PD-1^(+)and TIM-3^(+)T cells widely express commonγ-chain cytokine receptors in multiple myeloma patients,and IL-2,IL-7,IL-15 stimulation up-regulates PD-1 and TIM-3 on T cells

Background:Immune checkpoint ligand-receptor interactions appear to be associated with multiple myeloma(MM)progression.Simultaneously,previous studies showed the possibility of PD-1 and TIM-3 expression on T cells upon stimulation with commonγ-chain family cytokines in vitro and during homeostatic proliferation.The aim of the present work was to study the impact of homeostatic proliferation on the expansion of certain T cell subsets upregulating PD-1 and TIM-3 checkpoint molecules.Methods:The expression of CD25,CD122,CD127 commonγ-chain cytokine receptors,phosphorylated signal transducer and activator of transcription-5(pSTAT5)and eomesodermin(EOMES)was comparatively assessed with flow cytometry in PD-1-and TIM-3-negative and positive T cells before the conditioning and during the first post-transplant month in peripheral blood samples of MM patients.Results:Substantial proportions of PD-1-and TIM-3-positive T lymphocytes expressed commonγ-chain cytokine receptors and pSTAT5.Frequencies of cytokine receptor expressing cells were significantly higher within TIM-3+T cells compared to PD-1+TIM-3−subsets.Considerable proportions of both PD-1-/TIM-3-negative and positive CD8+T cells express EOMES,while only moderate frequencies of CD4+PD-1+/TIM-3+T cells up-regulate this transcription factor.Besides,the surface presence of CD25 and intranuclear expression of EOMES in CD4+T cells were mutually exclusive regardless of PD-1 and TIM-3 expression.The stimulation with commonγ-chain cytokines up-regulates PD-1 and TIM-3 during the proliferation of initially PD-1/TIM-3-negative T cells but fails to expand initially PD-1+and TIM-3+T cell subsets in vitro.Conclusions:Both PD-1 and TIM-3 expressing T cells appear to be able to respond to homeostatic cytokine stimulation.Differences in commonγ-chain cytokine receptor expression between PD-1+and TIM-3+T cells may reflect functional dissimilarity of these cell subsets.Checkpoint blockade appears to alleviate lymphopenia-induced proliferation of PD-1+T cells but may raise the possibility of immune-mediated adverse events.

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.

Immunization with autologous T cells enhances in vivo anti-tumor immune responses accompanied by up-regulation of GADD45β

Immunization with inactivated autoreactive T cells may induce idiotype anti-idiotypic reactions to deplete autoreactive T cells, which are involved in autoimmune diseases. However, it is unknown whether attenuated activated healthy autologous T-cell immunization could increase anti-tumor immune responses. To this end, C57B1/6 mice were immunized with attenuated activated autologous T cells. The splenocytes from immunized mice showed a higher proliferative ability than that from naive mice. The special phenotype analysis showed that there were more CD8+ T cells and CD62L+ T cells in immunized mice after 24 h of culture with 10% fetal calf serum complete medium in vitro (P〈0.01). These results demonstrated that this immunization may activate T cells in vivo. Furthermore, the splenocytes from immunized mice revealed resistance to activation-induced cell death (AICD) in vitro. To further study the relative genes that are responsible for the higher proliferation and resistance to AICD, the expression of Fas/Fas ligand (FasL) and GADD4513 was measured by real-time PCR. The results indicated that GADD45β transcription was higher in the splenocytes from immunized mice than that in the naive mice. In addition, the Fas expression showed a parallel higher, but FasL did not change obviously. To investigate the biologic functions induced by immunization in vivo, a tumor model was established by EL-4 tumor cell inoculation in C57/B1 mice. Mice receiving autologous T-cell immunization had significantly inhibited tumor growth in vivo (P〈0.01). This study implicated that immunization with attenuated activated autologous T cells enhances anti-tumor immune responses that participate in tumor growth inhibition.

Downregulation of CD4+CD25+ regulatory T cells may underlie enhanced Th1 immunity caused by immunization with activated autologous T cells

Regulatory T cells （Treg） play important roles in immune system homeostasis, and may also be involved in tumor immunotolerance by suppressing Th1 immune response which is involved in anti-tumor immunity. We have previously reported that immunization with attenuated activated autologous T cells leads to enhanced anti-tumor immunity and upregulated Thl responses in vivo. However, the underlying molecular mechanisms are not well understood. Here we show that Treg function was significantly downregulated in mice that received immunization of attenuated activated autologous T cells. We found that Foxp3 expression decreased in CD4＋CD25＋ T cells from the immunized mice. Moreover, CD4＋CD25＋Foxp3＋ Treg obtained from immunized mice exhibited diminished immunosuppression ability compared to those from naive mice. Further analysis showed that the serum of immunized mice contains a high level ofanti-CD25 antibody （about 30 ng/ml, p〈0.01 vs controls）. Consistent with a role ofanti-CD25 response in the downregulation of Treg, adoptive transfer of serum from immunized mice to naive mice led to a significant decrease in Treg population and function in recipient mice. The triggering of anti-CD25 response in immunized mice can be explained by the fact that CD25 was induced to a high level in the ConA activated autologous T cells used for immunization. Our results demonstrate for the first time that immunization with attenuated activated autologous T cells evokes anti-CD25 antibody production, which leads to impeded CD4＋CD25＋Foxp3＋ Treg expansion and function in vivo. We suggest that dampened Treg function likely contributes to enhanced Thl response in immunized mice and is at least part of the mechanism underlying the boosted anti-tumor immunity.

Synaptic development in the injured spinal cord cavity following co-transplantation of fetal spinal cord cells and autologous activated Schwann cells

Transplantation of activated transgenic Schwann cells or a fetal spinal cord cell suspension has been widely used to treat spinal cord injury. However, little is known regarding the effects of co-transplantation. In the present study, autologous Schwann cells in combination with a fetal spinal cord cell suspension were transplanted into adult Wistar rats with spinal cord injury, and newly generated axonal connections were observed ultrastructurally. Transmission electron microscopic observations showed that the neuroblast first presented cytoplasmic processes, followed by pre- and postsynaptic membranes with low electron density forming a dense projection. The number and types of synaptic vesicles were increased. Synaptic connections developed from single cell body-dendritic synapses into multiple cell body-dendritic and dendrite-dendritic synapses. In addition, the cell organs of the transplanted neuroblast, oligodendroblast and astroblast matured gradually. The blood-brain barrier appeared subsequently. Moreover, neurofilament, histamine, calcitonin-gene-related peptides, and glial fibrillary acidic protein positive fibers were observed in the transplant region. These findings demonstrate that fetal spinal cord cells in the presence of autologous activated Schwann cells can develop into mature synapses in the cavity of injured spinal cords, suggesting the possibility of information exchange through the reconstructed synapse between fetal spinal cord cells and the host.

Improved guided bone regeneration by combined application of unmodified, fresh autologous adipose derived regenerative cells and plasma rich in growth factors:A first-in-human case report and literature review

BACKGROUND Novel strategies are needed for improving guided bone regeneration(GBR) in oral surgery prior to implant placement, particularly in maxillary sinus augmentation(GBR-MSA) and in lateral alveolar ridge augmentation(LRA). This study tested the hypothesis that the combination of freshly isolated, unmodified autologous adipose-derived regenerative cells(UA-ADRCs), fraction 2 of plasma rich in growth factors(PRGF-2) and an osteoinductive scaffold(OIS)(UAADRC/PRGF-2/OIS) is superior to the combination of PRGF-2 and the same OIS alone(PRGF-2/OIS) in GBR-MSA/LRA.CASE SUMMARY A 79-year-old patient was treated with a bilateral external sinus lift procedure as well as a bilateral lateral alveolar ridge augmentation. GBR-MSA/LRA was performed with UA-ADRC/PRGF-2/OIS on the right side, and with PRGF-2/OIS on the left side. Biopsies were collected at 6 wk and 34 wk after GBRMSA/LRA. At the latter time point implants were placed. Radiographs(32 mo follow-up time) demonstrated excellent bone healing. No radiological or histological signs of inflammation were observed. Detailed histologic,histomorphometric, and immunohistochemical analysis of the biopsies evidenced that UA-ADRC/PRGF-2/OIS resulted in better and faster bone regeneration than PRGF-2/OIS.CONCLUSION GBR-MSA with UA-ADRCs, PRGF-2, and an OIS shows effectiveness without adverse effects.

Minimally manipulated autologous adherent bone marrow cells (ABMCs):a promising cell therapy of spinal cord injury

Spinal cord injury（SCI）is a devastating ailment that results in drastic life style alterations for the patients and their family members（Mc Donald and Sadowsky,2002）.Damage post injury causes necrosis,edema,hemorrhage and vasospasm.Post injury,secondary damage is caused by ischemia,

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

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

Effect of autologous bone marrow stem cells-scaffold transplantation on the ongoing pregnancy rate in intrauterine adhesion women:a randomized,controlled trial

Intrauterine adhesion is a major cause of female reproductive disorders.Although we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth,no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so far.To verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate,we conducted this randomized controlled clinical trial.Totally 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter(control group)from February 2016 to January 2020.The per-protocol analysis included 140 participants:72 in bone marrow stem cells-scaffold group and 68 in control group.The ongoing pregnancy occurred in 45/72(62.5%)participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group(28/68,41.2%)(RR=1.52,95%CI 1.08–2.12,P=0.012).The situation was similar in live birth rate(bone marrow stem cells-scaffold group 56.9%(41/72)vs.control group 38.2%(26/68),RR=1.49,95%CI 1.04–2.14,P=0.027).Compared with control group,participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic adhesiolysis.The incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were observed.In conclusion,transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and live birth rates,and this therapy was relatively safe.

Monomorphic epitheliotropic intestinal T-cell lymphoma with bone marrow involved: A case report

BACKGROUND Monomorphic epithelial intestinal T-cell lymphoma(MEITL)is a rare type of peripheral T-cell lymphoma.The clinical manifestations are diarrhea,abdominal pain,perforation and an abdominal mass.CASE SUMMARY We present a 52-year-old female patient who was diagnosed with MEITL.Further disease progression was observed after multiline chemotherapy.Eventually,the patient died of a severe infection.CONCLUSION MEITL is a rare intestinal primary T-cell lymphoma with aggressive behavior,a high risk of severe life-threatening complications,and a poor prognosis.

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.

Hepatitis B-related events in autologous hematopoietic stem cell transplantation recipients

AIM: To investigate the frequency of occult hepatitis B, the clinical course of hepatitis B virus (HBV) reactivation and reverse seroconversion and associated risk factors in autologous hematopoietic stem cell transplantation (HSCT) recipients. METHODS: This study was conducted in 90 patients undergoing autologous HSCT. Occult HBV infection was investigated by HBV-DNA analysis prior to transplantation, while HBV serology and liver function tests were screened prior to and serially after transplantation. HBV-related events including reverse seroconversion and reactivation were recorded in all patients. RESULTS: None of the patients had occult HBV prior to transplantation. Six (6.7%) patients were positivefor HBV surface antigen (HBsAg) prior to transplantation and received lamivudine prophylaxis; they did not develop HBV reactivation after transplantation. Clinical HBV infection emerged in three patients after transplantation who had negative HBV-DNA prior to HSCT. Two of these three patients had HBV reactivation while one patient developed acute hepatitis B. Three patients had anti-HBc as the sole hepatitis B-related antibody prior to transplantation, two of whom developed hepatitis B reactivation while none of the patients with antibody to HBV surface antigen (anti-HBs) did so. The 14 anti-HBs-and/or anti-HBc-positive patients among the 90 HSCT recipients experienced either persistent (8 patients) or transient (6 patients) disappearance of anti-HBs and/or anti-HBc. HBsAg seroconversion and clinical hepatitis did not develop in these patients. Female gender and multiple myeloma emerged as risk factors for loss of antibody in regression analysis (P < 0.05). CONCLUSION: Anti-HBc as the sole HBV marker seems to be a risk factor for reactivation after autologous HSCT. Lamivudine prophylaxis in HbsAg-positive patients continues to be effective.

The clinical effects of DC-CIK cells combined with chemotherapy in the treatment of advanced NSCLC

Objective: The aim of the study was to evaluate the safety and therapeutic effects of autologous dendritic cells co-cultured with cytokine-induced killer cells (DC-CIK) combined with chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. Methods: Fifty patients with advanced NSCLC (stages III to IV), who had received therapies in our Center (Department of Biotherapy, Affiliated to Cancer Hospital of Shanxi Medical University, Taiyuan, China) from August 2008 to January 2010, were treated by DC-CIK + chemotherapy as the combined treatment group; fifty advanced NSCLC patients treated with chemotherapy at the same time served as controls. The immunologic function, short-term therapeutic effects, the 1-year survival rate, the life quality, the chemotherapy side effects were compared between the two groups, the safety and therapeutic effects of DC-CIK cells therapy were observed too. Results: There was no obvious change of subsets of T cells in peripheral blood before and after therapy in DC-CIK + chemotherapy group, and IFN-γ was improved after therapy in this group (P < 0.05); in chemotherapy alone group, the ratios of CD3+CD4+, CD3+CD8+, CD3-CD56+ cells and the secretion of IL-2, TNF-α decreased significantly after therapy (P < 0.05); the ratios of CD3+CD8+, CD3+CD56+ were improved after cell culture (P < 0.05). The disease control rate (DCR) of DC-CIK + chemotherapy group was higher than that in the chemotherapy alone group (78.0% vs 56.0%, P < 0.05); the 1-year survival rates of DC-CIK + chemotherapy group and chemotherapy alone group were 50% and 44% respectively, had no significant difference. Compared with chemotherapy alone group, the occurrence of chemotherapy side effects (including bone marrow suppression, nausea and vomiting, peripheral nerve toxicity) was less in the DC-CIK + chemotherapy group (P < 0.05). The physical and appetite were better in DC-CIK + chemotherapy group after therapy. Conclusion: To compare with simple chemotherapy, DC-CIK + chemotherapy for advanced NSCLC is safe and effective, and it can improve patients' life quality and remission rate, and prolong their survival time.

Autologous bone marrow derived stem cell therapy in patients with type 2 diabetes mellitus-defining adequate administration methods

AIM To carry out randomized trial for evaluating effects of autologous bone marrow derived stem cell therapy(ABMSCT) through different routes.METHODS Bone marrow aspirate was taken from the iliac crest of patients. Bone marrow mononuclear cells were separatedand purified using centrifugation. These cells were then infused in a total of 21 patients comprising three groups of 7 patients each. Cells were infused into the superior pancreaticoduodenal artery(Group Ⅰ), splenic artery(Group Ⅱ) and through the peripheral intravenous route(Group Ⅲ). Another group of 7 patients acted as controls and a sham procedure was carried out on them(Group Ⅳ). The cells were labelled with the PET tracer F18-FDG to see their homing and in vivo distribution. Data for clinical outcome was expressed as mean ± SE. All other data was expressed as mean ± SD. Baseline and post treatment data was compared at the end of six months, using paired t-test. Cases and controls data were analyzed using independent t-test. A probability(P) value of < 0.05 was regarded as statistically significant. Measures of clinical outcome were taken as the change or improvement in the following parameters:(1) C-peptide assay;(2) HOMA-IR and HOMA-B;(3) reduction in Insulin dose; subjects who showed reduction of insulin requirement of more than 50% from baseline requirement were regarded as responders; and(4) reduction in HbA 1c. RESULTS All the patients, after being advised for healthy lifestyle changes, were evaluated at periodical intervals and at the end of 6 mo. The changes in body weight, body mass index, waist circumference and percentage of body fat in all groups were not significantly different at the end of this period. The results of intra-group comparison before and after ABMSCT at the end of six months duration was as follows:(1) the area under C-peptide response curve was increased at the end of 6 mo however the difference remained statistically non-significant(P values for fasting C-peptide were 0.973, 0.103, 0.263 and 0.287 respectively and the P values for stimulated C-peptide were 0.989, 0.395, 0.325 and 0.408 respectively for groups Ⅰ?to Ⅳ);(2) the Insulin sensitivity indices of HOMA IR and HOMA B also did not show any significant differences(P values for HOMA IR were 0.368, 0.223, 0.918 and 0.895 respectively and P values for HOMA B were 0.183, 0.664, 0.206 and 0.618 respectively for groups Ⅰto Ⅳ);(3) Group Ⅰshowed a significant reduction in Insulin dose requirement(P < 0.01). Group Ⅱ patients also achieved a significant reduction in Insulin dosages(P = 0.01). The Group Ⅰand Group Ⅱ patients together constituted the targeted group wherein the feeding arteries to pancreas were used for infusing stem cells. Group Ⅲ, which was the intravenous group, showed a non-significant reduction in Insulin dose requirement(P = 0.137). Group Ⅳ patients which comprised the control arm also showed a significant reduction in Insulin dosages at the end of six months(P < 0.05); and(4) there was a non-significant change in the Hb A1 c levels at the end of 6 mo across all groups(P = 0.355, P = 0.351, P = 0.999 and P = 0.408 respectively for groups Ⅰto Ⅳ). CONCLUSION Targeted route showed a significant reduction in Insulin requirement at the end of six months of study period whereas the intravenous group failed to show reduction.

High-dose Chemotherapy Combined with Autologous Hematopoietic Stem Cell Transplantation as Frontline Therapy for Intermediate/High-risk Diffuse Large B Cell Lymphoma

The role of autologous hematopoietic stem cell transplantation(auto-HSCT)following high-dose chemotherapy has been validated and accepted as a standard treatment for patients with relapsed diffuse large B-cell lymphoma(DLBCL).However,its clinical efficacy as frontline therapy remains to be elucidated.This study aimed to examine the feasibility of frontline auto-HSCT for newly diagnosed intermediate/high-risk DLBCL patients.We retrospectively reviewed the data of 223 patients treated with frontline auto-HSCT or chemotherapy alone(year 2008-2014)from four hospitals.The median follow-up time was 29.4 months.Between the two treatment arms among the intermediate/high-risk DLBCL patients,the 3-year overall survival(OS)and progression-free survival(PFS)rates of patients given frontline auto-HSCT were 87.6%and 81.9%,respectively,and the chemotherapy-alone group showed 3-year OS and PFS rates of 64.9%and 59.59%,respectively.Compared with the chemotherapy-alone group,the frontline auto-HSCT could eliminate the adverse impact of non-germinal center B-cell(GCB)type.In addition,in the frontline auto-HSCT group,patients who achieved complete response(CR)at auto-HSCT had a longer survival time than those who did not achieve CR.Our results suggested that frontline auto-HSCT could improve the prognosis of intennediate/high-risk DLBCL patients.

Autologous hematopoietic stem cell transplantation for diabetic foot:A meta-analysis

Objective:To systematically evaluate the efficacy and safety of autologous hematopoietic stem cell(AHSCs)transplantation for diabetic foot(DF).Methods:A systematic search of literatures in PubMed,Embase,the Cochrane Library,CNKI,WanFang and VIP from inception to March 2020 was conducted.Clinical randomized controlled trials of AHSCs transplantation for DF were screened according to inclusion and exclusion criteria,and meta-analysis was performed using RevMan 5.3 software.Results:A total of 13 articles were included,including 582 patients within 292 received conventional treatment in the control group and 290 additionally received AHSCs in the transplantation group.Meta-analysis results showed that compared with the control group,the transplantation group improved ulcer healing rate[RR=2.38,95%CI(1.91,2.98),P<0.00001],ankle brachial index[MD=0.14,95%CI(0.11,0.16),P<0.00001]and skin temperature of injured limb[MD=1.39,95%CI(0.93,1.86),P<0.00001].And lowered mutation rate[RR=0.10,95%CI(0.04,0.26),P<0.00001],pain scores[MD=-1.37,95%CI(-1.62,-1.12),P<0.00001]and indirect claudication scores[MD=-0.89,95%CI(-1.04,-0.75),P<0.00001].The above differences were all statistically significant(P<0.05).Conclusion:Existing evidence shows that AHSCs transplantation for DF has certain clinical effects and safety.However,more high-quality research are needed to further demonstrate the above results.

HIGH DOSE CHEMORADIOTHERAPY WITH AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THE TREATMENT OF ADVANCED HODGKIN's LYMPHOMA:A REPORT OF 11 CASES

Objective: High dose therapy (HDT) with autologous hematopoietic stem cell transplantation (ASCT) has become one of the important salvage treatments for the Hodgkin抯 Lymphoma patients with relapsed or resistant disease, but its role as the primary treatment remains indefinite. This study was designed to further evaluate its status in the combined modality treatment, especially, to discuss its value in the primary treatment of the patients who had advanced disease with poor prognostic factors. Methods: Eleven patients who had advanced or relapsed disease with poor prognostic factors were enrolled in this study. Among them, 9 cases had primary treatment, and 2 cases had secondary treatment; one patient received autologous bone marrow transplantation (ABMT), and 10 patients received autologous peripheral blood stem cell transplantation (APBSCT). After induction treatment 4 cases achieved complete response (CR) and 7 cases achieved partial response (PR). High dose chemotherapy combined with total body irradiation (TBI) or total lymph node irradiation (TLI)/subtotal lymph node irradiation (STLI) were adopted in 7 cases and only high dose chemotherapy were adopted in 4 cases as the transplant preparative regimens. 5 cases received complementary irradiation in the primary sites after transplant. Results: The patients who had CR before transplantation were given consolidative therapy. Among the rest with PR, 2 cases achieved CR, 1 case PR, and 4 cases SD. Furthermore all these patients who maintained SD had bone involvement. With a median follow-up for all patients of 13(1-80) months, all of them are alive currently. Four cases are event-free survival (EFS); 4 cases with bone involvement are progression-free survival (PFS); 3 cases experienced relapse after transplant, one of them is EFS for 42 months again after a local relapsed site irradiation; the other two cases are being given further salvaged treatment now. According to the Life Tables method, the cumulative probability of 6-year PFS and OS is 55.68% and 100% respectively. The dominating transplant- related toxicity was bone marrow suppression in grades IV. No obvious cardiac, hepatic, and nephritic toxicity was found. No transplant related mortality. Conclusion: HDT combined with ASCT is a method worthwhile to further study for the treatment of the patients with advanced or relapsed Hodgkin抯 Lymphoma with poor prognostic factors.

The safety of autologous peripheral blood stem cell transplantation by intracoronory infusionin in patients with acute myocardial infarction

Objective Bone-marrow stem-cell transplantation has been shown to improve cardiac function in patients with AMI, but the safety of intracoronory infusion of autologous peripheral blood stem-cell(PBSCs) in patients with AMI is unknown. For this reason, we observe the feasibility and safety of PBSCs transplantation by intracoronory infusion in such patients.Method Fourty one patients with AMI were allocated to receive Granulocyte Colony-Stimulating Factor (G-CSF:Filgrastim,300 μg) with the dose of 300 μg-600 μg/day to mobilize the stem cell, and the duration of applying G-CSF was 5 days . On the sixth day, PBSCs were separated by Baxter CS 3000 blood cell separator into suspend liquid 57 ml. Then the suspend liquid was infused into the infarct related artery (IRA)by occluding the over the wire balloon and infusing artery through balloon center lumen. In the process of the intracoronary infusion of PBSCs, the complications should be observed, which were arrhythmias including of bradycardia, sinus arrest or atrial ventricular block, premature ventricular beats ,ventricular tachycardia, ventricular fibrillation; and hypotention, etc. Results There were total 10 cases with complications during the intracoronary infusion of PBSCs. The incidence of complications was 24.4%(10/41), including bradycardia is 2.4 %(1/41), sinus arrest or atrial ventricular block is 4.9%(2/41), ventricular fibrillation is 2.4 %( 1/41), hypotention is14.6 % (6 /41).Conclusions In patients with AMI, intracoronary infusion of PBSCs is feasible and safe.

Preliminary Observation on the Influence of Tumor Osseous Metastasis on Autologous Peripheral Blood Stem Cell Collection

OBJECTIVE To examine the influence of tumor osseous metastasis on the patients undergoing autoiogous peripheral blood stem ceil collection. METHODS A total of 36 patients with malignant diseases who received an autoiogous peripheral blood stem ceil transplantation, during a period from April 2004 to June 2006, were chosen. The patients were divided into two groups, i.e. group A were patients with a complication of tumor osseous metastasis, and group B were without metastasis. Both groups were treated with Taxotere 120 mg/m^2 plus granuiocyte colony-stimulating factor （G-CSF） 5 μg/kg/d, for a mobilization regimen. A blood ceil separator was used to collect the mononuciear ceils. The proportion of harvested CD34＋ ceils in the peripheral blood and the collected mononuciear ceils were detected by flow cytometry. The number of CD34＋ ceils was used to determine the difference in the nature of the collections between the two groups. RESULTS After mobilization in groups A and B, the number of the peripheral blood mononuciear ceils （PBMC） was 39.3±14.7% and 41.1±12.4 % and the proportion of CD34＋ ceils was 0.16±0.07% and 0.17±0.10%, respectively. Following administration of the drugs, there was no significant difference between the number of harvested PBMC and CD34＋ cells of the two groups, i.e., 3.47±1.16×10^8/Kg and 2.52±1.43×10^6/Kg in group A and 4.02±1.31×10^8/Kg and 2.73±1.87×10^6/Kg in group B, respectively. CONCLUSION Osseous metastasis, as a single factor, may have no impact on mobilization and harvesting of hematopoietic stem ceils and their engraftment after autotransplantation.