Citations

AbstractT‐lymphoblastic leukemia/lymphoma (T‐ALL/LBL) accounts for approximately 15% of pediatric and 25% of adult ALL. While the underlying frequency of KMT2A (MLL) gene rearrangements has been identified in approximately 4‐8% of T‐ALL/LBL cases, a paucity of literature is available to characterize further the KMT2A rearrangements in pediatric/young adult T‐ALL/LBL. A 10‐year retrospective review was performed to identify KMT2A rearrangements in specimens sent for T‐ALL/LBL fluorescence in situ hybridization studies in patients under the age of 30 years. Of 806 T‐ALL/LBL FISH studies performed on unique individuals, 27 (3.3%) harbored KMT2A rearrangements. Nineteen patients were male and eight were female (M:F ratio, 2.4:1) with ages ranging from 1 to 20 years (mean 12, median 12). Of the 27 cases, nine (33%) had KMT2A/MLLT1 fusions, eight (30%) had KMT2A/AFDN fusions, two (7%) had KMT2A/ELL fusions, and one (4%) had a KMT2A/MLLT10 fusion. In addition, five (19%) had KMT2A rearrangements with unidentified gene fusion partners and two (7%) had 3’KMT2A deletions. Our results indicate that MLLT1 and AFDN account for the majority (63%) of KMT2A gene partners in pediatric/young adult T‐ALL/LBL, while no KMT2A/AFF1 or KMT2A/MLLT3 fusions were observed despite their common identification in B‐ALL and acute myeloid leukemia, respectively. In addition to diagnostic and prognostic value, detecting specific KMT2A fusions may also be of clinical importance in the era of targeted therapies.

TPS8584 Background: The first-line standard of care for the majority of patients (pts) with extensive-stage small-cell lung cancer (ES-SCLC) is platinum-based chemotherapy with etoposide, but survival outcomes remain poor (median OS, < 1 year) despite initial response rates ranging from 50-70%. Atezolizumab (atezo), an anti–PD-L1 mAb, prevents the binding of PD-L1 with its receptors PD-1 and B7.1 and restores anticancer T-cell activity. Tolerable safety with promising durability of response has been shown with atezo in pts with ES-SCLC: confirmed ORR was 6% (n = 1/17 [partial response]; DOR of 7 mo) by RECIST v1.1 and 24% by immune-related response criteria (irRC; n = 4/17, with 2 pts on atezo for ≥ 12 mo). Preliminary data also indicate the potential synergy between atezo and platinum-based chemotherapy in NSCLC, whereby durable responses may translate into improved survival over atezo alone. IMpower133 (NCT02763579), a global, Phase I/III, randomized, multicenter, double-blinded, placebo-controlled trial will evaluate the efficacy and safety of 1L atezo + carboplatin + etoposide compared with placebo + carboplatin + etoposide in treatment-naive pts with ES-SCLC. Methods: Pts with measurable (RECIST v1.1) ES-SCLC, who have ECOG PS 0-1 and no prior systemic anticancer treatment, are eligible for the study. Exclusion criteria include untreated CNS metastases and history of autoimmune disease. The study requires submission of tumor tissue, but pts will be enrolled regardless of biomarker status. Pts will be stratified by sex, ECOG PS and presence of treated brain metastases. Eligible pts will be randomized 1:1 to receive four 21-day cycles of atezo (1200 mg IV) or placebo in combination with carboplatin (AUC 5 mg/mL/min IV, d 1) and etoposide (100 mg/m2 IV, d 1-3), followed by maintenance therapy with atezo or placebo until PD per RECIST v1.1. Pts can continue with treatment until persistent radiographic PD, symptomatic deterioration or unacceptable toxicity. Co-primary endpoints are investigator-assessed PFS per RECIST v1.1 and OS. Secondary efficacy endpoints include investigator-assessed ORR and DOR. Safety and tolerability will also be assessed. Approximately 400 pts will be enrolled. Clinical trial information: NCT02763579.

AbstractIntroductionReconstruction of abdominal wall defects with enterocutaneous fistulas (ECF) remains challenging. The purpose of this report is to describe a single‐stage approach using combined microscopic enterolysis, pedicle seromuscular bowel flaps, mesh, fasciocutaneous, and myocutaneous flaps.MethodsBetween 1990 and 2016 a retrospective review identified a total of 18 patients with an average age of 39 years (ranging 26–59 years). Thirteen cases were associated with trauma, four were complication of previous mesh repair, and one was after an aortic dissection. Average diameter of defect size was 22 cm (ranging 20–24 cm). Surgical technique involved enterolysis using microscope magnification, a pedicle seromuscular bowel flap to reinforce the bowel anastomosis, mesh, musculocutaneous, and fasciocutaneous flaps to reconstruct the abdominal wall.ResultsFifteen patients required rotational flaps with an average skin paddle area of 442.7 cm2 (ranging 440 cm2–260 cm2) and 10 patients required a serosal patch with an average length of 5 cm (ranging 4–6 cm). Complications included three wound dehiscence and one abdominal wall bulging. Flap survival was 100%. The majority of patients (12 out of 18) were able to resume normal activities, and the remaining (n = 6) were able to resume most activities. Functional outcome as assessed by 36‐Item Short Form Survey (SF‐36) physical function component questionnaire at 18–24 months follow up was 67.8% (ranging from 59 to 72%). Mean length of hospital stay was 2.2 weeks (ranging 1.4–2.7 weeks). Mean follow‐up was 24 months (ranging 22–26 months) with clinical examination.ConclusionMicroscopically assisted intra‐abdominal dissection with resection of diseased bowel, replacement with well‐vascularized tissue at the anastomosis site in, and reinforcement with mesh combined with pedicle musculocutaneous and fasciocutaneous flaps may be an alternative when other local reconstructive options have failed.

Background Lower extremity salvage following significant soft tissue loss can be complicated by lack of recipient vessel for free tissue transfer. We describe our experience in lower limb salvage for patients with no recipient vessels with the use of pedicle, free and cable bridge flaps. Methods A retrospective review from 1985 to 2017 of patients undergoing lower limb salvage using a contralateral pedicle cross leg (PCL) flaps, free cross leg (FCL) flaps, or free cable bridge (FCB) flaps was conducted. Demographics, etiology of the reconstruction, type of flap used, donor-site vessels, defect size, operating time, time of pedicle division, length of hospital stay, time to ambulation, and complications were analyzed. Results A total of 53 patients (48 males and 5 females) with an average age of 35 years (range, 29–38 years) were identified. The etiology for the reconstruction was trauma in 52 patients and oncological resection in 1 patient. There were 18 PCL, 25 FCL, and 10 FCB completed. The recipient vessels for all flaps were the posterior tibial artery and vein. The average operating room times for PCL, FCL, and FCB flaps were 4, 9, and 10 hours, respectively. The average length of hospital stay was 5 weeks and average time to ambulation was 4 weeks. The average follow-up time was 7.5 years (range, 3–12 years). Complications encountered were hematoma (six), prolonged pain (six), total flap loss (two), reoperation (five), and infection (four). Limb salvage rates were 96.2%. Conclusion When ipsilateral limb vessels are not available, and other reconstructive options have been exhausted, cross leg flaps can be a viable option for limb salvage in the setting of extensive defects.