Acromioclavicular joint dislocation is a common shoulder injury, usually caused by direct violence on the shoulder. optimal treatment of type iii is still a hot discussion currently in orthopedic surgeons. With the advent of many flip-button techniques, Tightrope system and Endobutton system become popular techniques for reconstruction of coracoclavicular ligaments. the purpose of the study was to compare the clinical and radiological results between the two techniques. A retrospective casecontrol study was conducted in 60 patients with acute Rockwood III acromioclavicular joint dislocation. the two techniques conducted were open procedures using twin tail tightrope system (Group A, n = 30) and Endobutton system (Group B, n = 30). 60 patients were followed up at least two years. Surgical parameters including incision length, operation time and operative blood loss were analyzed. Functional outcomes were evaluated using the Constant-Murley Score. Radiological results were assessed based on coracoclavicular distance preoperatively, one day postoperatively, and at the final follow-up. 60 patients were followed up for at least 24 months (range 24 to 32). The incision length and operation time were shorter in Group A than that in Group B. The blood loss of surgery was significantly less in the Group A. There were no significant differences between the two groups regarding the Constant-Murley Score at the final follow-up. No significant differences were found in the coracoclavicular distance preoperatively, immediately postoperatively, and at the final follow-up. Both techniques offered satisfying functional outcomes, however the Tightrope system provided better surgical parameters.

Background Compared with the substantial efficacy of chimeric antigen receptor T-cell (CAR-T) therapy that has achieved in B-ALL, whether CAR-T therapy is effective and safe for patients with T-ALL is still being explored in early stage clinical trials. Here, we present outcomes from our phase 1 clinical trial of CD7-targeting CAR-T (CD7CAR) cells therapy for R/R T-ALL (NCT04572308). Methods Peripheral blood (PB) mononuclear cells were obtained by leukapheresis. T cells were separated and transduced with lentivirus. The second-generation CD7CAR is composed of an anti-CD7 single-chain antibody, a IgG4 hinge region, a CD28TM transmembrane domain, an intracellular co-stimulatory domain of 4-1BB and CD3ζ, and the truncated EGFR protein linked by T2A. All patients received intravenous fludarabine (30 mg/m 2/d) and cyclophosphamide (300 mg/m 2/d) for 3 days prior to CD7CAR infusion. Results Seventeen R/R T-ALL patients were enrolled between December 2020 and June 2021. Characteristics of patients are shown in Table 1. Data from 14 patients with a median age of 17 years (range: 3-42 years) were available for evaluation. The rest 3 patients were withdrawn from study within 14 days due to rapid disease progression. High-risk subtype patients enrolled including 1 with Ph-positive T-ALL and 3 with early T-cell precursor (ETP)-ALL. Seven of the 14 patients also had high-risk genotypes, namely SIL-TAL1, EZH2, TP53, RUNX1, BCR-ABL, JAK1 and JAK3. At enrollment, the median percentage of bone marrow (BM) blasts was 11.53% (range: 0.18%-65.03%), and 5 of 14 patients had extramedullary involvements, including optic nerve involvement (N=2), central nervous system leukemia (N=3), diffuse extramedullary involvements (N=2), and bulky lymph nodes in the neck (N=1). Patients were heavily pretreated with a median of 5 prior lines of therapies (range: 3-8 lines) and three relapsed from prior allogeneic hematopoietic stem cell transplantation (allo-HSCT). CD7CAR-T cells were 100% successfully manufactured with a transfection efficiency of 93.8% (range: 59.6%-99.9%). Twelve of 14 participants received bridging chemotherapy. A single dose of CD7CAR-T cells was infused to patients, with 2 receiving a low-dose (0.5x10 5 cells/kg), 11 receiving a medium dose (1-1.5x10 6 cells/kg) and 1 receiving a high-dose (2x10 6 cells/kg). By the data cutoff date (July 12, 2021), the median follow-up time was 105 days (range: 32-206 days, Fig.1A). By day 28 post infusion, 92.9% (13/14) of patients achieved complete remission (CR, N=4) or CR with incomplete hematological recovery (CRi, N=9) in their BM, with all 13 patients achieving minimal residual disease (MRD) negative CR/CRi. Additionally, 4/5 patients with extramedullary involvement also achieved extramedullary remission at a median of day 32 (range: 28-90 days) post infusion. Consolidation allo-HSCT was permitted at the treatment physician's discretion and the patient's preference. A total of 11/14 patients were bridged to consolidation allo-HSCT at a median of 57 days post CD7CAR infusion, of which 9 patients have remained MRD-negative CR/CRi. One patient who had allo-HSCT prior to CD7CAR infusion died following a second haplo-HSCT due to acute graft-versus-host disease. Of the other 3 patients who were not bridged to allo-HSCT, 1 patient relapsed on day 28 due to rapid disease progression after initial CRi on day 14. Thirteen of 14 patients experienced mild CRS (Grade ≤2). One patient had Grade 3 CRS. The median time to onset of CRS was 1 day (range: 0-11 days), with a median duration of 14 days (range: 3-25 days). Neurotoxicity (Grade 1) occurred in only 1 patient. After infusion, the median peak of CAR-T copy number was 2.38 ×10 5copies/µg DNA (range: 0.2-6.67 ×10 5 copies/µg DNA), which occurred on day 20 (range: 10-42 days, Fig.1B). Importantly, CD7CAR persisted well in PB at a median of 52.5 days (range:20-120 days) at last evaluation regardless of transplantation status. Maximum proportion of CD7CAR-T cells proliferation reached 84.95% by flow cytometry (Fig.1C). Conclusions Our results demonstrate that CD7CAR therapy is safe and highly effective in treating patients with heavily pretreated R/R T-ALL, including those with extramedullary involvements, a history of prior allo-HSCT or with high-risk subtypes. More patients and a longer observation time are needed to further evaluate the potential beneficial advantages and side effects of CD7CAR therapy for T-ALL patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Background T-cell lymphoblastic lymphoma is an aggressive hematological malignancy, often presenting with bulky mediastinal masses or diffuse extramedullary disease (EMD). There is evidence that T-LBL differs in various aspects from T-cell acute lymphoblastic leukemia in addition to differences in clinical presentation of diseases. To date, there are only a few clinical case reports of CAR-T therapy for T-LBL. Here, we explored the efficacy and safety of CD7-targeted CAR-T cells (CD7CAR) for R/R T-LBL in a phase I clinical trial (NCT04916860). Methods Eligible R/R T-LBL patients were enrolled between November 2020 and May 2021. Peripheral blood (PB) mononuclear cells were collected from either the donor (n=1) or patients (n=7) by leukapheresis. The CD7-CAR gene was obtained by gene synthesis and then ligated into a lentiviral vector by molecular cloning. We developed second-generation CAR-T cells with an intracellular co-stimulatory domain of 4-1BB and CD3ζ targeting CD7. Intravenous fludarabine (30 mg/m 2/d) and cyclophosphamide (300 mg/m 2/d) were given to all patients on Day -5 to Day -3 prior to CD7CAR infusion. Results Patient characteristics are summarized in Table 1. Eight R/R T-LBL patients were enrolled with a median age of 37 years (14-47 years) and a median of 5 prior lines of therapies (2-10 lines). Two patients had a history of central nervous system involvement. Two patients relapsed from a previous allogenic (N=1) or autologous (N=1) hematopoietic stem cell transplantation (HSCT). Four patients expressed high-risk genotypes including TP53, EZH2 and RUNX1. At enrollment, 7 patients had EMD relapse (diffuse involvement, N=5; bulky mediastinal masses, N=2). One patient had no EMD involvement at enrollment due to a prior palliative mediastinal radiotherapy, but relapsed with bone marrow (BM) blasts up to 87.27%. A total of 5/8 patients had BM blasts at enrollment with median BM blasts of 17%. Both patient- and donor-derived CD7CAR-T cells were successfully generated with a transfection efficiency of 86.55% (27%-98%). A single dose of CD7CAR-T cells was infused to patients at low dose (5x10 5 cells/kg, N=1), medium dose (1x10 6 cells/kg, N=6) or high dose (2x10 6 cells/kg, N=1). The median follow-up time was of 93 days (55-166 days) by July 18, 2021, the cutoff date. Following CD7CAR infusion, 5/5 patients who had prior BM blasts achieved minimal residual disease negative (MRD-) complete remission with incomplete hematologic recovery (CRi) on Day 28, among whom 3 had already achieved MRD- CRi on Day 14. The 3 patients who did not have BM blasts prior to CAR-T infusion maintained zero BM blasts post infusion. Of the 7 patients who had EMD involvements, 4 achieved EMD CR on Day 28, and 1 on Day 51. Of the 2 patients who had bulky mediastinal masses (~7 or 6 cm), 1 had partial response and 1 had stable disease on Day 28, respectively. Of all patients, 6 subsequently underwent allo-HSCT following CD7CAR-T infusion with a median time of 54 days (42-56 days), without relapse or progression. One patient with an allo-HSCT prior to CD7CAR infusion died after receiving a second haploidentical allo-HSCT due to acute graft-versus-host disease. The other 2 patients who did not receive a transplant were on Day 55 and 73 post CD7CAR infusion with ongoing remission by the cutoff date. Mild cytokine release syndrome (CRS, ≤Grade 2) was observed in 7/8 patients. Only 1/8 patient had Grade 3 CRS and Grade 1 neurotoxicity. The median onset of CRS was 1 day post infusion (0-15 days) with a median duration of 16 days (5-19 days). CD7CAR expansion in vivo occurred as early as 3.5 days (0-11 days) post infusion and reached a median peak of 2.07x10 5 copies/ug DNA (0.75-5.36 x10 5 copies/ug DNA) at a median of 19 days (13-28 days), and was still detectable up to the last follow-up, with a median duration of 50 days (26-120 days), as measured by qPCR (Figure.1). Conclusion Our clinical trial showed that CD7CAR-T cells derived either from the patients or the donor have a high initial efficacy and a good safety profile in R/R T-LBL patients. Initial high CR could be achieved both intramedullary and extramedullary in the majority of patients, even among those who harbored with high-risk features or had diffuse extramedullary lesions. However, patients with bulky mediastinal masses may require more than one-month time to achieve remission. Long-term observation and more patients are needed to further evaluate the safety and efficacy of CD7CAR. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.