Advances in the treatment of autism spectrum disorder:Wharton jelly mesenchymal stem cell transplantation

BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.There are studies suggesting that stem cell therapy may be effective in the treatment of ASD.AIM To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell transplantation.METHODS A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with neurorehabilitation.RESULTS The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor skills.No serious side effects were encountered during the 2-year follow-up.CONCLUSION The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.

Quality-adjusted time without symptoms or toxicity analysis of haploidentical-related donor vs.identical sibling donor hematopoietic stem cell transplantation in acute myeloid leukemia

Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematopoietic stem cell transplantation(HSCT).Methods:Five clinical health states were defined:toxicity(TOX),acute graft-versus-host disease(GVHD),chronic GVHD(cGVHD),time without symptoms and toxicity(TWiST)and relapse(REL).The equation used in this study was as follows:Q-TWiST=UTOX×TOX+UTWiST×TWiST+UREL×REL+UaGVHD×aGVHD+UcGVHD×cGVHD.Results:A total of 239 AML patients were enrolled.We established a mathematical model,i.e.,Q-TWiST HID HSCT>Q-TWiST ISD HSCT,to explore the range of utility coefficients satisfying the inequality.Based on the raw data,the utility coefficient is equivalent to the following inequality:10.57067UTOX-46.27733UREL+105.9374+3.388078UaGVHD-210.8198UcGVHD>0.The model showed that when UTOX,UREL,and UaGVHD were within the range of 0-1,as well as when UcGVHD was within the range of 0-0.569,the inequality Q-TWiST HID HSCT>Q-TWiST ISD HSCT was valid.According to the results of the ChiCTR1800016972 study,the median coefficients of TOX,acute GVHD(aGVHD),and cGVHD were 0.56(0.41-0.76),0.56(0.47-0.72),and 0.54(0.37-0.79),respectively.We selected a series of specific examples of the coefficients,i.e.,UTOX=0.5,UREL=0.05,UaGVHD-0.5,and UcGVHD-0.5.The Q-TWiST values of ISD and HID HSCT were 896 and 900 d,respectively(P=0.470).Conclusions:We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT.

Stem cell transplantation in cerebrovascular accidents:A global bibliometric analysis(2000-2023)

BACKGROUND Cerebrovascular accident(CVA)is a major global contributor to death and disability.As part of its medical management,researchers have recognized the importance of promising neuroprotective strategies,where stem cell transplantation(SCT)is thought to confer advantages via trophic and neuroprotective effects.AIM To evaluate the current state of research on SCT in patients with CVA,assess key trends and highlight literature gaps.METHODS PubMed was screened for SCT in CVA-related articles in October 2023,for each country during the period between 2000 and 2023.Using the World Bank data,total population and gross domestic product were collected for comparison.VOSviewer_1.6.19 was used to create the VOS figure using the results of the same query.Graphs and tables were obtained using Microsoft Office Excel.RESULTS A total of 6923 studies were identified on SCT in CVA,making 0.03%of all published studies worldwide.Approximately,68%were conducted in high-income countries,with a significant focus on mesenchymal stem cells.The journal“Stroke”featured the largest share of these articles,with mesenchymal SCT having the highest rate of inclusion,followed by hematopoietic SCT.Over time,there has been a noticeable shift from in vitro studies,which assess stem cell proliferation and neurogenesis,to in vivo studies aimed at evaluating efficacy and safety.Additionally,the number of reviews increased along this approach.CONCLUSION This bibliometric analysis provides a comprehensive guide for physicians and researchers in the field through an objective overview of research activity,and highlights both current trends and gaps.Having a potential therapeutic role in CVA,more research is needed in the future to focus on different aspects of SCT,aiming to reach a better treatment strategy and improve life quality in patients.

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.

The Impact of Blood Transfusion on the Efficiency of Stem Cell Transplants

Background: While blood product transfusion is essential for managing hematologic deficits in Allogenic Hematopoietic stem cell transplant (AHSCT) recipients, it has risks including infectious disease transmission, alloimmunization, and transfusion reactions. These risks have sparked an ongoing debate regarding the overall impact of transfusions on patient outcomes. Thus, this study aimed to evaluate the impact of Red Blood Cells (RBCs) and/or platelet transfusion on the infection incidence and overall survival in AHSCT patients. Methods: We performed a retrospective analysis of clinical and laboratory data of sixty adult patients with primary malignant hematological disorder who had undergone AHSCT. Participants’ data were categorized into two groups;Group 1 (low transfusion group) consisted of patients receiving 10 units. Quantitative data were expressed as mean ± SD. The t-test of significance and Chi-square (χ2) test were used, with p ≤ 0.05 considered significant. Result: A total of 60 patients’ data was included. In Group 1, out of 30 patients, 13 (43.33%) developed infections. In contrast, Group 2 had 21 (70%) out of 30 patients develop infections. Group 1 had a higher survival rate (57.8%) than Group 2 (transfusion > 10 units) (46.2%) with a chi-square value = 23.56, and p-value Conclusion: The volume of blood product transfusions has a considerable impact on patient outcomes, particularly infection and survival rates. Additional long-term prospective studies and larger randomized controlled trials are needed to strengthen the evidence for determining transfusion protocols for these patients.

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.

Development of Non-ABO Red Blood Cell Alloantibodies in Patient Undergoing Allogeneic Haematopoietic Stem Cell Transplant

Alloantibodies that are non ABO Alloimmunization to protein antigens happens only after exposure, in contrast to ABO isohaemagglutinins, which are present naturally, even in the absence of prior exposure. It is recognized that while non-ABO RBC antibodies are less common than ABO antibodies, they generate essentially the same issues that lead to unfavorable clinical results. If non-ABO alloantibodies are identified early on, these issues related complications may be avoided This call for an in-depth understanding of the recipient and donor’s ABO-Rh grouping, antibody screening, and the phenotype of certain antigens. Equally important, the temporal association time between transplantation and hemolysis can help identify the underlying mechanism of hemolysis and direct appropriate management. Therefore, for that, it is crucial to identify the etiology of post-HSCT anemia for prevention and therapy, in addition to a thorough grasp of the mechanism of anemia in non-ABO-incompatible HSCT and the temporal link between HSCT and anemia. Finding the cause of post-HSCT anemia is essential for prevention and therapy, in addition to a thorough grasp of the mechanism of anemia in non-ABO-incompatible HSCT and the temporal link between HSCT and anemia. Therefore, for that, it is crucial to identify the etiology of post-HSCT anemia. In this case report review, we would like to highlight the vital role of transfusion medicine services and stem cell clinical teams in paying particular attention to the clinical significance of non-ABO alloantibodies involved to avoid causing overt hemolysis of incompatible donor RBCs or delayed erythropoiesis. Considering the fact that some of the Haematopoietic stem cell transplant centers do not give an attention to the other non-ABO RBC antigens.

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.

Assessing the yield and safety of endoscopy in acute graft-vs-host disease after hematopoietic stem cell transplant

BACKGROUND Acute gastrointestinal(GI)graft-vs-host disease(aGVHD)is the most complication of hematopoietic stem cell transplant(HSCT)in patients with hematologic malignancy.Limited data exists on endoscopic evaluation of GVHD in post-HSCT patients with differing GI symptoms.Further,the diagnostic value of gross endoscopic findings as well as the safety of endoscopy in this commonly thrombocytopenic and neutropenic patient population remains unclear.AIM To understand the diagnostic value of symptoms and gross endoscopic findings as well as safety of endoscopy in aGVHD patients.METHODS We analyzed 195 endoscopies performed at City of Hope in patients who underwent allogeneic HSCT less than 100 d prior for hematologic malignancy and were subsequently evaluated for aGVHD via endoscopy.The yield,sensitivity,and specificity of diagnosing aGVHD were calculated for upper and lower endoscopy,various GI tract locations,and presenting symptoms.RESULTS Combined esophagogastroduodenoscopy(EGD)and flexible sigmoidoscopy(FS)demonstrated a greater diagnostic yield for aGVHD(83.1%)compared to EGD(66.7%)or FS(77.2%)alone with any presenting symptom.The upper and lower GI tract demonstrated similar yields regardless of whether patients presented with diarrhea(95.7%vs 99.1%)or nausea/vomiting(97.5%vs 96.8%).Normalappearing mucosa was generally as specific(91.3%)as abnormal mucosa(58.7%-97.8%)for the presence of aGVHD.Adverse events such as bleeding(1.0%),infection(1.0%),and perforation(0.5%)only occurred in a small proportion of patients,with no significant differences in those with underlying thrombocytopenia(P=1.000)and neutropenia(P=0.425).CONCLUSION Combined EGD and FS with biopsies of normal and inflamed mucosa demonstrated the greatest diagnostic yield regardless of presenting symptom and appears to be safe in this population of patients.

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

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.

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）.

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.

Cognitive improvement following transvenous adipose-derived mesenchymal stem cell transplantation in a rat model of traumatic brain injury

The effects of adipose-derived mesenchymal stem cell (ADMSC) transplantation for the repair of traumatic brain injury remain poorly understood. The present study observed neurological functional changes in a rat model of traumatic brain injury following ADMSC transplantation via the tail vein. Cell transplants were observed in injured cerebral cortex, and expression of brain-derived nerve growth factor was significantly increased in the injured hippocampus following transplantation. Results demonstrated that transvenous ADMSC transplants migrated to the injured cerebral cortex and significantly improved cognitive function.

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.

Determining the optimal time for bortezomib-based induction chemotherapy followed by autologous hematopoietic stem cell transplant in the treatment of multiple myeloma

In our study, we determined the efficacy of bortezomib-based induction therapy followed by autologous stem cell transplant （ASCT） in newly diagnosed and relapsed/refractory （R/R） multiple myeloma （MM） patients and compared the advantages of early versus late transplant. We used a retrospective analysis to examine 62 patients, including 46 cases of newly diagnosed MM （early transplant group） and 16 cases of relapsed/refractory MM （late transplant group）. All of these patients received bortezomib-based induction therapy followed by ASCT. The efficacy and side effects of the treatment regimen were analyzed. Patients＇ overall survival （OS） and progression-free survival （PFS） times were determined. The ratio of complete remission to near-complete remission （CR/nCR） was 69.5% versus 56.2% （P=0.361）, respectively, for the early transplant group versus the late transplant group, respectively, after receiving bortezomib-based induction therapy; the overall response rates of the two group were 91.3 % and 81.2 %, respectively （P=0.369）. After receiving ASCT, the CR/nCR of the two groups increased to 84.8% and 81.3%, respectively. The median time required for neutrophil engraftment of the early transplant group and the late transplant group was 11 and 14.5 days, respectively （P=0.003）; the median time required for platelet engra^nent was 13 and 21.5 days （P=0.031）, respectively. There were no significant differences in the toxic side effects observed during induction therapy and ASCT between the two groups. The OS of the two groups was not statistically different （P=0.058）. The PFS of the early transplant group and the late transplant group was 41.6 and 26.5 months, respectively （P=0.008）. Multivariate analysis demonstrated that the time of receiving ASCT, the types of M protein, and the International Staging System （ISS） stage were all independent factors that influenced PFS. In conclusion, patients in a suitable condition for ASCT should be recommended to have an early ASCT immediately after diagnosis.