Autologous Group Research Articles

Autologous platelet rich plasma versus ultrasound therapy: What works better in elbow tendinopathies?

The specific goal of this study is to compare the efficacy of commonly used ultrasound therapy and autologous PRP in relieving the pain and improving functional status of patients with elbow tendinopathies.This was a prospective study of 60 patients who were diagnosed to have elbow tendinopathies for the period from April 2017 to June 2018. The recruited participants were randomized into two groups: Group A were given a single dose of Autologous PRP injection and group B were given low intensity Pulsed Ultrasound Therapy for a duration of 3 times a week for 3 weeks. The patient’s clinical outcome was measured by using VAS and MAYO Elbow Performance Score.At the end of 3 weeks there was a 16% and 10.6% decrease in VAS score and there was improvement in MAYO score by 9.2% and 3.9% respectively in PRP and US group. At the end of 6 weeks, VAS score had decreased by 40% and 31% while the MAYO score improved by 22.4% and 15% in PRP and US groups respectively.At the end of 12 weeks, VAS score decreased by 68.9% and 53.8%. MAYO score had improved to 32.4% and 20.8% in PRP and US groups respectively.In our study, autologous platelet rich plasma was found to give better results compared to Ultrasound therapy. But the values were significant only after 12 weeks. Platelet rich plasma and Ultrasound therapy can be used both in acute and chronic cases.

Efficacy of Intravenous Mesenchymal Stem Cells for Motor Recovery After Ischemic Stroke: A Neuroimaging Study.

Stem cell-based therapy is a promising approach to repair brain damage after stroke. This study was conducted to investigate changes in neuroimaging measures using stem cell-based therapy in patients with ischemic stroke. In this prospective, open-label, randomized controlled trial with blinded outcome evaluation, patients with severe middle cerebral artery territory infarct were assigned to the autologous mesenchymal stem cell (MSC) treatment or control group. Of 54 patients who completed the intervention, 31 for the MSC and 13 for the control groups were included in this neuroimaging analysis. Motor function was assessed before the intervention and 90 days after randomization using the Fugl-Meyer assessment scale. Neuroimaging measures included fractional anisotropy values of the corticospinal tract and posterior limb of the internal capsule from diffusion tensor magnetic resonance imaging and strength of connectivity, efficiency, and density of the motor network from resting-state functional magnetic resonance imaging. For motor function, the improvement ratio of the Fugl-Meyer assessment score was significantly higher in the MSC group compared with the control group. In neuroimaging, corticospinal tract and posterior limb of the internal capsule fractional anisotropy did not decrease in the MSC group but significantly decreased at 90 days after randomization in the control group. Interhemispheric connectivity and ipsilesional connectivity significantly increased in the MSC group. Change in interhemispheric connectivity showed a significant group difference. Stem cell-based therapy can protect corticospinal tract against degeneration and enhance positive changes in network reorganization to facilitate motor recovery after stroke. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01716481.

Efficacy of Enhanced Cytokine-Induced Killer Cells as an Adjuvant Immunotherapy for Renal Cell Carcinoma: Preclinical and Clinical Studies.

Cytokine-induced killer (CIK) cells have been proved to be an effective method of tumor immunotherapy in numerous preclinical and clinical studies. In our previous study, a new method was developed to prime and propagate CIK cells by the combination of IL-2 and IL-15, and this kind of CIK cells had enhanced antitumor effect on lung cancer. For renal cell carcinoma (RCC), immunotherapy plays an important role because of the poor efficacy of radiotherapy and chemotherapy. In this study, we further evaluated the antitumor effects of these enhanced CIK cells against RCC. Enhanced CIK cells were generated by IL-2 combined with IL-15 and identified by flow cytometry. HEK-293 and ACHN cell lines were used to verify the efficiency of CIK cells in vitro, and then the ACHN tumor xenograft model was also employed for in vivo study. In addition, the secreted cytokines including IFN-γ, granzyme B, TNF-α, and perforin, as well as the local microstructure were also studied. Subsequently, 20 patients with RCC were enrolled into our study, and 11 patients were randomly divided into the autologous CIK treatment group for clinical research. The results showed that enhanced CIK cells exert better antitumor effects in RCC in vitro (p < 0.01 in HEK-293 and p < 0.05 in ACHN）and in vivo (p < 0.05). Patients benefit overall survival from enhanced CIK therapy in our clinical study. Our present preclinical and clinical studies for the first time elucidated that these enhanced CIK cells would be used as an effective adjuvant therapy in the treatment of RCC.

Long-term survival of patients with mantle cell lymphoma after autologous haematopoietic stem-cell transplantation in first remission: a post-hoc analysis of an open-label, multicentre, randomised, phase 3 trial

Autologous haematopoietic stem-cell transplantation (HSCT) in first remission is the current standard treatment in fit patients with mantle cell lymphoma. In this long-term follow-up study, we aimed to evaluate the efficacy of autologous HSCT versus interferon alfa maintenance after chemotherapy without or with rituximab in patients with primary advanced-stage mantle cell lymphoma. We did a post-hoc, long-term analysis of an open-label, multicentre, randomised, phase 3 trial done in 121 participating hospitals or practices across six European countries. Patients who were aged 18-65 years with previously untreated stage III-IV mantle cell lymphoma and an ECOG performance score of 0-2 were eligible for participation. Patients were randomly assigned (1:1) to receive either myeloablative radiochemotherapy (fractionated total body irradiation with 12 Gy/day 6-4 days before autologous HSCT and cyclophosphamide 60 mg/kg per day intravenously 3-2 days before autologous HSCT) followed by autologous HSCT (the autologous HSCT group) or interferon alfa maintenance (the interferon alfa maintenance group; 6 × 106 IU three times a week subcutaneously until progression) after completion of CHOP-like induction therapy (cyclophosphamide 750 mg/m2 intravenously on day 1, doxorubicin 50 mg/m2 intravenously on day 1, vincristine 1·4 mg/m2 [maximum 2 mg] intravenously on day 1, and prednisone 100 mg/m2 orally on days 1-5; repeated every 21 days for up to 6 cycles) without or with rituximab (375 mg/m2 intravenously on day 0 or 1 of each cycle; R-CHOP). The primary outcome was progression-free survival from end of induction until progression or death among patients who had a remission and the secondary outcome was overall survival from the end of induction until death from any cause. We did comparisons of progression-free survival and overall survival according to the intention-to-treat principle between both groups among responding patients and explored efficacy in subgroups according to induction treatment without or with rituximab. Hazard ratios (HRs) were adjusted for the mantle cell lymphoma international prognostic index (MIPI) numerical score, and in the total group also for rituximab use (adjusted HR [aHR]). This trial was started before preregistration was implemented and is therefore not registered, recruitment is closed, and this is the final evaluation. Between Sept 30, 1996, and July 1, 2004, 269 patients were randomly assigned to receive either autologous HSCT or interferon alfa maintenance therapy. The median follow-up was 14 years (IQR 10-16), with the intention-to-treat population consisting of 174 patients (93 [53%] in the autologous HSCT group and 81 [47%] in the interferon alfa maintenance group) who responded to induction therapy. The median age was 55 years (IQR 47-60), and R-CHOP was used in 68 (39%) of 174 patients. The median progression-free survival was 3·3 years (95% CI 2·5-4·3) in the autologous HSCT group versus 1·5 years (1·2-2·0) in the interferon alfa maintenance group (log-rank p<0·0001; aHR 0·50 [95% CI 0·36-0·69]). The median overall survival was 7·5 years (95% CI 5·7-12·0) in the autologous HSCT group versus 4·8 years (4·0-6·6) in the interferon alfa maintenance group (log-rank p=0·019; aHR 0·66 [95% CI 0·46-0·95]). For patients treated without rituximab, the progression-free survival adjusted HR for autologous HSCT versus interferon alfa was 0·40 (0·26-0·61), in comparison to 0·72 (0·42-1·24) for patients treated with rituximab. For overall survival, the adjusted hazard ratio for HSCT versus interferon alfa was 0·52 (0·33-0·82) without rituximab and 1·05 (0·55-1·99) for patients who received rituximab. Our results confirm the long-term efficacy of autologous HSCT to treat mantle cell lymphoma established in the pre-rituximab era. The suggested reduced efficacy after immunochemotherapy supports the need for its re-evaluation now that antibody maintenance, high-dose cytarabine, and targeted treatments have changed the standard of care for patients with mantle cell lymphoma. Deutsche Krebshilfe, the European Community, and the Bundesministerium für Bildung und Forschung, Kompetenznetz Maligne Lymphome.

Comparison of the efficacy of topical insulin with autologous serum eye drops in persistent epithelial defects of the cornea.

To investigate the effect of topical insulin on epithelization in persistent epithelial defects (PED) refractory to usual treatment compared to autologous serum. Retrospective, consecutive case-control series. The charts of 61 consecutive patients with PED treated with topical insulin (case group) and 23 treated with autologous serum (control group) were reviewed. Primary efficacy end points were the percentage of patients in which epithelization was achieved, as well as the rate and time until epithelization. Secondary efficacy point was need for amniotic membrane transplantation (AMT) or other surgeries. Mean time between PED diagnosis and start of topical insulin was 22.7 ± 18.5 days (range 13-115) and the mean area was 14.8 ± 16.2 mm2 (range 1.1-70.6). In the control group, mean time was 27.9 ± 16.8 days, mean epithelial defect area being 18.6 ± 15.0 mm2 (range 1.7-52.9). No differences in baseline characteristics were found between groups (p > 0.05). Epithelization was achieved in 51 patients (84%) on insulin and 11 patients (48%) on autologous serum (p = 0.002). In those patients, mean time until reepithelization was 32.6 ± 28.3 days (range 4-124) in the insulin group and 82.6 ± 82.4 days (range 13-231) in the autologous serum group (p = 0.011). The need for AMT was significantly lower in the insulin group (p = 0.005). PED recurrence was higher in patients treated on autologous serum (43%) compared with insulin (11%) (p = 0.002). Topical insulin is an effective treatment and safely promotes healing of PED. In our series, topical insulin presented better epithelization outcomes than autologous serum and could thus be considered as a first-line treatment.

P1. Efficacy of a calcium phosphate collagen matrix bone graft with needle-shaped submicron surface topography in a rabbit posterolateral lumbar spine fusion model

<h3>BACKGROUND CONTEXT</h3> Synthetic bone grafts are a promising alternative for the treatment of degenerative spine conditions and are available without the added drawbacks associated autografts including limited availability and donor-site morbidity. Of these synthetic materials, calcium phosphate (CaP) with a characteristic needle-shaped submicron surface topography (BCP<µm) has attracted much attention due to its unique bone-forming ability which is essential for repairing critical-size bone defects such as those found in the posterolateral spine [1,2]. Previous in vitro and ex-vivo data presented by van Dijk LA [3] and Yuan H [4] at NASS, 2020 demonstrated that these specific surface characteristics drive a favorable response from the innate immune system. <h3>PURPOSE</h3> This study was to evaluate the efficacy of a novel synthetic bone graft using a clinically-relevant "Boden" rabbit posterolateral spine fusion model. The synthetic bone graft comprised of CaP granules with a needle-shaped submicron surface structure (BCP<µm) embedded in a highly porous and fibrillar bovine type I collagen matrix (col-BCP<µm). The fibrillar collagen was introduced as a carrier, designed to facilitate admixing of the graft with biological fluids perioperatively and to minimize graft migration postoperatively. <h3>STUDY DESIGN/SETTING</h3> The novel synthetic bone graft was first mixed in a 1:1 volume ratio with autologous bone (ABG). Subsequently, grafts were implanted in the rabbit posterolateral spine environment for 3 days, 6, 9 and 12 weeks. An autologous bone graft group was used as a positive control in this study. Outcomes for the test article were additionally compared to historical data for the same material (BCP<µm) implanted alone, without the fibrillar collagen carrier. <h3>OUTCOME MEASURES</h3> Spinal fusion was determined by manual palpation (MP), X-ray and µCT imaging (based on the Lenke scale), mechanical testing (range of motion testing at 12 weeks only) and histology (decalcified and undecalcified). <h3>METHODS</h3> Forty skeletally mature New Zealand white rabbits were divided into two groups and underwent single-level bilateral posterolateral intertransverse process spine arthrodesis at L4-5. Animals were euthanized after 3 days, 6, 9 and 12 weeks. <h3>RESULTS</h3> Based on all endpoints, the test group and positive control group showed an equivalent and gradual progression in bone formation and implant resorption over time, leading to mature fusion masses at 12 weeks. No adverse reactions were observed in any of the groups. Bilateral fusion rates by MP were consistent with the literature (0-40% at 6 weeks; 60-70% at 12 weeks) and similar trends were seen by histological and radiographic assessment (both X-ray and µCT). Flexion-extension and lateral bending results at 12 weeks demonstrated fusion of the treated level consistent with the MP results. The results observed for the test group were consistent with those seen historically for the same material implanted without the fibrillar collagen carrier. <h3>CONCLUSIONS</h3> These results show that BCP with needle-shaped submicron-scale surface topography (BCP<µm) combined with a fibrillar collagen matrix (col-BCP<µm) could achieve equivalent fusion rates to ABG when used as a bone graft extender in a clinically relevant single level rabbit intertransverse process posterolateral lumbar fusion model. Over time, a progression in bone healing, graft resorption and remodeling were seen with all experimental endpoints, with equivalency between the groups. The results for col-BCP<µm were consistent with those previously seen for BCP<µm alone, confirming that the fibrillar collagen carrier improved handling properties but was not detrimental to the bone-forming capacity of the BCP<µm. <h3>FDA DEVICE/DRUG STATUS</h3> Col-BCP<µm (Investigational/Not approved)

Management of Recurrent Carpal Tunnel Syndrome: Systematic Review and Meta-Analysis

Few comparisons have been performed between the outcomes of surgical techniques for recurrent carpal tunnel syndrome. Using a meta-analysis, this studyaimed to compare the outcomes of different surgical techniques using the Boston Carpal Tunnel Questionnaire (BCTQ) and visual analog scale (VAS) for pain as outcomes. The following categories were used to define the study's inclusion criteria: population, intervention, comparator, outcomes, and study design. Studies were examined by 2 reviewers, and the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines were followed. The studies were assigned to 1 of the following treatment groups: decompression with or without neurolysis, autologous fat transfer, hypothenar fat pad, pedicled or free flap, and "other." For our primary outcome, we compared improvement using the BCTQ and VAS for pain between the treatment groups. For our secondary outcome, postoperative BCTQ and VAS pain values were compared. Fourteen studies were included: 5 case series with postoperative data only and 9 pre-post studies without a control group. With regard to our primary outcome, the studies reported an average improvement of 1.2 points (95% confidence interval [CI][1.5, 0.9]) on a scale of 1-5 on the symptoms severity scale (SSS) of the BCTQ, 1.9 points (95% CI [1.37, 0.79]) on a scale of 1-5 on the function severity scale of the BCTQ, and 3.8 points (95% CI [4.9, 2.6]) on a scale of 1-10 on the VAS for pain. We only found significantly lesser improvement in the "other" treatment group than in the hypothenar fat pad group and autologous fat transfer group using the SSS. The hypothenar fat pad group had the best reported postoperative SSS score of 1.75 (95% CI [1.24, 2.25]), function severity scale score of 1.55 (95% CI [1.20, 1.90]), and VAS pain score of 1.45 (95% CI [0.83, 2.07]). All the techniques showed clinically important improvements in all the outcomes. We found lesser improvement in the "other" treatment group than in the hypothenar fat padgroup and autologous fat transfer group using the SSS. We found that the hypothenar fat pad group had thebest reported postoperative values in our secondary analysis. Therapeutic IV.

Porous nerve guidance conduits reinforced with braided composite structures of silk/magnesium filaments for peripheral nerve repair

Peripheral nerve repair is a common but challenging surgical treatment. Many artificial nerve grafts have been developed, including nerve guidance conduits (NGCs) with biocompatibility, suitable mechanical properties and topography to guide axon growth. However, there remains a need to promote nerve regeneration and accelerate functional recovery using NGCs for nerve reconstruction. Here, silk fibroin (SF) and magnesium (S/Mg) filaments were braided into an inner layer of NGC and freeze-dried with a solution of SF and chitosan (CS). The mechanical stress of these S/Mg-SF/CS conduits reached 2.8 ± 0.2 N and possessed high compression strength. The conduits were evaluated with subcutaneous implantation. Sustainable mechanical function was demonstrated when used to repair 10 mm sciatic nerve gaps in rats. The hollow NGCs improved neurochemotaxis from the damaged nerves. The wet weight ratio of the gastrocnemius muscle, a target muscle for the sciatic nerve related to motor and sensory functions in the NGC group, reached 83.5% of that in the autologous group in 8 weeks; the nerve ports at both ends of the NGC grew well. When the distal end of the regenerated nerve was observed by Transmission Electron Microscopy (TEM), there was no significance difference in the diameter and thickness of the myelin sheath of the distal nerve between the autograft and S/Mg-SF/CS group, indicating that S/Mg-SF/CS NGC in this study promoted the growth of damaged nerves and provided appropriate physio mechanical guidance, thus suggesting potential utility for this approach in artificial nerve transplantation. Statement of significance1. Porous nerve guidance conduits (NGCs) is reinforced by a braided composite structure consisting of silk/magnesium filaments, which provides the NGC with appropriate physio-mechanical guidance as well as sufficient stability to support the biological micro-environment during early-stages of nerve regeneration and functional recovery.2. Sufficient mechanical properties, biocompatibility with Schwan cells and good performance after sciatic nerve transplantation demonstrates that the S/Mg-SF/CS NGC in this study promotes the growth of damaged nerves and provides a suitable physio-mechanical guide for potential in artificial nerve transplantation.3. A facile scalable manufacturing process is achieved by utilizing multidisciplinary engineering, such as textile technologies, biomaterial engineering and medical science.

Autologous Hematopoietic Cell Transplantation (HCT) Is Superior To Allogeneic Transplantation For Acute Promyelocytic Leukemia In Second Complete Remission (CR2)

Acute promyelocytic leukemia (APL) is often curable in adults. However, in 10-20% of patients with initial remission, leukemic relapse occurs. For these patients extended disease free survival is possible following stem cell infusion during second complete remission (CR2). The choice between allogeneic and autologous transplantion is dependent on the availability of suitable donors, the presence of minimal residual disease (MRD) and comorbid illnesses. The risks of treatment related mortality (TRM) associated with allografts must be balanced against a possible higher recurrence rate when autografts are used. To compare the utility of allogeneic and autologous transplantation in the arsenic era, we reviewed 294 patients with APL undergoing HCT in CR2 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1995 to 2006. Outcomes included overall survival (OS), disease free survival (DFS), relapse incidence, and TRM following either allogeneic or autologous HCT. The influence of pre-HCT molecular MRD status on outcome was examined in 114/232 allogeneic grafts and 41/62 autologous grafts. As summarized in Table 1, OS significantly favored autologous transplant, largely related to differences in TRM. Multivariate analysis confirmed that treatment failure was increased with age >40 years (HR=2.30, 95% CI 1.44-3.67, p= 0.0005), and after allogeneic HCT (HR=1.88, 95% CI=1.16-3.06, p=0.011). OS was significantly worse with allogeneic vs. autologous HCT (HR= 2.66, 95%CI 1.52-4.65, p=0.0006; age >40 (HR=3.29, 95% CI 1.95-5.54, p<0.001) and short CR1 (HR=1.56 95% CI 1.07-2.26, p=0.021). Relapse rates (RR) at 5 years were similar after autologous 30% (95% CI 19-42%) vs. allogeneic HCT (18% (95% CI 14-24%); adjusted HR=0.71, 95%CI 0.4-1.28, p=0.26). As expected, TRM in allogeneic was significantly higher at 31% (25-37) compared to autologous 7 % (2-17) with a HR of 7.07(2.56-19.57) P=0.0002. These results are summarized in Table 1. In patients with pre-HCT positive molecular or cytogenetic MRD, the allogeneic group (n=17) had a 5 year relapse rate of 27%, DFS 60%, and OS 65%. Notably, in MRD+ autologous group (n=6), only 1 relapsed at 6 months and died; 5 remain alive and disease-free at 47, 60, 61, 72, and 129 months after HCT. Surprisingly, pre-HCT molecular status did not influence relapse, treatment failure or OS in either group. Although the mechanism is not clear, this observation suggests effective eradication of residual disease in vivo. In this diverse cohort of patients, this retrospective study identifies that autologous transplantation offers superior overall survival when compared to allogeneic transplantation. The finding of long term survival in autologous transplanted patients with MRD+ grafting remains an important subject for further study.Table 1Outcome of Patients with APL Undergoing HCT in C2OutcomeAutoAlloP-valueOS54%(48-61)75%(68-85)0.02TRM31%(25-37)7%(2-17)<0.0001DFS50%(44-57)63%(49-75)0.10RR18%(14-24)30%(19-42)0.40 [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Cognitive Impairment and Quality of Life of Patients Subjected to Hematopoietic Stem Cell Transplantation

Objective: To assess and correlate overall quality of life and the cognitive function of adult patients with hematologic cancer subjected to autologous and allogeneic hematopoietic stem cell transplantations up to three years after treatment. Materials and method: A longitudinal, observational, and analytical study was conducted with 55 patients in a reference hospital in Latin America, from September 2013 to February 2019, with the Quality of Life Questionnaire-Core 30, analyzed with the Spearman’s correlation coefficient and Generalized Linear Mixed Model tests. Results: Overall quality of life in autologous and allogeneic transplantations presented a decline in the pancytopenia phase (59.3 and 55.3, respectively). There was impairment of the cognitive function in the autologous group in post-transplantation after two years (61.90) and, in the allogeneic group (74), in pancytopenia. In the autologous group, a positive (0.76) and significant (p &lt; 0.04) correlation is observed between the cognitive domain and quality of life in post-transplantation after two years. In the allogeneic group, there was a positive (0.55) and significant (p &lt; 0.00) correlation from 180 days after transplantation. Conclusions: Quality of life and the cognitive function present impairment and there is a correlation after the hematopoietic stem cell transplantation for both groups: autologous and allogeneic.

Long Term Follow up after Adoptive Transfer of CD19-Specific CAR+ T Cells Genetically Modified Via Non-Viral Sleeping Beauty S ystem Following Hematopoietic Stem Cell Transplantation (HSCT)

BACKGROUND. We evaluated a human application of T cells genetically modified using the Sleeping Beauty (SB) transposon/transposase system to express a CD19-specific chimeric antigen receptor (CAR, designated CD19RCD28). The SB system uses a synthetic DNA transposon for nonviral somatic gene transfer. The initial data were reported (J Clin Invest. 2016 Sep 1;126(9):3363-76) and we now present long-term follow-up (LTFU).METHODS. T cells were genetically modified using DNA plasmids from the SB platform to stably express CD19RCD28 and selectively propagated ex vivo with activating and propagating cells (AaPC) with cytokines. Twenty-six patients with advanced non-Hodgkin lymphoma (n=9) or acute lymphoblastic leukemia (n=17) underwent autologous (n=7) or allogeneic (n=19) HSCT followed by a T-cell infusion as adjuvant therapy on two clinical trials NCT00968760 and NCT01497184, respectively. Patients were subsequently enrolled onto a LTFU study, NCT01492036, to be followed for up to 15 years. During this time, patients could be tested annually for the persistence of genetically modified T cells using PCR and flow cytometry.RESULTS. The persistence of SB-modified T cells was measured in two of the seven autologous HSCT/CAR+T patients as long as 4-years post infusion and both remain progression-free. Similarly, CAR expression was detected in three allogeneic HSCT recipients one-year post T-cell infusion with no disease progression. Upon LTFU of the autologous HSCT group, six of seven patients continue in complete remission (CR) at a median of 3.4 years (range: 1.7 to 4.2 years). The 3-year progression-free (PFS) and overall survival (OS) rates are 86% and 100%, respectively (Figure). After allogeneic HSCT, recipients received donor-derived CAR+ T cells (8 haploidentical, 10 matched-sibling, one 1Ag-mismatched sibling). For this allogeneic group, six patients remain alive and in CR following haplo (n=4) or matched sibling donor (n=2) HSCT with a median follow-up of 1.5 years (range: 0.003 to 2.9 years). The 2-year PFS and OS rates are 45% and 49%, respectively (Figure). Additionally, the 2-year PFS and OS rates for haplo-identical transplants were 57% and 71%, respectively. No long-term safety issues were identified; specifically, no graft failure or excess graft-versus-host-disease.CONCLUSIONS. CD19-specific CAR+ T cells could be detected and were well-tolerated years after adoptive transfer and appear to provide long-term cancer control when infused after HSCT for patients with advanced disease. These encouraging results support further clinical development of this non-viral gene therapy approach.Figure: Overall and progression-free survivals of recipients of SB-modified CAR+ T cells after autologous and allogeneic HSCT. [Display omitted] DisclosuresHuls:Former employee of Intrexon: Employment. De Groot:Ziopharm: Employment. Smith:Ziopharm: Employment. Yang:Ziopharm: Employment. Kantarjian:Bristol-Meyers Squibb: Research Funding; Novartis: Research Funding; Delta-Fly Pharma: Research Funding; Amgen: Research Funding; ARIAD: Research Funding; Pfizer: Research Funding. Cooper:Immatics: Equity Ownership, Patents & Royalties, Research Funding; Intrexon Corporation: Equity Ownership, Patents & Royalties; Sangamo Biosciences: Patents & Royalties; Organovo Holdings: Equity Ownership; Ziopharm: Employment, Equity Ownership, Research Funding; Procter & Gamble: Equity Ownership; Miltenyi Biotec: Honoraria; Ampliphi Biosciences: Equity Ownership; Argos Therapeutics: Equity Ownership; Ferring: Consultancy; Targazyme, Inc.: Equity Ownership.

Final Analysis of Day +100 Survival By Prior Hematopoietic Stem Cell Transplant Type from an Expanded Access Study of Defibrotide for Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome

BackgroundHepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is an unpredictable, life-threatening complication of conditioning for hematopoietic stem cell transplant (HSCT) and has an estimated overall incidence of 13.7% post-HSCT. VOD/SOS with multi-organ dysfunction (MOD, sometimes referred to as multi-organ failure) may be associated with >80% mortality. In the United States (US), defibrotide is approved for the treatment of adult and pediatric patients with hepatic VOD/SOS and renal or pulmonary dysfunction following HSCT, and it is approved in the European Union for treatment of severe hepatic VOD/SOS after HSCT therapy in patients older than 1 month. Prior to US approval, defibrotide was made available through an expanded-access protocol (T-IND). The present post hoc analysis of final data from the T-IND investigates Day +100 survival in groups of patients receiving autologous or allogeneic transplant.MethodsPatients received defibrotide 25 mg/kg/day in 4 divided doses, and treatment was recommended for ≥21 days. The original eligibility criteria were VOD/SOS by biopsy or Baltimore criteria (bilirubin ≥2 mg/dL and ≥2 of: hepatomegaly, ascites, ≥5% weight gain) post-HSCT, with MOD (renal and/or pulmonary); the protocol was amended to include also patients after chemotherapy without HSCT (off label), patients without MOD (off label), and patients with VOD/SOS per modified Seattle criteria (≥2 of: bilirubin >2 mg/dL, hepatomegaly, or ≥5% weight gain [in this study]).ResultsFrom 2007 to 2016, 1000 post-HSCT patients were enrolled and received defibrotide. Of these, 843 (52% pediatric; 48% adult) patients received allografts (450 of whom had MOD), and 155 (82% pediatric; 18% adult) received autografts (61 had MOD) (Table); 2 had unknown graft types. Acute leukemias were most common in the allograft group, and neuroblastoma was most common in the autograft group. Kaplan-Meier estimated survival rate at Day +100 in the allograft group was 55% (95% confidence interval [CI]: 52%-58%) overall, 47% (95% CI: 43%-52%) for those with MOD, and 64% (95% CI: 59%-69%) for those without MOD (Figure). Kaplan-Meier estimated survival rate at Day +100 in the autograft group was 80% (95% CI: 72%-85%) overall, 67% (95% CI: 53%-77%) for those with MOD, and 88% (95% CI: 80%-93%) for those without MOD (Figure).Adverse events (AEs) occurred in 74% of allograft patients (in 77% of the MOD subgroup) and 53% of autograft patients (in 64% of the MOD subgroup). Hemorrhage and hypotension were more common post-allograft (31% and 13%, respectively) than post-autograft (17% and 7%). Treatment-related AEs (TRAEs), as determined by investigators, occurred in 21% of allograft patients (22% with MOD) and 20% of autograft patients (30% with MOD); most common (≥2%, either transplant group) were pulmonary hemorrhage (allograft, 5%; autograft, 3%), gastrointestinal hemorrhage (allograft, 3%; autograft, 1%), and epistaxis (allograft, 2%; autograft, 2%). TRAEs leading to discontinuation were more frequent post-allograft (13%) than post-autograft (10%); most common (≥2%) were pulmonary hemorrhage (allograft, 4%; autograft, 3%) and gastrointestinal hemorrhage (allograft, 2%; autograft, 0.6%). TRAEs leading to death occurred in 3% of the allograft group and 0.6% of the autograft group; most common (≥1%) was pulmonary hemorrhage (allograft, 1%; autograft, 0.6%).ConclusionIn this post hoc analysis of T-IND transplant groups, Day +100 survival rates in both allograft and autograft patients with VOD/SOS, with and without MOD, were consistent with prior defibrotide studies. Taken together, the current results support the overall efficacy and safety profile of defibrotide in patients with VOD/SOS after either allogeneic or autologous HSCT. For both allogeneic and autologous transplant groups, the higher survival rates in the subgroups of patients without vs those with MOD (reinforced by 95% CIs that did not cross) indicate that further study is warranted to determine the impact of treatment earlier in the course of VOD/SOS.Support: Jazz Pharmaceuticals. [Display omitted] DisclosuresRichardson:Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Oncopeptides AB: Membership on an entity's Board of Directors or advisory committees. Kernan:Gentium: Other: NAK received grants from Gentium during the conduct of the study, and her research was supported by The National Cancer Institute of the National Institutes of Health under award number P30 CA008748; the content is solely the responsibility of the author . Ryan:Celator/Jazz: Employment, Equity Ownership. Hume:Jazz Pharmaceuticals, Inc.: Employment, Other: stock options. Tappe:Jazz Pharmaceuticals, Inc.: Employment, Other: stock options. Grupp:Adaptimmune: Consultancy; Jazz Pharmaceuticals: Consultancy; University of Pennsylvania: Patents & Royalties; Novartis Pharmaceuticals Corporation: Consultancy, Other: grant.

Reparative effect of super active platelet combined with allogeneic bone for large bone defects.

In clinical practice, autologous bone transplantation is usually used to treat large-scale bone defects. However, autologous bone can cause complications such as secondary injury to patients, the scarcity of autografts. In this study, the study of using super active platelet lysate (sPL) and allogeneic bone to treat the 15mm long bone defect in right radius of rabbits, and provide an experimental basis for the next step of clinical bone defect treatment. The critical-size defect of New Zealand white rabbits was made and divided into three groups: autologous bone group, allogeneic bone group, and sPL group. They were euthanized 1, 2, and 3months after the operation, perform imaging and histological observation on the repair of bone defect area. The results showed that there were varying degrees of new bone in the bone defect. CT data showed that the bone defect repair rate and new bone mass in each group increased month by month (P<.05). Bone tissue (BV) and bone tissue to the total volume (BV/TV, %) in the sPL group > allogeneic bone group, autologous bone group > allogeneic bone group, with statistical significance (P<.05). Compared with the allogeneic bone group, the sPL group can significantly promote the healing of bone defects, enhance the bone density after fracture healing. The repair effect after 3months was similar to that of the autogenous bone group. The use of allogeneic bone and sPL therapy may become part of a comprehensive strategy for tissue engineering to treat bone defects.

Comparison of Allogeneic Stem Cell Transplant and Autologous Stem Cell Transplant in Refractory or Relapsed Peripheral T-Cell Lymphoma

Hematopoietic stem cell transplant (HSCT) is an advisable option for refractory or relapsed peripheral T-cell lymphoma (R/R-PTCL), but whether allogeneic HSCT or autologous HSCT is more beneficial is unknown. To compare the effectiveness and safety of allogeneic HSCT vs autologous HSCT in patients with R/R-PTCL. A systematic search of the PubMed, Embase, the Cochrane Central Register of Controlled Trials, Wanfang, and China National Knowledge Infrastructure databases with the search items refractory or relapsed peripheral T-cell lymphoma, ASCT/autologous stem-cell transplantation, allo-HSCT/allogeneic stem-cell transplantation, therapeutic effect, and treatment was conducted for articles published from January 12, 2001, to October 1, 2020. After duplicate and irrelevant publications were discarded, 329 were ineligible according to the inclusion (clinical trials or retrospective studies with >10 samples) and exclusion criteria (articles without overall survival [OS], progression-free survival [PFS], and transplantation-related mortality [TRM]). Thirty trials were included in the meta-analysis. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data on study design, individual characteristics, and outcomes were extracted. All statistics were pooled by applying a random-effects model. The prespecified main outcomes were OS, PFS, and TRM. Of 6548 articles, data extracted from the 30 studies (including 880 patients who underwent allogeneic HSCT and 885 who underwent autologous HSCT) were included in this meta-analysis. In the allogeneic HSCT group, a 3-year OS of 50% (95% CI, 41%-60%) and PFS of 42% (95% CI, 35%-51%), a 5-year OS of 54% (95% CI, 47%-62%) and PFS of 48% (95% CI, 40%-56%), and a 3-year TRM of 32% (95% CI, 27%-37%) were observed. In the autologous HSCT group, a 3-year OS of 55% (95% CI, 48%-64%) and PFS of 41% (95% CI, 33%-51%), a 5-year OS of 53% (95% CI, 44%-64%) and PFS of 40% (95% CI, 24%-58%), and a 3-year TRM of 7% (95% CI, 2%-23%) were observed. In this systematic review and meta-analysis, OS and PFS were similar in the allogeneic HSCT and autologous HSCT groups; however, allogeneic HSCT was associated with specific survival benefits among patients with R/R-PTCL.

Tissue-Engineered Hydroxyapatite Bone Scaffold Impregnated with Osteoprogenitor Cells Promotes Bone Regeneration in Sheep Model.

Managing massive bone defects, a great challenge to orthopaedics reconstructive surgery. The problem arise is the supply of suitable bone is limited with many complications. Tissue-engineered hydroxyapatite bone (TEHB) scaffold impregnated with osteoprogenitor cells developed as an alternative to promote bone regeneration. This animal protocol has been approved by Universiti Kebangsaan Malaysia Animal Ethical Committee. The TEHB scaffold prepared from hydroxyapatite using gel casting method. A total of six adolescent female sheep were chosen for this study. Later, all the sheep were euthanized in a proper manner and the bone harvested for biomechanical study. Bone marrow was collected from iliac crest of the sheep and bone marrow stem cells (BMSCs) isolated and cultured. BMSCs then cultured in osteogenic medium for osteoprogenitor cells development and the plasma collected was seeded with osteoprogenitor cells mixed with calcium chloride. Bone defect of 3cm length of tibia bone created from each sheep leg and implanted with autologous and TEHB scaffold in 2 different groups of sheep. Wound site was monitored weekly until the wound completely healed and conventional X-ray performed at week 1 and 24. Shear test was conducted to determine the shear force on the autologous bone and TEHB scaffold after implantation for 24weeks. All of the sheep survived without any complications during the study period and radiograph showed new bone formation. Later, the bone harvested was for biomechanical study. The highest shear force for the autologous group was 13MPa and the lowest was 5MPa while for the scaffold group, the highest was 10MPa and the lowest was 3MPa. Although, proximal and distal interface of autologous bone graft shows higher shear strength compared to the TEHB scaffold but there is no significant difference in both groups, p value > 0.05. Histologically in both proximal and distal interface in both arms shows bone healing and woven bone formation. TEHB scaffold impregnated with osteoprogenitor cells has the potential to be developed as a bone substitute in view of its strength and capability to promote bone regeneration.

Oncologic Safety of Autologous Fat Grafting after Breast Cancer Surgical Treatment: A Matched Cohort Study.

Autologous fat grafting has been an increasingly popular procedure for remodeling the breast of patients undergoing breast cancer surgery. This study's objective was to investigate whether autologous fat grafting is associated with a higher risk of disease recurrence in the context of late breast reconstruction for patients diagnosed with breast cancer who have undergone either breast-conserving surgery or mastectomy. A retrospective matched cohort study was performed in a single tertiary health care center. Data were collected from 42 patients formerly treated for breast cancer who underwent the first session of autologous fat grafting between August of 2007 and June of 2016. A total of 126 patients with similar features, who did not undergo autologous fat grafting, were individually matched at a 1:3 ratio with the autologous fat grafting group. The primary endpoint was locoregional recurrence. Secondary outcomes were rates of local and distant recurrences, disease-free survival, and overall survival. At a mean follow-up of 65 months after fat grafting, no significant differences were found between the lipofilling and control groups for locoregional recurrence (7.1 percent versus 6.3 percent; p = 0.856), local recurrence (7.1 percent versus 5.6 percent; p = 0.705), distant recurrence (14.3 percent versus 7.9 percent; p = 0.238), disease-free survival (21.4 percent versus 19.0 percent; p = 0.837), and overall survival (14.3 percent versus 7.1 percent; p = 0.181). No evidence of increased risk in any of the survival outcomes was identified. Lipofilling seems to be a safe procedure for breast reconstruction after surgical treatment of breast cancer. Therapeutic, III.

Postoperative Epidural Fibrosis Prevention: Which Is Better-Autologous Fat versus Gelfoam.

Study DesignProspective, randomized study of 100 patients with prolapsed intervertebral disc with an average of 12- to 18-month follow-up postoperatively.PurposeTo compare the role of Gelfoam and autologous fat in the prevention of postoperative epidural fibrosis (EF) after lumbar spine surgery.Overview of LiteratureEF is a possible sequelae of lumbar disc surgery. Different treatments and surgical strategies have been attempted to prevent postoperative fibrosis without providing consistent long-term results.MethodsThe study was conducted on 100 adult patients. The patients were randomly allocated into two groups of 50 patients each: group A, autologous fat group, and group B, Gelfoam group. The postoperative follow-up was conducted at intervals of 6 weeks, 3 months, 6 months, and 12 months. Both groups were evaluated clinically (Oswestry Low Back Pain Disability Questionnaire [ODI], Visual Analog Scale [VAS], Straight Leg Raising Test [SLRT]) and radiologically (using Ross grading by contrast magnetic resonance imaging [MRI]) for development of radicular pain and hence EF.ResultsBased on the analysis, improvement in mean values of ODI score, VAS score, and SLRT were found to be statistically significant postoperatively at intervals of 6 weeks, 3 months, 6 months, and 12 months when compared individually in both groups. However, improvement was greater in the autologous fat group than in the Gelfoam group. Based on contrast-enhanced MRI, the number of patients who developed EF was smaller in the autologous fat group than in the Gelfoam group.ConclusionsIn the present study, on clinical and radiological assessment, we conclude that both groups prevent radicular pain and postoperative EF individually but relatively autologous fat was found to be more effective than Gelfoam in the prevention of EF and hence radicular pain.

Outcome after hematopoietic stem cell transplantation in patients with extranodal natural killer/T-Cell lymphoma, nasal type: A French study from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

We evaluated the outcome of 65 French patients with Extranodal NK/T-cell lymphoma, nasal type (ENKTL) undergoing hematopoietic stem cell transplantation (HSCT) (19 allogeneic and 46 autologous). Fifty-four patients (83%), most of which receiving L-asparaginase (L-aspa) containing regimens (81%), achieved complete or partial response at time of HCST. After a median follow-up of 79.9months, 4-years progression-free survival (PFS) and overall survival (OS) were similar in both autologous and allogeneic groups (PFS: 34% vs. 26%, p=.12 and OS: 52% vs. 53%, p=.74). Response status at HSCT was the major independent prognostic factor on survival (OS: HR: 4.013 [1.137; 14.16], p=.031 and PFS: HR: 5.231 [1.625; 16.838], p=.006). As compared to control patients receiving chemotherapy and/or radiotherapy containing regimens only, upfront HSCT did not improve the outcome of responder patients, including those treated by L-aspa. However, it tends to provide survival benefit for relapsed patients with initial high-risk clinical features who achieved second remission. Whereas the place of HSCT in upfront therapy has still to be clarified, these data confirm that HSCT should be considered for consolidation in selected patients with relapsed ENKTL. Based on a large non Asian ENKTL cohort since the L-aspa era, this study provides some insight into the survival patterns of ENKTL patients with HSCT in the Western hemisphere and may give future direction for the next clinical trial design.

Pleurodesis with an Autologous Blood Patch in the Treatment of Persistent Air Leak after Lung Resection

Objective To evaluate the efficacy and risks of autologous blood patch pleurodesis in patients with persistent air leak(PAL)after lung resection. Methods A total of 97 patients with PAL after lung resection in Beijing Shijitan Hospital from October 2014 to October 2019 were retrospectively reviewed,including 53 treated by autologous blood patch pleurodesis and 44 by the conventional way.The therapeutic effect,adverse reactions and complications were analyzed. Results All the patients with PAL were cured with autologous blood patch pleurodesis.Most air leaks(81.1%)ceased within 48 hours after treatment,and the left 18.9% patients got cured after a repeat.The mean tube retention time and the mean in-hospital stay were 8.4 days and 10.0 days in the autologous blood patch pleurodesis group and 13.5 days and 15.3 days in the conventional treatment group.A prolonged drainage time(P=0.00)and in-hospital stay(P=0.00)were observed in the conventional treatment group.No severe complications were observed except two patients developed slight fever and cutaneous emphysema. Conclusion In our experience,the autologous blood patch pleurodesis is an effective way with low risk of adverse reactions in the treatment of PAL.

644 Bioprinted skin integrates into full-thickness porcine wounds and supports healthy skin repair by modulating inflammation and tissue remodeling

The purpose of this study is to assess the feasibility and efficacy of autologous bioprinted skin in the treatment of full-thickness porcine wounds. We hypothesize that bioprinted skin constructs will improve wound healing by modulating inflammation, skin remodeling, and epidermal maturation. Porcine keratinocytes, fibroblasts, pre-adipocytes, and endothelial cells were isolated, expanded, suspended in bioink, and bioprinted to form a biomimetic tri-layer skin construct. 5x5cm excisional full-thickness wounds were then treated with bioprinted skin from autologous or allogeneic cells, skin autograft or allograft, hydrogel, or left without treatment. Digital planimetry of photographs taken over 28 days demonstrated improved wound closure in autologous bioprinted skin treated wounds. Histological analysis confirmed these results and showed improved epidermal maturity, less fibrosis, and more normal collagen organization in the bioprinted autologous skin group. Hydrogel and skin allograft groups had increased total wound serum proteins and proteolytic activity, with an associated increase in inflammatory and proteolytic gene expression compared to the bioprinted autograft. These findings suggest that treatment of full-thickness porcine wounds with hydrogel generates inflammatory wound healing and protease activity. Alternatively, bioprinted constructs composed of autologous skin cells embedded in hydrogel induce healthy, pro-remodeling protease activity, resulting in normal wound healing. Taken together, our results suggest that bioprinted autologous skin rapidly integrates into the wound to support skin regeneration and confirms the feasibility of skin bioprinting technology for clinical treatment of full-thickness wounds in human patients.