Study DesignPreliminary clinical trial.PurposeTo determine the safety and initial efficacy of intradiscal injection of autologous platelet-rich plasma (PRP) releasate in patients with discogenic low back pain.Overview of LiteraturePRP, which is comprised of autologous growth factors and cytokines, has been widely used in the clinical setting for tissue regeneration and repair. PRP has been shown in vitro and in vivo to potentially stimulate intervertebral disc matrix metabolism.MethodsInclusion criteria for this study included chronic low back pain without leg pain for more than 3 months; one or more lumbar discs (L3/L4 to L5/S1) with evidence of degeneration, as indicated via magnetic resonance imaging (MRI); and at least one symptomatic disc, confirmed using standardized provocative discography. PRP releasate, isolated from clotted PRP, was injected into the center of the nucleus pulposus. Outcome measures included the use of a visual analog scale (VAS) and the Roland-Morris Disability Questionnaire (RDQ), as well as X-ray and MRI (T2-quantification).ResultsData were analyzed from 14 patients (8 men and 6 women; mean age, 33.8 years). The average follow-up period was 10 months. Following treatment, no patient experienced adverse events or significant narrowing of disc height. The mean pain scores before treatment (VAS, 7.5±1.3; RDQ, 12.6±4.1) were significantly decreased at one month, and this was generally sustained throughout the observation period (6 months after treatment: VAS, 3.2±2.4, RDQ; 3.6±4.5 and 12 months: VAS, 2.9±2.8; RDQ, 2.8±3.9; p<0.01, respectively). The mean T2 values did not significantly change after treatment.ConclusionsWe demonstrated that intradiscal injection of autologous PRP releasate in patients with low back pain was safe, with no adverse events observed during follow-up. Future randomized controlled clinical studies should be performed to systematically evaluate the effects of this therapy.

The aim of this study was to determine whether the level of circulating C-reactive protein (CRP) before treatment predicted overall disease-specific survival and local tumour control in patients with a sarcoma of bone. We retrospectively reviewed 318 patients who presented with a primary sarcoma of bone between 2003 and 2010. Those who presented with metastases and/or local recurrence were excluded. Elevated CRP levels were seen in 84 patients before treatment; these patients had a poorer disease-specific survival (57% at five years) than patients with a normal CRP (79% at five years) (p < 0.0001). They were also less likely to be free of recurrence (71% at five years) than patients with a normal CRP (79% at five years) (p = 0.04). Multivariate analysis showed the pre-operative CRP level to be an independent predictor of survival and local control. Patients with a Ewing’s sarcoma or chondrosarcoma who had an elevated CRP before their treatment started had a significantly poorer disease-specific survival than patients with a normal CRP (p = 0.02 and p < 0.0001, respectively). Patients with a conventional osteosarcoma and a raised CRP were at an increased risk of poorer local control. We recommend that CRP levels are measured routinely in patients with a suspected sarcoma of bone as a further prognostic indicator of survival. Cite this article: Bone Joint J 2013;95-B:411–18.

The aim of this study was to determine whether the tumor infiltrative growth pattern on magnetic resonance imaging (MRI) was associated with blood inflammatory markers (C-reactive protein; CRP and Neutrophil-lymphocyte ratio; NLR) and survival in patients with high-grade soft-tissue sarcoma (STS). The cohort for this retrospective study included 81 patients with a mean age of 63 years. The tumor depth was superficial or deep in 15 and 66 patients, respectively. The mean CRP and NLR were 1.31 mg/dL and 2.81, respectively. The assessment of a peripheral growth pattern which divided into three patterns on MRI was based on the largest midsection of the tumor. On MRI scans, diffuse-type, focal-type, and pushing-type growth patterns were observed in 18, 33, and 30 patients, respectively. Superficial high-grade STS were prone to show a focal-type pattern on MRI. There were no correlations between growth pattern type and clinicopathological factors such as age, sex, tumor size, and histological grade. However, the incidence of infiltrative growth was significantly higher in patients with elevated CRP (p = 0.0002). In multivariate analysis, growth pattern and CRP were independent prognostic factors for disease-specific survival, metastasis-free survival. Growth pattern was also related to local tumor control. There were significant associations between the tumor growth pattern and CRP levels in patients with high-grade soft-tissue sarcoma. An infiltrative growth pattern and elevated CRP may be associated with inferior disease-specific and metastasis-free survival rates in these patients. Therefore, careful post-treatment follow-up should be conducted in such patients.

Purpose: To determine, for patients with advanced or recurrent synovial sarcoma (SS) not suitable for surgical resection and resistant to anthracycline, the safety and efficacy of the infusion of autologous T lymphocytes expressing NY-ESO-1 antigen-specific T-cell receptor (TCR) gene and siRNA to inhibit the expression of endogenous TCR (product code: TBI-1301). Patients and Methods: Eligible Japanese patients (HLA-A*02:01 or *02:06, NY-ESO-1-positive tumor expression) received cyclophosphamide 750 mg/m2 on days −3 and −2 (induction period) followed by a single dose of 5×109 (±30%) TBI-1301 cells as a divided infusion on days 0 and 1 (treatment period). Primary endpoints were safety-related (phase I) and efficacy-related [objective response rate (ORR) by RECIST v1.1/immune-related RECIST (irRECIST); phase II]. Safety- and efficacy-related secondary endpoints were considered in both phase I/II parts. Results: For the full analysis set (N = 8; phase I, n = 3; phase II, n = 5), the ORR was 50.0% (95% confidence interval, 15.7–84.3) with best overall partial response in four of eight patients according to RECIST v1.1/irRECIST. All patients experienced adverse events and seven of eight patients (87.5%) had adverse drug reactions, but no deaths were attributed to adverse events. Cytokine release syndrome occurred in four of eight patients (50.0%), but all cases recovered with prespecified treatment. Immune effector cell-associated neurotoxicity syndrome, replication-competent retrovirus, and lymphocyte clonality were absent. Conclusions: Adoptive immunotherapy with TBI-1301 to selectively target NY-ESO-1-positive tumor cells appears to be a promising strategy for the treatment of advanced or recurrent SS with acceptable toxicity.