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Incidence of ocular manifestations in patients with graft versus host disease after allogeneic stem cell transplant in Riyadh, Saudi Arabia

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International Journal of Ophthalmology(English edition) 2022年第7期15卷 1149-1156页

作者： Tariq Aldebasi Rabia Bashir Shiji Gangadharan Naila AShaheen Basil Alhussain Tariq Almudhaiyan Bader Alahmari Department of Ophthalmology King Abdulaziz Medical CityNational Guard Health AffairsRiyadh 11426Saudi Arabia King Abdullah International Medical Research Center(KAIMRC) Riyadh 11426Saudi Arabia King Saud bin Abdulaziz University for Health Sciences Riyadh 11426Saudi Arabia Divisions of Adult Hematology and SCT King Abdulaziz Medical CityNational Guard Health AffairsRiyadh 11426Saudi Arabia

AIM: To evaluate the incidence and severity of ocular graft versus host disease(o GVHD) in patients who underwent allogeneic stem cell transplant(SCT) in King Abdul-Aziz Medical City, Saudi ***: This is a retrospective cohort study conducted in King Abdul Aziz Medical City on patients who underwent allogeneic hematopoietic cell transplant(allo-HCT) from 2010 to 2017. The ocular examination findings including visual acuity, meibomian gland dysfunction, corneal and conjunctival staining with severity, corneal scarring, tear film meniscus and breakup time, anterior and posterior segment examination findings, intraocular pressure, treatment given, punctual plugs used or not, and follow up response were ***: The five years cumulative incidence of o GVHD among post-transplant patients was 56.98%(95%CI 38.6%-71.7%). The potential risk factors assessed for developing ocular manifestation were age, gender, donor’s age, donor gender mismatch CD3 and CD34 infusion, while none of the correlates were identified as statistically significant risk factors of developing ocular manifestation. However, the incidence was statistically significantly different betweenpatients diagnosed with acute myelocytic leukemia and acute lymphocytic leukemia(P=0.038). The mean latent period to develop ocular symptoms was 20.5 mo. All patients had variable degree of dry eyes. None of the patients developed any posterior segment ***: The incidence of o GVHD is low in King Abdul-Aziz Medical City. This can be attributed to the preconditioning and immunosuppressive regime.

关键词： graft versus host disease allogenic stem cell transplant dry eye

Colonoscopy in the diagnosis of intestinal graft versus host disease and cytomegalovirus enteritis following allogeneic haematopoietic stem cell transplantation

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Chinese Medical Journal 2008年第14期121卷 1285-1289页

作者： HE Jin-de LIU Yu-lan WANG Zhi-feng LIU Dai-hong CHEN Huan CHEN Yu-hong Department of Gastroenterology People's Hospital Peking University Beijing 100044 China Department of Haematology People's Hospital Peking University Beijing 100044 China

Background Gastrointestinal graft versus host disease （GI-GVHD） and cytomegalovirus （CMV） enteritis are important complications following allogeneic haematopoietic stem cell transplantation （allo-HSCT）. We explored the role of colonoscopy in the diagnosis of GI-GVHD and CMV enteritis following alIo-HSCT to identify the endoscopic manifestations of GI-GVHD and CMV enteritis was made. Methods A retrospective analysis of the colonoscopic manifestations of GI-GVHD, CMV enteritis and GI-GVHD with concurrent CMV enteritis （GconC） and their related clinical issues. Results Forty-seven patients underwent 50 colonoscopies with diagnoses of 32 GI-GVHD, 7 CMV enteritis and 11 GconC. Both GI-GVHD and CMV enteritis had colonic mucosal lesions with various manifestations under colonoscopy. Tortoise shell like changes of the mucosa （12 of 32） and deep ulcers （2 of 7） were specific endoscopic manifestations for GI-GVHD and CMV enteritis, respectively, while mucosal oedema, erythema, congestion, erosion and shallow ulcers could not be used to differentiate GI-GVHD from CMV enteritis. GconC patients were prone to have oozing bleeding of the end ileal mucosa and typhlodicliditis. Of the biopsed specimens for GI-GVHD, CMV enteritis and GconC, 64%, 70% and 44% were taken from the rectum and sigmoid colon respectively. Conclusions Following allo-HSCT, tortoise shell like changes and deep ulcers of the colonic mucosa are characteristic changes for GI-GVHD and CMV enteritis, respectively, while the other lesions are not. Most of the GI-GVHDs and CMV enteritis cases can be diagnosed by left colon examination and tissue biopsy, but total colon examination to the terminal ileum is preferred.

关键词： graft versus host disease cytomegalovirus enteritis stem cell transplantation colonoscopy

Glucocorticoid and glycolysis inhibitors cooperatively abrogate acute graft-versus-host disease

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Science China(Life Sciences) 2023年第3期66卷 528-544页

作者： Qi Wen Zheng-Li Xu Yu Wang Meng Lv Yang Song Zhong-Shi Lyv Tong Xing Lan-Ping Xu Xiao-Hui Zhang Xiao-Jun Huang Yuan Kong Peking University People's Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationCollaborative Innovation Center of HematologyPeking UniversityBeijing 100044China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100044China

Although glucorticosteroids(GCs)are the standard first-line therapy for acute graft-versus-host disease(a Gv HD),nearly 50%of a Gv HD patients have no response to *** role of T cell metabolism in murine a Gv HD was recently ***,whether GCs and metabolism regulators could cooperatively suppress T cell alloreactivity and ameliorate a Gv HD remains to be *** glycolysis,characterized by elevated 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3),and higher rates of glucose consumption and lactate production were found in Tcells from a Gv HD *** upregulation of PFKFB3 induced T cell proliferation and differentiation into proinflammatory *** a humanized mouse model,PFKFB3-overexpressing or PFKFB3-silenced T cells aggravated or prevented a Gv HD,***,our integrated data from patient samples in vitro,in a humanized xenogeneic murine model of a Gv HD and graft-versus-leukaemia(GVL)demonstrate that GCs combined with a glycolysis inhibitor could cooperatively reduce the alloreactivity of T cells and ameliorate a Gv HD without loss of GVL ***,the current study indicated that glycolysis is critical for T cell activation and induction of human a Gv ***,the regulation of glycolysis offers a potential pathogenesis-oriented therapeutic strategy for a Gv HD *** combined with glycolysis inhibitors promises to be a novel first-line combination therapy for a Gv HD patients.

关键词： allogeneic haematopoietic stem cell transplantation graft versus host disease human T cells glycolysis

Neurological complications of hematopoietic cell transplantation in children and adults

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Neural Regeneration Research 2018年第6期13卷 945-954页

作者： Adriana Octaviana Dulamea Ioana Gabriela Lupescu University of Medicine and Pharmacy Carol Davila Bucharest Romania Department of Neurology Fundeni Clinical Institute Bucharest Romania Radiology and Medical imaging Department Fundeni Clinical Institute Bucharest Romania

Hematopoietic cell transplantation（HCT） is widely performed for neoplastic and non-neoplastic diseases. HCT involves intravenous infusion of hematopoietic progenitor cells from human leukocyte antigen（HLA）-matched donor（allogeneic） or from the patient（autologous）. Before HCT, the patient is prepared with high dose chemotherapy and/or radiotherapy to destroy residual malignant cells and to reduce immunologic resistance. After HCT, chemotherapy is used to prevent graft rejection and graft versus host disease（Gv HD）. Neurological complications are related to the type of HCT, underlying disease, toxicity of the conditioning regimens, immunosuppression caused by conditioning regimens, vascular complications generated by thrombocytopenia and/or coagulopathy, Gv HD and inappropriate immune response. In this review, neurological complications are presented according to time of onset after HCT：（1） early complications（in the first month）-related to harvesting of stem cells, during conditioning（drug toxicity, posterior reversible encephalopathy syndrome）, related to pancytopenia,（2） intermediate phase complications（second to sixth month）-central nervous system infections caused by prolonged neutropenia and progressive multifocal leukoencephalopathy due to JC virus,（3） late phase complications（after sixth month）-neurological complications of Gv HD, second neoplasms and relapses of the original disease.

关键词： neurological complications hematopoietic cell transplantation posterior reversible encephalopathy syndrome central nervous system infections progressive multifocal leukoencephalopathy graft versus host disease second neoplasm immune reconstitution inflammatory syndrome post-transplant acute limbic encephalitis drug reaction with eosinophiIia and systemic symptoms

Attenuation of GVHD for Allo-Bone Marrow Transplantation Recipient by FasL-Fas Pathway in an H-2 Haplotype Disparate Mouse Combination

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2004年第4期24卷 329-333页

作者：刘凌波邹萍胡中波仲照东肖娟郭荣徐之良 Institute of Hematology Union Hospital Tongji Medical College Huazhong University of Science and Technology

In order to explore a new special and effective way to prevent graft versus host disease (GVHD) after allogenic bone marrow transplantation (allo-BMT), the stem cell antigen-1 (Sca-1) + early hematopoietic cells (EHC) from BALB/c mouse (H-2 d) were introduced with exogenous mouse Fas ligand (mFasL) cDNA gene by the retrovirus-mediated gene transfer and expanded for one week, and then they were co-cultured with the spleen mononuclear cells (SMNC) from BAC mouse (H-2 d×b) as one way mixed lymphocyte reaction (OWMLR). The cytotoxicity of treated BAC mouse SMNC against Na 2 51CrO 4 labeling SMNC from BALB/c mouse was observed. The bone marrow mononuclear cells (BMMNC) from BAC mouse treated by the above methods were transplanted into lethally-irradiated congenic BALB/c mice to observe the occurrence of GVHD. The results showed that the SMNC from BAC mouse after OWMLR with exogenous mFasL cDNA gene-transduced hematopoietic cells (HC) from BALB/c mouse in a ratio of 1 to 5 exhibited an obvious inhibition of the cytotoxicity against the BALB/c mouse spleen cells at different effector/target ratios as compared to the control group (P<0.01). The gradeⅠ GVHD or no GVHD and the 80 % survival rate at day 60 post-BMT were observed in the BALB/c mouse receiving BAC mouse BMMNC treated with similar way, while the grade Ⅱ-Ⅲ GVHD and the 20 % survival rate were noted in the control group (P<0.01). It is suggested that the attenuation of GVHD in allo-BMT recipient could be successfully achieved through FasL-Fas pathway in an H-2 haplotype disparate mouse combination.

关键词： Fas ligand Fas allogenic bone marrow transplantation graft versus host disease

graft-versus-leukemia effects from donor lymphocyte infusion after nonmyeloablative allogeneic bone marrow transplantation in mice

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Chinese Medical Journal 2005年第6期118卷 474-479页

作者： DUBing LIDe-peng XUKai-lin PANXiu-ying DepartmentofHematology AffiliatedHospitalofXuzhouMedicalCollegeXuzhou221002China

BABSTRACTackground Nonmyeloablative allogeneic bone marrow transplantation has been used since the 1990s as a new hematological stem cell transplantation strategy for treating hematological diseases. The purpose of this study was to explore the graft-versus-leukemia (GVL) effects of donor lymphocyte infusions (DLIs) after nonmyeloablative allogeneic bone marrow transplantations, while assessing the declines in treatment-associated morbidity, mortality, and graft-versus-host disease (GVHD).Methods A total of 615 (H-2~k) mice were injected with L615 tumor cells and received 500 cGy (^(60)Coγ-ray) irradiation three days later, followed by an allogeneic bone marrow transplantation (allo-BMT). The allo-grafts consisted of 3×10~7 bone marrow cells and 1×10~7 spleen cells from BALB/C (H-2~d) donor mice. Two days after the allo-BMT, the recipient mice were given 200 mg/kg of cyclophosphamide. Subsequently, recipient mice were infused with either donor spleen cells (2×10~7) on day 14 or 21, or donor spleen cells (5×10~7) pretreated with hydrocortisone and cyclosporin A (CsA) in vitro on day 14 *** The median survival time of mice that received DLI on day 21 and pretreated DLI on day 14 post-BMT was longer than that of controls and the day 14 DLI group (Pgraft-versus-leukemia effects.

关键词： bone marrow transplantation nonmyeloablative lymphocyte donor graft versus host disease graft versus leukemia effect

A novel approach to human leukocyte antigen-mismatched transplantation in patients with malignant hematological disease

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Chinese Medical Journal 2004年第12期17卷 1778-1785页

作者：黄晓军韩伟许兰平陈育红刘代红路谨陈欢张耀臣江倩刘开彦陆道培 Peking University Institute of Hematology People’s Hospital Beijing 100044 China

Background Many patients requiring allogeneic hematopoietic stem cell transplantation (HSCT) do not have an human loukocyte antigen (HLA) matched donor Alternative donors, such as HLA mismatched family donors, are associated with higher rates of graft rejection and acute graft versus host disease (aGVHD) if T cells are not first depleted We developed a new technique for HLA mismatched allogeneic HSCT using G CSF primed bone marrow plus G CSF mobilized peripheral blood stem cells without ex vivo T cell depletion Methods In this study, 58 patients, including 33 with high risk or advanced leukemia, were transplanted with cells from an HLA haploidentical family donor with 1-3 mismatched loci After conditioning, patients received G CSF primed bone marrow grafts that had not been depleted ex vivo of T cells, in combination with G CSF mobilized peripheral blood stem cells, as well as GVHD prophylaxis Result All patients achieved sustained, full donor type engraftment The incidence of grade Ⅱ Ⅳ aGVHD was 37 9%, including 3 patients with grade Ⅲ Ⅳ aGVHD The development of aGVHD was not associated with the extent of HLA disparity Chronic GVHD was observed in 30 of 51 evaluable patients (65 4%) Fourteen patients died among whom 7 died of recurrent disease and 7 of transplant related complications Forty four of the 58 patients survived, and 42 remained disease free at the time of a median follow up of 12 months (3 5 to 39 5 months) The 2 year probabilities of disease free survival were 74 8% and 69 3% for standard and high risk patients, respectively Conclusion We developed a new method to use bone marrow from haploidentical family donors without ex vivo T cell depletion, in combination with G PBSCs, as a source of stem cells even in cases of HLA mismatched transplantation

关键词： hematopoietic stem cell transplantation human leukocyte antigen leukemia therapy graft versus host disease

Treatments of disease relapse after allogeneic stem cell transplantation focusing on donor lymphocyte infusion

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Chinese Medical Journal 2013年第22期126卷 4380-4388页

作者： LIU Hong-tao LIU Dai-hong HUANG Xiao-jun Andrew Artz Michael R. Bishop Section of Hematology/Oncology University of Chicago Chicago IL USA Institute of Hematology Peking University People's Hospital Beijing 100044 China

Hematopoietic stem cell transplantation （SCT） is a potentially curative treatment for patients with hematologic malignancies, such as acute myeloid leukemia （AML） and myelodysplastic syndromes （MDS）. There has been tremendous progress in the past several decades in allogeneic SCT with better outcomes through improvements in supportive care, expansion of stem cell donor options （HLA-matched unrelated donors （MUD）, haploidentical related donors, and cord blood units （CBUs） etc.）, and introduction of better tolerated reduced intensity conditioning （RIC） regimens.

关键词： donor lymphocyte infusion acute myeloid leukemia allogeneic stem cell transplantation graft versus leukemia effect graft versus host disease

1例异基因造血干细胞移植术后慢性移植物抗宿主病合并慢性心力衰竭患者的护理

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中国实用护理杂志 2010年第5期26卷 58-59页

作者：李桂兰蒋艳广州军区广州总医院血液病科

慢性移植物抗宿主病(chronic graft versus host disease,GVHD)是异基因造血干细胞移植后晚期的主要并发症,是一种全身性、累及多器官的综合征。慢性GVHD是造血干细胞移植后长期存活患者主要的死亡原因,合并慢性心力衰竭时2种病变协同作... 详细信息

慢性移植物抗宿主病(chronic graft versus host disease,GVHD)是异基因造血干细胞移植后晚期的主要并发症,是一种全身性、累及多器官的综合征。慢性GVHD是造血干细胞移植后长期存活患者主要的死亡原因,合并慢性心力衰竭时2种病变协同作用,病情复杂,难以控制,患者随时面临生命危险,应及时给予有效的医疗和护理措施,控制病情,保护生命。2009年2月17日,我科收治了1例急性白血病行亲缘异基因造血干细胞移植术后7年并发慢性GVHD(肝、肺、眼)合

关键词：异基因造血干细胞移植移植术后慢性移植物抗宿主病心力衰竭患者 graft versus host disease 慢性心力衰竭协同作用死亡原因生命危险控制病情护理措施长期存活全身性多器官并发症综合医疗病变保护 GVHD