear differential diagnosis.It has been shown that median LSM of patients with SOS is significantly higher than that of patients with other treatment-related liver complications(e.g.,acute cholecystitis,cholangitis,antifungal drug-related liver injury,liver graft-versus-host disease,isolated liver biochemical changes,and fulminant Epstein Barr virus related hepatitis reactivation).Therefore,the above data confirmed the utility of LSM and strongly suggested that LSM improves the positive predictive value of the SOS diagnostic clinical score after allogeneic HSCT.Early diagnosis of SOS is beneficial in preventing severe HSCT complications.

关键词： hematopoietic stem cell transplantation Sinusoidal obstruction syndrome Liver stiffness measurement stem cell

hematopoietic stem cell transplantation for Crohn's disease: Gaps, doubts and perspectives

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World Journal of stem cells 2018年第10期10卷 134-137页

作者： Milton Artur Ruiz Roberto Luiz Kaiser Junior Lilian Piron-Ruiz Tatiana Pena-Arciniegas Priscila Samara Saran Luiz Gustavo De Quadros Bone Marrow Transplant Department Associaaao Portuguesa de BeneficenciaSao Joseo Rio PretoSP 15090 470Brazil

Crohn's disease(CD) is an inflammatory bowel disease that can affect any site of the digestive system. It occurs due to an immunological imbalance and is responsible for intestinal mucosal lesions and complications such as fistulas and stenoses. Treatment aims to stabilize the disease, reducing the symptoms and healing intestinal lesions. Surgical procedures are common in patients. cell therapy was initially used to treat this disease in patients who also suffered from lymphoma and leukemia and were considered to be good candidates for autologous and allogeneic transplantation. After transplantation, an improvement was also observed in their CD. In 2003, the procedure began to be used to treat the disease itself, and several case series and randomized studies have been published since then; this approach currently comprises a new option in the treatment of CD. However, considerable doubt along with significant gaps in our knowledge continue to exist in relation to cell therapy for CD. cell therapy is currently restricted to the autologous modality of hematopoietic stem cell transplantation and, experimentally, to mesenchymal stromal cells to directly treat lesions of the anal mucosa. This article presents the supporting claims for transplantation as well as aspects related to the mobilization regime, conditioning and perspectives of cell therapy.

关键词： stem cell therapy hematopoietic stem cell transplantation Treatment Crohn's disease

Advancement of human leukocyte antigen-partially matched related hematopoietic stem cell transplantation

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Frontiers of Medicine 2013年第3期7卷 306-315页

作者： Xiaodong Mo Xiaojun Huang Peking University People’s Hospital&Institute of Hematology Beijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China

Allogeneic hematopoietic stem cell transplantation(HSCT)is one of the most effective options for hematological malignancies,and human leukocyte antigen-partially matched related donors(PMRDs)are a valuable option for HSCT.Several protocols(with or without ex vivo T-cell depletion(TCD))have been established worldwide.TCD including CD34+positive selection and CD3/CD19 depletion has successfully overcome the human leukocyte antigen disparity.However,TCD is associated with prolonged immune deficiencies,increased risks of infectious complications,and high transplantation-related mortality.PMRD HSCT without ex vivo TCD is well developed,and numerous patients have benefitted from it.Here,we review the literature on PMRD HSCT.

关键词： partially matched related donor hematopoietic stem cell transplantation allogeneic