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2538 Background: Allogeneic HCT is a potentially curative therapy for many patients with AML that relies on a graft-versus-leukemia (GvL) effect. Patients who relapse after allogeneic HCT have a poor prognosis and few treatment options. Donor lymphocyte infusion (DLI) can achieve a GvL effect in some patients, however, efficacy is frequently associated with the development graft-versus-host disease (GVHD). There is a substantial need for treatment approaches that enhance the benefit of GVL while decoupling toxicities associated with GVHD. Methods: We report ongoing results from a first-in-human study (NCT04284228) of a non-genetically engineered, donor-derived adoptive cellular therapy product, NEXI-001, which contains multiple populations of CD8+ T cells that recognize different HLA 02.01-restricted peptides from the WT1, PRAME, and Cyclin A1 antigens. NEXI-001 contains T cell memory subtypes that combine anti-tumor potency with long-term persistence. Results: At the time of this analysis, 7 patients with relapsed AML after allogeneic HCT were enrolled. Five Patients were treated with single infusions of NEXI-001 at three different dose levels: 50, 100 and 200 million. Currently, the median follow-up is 5 months. Significantly, GVHD, cytokine release syndrome, neurotoxicity, or NEXI-001-related adverse events were not observed. NEXI-001 treatment resulted in reductions in red blood cell and platelet transfusions and increased donor chimerism. Decreases in myeloblasts in bone marrow and peripheral blood and reduction in the size of an extramedullary myeloid sarcoma were suggestive of an anti-leukemia effect (Table). Correlative studies indicate that NEXI-001 CD8+ cells undergo a rapid proliferation after infusion and are also associated with a robust hostlymphocyte recovery that occurs as quickly Day 3 after infusion. NEXI-001 infused CD8+T cells are detectable by multimer staining in peripheral blood of patients and proliferate over time. TCR sequencing analyses determined that infused NEXI-001 cells contain T cell clones that were undetectable in the peripheral blood of patients at baseline but were detected in blood and bone marrow and persist over time. Conclusions: NEXI-001 has the potential to enhance GvL effect without the associated toxicities of GVHD, cytokine release syndrome, and neurotoxicity. Due to these encouraging results, the trial will proceed with an evaluation of repeated NEXI-001 dosing Clinical trial information: NCT04284228. [Table: see text]

Pleural effusion is a known entity in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT); however, the incidence, risk factors, and morbidity-mortality outcomes associated with pleural effusions remain unknown. We retrospectively evaluated pleural effusions in 618 consecutive adult patients who underwent allogeneic HSCT from January 2008 to December 2013 at our institution. Seventy one patients developed pleural effusion at a median of 40 days (range, 1 - 869) post-HSCT with the cumulative incidence of 9.9% (95% CI, 7.7 - 12.5%) at 1 year. Infectious etiology was commonly associated with pleural effusions followed by volume overload and serositis type chronic GVHD. In multivariate analysis, higher comorbidity index (P = 0.03) and active GVHD (P = 0.018) were found to be significant independent predictors for pleural effusion development. Higher comorbidity index, very high disease risk index, ≤7/8 HLA matching, and unrelated donor were associated with inferior overall survival (OS) (P < 0.03). More importantly, patients with pleural effusion were noted to have poor OS in comparison to patients without pleural effusion (P

7546 Background: Haploidentical transplant (HIDT) with post-transplant cyclophosphamide (pCY) is being increasingly used because of the universal availability of donor and rapid graft acquisition time. Cytokine release syndrome (CRS) is one of the commonly occurring complications in this population. The information on the impact of CRS on the post-HIDT outcomes is limited. Methods: We retrospectively evaluated 91 patients who underwent HIDT between June 2012 and June 2019 for the onset and severity of CRS. CRS was graded per ASTCT guidelines. The primary objective was to compare RFS (relapse-free survival), NRM (non-relapse mortality), OS (overall survival) and GVHD in patients with no CRS, CRS grade 1-2 and 3-4. Results: All received peripheral blood stem cells and pCY/tacrolimus/mycophenolate as GVHD prophylaxis. Fifty-six (62%) received reduced intensity and 35 (38%) received full intensity conditioning regimen. Ten (10.9%) had no CRS, 74 (81.3%) developed grade 1-2 CRS and seven (7.7%) experienced grade 3-4 CRS. Median time to onset of CRS was one day post-transplant. The most common symptoms were fever (87%), fatigue (30%), nausea/vomiting (24%), rigors (24%), diarrhea (20%) and rash (11%). Fifteen (20%) with grade 1-2 and six (85%) with grade 3-4 CRS received tocilizumab. Day +100 cumulative incidence of grade III-IV acute GVHD for no CRS, grade 1-2 and grade 3-4 CRS was 0%, 2.7%, and 14.3%, respectively (P = 0.36). One-year cumulative incidence of chronic GVHD for no CRS, grade 1-2 and grade 3-4 CRS was 30%, 31.9% and 14.3%, respectively (P = 0.70). One-year NRM for no CRS, grade 1-2 and grade 3-4 CRS was 30%, 16.5%, and 57.1%, respectively (P = 0.002). One-year RFS for no CRS, grade 1-2 and grade 3-4 CRS was 48%, 63.4% and 28.6%, respectively (p = 0.03). OS at 1-year for no CRS, grade 1-2 and grade 3-4 CRS was 60%, 73.9%, and 28.6%, respectively (P = 0.008). Multivariable analysis revealed that grade 3-4 CRS was associated with significantly higher NRM (HR 5.54, P = 0.002), worse RFS (HR 3.41, P = 0.011) and worse OS (HR 4.91, P = 0.001). Conditioning regimen, degree of HLA match and disease risk index did not affect post-transplant outcomes and were not predictors for developing CRS. Conclusions: Our study showed that grade 3-4 CRS was associated with inferior post-transplant outcomes. However, no impact on acute or chronic GVHD was noted. Therefore, early recognition and prompt management of CRS may help improve outcomes.

7545 Background: Post-transplant cyclophosphamide (pCY) when given at 50mg/kg on day +3 and +4 in haploidentical donor transplants (HIDT) leads to considerable morbidity. Information on its toxicity and impact on outcomes is limited. Methods: We analyzed 91 patients (pt) undergoing HIDT with pCY to estimate incidence and risk factors of mucositis, hemorrhagic cystitis, renal and cardiac toxicities during the first 6 months after transplant and its impact on overall survival (OS). We compared these complications with 91 pt who were matched for age, disease, disease status at transplant, conditioning regimen and received 8/8 HLA-matched transplants without pCY (non-pCY cohort). Results: Fourteen pt (15%) in non-pCY and 28 (31%) in pCY experienced hypoxia requiring oxygen (p = 0.03). Ten pt (11%) in non-pCY and 21 (23%) in pCY developed clinically significant hypotension (p = 0.05). Day +100 cumulative incidence rate (CIR) of mucositis was 59.3% for non-pCY and 84.6% for pCY (p < 0.001). Seven pt (13%) in non-pCY cohort and 39 (51%) in pCY developed grade 3-4 mucositis (p < 0.001). Two pt (2%) in non-pCY and 22 (24%) in pCY developed gross hematuria (p = 0.05). Day +180 CIR of hemorrhagic cystitis was 13.2% for non-pCY and 29.7% for pCY (p = 0.005). Hemorrhagic cystitis did not have an adverse impact on non-relapse mortality (NRM) and OS. Day +180 CIR of renal toxicities was 17.6% for non-pCY and 28.6% for pCY (p = 0.10). The CIR of cardiac toxicities at day +180 was 9.9% for non-pCY and 14.3% for pCY (p = 0.34). Congestive heart failure (59%) and atrial fibrillation (36%) were the most common cardio-toxicities. One-year NRM was 38.5% in pt developing cardio-toxicity in the pCY cohort compared to no cardio-toxicity (15.3% in non-pCY and 18.3% in pCY, p = 0.004). OS was inferior in pt with cardio-toxicity in non-pCY (HR 5.49, p < 0.001) and pCY (HR 2.3, p = 0.03) compared to pt without cardio-toxicity. In multivariable analysis, pCY was associated with an increased risk of mucositis (HR 1.48, p = 0.03), and hemorrhagic cystitis (HR 2.67, p = 0.004). The number of infused CD34 cells was associated an increased risk of cardiac toxicity (HR 1.13, p = 0.005). pCY was not associated with higher cardiac complications, and no impact of the number of infused CD34 cells, conditioning regimen and prior transplant was observed on hemorrhagic cystitis and mucositis. Conclusions: pCY was associated with significant morbidity compared to HLA-matched non-pCY cohort. Although cardio-toxicities were similar between both groups, it was associated with worse survival.

Introduction Failure to achieve morphological complete remission occurs in 30% AML patients resulting in dismal outcomes. Data addressing influence of pre-transplant PDL-1 status on post-transplant outcomes is limited. We hypothesize that PDL-1 expression by immunohistochemistry (IHC) or Fluorescent in situ hybridization (FISH) prior to transplantation may predict a poor outcome. Methods This was a retrospective, observational single center pilot study involving refractory AML patients who underwent allogeneic stem cell transplantation (ASCT) at Karmanos Cancer Institute from 01/01/2012 to 01/01/2018. A planned sample size of 24 patients were selected and assigned to two cohorts based on their respective responses to ASCT: a) poor responders: persistent leukemia by bone marrow biopsy within 30 days of ASCT, and b) good responders: no evidence of leukemia at 1-year post-transplant. Descriptive analyses evaluated differences in demographic, disease and treatment variables. FISH assay was used to evaluate PDL-1 alterations in the pre-transplant archival, formalin-fixed, paraffin-embedded bone marrow biopsy specimens including frequency and magnitude of 9p24.1 alterations— low-level disomy, polysomy, copy gain, and amplification. The expression of PD-L1 was evaluated by IHC in a semi-quantitative (0 through +3) manner. Results Of the total 24 patients, 12 patients were poor responders and 12 were good responders; among poor responders, median age was 58 years (range, 31- 72) and gender distribution was 1:1. Seven patients (58%) had prior MDS, Myelofibrosis or CMML, while five patients had de-novo AML. Treatment information is provided in table 1. At pre-transplant bone marrow biopsy assessment, median number of bone marrow and peripheral blood blast counts were 8.1% (1.7-37) and 2% (0-37), respectively. Bone marrow cytogenetics assessed prior to transplant included intermediate risk in 2 (17%) and high risk disease in 9 (75%) patients and one patient without cytogenetic evaluation. PD-L1 expression was negative by IHC in all samples, but FISH testing was positive in 3 of 12 (25%) poor responders, characterized by copy gain. In good responders, median age was 59 years (range, 43-70) with a 3:2 male predominance. Four patients (25%) had prior MDS or Myelofibrosis and 8 had de-novo AML. Five patients (42%) had intermediate risk and 7 (58%) had high-risk cytogenetics. At pre-transplant bone marrow biopsy assessment, median number of bone marrow and peripheral blast counts were 6% (1-40) and 1% (0-7), respectively. PD-L1 expression was negative by both IHC and FISH examination in this cohort. Conclusion Our study demonstrates that PDL-1 expression by FISH was specifically detected in 25% of patients with poor responders following ASCT, which could possibly provide an insight into the poor outcome. A larger sample will be required to validate this observation in this population.

Introduction The outcomes of diffuse large B cell lymphoma (DLBCL) patients failing autologous transplant (autoSCT) are poor. Moreover, patients with high risk DLBCL and refractory disease have lower chances of remission to autoSCT. Allogeneic stem cell transplant (alloSCT) could be a viable option in these circumstances. Here we report outcomes of DLBCL patients who received alloSCT in upfront settings or following failed autoSCT. Methods The objectives were to determine GVHD, overall survival (OS), relapse rate, progression-free survival (PFS) and non-relapse mortality (NRM) of adult DLBCL patients following alloSCT. Results Between January 2005 and December 2017, 81 patients underwent alloSCT. Of these, 73 patients had de novo, 7 had transformed and one had testicular DLBCL. The median age at transplant was 52 years (range, 21-68). The median number of treatments prior to alloSCT was 3 (range, 1-6). Twenty-four patients (30%) had prior failed autoSCT, and 57 (70%) underwent upfront alloSCT. Disease status at transplant were: complete remission in 22 patients (27%), partial remission in 6 (7%), relapse in 31 (38%) and refractory in 22 (27%). Thirty-three patients (41%) underwent matched related and 48 (59%) had matched unrelated alloSCT. CNS and bone marrow involvement at the time of transplant was noted in 10% and 47% of patients, respectively. Patients received following conditioning regimens: R-BEAM (58%), BU-FLU-TBI (27%), BU-FLU (2%), CY-TBI (2%), BU-CY (2%), CY-FLU-TBI (2%), and others (5%). With a median follow-up of 5 years (95% CI, 4.01-9.89), the 1-year cumulative incidences of grade III-IV acute GVHD and chronic GVHD were 27.2% (95% CI, 18-37.2%) and 37% (95% CI, 26.5-47.6%), respectively. At 1-year, OS was 48% (95% CI, 38.4-60.3%), PFS was 43.2% (95% CI, 33.6-55.4%) and GRFS was 13.5% (95% CI, 7.8-23.5%). One-year relapse rate was 24.7% (95% CI, 15.9-34.5%), and NRM was 32.1% (95% CI, 22.2-42.4%). Sixteen patients (20%) patients were alive without chronic GVHD and relapse. Relapse disease at the time of transplant was associated with higher post-transplant relapse rate, and poor performance status was adversely associated with OS and PFS. No effect of prior autoSCT, conditioning regimen or type of donor was found in multivariable analysis on OS, PFS, relapse and NRM. Twenty-seven out of 81 patients (33%) were alive at the time of data analysis. Causes of death included relapse (37%), infection (31%), acute GVHD (13%) and multiorgan failure (11%). Conclusion Our study indicates that alloSCT provides long-term survival in these high-risk patients indicating graft-verus-lymphoma effect with low relapse rate; although non-relapse mortality was high in this group where about a third had failed prior autoSCT.

Allogeneic hematopoietic stem cell transplant (AHSCT) outcomes data of older AML/myelodysplastic syndrome (MDS) patients are limited. We retrospectively evaluated consecutive patients ⩾60 years old with AML/MDS who underwent AHSCT between January 2005 and December 2014. The primary objectives were to determine nonrelapse mortality (NRM), relapse, relapse-free survival (RFS) and overall survival (OS) at 1 year post AHSCT. A total of 159 patients underwent AHSCT with a median age of 64 (range, 60–75) years. Of these, 103 patients (65%) had AML and 56 patients (35%) had MDS. At 1 year post AHSCT, grade III–IV acute GvHD and chronic GvHD occurred in 20.8% (95% confidence interval (CI), 14.9–27.5%) and 54.1% (95% CI, 46.0–61.5%) of patients, respectively. NRM, RFS, relapse rate and OS at 1 year post AHSCT were 25.3% (95% CI, 18.8–32.3%), 53.3% (95% CI, 46.1–61.7%), 21.4% (95% CI, 15.4–28.1%) and 56.4% (95% CI, 49.2–54.7%), respectively. High disease risk index was associated with poor RFS, OS and higher relapse rate (P < 0.03), whereas non-thymoglobulin-based GvHD prophylaxis, higher comorbidity index (⩾3) and MDS were associated with higher NRM (P < 0.03). Importantly, age did not have an adverse effect on NRM, relapse, RFS and OS. AHSCT was well tolerated. Hence, older age alone should not be considered a contraindication to AHSCT.

A multistate model is more complicated than competing risk models and composed of finite number of states and transitions between states. Unlike competing risk models, this model has the ability to assess the effect of occurrence order of time-to-event data. Pleural effusion (PE) is a severe complication that often occurs after allogeneic hematopoietic stem cell transplantation (HSCT). Many patients develop pleural effusion during the first 100 days after allogeneic HSCT and graft-versus-host disease (GVHD) occurs either before or after the development of PE, implying that the occurrence order of PE and GVHD (i.e., PE after GVHD vs. GVHD after PE) would influence on the incidence, risk factors and mortality of pleural effusion. One can use either Cox proportional models or competing risk models to evaluate these values, but neither method is able to incorporate the occurrence order of incidence into the model. To resolve this difficulty, we developed a multistate model describing several possible events and event-related dependences and applied to a retrospective study of 606 patients, including eight covariates.

Introduction: Post-transplant relapse and GVHD are two major barriers of success of allogeneic hematopoietic stem cell transplantation (AHSCT) for AML. These outcomes are often dependent on the complex interaction between the post-transplant immunosuppression and the conditioning regimen. We as well as others have used rabbit thymoglobulin for the reduction of both acute and chronic GVHD in unrelated transplant in AML. The interaction between different conditioning regimens and thymoglobulin may play an important role in the outcomes, but it has not been fully investigated. In this study, we compared outcomes of patients undergoing unrelated donor AHSCT for AML using thymoglobulin with either a myeloablative or reduced intensity conditioning regimen. Patients received busulfan/fludarabine (Bu/Flu)-based myeloablative conditioning (MAC) regimen with 4 days of busulfan or reduced intensity conditioning (RIC) regimen using 2 days of busulfan with fludarabine. Since 2 days of busulfan as RIC may have a higher relapse rate, we added low dose TBI (200cGY) to the RIC regimen (Bu/Flu/TBI). Methods: We retrospectively evaluated outcomes of adult AML patients who underwent unrelated donor AHSCT utilizing tacrolimus, mycophenolate (MMF) and thymoglobulin as GVHD prophylaxis. All patients received either a Bu/Flu/TBI-based RIC or a Bu/Fu-based MAC regimen. Thymoglobulin was administered at a total dose of 4.5mg/kg in divided fashion (0.5mg/kg on day-3, 1.5mg/kg on day -2, 2.5mg/kg on day -1). Tacrolimus and MMF were started on day -3. The objectives were to determine the rates of acute and chronic GVHD, overall survival (OS), relapse free survival (RFS) and non-relapse mortality (NRM) using Cox proportional hazard regression and competing risk models. Results: One hundred twenty-two patients with AML received unrelated donor AHSCT between January 2005 and December 2017. Of these, 88 (72%) patients had de-novo and 34 (28%) had secondary AML. Sixty-four patients received Bu/Flu/TBI-based RIC, and 58 received Bu/Flu as MAC regimen. All patients received peripheral blood stem cells. The patients receiving RIC regimen were older (median age 66 vs 53 years, p The 6-month cumulative incidence rate (CIR) of grade III-IV acute GVHD (aGVHD) was 6% in RIC and 26% in MAC regimen (p=0.004). The 2-year CIR of chronic extensive GVHD was 35% and 29% in RIC and MAC regimen, respectively (p=0.50). Median follow-up of surviving patients after RIC and MAC regimen was 4.4 years and 4 years, respectively. Two-year OS after RIC and MAC regimen was 50% and 49%, respectively (p=0.69). Two-year relapse rate with RIC and MAC was 37% and 24%, respectively (p=0.25), whereas two-year NRM with RIC and MAC was 21% and 31%, respectively (p=0.41). Two-year RFS was 43% with RIC and 45% with MAC regimen (p=0.80). In all, CMV and EBV reactivation rates were 34% and 7%, respectively. Eight patients (7%) developed gastrointestinal CMV disease. Multivariable analysis revealed that relapsed and refractory AML at AHSCT was associated with adverse OS (HR 1.71, p=0.04), RFS (HR 1.84, p=0.01) and higher NRM (SHR 2.96, p=0.006) compared to first complete remission. Secondary AML was associated with higher NRM (HR 2.44, p=0.02). No impact of HLA matching and conditioning regimen on OS, relapse, NRM and RFS was observed. Subgroup analysis showed that HLA matching had an interaction with the conditioning regimen for RFS (p=0.03). Otherwise, none of the factors appeared to have any significant interaction with the conditioning regimen for survival outcomes. Conclusion: Our study shows that thymoglobulin when used with lower dose of busulfan (in the form of Bu/Flu/TBI-based RIC regimen) provided significantly lower rate of acute GVHD compared to Bu/Flu-based MAC in AML patients undergoing unrelated donor AHSCT without affecting leukemia-free and overall survival. Disease status at transplant remains a significant predictor of post-transplant outcomes. Disclosures Deol: Novartis: Other: Advisory board; Kite: Other: Advisory board; Agios: Other: Advisory board.

Introduction: Rabbit thymoglobulin, an in-vivo T-cell depleting agent, is widely used as a part of GVHD prophylaxis regimen. Current dosing of thymoglobulin is often weight based and does not consider patient related factors. This results in highly variable exposure of thymoglobulin. Although higher doses (>7mg/kg) of thymoglobulin have shown to reduce the risk of GVHD, it is associated with increased rate of opportunistic infections and disease recurrence. Conversely, lower dose (2.5mg/kg) of thymoglobulin is associated with increased risk of GVHD. Thus, optimum dosing of thymoglobulin remains undefined. We hypothesized that recipient peripheral blood ALC on the first day of thymoglobulin infusion would interact with the dose of thymoglobulin administered and predict post-transplant outcomes. We plan to identify association of thymoglobulin dose with the ALC on the first day of thymoglobulin. Methods: We retrospectively evaluated clinical outcomes of adult patients (pts) who underwent matched unrelated donor AHSCT and received tacrolimus, mycophenolate (cellcept) and thymoglobulin as GVHD prophylaxis. Thymoglobulin was given at a total dose of 4.5mg/kg in divided fashion (0.5mg/kg on day -3, 1.5mg/kg on day -2 and 2.5mg/kg on day -1). The objectives were to determine rate of GVHD, overall survival (OS), relapse-free survival (RFS), relapse rate and non-relapse mortality (NRM) following AHSCT using Cox proportional hazard regression and competing risk models. Results: Between January 2005 and December 2017, 217 pts underwent AHSCT. The most common indications for AHSCT were AML (n=95, 44%), MDS (n=57, 26%), non-Hodgkin's lymphoma (n=23, 11%), and ALL (n=22, 10%). Median age of pts was 60 years (range, 18-79). All pts received peripheral blood stem cells. Ninety-eight pts (45%) received full intensity conditioning regimen and 119 pts (55%) received reduced intensity regimen. The median ALC on the first day of thymoglobulin administration was 200 K/cubic millimeter. The 6-month cumulative incidence rate (CIR) of grade III-IV acute GVHD was 14.8% and the 2-year CIR of chronic extensive GVHD was 35.4%. With a median follow up of 3.82 years for surviving patients, the 2-year RFS, OS, relapse and NRM were 50%, 57.1, 20.1%, and 30.2%, respectively. CMV and EBV reactivation rates were 37% and 11%, respectively. Four pts developed CMV disease. By our lowest ALC cutoff of 100 K/cubic millimeter, pts were divided into two groups (ALC ≤ 100 vs. ALC > 100). Multivariable analysis revealed that ALC > 100 was associated with significantly superior OS (HR 0.51, 95% CI 0.33-0.79, p=0.002), RFS (HR 0.49, 95% CI 0.33-0.74, p=0.001) and lower NRM (SHR 0.57, 95% CI 0.34-0.97, p=0.038) and marginally lower relapse rate (SHR 0.57, 95% CI 0.31-1.05, p=0.070). In addition, higher infused total nucleated cells was associated with higher NRM (SHR 1.70, 95% CI 1.02-2.83, p=0.041). No impact of disease risk index, KPS, conditioning regimen, infused CD34 cells on NRM, relapse, RFS or OS was observed. Conclusion: Our study indicates that ALC ≤ 100 is associated with adverse post-transplant outcomes when thymoglobulin dose of 4.5mg/kg is used for in-vivo T cell depletion. This finding may indicate that in pts with lower ALC, thymoglobulin dose may need to be adjusted to optimize its efficacy and avoid toxicities. In the future prospective studies, which evaluate dose reduction of thymoglobulin in pts with low ALC need to be planned to confirm these results. Disclosures Deol: Agios: Other: Advisory board; Novartis: Other: Advisory board; Kite: Other: Advisory board.

Introduction: Low dose lenalidomide as a maintenance therapy after the first autologous transplant (autoSCT) has been shown to improve progression free survival (PFS) and possibly overall survival (OS) in standard-risk multiple myeloma (MM). Proteasome inhibitor-based maintenance therapy provides an alternative to lenalidomide and offers PFS and OS advantage in high-risk MM. Most recently oral ixazomib as a maintenance therapy has been shown to reduce the risk of progression by 28%. Despite the advances in maintenance therapy after first autoSCT, no prospective or retrospective studies exist evaluating efficacy of maintenance therapy after second autoSCT. In this retrospective study, we evaluated the impact of maintenance therapy after second autoSCT. Methods: We retrospectively evaluated clinical outcomes of adult MM patients (pts) who received maintenance therapy following second autoSCT. Lenalidomide dose up to 15mg daily and subcutaneous bortezomib 1.3mg/m2 every 2 weeks were considered maintenance therapy. The pts who received higher doses or combinational therapy as maintenance were excluded. We compared outcomes between pts who did and did not receive maintenance therapy following second autoSCT. The objectives were to determine OS, relapse-free survival (RFS), relapse rate and non-relapse mortality (NRM) with maintenance therapy following second autoSCT using Cox regression and competing risk models. Results: Between January 2000 and December 2018, 117 pts underwent second autoSCT and met the inclusion criteria. Of these, 39 received maintenance therapy and 78 did not. Median time between first and second autoSCT was 57 months (range, 4.9-124.2) in the maintenance group and 46 months (range, 3.7-193.5) in the no-maintenance group (p=0.32). Disease status at second autoSCT was complete response (CR) (n=7, 6%), very good partial response (VGPR) (n=22, 19%), partial response (PR) (n=30, 26%), stable (n=21, 18%) and progressive disease (n=32, 27%). Melphalan-based preparative regimen was used in 87% of pts, and BEAM was used in 13% of pts. All pts successfully engrafted and median time to neutrophil and platelet engraftment was 11 and 19 days, respectively. Maintenance therapy after second autoSCT was started at a median day of 105 (range, 62-317). Lenalidomide-based maintenance therapy was commonly used in 23 (59%) pts, and bortezomib as maintenance was used in 16 (41%) pts. Sixteen pts received maintenance therapy after both first and second autoSCT, and 23 received second maintenance only. Median duration of second maintenance therapy was 16 months (range, 8.7-26.5). The best response during maintenance was CR (n=8, 21%), VGPR (n=20, 51%), PR (n=9, 23%), and stable disease (n=2, 5%). Median follow-up for OS was 48 and 60 months in the maintenance and no-maintenance group, respectively. Median OS was not reached in the maintenance group and was 40.8 months in the no-maintenance group (HR 2.32, p=0.02). At 3-year, maintenance group had superior RFS (18% vs 12%; HR 1.65, p=0.03), lower relapse rate (69 vs 81%; SHR 0.58, p=0.02). Median time to progression was 24 months in the maintenance group and 14 months in the no-maintenance group (p=0.04). Although limited by small numbers, we did not observe any impact of cytogenetics at diagnosis on OS and RFS after second autoSCT. RFS was superior with lenalidomide-based maintenance compared to bortezomib-based maintenance (HR 2.17, p=0.05). However, OS was not different. The multivariable analysis revealed that maintenance after second autoSCT was associated with significantly superior OS (HR 0.38, p=0.01), RFS (HR 0.59, p=0.03) and lower relapse rate (SHR 0.63, p=0.04). The common reasons for maintenance therapy discontinuation were disease progression (n=20, 51%), side effects (n=7, 18%), and unknown (n=12, 31%). A total of 10/39 pts who received maintenance therapy and 44/77 pts who did not receive maintenance have died. Conclusion: This is the first study showing efficacy of maintenance therapy after second autoSCT. Maintenance therapy after second autoSCT significantly improved overall and relapsed-free survival and should be considered in all pts after second transplant. Our study also reveals real world practice pattern of using variable dose of maintenance therapy among physicians. Disclosures Deol: Novartis: Other: Advisory board; Kite: Other: Advisory board; Agios: Other: Advisory board.

Background A principal goal for the use of positron emission tomography (PET) in oncology is for real-time evaluation of tumor response to chemotherapy. Given that many contemporary anti-neoplastic agents function by impairing cellular proliferation, it is of interest to develop imaging modalities to monitor these pathways. Here we examined the effect of capecitabine on the uptake of thymidine analogs used with PET: 3’-deoxy-3’-[18F]fluorothymidine (18F-FLT), 1-(2’-deoxy-2’-[18F]fluoro-β-D-arabinofuranosyl) thymidine (18F-FMAU), and 1-(2’-deoxy-2’-[18F]fluoro-β-D-arabinofuranosyl) uracil (18F-FAU) in patients with advanced cancer. Methods Fifteen patients were imaged, five with each imaging agent. Patients had been previously diagnosed with breast, colorectal, gastric, and esophageal cancers and had not received therapy for at least 4 weeks prior to the first scan, and had not been treated with any prior fluoropyrimidines. Subjects were imaged within a week before the start of capecitabine and on the second day of treatment, after the third dose of capecitabine. Tracer uptake was quantified by mean standard uptake value (SUVmean) and using kinetic analysis. Results Patients imaged with 18F-FLT showed variable changes in retention and two patients exhibited an increase in SUVmean of 172.3 and 89.9 %, while the other patients had changes ranging from +19.4 to -25.4 %. The average change in 18F-FMAU retention was 0.2 % (range -24.4 to 23.1) and 18F-FAU was -10.2 % (range -40.3 to 19.2). Observed changes correlated strongly with SUVmax but not kinetic measurements. Conclusions This pilot study demonstrates that patients treated with capecitabine can produce a marked increase in 18F-FLT retention in some patients, which will require further study to determine if this flare is predictive of therapeutic response. 18F-FAU and 18F-FMAU showed little change, on average, after treatment. Electronic supplementary material The online version of this article (doi:10.1186/s40644-016-0092-2) contains supplementary material, which is available to authorized users.

Introduction: Peripheral T-cell Lymphoma represents a heterogeneous group of lymphoid malignancies characterized by poor prognosis with 5-year overall survival (OS) about 25% with conventional chemotherapy. Autologous stem cell transplant (Auto-SCT), as consolidation, is often considered in first complete remission (CR), providing between 30 to 40% long term disease-free survival. However, patients receiving Auto-SCT in second CR or with refractory disease have poor outcomes with progression-free survival ranging from 15-20% to 0%, respectively. In such cases, allogeneic stem cell transplant (Allo-SCT) may provide long term disease control. We intended to study outcomes of Allo-SCT in peripheral T-cell lymphoma patients. Methods: We have retrospectively evaluated long-term outcomes of adult peripheral T-cell lymphoma patients at Karmanos Cancer Institute. The objectives were to determine GVHD rate, overall survival (OS), relapse rate, progression-free survival (PFS) and non-relapse mortality (NRM) following Allo-SCT. Results: Between January 2005 and December 2017, 39 patients underwent Allo-SCT. The different diagnoses included peripheral T-cell lymphoma, not-otherwise-specified (n=16), angioimmunoblastic T-cell lymphoma (n=8), anaplastic T-cell lymphoma (n=8), hepatosplenic T-cell lymphoma (n=2), cutaneous T-cell (n=3) and NK cell lymphoma (n=2). The median age at transplant was 50 years (range, 21-67). The median number of prior therapies was 2 (range, 1-5) and 12 patients (31%) had failed prior Auto-SCT. Sixteen patients (41%) were in CR and 2 (5%) were in partial remission at the time of Allo-SCT, whereas 12 (31%) patients had relapsed disease and 9 (23%) had refractory disease. Twenty-one patients (54%) received matched related and 18 patients (46%) had unrelated Allo-SCT. Myeloablative conditioning regimen was used in 22 patients (56%), whereas reduced intensity regimen was used in 17 (44%) patients. Grade III-IV acute GVHD occurred in 25.6% (95% CI, 13.2-40.1%) and chronic GVHD occurred in 41% (95% CI, 25.1-56.3%). After a median follow-up of 3.08 years (95% CI, 2.49-7.28) among surviving patients, the estimated probabilities of 3-year OS and PFS were 35.9% (95% CI, 22.4-57.6%) and 32.5% (95% CI, 19.9-53%), respectively. The 3-year relapse rate was 23.9% (95% CI, 11.5-38.7%), whereas NRM was 35.9% (95% CI, 21.1-50.9%). No difference in OS and PFS was noticed in patients receiving Allo-SCT in first CR compared with patients receiving Allo-SCT beyond first CR (p=0.81; p=0.94). Similarly, no difference in OS and PFS was noted in patients with Allo-SCT followed by failed prior Auto-SCT compared with patients with upfront Allo-SCT (p=0.31; p=0.47). Seventeen of 39 patients were alive and 22 were deceased (n=7 disease relapse; n=15 NRM). Out of 39 patients, 13 (33%) alive patients are free of relapse and GVHD as of data analysis. Conclusion: Our study suggests that Allo-SCT is a viable treatment option for peripheral T-cell lymphoma and appears to provide cure in these highly selected patients. The survival advantage was noted in patients beyond first remission; therefore, it should be considered in all transplant eligible patients. In addition, certain proportion of patients who failed prior Auto-SCT benefited from Allo-SCT, which points towards potential role of graft-versus-lymphoma effect. Disclosures Deol: Novartis: Consultancy; Kite Pharmaceuticals: Consultancy.

Introduction: Use of cytoreductive therapy pre-transplant has remained a debatable issue in the management of MDS. Induction chemotherapy has been attempted with no clear advantage. However, the information on pre-transplant hypomethylating agents (HMA) as a debulking/bridging therapy in MDS is unclear. This study evaluates the impact of pre-transplant HMA on post-transplant outcomes in MDS. Methods: We retrospectively evaluated clinical outcomes of adult MDS patients, who underwent allogeneic stem cell transplant (ASCT) at out institute. We divided patients who received pre-transplant HMA into Results: Between January 2000 and December 2016, 174 patients with MDS underwent ASCT. Of these, 80 patients received pre-transplant HMA, and 42 had With a median follow up of 4.08 years, the cumulative incidence of grade III-IV aGVHD at 6 months was 9.5% (95% CI, 3-20.7%), 28.9% (95% CI, 15.5-43.9%), and 27.7% (95% CI, 19-37%) for group 1, 2 and 3, respectively (p=0.05). The 1-year cumulative incidence of cGVHD was 54.9% (95% CI, 37.4-69.4%), 28.4% (95% CI, 14.4-44.3%), and 51.1% (95% CI, 40.4-60.7%) (p=0.04), for group 1, 2 and 3, respectively. The 1-year OS for group 1, 2 and 3 was 75% (95% CI, 62.6-89.7%), 40.2% (95% CI, 26.5-61%), and 59.3% (95% CI, 50.1-70.1%), respectively; whereas PFS was 67.5% (95% CI, 54.4-83.8%), 34.8% (95% CI, 22.2-54.7%), 55.1% (95% CI, 45.9-66.2%), respectively. The 1-year outcomes in group 1, 2 and 3 were 17.6% (95% CI, 7.6-31%), 26.6% (95% CI, 13.6-41.6%), and 9.6% (95% CI, 4.7-16.6%) (p=0.07), respectively, for relapse; 14.8% (95% CI, 5.9-27.6%), 38.2% (95% CI, 22.4-53.9%), and 35.2% (95% CI, 25.7-44.9%) (p=0.11), respectively, for NRM. Multivariable analysis demonstrated that ≥5% blast at transplant, complex karyotype and high R-IPSS were associated with poor PFS and OS, whereas Complex karyotype was associated with higher relapse rate, poor PFS and OS. Conclusion: Our study shows pre-transplant disease burden and complex karyotype as independent risk factors for poor outcomes. No survival benefit was noted with pre-transplant HMA in MDS. Disclosures Deol: Novartis: Consultancy; Kite Pharmaceuticals: Consultancy.

Introduction: Salvage immunochemotherapy (IC), followed by high-dose chemotherapy with autologous stem cell transplantation if chemosensitive is standard-of-care second-line (2L) therapy (tx) for fit patients (pts) with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) when treated with first-line (1L) R-CHOP as shown in the CORAL study. Outcomes following receipt of salvage IC in the 2L setting for pts with DLBCL or high grade B cell lymphoma/B cell lymphoma unclassifiable (HGBL/BCLU) receiving intensive 1L tx remain unknown, and may be worse than those reported in CORAL given prior exposure to higher-dose IC in 1L setting. Here we report the results of a multicenter retrospective analysis of R/R DLBCL and HGBL/BCLU pts treated with intensive 1L tx who receive standard salvage 2L tx. Methods: Inclusion criteria were histologic diagnosis of DLBCL or HGBL/BCLU, R/R disease following 1L tx with R-EPOCH, R-HyperCVAD or R-CODOX-M/IVAC and receipt of 2L tx with R-ICE, R-DHAP, R-DHAC, R-ESHAP or R-GDP. Exclusion criteria were HIV positivity, post-transplant lymphoproliferative disorder, prior chronic lymphocytic leukemia and inadequate data. Therapy was given at the discretion of the treating physician. Progression free survival (PFS) was defined as the interval between time of first relapse or primary refractory disease and disease progression, change in therapy if no disease response or last follow-up in remission, and overall survival (OS) between time of first relapse or primary refractory disease and death or last follow-up while alive. Pts were treated from 2007-2017 and data were censored on 10/15/17. Results: A total of 195 pts treated at 20 US and Canadian academic medical centers were included. Clinicopathologic characteristics at time of R/R disease were 39% age >60 years, 62% male, 77% stage III-IV, 72% elevated LDH, 24% bone marrow (BM) involvement, 28% B symptoms present, 44% extranodal (EN) disease at >1 site, 19% ECOG performance status (PS) >1, 49% with International Prognostic Index score (IPI) ≥3, 46% HGBL/BCLU histology, 49% Ki67 ≥90%, and 61% germinal center (GCB) cell of origin (COO) by Hans algorithm. Of pts with available fluorescence in situ hybridization (FISH) data, 51%, 45% and 30% demonstrated MYC, BCL2 and BCL6 rearrangements (-R), respectively, and 37% were double hit lymphoma (DHL). Tx received in 1L were R-EPOCH in 82%, R-HyperCVAD in 16% and R-CODOX-M/IVAC in 2% of pts. R-ICE was received by 64% and other platinum-containing regimens by 36% as 2L tx. Most (86%) pts relapsed within 12 months (mo) of completion of 1L tx (early) and 58% of pts had primary refractory disease. For all pts, the median length of follow-up was 25.0 mo with a median PFS of 3.0 mo and median OS of 8.0 mo. Overall response rate to 2L tx among all pts was 44% (23% complete response [CR] and 21% partial response [PR]), and 48% with progressive disease. Pts achieving CR had significantly longer median PFS (32.0 vs 4.0 mo, p = 0.0001) and OS (not reached vs 13.0 mo, p = 0.0004) as compared to pts achieving PR. In pts who achieved CR or PR following 2L tx, 64% received consolidative transplant (42 autologous and 13 allogeneic) and achieved a median PFS and OS of 18.3 mo and 62.0 mo, respectively. As compared to pts relapsing ≥12 mo after completion of 1L tx (late), pts relapsing early were less likely to achieve CR (17% vs. 61%, p=0.0001) and experienced significantly shorter median PFS (2.8 vs. 23.0 mo, p1 site, B symptoms, ECOG PS >1 and Ki67 ≥90%, but not BCL2-R, demonstrated a statistically significant increased HR for death. Multivariate analysis demonstrated only early relapse to have a statistically significant increased HR for progression (HR 2.47, p=0.024) and death (HR 5.90, p=0.001). Conclusion: Relapse Figure. Figure. Disclosures Maddocks: Pharmacyclics: Research Funding; BMS: Research Funding; Teva: Honoraria; AstraZeneca: Honoraria; Novartis: Research Funding; Pharmacyclics/Janssen: Honoraria; Merck: Research Funding. Wagner-Johnston:Novartis: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; ASTEX: Research Funding; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Merck: Research Funding; JUNO: Honoraria, Membership on an entity's Board of Directors or advisory committees. Karmali:Gilead: Speakers Bureau; AstraZeneca: Speakers Bureau. Kahl:Genentech: Consultancy; Juno: Consultancy; Celgene: Consultancy; Seattle Genetics: Consultancy; ADC Therapeutics: Consultancy; Gilead: Consultancy; Acerta: Consultancy; CTI: Consultancy; Abbvie: Consultancy; AstraZeneca: Consultancy. Cohen:AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BioInvent: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Reddy:MEI Pharma: Research Funding. Ramchandren:Seattle Genetics: Consultancy, Research Funding; Pharmacyclics LLC an AbbVie Company: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Merck: Research Funding; Janssen: Consultancy, Research Funding. Diefenbach:Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Incyte: Research Funding; Trillium: Research Funding; Millenium/Takeda: Research Funding; Denovo: Research Funding; Acerta: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Genentech: Consultancy. Olszewski:TG Therapeutics: Research Funding; Genentech: Research Funding; Spectrum Pharmaceuticals: Consultancy, Research Funding. Barta:Janssen: Membership on an entity's Board of Directors or advisory committees; Merck, Takeda, Celgene, Seattle Genetics, Bayer: Research Funding. Hill:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Assouline:Roche: Honoraria, Research Funding, Speakers Bureau; Novartis: Research Funding; BMS: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Landsburg:Curis: Consultancy, Research Funding; Takeda: Consultancy.

Introduction: About 40-45% of relapsed chemo-sensitive diffuse large B cell lymphoma (DLBCL) patients achieve long term survival with autologous transplant (autoSCT). However, the outcomes of patients who fail autoSCT are extremely poor. In addition, patients with high risk DLBCL and refractory disease have lower chances of response to autoSCT. Allogeneic stem cell transplant (alloSCT) could be a viable option in these circumstances, in part due to cytoreductive effect of conditioning regimen and graft-versus-lymphoma effect. Here we report outcomes of DLBCL patients who received alloSCT in upfront settings or following failed autoSCT. Methods: We retrospectively evaluated clinical outcomes of adult DLBCL patients at Karmanos Cancer institute. The objectives were to determine rate of GVHD, overall survival (OS), relapse rate, progression-free survival (PFS) and non-relapse mortality (NRM) following alloSCT. Results: Between January 2005 and December 2017, 81 patients underwent alloSCT. Of these, 73 patients had de novo, 7 had transformed DLBCL and one had testicular involvement. The median age at transplant was 52 years (range, 21-68). The median number of treatments prior to alloSCT was 3 (range, 1-6). Twenty-four patients (30%) had prior failed autoSCT, and 57 (70%) had upfront alloSCT. Disease status at transplant were: complete remission in 22 patients (27%), partial remission in 6 (7%), relapse in 31 (38%) and refractory in 22 (27%). Thirty-three patients (41%) underwent matched related and 48 (59%) had matched unrelated alloSCT. CNS and bone marrow involvement at the time of transplant were noted in 10% and 47% of patients, respectively. Patients received following conditioning regimens: R-BEAM (58%), BU-FLU-TBI (27%), BU-FLU (2%), CY-TBI (2%), BU-CY (2%), CY-FLU-TBI (2%), and others (5%). With a median follow-up of 5 years (95% CI, 4.01-9.89), the cumulative incidences of grade III-IV acute GVHD at 6-month and chronic GVHD at 1-year were 27.2% (95% CI, 18-37.2%) and 37% (95% CI, 26.5-47.6%), respectively. At 1-year, OS was 48% (95% CI, 38.4-60.3%), PFS was 43.2% (95% CI, 33.6-55.4%) and GRFS was 13.5% (95% CI, 7.8-23.5%). One-year relapse rate was 24.7% (95% CI, 15.9-34.5%), and NRM was 32.1% (95% CI, 22.2-42.4%). Sixteen patients (20%) patients were alive without chronic GVHD and relapse. Relapse disease at the time of transplant was associated with higher post-transplant relapse rate, and poor performance status was adversely associated with OS and PFS. No effect of prior autoSCT, conditioning regimen or type of donor was found in multivariable analysis on OS, PFS, relapse and NRM. Twenty-seven out of 81 patients (33%) were alive at the time of data analysis. Causes of death included relapse (37%), infection (31%), acute GVHD (13%) and multiorgan failure (11%). Conclusion: Our study indicates that alloSCT provides long-term survival in these high-risk patients with low relapse rate; although non-relapse mortality was high in this group where about a third had failed prior autoSCT. Disclosures Deol: Kite Pharmaceuticals: Consultancy; Novartis: Consultancy.

Background: TMPRSS2-ERG fusions are highly prevalent in prostate cancer patients, where androgen responsive TMPRSS2 gene promoter fused with coding sequence of ERG transcription factor resulting in androgen mediated expression of ERG factor. Metastatic cancer patients harbor the TMPRSS2-ERG fusions and presence of fusions associate with poor overall survival. The association between ERG transcription factor and anti-androgen therapy (enzalutamide (arm A) vs. bicalutamide (arm B)) responsiveness was evaluated in a randomized trial in metastatic hormone sensitive prostate cancer (mHSPC). Methods: 40 of 71 patients had evaluable tissue from metastatic biopsy. 18 patients were on enzalutamide arm (A) and 22 patients were on bicalutamide arm (B). PSA was monitored monthly for first 7 months and then every 3 months. Total RNA was isolated from biopsy specimens, QPCR analysis was performed for ERG gene. A standard curve was developed with ERG expressing plasmid in QPCR experiment and the copy number of ERG was determined in the metastatic biopsies. Seven month PSA Response (SMPR) rates were calculated for the high and low subset categories of median-dichotomized ERG copy number. The odds of SMPR was modeled as a function of continuous ungrouped correlative via univariable logistic regression. Results: 15/40 patients had both pre and post treatment biopsies available. The mean ERG copy number was increased in post treatment biopsy in both arms (enzalutamide, n=10 and bicalutamide, n=5). The mean copy increased (pre= 8541 and post =9789) upon enzalutamide treatment and also increased (pre=17186 and post = 23368) upon bicalutamide treatment. SMPR rates show that low copy number patients responded better (19/20) compared to high copy number patients (14/20). In arm A response rate is 100% (18/18), whereas in arm B, low ERG copy number patients responded better (8/11) compared to high copy number patients (7/11). Finally, the SMPR odds ratio remained close to 1.000 even for large copy number increase. Selective ERG responsive gene expression levels were determined in metastatic biopsies and will be associated with clinical endpoints. Conclusions: Enzalutamide improved the likelihood of PSA remission in mHSPC and follow up is ongoing. Metastatic biopsy specimen analysis show that higher ERG copy number had a lower likelihood of PSA response with ADT and may serve as a prognostic or predictive marker, but further analysis is warranted. Citation Format: Sreenivasa R. Chinni, Ulka N. Vaishampayan, Lance K. Heilbrun, Louie Semaan, Daryn Smith, Dipenkumar Modi, Paul Monk, Shiela Tejwani, Guru Sonpavde, Kimberlee Dobson, Brenda Dickow, Elisabeth Heath, Joseph Fontana, Micheal L. Cher. Evaluation of ERG as a biomarker of responsiveness in a randomized trial of enzalutamide in combination with androgen deprivation in metastatic hormone sensitive prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-309.

A Phase II study of Tacrolimus and Thymoglobulin, as Graft-Versus-Host-Disease Prophylaxis in Patients Undergoing Related Donor Allogeneic Hematopoietic Cell Transplantation Introduction: Regimens used for the prevention of acute GVHD in allogeneic transplantation usually consist of combinations of a calcineurin inhibitor with an additional agent such as methotrexate, mycophenolate or sirolimus. Previously, we and others have demonstrated efficacy of the addition of thymoglobulin to these standard GVHD regimens in preventing both acute and chronic GVHD without increasing relapse rates. Given the proven activity of thymoglobulin, we now report the outcomes of a prospective phase II trial testing the combination of tacrolimus and thymoglobulin in the prevention of GVHD in patients undergoing matched related allogeneic transplants. Patients and Methods: Patients were eligible if they were between ages 18 to 75 years with hematologic malignancies in complete or partial remission at the time of transplant. Patients received thymoglobulin (4.5 mg/kg total dose) in divided doses from day -3 to -1 days prior to transplant. All patients were also given tacrolimus to maintain a therapeutic level from day -3 to day +60. After 60-days post-transplant, tacrolimus was tapered in the absence of GVHD and discontinued by day + 181. Primary objective was to determine incidence and severity of acute GVHD (aGVHD). Secondary objectives were to determine neutrophil and platelet engraftment time, estimate incidence of chronic GVHD (cGVHD), overall survival (OS), relapse free survival (RFS) and GVHD-free relapse-free survival (GRFS) at 1-year post-transplant. The cumulative incidence of GVHD was calculated using relapse and NRM as competing risks. The OS, RFS and GRFS were reported using KM method. The proportions of incidence of infections were reported with the Wilson's 95% Confidence Interval. Results: A total 20 patients were enrolled in our study. The median age was 59 years (range, 38-69) and the median follow-up duration was 54.3 months (95% CI, 43.6-NA). Seven patients had MDS, 5 had AML, 4 had NHL, one with CLL, 2 had CML, and one had ALL. Low, intermediate and high disease risk index was noted in 5%, 70%, and 25% of these patients respectively. Conditioning regimens included busulfan (BU)/fludarabine (FLU) (n=7), BEAM (BCNU, etoposide, ara-c and melphalan) ± rituximab (n=4), BU/FLU/total-body irradiation (TBI) (n=7), FLU/melphalan/TBI (n=2). All patients received peripheral blood stem cell transplants (PBSCT). The median day to neutrophil and platelet engraftment was 11 days (range, 7-12) and 17 days (range, 0-25) respectively. The 1-year incidence of grade II-IV aGVHD was 45% (95% CI, 22.3-65.4) and of grade III-IV aGVHD was 10% (95% CI, 1.6%-27.8%). The median time to development of grade II-IV aGVHD was 21 days (range, 14-105). The incidence of cGVHD at 1-year post-transplant was 70% (95% CI, 42.9-86.0) and the median time to development of cGVHD was 114 days (range, 46-616). Fourteen patients (60% with 95% CI, 34.3-78.4) developed extensive cGVHD at 1-year post-transplant. The incidence of relapse and non-relapse mortality at 2-year post-transplant were 35% (95% CI, 15.1-55.9) and 10.0% (95% CI, 1.6-27.8) respectively. Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) reactivation were noted among 35% and 40% of patients respectively. Eight patients relapsed and the median time of relapse was 317 days (range, 31-994). OS, RFS and GRFS at 1-year post-transplant were 85% (95% CI, 70.7-100), 65% (95% CI, 47.1-89.7) and 25% (95% CI, 11.7-53.4) respectively. Causes of death for 8 patients were: 5 relapse, 2 cGVHD, and 1 multiorgan failure. Conclusion: We reported a novel GVHD prevention regimen using tacrolimus and thymoglobulin. Our data suggest that combination can be used safely and thymoglobulin may replace either mycophenolate, methotrexate or sirolimus while avoiding some of the toxicities commonly associated with these agents. More importantly, rates of acute and chronic GVHD as well as GRFS appear to be comparable to other GVHD regimens. No significantly increased rates of opportunistic infections were noticed. Further studies in larger patient groups are warranted to better define the role of this regimen in GVHD prevention. Cumulative incidence of cGVHD, Grade II-IV and III-IV aGVHD, relapse and NRM Cumulative incidence of cGVHD, Grade II-IV and III-IV aGVHD, relapse and NRM Figure 1 OS, RFS and GVHD-free relapse-free survival Figure 1. OS, RFS and GVHD-free relapse-free survival Figure 2 Figure 2. Disclosures Deol: Jazz Pharmaceuticals: Consultancy.

Introduction: Patients with AML and MDS who are age 60 or above represent a discrete group of patients with a different disease biology compared to younger patients. These patients are often not offered allogeneic hematopoietic stem cell transplant (HSCT) as a curative intent because of concern of increased nonrelapse mortality (NRM) and poor overall survival (OS). Hence, the information on transplant outcomes among this population is very limited. Recently with the use of better supportive care measures and reduced intensity preparative regimens, patients greater than 60 are often recommended to proceed to transplant. This study evaluates our single center experience of allogeneic transplantation in patients with MDS and AML aged 60 and older. Patients and Methods: We retrospectively evaluated 60 years or older consecutive patients with AML and MDS who underwent allogeneic HSCT between January 2005 and December 2014. The primary objectives of our study were to determine NRM, relapse, relapse free survival (RFS) and OS at 1 year following transplant. The secondary objectives were to estimate cumulative incidence of acute (aGVHD) and chronic GVHD (cGVHD) at 1 year, length of stay and readmission rate in the first 100 days following transplant. Results: Between January 2005 and December 2014, 159 patients underwent allogeneic HSCT with the median age of 64 (range, 60-75) years and median follow-up duration for OS of 3.34 (95% CI, 2.51-3.87) years. Increasing number of patients were transplanted in recent years, i.e., 67% patients between 2010-2014 compared to 33% between 2005-2009. One hundred three patients (65%) had AML and 56 patients (35%) had MDS. Forty-nine patients (31%) received full intensity regimen and 110 patients (69%) received reduced intensity regimen. Fifty-two patients (33%) underwent allogeneic related transplant and 107 patients (67%) had allogeneic unrelated transplant. Thymoglobulin based GVHD prophylaxis was given in 77 patients (48%) whereas non-thymoglobulin based GVHD prophylaxis was given in 82 patients (52%). The median day to neutrophil and platelet engraftment was 11 (range, 7-22) days and 16 (range, 0-675) days, respectively. Graft failure occurred in 3 patients. At 1-year follow-up, the cumulative incidence of grade II-IV aGVHD was 39.7% (95% CI, 32.0-47.2%), grade III-IV aGVHD was 20.8% (95% CI, 14.9-27.5%) and cGVHD was 54.1% (95% CI, 46.0-61.5%). The cumulative incidence of chronic extensive GVHD was 39.8% (95% CI, 32.1-47.4%). Blood stream infection, cytomegalovirus reactivation, Epstein-Barr virus reactivation, C. difficile diarrhea occurred in 44%, 35%, 22% and 26% of patients, respectively. At 1-year follow-up, NRM was 25.3% (95% CI, 18.8-32.3%), RFS was 53.3% (95% CI, 46.1-61.7%), relapse rate was 21.4% (95% CI, 15.4-28.1%) and OS was 56.4% (95% CI, 49.2-54.7%). The median day of hospitalization following transplant was 26 (range, 19-112) days and almost half (52%) of patients were readmitted in the first 100 days following transplant. Leukemia recurrence was the most common cause of death. Multivariable analysis demonstrated high disease risk index to be the independent predictor of poor RFS, OS and higher relapse rate (p Conclusion: Our results indicate that allogeneic HSCT is well tolerated and had acceptable NRM, and OS among this group. Hence, older age alone should not be considered a contraindication to HSCT. Figure 1 Overall survival (OS) and relapse-free survival (RFS) estimates. The median OS is 1.60 years (95% CI, 0.94 to 5.00 years) and the median RFS is 1.15 years (95% CI, 0.63 to 3.07 years). The median follow-up time of OS and RFS are 3.34 years (95% CI, 2.51 to 3.87 years) and 3.25 years (95% CI, 2.51 to 3.87 years), respectively. Figure 1. Overall survival (OS) and relapse-free survival (RFS) estimates. The median OS is 1.60 years (95% CI, 0.94 to 5.00 years) and the median RFS is 1.15 years (95% CI, 0.63 to 3.07 years). The median follow-up time of OS and RFS are 3.34 years (95% CI, 2.51 to 3.87 years) and 3.25 years (95% CI, 2.51 to 3.87 years), respectively. Figure 2 Cumulative incidences of aGVHD, cGVHD, relapse and non-relapse mortality after transplantation. Figure 2. Cumulative incidences of aGVHD, cGVHD, relapse and non-relapse mortality after transplantation. Disclosures Deol: Jazz Pharmaceuticals: Consultancy.

An increasing prostate-specific antigen (PSA) level during radium therapy for metastatic castrate-resistant prostate cancer (mCRPC) is not an uncommon phenomenon, especially in heavily pretreated patients; however, an increasing PSA level does not always indicate progressive disease. Bone scan, chest and abdomen imaging should be performed to determine the cause of PSA increase, which could be true disease progression in the form of new visceral metastasis or flare reaction. BACKGROUND: Radium-223 is a bone-targeting radiopharmaceutical that extends survival in mCRPC. Postapproval data are limited, and the value of biochemical and radiologic monitoring during radium therapy is unknown. PATIENTS AND METHODS: We conducted a retrospective study of 29 patients with mCRPC who received radium-223 at 1 of 3 participating institutions between August 2013 and December 2014. Trend of PSA, radiographic changes, and association of biochemical and clinical variables with PSA trend were measured. RESULTS: The median age of patients was 70 years, 79% of patients (N = 23) were European Americans, and 17% of patients (N = 5) were African Americans. Twenty patients (69%) had received at least 3 lines of prior therapies. Some 38% of patients (N = 11) received all 6 cycles of radium-223. Twenty patients (69%) had an increase in PSA during radium therapy, and 4 patients (14%) had a decline in PSA levels. Five patients had visceral metastases on computed tomography imaging performed during the course of radium-223. CONCLUSIONS: Radium therapy in mCRPC was associated with an increase in PSA in the majority of these heavily pretreated patients. The development of visceral disease was not uncommon, suggesting a need for follow-up computed tomography monitoring during radium-223 therapy. The significance of early increases in PSA and pain with radium-223 is still uncertain. Although pain and PSA flare have been reported in patients who subsequently have a dramatic response to therapy, we observed that a PSA increase or pain flare correlates to an improvement in bone scans only in a minority of patients.

Introduction: Pleural effusions are common clinical finding in patients undergoing hematopoietic stem cell transplantation (HSCT). It can be a manifestation of underlying lung injury or a part of a systemic process. This study will investigate the incidence, risk factors, and clinical outcomes associated with pleural effusion in allogeneic HSCT. Methods: We conducted a retrospective study of 618 consecutive adult patients who underwent allogeneic HSCT for hematological disorders, between January 2008 and December 2013. Results: The baseline characteristics of the groups with and without pleural effusions are shown in table 1. The only significant difference was GVHD prophylaxis (p =0.002). A total 71 patients developed pleural effusions with the cumulative incidence of 12.6 % (95% CI, 10.0% to 15.6%) in five years. The median time of onset of pleural effusion from HSCT was 40 days (range, 1, 869). The onset of pleural effusion had a bimodal distribution with the first peak at 23 days (range 17, 29) and second peak at 362 days (range 277, 450). Based on chest CT criteria, the effusions were judged as large, moderate and small in size in 15%, 51% and 34% of patients respectively. Twenty five (35%) patients with pleural effusions underwent thoracentesis for respiratory difficulty and had a median of 800cc (range, 250 to 13500cc) of pleural fluid removed. Fourteen patients (56%) had exudative and 9 (36%) had transudative pleural effusions. Pleurx catheter was placed in 2 (3%), and chest tube in 3 (4%) patients. Causes of effusion listed in order of frequency are infection (38%), volume overload (23%), chronic GVHD (20%), heart failure (6%), engraftment syndrome (4%), veno-occlusive disease (4%), malignant pleural effusion (3%), hypersensitivity pneumonitis (1%) and iatrogenic (1%). Time of onset is different among various etiologies (p=0.006). Although thoracentesis was performed in 25 patients, the specific etiology by pleural fluid analysis was identified in only 2 patients. Pleural effusion secondary to infections, hypersensitivity pneumonitis, and engraftment syndrome occurred in the first 100 days after transplant, whereas pleural effusion due to chronic GVHD/polyserositis, bronchiolitis obliterans occurred 200 days after transplant.Fifty seven patients (80%) with pleural effusions had evidence of GVHD however; fourteen (20%) patients with pleural effusion had no evidence of acute or chronic GVHD. Twenty three (32%) patients had both pleural effusion and ascites, 27 (38%) had both pleural and pericardial effusion and 29 patients had pleural effusion alone. Multivariate cox regression analysis showed age, African American race, higher comorbidity index, unrelated donor, HLA-match 7/8, intermediate to high risk disease to be associated with worse survival among patients who developed pleural effusion after HSCT. There was no significant difference in overall survival between patients with or without pleural effusion (p=0.257). Conclusion: Majority of the patients who developed pleural effusions responded well with the treatment of the underlying disease. Although thoracentesis was often done for therapeutic reasons, it was a weak diagnostic tool. We did not identify any adverse impact of development of post HSCT pleural effusions on overall survival. Table 1. Characteristics Pleural Effusion (N=71) No Pleural Effusion (N=547) Signif Age - Median (range) year 55(25,73) 58(22,78) 0.514 Sex - no. (%) 0.522 Male/Female 43(61)/28(39) 305(56)/242(44) Diagnosis - no. (%) 0.490 AML 25(35) 213 (39) ALL 9(13) 53 (10) CLL 4(6) 27 (5) CML 2 (3) 16 (3) NHL 13 (18) 94 (17) Multiple Myeloma 3 (4) 16 (3) MDS 9 (13) 74 (14) Myelofibrosis 1 (1) 18 (3) Hodgkin's Lymphoma 1 (1) 8 (1) PLL 4 (6) 7 (1) Aplastic Anemia 0 (0) 17 (3) CMML 0 (0) 4 (1) Comorbidity-Median (range) 3 (0,8) 3 (0,9) 0.055 Disease risk status - no. (%) 0.389 Low 4 (6) 48 (9) Intermediate 32 (45) 284 (52) High 31 (44) 193 (35) Very High 4 (6) 22 (4) HLA - no. (%) 0.566 8/8 56 (79) 413 (76) 7/8 12 (17) 117 (21) 0.99 Matched related 25 (35) 197 (36) Matched unrelated 46 (65) 350 (64) Conditioning regimen - no. (%) 0.761 Full intensity 45 (63) 361 (66) Reduced intensity 26 (37) 186 (34) GVHD prophylaxis - no. (%) 0.002 Mycophenolate-Tacrolimus 41 (58) 328 (60) Mycophenolate-Tacrolimus-Thymoglobulin 26 (37) 131 (24) Tacrolimus- Thymoglobulin 3 (4) 17 (3) Thymoglobulin-Tacrolimus-Sirolimus 0 (0) 64 (12) Others 0 (0) 5 (1) Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Deol: Bristol meyer squibb: Research Funding.

275 Background: Ra 223 has been shown to improve overall survival in mCRPC patients with symptomatic bone metastases. Little is known about the utility of following PSA during Ra 223 therapy in heavily pretreated patients. Here we report our experience with Ra 223 in such a setting. Methods: We reviewed 26 heavily pretreated mCRPC patients who received Ra 223 at 3 institutions and evaluated the trend of PSA during treatment, the association of various demographic, clinical and biochemical variables with PSA trend, and the correlation of PSA trend with clinical outcomes. Patients received IV Ra 223 every 4 weeks with a planned total of 6 cycles. Results: Twenty six patients were treated between August 2013 and August 2014. Median age was 70 years (range 49-80); 77% (N=20) were European American (EA), 19% (N=5) were African Americans (AA), unknown for 1 patient. Prior therapy included docetaxel in 77% (N=20) of patients, cabazitaxel in 19% (N=5), enzalutamide in 65% (N=17), and abiraterone in 54% (N=14). 62% (N=16) received at least 3 prior therapies.35% (N=9) received all 6 cycles of Ra 223, while 18% (N=4) received only 1 cycle. Median alkaline phosphatase level increased from 126.0 U/L (54.0, 514.0) to 332.0 U/L (136.0, 566.0) at the end of Ra 223 therapy. Median pre-therapy PSA was 100.3 and median post-therapy PSA was 429.5. 54% (N=14) patients had >50% rise in PSA. Higher pre-therapy PSA was strongly associated with higher post-therapy PSA (Pearson’s correlation coefficient = 0.84, p 50% PSA rise had reported overall higher pain scores by visual assessment scale. Ra 223 was discontinued in 15% (N=4) patients due to myelosuppression and in 8% (N=2) due to side effects. Conclusions: All heavily pretreated patients receiving Ra 223 therapy for mCRPC showed PSA progression and reasonable tolerability. Only 35% of patients were able to receive all 6 cycles of Ra 223.

A principal goal for the use of positron emission tomography (PET) in oncology is for real-time evaluation of tumor response to chemotherapy. Given that many contemporary anti-neoplastic agents function by impairing cellular proliferation, it is of interest to develop imaging modalities to monitor these pathways. Here we examined the effect of capecitabine on the uptake of thymidine analogs used with PET: 3’-deoxy-3’-[18F]fluorothymidine (18F-FLT), 1-(2’-deoxy-2’-[18F]fluoro-β-D-arabinofuranosyl) thymidine (18F-FMAU), and 1-(2’-deoxy-2’-[18F]fluoro-β-D-arabinofuranosyl) uracil (18F-FAU) in patients with advanced cancer. Fifteen patients were imaged, five with each imaging agent. Patients had been previously diagnosed with breast, colorectal, gastric, and esophageal cancers and had not received therapy for at least 4 weeks prior to the first scan, and had not been treated with any prior fluoropyrimidines. Subjects were imaged within a week before the start of capecitabine and on the second day of treatment, after the third dose of capecitabine. Tracer uptake was quantified by mean standard uptake value (SUVmean) and using kinetic analysis. Patients imaged with 18F-FLT showed variable changes in retention and two patients exhibited an increase in SUVmean of 172.3 and 89.9 %, while the other patients had changes ranging from +19.4 to -25.4 %. The average change in 18F-FMAU retention was 0.2 % (range -24.4 to 23.1) and 18F-FAU was -10.2 % (range -40.3 to 19.2). Observed changes correlated strongly with SUVmax but not kinetic measurements. This pilot study demonstrates that patients treated with capecitabine can produce a marked increase in 18F-FLT retention in some patients, which will require further study to determine if this flare is predictive of therapeutic response. 18F-FAU and 18F-FMAU showed little change, on average, after treatment.