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Background: The preoperative number of dislocations has been previously proved to be a major factor influencing the results after Bankart repair with more preoperative dislocations correlated with higher recurrence rates and more reoperations. This could possibly be because of the lower quality of the tissue repaired during the procedure after multiple dislocations. On the other hand, the Latarjet procedure does not “repair” but rather reconstructs and augments the anterior glenoid. Purpose/Hypothesis: The main objective was to report the clinical outcomes of patients undergoing a Latarjet procedure after 1 dislocation versus multiple (≥2) dislocations. The hypothesis was that the preoperative number of dislocations would not influence clinical results. Study Design: Cohort study; Level of evidence, 3. Methods: Patients older than 18 years who had undergone a primary Latarjet procedure for shoulder instability with at least 2 years of follow-up were included. Three different techniques were used: a mini-open technique using 2 screws, an arthroscopic technique using 2 screws, and an arthroscopic technique using 2 cortical buttons. Patients were evaluated and answered a questionnaire to assess the number of episodes of dislocation before surgery, the time between the first dislocation and surgery, recurrence of the dislocation, revision surgery, the Walch-Duplay score, the Simple Shoulder Test score, and the visual analog scale (VAS) score for pain. Results: A total of 308 patients were included for analysis with a mean follow-up of 3.4 ± 0.8 years. Of that, 83 patients were included in the first-time dislocation group and 225 in the recurrent dislocation group. At last follow-up, the rates of recurrence and reoperation were not significantly different between groups: 4.8% in the first-time dislocation group versus 3.65% in the recurrent dislocation group and 6.1% versus 4.0%, respectively. The overall Walch-Duplay scores at last follow-up were also comparable between the 2 groups, 67.3 ± 24.85 and 71.8 ± 25.1, even though the first-time dislocation group showed a lower pain subscore (15.0 ± 8.6 vs 18.0 ± 7.5; P = .003). The VAS for pain was also significantly higher in the first-time dislocation group compared with the recurrent dislocation group (1.8 ± 2.3 vs 1.2 ± 1.7; P = .03). Conclusion: The number of episodes of dislocation before surgery does not affect postoperative instability rates and reoperation rates after the Latarjet procedure. However, patients with first-time dislocations had more postoperative pain compared with patients with recurrent dislocations before surgery.

Abstract Introduction Right ventricular (RV) size informs about prognosis and need for pulmonary valve replacement in patients with repaired tetralogy of Fallot (rTOF). Cardiac magnetic resonance (CMR) is considered the reference standard for measurement of RV volumes. Despite known limitations for RV evaluation, 2D transthoracic echocardiography (TTE) remains the primary and most available imaging modality in the rTOF population. Purpose To determine which TTE RV size parameters best correlate with CMR-derived indexed RV end-diastolic (RVEDVi) and end-systolic (RVESVi) volumes in the rTOF population. We sought to determine the best TTE measurement thresholds to predict normal RV volume (RVEDVi ≤110 mL/m2) and significant RV dilatation by CMR (RVEDVi ≥150ml/m2). Method We retrospectively enrolled all rTOF patients followed at a single-center between 2010 and 2018 who had both TTE and CMR exams performed within a 12-month interval. All TTE exams were reviewed by an observer measuring RV areas, RV inlet and RV outlet at end-diastole and end-systole. Analyses of CMR studies were performed by 3 observers who measured RV area, RV inlet, RV outlet and RV volumes at end-diastole and end-systole. Correlations between TTE and CMR parameters were performed using Pearson correlation coefficients. Using the TTE RV parameters with the strongest correlation with CMR, we subsequently determined thresholds to predict a CMR RVEDVi ≤110ml/m2 and ≥150ml/m2 using ROC analysis. Results We enrolled 130 patients (59 women [45%], mean age 43±12.8 years). Median age at TOF repair was 4 [3–6] years; 18 patients (14%) had subsequent pulmonary valve replacement. Median interval between TTE and CMR exams was 114 [59–239] days. There were significant correlations between all TTE parameters and CMR RVEDVi. TTE indexed RV end-diastolic area (RVEDAi) most strongly correlated with CMR RVEDVi (r=0.73, p<0.0001). All TTE RV parameters significantly correlated with CMR RVESVi but indexed RV end-systolic area had the strongest correlation (r=0.77, p<0.0001). ROC analysis performed to predict RVEDVi of ≤110ml/m2 and ≥150ml/m2 using TTE RVEDAi revealed areas under the curve of 0.86±0.04 and 0.90±0.03, respectively. A TTE RVEDAi ≤17cm2/m2 predicted a normal CMR RV volume (≤110ml/m2) with a sensitivity of 90% and a specificity of 74%. A TTE RVEDAi ≥19cm2/m2 predicted a CMR RVEDVi ≥150 mL/m2 with a sensitivity of 93% and a specificity of 76%. Conclusion In rTOF patients, both diastolic and systolic TTE RV area best correlate with CMR-derived RV end-diastolic and end-systolic volumes. A cut-off value of TTE RVEDAi of 19cm2/m2 is 93% sensitive and 76% specific to predict a CMR RVEDVi ≥150ml/m2. Simple RV size measurement using TTE may help inform the need and frequency of CMR evaluations in rTOF patients.

Abstract BACKGROUND: Patients with TD lower-risk (LR)-MDS relapsed or refractory to ESA have limited treatment options. Imetelstat is a first-in-class telomerase inhibitor that targets cells with short telomere lengths and active telomerase, characteristics observed in some MDS patients. IMerge is an ongoing global study of imetelstat in RBC TD patients with LR-MDS (IPSS Low or Int-1). In the first 32 patients enrolled, 8-week TI rate was 34%, with 24-week TI of 16%, and HI-E of 59%. The most frequently reported adverse events were reversible grade ≥3 cytopenias (Fenaux et al EHA 2018 Abstr S1157). Higher response rates were observed in patients (n=13) who were LEN and HMA naïve without del(5q). We report here results in an additional 25 LEN and HMA naïve patients without del(5q), with longer term follow-up of the 13 initial patients meeting the same criteria. METHODS: IMerge is a phase 2/3 trial (NCT02598661) that includes LR-MDS patients with a high transfusion burden (≥4 units / 8 weeks) who are relapsed/refractory to ESA or have sEPO >500 mU/mL. The additional 25 were required to be LEN and HMA naïve and lack del(5q). Imetelstat 7.5 mg/kg was administered IV every 4 weeks. In addition to the key endpoints noted above, secondary endpoints include safety, time to and duration of TI. Biomarkers are also being explored, including telomerase activity, hTERT, telomere length, and genetic mutations. RESULTS: Overall, for the 38 LEN/HMA naïve and non-del(5q) patients, median age was 71.5 years and 66% were men. 63% of patients were IPSS Low and 37% Int-1. Median prior RBC transfusion burden was 8.0 (range 4-14) U, and 71% had WHO 2008 RARS or RCMD-RS. 9/37 (24%) patients with evaluable sEPO levels had baseline level >500 mU/mL. As of July 2018, with a median follow-up of 25.8 months for the initial 13 patients, and 5.2 months for the 25 recently included patients, the 8-week RBC-TI rate was 37% (14/38). Durability of 24-week TI responses was demonstrated, with a median duration of 10 months and the longest ongoing response now >2 years. Among the patients achieving durable TI, all showed a Hb rise of ≥3.0 g/dL compared to baseline during the transfusion-free interval. Response rates were similar in RARS/RCMD-RS (33% [9/27]) and other patients (27% [3/11]), and those with baseline EPO levels >500 mU/mL (33% [3/9]) and ≤500 mU/mL (32% [9/28]). Reversible grade ≥3 neutropenia and thrombocytopenia were each reported in 58% of the patients. Liver function test (LFT) elevations were mostly grade 1/2. Reversible grade 3 LFTelevations were observed in 3 (8%) patients on study. An independent Hepatic Review Committee deemed the observed LFT elevations were not imetelstat-related hepatic toxicities. SUMMARY / CONCLUSIONS: In this cohort of 38 non-del(5q) LR-MDS patients with a high RBC transfusion burden who were ESA relapsed/refractory and naïve to LEN/HMA, single-agent imetelstat yielded a TI rate of 37%, with a median duration of 10 months and limited side effects. Durable responses were characterized by transfusion independence >24 weeks and accompanied by Hb rise. Updated data will be presented. Disclosures Steensma: Takeda: Consultancy; Syros: Research Funding; Otsuka: Membership on an entity's Board of Directors or advisory committees; Onconova: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Kura: Research Funding; Janssen: Consultancy, Research Funding; H3 Biosciences: Research Funding; Celgene: Research Funding; Amphivena: Membership on an entity's Board of Directors or advisory committees; Acceleron: Consultancy. Platzbecker:Celgene: Research Funding. Van Eygen:Janssen: Consultancy, Research Funding; Roche: Research Funding; Amgen: Research Funding. Raza:Kura Oncology: Research Funding; Onconova: Research Funding, Speakers Bureau; Celgene: Research Funding; Novartis: Speakers Bureau; Geoptix: Speakers Bureau; Janssen: Research Funding; Syros: Research Funding. Santini:Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; AbbVie: Membership on an entity's Board of Directors or advisory committees; Otsuka: Consultancy; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Research Funding. Germing:Celgene: Honoraria, Research Funding; Janssen: Honoraria; Novartis: Honoraria, Research Funding. Font:Celgene: Membership on an entity's Board of Directors or advisory committees. Samarina:Janssen: Research Funding. Díez-Campelo:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Bussolari:Janssen: Employment, Equity Ownership. Sherman:Janssen: Employment, Equity Ownership. Sun:Janssen: Employment, Equity Ownership. Varsos:Janssen: Employment, Equity Ownership. Rose:Janssen: Employment, Equity Ownership. Fenaux:Roche: Honoraria; Otsuka: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding.

Abstract Introduction: Donor T cell chimerism is tested frequently early after allogeneic hematopoietic cell transplantation (HCT). However, the predictive ability of testing this early after HCT, i.e. at day +30 or day +60, has not been well described, outside of smaller single center studies. Herein, we evaluate the correlation of early donor T cell chimerism with clinical outcomes of overall survival (OS) and relapse in patients undergoing HCT for various hematological malignancies. Methods: We identified patients who received HCT with 8/8 matched unrelated donors at our center between 2007 and 2016 and obtained the clinical data retrospectively. Chimerism studies were included for patients who had testing done at day+30 and/ or day +60. Chimerism is tested using PCR based technique. Due to limited variability in chimerism levels <100% donor chimerism, a cut-off of 100% was used for analysis. Hence, patients were divided into those who achieved full donor chimerism in CD3 fraction (100%) and those in whom CD3 donor chimerism was < 100% at the respective time points. Clinical outcomes evaluate for this abstract were OS and time to relapse. Univariate and multivariate Cox proportional hazard regression models were used using variables of interest, the later adjusted for age at HCT, use of ATG, conditioning regimen and disease risk index (DRI). Results: Baseline patient and HCT data: There were 209 patients who met the selection criteria of which 4 died within 30 days from HCT and hence, were not included in the analysis. Among the 205, 87 (42%) were women and median age at HCT was 55 (range, 18 - 74) years. The hematological malignancy diagnosis was acute myeloid leukemia (AML)/ myelodysplastic syndrome (MDS) in 112 (55%), acute lymphoblastic leukemia (ALL) in 35 (17%), chronic leukemias in 13 (6%), lymphomas in 13 (6%) and myeloproliferative neoplasm in 20 (10%); with DRI being very high in 9 (5%), high in 53 (27%), intermediate in 120 (60%) and low in 17 (9%) patients. Myeloablative conditioning was used in 81 (40%) and reduced intensity conditioning in 124 (60%). Graft versus host disease prophylaxis used was calcineurin inhibitor with methotrexate of mycophenolate in all patients while anti-thymocyte globulin was used in 125 (61%) patients. All patients received a peripheral blood graft. Outcomes: Median follow-up for all included patients was 615 (range, 30 - 3147) days. At day +30, 138 patients had achieved 100% donor CD3 chimerism of 189 patients in whom this data was available (73%) while at day +60, 131 (76%) out of 173 had 100% donor CD3 chimerism. In the univariate model, CD3 donor chimerism level at day +30 as well as day +60, was not predictive of OS (HR 1.5, 95% CI 0.82 - 2.9; p = 0.18 for day +30, HR 1.8, 95% CI 0.81 - 4.0, p = 0.15 for day +60). As for time to relapse, CD3 chimerism did not significantly affect the risk of relapse at these time points (HR 0.43, 95% CI 0.17 - 1.1, p = 0.08 for day +30; HR 0.55, 95% CI 0.18 - 1.6, p = 0.28 for day +60). In the multivariate model also, after adjustment as described above, CD3 at day +30 or at day +60 was not significantly associated with the risk of OS or time to relapse (Figure 1). Kaplan Meier curves for OS for CD3 chimerism at day +30 and day +60 are shown in Figure 2. Conclusions: In this study, T cell chimerism as early as day +30 or day +60 does not seem to predict OS or relapse in patients undergoing HCT for various hematological malignancies. Given the limitations of a smaller retrospective design, this must be validated in a larger study, possibly using registry data. If these findings are indeed confirmed, then the practice of testing chimerism early and frequently, that adds additional expense to the overall cost of HCT, must be reconsidered. Disclosures Palmer: Novartis: Research Funding.

Abstract Background: Guadecitabine SC (SGI-110) is a dinucleotide next generation HMA resistant to degradation by cytidine deaminase resulting in extended in vivo exposure to its active metabolite decitabine. A Phase 1 established 60 mg/m2 QDx5 as the biologically effective dose (BED), and 90 mg/m2 QDx5 as the Maximum tolerated dose (MTD) in MDS patients given in 28-day cycles (Issa et al, 2015, Lancet Oncology). Phase 2 is conducted to evaluate dose response between the BED and MTD in both untreated MDS patients, and patients previously treated with other HMAs. M ethods: Int, or HR MDS, and CMML patients who were either treatment-naïve (TN) or relapsed/refractory to other HMAs (r/r) were randomized to either 60 mg/m2 or 90 mg/m2 QDx5 every 28 days. Efficacy was evaluated by the clinical responses of CR, PR, marrow CR (mCR), and Hematological Improvement (HI) based on the International Working Group Criteria 2006, as well as transfusion-independence, and overall survival (OS). Adverse events (AEs) were graded by the CTCAE v4 criteria. Results: The study completed target enrolment with 102 patients: 53 r/r MDS, and 49 TN MDS. Fifty three patients were randomized to 60 mg/m2 and 49 patients to 90 mg/m2 QDx5 with a median follow up of 3.2 years (IQR 2.8-3.5 years). Median age was 72 and 71 years for r/r and TN MDS respectively. Most baseline patient characteristics were well balanced between the 2 treatment dose groups except that more CMML patients were randomized to the 60 mg/m2 group (28%) vs. 14% in the 90 mg/m2 group, and more patients with baseline BM blasts >5% were in the 90 mg/m2 group (67%) vs. 38% in the 60 mg/m2 group. Most patients were RBC transfusion-dependent at baseline (57%). In the r/r MDS cohort, most patients (58%) received their last HMA treatment <3 month before enrolment, and most of them received ≥6 months of prior HMA treatment (77%). Median number of treatment cycles was 5 for both r/r and TN MDS (range 1-37 in r/r MDS and 1-49 in TN MDS). In the TN MDS cohort CR was achieved in 11 (22%) of patients with no major difference between the 2 dose groups (19% in the 60 mg/m2 group vs 27% in the 90 mg/m2 group). Overall CR+mCR was achieved in 18 patients (37%) in TN MDS patients and median OS was 23.4 months. In the r/r MDS cohort, CR was achieved in 4% of patients in each of the 2 dose groups. Overall CR+mCR in the r/r MDS cohort was achieved in 17 patients (32%), with a median duration of response of 7.9 months, and median OS of 11.7 months. No significant difference in response or OS between the 2 dose groups was observed. In patients who were RBC transfusion-dependent at baseline, transfusion independence for at least 8 weeks was achieved in 42% of TN MDS, and 15% in r/r MDS patients. In the overall population of 102 TN and r/r MDS patients there were no major differences in OS based on DNMT3A or TET2 mutation status while patients with TP53 mutations had worse median OS (7.4 months) compared to those without TP53 mutations (22.6 months). Other baseline prognostic factors for worse OS were BM blasts >5%; RBC transfusion-dependence; IPSS High Risk; and ECOG Performance Status of >1. Overall incidence of Grade ≥3 AEs regardless of relationship to treatment was reported in 83 vs. 96% for 60 and 90 mg/m2 dose groups respectively. There was a slightly higher but non-significant difference in Grade ≥3 thrombocytopenia (57 vs 41.5%); neutropenia (51 vs 39.6%); febrile neutropenia (43% vs 32%); and pneumonia (32.7 vs. 26.4%) for the 90 mg/m2 compared to 60 mg/m2 dose group. Early 30, 60, and 90-day all-cause mortality was observed in 0, 3.7%, and 5.7% in the 60 mg/m2 dose group respectively; and in 2%, 4%, and 12% in the 90 mg/m2 dose group respectively. Conclusions: Guadecitabine at both dose groups is a well-tolerated novel HMA with clinical activity in the treatment of both TN and r/r Int and HR MDS, and CMML patients. In TN MDS patient CR rate of 22% and median OS of 23.4 months compare well with first generation HMA efficacy (Fenaux et al, 2009, Lancet Oncology). Activity in r/r MDS who previously failed prior HMAs is particularly promising (CR+mCR in 32% of patients with median duration of response and overall survival of almost 8 and 12 months respectively). A phase 3 trial (ASTRAL-3) of guadecitabine vs Physician Treatment Choice in r/r MDS and CMML patients previously treated with azacitidine or decitabine is actively enrolling (ClinicalTrials.gov ID: NCT02907359). Disclosures Ritchie: NS Pharma: Research Funding; Bristol-Myers Squibb: Research Funding; Novartis: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Celgene: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau; Pfizer: Consultancy, Research Funding; ARIAD Pharmaceuticals: Speakers Bureau; Astellas Pharma: Research Funding. Savona:Boehringer Ingelheim: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kropf:Celegene: Consultancy; Takeda: Consultancy. Daver:Pfizer: Consultancy; Sunesis: Consultancy; Pfizer: Research Funding; ImmunoGen: Consultancy; ARIAD: Research Funding; Novartis: Research Funding; Incyte: Research Funding; Otsuka: Consultancy; Novartis: Consultancy; Karyopharm: Consultancy; Alexion: Consultancy; Incyte: Consultancy; Karyopharm: Research Funding; BMS: Research Funding; Kiromic: Research Funding; Daiichi-Sankyo: Research Funding; Sunesis: Research Funding. Jabbour:Pfizer: Consultancy, Research Funding; Novartis: Research Funding; Abbvie: Research Funding; Takeda: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding. Yee:Celgene, Novartis, Otsuka: Membership on an entity's Board of Directors or advisory committees; Agensys, Astex, GSK, Onconova, Genentech/Roche: Research Funding. Stock:Jazz Pharmaceuticals: Consultancy. Griffiths:Alexion Inc.: Honoraria, Research Funding; Astex/Otsuka Pharmaceuticals: Honoraria, Research Funding; Celgene, Inc: Honoraria, Research Funding; Novartis, Inc.: Research Funding; Pfizer, Inc.: Research Funding. Podoltsev:Astex Pharmaceuticals: Research Funding; LAM Therapeutics: Research Funding; Sunesis Pharmaceuticals: Research Funding; Genentech: Research Funding; Boehringer Ingelheim: Research Funding; Daiichi Snakyo: Research Funding; Astellas Pharma: Research Funding; Pfizer: Research Funding; Celator: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding. Berdeja:Genentech: Research Funding; Bluebird: Research Funding; Amgen: Research Funding; Novartis: Research Funding; Glenmark: Research Funding; Takeda: Research Funding; Bristol-Myers Squibb: Research Funding; Teva: Research Funding; Sanofi: Research Funding; Poseida Therapeutics, Inc.: Research Funding; Celgene: Research Funding; Janssen: Research Funding. Naim:Astex Pharmaceuticals, Inc.: Employment. Hao:Astex Pharmaceuticals, Inc.: Employment. Azab:Astex Pharmaceuticals, Inc.: Employment. Roboz:Orsenix: Consultancy; Roche/Genentech: Consultancy; Roche/Genentech: Consultancy; Otsuka: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Jazz Pharmaceuticals: Consultancy; Argenx: Consultancy; Sandoz: Consultancy; Celltrion: Consultancy; Bayer: Consultancy; Orsenix: Consultancy; Pfizer: Consultancy; Astex Pharmaceuticals: Consultancy; Daiichi Sankyo: Consultancy; Sandoz: Consultancy; Daiichi Sankyo: Consultancy; Novartis: Consultancy; Janssen Pharmaceuticals: Consultancy; Cellectis: Research Funding; Eisai: Consultancy; Celgene Corporation: Consultancy; Jazz Pharmaceuticals: Consultancy; Celgene Corporation: Consultancy; Janssen Pharmaceuticals: Consultancy; Eisai: Consultancy; Novartis: Consultancy; Otsuka: Consultancy; Argenx: Consultancy; Celltrion: Consultancy; Astex Pharmaceuticals: Consultancy; Aphivena Therapeutics: Consultancy; AbbVie: Consultancy; Aphivena Therapeutics: Consultancy; AbbVie: Consultancy; Cellectis: Research Funding.

Abstract Introduction: Primary refractory and early relapsed acute myeloid leukemia (RR-AML) continue to pose a therapeutic challenge. Salvage therapy treatment regimens for refractory and relapsed disease are not standardized but include the commonly-used mitoxantrone, etoposide, and cytarabine (MEC) and cladribine, cytarabine, filgrastim, and mitoxantrone (CLAG-M). Previous studies have suggested a potential benefit of CLAG-M, and therefore we performed an analysis of consecutive patients selected to receive either CLAG-M or MEC as salvage therapy for RR-AML. Methods: The study included 150 consecutive patients with RR-AML who received either CLAG-M or MEC between 09/01/2009 and 12/31/2017. Patients were identified through a pharmacy database based on use of mitoxantrone. Baseline disease and patient-related characteristics and clinical outcomes including allogeneic transplantation (ASCT) were obtained by systematic review of EMR. Overall survival (OS) and progression free survival (PFS) were estimated according to the Kaplan Meier method and log-rank test was used to compare outcomes between patients who received either of the two regimens. Results: There were 150 consecutive treated patients with RR-AML included in this analysis, 34 patients received CLAG-M and 116 patients received MEC. The median age was 57 years (18-76), and, and 52% were male. Forty-seven (31%) were treated for early relapsed disease (<6 months after successful induction), 17% (>6 months after induction), and the remainder had primary refractory disease (mean number of induction regimens was 1.8, range 1-6). AML risk was defined by cytogenetic criteria. There were a predominance of intermediate-risk subtypes at 47% (71/150) and followed by high-risk at 37% (55/150). Overall CR/CRi rates for CLAG-M and MEC were 74% (23/31) and 58% (63/108) in patients eligible for analysis (p=0.18). The median follow-up from relapse was 23.5 months (1-76). The median OS was 9.5 months for CLAG-M and 10.0 months for MEC (HR=0.88, 95%CI=0.54-1.41, p=0.59). In total, 76 patients (51%) were able to proceed to ASCT following salvage therapy with either CLAG-M or MEC. Among transplant recipients 56% (19/34) and 49% (57/116) were treated with CLAG-M and MEC, respectively. Median OS after ASCT was 13.0 months for CLAG-M and 31.0 months for MEC (HR=1.76, 95%CI=0.87-3.56, p=0.12). The median OS for refractory AML was 13.0 and 66.0 months for CLAG-M and MEC recipients, respectively (HR=0.92, 95%CI=0.46-1.84, p=0.24). Median OS for those with early relapse was 12.0 months for CLAG-M and 10.0 months for MEC (HR=0.69, 95%CI=0.22-2.11, p=0.51). Lastly, among those who had late relapse, median OS was 9.0 and 48.0 months for CLAG-M and MEC, respectively (HR=17.6, 95%CI=1.57-198, p<0.001). A univariate analysis was performed to investigate the impact of factors associated with OS, including treatment, age, gender, whether they proceeded to ASCT, cytogenetic risk type, and donor source. ASCT was associated with significant improvement in both PFS (HR=0.24, 95%CI=0.16- 0.37, p<0.001) and OS (HR=0.26, 95%CI=0.17-0.40, p<0.001) in this cohort. Age greater than 65 was associated with worse PFS (HR=1.02, 95%CI=1.00-1.03, p=0.04) but not OS (HR=1.01, 95%CI=1.00-1.03, p=0.06) after controlling for other variables including the impact of ASCT. Discussion: Despite a lower 30-day induction mortality we did not identify significant differences in outcomes among patients selected to receive CLAG-M vs. MEC. There was a statistically significant improvement in survival in patients who had late relapses and were treated with MEC, and a trend towards improvement in OS of those treated with MEC who proceeded to ASCT. As expected, ASCT was associated with significant improvement in OS in this cohort, and our results strongly support the use of ASCT as consolidation of remission after relapse for AML. Our data suggests that MEC may be a superior regimen, in particular including those with late relapse. Figure. Figure. Disclosures Foran: Agios: Research Funding; Xencor, Inc.: Research Funding. Al-Kali:Novartis: Research Funding. Palmer:Novartis: Research Funding.

Abstract Introduction Myelofibrosis (MF), both primary myelofibrosis (PMF) and post essential thrombocytosis/polycythemia vera myelofibrosis (post ET/PV-MF), are chronic myeloproliferative neoplasms that are incurable with standard medical therapy. The only potential curative therapeutic modality remains allogeneic stem cell transplant (ASCT), but the optimum conditioning regimen has yet to be defined and may vary due to pre-ASCT factors such as age, donor source, and comorbidities. In the past, traditional myeloablative (MA) regimens have proven toxic. Reduced intensity conditioning (RIC) regimens have generally become the accepted standard of care for patients with PMF or Post PV/ET MF in need of ASCT, but with the potential for increase in relapse especially for high risk disease. The optimal conditioning regimen has yet to be defined. The regimen of Fludarabine, BCNU, and melphalan (FBM) is considered a reduced toxicity regimen that may afford the benefit of reduction in relapse without increase in toxicity and may “bridge the gap” between MA and RIC especially in older patients. Patients with MF have high inflammatory cytokine levels which may act as mediators of MF symptom burden and may further aggravate mediators of acute GVHD, which is one of the most frequent and severe complications of ASCT. Selection of conditioning regimen and GVHD prophylaxis are keys to MF transplant outcomes. We report here the results of 16 patients who received conditioning with FBM with rATG (FBM-A) with PMF and post PV/ET MF. Methods We conducted a retrospective review of all patients from October 2009 to November 2012 with PMF or post ET/PV-MF who underwent an ASCT with FBM-A. Patient demographic and transplant data were analyzed from a comprehensive database. The use of such data for reporting purpose was approved by the Mayo Clinic Arizona Institutional Review Board. Overall survival was estimated using Kaplan-Meier. Results There were 16 patients analyzed who had PMF or post PV/ET MF or overlap syndromes. The median follow-up of surviving patients is 20.4 months (range 8 months – 46 months). The median age was 60 (range 47-68 yrs) with 56% of patients being ≥ 60yrs. There were 8 males and 8 females. The JAK2 V617F mutation was present in 64% of patients. 86% were high risk according to the DIPSS system with 14% being intermediate-2 risk. None of the patients underwent splenectomy prior to transplant. The median HCT-CI score was 1.5 with 6 (38%) of the patients having an HCT-CMI ≥3. Donors were related in 10 patients (8 matched, 2 mismatched at 1 antigen) and unrelated in 6 (matched, n=3, 1-antigen mismatch, n=3). GVHD prophylaxis consisted of tacrolimus, MMF, and ATG 2.5 – 5.0 mg/kg. The cumulative incidence of acute GVHD grades III-IV was 15.3% at 6 months, and the cumulative incidence of NIH-defined moderate-to-severe chronic GVHD was 25% at 2 years. No patient has relapsed, and no patient has developed graft failure. There have been 4 deaths, 3 from GVHD, and 1 from infection. Among the 3 patients who died from GVHD, all were unrelated donor transplants, and 2 were mismatched unrelated transplants. The 2-year Kaplan-Meier estimate of overall survival (OS) is 72% (95% CI, 45 – 91%). The cumulative incidence of TRM was 12.6% (95% CI 3.9%-34%) at 1 year. Conclusion The reduced-toxicity regimen of FBM-A in PMF, Post ET/PV MF and overlap syndromes appear to provide the benefit of an ablative regimen with the tolerance of a RIC. The 2-year overall survival of 72% in our series is encouraging in an older population of predominantly high-risk patients. Treatment failure was related predominately to GVHD, which continues to be a significant obstacle to better long-term outcomes, especially in unrelated and mismatched patients. Reduced toxicity ASCT conditioning regimens in the setting of MF warrant further investigation. Disclosures: Reeder: Celgene: Research Funding; Novartis: Research Funding; Millenium: Research Funding.

Abstract Abstract 4479 Background: In vivo T-cell depletion with antithymocyte globulin (ATG) is known to decrease the incidence of acute and chronic graft vs. host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). However, the detailed patterns of GVHD (incidence, severity, timing, and quality) after ATG-based conditioning have not been examined in large patient cohorts, and it is unknown whether they differ from those seen in patients who do not receive ATG during conditioning therapy. Patients and Methods: We analyzed the incidence and characteristics of acute and chronic GVHD, requirements for immunosuppressive therapy (IST) and survival in a cohort of 174 patients who underwent a first HCT for hematologic malignancy with ATG as a part of their conditioning regimen. The median age was 54 years (range 19–76); all but 5 pts received PBSC, and median follow-up of survivors was 16.9 months (range 3–70 months). Donors were matched related in 18% (n=32), matched unrelated in 44% (n=77), and mismatched unrelated in 37% (n=65). Conditioning regimens were myeloablative in 33% (n=57) and reduced intensity in 67% (n=117). Additional GVHD prophylaxis included tacrolimus in all patients combined with either methotrexate (42%) or MMF (58%). Results: The cumulative incidence of grade II-IV and III-IV acute GVHD at 100 days was 34% and 7%, respectively, with the median time of onset at 43 days (range 11–98 days) after transplant. Eleven patients (6.3%) required additional immunosuppressive treatment due to steroid refractory GVHD. Late/persistent acute GVHD without any evidence of chronic occurred in 25% of patients. NIH chronic GVHD developed in 25 patients, with a cumulative incidence of 24.4% at 2 years. Forty four percent of these patients were classified as classic chronic, and 56% as overlap. The onset of chronic GVHD was quiescent in 20 (80%), progressive in 3 (12%), and de-novo in 2 (8%) patients. The global severity was mild in 9 (36%), moderate in 11 (44%) and severe in 5 (20%) cases. The median time of onset for chronic GVHD was 185 days (range 99–763). In a multivariate analysis of factors predictive for development of chronic GVHD, the only factor associated with development of chronic GVHD was prior grade II-IV acute GVHD (HR 2.5, p =.03). The most common diagnostic organ was mouth (n=16), followed by skin (n=8) and eye (n=1). The median number of sites involved during the course of chronic GVHD was 4 (range 1–7), and the median number of systemic immunosuppressive agents for treatment was 2 (range 0–4). Among the 25 chronic GVHD patients, 5 have discontinued immunosuppression at a median time of 13.1 months (range 6–26) since the diagnosis of chronic GVHD. The cumulative incidence of discontinuation of IST was 23% at one year and 50% at two years. Three deaths in the overall cohort were attributed to complications related to acute (n=2) or chronic GVHD (n=1). At 2 years, the overall survival among all 174 pts was 62.4%, cumulative incidence of relapse was 23.1%, and non-relapse mortality was 22.7%. Conclusion: These data from a large, uniformly treated and graded, predominantly peripheral blood stem cell transplant recipient population, confirm that ATG decreases both the incidence and severity of acute and chronic GVHD. In particular, the rate of moderate to severe chronic GVHD is extremely low, resulting in minimal need for tertiary treatment and decreased duration of immunosupression. Disclosures: No relevant conflicts of interest to declare.