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Introduction: Clinical scoring systems, such as the Hemophilia Joint Health Score (HJHS), and imaging modalities (radiographs and magnetic resonance) are important instruments for the evaluation of hemophilic joint health. However, they are semi-quantitative scales, exhibit ceiling effects, and may not capture subtle dynamic changes of intra-articular structures. We developed the Joint tissue Activity and Damage Exam (JADE) protocol to quantitatively evaluate the extent of hemophilic arthropathy at the tissue level, individualize management, and objectively assess the efficacy of novel therapies. JADE is an economical, convenient, and radiation free point-of-care musculoskeletal ultrasound protocol. JADE uses quantitative numerical measurements (1/10th of millimeter) for osteochondral alterations, cartilage thickness and soft tissue expansion in hemophilic joints and is validated per international OMERACT guidelines for pathological tissue recognition with high intra/inter-rater and inter-operator reliability. Furthermore, we previously reported JADE association with clinical and functional joint assessments at baseline for patients with hemophilia. Herein, we examined JADE protocol ability to capture tissue changes over time and their associations with HJHS, a clinical joint assessment. We assumed the regression lines for joint HJHS on each JADE measurement at each time point would lie parallel to each other. Verifying this assumption would enhance JADE protocol validity and provide confidence that it could be used to monitor hemophilic arthropathy progression by quantifying specific tissue abnormalities. Methodology: We recruited adult patients (≥ 18 years) with congenital hemophilia and arthropathy in a prospective study performed at 3 sites in North America. We assessed joint HJHS and JADE parameters for each patient (n=44; 264 joints [bilateral elbows, ankles, and knees]) at study entry (baseline), at ~12-18 months (midpoint), and ~24-36 months (final). JADE measurements included osteochondral alterations, cartilage thickness, and soft tissue expansion at sentinel positions for each joint. The association between joint HJHS and each JADE variable was examined by fitting random intercept models with outcomes transformed to ensure normal residuals. We examined the assumption of parallel regression lines for the three time points by applying a test for homogeneity of slopes. If no difference between slopes was found, then we applied an analysis of covariance to test whether the lines for each joint were coincident. Results: Joint HJHSs deteriorated measurably during the study period, reflecting clinically worsening arthropathy over time. Importantly, clinical assessment of deterioration for the elbows, knees, and ankles was associated with JADE measurements that changed in the expected direction, namely increased length of osteochondral alterations, decreased cartilage thickness, and increased soft tissue expansion. As an example, figure 1 shows the association of deteriorating HJHS and osteochondral alterations for elbows, knees, and ankles at baseline, midpoint, and final visits. In each graph, the regression lines were similar in shape. Lines were parallel for the elbow (midpoint vs baseline: p = 0.185; final vs baseline: p = 0.398), and the ankle (midpoint vs baseline: p = 0.225; final vs baseline: p = 0.293). But, the assumption of parallel lines was rejected for the knee (midpoint vs baseline: p = 0.047; final vs baseline: p = 0.024). Conclusions: This study demonstrates a tight association between JADE direct ultrasonographic measurements and clinical deterioration (HJHSs) during several assessments over 3 years. Importantly, the associations are consistent across time, despite clinical joint health examinations and ultrasound measurements being performed at three different centers by multiple providers, with long intervals between assessments. Altogether, these findings constitute a major milestone for the clinical relevance validity of the JADE protocol as a precise instrument for tissue-specific alterations measurements over time. These findings support the use of the JADE protocol to monitor the progression of hemophilic arthropathy longitudinally, permit prompt identification of potentially reversible osteochondral and/or soft tissue changes, and study early interventions that could curb arthropathic progression. Disclosures Kruse-Jarres: F. Hoffmann-La Roche Ltd: Speakers Bureau; Biomarin, Chugai Pharmaceutical Co., CSL Behring, CRISPR Therapeutics, Genentech, Inc.: Honoraria; CSL Behring, Genentech, Inc., Spark: Research Funding; Biomarin, Chugai Pharmaceutical Co., CSL Behring, CRISPR Therapeutics, Genentech, Inc.: Consultancy. Steiner:Uniqure: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi/Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees. Quon:Bayer: Honoraria; Orthopaedic Institute for Children: Current Employment; Biomarin: Honoraria, Speakers Bureau; Novo Nordisk: Honoraria, Speakers Bureau; Bioverativ/Sanofi: Honoraria, Speakers Bureau; Genentech, Inc./F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Octapharma: Honoraria; Shire/Takeda: Speakers Bureau. von Drygalski:Biomarin: Honoraria; Hematherix LLC: Membership on an entity's Board of Directors or advisory committees, Other: co-founder; Uniqure: Honoraria; Bioverativ/Sanofi: Honoraria, Research Funding; Pfizer: Research Funding; Novo-Nordisk: Honoraria; Takeda: Honoraria.

Cutaneous T-cell lymphomas (CTCL) represent up to 80% of extranodal non-Hodgkin Lymphomas, the most common being Mycosis Fungoides (MF) with or without its leukemic stage Sezary Syndrome and Primary cutaneous CD30+ T-cell lymphoproliferative disorders. Prognosis for advanced stages is poor, with 5-year survival 40-70% for patients with advanced skin stages, and 15-40% for those with extracutaneous involvement and CD30+ transformed CTCL. The disease is considered incurable, and most patients will undergo at least two different lines of therapy, and up to 36% undergo at least four different lines due to a short duration of remissions. Local and systemic therapies are provided stepwise based on extension and aggressive histologic features. Systemic options for advanced-stages include bexarotene, methotrexate, interferon, histone deacetylates inhibitors, extracorporeal photopheresis (ECP), antibody drug conjugates, and systemic single or multiple agent chemotherapies. The longest response durations were reported after allogeneic stem cell transplantation in contrast to autologous transplantation and conventional chemotherapy. Disease status prior to transplant is a major predictive of better outcome, but it is typically difficult to achieve strong pretransplant remissions. Some suggested utilizing total electron beam radiation but this can predispose the patient to more infection due to skin injury. We had the case of a patient with refractory CD30+ transformed CTCL who successfully achieved clinical remission in anticipation for transplant with a novel outpatient regimen including high-dose methotrexate with limited toxicity. Table 1 shows the regimen that was employed to achieve a complete cutaneous remission, allowing progression to haploidentical allogeneic stem cell transplantation. We designed this for a 58-year-old male, previously treated over a period of 12 years for skin rashes that ultimately were diagnosed as CTCL/MF: C6D4+, CD8+ and CD25-, CD30- and positive T-cell receptor gene rearrangement. Sezary cell count was 2%, and there was no evidence of systemic involvement. Sequential therapies were employed by dermatology, including topical clobetasol, weekly oral (PO) methotrexate (MTX), ECP and bexarotene up to 150mg/m2 PO twice a day, but disease progressed to skin tumor stage, biopsy confirmed. Multiple additional therapies followed including phototherapy and interferon, but the disease began progressing aggressively by fall 2017 when hematology became involved. Again there was no evidence of systemic disease, and the Sezary count was 0%, but skin disease progressed, with ~80% skin involvement, some biopsy proved to be CD30+ with large cell transformation. The patient was started on Brentuximab Vedotin (BV) 1.8mg/Kg intravenous (IV) every 21 days (Q21D) and after 5 cycles developed major resolution of most tumor lesions, but developed progression of residual lesions that were biopsy proven to be MF, CD30- with no large cell transformation. Bendamustine 90mg/m2 IV on day 1 and day 2 Q21D was added to BV regimen for 2 cycles with further progression so was discontinued. The patient was referred for allogeneic transplant, but a strong remission was desired prior to proceeding, and we therefore designed the regimen in Table 1 as a novel approach to allow transplant. The patient achieved a complete cutaneous clinical response after cycle 2 and went on to receive a third cycle, after which he proceeded in July 2018 to haploidentical allogenic transplantation conditioned with Fludarabine, total body irradiation and post-transplant cyclophosphamide. Etoposide IV and MTX PO are both approved as systemic therapies of disease as per National Comprehensive Cancer Network Guidelines, although no reports of use of IV MTX or in combination with Etoposide have been found on literature. High-dose IV MTX is given as inpatient as requires close toxicity surveillance, hydration, urine alkalization and MTX serum level monitoring in parallel to folinic acid rescue by protocol. Side effect profile was limited to mild nausea controlled on ondansetron PO and no evidence of renal or liver toxicity was found. Surveillance and supportive care were successfully provided as an outpatient as per Table 1. This exemplifies an effective outpatient regimen with low toxicity and significant cost reduction that successfully achieved remission in anticipation for transplantation. Disclosures No relevant conflicts of interest to declare.