Cell Transplantation Group Research Articles

Prognostic value of the FUT family in acute myeloid leukemia

Genetic abnormalities are more frequently viewed as prognostic markers in acute myeloid leukemia (AML) in recent years. Fucosylation, catalyzed by fucosyltransferases (FUTs), is a post-translational modification that widely exists in cancer cells. However, the expression and clinical implication of the FUT family (FUT1-11) in AML has not been investigated. From the Cancer Genome Atlas database, a total of 155 AML patients with complete clinical characteristics and FUT1-11 expression data were included in our study. In patients who received chemotherapy alone showed that high expression levels of FUT3, FUT6, and FUT7 had adverse effects on event-free survival (EFS) and overall survival (OS) (all P < 0.05), whereas high FUT4 expression had favorable effects on EFS and OS (all P < 0.01). However, in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) group, we only found a significant difference in EFS between the high and low FUT3 expression subgroups (P = 0.047), while other FUT members had no effect on survival. Multivariate analysis confirmed that high FUT4 expression was an independent favorable prognostic factor for both EFS (HR = 0.423, P = 0.001) and OS (HR = 0.398, P < 0.001), whereas high FUT6 expression was an independent risk factor for both EFS (HR = 1.871, P = 0.017) and OS (HR = 1.729, P = 0.028) in patients who received chemotherapy alone. Moreover, we found that patients with low FUT4 and high FUT6 expressions had the shortest EFS and OS (P < 0.05). Our study suggests that high expressions of FUT3/6/7 predict poor prognosis, high FUT4 expression indicates good prognosis in AML; FUT6 and FUT4 have the best prognosticating profile among them, but their effects could be neutralized by allo-HSCT.

Therapeutic effects of combined cell transplantation and locomotor training in rats with brain injury

Cell-based therapies are attracting attention as alternative therapeutic options for brain damage. In this study, we investigated the therapeutic effect of a combined therapy of cell transplantation and locomotor training by evaluating the neuronal connectivity. We transplanted neural cells derived from the frontal cortex of E14.5 GFP-expressing mice into the frontal lobe of 3-week-old rats with brain injury, followed by treadmill training (TMT) for 14 days. In the TMT(−) group, graft-derived neurites were observed only in the striatum and internal capsule. In contrast, in the TMT(+) group, they were observed in the striatum, internal capsule, and the cerebral peduncle and spinal cord. The length of the longest neurite was significantly longer in the TMT(+) group than in the TMT(−) group. In the TMT(+) group, Synaptophysin+ vesicles on the neuronal fibers around the ipsilateral red nucleus were found, suggesting that neuronal fibers from the grafted cells formed synapses with the host neurons. A functional analysis of motor recovery using the foot fault test showed that, 1 week after the transplantation, the recovery was significantly better in the cell transplantation and TMT group than the cell transplantation only group. The percentage of cells expressing C-FOS was increased in the grafts in the TMT(+) group. In conclusion, TMT promoted neurite extensions from the grafted neural cells, and the combined therapy of cell transplantation and locomotor training might have the potential to promote the functional recovery of rats with brain injury compared to cell transplantation alone.

Clinical characteristics, treatment and prognosis of paediatric patients with metastatic neuroblastoma to the brain

ObjectiveNeuroblastoma (NB) is the most common extracranial solid malignancy in children. Metastatic involvement of brain is rare in NB. This study was established to evaluate the clinical characteristics, treatment and prognosis of NB patients with brain metastases. Patients and methodsFrom September 2005 to December 2016, the clinical data of 15 cases with brain metastases among 264 NB patients admitted to Beijing Tongren Hospital, Capital Medical University were collected and retrospectively analysed. The clinical features of the 15 patients were summarised, and the patients were grouped according to different treatment methods and followed up for a median time of 41 months. The survival curves were plotted, and the Log-rank test was performed to compare the effect of different treatment methods on the prognosis. ResultsThe proportion of brain metastases in NB patients in our hospital is 5.68% (15/264). For the prognosis of 15 NB cases, the survival time of combined radiotherapy and/or autologous peripheral blood stem cell transplantation group was longer than that of simple operation and chemotherapy group (61.79 ± 9.59 vs. 30.00 ± 5.99 months, P = 0.03). Among the 15 patients, 4 cases underwent intracranial tumor resection, 4 cases received craniospinal irradiation, and the rest received maintenance chemotherapy. The 2-year survival rate was 82.2%, and the 5-year survival rate was 19.9%. The survival time of combined intracranial surgery and/or radiotherapy group was significantly longer than that of the chemotherapy group (46.67 ± 6.69 vs. 16.42 ± 1.42 months, P = 0.003). ConclusionsThe incidence of brain metastases NB in children is relatively small, but the prognosis is very poor. Active chemotherapy, radiotherapy and surgery-based comprehensive treatment can prolong the survival time.

Outcomes of pediatric oncology and hematopoietic cell transplant patients receiving extracorporeal membrane oxygenation.

There is controversy regarding the utilization of extracorporeal membrane oxygenation in pediatric patients with an underlying oncologic diagnosis or who have undergone hematopoietic cell transplant. We hypothesized that these patients have higher mortality, more bleeding complications, more blood product utilization, and a higher rate of new infections than the general pediatric intensive care unit population supported with extracorporeal membrane oxygenation. This is a retrospective chart review at a single center quaternary care pediatric hospital including all pediatric intensive care unit extracorporeal membrane oxygenation patients from 2011 to 2016. Patients were categorized as either oncology/hematopoietic cell transplant or general pediatric intensive care unit. Patients from the cardiovascular intensive care unit or the neonatal intensive care unit were excluded. A total of 38 patients met inclusion criteria of which 7 were oncology/hematopoietic cell transplant patients. The oncology/hematopoietic cell transplant group had lower platelets at the start of extracorporeal membrane oxygenation (p = 0.02) but other pre-extracorporeal membrane oxygenation characteristics were similar. Extracorporeal membrane oxygenation survival was lower in the oncology/hematopoietic cell transplant group (29% vs 77%, p = 0.02). The incidence of bleeding complications and new infections did not differ. The oncology/hematopoietic cell transplant group received more platelets (median of 15.9 mL/kg/day (interquartile range 8.4, 36.6) vs 7.9 mL/kg/day (3.3, 21.9), p = 0.04) and fresh frozen plasma (14.0 mL/kg/day (3, 15.7) vs 1.8 mL/kg/day (0.5, 5.9), p = 0.04). Oncology and hematopoietic cell transplant patients had a higher mortality and received more blood products while on extracorporeal membrane oxygenation than the general pediatric intensive care unit patients despite similar pre-extracorporeal membrane oxygenation characteristics. Physicians should use caution when deciding whether or not to utilize extracorporeal membrane oxygenation in this population.

High expression of miR-338 is associated with poor prognosis in acute myeloid leukemia undergoing chemotherapy.

Acute myeloid leukemia (AML) is a heterogeneous disease with unfavorable outcomes. MicroRNAs (miRNAs) are important regulators and prognostic factors involved in AML. To determine the clinical role of miR-338 in AML, a total of 164 adults with de novo AML were collected. These patients were classified into a chemotherapy group and an allogeneic hematopoietic stem cell transplantation (allo-HSCT) group according to the clinical treatment, and then each group was divided into two subgroups based on the median miR-338 expression values. We found that upregulated miR-338 positively correlates with higher frequencies of complex karyotype, RUNX1 mutation, and poor risk status. In the chemotherapy group, high expression of miR-338 was independently associated with shorter EFS and OS. However, no significant differences were observed between the two subgroups within the allo-HSCT group. We also divided all patients into two groups according to the median miR-338 expression values of the whole cohort. In the miR-338 high expression group, patients receiving allo-HSCT had longer OS and EFS than those receiving chemotherapy only. In contrast, patients receiving different therapies had similar OS and EFS in the miR-338 low expression group. Our study suggests that high expression of miR-338 is an adverse prognostic biomarker in patients with AML undergoing chemotherapy and may guide treatment decisions for AML. Furthermore, allo-HSCT could significantly overcome the negative effect of high miR-338 expression, but it seemed to be unbeneficial and unnecessary for low miR-338 expressions.

Effects of transplanted olfactory ensheathing cells on functional improvement and axonal regeneration in acute and delayed spinal cord injury in rats: A comparative study

Introduction: Cell therapy is known as one of the most common methods used for treating a spinal cord injury (SCI); particularly, olfactory ensheathing cells (OECs), which have attracted much more attention among scholars due to their properties such as promotion of axonal regeneration, remyelination, and angiogenesis. Thus, the present study compared the effects of transplanted OECs on functional improvement and axonal regeneration of contused rats during acute and delayed phases. Material and Methods: For this purpose, a total of 56 male Wistar rats were randomly divided into eight groups including sham, control, three vehicle groups (immediately, 3 and 7 days after injury), and three cell transplantation groups (immediately, 3 and 7 days following injury). The sham group had experienced only laminectomy and other groups had undergone the SCI. The olfactory mucosa of the 7-day-old rat pups was also used for cell culture. The cell type was then confirmed by immunocytochemistry. In the vehicle and cell transplantation groups, the cell culture medium was injected by itself or accompanied by cells, respectively. Subsequently, the motor function was evaluated. Finally, luxol fast blue (LFB) staining was used for histological assessment. Results: Motor test results showed an increase in the Basso, Beattie, and Bresnahan locomotor scale scores immediately after injury in the transplantation group compared to those in other two cell-treated groups; but it was not significant. Discussion and Conclusion: Based on the LFB staining results, the regeneration rate in the transplantation group immediately after injury was considerably higher than that in two other treated groups. Therefore, considering these findings, it seemed that cell transplantation immediately after injury was better than that 3 and 7 days following injury.

High expression of MiR-98 is a good prognostic factor in acute myeloid leukemia patients treated with chemotherapy alone.

It has been demonstrated that microRNA-98 (miR-98) is dysregulated in multiple types of solid tumors, but its expression and impact in acute myeloid leukemia (AML) is unclear. To explore the prognostic role of miR-98 in AML, 164 AML patients with the miR-98 expression data were extracted from The Cancer Genome Atlas (TCGA) database and enrolled in this study. First, patients were divided into chemotherapy-only (chemotherapy) group and allogeneic hematopoietic stem cell transplant (allo-HSCT) group. Each group was then divided in two groups by the median expression level of miR-98. In chemotherapy group, high miR-98 expression was associated with longer event-free survival (EFS, P = 0.003) and overall survival (OS, P = 0.004), but in allo-HSCT group, EFS and OS were not significantly different between high and low miR-98 expressers. Second, All patients were divided in two groups by the median expression level of miR-98. In low miR-98 expressers, those treated with allo-HSCT had longer EFS (P = 0.001) and OS (P < 0.001) than chemotherapy, but in high miR-98 expressers, survival was independent from treatment modalities. Gene ontology enrichment analysis indicated that the genes associated with miR-98 expression were mainly concentrated in “definitive hemopoiesis”, “negative regulation of myeloid cell differentiation” and “signaling pathways regulating pluripotency of stem cells” pathways. In conclusion, our results indicated that high miR-98 expression confers good prognosis in AML patients treated with chemotherapy alone. Patients with low miR-98 expression may benefit from allo-HSCT.

High expression of DOCK2 indicates good prognosis in acute myeloid leukemia.

DOCK family proteins are evolutionarily conserved guanine nucleotide exchange factors for Rho GTPase with different cellular functions. It has been demonstrated that DOCK1 had adverse prognostic effect in acute myeloid leukemia (AML). We first analyzed data of 85 AML patients who were treated with chemotherapy and had available DOCK1 to DOCK11 expression information and found that DOCK1 and DOCK2 had prognostic significance in AML. In view of the known prognosis of DOCK1 in AML, we then explored the prognostic role of DOCK2. One hundred fifty-six AML patients with DOCK2 expression data were extracted from The Cancer Genome Atlas (TCGA) database and enrolled in this study. Patients were divided based on treatment modality into the chemotherapy group and the allogeneic hematopoietic stem cell transplant (allo-HSCT) group. Each group was divided into two groups by the median expression levels of DOCK2. In the chemotherapy group, high DOCK2 expression was associated with longer event-free survival (EFS, P=0.001) and overall survival (OS, P=0.007). In the allo-HSCT group, EFS and OS were not significantly different between high and low DOCK2 expression groups. Multivariate analysis showed that high DOCK2 expression was an independent favorable prognostic factor for both EFS and OS in all patients (all P<0.05). In conclusion, our results indicated that high DOCK2 expression, in contrast to DOCK1, conferred good prognosis in AML.

The effect of bone marrow mesenchymal stem cell transplantation on hypoxic pulmonary hypertension in rats

Objective: To study the influence of bone marrow mesenchymal stem cells (MSCs) transplantation on hypoxic pulmonary hypertension (HPH) in rats. Methods: MSCs in SD rats were separated, cultivated, identified in vitro, and labeled by the green fluorescence protein (GFP) adenovirus. Healthy male SD rats were randomly divided into four groups: normal control group (NC group) and HPH group, with eight rats in each group respectively; HPH + mesenchymal stem cell transplantation group (MSCs group) and HPH + vascular endothelial growth factor + mesenchymal stem cell transplantation group (VEGF + MSCs group), with twenty-four rats in each group respectively. In this experiment, intermittent normobaric hypoxia was employed to establish the pulmonary hypertension rat models, with stem cells transfected and transplanted. The mean pulmonary artery pressure (mPAP) was observed in rats to calculate the right ventricular hypertrophy index (RVHI); the morphological changes of pulmonary arterioles in each group of rats were observed under the microscope; the distribution and manifestation of MSCs fluorescently labeled by adenovirus transfection were observed in pulmonary arterioles under the fluorescence microscope at the set time points of 7 d, 14 d and 28 d after the transplantation of stem cells. Results: For NC group, the mPAP (mmHg) was 15.5 ± 1.5 at 28 d, while the mPAP in HPH, MSCs and VEGF + MSCs groups were 26.1 ± 1.9, 21.6 ± 2.7 and 20.1 ± 2.9 respectively which were apparently higher than that in NC group ( p < .01). Compared with HPH group ( p < .01), the mPAP was obviously decreased in MSCs and VEGF + MSCs groups. There was no significant difference between MSCs and VEGF + MSCs groups. At 28 d, RVHI for NC group was 0.28 ± 0.02, while the RVHI in HPH, MSCs and VEGF + MSCs groups were 0.43 ± 0.07, 0.34 ± 0.03 and 0.35 ± 0.01 respectively which were apparently higher than that in NC group ( p < .01). In comparison with HPH group, RVHI was significantly decreased in MSCs and VEGF + MSCs groups ( p < .05). There was no significant difference between MSCs and VEGF + MSCs groups. For HPH group, at 28 d, pulmonary arterioles were apparently thickened, with luminal stenosis & obliteration and incomplete endothelial cells. Compared with HPH group, pulmonary arterioles in MSCs group became thinning, with the lumen unobstructed and the integrity of endothelial cells improved. The changes in the manifestation of MSCs and VEGF + MSCs groups were not significant. Conclusions: The transplantation of MSCs can improve the remodeling of pulmonary arterioles to partially reverse the progress of HPH; the combined transplantation of VEGF and MSCs doesn’t improve the effect of MSC transplantation.

ELN Genetic Risk Stratification Not Affect the Mid-Term Survival in Childhood AML: Report from Southern China Childhood AML Group

OBJECTIVETo evaluate the survival of children with acute myeloid leukemia (AML) in the ELN genetic risk stratification. To explore the precise treatment and efficacy in childhood AML. MethodsThe information of genetics of 151 newly diagnosed AML children enrolled in the Southern China Childhood AML Collaboration Group from December 2014 to June 2017 were retrospectively analyzed. These patients was divided into low-risk, intermediate-risk and high-risk groups according to the ELN genetic risk stratification. All cases were treated with the Southern China Childhood AML Collaborative Group protocol. The induction of remission was not randomized using FLAG-IDA and DAE regimens for 2 courses of treatment. The consolidation therapy was performed using HAE and MidAC regimens. 20 cases underwent hematopoietic stem cell transplantation. The mediate follow-up time was 18 months. Survival analysis and Log-Rank test were investigated by Graphpad Prism software. RESULTSOf 151 children with AML, AML1/ETO positive in 46(30.5%) cases, CBFβ/MYH11 positive in 12(7.9%) cases, MLL gene in 18(11.9%) cases (including MLLT3-KMT2A in 7 cases). There were mutation gene FTL3/ITD in 24(15.9%) cases, ASXL1 mutation In 10(6.6%) cases, NPM1 mutation in 3(2.0%) cases and CEBPA double mutation in 4(2.6%) cases. Chromosome -7 or 7q- was found in 5(3.3%) cases. According to the ELN genetic risk stratification, 60/151(39.7%), 52/151(34.4%) and 39/151(25.8%) of patients were classified as low-risk, intermediate-risk and high-risk respectively. In the cohort of DAE induction, the CR+CRi rate was 95%, 69% and 80% in the low-risk, intermediate-risk and high-risk group. In the cohort of FLAG-IDA induction, the CR+CRi rate was 100%, 95% and 100% in the low-risk, intermediate-risk and high-risk group. The significance of CR+CRi rate only were be seen in the intermediate-risk group( P=0.02). The 2 year overall OS and DFS were 82.56% and 75.74% respectively. The 2-year DFS of the FLAG-IDA and DAE groups were 85.38% and 53.72% respectively (P=0.0004). The 2-year DFS of the LR, IR, and HR groups in the FLAG-IDA group were 89.23%, 92.29%, and 91.67% respectively, and no statistical difference was found among the groups (P=0.909). The 2-year DFS of the chemotherapy group and the hematopoietic stem cell transplantation group were 82.24% and 63.38%. There were no statistical differences between the groups. DiscussionThe FLAG-IDA induction group significantly improved DFS compared with the DAE group. Hematopoietic stem cell transplantation failed to improve the survival of children with AML in the short period in our multicentre study. Our mid-term results show that the ELN genetic risk stratification had not a significant impact on the prognosis of newly diagnosed childhood AML with high-intensity therapy. DisclosuresNo relevant conflicts of interest to declare.

Effect of bone marrow mesenchymal stem cell transplantation on CCl₄-induced liver injury in rats and intervention effects of Yiguanjian

The aim of this paper was to observe the function of bone marrow mesenchymal stem cell (BMSC) transplantation in process of liver injury induced by carbon tetrachloride (CCl₄) in vivo and the intervention effect of Yiguanjian (YGJ), a compound of Chinese herbal medicine. Wistar rats were randomly divided into five groups: normal group, model group, cell transplantation (CT) group, YGJ group and cell transplantation plus Yiguanjian (CTY) group. Liver injury was induced through subcutaneous injection with CCl₄ at a dose of 3 mL·kg⁻¹ body weight for 4 weeks, twice a week. They were injected for a total of 9 times. After the first injection with CCl₄, rats in the CT group and CTY group were injected with the third-generation BMSCs at dose 1×10⁶ (suspended in 1 mL saline solution) via tail vein. Rats in the YGJ and CTY groups were also intragastrically administered with Yiguanjian once a day. Rat serum ALT and AST activities were increased significantly on the second day after injection with CCl₄, while BMSC transplantation and Yiguanjian decreased their activities. After 4 weeks of injection with CCl₄, serum ALT, AST and γ-GT activities, and serum TNF-α and IL-6 expressions were increased, while TBIL were decreased in model rats compared with normal rats. Meanwhile, liver cells edema, plasmatic loose, and numerous lipid droplets were observed in rats of the model group. BMSC transplantation aggravated liver injury compared with model rats, which was manifested by decreasing SOD activity, increased MDA, TG, TNF-α and IL-6 levels, and aggravated necrosis level of hepatocytes, fusion of lipid droplets, and collagen deposition in liver tissue. Yiguanjian decreased liver injury induced by CCl₄ alone and CCl₄ plus BMSC transplantation. SRY gene in situ hybridization method was used to detect the positive SRY expressions in heart, liver, spleen, lung and kidney, especially in liver, while Yiguangjian decreased liver SRY expression. Wnt and β-catenin showed high expressions in rats of normal group, which were decreased significantly in rats of models group, while Yiguanjian increased their expressions. In conclusion, BMSC transplantation could exacerbate liver injury, while Yiguanjian could protect liver injury induced by CCl₄ and BMSC transplantation, which was related to decreasing the homing of BMSCs to liver and up-regulating Wnt/β-catenin signaling pathway.

Otolog periferik kan kök hücre transplantasyonu sonrası mobilizasyon başarı oranı

Aim: If there issuccessful mobilization following a conditioning regimen forstem cell transplantation, the in vivo purged stem cell products may be collected for a second transplantation. Materials and Methods: In this prospective study, peripheral blood CD34+ cells were quantified between 6 th day after stem cell infusion and 3 rd day after neutrophil engraftment in 20 patients using flow cytometry. Results: In the autologous peripheral blood stem cell transplantation (auto-PBSCT)group(n= 16), the CD34+ cell count was lowest during the first 10 days. The median CD34+ cell count began to increase at the 11 th day and the highest value was achieved at the 14 th day. We documented evidence of mobilization in only one patient (6.25%). Conclusion: Our results indicate thatthe rate of successful stem cell mobilization is very lowfollowing auto-PBSCT. In conclusion, collecting CD34+ stem cells following the first auto-PBSCT is not an effective method for tandem transplantation.

Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease after Autologous or Allogeneic Hematopoietic Stem Cell Transplantation in Children: a retrospective study of the Italian Hematology-Oncology Association–Hematopoietic Stem Cell Transplantation Group

Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD), is a potentially life-threatening complication that may develop after hematopoietic stem cell transplantation (HSCT). The aims of this retrospective multicenter study were to evaluate the incidence of SOS/VOD in a large cohort of children transplanted in centers across Italy by applying the new European Society for Blood and Marrow Transplantation (EBMT) criteria and to analyze the risk factors underlying this complication. We retrospectively reviewed data of pediatric HSCTs performed in 13 AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica)-affiliated centers between January 2000 and April 2016. The new pediatric EBMT criteria were retrospectively applied for diagnoses of SOS/VOD and severity grading. Among 5072 transplants considered at risk for SOS/VOD during the study period, 103 children (2%) developed SOS/VOD, and the grade was severe or very severe in all patients. The median time of SOS/VOD occurrence was 17 days after HSCT (range, 1 to 104). Sixty-nine patients (67%) were treated with defibrotide for a median time of 16 days (range, 4 to 104). In multivariable analysis age < 2 years, use of busulfan during the conditioning regimen, female gender, and hemophagocytic lymphohistiocytosis were risk factors statistically associated with the development of SOS/VOD. The overall mortality directly related to SOS/VOD was 15.5%. Overall survival at 1 year was worse in patients with SOS/VOD (P = .0033), and this difference disappeared 5 years after HSCT. Nonrelapse mortality was significantly higher 1 and 5 years after transplantation in patients who developed SOS/VOD (P < .001). Based on the application of new EBMT criteria, the overall incidence of SOS/VOD recorded in this large Italian pediatric retrospective study was 2%. Nonrelapse mortality was significantly higher in patients who developed SOS/VOD. Identifying the risk factors associated with SOS/VOD can lead to more effective early treatment strategies of this potentially fatal HSCT complication in childhood.

Schwann Cell Precursor Transplant in a Rat Spinal Cord Injury Model.

Differentiation of mesenchymal stem cells into Schwann cell precursors could reverse established lesions and sequelae of medullary transection. The objective of this study was to study the clinical response of mesenchymal stem cell transplantation with Schwann precursor cell transplantation in a rat spinal cord injury model, using motor function and histopathologic studies. A total of 28 Sprague-Dawley rats were randomly divided among four groups (n = 7 in each): sham group, control group, mesenchymal stem cell transplant group, and Schwann cell precursor transplant group. The surgical procedure was a laminectomy with transection of the spinal cord at the T11 level in the transplant groups and the injury control group. After 1 week, the transplant groups received stem cells directly in the injury site. Hind limb motor function was assessed using the locomotive scale of Basso, Beattie, and Bresnahan. 1 month after transplantation, all specimens were sacrificed to make a histopathologic description of sections taken from the site of injury and where stem cells were transplanted. Mean scores of mobility were compared using analysis of variance (ANOVA) of one factor with 95% reliability between groups and ANOVA of repetitive measures to evaluate evolution in the same group. We observed that the control group had statistically greater mobility than the other groups (p < 0.0001) and that the group with spinal injury without treatment had the lowest mean mobility. The mobility score values from the Schwann cell precursor group were statistically higher than the group treated with mesenchymal stem cells (p < 0.0001). Schwann precursor cells had a greater effect on locomotive function than mesenchymal stem cells.

Prognostic value of ABO blood group in patients with nonseminomatous testicular cancer who treated with autologous stem cell transplantation

Abstract Aim Even though ABO blood group surface antigens are expressed in red blood cells, they can be observed in many normal and pathologic cells. Relationship between ABO blood groups and progression and prognosis of cancer has been mainly demonstrated in gastric and pancreatic cancer. However there is no study in current literature about its relation with testicular cancer. The aim of this study is to demonstrate the prognostic value of the ABO blood group in nonseminomatous testicular cancer patients who treated with high dose chemotherapy and autologous stem cell transplantation. Material and method 64 patients who diagnosed as non-seminomatous testicular cancer and treated with HDC and OSCT in Gulhane Medical Oncology Clinic between January 2011 and December 2016 were enrolled to the study. Patients' age, TNM stage, chemotherapy protocols and blood group characteristics were obtained retrospectively. Results The mean age of patients was 31.4 (18–61) years. Blood groups of patients' were as follows: A blood group 19 (29.7%), B blood group 7 (10.9%), O blood group 34 (53.1%), AB blood group 4 (6.3%). Rh was negative in 3 patients (4.7%) and Rh positive in 61 patients (95.3%). 1-year progression-free survival (PFS) was 72.5% and 2-year PFS was 68.4%. 1-year overall survival (OS) was 82% and 2-years OS was 72%. While 1-year and 2-year OS was 88.2% and 84.4% in O blood group individuals, respectively, it was 75.6% and 59.5% in all other blood types, respectively. Although the OS was superior in individuals with O blood group, the difference was not reached the statistically significance (p = 0.071). When O blood group was compared with other blood groups in terms of PFS, 1 year PFS was 79.1% in O blood group and 65.2% in the all other blood groups (p = 0.19). Conclusion OS and PFS were superior in O blood group than other blood groups, however the difference was not reached statistical significance. In the literature, there is no study that focused on the relationship between stem cell transplantation and blood groups. ABO blood groups are the phenotype of a person's genotype and may reflect differences in the individual's immune mechanisms. However, due to small number of cases and heterogeneity of the group, the results and the strength of the study may have affected negatively. So, the prognostic importance of ABO blood groups can be shown with multi-center studies that performed with larger number of cases.

Haematopoietic cell transplantation in Switzerland, changes and results over 20 years: a report from the Swiss Blood Stem Cell Transplantation Working Group for Blood and Marrow Transplantation registry 1997-2016.

In 1997, the Swiss Blood Stem Cell Transplantation Group (SBST) initiated a mandatory national registry for all haematopoietic stem cell transplants (HCTs) in Switzerland. As of 2016, after 20 years, information was available for 7899 patients who had received an HCT (2781 allogeneic [35%] and 5118 autologous [65%]). As some patients had more than one transplant the total number of transplants was 3067 allogeneic and 6448 autologous. We compared patient characteristics and outcome of the first decade (1997-2006) and second decade (2007-2016) of the registry. There were numerous changes over time. For allogeneic HCT, transplant rates, and therefore use of HCT technology, increased from 14 to 21.8 HCTs per 1 million inhabitants per year from the first to the second decade. Likewise autologous HCTs increased from 24.8 to 37.2 annually corrected for population growth. Allogeneic transplant recipients were older (38.4 vs 48.3 years) and more frequently had unrelated donors in the second decade. Similarly, age increased for recipients of autologous HCT (50.8 vs 56.4 years). Analysis of outcome showed that the probabilities of overall and progression-free survival were stable over time, in spite of the treatment of older and higher risk patients. In multivariate analysis, nonrelapse mortality decreased in recipients of allogeneic HCT (relative risk 0.68, 95% confidence interval 0.52-0.87) over the two decades. Improvement in adjusted nonrelapse mortality compensated for the fact that higher risk patients were treated in more recent years, resulting in similar overall survival. Five-year survival probabilities were 56% (53-59%) in the first and 54% (51-57%) in the second decade for allogeneic HCT, and 59% (57-61%) in the first and 61% (59-63%) in the second decade for autologous HCT. Detailed analyses of changes over time are presented. This study included all HCTs performed in Switzerland during the period of observation and the data are useful for quality assurance programmes, healthcare cost estimation and healthcare planning. Between 50 and 60% of patients were long-term survivors after both types of HCT, indicating growing populations of surviving patients requiring long-term care and observation.

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.

Transplantation effects of dental pulp-derived cells on peripheral nerve regeneration in crushed sciatic nerve injury.

The effects of transplanted human dental pulp-derived cells (DPCs) on peripheral nerve regeneration were studied in a rat model of sciatic nerve crush injury. In one group, DPCs were transplanted into the compression site (cell transplantation group); the control group underwent no transplantation (crushed group). Sciatic nerve regeneration was determined based on the recovery of motor function and histological and immunohistochemical analyses. The cell transplantation group showed improved motor function compared with the crushed group using the CatWalk XT system, which corresponded to a higher ratio of tibialis to anterior muscle weight 14 days after surgery. Histological analysis revealed a smaller interspace area and few vacuoles in the sciatic nerve after cell transplantation compared with the crushed group. The myelin sheath was visualized with Luxol Fast Blue (LFB) staining and anti-myelin basic protein (anti-MBP) antibody labeling; the percentages of LFB- and MBP-positive areas were higher in the cell transplantation group than in the crushed group. Human mitochondria-positive cells were also identified in the sciatic nerve at the transplantation site 14 days after surgery. Taken together, the observed correlation between morphological findings and functional outcomes following DPC transplantation indicates that DPCs promote peripheral nerve regeneration in rats.

Co-Transplantation of Human Neurotrophic Factor Secreting Cells and Adipose-Derived Stem Cells in Rat Model of Multiple Sclerosis.

Objective The presence of neurotrophic factors is critical for regeneration of neural lesions. Here, we transplanted combination of neurotrophic factor secreting cells (NTF-SCs) and human adipose derived stem cells (hADSCs) into a lysolecithin model of multiple sclerosis (MS) and determined the myelinization efficiency of these cells. Materials and Methods In this experimental study, 50 adult rats were randomly divided into five groups: control, lysolecithin, vehicle, hADSCs transplantation and NTF-SCs/ hADSCs co-transplantation group. Focal demyelization was induced by lysolecithin injection into the spinal cord. In order to assess motor functions, all rats were scored weekly with a standard experimental autoimmune encephalomyelitis scoring scale before and after cell transplantation. Four weeks after cell transplantation, the extent of demyelination and remyelination were examined with Luxol Fast Blue (LFB) staining. Also, immunofluorescence method was used for evaluation of oligodendrocyte differentiation markers including; myelin basic protein (MBP) and Olig2 in the lesion area. Results Histological study show somewhat remyelinzation in cell transplantation groups related to others. In addition, the immunofluorescence results indicated that the MBP and Olig2 positive labeled cells were significantly higher in co-cell transplantation group than hADSCs group (P<0.05). Also, outcome of motor functional test showed significant improvement function in cell transplantation groups, as compared to the others (P<0.01). ConclusionOur results indicated that the remyelinization process in co-cell transplantation group was better than other groups. Thus, NTF-SCs/ hADSCs transplantation can be proper candidate for cell based therapy in neurodegenerative diseases, such as MS.

Study on the efficacy of CD34+ cells combined with sarpogrelate hydrochlotride tablets for the reconstruction of the blood supply of thromboangiitis obliterans

Objective To investigate the effect of autologous peripheral blood stem cell transplantation combined with CD34+ cells and oral sarpogrelate hydrochloride for the treatment of vascular reconstruction and blood supply on the thromboangiitis obliterans. Methods Thromboangiitis obliterans (TAO) of 262 patients with 262 lower limbs were divided into stem cells CD34+ cells transplantation combined with sarpogrelate hydrochloride group (group A) with 100 lower limbs, CD34+ stem cell transplantation group (group B) with 91 lower limbs, and sarpogrelate hydrochloride oral group ( group C) with 71 lower limbs. The degree of lower limb local blood flow variability were calculated at the three levels of skin, blood vessels and blood by preoperative and postoperative use of multi-function monitoring instrument, Doppler detector, transcutaneous oxygen pressure monitor, and digital subtraction angiography (DSA), respectively. Results ⑴ The degree of shank, foot cyanosis, cool skin, and pain was relieved significantly in groups A and B than in group C for 1 month after the treatment (P<0.05). ⑵ Intermittent claudication distance, the skin temperature of the lower leg and foot to patients in the groups A and B than in group C, with a significant difference (F=7.01, F=7.04, P<0.05) for 3 months after the treatment. ⑶ Among the patients with amputation, 10 cases were in group A, 16 cases in group B, and 31 cases in group C for 6 months after the treatment. ⑷ Transcutaneous oxygen pressure was increased from (30.43±4.31)mmHg to (37.21±9.01)mmHg (F=5.69, P<0.05), ankle brachial index from (0.32±0.23) to (0.91 ± 0.16) (F=6.71, P<0.05), the volume of blood flow index from the photoelectric (0.22±0.04) to (0.83±0.13 (F=5.69, P<0.05), oxygen saturation from (42.41±9.61)% to (79.61±20.34)% (F=5.74, P<0.05), and DSA score (0.23±0.03) increased to (1.35±0.23) (F=7.14, P<0.05), which was significantly higher than group B and group C (F=7.01, F=7.04, F=7.12, F=7.08, F=7.15, P<0.05) for one year after treatment. Conclusions Treatment of peripheral blood stem cells CD34+ cell transplantation combined with oral sarpogrelate hydrochloride can significantly improve the vascular regeneration and its blood supply in TAO lower extremity limb. Key words: Peripheral blood stem cell transplantation; Antigens, CD34/AD; Platelet aggregation inhibitors/AD; Thromboangiitis obliterans/TH; Blood circulation