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Long-term outcome of stem cell transplantation with and without anti-tumor necrotic factor therapy in perianal fistula with Crohn’s disease

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World Journal of stem cells 2024年第3期16卷 257-266页

作者： Min Young Park Yong Sik Yoon Jae Ha Park Jong Lyul Lee Chang Sik Yu Division of Colon and Rectal Surgery Department of SurgeryYonsei University College of MedicineSeoul 03722South Korea Division of Colon and Rectal Surgery Department of SurgeryUniversity of Ulsan College of MedicineAsan Medical CenterSeoul 05505South Korea

BACKGROUND stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn’s disease(CD).Anti-tumor necrotic factor(TNF)therapy combined with drainage procedure is effective as well.However,previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula closure.AIM This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare Crohn’s perianal fistula(CPF)closure rates after stem cell transplantation with and without anti-TNF therapy,and to identify the factors affecting CPF closure and recurrence.METHODS The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were enrolled.Clinical data were compared according to anti-TNF therapy and CPF closure.RESULTS A total of 65 patients were included.The median age of females was 26 years(range:21-31)and that of males was 29(44.6%).The mean follow-up duration was 65.88±32.65 months,and complete closure was observed in 50(76.9%)patients.The closure rates were similar after stem cell transplantation with and without anti-TNF therapy(66.7%vs 81.6%at 3 year,P=0.098).The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture(P=0.027,0.002,and 0.008,respectively).Clinical factors such as complexity,number of fistulas,presence of concurrent abscess,and medication were not significant for closure.The cumulative 1-,2-,and 3-year closure rates were 66.2%,73.8%,and 75.4%,respectively.CONCLUSION Anti-TNF therapy does not increase CPF closure rates in patients with stem cell transplantation.However,both refractory and non-refractory CPF have similar closure rates after additional anti-TNF therapy.Fistulous tract length,proctitis,and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation.

关键词： Crohn’s disease Anus Fistula stem cell transplantation Tumor necrosis factor-alpha inhibitors Infliximab

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Intraportal mesenchymal stem cell transplantation prevents acute liver failure through promoting cell proliferation and inhibiting apoptosis

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Hepatobiliary & Pancreatic Diseases International 2016年第6期15卷 602-611页

作者： Jian-Feng Sang Xiao-Lei Shi Bin Han Tao Huang Xu Huang Hao-Zhen Ren Yi-Tao Ding Department of General Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical School

BACKGROUND： transplantation of mesenchymal stem cells （MSCs） has been regarded as a potential treatment for acute liver failure （ALF）, but the optimal route was unknown. The present study aimed to explore the most effective MSCs transplantation route in a swine ALF model. METHODS： The swine ALF model induced by intravenous injection of D-Gal was treated by the transplantation of swine MSCs through four routes including intraportal injection （InP group）, hepatic intra-arterial injection （AH group）, peripheral intravenous injection （PV group） and intrahepatic injection （IH group）. The living conditions and survival time were recorded. Blood samples before and after MSCs trans- plantation were collected for the analysis of hepatic function. The histology of liver injury was interpreted and scored in terminal samples. Hepatic apoptosis was detected by TUNEL assay. Apoptosis and proliferation related protein expressions including cleaved caspase-3, survivin, AKT, phospho-AKT （Ser473）, ERK and phospho-ERK （Tyr204） were analyzed by Western blotting. RESULTS： The average survival time of each group was 10.7± 1.6 days （InP）, 6.0±0.9 days （AH）, 4.7±1.4 days （PV）, 4.3± 0.8 days （IH）, respectively, when compared with the average survival time of 3.8±0.8 days in the D-Gal group. The survival rates between the InP group and D-Gal group revealed a statistically significant difference （P〈0.01）. Pathological and biochemical analysis showed that liver damage was the worst in the D-Gal group, while less injury in the InP group. Histopathological scores revealed a significant decrease in the InP group （3.17±1.04, P〈0.01） and AH group （8.17±0.76, P〈0.05） as compared with that in the D-Gal group （11.50±1.32）. The apoptosis rate in the InP group （25.0%±3.4%, P〈0.01） and AH group （40.5%±1.0% , P〈0.05） was lower than that in the D-Gal group （70.6%±8.5%）. The expression of active caspase-3 was inhibited, while the expression of survivin, AKT, phospho- AKT （Ser473）, ERK and phospho-ERK （Tyr204） was elevated in the InP group. CONCLUSIONS： I

关键词： mesenchymal stem cells stem cell transplantation acute liver failure apoptosis regeneration

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Zhichan decoction induces differentiation of dopaminergic neurons in Parkinson's disease rats after neural stem cell transplantation

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Neural Regeneration Research 2014年第9期9卷 931-936页

作者： Huifen Shi Jie Song Xuming Yang Department of Neurology Shanghai Municipal Hospital of Traditional Chinese Medicine Department of Encephalopathy Liu’an Hospital of Traditional Chinese Medicine College of Acupuncture and Massage Shanghai University of Traditional Chinese Medicine

The goal of this study was to increase the dopamine content and reduce dopaminergic metabolites in the brain of Parkinson’s disease rats. Using high-performance liquid chromatography, we found that dopamine and dopaminergic metabolite（dihydroxyphenylacetic acid and homovanillic acid） content in the midbrain of Parkinson’s disease rats was increased after neural stem cell transplantation ＋ Zhichan decoction, compared with neural stem cell transplantation alone. Our genetic algorithm results show that dihydroxyphenylacetic acid and homovanillic acid levels achieve global optimization. Neural stem cell transplantation ＋ Zhichan decoction increased dihydroxyphenylacetic acid levels up to 10-fold, while transplantation alone resulted in a 3-fold increment. Homovanillic acid levels showed no apparent change. Our experimental findings show that after neural stem cell transplantation in Parkinson’s disease rats, Zhichan decoction can promote differentiation of neural stem cells into dopaminergic neurons.

关键词： nerve regeneration traditional Chinese medicine neurodegeneration Parkinson’s disease rat model Zhichan decoction stem cell transplantation dopamine metabolite dihydroxyphenylacetic acid homovanillic acid curve fitting equation genetic algorithm optimization model NSFC grant neural degeneration

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Fludarabine and intravenous busulfan conditioning with post-transplantation cyclophosphamide for allogeneic peripheral stem cell transplantation for adult patients with lymphoid malignancies:a prospective single-arm phase Ⅱ study

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Frontiers of Medicine 2021年第1期15卷 108-115页

作者： Ling Wang Lining Wang Xing Fan Wei Tang Jiong Hu Department of Hematology Blood&Marrow Transplantation CenterCollaborative Innovation Center of HematologyRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China

Post-transplantation cyclophosphamide(PT-Cy)alone or in combination with other immunosuppressive drugs has emerged as a promising strategy in the setting of allogeneic hematopoietic stem cell transplantation.Improved survival rate was reported in lymphoid malignancies following PT-Cy strategy compared with myeloid disease in non-myeloablative bone marrow transplant setting.Thus,we aimed to evaluate the safety and efficacy of PT-Cy combined with cyclosporine as graft-versus-host disease(GVHD)prophylaxis after myeloablative conditioning and T cell-replete peripheral stem cell transplantation in lymphoid malignancies.This single-arm phase Ⅱ clinical trial(NCT01435447)involving 31 adult patients was conducted from January 2013 to June 2018.The donor-type neutrophil engraftment rate was 100%,and the overall incidence of grade Ⅱ to Ⅳ and grade Ⅲ to Ⅳ acute GVHD was 39%and 24%,respectively.The cumulative incidence rates of chronic GVHD(35%),including moderate to severe forms(10%),were reduced compared with those of the historical group(P=0.03 and P=0.04,respectively).With a median follow-up of 18 months,the estimated 2-year overall and event-free survival was 64.8%(95%confidence interval:47.8%–86.7%)and 58.4%(95%CI:41.9%–81.7%),respectively.The 2-year cumulative incidence rate of relapse was 19.5%(95%CI:9.0%–35.8%),whereas the non-relapse mortality rate was 21.8%(95%CI:11.3%–38.1%).These results demonstrated the feasibility of PT-Cy as GVHD prophylaxis in this clinical setting.This strategy could significantly reduce the incidence of chronic GVHD and its moderate to severe forms but not of acute GVHD and results in similar survival outcomes compared with the historical group.A prospective study with additional patients is warranted to confirm the role of PT-Cy in lymphoid malignancy.

关键词： post-transplantation cyclophosphamide allogeneic hematopoietic stem cell transplantation lymphoid malignancies

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Sequential treatment with bortezomib plus dexamethasone followed by autologous hematopoietic stem cell transplantation in patients with multiple myeloma

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Chinese Medical Journal 2012年第24期125卷 4454-4459页

作者： ZHENG Dong LI Juan, HUANGBei-hui LIU Jun-ru ZOU Wai-yi SU Chang Department of Hematology First Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong 510080 China

Background Whether the sequential treatment with bortezomib plus dexamethasone （BD） followed by autologous hematopoietic stem cell transplantation （ASCT） could extend the overall survival period in multiple myeloma patients is still not clear. Few large case studies about this therapeutics in multiple myeloma were reported in China. Our purpose was to assess the efficacy and adverse effects of sequential treatment with BD chemotherapy and ASCT in patients with multiple myeloma. Methods Fifty-three patients with newly diagnosed or relapsed/refractory multiple myeloma received BD as induction therapy before ASCT. stem-cell mobilization was undertaken with cyclophosphamide 3-5 g/m2 plus granulocyte colony-stimulating factor 300 IJg/d. Target yield was 2.0x106 CD34＋ cells/kg. Conditioning for ASCT consisted of melphalan 200 mg/m2. Thalidomide and/or Q-interferon was used as post-transplantation maintenance treatment. Results The BD chemotherapy before transplantation was effective in 86.7% of the 53 patients, including 22.6% with complete remission （CR）, 39.6% with near complete remission （nCR）, and 24.5% with partial remission （PR）. The best effect was achieved after two treatment courses. Most bortezomib-related adverse effects were classes 1-2. All patients were successfully mobilized after BD for autologous peripheral blood stem cell transplantation. The ASCT was effective in 96.3% of patients, including 49.1% with CR, 32.1% with nCR, and 15.1% with PR. The CR rate was significantly increased （49.1% vs. 22.6%, P 〈0.05） by sequential ASCT. Within 27 （range, 6-53） months of follow-up, the efficacy of ASCT was maintained in 29 patients and further enhanced by post-transplantation maintenance treatment in four patients. Eleven patients died after transplantation. Among the patients undergoing BD/ASCT treatment, overall survival （OS） was significantly better in newly diagnosed patients in comparison to relapsed/refractory patients （P=0.046）. Conclusions BD chemotherapy can be used as an induction therapy prior to ASCT

关键词： bortezomib stem cell transplantation multiple myeloma

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Modified conditioning regimen busulfan-cyclophosphamide followed by allogeneic stem cell transplantation in patients with multiple myeloma

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Chinese Medical Journal 2007年第6期120卷 463-468页

作者： ZHANG Xiao-hui HUANG Xiao-jun LIU Kai-yan XU Lan-ping LIU Dai-hong CHEN Huan CHEN Yu-hong WANG Jing-zhi HAN Wei LU Dao-pei Institute of Hematology Peking University People＇s Hospital Beijing 100044 China

Background Allogeneic stem cell transplantation is a potential curative approach in patients with multiple myeloma. The very high transplant related mortality associated with standard allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative treatment modality. The challenge for clinical investigators is to reduce the incidence of post-transplant complications for patients receiving autologous hematopoietic stem cell transplantion for multiple myeloma. In this study the toxicity and efficacy of modified myeloablative conditioning regimen followed by allogeneic stem cell transplantation was investigated in patients with multiple myeloma. Methods The conditioning regimen consisted of hydroxyurea, cytarabine, busulfan, cyclophosphamide, and semustine. Ten patients underwent allogeneic transplantation among them hydroxyurea （40 mg/kg） was administered twice on day -10 and cytarabine （2 g/ms） was given on day -9, busulfan was administered orally in four divided doses daily for 3 days （days -8 to -6）. The dose of busulfan was 12 mg/kg in the protocol followed by cyclophosphamide intravenously over 1 hour on days -5 and -4 （1.8 g/m^2）, and with semustine （Me-CCNU） 250 mg/m^2 on day -3. Results Chimerism data were available on all patients and all patients achieved full donor chimerism without graft failure. Six patients had not acute graft-versus-host disease （GVHD, 36.4%; 95% CI： 13.9%-38.6%）. Two patients （18.2%） developed grade Ⅰ acute GVHD （95% CI： 10.9%-35.9%） and grade Ⅱ acute GVHD occurred in one patient （9.1%; 95% Cl. 8.4%-32.3%）. Severe grade IVa GVHD was seen in one patient, who died from acute GVHD. The incidence of chronic GVHD was 22.2% （95% Cl： 11.7%-36.7%）, among them one died of severe grade IV GVHD and one developed multiorgan failure on day ＋170; the treatment-related mortality was 22.0% （95% Cl： 10.3%-34.1%）. The overall 4-year survival rate was 67.8% （95% Cl： 16.3%-46.7%）. The estimated 4-year progression-free survival rate was 58.5% （95% CI： 13.

关键词： multiple myeloma stem cell transplantation modified conditioning regimen

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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

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Infusions of recipient-derived cytokine-induced killer cells of donor origin eradicated residual disease in a relapsed leukemia patient after allo-hematopoietic stem cell transplantation

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Chinese Medical Journal 2012年第9期125卷 1669-1671页

作者： ZHONG Zhao-dong LUO Yi ZOU Ping ZHENG Jin-e YAO Jun-xia HUANG Shi-ang ZHOU Dong-feng YOU Yong Department of Hematology Union Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430022 China Center for stem cell Research and Application Union Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430022 China Department of Pediatric Hematology Union Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430022 China

A female patient diagnosed with acute myelocytic leukemia M5a （AML-M5a） relapsed 986 days after her allogeneic peripheral blood stem cell transplantation （alIo-PBSCT） from an unrelated male donor with matched human leukocyte antigen （HLA）. Three re-induction chemotherapies were administered, and partial remission was achieved. The patient was given repetitive infusion of cytokine-induced killer （CIK） cells expanded from recipient peripheral mononuclear cells of full donor chimerism due to loss of contact of quondam donor for donor lymphocyte infusion （DLI） and rejection of second transplantation. The patient achieved complete cytogenetical remission. This strategy might overcome the obstacle of donor unavailability and present an appealing new therapeutic alternative to donor-recruited adoptive immunotherapy for relapsed disease at post-transplantation.

关键词： cytokine-induced killer cells stem cell transplantation relapsed leukemia minor residual disease donor lymphocyte infusion

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Haploidentical hematopoietic stem cell transplantation as promising therapy in the improved survival of pediatric patients with leukemias and myelodysplasias

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World Journal of Meta-Analysis 2023年第5期11卷 181-195页

作者： Ana Clara Carvalho Cardoso Brito Everton Oliveira Carneiro Ribeiro Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

BACKGROUND Haploidentical hematopoietic stem cell transplantation(Haplo-HSCT)is often performed in children with hematologic malignancies.Faced with the gap in the literature regarding the approach to experiences related to Haplo-HSCT with pediatric patients with leukemias and myelodysplasias aged up to 18 years,there was an interest in exploring the clinical outcomes of patients undergoing this treatment.AIM To identify and summarize the scientific contributions available on Haplo-HSCT performed in the last 10 years in children and adolescents with myeloid and lymphoid leukemias and myelodysplasias,aged up to 18 years.METHODS This is a descriptive systematic review.We extracted data including characteristics of participants,health condition,characteristics of the donation,conditioning regimen,recurrent clinical complications and clinical outcomes.The Virtual Health Library Brazil,PubMed,EMBASE,and SciELO platforms were used,finding a total of 1052 studies.After the eligibility criteria and complete reading of the texts,18 articles were included for analysis.RESULTS The total sample of all study cohorts was 1825 patients,mostly male,the highest reported median age was 15.0 years and the lowest was 1.2 years.Acute graftversus-host disease and chronic graft-versus-host disease were observed in almost all studies.Relapse,graft rejection and delayed immune recovery were identified as major clinical challenges.Pre-transplant minimal positive residual disease was identified in 288 patients.Infections are also among the main clinical complications,viral,bacterial and fungal infections being reported.It is observed that in the 5-year interval,the lowest rates of EFS and overall survival(OS)were 29.5%and 68.0%,respectively.While,the highest rates of EFS and OS,in the same interval,were 80.1%and 81.0%.CONCLUSION Haplo-HSCT represents a promising therapy,considering the potential number of possible donors and the conditioning and treatment platforms that can be offered.The results obtained show that this type of transplant

关键词： Haploidentical stem cell transplantation Children Cancer Treatment outcome Prognosis

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A HIGHER INCIDENCE OF RELAPSE FOR ACUTE LYMPHOCYTIC LEUKEMIA TREATED WITH ALLOGENEIC HEMATOPOIETIC stem cell transplantation CONDITIONED WITH BU-CY_2 REGIMEN

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Chinese Journal of Cancer Research 2003年第3期15卷 213-216页

作者：朱康儿钟隽张涛曾慧兰 Department of Hematology First Affiliated Hospital Jinan University Guangzhou 510630

Objective: To analyze long-term outcome in sixty leukemia patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) following busulfan and cyclophosphamide (BU-CY2) between 1994 and 2000. Methods: BU-CY2 was used as the conditioning regimen and allo-HSCT was performed for all patients. All the patients were followed-up until August 2001 or death. The leukemia-free survival, relapse and transplant-related mortality were discussed. Results: All 60 patients had sustained engraftment. Acute GVHD occurred in 22 out of 60 patients (36.7%), and the incidence of acute GVHD was 48% in the patients with CML, 30% in AML and 26.7% in ALL. 38 patients are still alive in continuous remission with a median follow-up of 30 months (range 12–84) and 22 patients have died. The main causes of death were acute GVHD in 3 patients, CMV-IP in 7 patients and relapse in 11 patients, the remaining one died of pulmonary infection. Among 11 patients who died of relapse, 8 patients with ALL relapsed in the early stage post transplant (8/15, 53.3%), relapse was observed in the remaining 3 patients with AML, and however, no relapse was observed in CML. The probability of disease-free survival at 3 years for CML. AML and ALL patients was 80%, 70% and 26.7%, respectively. Conclusion: This results suggests that BU-CY2 is an effective conditioning regimen in patients with AML and CML, resulting in a low relapse rate and high long-term survival rate, but not as effective in patients with ALL, with a higher incidence of relapse and therefore, not recommended for ALL patients.

关键词： stem cell transplantation Allogeneic Busulfan Leukemia

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