Stem Cell Transplantation For Treatment Research Articles

Racial and Socioeconomic Disparities in the Utilization of Autologous Stem Cell Transplant for Treatment of Multiple Myeloma in the Era of Novel Agents

INTRODUCTION: The prognosis of multiple myeloma (MM) has improved drastically in the last 20 years with the advent of novel agents, specifically with the introduction of bortezomib in late 2003. Novel agents in combination with autologous stem cell transplant (ASCT), have led to the achievement of high response rates in many patients. ASCT is now considered standard of care for all eligible patients, and previous studies have found increasing rates of ASCT in all age groups since the introduction of novel agents. Studies have also revealed disparities with decreased ASCT utilization in racial and socioeconomic minorities. This study utilizes the National Cancer Database (NCDB) to determine how the use of ASCT has changed for MM in the bortezomib era. METHODS:The NCDB was used to identify 157,443 patients diagnosed between 2004-2016 with Multiple Myeloma. Only patients with information on ASCT were included, and demographic characteristics between those patients that received and did not receive ASCT were compared. Race, insurance type, facility type, average income, education, and Charleson-Deyo comorbidity score, among other factors, were included in this analysis (Table 1). To determine the trends in ASCT over the era of novel agents, the proportion of patients receiving ASCT within these groups was trended over each year, and linear models to determine the rate of change in each group was compared. Bivariate and Multivariate regression analysis for each characteristic was used to determines odds ratios (OR) for receiving ASCT by demographic factors. RESULTS: Between 2004 to 2016 the proportion of all patients receiving ASCT as part of initial therapy more than doubled from 10.1% to 22.0%; increasing by approximately 1.06% per year on a linear regression model (R20.98) (Table 2). The greatest proportional increases were seen in Blacks, Hispanics, patients over 65 years of age, patients with higher comorbidity scores, Medicare, and patients treated at community centers. On multivariate analysis the patients that were most likely to receive ASCT (p<0.05) had private insurance (OR 5.4), were treated at academic centers (OR 7.3) and were highly educated (OR 1.7) (Table 3). For each increased year of diagnosis patients were significantly more likely (OR 1.1) to receive ASCT. Patients with a decreased chance of receiving transplant (p<0.05) were black (OR 0.6) or other non-white race (OR 0.7), Hispanic (OR 0.8), or had increased comorbidities (OR 0.4 for Charleson-Deyo score of 3 or greater). For every year of increased age, the likelihood of ASCT decreased (OR 0.92) (Table 3). DISCUSSION: In the era of novel agents, the rate of ASCT has rapidly increased each year, with the greatest increases seen in elderly patients, those with higher comorbidity indexes, and in patients who are racially and socioeconomically disadvantaged. However, significant racial and socioeconomic disparities still exist in the treatment of MM, and must be considered as treatment continues to advance. Disclosures No relevant conflicts of interest to declare.

Logistical Considerations Related to Melphalan As a Conditioning Agent in Autologous Stem Cell Transplant for Multiple Myeloma: Results of a Survey of Oncology Pharmacists, Nurses and Pharmacy Technicians

Introduction: Melphalan is often part of the standard conditioning regimen for autologous stem cell transplantation (SCT) for multiple myeloma (MM). Due to the short stability time for IV admixtures of traditional propylene glycol-containing melphalan products, careful alignment is required between pharmacy, nursing, and patients to ensure timely dose delivery. Propylene glycol-free (PGF) melphalan (Evomela®) has improved stability that may allow for greater medical staff flexibility for scheduling, reconstitution, admixture delivery, and infusion to patients. The aim of this study was to document the steps, time and resource burden incurred when preparing generic propylene glycol containing melphalan and estimate the benefits of stable PGF melphalan. Methods : A survey was conducted with healthcare providers (HCPs) specializing in the care and management of MM patients. HCPs (5 oncology pharmacists, 5 oncology nurses, 5 oncology pharmacy technicians) included those involved in the preparation, administration and monitoring of melphalan when used as a conditioning agent for SCT. HCPs were selected based on a purposeful sampling design to capture a geographically representative sample among US SCT centers. Part 1 of survey consisted of an exploratory qualitative interview with each HCP to capture insights on preparing oncology treatments for administration as well as melphalan-specific insights related to preparation, administration and monitoring. Part 2 of the survey consisted of a quantitative evaluation based on the insights from part 1 of the survey. The quantitative portion focused on capturing facility characteristics as well as melphalan utilization patterns as well as timing and resource consumption related to the preparation, administration, and monitoring of generic melphalan. Additionally, HCPs provided their attitudes towards the potential time benefits of a more stable form of melphalan as it relates to alignment between the pharmacy and the nurses managing the patients during treatment with melphalan. Results are presented as descriptive statistics with mean and standard deviation for continuous variables and counts and percentages for categorical variables. Results: Sixty percent of those surveyed utilized generic melphalan. The steps involved in the preparation of melphalan (generic or PGF) included 1) verification of melphalan prescription, 2) preparation and release of melphalan admixture, 3) delivery of melphalan to the floor, 4) preparation of the patient for administering melphalan, 5) setup and verification of the melphalan pump and administration, and 6) patient monitoring during administration. The total time from start to finish averaged 75.3 (standard deviation: 46.7) minutes (min). The total time spent varied, but the cumulative total time spent incurred across all provider average times was 108.2 min (Table 1). On average, the time of 2.1 pharmacists, 0.9 technicians and 1.5 nurses were utilized in the preparation, administration and monitoring of a melphalan prescription (Table 1). Forty percent of those surveyed had changed from generic to PGF melphalan for the following reasons: convenience for a more stable product (61.5%); convenience for pharmacy preparation planning (46.2%); convenience for patient scheduling (38.5%); improved safety for staff rushing due to risk of precipitation (30.8%); and to reduce the risk of lost treatment due to precipitation (15.4%). HCPs also estimated the potential time benefits of PGF melphalan, which included reducing preparation time by a mean of 4.96 min for pharmacy and nurse alignment to initiate preparation, 3.77 min for pharmacy and nurse to align on pick up, 8.34 min due to nurse time waiting to pick up and 9.77 min for the pharmacy technician or runner to deliver directly to the floor. Conclusions: In this survey of healthcare providers involved in the preparation, administration and monitoring of melphalan as a conditioning treatment for SCT among MM patients, the total time spent was ~1.8 hours for preparing generic melphalan with a potential opportunity to reduce the time by ~0.45 hours when using a PGF melphalan. There may be a potential time and convenience benefit to oncology pharmacists, technician and nurses. Future comparative effectiveness research is needed to confirm these findings in a larger sample of SCT centers using melphalan as a conditioning regimen for SCT among MM patients. Disclosures Acosta: Acrotech Biopharma: Employment. Darban:BluePath Solutions: Consultancy. Gitlin:BluePath Solutions: Consultancy.

Essential Role of Chinese Medicines in Mesenchymal Stem Cells Transplantation for Treatment of Ischemic Stroke.

Ischemic stroke accounts for the majority of all strokes and has been primary causes of long-term disability and mortality in worldwide. Mesenchymal stem cell (MSC) therapy suggests significantly improved effects on neurological functional outcome, neurogenesis, angiogenesis, blood-brain barrier permeability, inflammatory injury, neuroprotection and so on, following stroke. However, the occurrence of adverse effects results in restriction of the therapy. Chinese medicine accumulates abundant clinical experiences on stroke for over two thousand years, and some formulae and active ingredients of Chinese medicines have presented obvious efficacies in clinical treatment. Therefore, based on Chinese medicine theory, we provide some ideas of screening agents for combination treatment of Chinese medicines and MSC for ischemic stroke, and summarize the potentials of Chinese medicines in MSC treatment and analyze the feasibilities of Chinese medicines against side effects of MSC therapy. Consequently, we propose Chinese medicines combing with MSC should be a promising approach to clinical stroke treatment in future.

Advances in allogeneic hematopoietic stem cell transplantation in treatment of acquired severe aplastic anemia

Acquired severe aplastic anemia (SAA) is a life-threatening bone marrow failure syndrome. Immunosuppressive therapy (IST) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) are the main treatments for acquired SAA. Matched sibling donor (MSD)-hematopoietic stem cell transplantation (HSCT) is the best treatment for acquired SAA patients who are younger than 40 years old. Outcomes of unrelated donor (URD)-HSCT, haploidentical hematopoietic stem cell transplantation (haplo-HSCT) and umbilical cord blood transplantation (UCBT) have improved in the recent decade, and provide more options with respect to the clinical treatment of acquired SAA. In order to improve clinicians′ understanding of allo-HSCT for acquired SAA, this article reviews the research progress of acquired SAA treated by allo-HSCT in recent years. Key words: Anemia, aplastic; Hematopoietic stem cell transplantation; Donor selection; Transplantation conditioning; Graft vs host disease; Transplantation, haploidentical; Cord blood stem cell transplantation

Advances and current status of stem cell transplantation in treatment of hematological malignancies in China

Since the founding of the People's Republic of China, much progress has been made in the field of stem cell transplantation by Chinese scholars. From the successful treatment of the first case with syngeneic bone marrow transplantation to the international original establishment of T-cell-replete haploidentical blood and marrow transplant system(known as the Beijing Protocol). The transformation of hematopoietic stem cell transplantation from follow-up to lead-up has been realized, and the problem of donor source has been basically solved. This article summarized the development status of stem cell transplantation in treatment of hematological malignancies in China, and the challenges that need to be addressed. Key words: Hematological neoplasms; Allogeneic stem cell transplantation; Haploidentical allograft

Efficacy and influencing factors of allogeneic hematopoietic stem cell transplantation in treatment of 71 children with leukemia.

Efficacy and influencing factors of allogeneic hematopoietic stem cell transplantation in treatment of 71 children with leukemia.

Study on Umbilical Cord-Matrix Stem Cells Transplantation for Treatment of Acute Traumatic Brain Injury in Rats.

To evaluate the effect of umbilical cord derived mesenchymal stem cells (UC-MSCs) transplantation on traumatic brain injury (TBI). UC-MSCs were isolated from human umbilical cord and TBI rat model was constructed. 30 male SD rats were randomly divided into 3 groups: control group, TBI group and MSCs transplantation group. Rats in MSCs group received the injection of a total of 1.5 Ć- 106 MSCs (25 Ī¼l) via ventricle at operated ventricular coordinates (0 at bregma, 1.5 mm at lateral, 1.1 mm at behind, 4.5 mm in depth). 80% confluence of cells was formed from tissue at day 10 and the amount of CD90, CD73, CD105 positive cells increased correspondingly. In TBI model, clear hyperemia, edema and obvious infiltration of inflammatory cells in brain tissue were found. However, the manifestations were alleviated after the treatment of MSCs. In MSCs group, GFP in the brain tissue and the area around the vessels were found after the injection, while the expression levels of micro-vessel density (MVD), brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) were elevated. UC-MSCs transplantation for treatment of acute TBI could effectively reduce the injury and improve the vascular reconstruction.

Autologous Mesenchymal Stem Cell Transplant in Patients with Type 1 Diabetes Mellitus.

Our goal was to determine the efficacy of autologous mesenchymal stem cell transplant for treatment in patients with type 1 diabetes mellitus. We examined 5 patients (4 male, 1 female; age 20-42 y) with type 1 diabetes mellitus who received autologous mesenchymal stem cell transplant (cells were obtained from the patient's iliac crest and cultured for 3-4 weeks) performed by intravenous infusion. The quantity of autologous mesenchymal stem cells infused was 95 to 97 × 106. We analyzed daily insulin dosages and leptin and glycated hemoglobin levels in patients before and 1, 2, and 3 months after their autologous mesenchymal stem cell transplant procedure. In patients with type 1 diabetes mellitus, autologous mesenchymal stem cell transplant led to a decrease in daily insulin dosage levels, from 63 ± 8.83 to 50.2 ± 12.1 U (P = .064) after 1 month, with significantly increased leptin levels and trend to decreased glycated hemoglobin levels, from 6.86 to 10.77 ng/mL (P = .016) and 9.11% to 8.74% (P = .84) after 3 months, respectively. Daily insulin dosage level decreased within 1 month and leptin levels increased significantly within 3 months after autologous mesenchymal stem cell transplant in patients with type 1 diabetes mellitus.

Efficacy of Newer Combinations and Fibril-Targeting for AL Amyloidosis: A Systematic Review of Transplant and Innovative Non-Transplant Therapies

BackgroundLight-chain (AL) amyloidosis is a multi-organ amyloid deposition disease caused by misfolded protein aggregation. Current treatments have improved overall (OS) and progression-free survival (PFS) but challenges remain in improving therapy with newer agents and targeting amyloid protein deposits with novel immunotherapy. We review the literature regarding efficacy of existing chemotherapy in AL amyloidosis and summarize non-FDA approved novel drugs and monoclonal antibodies (mAbs) in early phase clinical development.MethodsWe searched databases including Cochrane library, PubMed and ClinicalTrials.gov for all prospective and retrospective studies (As of 4/15/2018) with measured hematologic response rate (HR) in patients with AL amyloidosis since 2000. Inclusion criteria included all prospective and retrospective studies with melphalan-based treatments, bortezomib combinations including bortezomib, cyclophosphamide and dexamethasone (VCD), bortezomib and dexamethasone (VD) and immunotherapies. We included all studies with at least 5 or more patients and reported HR.ResultsFrom 918 studies, we selected 57 studies (2640 patients) evaluating HR with melphalan-based stem cell transplant (SCT) treatments and non-stem cell transplant treatments including melphalan and bortezomib combinations. Other agents included daratumumab (anti-CD38 mAb), and ixazomib (proteasome inhibitor). Mean aggregate HR reported from studies with melphalan-based SCT treatment (17 studies, n=587) was 67%. Mean aggregate HR from all non-transplant treatments (40 studies, n=2053) was 64%. Of the non-transplant treatments, HR for melphalan-based treatments (21 studies, n=1148) was 59% and varied as follows: melphalan + lenalidomide + dexamethasone (57%) and melphalan + dexamethasone (52%). Mean aggregated HR for non-transplant bortezomib-based treatment (17 studies, n=859) was 72% consisting of VD (69%) and VCD (76%). HR with Ixazomib (1 study) and Daratumumab (1 study) was 52% and 76% respectively. Other novel drugs currently being studied include 11-1F4 (chimeric fibril-reactive mAb), GSK2398852 and GSK2315698 (anti-serum amyloid protein mAbs), and NEOD001 (anti-circulating soluble and deposited aggregated amyloid mAb).ConclusionFor AL amyloidosis, melphalan-based SCT has shown effectiveness while VD and VCD demonstrate effectiveness in non-transplant patients. Further studies are warranted to evaluate novel proteasome inhibitors (Ixazomib) and emerging immunotherapy with daratumumab. Current trials including amyloid protein and fibril targeting (circulating and tissue-fixed) with novel immunotherapy are innovative and may have higher clinical efficacy, but need further testing. DisclosuresNo relevant conflicts of interest to declare.

Comparison of efficacy of antithymocyte globulin/antilymphocyte globulin combined with cyclosporin A and allogeneic hematopoietic stem cell transplantation in treatment of patients with aplastic anemia

Objective To analyze efficacy and safety of antithymocyte globulin (ATG)/antilymphocyte globulin (ALG) combined with cyclosporine A and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of patients with aplastic anemia (AA). Methods From February 2014 to February 2017, a total of 68 AA patients who were admitted to Department of Hematology, Tangdu Hospital, Fourth Military Medical University were included in this study. According to different treatment strategies, they were divided into ATG/ALG combined with cyclosporin A group (n=27) and allo-HSCT group (n=41). Clinical data of patients in two groups were analyzed retrospectively, and efficacy and treatment-related adverse reactions of patients in two groups were compared. Age, neutrophil count (ANC), platelet count, reticulocytes absolute count, hemoglobin (Hb) value, and follow-up period of patients in two groups were analyzed by two-sample t test or Mann-Whitney U test. Ratio of patients with severe aplastic anemia (SAA), good hematologic response rate, hematologic response rate, treatment-related adverse reaction rate, early case fatality ratio, total case fatality ratio, ratio of patuients with recurrence or progression were analyzed by χ2 test or corrected χ2 test. Overall survival (OS) rates and progression free survival (PFS) rates of patients in two groups were analyzed by Kaplan-Meier method and Log-rank test. The procedure of this study is accordance with the requirement of the revised World Medical Association Declaration of Helsinki in 2013. Informed consent was obtained from all participants. Results ① Gender of male and female composition ratio was 0.7∶1 in ATG/ALG combined with cyclosporine A group, and was lower than that of 2.2∶1 in allo-HSCT group, and the difference was statistically significant (χ2=5.052, P=0.025). There were no significant differences in average age, average ANC, median platelet count, median reticulocytes absolute count, median Hb value, and ratio of patients with SAA between 2 groups (P>0.05). ② Good hematological response rate (58.5%, 24/41) and hematologic response rate (82.9%, 34/41) of patients in allo-HSCT group were higher than those in ATG/ALG combined with cyclosporine A group, which were 14.8% (4/27) and 51.9% (14/27), and the differences were statistically significant (χ2=12.850, P 0.05). ⑤ Median follow-up period was 9.0 months (5.0-19.0 months) in ATG/ALG combined with cyclosporin A group, and 12.0 months (7.0-22.5 months) in allo-HSCT group, and the differences were not statistically significant (P>0.05). Results of survival analysis showed that OS rates of patients in two groups were 96.3% and 86.3%, and PFS rates were 92.4% and 84.0%, and both differences were not statistically significant (P>0.05), respectively. Conclusions Clinical efficacy of ATG/ALG combined with cyclosporin A in the treatment of AA patients was not as good as allo-HSCT, but its safety was higher than that of allo-HSCT treatment strategy. Applying allo-HSCT for AA treatment, prevention and treatment of transplant-related adverse reactions should be highly addressed. Key words: Anemia, aplastic; Immunosuppression; Hematopoietic stem cell transplantation; Comparative effectiveness research; Retrospective studies

Efficacy and safety of autologous stem cell transplantation for decompensated liver cirrhosis: A retrospective cohort study.

AIMTo evaluate the long-term efficacy and safety of autologous stem cell transplantation (SCT) for decompensated liver cirrhosis.METHODSConsecutive patients with decompensated liver cirrhosis were included and assigned into the SCT group and non-transplantation (non-SCT) group according to whether they received SCT treatment. Patients were followed up for ten years. The long-term survival rate and incidence of hepatocellular carcinoma (HCC) were compared between groups.RESULTSA total of 159 patients were enrolled, including 27 cases in the SCT group and 132 cases in the non-SCT group. The baseline characteristics were significantly different between the two groups. Propensity score matching (PSM) was used to match SCT and non-SCT patients. After PSM, 92 subjects were enrolled in the final analysis, including 23 cases in the SCT group and 69 cases in the non-SCT group. The overall mortality was 73.9% and 55.1%, and the median survival period was 48 and 64 mo, respectively. However, no significant difference was found in the long-term survival rate between the two groups (P > 0.05). In addition, the incidence of HCC was higher in the SCT group than in the non-SCT group (47.8% vs 21.7%, P < 0.05). After adjusting for other covariates, SCT (OR = 3.065, 95%CI: 1.378-6.814) and age (OR = 1.061, 95%CI: 1.021-1.102) were independently correlated with the development of HCC in this decompensated liver cirrhosis cohort.CONCLUSIONAutologous SCT may fail to improve the long-term efficacy and increase the incidence of HCC for decompensated liver cirrhosis. Close monitoring of HCC is strongly recommended in patients undergoing autologous SCT.

Autologous Hematopoietic Stem Cell Transplantation for Treatment of Systemic Sclerosis.

Systemic Sclerosis (SSc) is a complex autoimmune disease, characterized by high mortality and morbidity. The heterogeneity in terms of extent, severity, and rate of progression of skin and internal organ involvement gives rise to many difficulties in finding the optimal therapeutic interventions for SSc and, to date, no disease-modifying agents are available. In this scenario, it is not surprising that SSc was one of the first autoimmune diseases challenged with high-dose immunosuppressive treatment followed by autologous hematopoietic stem cell transplantation (AHSCT). In the last decades, AHSCT has emerged as a treatment option for refractory SSc through a reduction of the aberrant immune cells, followed by re-constitution of a new, self-tolerant immune system. After several case series and pilot studies, more recently three randomized controlled trials have shown a benefit in skin involvement, organ functions and quality of life measures in AHSCT compared to monthly cyclophosphamide. In addition, although AHSCT presents a certain risk of mortality, it has been shown that the overall survival is better, compared to the cyclophosphamide group. Current evidence suggests that SSc patients who are most likely to benefit from AHSCT are early, active, with rapidly progressing diffuse skin disease, and mild involvement of internal organs. As the studies have progressed, it has become evident the need for a more rigorous patient selection, the optimization of transplant and post-transplant procedures, and the intervention of multidisciplinary teams of specialists to increase the safety and efficacy of AHSCT in SSc.

Allogeneic hematopoietic stem cell transplantation for treatment of mixed phenotype acute leukemia: report of two cases and review of literature

目的 探讨异基因造血干细胞移植（allo-HSCT）治疗混合表型急性白血病（MPAL）的效果及预后。 方法 报道郑州大学附属肿瘤医院收治的2例接受allo-HSCT治疗的MPAL患者，并对相关文献进行复习。 结果 2例患者给予髓淋二系方案诱导化疗后，1例获得完全缓解，1例未达完全缓解，再行allo-HSCT。随访至截稿前，2例患者均达完全缓解。 结论 MPAL的化疗方案多样，缓解率低，allo-HSCT可能是根治的唯一方法，能使患者生存受益。

Ascorbic acid inhibits senescence in mesenchymal stem cells through ROS and AKT/mTOR signaling.

Mesenchymal stem cell (MSC) aging seriously affects its function in stem cell transplantation for treatment. Extensive studies have focused on how to inhibit senescence in MSCs. However, the mechanism of senescence in MSC was not clear. In this study, we used D-galactose to induce MSC aging. Then we found that the number of aging cells was increased compared with untreated MSCs. We discovered that ascorbic acid could inhibit the production of reactive oxygen species (ROS) and activation of AKT/mTOR signaling in MSCs caused by D-galactose. Especially, when treated together with a ROS scavenger or AKT inhibitor, the senescent cells were obviously decreased in D-galactose-induced MSCs. Taken together, we identify that ascorbic acid owns the potential to inhibit the senescence of MSCs through ROS and Akt/mTOR signaling. Together, our data supports that ascorbic acid can be used to prevent MSCs from senescence, which can enhance the efficiency of stem cell transplantation in the clinic.

Autologous Haematopoietic Stem Cell Transplantation in Treatment Naïve Patients with Rapidly Evolving Severe Multiple Sclerosis (P6.350)

Autologous Haematopoietic Stem Cell Transplantation in Treatment Naïve Patients with Rapidly Evolving Severe Multiple Sclerosis (P6.350)

Peripheral blood haploidentical hematopoietic stem cell transplantation for treatment of acute lymphoblastic leukemia in adults: monitoring minimal residual diseases to intervene recurrence

Peripheral blood haploidentical hematopoietic stem cell transplantation for treatment of acute lymphoblastic leukemia in adults: monitoring minimal residual diseases to intervene recurrence

Stem Cells Transplantation in the Treatment of Patients with Liver Failure.

Liver failure is a life-threatening liver disease encompassing severe acute deterioration of liver function. Emergency liver transplantation is the only curative treatment for liver failure, but is restricted by the severe shortage of organ donors. Stem cell, including embroyonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells and hepatic progenitor cells, have capacity to proliferate and differentiate and could be used in a variety of liver diseases including hereditary liver diseases, cirrhosis and liver failure. We summarized the basic experimental and clinical advances of stem cell transplantation in liver failure treatment, and also discussed the advantages and disadvantage of different stem cells subtype in this field, aiming to provide a perspective on the stem cell-based therapy for liver failure. Stem cells, especially mesenchymal stem cells (mainly low immunogenicity and paracrine characteristics) and induced pluripotent stem cells (generation of desired cell type from somatic cell), are feasible candidates for cell therapy in the treatment of liver failure, but there are some drawbacks remaining to be resolved, such as low engraftment, cryotpreservation methods and tumorigenesis. Stem cell transplantation is a promising but challenging strategy and paves a new way for curing liver failure. But more efforts need to be made to overcome problems before this new strategy could be safely and effectively applied to humans.

Therapeutic effect of haploidentical hematopoietic stem cell transplantation for treatment of 59 children with hematological diseases

Objective To evaluate the safety and efficacy of haploidentical hematopoietic stem cell transplantation(haplo-HSCT) treatment in children with hematological diseases. Methods Fifty-nine cases of less than 14 years old children with hematonosis were analyzed retrospectively, who were enrolled in the Aerospace Central Hospital from July 2012 to June 2016.And the evaluation was carried out by analyzing the success rate of implantation, occu-rrence rate of graft versus host disease (GVHD), infection rate and transplant related mortality (TRM), cumulative recurrence rate, overall survival rate(OS) and disease-free survival rate(DFS). Results In total of 59 cases, the 59 engraftments were successfully transplanted, the median time of leukocyte engraftment was 18 (8-23) days, the median time of platelet engraftment was 21 (11-68) days, the bone marrow was assessed 28 days after transplantation, which showed that 59 patients achieved complete remission(CR) and DNA test confirmed complete donor chime-rism.With a median of follow-up time of 19 (5-56) months, the cumulative recurrence rates of Ⅰ, Ⅱ grade and Ⅲ, Ⅳ grade acute GVHD were (38.3±6.3)% (23 cases) and (16.7±4.8)% (10 cases), respectively, the chronic GVHD cumulative recurrence rate was (65.6±7.5)% (30 cases), the cytomegalovirus (CMV) viremia cumulative recurrence rate was (45.1±6.5)% (27 cases), the Epstein-Barr virus(EBV) viremia cumulative recurrence rate was (10.0±3.9)% (6 cases), the viral cystitis cumulative recurrence rate was (20.0±5.5)% (12 cases), the transplant related mortality was (12.8±6.0)%, the 2-year cumulative recurrence rate of CR group was (8.0±5.4)%, and that of non-remission(NR) group was (64.1±11.9)%.The 2-year OS of CR group was (78.9±7.5)%, the 2-year OS of NR group was (32.5±12.9)%, the 2-year DFS of CR group was (79.5±9.8)%, the 2 years DFS of NR group was (27.4±7.9)%. Conclusions Haplo-HSCT is safe and effective in treating children with hematonosis, and haplo-HSCT has high survival rate and low recurrent, especially when transplantation is performed in the remission stage.But the prognosis of haplo-HSCT is poor in the refractory and relapsed patients, and to explore the preventing recurrence measures are very urgent. Key words: Hematopoietic stem cell transplantation; Haploidentical; Child; Hematological disease; Disease-free survival rate

Effect of adipose tissue-derived mesenchymal stem cell transplantation in treatment of liver fibrosis and possible mechanism

Objective: To investigate the effect of adipose tissue-derived mesenchymal stem cell (ADSC) transplantation in the treatment of liver fibrosis rats and possible mechanism. Methods: Subcutaneous adipose tissue in the inguinal region of rats was collected to isolate ADSCs. The rats with liver fibrosis induced by intraperitoneally injected carbon tetrachloride were divided into cell transplantation group and phosphate buffer saline (PBS) injection group, and the rats which were fed normally were enrolled as negative control group. The rats in the cell transplantation group were given tail vein injection of ADSCs, and those in the PBS injection group were given injection of 0.5 ml PBS. At 7 days after transplantation, blood samples were collected from the inferior vena cava to evaluate liver function; liver tissue was collected to measure the protein expression of hepatocyte growth factor (HGF) and alpha-smooth muscle actin (α-SMA); Masson trichrome staining was used to evaluate intrahepatic collagen deposition. Hepatic stellate cells (HSCs) were collected from the rats with liver fibrosis, and indirect co-culture of HSCs and ADSCs was performed in vitro to analyze the influence of ADSCs on the proliferation and apoptosis of HSCs. The independent samples t-test was used for comparison between groups, and an analysis of variance was used for comparison of means between multiple samples. Results: ADSCs were found in liver tissue in the transplantation group, and compared with the PBS injection group, the transplantation group had significant alleviation in hepatocyte necrosis, vacuolization, and area of fibrosis and significant reductions in the serum levels of aminotransferases, while there was no significant difference in the level of albumin between the two groups. Compared with the PBS injection group, the transplantation group had significant upregulation in the protein expression of HGF and significant downregulation in the protein expression of α-SMA (both P < 0.05). In vitro co-culture for 72 hours showed that ADSCs inhibited the proliferation of HSCs, and there was a significant difference between the co-culture group and the control group with HSCs cultured alone. Caspase-3 immunostaining showed that after co-culture for 72 hours, there was a significant difference in the apoptosis rate of HSCs between the co-culture group and the control group with HSCs cultured alone (23.42% ± 3.02% vs 14.82% ± 3.93%). Conclusion: ADSC transplantation can upregulate the expression of HGF in the liver, promote the apoptosis of HSCs, and thus alleviate liver fibrosis.

Allogeneic peripheral blood stem cell transplantation for treatment of AA-PNH syndrome: a case report

Allogeneic peripheral blood stem cell transplantation for treatment of AA-PNH syndrome: a case report