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

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.

COVID-19 impact in Crohn’s disease patients submitted to autologous hematopoietic stem cell transplantation

BACKGROUND Severe acute respiratory syndrome coronavirus 2 is the virus responsible for coronavirus disease 2019(COVID-19),a disease that has been blamed for inducing or exacerbating symptoms in patients with autoimmune diseases.Crohn's disease(CD)is an inflammatory bowel disease that affects genetically susceptible patients who develop an abnormal mucosal immune response to the intestinal microbiota.Patients who underwent hematopoietic stem cell transplantation(HSCT)are considered at risk for COVID-19.AIM To describe for the first time the impact of COVID-19 in CD patients who had undergone autologous,non-myeloablative HSCT.METHODS In this descriptive study a series of 19 patients were diagnosed with positive COVID-19.For two patients there were reports of the occurrence of two infectious episodes.Parameters related to HSCT,such as time elapsed since the procedure,vaccination status,CD status before and after infection,and clinical manifestations resulting from COVID-19,were evaluated.RESULTS Among the patients with COVID-19,three,who underwent Auto HSCT less than six months ago,relapsed and one,in addition to the CD symptoms,started to present thyroid impairment with positive anti-TPO.Only one of the patients required hospitalization for five days to treat COVID-19 and remained in CD clinical remission.Nine patients reported late symptoms that may be related to COVID-19.There were no deaths,and a statistical evaluation of the series of COVID-19 patients compared to those who did not present any infectious episode did not identify significant differences regarding the analyzed parameters.CONCLUSION Despite the change in CD status in three patients and the presence of nine patients with late symptoms,we can conclude that there was no significant adverse impact concerning COVID-19 in the evaluated patients who underwent HSCT to treat CD.

Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities

As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and posttransplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.

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

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 associated with SP in patients with hematological disorders. Further research is needed to explore the underlying mechanisms and potential therapeutic targets.

Ocular manifestations and quality of life in patients after hematopoietic stem cell transplantation

AIM:To explore the relationship between ocular and systemic conditions and the impact of ocular complications on the quality of life(QOL)in patients after allogeneic hematopoietic stem cell transplantation(ALLO-HSCT).METHODS:Forty-four patients with severe hematopoietic disease were enrolled after ALLO-HSCT at our center from July 2018 to October 2020.They completed two questionnaires:the Ocular Surface Disease Index(OSDI)and the quality-of-life scale for Chinese patients with visual impairment(SQOL-DV1).Ocular conditions and systemic conditions were also assessed.RESULTS:Eye damage was correlated with total bilirubin(P=0.005),and gamma-glutamyl transferase(GGT)(P=0.021).There was no significant correlation between the overall QOL score and OSDI(P=0.8226)or SQOLDV1(P=0.9526)scores.The OSDI and the overall QOL score were not correlated with ocular conditions,including best-corrected visual acuity(BCVA),intraocular pressure,Schirmer tear test II,sodium fluorescein staining,tear film breakup time,and tear meniscus height.SQOLDV1 was correlated with BCVA(P=0.0007),sodium fluorescein staining(P=0.007),and tear film breakup time(P=0.0146).CONCLUSION:In some patients,early ocular symptoms are not evident after ALLO-HSCT,while ocular surface complications can be observed after a comprehensive ophthalmological examination.Especially for those with elevated total bilirubin or GGT,regular ophthalmic follow-up visits are essential to diagnose and treat ocular graft versus host disease(o GVHD),especially for patients with elevated total bilirubin or GGT.

Hemophagocytic lymphohistiocytosis after autologous stem cell transplantation in angioimmunoblastic T-cell lymphoma:A case report

BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL), a unique subtype of peripheral Tcell lymphoma, has relatively poor outcomes. High-dose chemotherapy with autologous stem cell transplantation(ASCT) can achieve complete remission and improve outcomes. Unfortunately, subsequent T-cell lymphoma-triggered hemophagocytic lymphohistiocytosis(HLH) has a worse prognosis than B-cell lymphoma-triggered HLH.CASE SUMMARY We here report a 50-year-old woman with AITL who achieved a favorable outcome after developing HLH 2 mo after receiving high-dose chemotherapy/ASCT. The patient was initially admitted to our hospital because of multiple enlarged lymph nodes. The final pathologic diagnosis, made on biopsy of a left axillary lymph node was AITL(Stage Ⅳ, Group A). Four cycles of the following chemotherapy regimen were administered: Cyclophosphamide 1.3 g, doxorubicin 86 mg, and vincristine 2 mg on day 1;prednisone 100 mg on days 1-5;and lenalidomide 25 mg on days 1-14. The interval between each cycle was 21 d. The patient received a conditioning regimen(busulfan, cyclophosphamide, and etoposide) followed by peripheral blood stem cell infusion. Unfortunately, she developed sustained fever and a low platelet count 17 d after ACST, leading to a diagnosis of HLH after ASCT. During treatment, she experienced thrombocytopenia and Pneumocystis carinii pneumonia. The patient was successfully treated with etoposide and glucocorticoids.CONCLUSION It is possible that development of HLH is related to immune reconstitution after ASCT.

Hematopoietic stem cell transplantation of aplastic anemia by relative with mutations and normal telomere length: A case report

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.

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

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 has a strong antileukemic effect,with generally favorable OS rates.Overcoming relapse as the first cause of transplant failure is the great clinical challenge.

Advantageous tactics with certain probiotics for the treatment of graft-versus-host-disease after hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation(HSCT)becomes a standard form of cellular therapy for patients with malignant diseases.HSCT is the first-choice of immunotherapy,although HSCT can be associated with many complications such as graft-versus-host disease(GVHD)which is a major cause of morbidity and mortality after allogeneic HSCT.It has been shown that certain gut microbiota could exert protective and/or regenerative immunomodulatory effects by the production of short-chain fatty acids(SCFAs)such as butyrate in the experimental models of GVHD after allogeneic HSCT.Loss of gut commensal bacteria which can produce SCFAs may worsen dysbiosis,increasing the risk of GVHD.Expression of G-protein coupled receptors such as GPR41 seems to be upre-gulated in the presence of commensal bacteria,which might be associated with the biology of regulatory T cells(Tregs).Treg cells are a suppressive subset of CD4 positive T lymphocytes implicated in the prevention of GVHD after allogeneic HSCT.Here,we discuss the current findings of the relationship between the modification of gut microbiota and the GVHD-related immunity,which suggested that tactics with certain probiotics for the beneficial symbiosis in gut-immune axis might lead to the elevation of safety in the allogeneic HSCT.

TSR:A User-friendly R Shiny Application for Assessment of Optimal Blood Product Selection in ABO-incompatible Hematopoietic Stem Cell Transplantation

Objective:Patients undergoing hematopoietic stem cell transplant(HSCT)need frequent transfusions,until their red blood cells(RBCs)and platelets start to recover.The safe transfusion for patients who receive ABO-incompatible HSCT is essential to the transplant process.To date,there is no user-friendly tool to choose the right blood product for transfusion treatment,despite the number of guidelines and expert advice on the subject.Methods:R/shiny is a powerful programming language for clinical data analysis and visualization.It can create interactive web applications that work in real-time.The web application named TSR was built using R programming,simplifying blood transfusion practice for ABO-incompatible HSCT witha one-click solution.Results:The TSR is divided into four main tabs.The home tab provides an overview of the application,while RBC,plasma and platelet transfusion tabs offer tailored suggestions for blood product selection in each category.Unlike traditional methods that rely on treatment guidelines and specialist consensus,TSR leverages the power of the R/Shiny interface to extract critical content based on user-specified parameters,providing an innovative approach to improve transfusion support.Conclusion:The present study highlights that the TSR enables real-time analysis,and promotes transfusion practice byoffering a unique and efficient one-key output for blood product selection to ABO-incompatible HSCT.TSR has the potential to become a widely-utilized tool for transfusion services,providing a reliable and user-friendly solution that enhances transfusion safety in clinical practice.

Allogeneic hematopoietic stem cell transplantation in a 3-year-old boy with congenital pyruvate kinase deficiency: A case report

BACKGROUND The understanding regarding genetic variation,pathophysiology,and complications associated with pyruvate kinase deficiency(PKD)in red blood cells has been explained largely,and supportive treatment is currently the main management strategy.Etiotropic managements,including transplantation and genome editing,supplying for substitute dugs of the pyruvate kinase,are all under research.CASE SUMMARY We herein report a 3-year-old boy with severe transfusion-dependent PKD cured by unrelated identical peripheral blood stem cell transplantation(PBSCT).Hemoglobin was corrected to a normal level by gene correction after PBSCT,with no complication related to the transplantation.CONCLUSION Hematopoietic stem cell transplantation could be a substitute for transfusiondependent PKD.

NRS2002 assesses nutritional status of leukemia patients undergoing hematopoietic stem cell transplantation

Objective： To discuss whether nutritional risk screening 2002 （NRS2002） is appropriate for nutritional risk screening for leukemia patients before and after hematopoietic stem cell transplantation （HSCT）, and whether there are risk differences in other conditions, such as age, gender and matching degree; to find the methods and indicators of nutritional risk screening for these patients before and after HSCT, in order to give timely intervention to guarantee the successful completion of the entire transplantation process. Methods： Nutritional risk of 99 leukemia patients was screened with NRS2002 before and after HSCT. The ^（2 test was applied to compare the risk differences between groups such as age, gender and matching degree, while the differences of other enumeration data, such as recent （1-3 months） weight loss, reduced food intake within one week and BMI, were compared by continuity correction. Results： Of the 99 leukemia patients, 22 cases （22.2 %） had nutritional risk before HSCT, while all patients had nutritional risk after ttSCT; there is no significant difference in nutritional risk between male and female, and patients of less than 30 years old, not-full matched, recent （1-3 months） weight loss, reduced food intake within a week or BMI 〈18.5 were more likely to have nutritional risk; and 77 cases （77.8%） had weight loss, among which 49 patients （63.6%） had more than 5% weight loss within one month. Conclusions= This study showed that leukemia patients should receive the nutritional risk screening conventionally before and after HSCT, and NRS2002 was only appropriate for nutritional risk screening before HSCT. More attention should be paid to the patients less than 30 years old or not-full matched. Weight change was one of the important nutritional indicators for patients after HSCT.

Comprehensive evaluation of nutritional status before and after hematopoietic stem cell transplantation in 170 patients with hematological diseases

Objective： To investigate the nutritional status of patients before and after hematopoietic stem cell transplantation（HSCT）, and explore optimal methods for assessing nutritional status in patients with hematological diseases.Methods： This cohort study enrolled 170 patients who were diagnosed with hematological diseases and underwent allogeneic HSCT in the Department of Hematology, Peking University People＇s Hospital between May2011 and April 2013. We used fixed-point continuous sampling and four nutritional screening tools, Nutritional Risk Screening 2002（NRS-2002）, Mini Nutritional Assessment（MNA）, Subjective Global Assessment（SGA） and Malnutrition Universal Screening Tools（MUST）, in combination with body measurements, to extensively screen and evaluate nutritional risks and status in patients receiving HSCT before entering and after leaving laminar air flow rooms.Results： After HSCT, patients had significant reduction in weight, hip circumference, waist-hip ratio, calf circumference, mid-upper arm circumference, and suprailiac skinfold thickness compared with pre-HSCT measurements. Before HSCT, NRS-2002 identified that 21.2% of patients were at nutritional risks, compared with100% after HSCT. MUST indicated that before HSCT, 11.77% of patients were at high nutritional risk,compared with 59.63% after HSCT. MNA assessed that 0.06% of patients were malnourished before HSCT,compared with 19.27% after HSCT. SGA identified that before HSCT, 1.76% of patients had mild to severe malnutrition, which increased to 83.3% after HSCT. There is a significant increase in the nutritional risk and malnutrition in patients who received HSCT.Conclusions： Before HSCT, some patients already had nutritional risk or nutritional deficiencies, and prompt and close nutritional screening or assessment should be performed. The nutritional status of patients after HSCT was generally deteriorated compared with that before transplantation. Body measurements should be taken more frequently during the subsequent treatment window in the laminar air flow rooms. After HSCT, it is recommended to combine MNA and SGA to fully evaluate the nutritional status, and thus provide timely and reasonable nutritional support.

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

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： Intraportal injection was superior to other pathways for MSC transplantation. Intraportal MSC trans- plantation could improve liver function, inhibit apoptosis and prolong the survival time of swine with ALE The transplanted MSCs may participate in liver regeneration via promoting cell proliferation and suppressing apoptosis during the initial stage of ALE

Autologous hematopoietic stem cell transplantation in chemotherapy-sensitive lymphoblastic lymphoma: treatment outcome and prognostic factor analysis

Objective： The study evaluated the effectiveness of autologous hematopoietic stem cell transplantation （AHSCT） in the treatment of lymphoblastic lymphoma （LL）. Methods： We relxospectively analyzed the data from 41 patients with chemotherapy-sensitive LL who underwent hematopoietic stem cell transplantation （HSCT） from December 1989 to December 2009 in a single institution. Results： HSCT was conducted as first-line consolidation therapy and salvage therapy in 36 and 5 patients, respectively. The median follow-up was 97.1 months （range, 24.6-173.1 months）. The 5-year overall survival （OS） and event-free survival （EFS） rate were 64% and 47% for the initially treated patients, respectively, and were both 20% for the relapsed ones. Bone marrow （BM） involvement and chemotherapy cycles prior to transplantation were identified as significant prognostic factors for EFS in multivariate analysis. Conclusions These results confirm that AHSCT is a reasonable option for chemotherapy-sensitive LL patients in first complete remission （CR1）.

Combined acupuncture and HuangDiSan treatment affects behavior and synaptophysin levels in the hippocampus of senescence-accelerated mouse prone 8 after neural stem cell transplantation

Sanjiao acupuncture and HuangDiSan can promote the proliferation, migration and differentiation of exogenous neural stem cells in senescence-accelerated mouse prone 8 （SAMP8） mice and can improve learning and memory impairment and behavioral function in dementia-model mice. Thus, we sought to determine whether Sanjiao acupuncture and HuangDiSan can elevate the effect of neural stem cell transplantation in Alzheimer’s disease model mice. Sanjiao acupuncture was used to stimulate Danzhong （CV17）, Zhongwan （CV12）,Qihai （CV6）, bilateral Xuehai （SP10） and bilateral Zusanli （ST36） 15 days before and after implantation of neural stem cells （5 × 10^5） into the hippocampal dentate gyrus of SAMP8 mice. Simultaneously, 0.2 mL HuangDiSan, containing Rehmannia Root and Chinese Angelica,was intragastrically administered. Our results demonstrated that compared with mice undergoing neural stem cell transplantation alone,learning ability was significantly improved and synaptophysin mRNA and protein levels were greatly increased in the hippocampus of mice undergoing both Sanjiao acupuncture and intragastric administration of HuangDiSan. We conclude that the combination of Sanjiao acupuncture and HuangDiSan can effectively improve dementia symptoms in mice, and the mechanism of this action might be related to the regulation of synaptophysin expression.

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

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.

Decitabine for Relapsed Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

Relapse after allogeneic hematopoietic stem cell transplantation（allo-HSCT） remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic infusion and second transplantation. Our study assessed the efficacy of decitabine（DAC） for treating patients with acute lymphoblastic leukemia（ALL） who relapsed after allogeneic hematopoietic stem cell transplantation（allo-HSCT）. We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy. Nine patients received DAC combined with chemotherapy and donor stem cell infusion, and 3 patients received single-agent DAC. Ten of the 12 patients achieved complete remission（CR）, 1 achieved a partial remission（PR）, and 1 had no response（NR） after treatment at the latest follow-up（LFU）, the median survival was 11.2 months（range, 3.8–34, 7 months）. The 1-and 2-year overall survival（OS） rates were 50%（6/12） and 25%（3/12）, respectively. Five patients were still alive; 4 had maintained CR and 1 was alive with disease. Patients with Philadelphia chromosome-positive ALL had higher survival rate than patients with Philadelphia chromosome-negative ALL（57.1% vs. 20%）. No aggravated flares of graft-versus-host disease（GVHD） were observed during DAC treatment. Therefore, DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.

Clinical Observation of Patients with Hematologic Malignancies Treated with Hematopoietic Stem Cell Transplantation

To evaluate the therapeutic effect of hematopoietic stem cell transplantation (HSCT), we performed HSCT in 30 patients with hematologic maligancies. Of the 30 patients, 10 underwent autologous peripheral blood stem cell transplantation (auto-PBSCT), 13 underwent myeloablative allogeneic HSCT while 7 underwent nonmyeloablative allogeneic HSCT, which were designated as autologous group, myeloablative group and nonmyeloablative group, respectively. All patients except the one who underwent cord blood transplantation, were successfully engrafted. Median time for the granulocytes≥0.5×10\+9/L and platelets≥20×10\+9/L were 12 days and 13 days respectively in autologous group, 16 days and 19 days in myeloablative group, 15 days and 12 days in nonmyeloablative group. In myeloablative group, acute graft-versus-host diseases (aGVHD) was observed in 3 patients, all of which were I—Ⅱgrade. Oral mucous cGVHD was observed in 1 patient. In nonmyeloablative group, 1 patient developed intestinal aGVHD grade Ⅳ and cutaneous cGVHD was induced by donor lymphocyte infusions (DLI) in 3 patients. 1 patient had hematological relapse in autologous group. 1 patient had cytogenetic relapse in myeloablative group. In nonmyeloablative group 3 patients had cytogenetic relapse and were cured by DLI, 1 patient had hematological relapse. 4 of the 30 patients died of infection (2 patients), grade Ⅳ aGVHD (1) and relapse (1) respectively. 26 patients are still alive. 3 years overall survival (OS) and 3 years disease free survival (DFS) were 100 % and 64.81 % respectively in autologous group, 78.75 % and 63 % respectively in myeloablative group while both 66.67 % in nonmyeloablative group. In conclusion, autologous group had less transplant-related complications and mortality. Active prophylaxis of relapse could significantly promote DFS. The transplant-related mortality limited DFS in myeloablative group. More relapses occurred in nonmyeloablative group, but could be cured by DLI.

Umbilical Cord Blood-derived Mesenchymal Stem Cells Ameliorate Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation through Multiple Immunoregulations

Summary： Although mesenchymal stem cells （MSCs） are increasingly used to treat graft-versus-host disease （GVHD）, their immune regulatory mechanism in the process is elusive. The present study aimed to investigate the curative effect of third-party umbilical cord blood-derived human MSCs （UCB-hMSCs） on GVHD patients after allogeneic hematopoietic stem cell transplantation （allo-HSCT） and their immune regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were treated with UCB-hMSCs. Immune cells including T lymphocyte subsets, NK ceils, Treg cells and dendritic cells （DCs） and cytokines including interleukin-17 （IL-17） and tumor necrosis factor-alpha （TNF-α） were monitored before and after MSCs transfusion. The results showed that the symptoms of GVHD were alleviated significantly without increased relapse of primary disease and transplant-related complications after MSCs transfusion. The number of CD3^＋, CD3＋CD4^＋ and CD3＋CD8^＋ cells decreased significantly, and that of NK cells remained unchanged, whereas the number of CD4^＋ and CD8^＋ Tregs increased and reached a peak at 4 weeks; the number of mature DCs, and the levels of TNF-α and IL-17 decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate GVHD and spare GVL effect via immunoregulations.