In our previous SMC NB-2004 study of patients with high-risk neuroblastomas, which incorporated total-body irradiation (TBI) with second high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), the survival rate was encouraging; however, short- and long-term toxicities were significant. In the present SMC NB-2009 study, only TBI was replaced with 131I-meta-iodobenzylguanidine (MIBG) treatment in order to reduce toxicities. From January 2009 to December 2013, 54 consecutive patients were assigned to receive tandem HDCT/auto-SCT after nine cycles of induction chemotherapy. The CEC (carboplatin + etoposide + cyclophosphamide) regimen and the TM (thiotepa + melphalan) regimen with (for metastatic MIBG avid tumors) or without (for localized or MIBG non-avid tumors) 131I-MIBG treatment (18 or 12 mCi/kg) were used for tandem HDCT/auto-SCT. Local radiotherapy, differentiation therapy with 13-cis-retinoic acid, and immunotherapy with interleukin-2 were administered after tandem HDCT/auto-SCT. Fifty-two patients underwent the first HDCT/auto-SCT and 47 patients completed tandem HDCT/auto-SCT. There was no significant immediate toxicity during the 131I-MIBG infusion. Acute toxicities during the tandem HDCT/auto-SCT were less severe in the NB-2009 study than in the NB-2004 study. Late effects such as growth hormone deficiency, cataracts, and glomerulopathy evaluated at 3 years after the second HDCT/auto-SCT were also less significant in the NB-2009 study than in NB-2004 study. There was no difference in the 5-year event-free survival (EFS) between the two studies (67.5 ± 6.7% versus 58.3 ± 6.9%, P = 0.340). Incorporation of high-dose 131I-MIBG treatment into tandem HDCT/auto-SCT could reduce short- and long-term toxicities associated with TBI, without jeopardizing the survival rate. ClinicalTrials.gov NCT03061656

Background: Mesenchymal stem cells (MSCs) are multi-potent non-hematopoietic progenitor cells possessing an immune-regulatory function, with suppression of proliferation of activated lymphocytes. In this study, adult living donor kidney transplantation (LDKT) recipients were given MSCs derived from the donor bone marrow to evaluate the safety and the feasibility of immunological changes related to the intra-osseous injection of MSC into the bone marrow. Methods: MSCs were derived from negative HLA cross-match donors. Donor bone marrow was harvested 5 weeks prior to KT. At the time of transplantation, 1 x 10⁶ cell/kg of donor MSC was directly injected into the bone marrow of the recipient’s right iliac bone. Patients’ clinical outcomes, presence of mixed chimerism by short tandem repeat polymerase chain reaction, analysis of plasma FoxP3 mRNA and cytokine level, and mixed lymphocyte reaction (MLR) were performed. Results: Seven patients enrolled in this study and received donor MSC injections simultaneously with LDKT. The median age of recipients was 36 years (32 ~ 48). The number of HLA mismatches was 3 or less in 5 and more than 3 in 2. No local complications or adverse events such as hypersensitivity occurred during or after the injection of donor MSC. There was no graft failure, but the biopsy-proven acute rejections were observed in 3 recipients during the follow-up period controlled well with steroid pulse therapy (SPT). The last serum creatinine was a median of 1.23 mg/dL (0.83 ~ 2.07). Mixed chimerism was not detected in the peripheral blood of the recipients at 1 and 8 week of post-transplantation. Donor-specific lymphocyte or T cell proliferation and Treg priming responses were observed in some patients. Plasma level of IL-10, a known mediator of MSC-induced immune suppression, increased in the patients with Treg induction. Conclusion: Donor MSC injection into the iliac bone at the time of KT was feasible and safe. A possible correlation was observed between the induction of inhibitory immune responses and the clinical outcome in the MSC-kidney transplanted patients. Further research will be performed to evaluate the efficacy of MSC injection for the induction of mixed chimerism and subsequent immune tolerance in KT.

A percolation network of silver nanoflowers dramatically increased the thermal conductivity (42.4 W m⁻¹K⁻¹) in soft polyurethane-matrix thermal interface materials.

This study analyzed factors related to allograft fibrosis in clinically stable pediatric liver transplantation patients. Pediatric patients who underwent liver transplantation from January 1997 to January 2008 and further underwent 10-year protocol biopsies were examined. Grades of inflammation and fibrosis were classified based on Banff criteria and the Liver Allograft Scoring (LAF) system, respectively. Risk factors for fibrosis were analyzed using logistic regression. Sixty-six patients with no clinical signs of chronic liver disease were included. Forty-one patients out of 66 (62.1%) had certain stage of allograft fibrosis. More than five events with aminotransferase >50 U/L was a risk factor for a LAF score 1–2 portal fibrosis (OR = 3.156, CI 1.059–9.410, P = 0.039). More than five events with aminotransferase >100 U/L was a risk factor for LAF score 2 portal fibrosis (OR = 13.978, CI 2.025–97.460, P = 0.007) and LAF score 1–2 sinusoidal fibrosis (OR = 4.897, CI 1.167–20.548, P = 0.030). Positive autoantibody (OR = 3.298, CI 1.039–10.473, P = 0.043) and gamma-glutamyl transferase 60 U/L (OR = 6.201, CI 1.096–35.097, P = 0.039) were related to sinusoidal fibrosis with LAF score of 1–2 and 2, respectively. Experience of post-transplantation lymphoproliferative disease was related to LAF score 1–2 portal fibrosis (OR = 7.371, CI 1.320–41,170, P = 0.023) and LAF score 1–2 centrolobular fibrosis (OR = 8.822, CI = 1.378–56.455, P = 0.022). Our results indicate that liver fibrosis is common in patients with no clinical signs of graft deterioration and repeated elevation of aminotransferases, positive autoantibodies, elevated gamma-glutamyl transferase and experience of post-transplantation lymphoproliferative disease are suspicious signs for fibrosis.

Background: This retrospective study aimed to evaluate overall survival and the risk factors for mortality among Korean pediatric liver transplantation (LT) patients using data from two national registries: the Korean Network Organ Sharing (KONOS) of the Korea Centers for Disease Control and Prevention and the Korean Organ Transplantation Registry (KOTRY). Methods: Prospectively collected data of 755 pediatric patients who underwent primary LT (KONOS, February 2000 to December 2015; KOTRY, May 2014 to December 2017) were retrospectively reviewed. Results: The 1-, 5-, 10-, and 15-year survival rates were 90.6%, 86.7%, 85.8%, and 85.5%, respectively, in KONOS, and the 1-month, 3-month, 1-year, and 2-year survival rates were 92.1%, 89.4%, 89.4%, and 87.2%, respectively, in KOTRY. There was no significant difference in survival between the two registries. Multivariate analysis identified that body weight ≥6 kg (p <0.001), biliary atresia as underlying liver disease (p = 0.001), and high-volume center (p < 0.001) were associated with better survival according to the KONOS database, while hepatic artery complication (p < 0.001) was associated with poorer overall survival rates according to the KOTRY database. Conclusion: Long-term pediatric patient survival after LT was satisfactory in this Korean national registry analysis. However, children with risk factors for poor outcomes should be carefully managed after LT.