ALBERT

Description: Despite recent advancements, approximately 50% of patients with acute myeloid leukemia (AML) do not respond to induction therapy (primary induction failure, PIF) or relapse after

Description: Introduction Patients aged 〉60 years (y) with acute myeloid leukemia (AML) have inferior outcomes compared to those 60y with newly diagnosed AML or high-risk MDS combining pano at doses ranging from 20 mg to 60 mg given orally on days 1, 3, 5, and 8 of induction with daunorubicin (dauno) 60 mg/m2 on days 3-5 and ara-C 100mg/m2 continuously on days 3-10 (p+7+3). Patients were allowed retreatment on p+5+2, with pano on days 1, 3, and 5 at the same doses, if the nadir BM biopsy had residual leukemia. Upon attainment of CR/CRi, patients were offered a second p+7+3 or alternative consolidation including allogeneic stem cell transplantation (alloHCT). Dose-limiting toxicity was defined based on unexpected toxicities from 7+3 induction and a standard 3+3 design was utilized for dose escalation. Peripheral blood mononuclear cells were isolated on days 1-5 and HDAC expression and histone acetylation were evaluated by western blot and quantified by densitometry. Results Overall, 22 patients were treated on the PanDA protocol. Treatment was well-tolerated in all dose-cohorts and the MTD was not reached. We treated 6 patients each at the 60 mg and 50 mg dose in the dose expansion phase due to recurrent grade 1 bradycardia. The median age was 67y-60-69y (13), 70-79y (5), and 〉80y (4). Eleven patients had de novo AML, 7 had AML with myelodysplasia related changes, 2 had 2ary AML from MPD, 1 treatment-associated myeloid neoplasm, and 1 had RAEB-2. Two patients had progressed on hypomethylating agents. Thirteen (62%) had intermediate-risk cytogenetics (cyto). Amongst 8 euploid patients, 2 had FLT3-ITDmut, 1 had FLT3-TKDmut and 2 had NPM1mut as the sole abnormality. Seven (33%) patients had complex/monosomic cyto. There were no patients with favorable cyto. There were no protocol-defined DLTs. The most common grade 2-4 TEAEs were febrile neutropenia (77%), electrolyte abnormalities (64%), diarrhea (55%), rash (55%), LFT abnormalities (32%), nausea (27%) and anorexia (27%). Of note, 36% experienced asymptomatic sinus bradycardia peaking on day 6 following pano, dauno, and 5HT3 inhibitor anti-emetics. Additionally, 9% experienced new onset grade 2 atrial fibrillation. There was no evidence of myocardial dysfunction on echocardiogram following induction. SAEs reported on study were sepsis (9%), typhlitis (5%), DIC (5%), pneumonitis (5%), and bowel perforation due to mucorales (5%). There were 2 deaths (9%) during induction, one related to typhlitis and the other to sepsis. Of 20 evaluable patients, 8 (40%) achieved CR/CRi . One patient received study treatment as consolidation, 3 received intermediate/high-dose ara-C, 1 received a hypomethylating agent, 2 underwent alloHCT and 1 had no further therapy. Median overall survival was 10 mos (ITT) and 16 mos for those who achieved a CR/CRi (p=0.005). Median relapse-free survival was 10 mos, range 3-27 mos (Figure 1). Baseline expression of HDAC class 1, 2, 3 and 6 was evaluated and was not found to be associated with response to p+7+3 arguing against a direct role in p+7+3-induced cytotoxicity. However, global histone acetylation change after pano exposure (days 1-3) was significantly associated with eventual chemo-ablation at nadir (Figure 2). Ongoing studies are evaluating markers of DNA damage response and apoptosis in patients treated with PanDA vs. concurrent 7+3 controls. Conclusions The addition of pano to 7+3 induction for older patients with AML is well-tolerated and results in clinical outcomes that are favorable in our very high-risk population. The recommended dose of pano is 50 mg daily on days 1, 3, 5, and 8 when combined with 7+3 induction in future studies. Importantly, histone acetylation change following exposure to pano but not baseline HDAC expression predicts sensitivity to combined therapy. Disclosures Wieduwilt: Sigma-Tau: Research Funding; Alexion: Honoraria. Off Label Use: Panobinostat is approved for multiple myeloma. This paper reports it's use in patients with acute myeloid leukemia.. Olin:Daiichi-Sankyo: Research Funding. Logan:Pharmacyclics: Consultancy; Jazz Pharmaceuticals: Consultancy; Amgen: Consultancy. Damon:Atara: Consultancy; Sunesis: Research Funding; McGraw-Hill: Patents & Royalties: Book Chapter; Sigma-Tau: Research Funding. Boyer:Onyx: Speakers Bureau. Andreadis:genentech: Employment; novartis oncology: Research Funding; cellerant: Research Funding; karyopharm: Research Funding; McGraw-Hill: Patents & Royalties: Book Chapter; Pfizer: Honoraria; Pharmacyclics: Honoraria.

Description: Background: Cytokine release syndrome (CRS) management in acute myeloid leukemia (AML) patients treated with flotetuzumab, an investigational CD123xCD3 bispecific DART® molecule for T cell redirected therapy. CRS is a hallmark of T cell activating therapy and can be correlated with efficacy, specifically, with CAR-T cells(1). Identification of patients at risk for high grade CRS will help guide CRS management. Flotetuzumab (MGD006) is anovel CD123xCD3 bispecific DART® molecule in Phase 1/2 testing in patients with relapsed/ refractory AML. Several strategies have been successfully employed to mitigate CRS severity, some have been previously reported (2, 3). Here we report on further refinement of CRS management and subsequent investigation of potentiel predictive biomarkers of severity. Methods: The recommended phase 2 dose (RP2D) of flotetuzumab is 500ng/kg/d CIV. Week 1 comprises a step-wise lead-in dose (LID) (1-step: 100 ng/kg/day days 1-4; 2-step: 30ng/kg/d for 3days, 100ng/kg/d for 4days, or multi-step (MS) LID at 30, 60, 100, 200, 300, 400 and 500 ng/kg/day each for 24 hours) in order to improve flotetuzumab tolerability. Tocilizumab usage recommended early in CRS management. The relationships between immune cells (T-cell subsets, monocytes) and tumor burden (percent CD123+ AML blasts, CD123 expression) were further interrogated as potential determinants of CRS. Results: 50 patients have been treated at the RP2D. While almost all patients experienced IRR/CRS events, the majority of these patients experienced IRR/CRS that were mild-moderate in severity (28% Grade(G)1, 62% G2, and 8% G3), of short duration (median 1 day for G1, 2 days G2, 2.5 days G3), and resolved completely with no clinical sequalae reported. Most CRS events occured in the first week of treatment (38.3%) and gradually decreased with continuous dosing (24.8%, 7.4%, and 4.3% during weeks 2-4, respectively). Several key interventions have helped mitigate CRS severity. Sequential increment in steps of LID schedules (1 step, 2-step or multi-step LID) have successfully decreased CRS severity and incidence. For example, CRS mean grade±SEM for week 1 was 2.0±0.26 vs 1.4±0.72 vs 1.5±0.63 and for week 4, 0.67±0.42 vs 0.2 ±0.50 vs 0.1 ±0.50 (1 step, 2-step or multi-step LID, respectively). Moreover, LID improved overall tolerability. Introduction of early use of tocilizumab has helped forestall CRS development; 27 patients received tocilizumab (10 doses for G1, 27 for G2, and 2 for G3 events), only 5 pts have required steroids (4 for G2 and 1 for G3), and no pts have required vasopressor support. Blunting of CRS events did not impact antileukemic activity. CRS severity showed a relationship with baseline frequency of circulating CD4+ cells (mean 0.2 K/µL in patients with no CRS vs. 1.0 K/µL in G1 vs 1.6 K/µL in G ≥2, p 〈 0.000.1), and peak CRS grade in week 1. Conclusion: Like other T-cell activating therapies, flotetuzumab is associated with CRS. Several mitigating factors have helped to blunt the severity of CRS, including lead-in dosing and early tocilizumab usage. Circulating CD4+ cells at baseline continues to be associated with CRS risk, and may be a helpful marker to identify patients at increased risk for CRS. 1. Maude, SL. et al. Managing Cytokine Release Syndrome Associated With Novel T Cell-Engaging Therapies. Cancer J. 2014; 20(2): 119-122. 2. Jacobs, K, et al.Lead-in Dose Optimization to Mitigate Cytokine Release Syndrome in AML and MDS Patients Treated with Flotetuzumab, a CD123 x CD3 Dart® Molecule for T-Cell Redirected Therapy. Blood 2017 130:3856. 3. Jacobs, K, et al.Management of Cytokine Release Syndrome in AML Patients Treated with Flotetuzumab, a CD123 x CD3 Bispecific Dart® Molecule for T-Cell Redirected Therapy. Blood 2018 132:2738. Disclosures Bakkacha: Macrogenics,Inc: Employment, Equity Ownership. Uy:Astellas: Consultancy; Pfizer: Consultancy; Curis: Consultancy; GlycoMimetics: Consultancy. Aldoss:Helocyte: Consultancy, Honoraria, Other: travel/accommodation/expenses; AUTO1: Consultancy; Jazz Pharmaceuticals: Honoraria, Other: travel/accommodation/expenses, Speakers Bureau; Agios: Consultancy, Honoraria. Foster:Bellicum Pharmaceuticals, Inc: Research Funding; Daiichi Sankyo: Consultancy; MacroGenics: Research Funding; Celgene: Research Funding. Sallman:Celyad: Membership on an entity's Board of Directors or advisory committees. Sweet:Pfizer: Consultancy; Incyte: Research Funding; Agios: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Stemline: Consultancy; Jazz: Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Rizzieri:Celgene, Gilead, Seattle Genetics, Stemline: Other: Speaker; AbbVie, Agios, AROG, Bayer, Celgene, Gilead, Jazz, Novartis, Pfizer, Sanofi, Seattle Genetics, Stemline, Teva: Other: Advisory Board; AROG, Bayer, Celgene, Celltron, Mustang, Pfizer, Seattle Genetics, Stemline: Consultancy; Stemline: Research Funding. Advani:Glycomimetics: Consultancy, Research Funding; Kite Pharmaceuticals: Consultancy; Amgen: Research Funding; Pfizer: Honoraria, Research Funding; Macrogenics: Research Funding; Abbvie: Research Funding. Emadi:Genentech: Consultancy, Honoraria; KinaRx: Membership on an entity's Board of Directors or advisory committees, Other: Co-Founder and Scientific Advisor, Patents & Royalties; NewLink Genetics: Research Funding; Jazz Pharmaceuticals: Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Wieduwilt:Reata Pharmaceuticals: Equity Ownership; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen, Leadiant, Merck, Servier: Research Funding. Vey:Novartis: Consultancy, Honoraria; Janssen: Honoraria. Arellano:Gilead: Consultancy. Löwenberg:Up-to-Date", section editor leukemia: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Astex: Membership on an entity's Board of Directors or advisory committees; Chairman, Leukemia Cooperative Trial Group HOVON (Netherlands: Membership on an entity's Board of Directors or advisory committees; Clear Creek Bio Ltd: Consultancy, Honoraria; Editorial Board "European Oncology & Haematology": Membership on an entity's Board of Directors or advisory committees; Elected member, Royal Academy of Sciences and Arts, The Netherlands: Membership on an entity's Board of Directors or advisory committees; Frame Pharmaceuticals: Equity Ownership; Hoffman-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees; Royal Academy of Sciences and Arts, The Netherlands: Membership on an entity's Board of Directors or advisory committees; Supervisory Board, National Comprehensive Cancer Center (IKNL), Netherland: Membership on an entity's Board of Directors or advisory committees; Chairman Scientific Committee and Member Executive Committee, European School of Hematology (ESH, Paris, France): Membership on an entity's Board of Directors or advisory committees; CELYAD: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Ravandi:Cyclacel LTD: Research Funding; Menarini Ricerche: Research Funding; Selvita: Research Funding; Xencor: Consultancy, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Macrogenix: Consultancy, Research Funding. Tran:MacroGenics: Employment. Muth:MacroGenics, Inc.: Employment, Equity Ownership. Baughman:MacroGenics, Inc.: Employment, Equity Ownership. Timmeny:MacroGenics, Inc.: Employment, Other: Stock Ownership. Topp:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Guo:Macrogenics: Employment. Zhao:MacroGenics, Inc.: Employment. Wigginton:macrogenics: Employment, Equity Ownership; western oncolytics: Consultancy, Other: consultancy. Bonvini:MacroGenics, Inc.: Employment, Equity Ownership. Walter:Daiichi Sankyo: Consultancy; Amgen: Consultancy; Agios: Consultancy; Boston Biomedical: Consultancy; Covagen: Consultancy; Amphivena Therapeutics: Consultancy, Equity Ownership; Aptevo Therapeutics: Consultancy, Research Funding; Argenx BVBA: Consultancy; Astellas: Consultancy; BioLineRx: Consultancy; BiVictriX: Consultancy; Boehringer Ingelheim: Consultancy; Pfizer: Consultancy, Research Funding; Race Oncology: Consultancy; Seattle Genetics: Research Funding; Jazz Pharmaceuticals: Consultancy; Kite Pharma: Consultancy; New Link Genetics: Consultancy. Davidson:Macrogenics,Inc: Employment, Equity Ownership. DiPersio:Incyte: Consultancy, Research Funding; Celgene: Consultancy; Karyopharm Therapeutics: Consultancy; Bioline Rx: Research Funding, Speakers Bureau; RiverVest Venture Partners Arch Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cellworks Group, Inc.: Membership on an entity's Board of Directors or advisory committees; Magenta Therapeutics: Equity Ownership; WUGEN: Equity Ownership, Patents & Royalties, Research Funding; Amphivena Therapeutics: Consultancy, Research Funding; NeoImmune Tech: Research Funding; Macrogenics: Research Funding, Speakers Bureau. Jacobs:Macrogenics,Inc: Employment, Equity Ownership.

Description: Abstract 3075 Multiple sclerosis (MS) is an autoimmune disease which in most patients presents as defined relapses followed by remissions (relapsing-remitting (RR)). Over time the clinical course evolves to a gradual but irreversible loss of neurological function to which a neurodegenerative process likely contributes. Previous studies of high-dose immunosuppressive therapy (HDIT) and autologous hematopoietic cell transplantation (HCT) were done in patients with advanced progressive MS and many patients continued to lose neurological function. To investigate the potential benefit of HDIT/HCT to halt the evolution of MS and prevent the development of the neurodegenerative processes, HDIT/HCT was studied in RRMS. A phase II clinical trial of HDIT (BCNU, etoposide, ara-C and melphalan (BEAM) and antithymocyte globulin (ATG)) and autologous HCT was conducted in patients with highly active RRMS who had failed conventional therapy to determine if sustained remissions could be induced. Eligibility criteria required Expanded Disability Status Scale (EDSS) 3.0 (moderate disability, fully ambulatory) -5.5 (severe disability, ambulatory only 100 meters without aids) and ≥2 relapses on MS treatment with EDSS worsening over the previous 18 months. Hematopoietic progenitor cells were mobilized with G-CSF and a 10-day course of prednisone. The graft was CD34-selected (Baxter, Isolex). The primary endpoint was treatment-failure defined as a composite endpoint of 1) mortality 2) relapse 3) new lesions on MRI or 4) progression in disability ≥1.0 EDSS point. Adverse events (AE) were recorded according to NCI-CTCAE v3.0. Twenty-five patients at a median age of 38(27–53) years had autologous hematopoietic stem cells collected. There were 7 Grade 3 non-hematopoietic AEs during mobilization; mostly line-associated thromboses and infections. There was 1 Grade 4 AE with pretransplant withdrawal from study; a pulmonary embolus associated with heparin-induced thrombocytopenia and pre-existing arteriovenous malformation in the brain. During mobilization, a MS flare occurred in one patient who was non-compliant with the prednisone prophylaxis. Twenty-four patients proceeded to transplant. Median follow-up is 80(52–232) weeks. Patients were infused with a median of 4.58(2.95–9.73) × 106 CD34+ cells/kg. Neutrophil recovery occurred at a median of +11(9–15) days. In the 1st year after transplant, there were 17 Grade 3 and 4 Grade 4 non-hematopoietic, non-GI AEs. The Grade 4 AEs were suicide attempt (recorded as 2 separate events), hypokalemia and increase in ALT. At baseline (n=24), one (n=23) and two (n=8) years after HDIT/HCT, the mean EDSS (SD) was 4.42(+/−0.637), 3.78(+/−0.951) and 4.13(+/−0.916) respectively. There was only one case with gadolinium-enhancing lesions after 6 months (at Year 3) (Table 1). T2 lesion volume decreased and T1 lesion volume increased from baseline to Month 12. Despite the decrease in T2 lesion volume, there was early posttransplant loss in brain volume. Four patients failed by the composite endpoint (relapses at +22 and +96 weeks; new MRI brain lesions at +197 weeks and progression of disability/death at +82/138 weeks). Event-free survival at 1 and 2 years was 95.8(90% CI :73.9, 99.4)% and 76.7(90% CI :41.1, 92.4)% respectively. 22/24 patients were without progression of disability at last follow-up.Table 1:Brain MRI: Changes in first year after transplant.Baseline n=24Month 2 n=24Month 6 n=24Month 12 n=23Total Gd+ lesions [n (%)]014 (58%)19 (90%)22 (96%)22 (100%)14 (17%)0 (0%)1 (4%)0 (0%)2+6 (25%)2 (10%)0 (0%)0 (0%)T2 lesion volume change (cc)*n202320Median(min, max)-0.13 (-6.51,1.26)-0.60 (-6.46,1.73)-0.58 (-5.14,0.97)1T1 lesion volume change (cc)*n202320Median (min, max)-0.002 (-1.10, 0.87)0.02 (-0.87, 0.99)0.11 (-0.40,1.74)2Brain volume change (%)*n202419Mean (SD)-0.91 (0.73)3-1.19 (0.86)-1.28 (1.01)*Change from baselineWilcoxon signed rank test: 1) p=0.0014; 2) p=0.0186 3) t-test: p

Description: Background Although multiple studies have shown superiority of allogeneic hematopoietic cell transplantation (alloHCT) over autologous hematopoietic cell transplantation (autoHCT) for patients with "high-risk" acute lymphoblastic leukemia (ALL), these findings may be explained, in part, by contamination of the peripheral blood progenitor cell (PBPC) leukapheresis product by residual leukemic cells in patients undergoing autoHCT. Methods We retrospectively evaluated minimal residual disease (MRD) via next-generation sequencing (NGS) (Adaptive Biotechnologies, S. San Francisco, CA) in the PBPC leukapheresis products from 32 ALL patients who underwent autoHCT. All patients had "high-risk" ALL, as defined by B-lineage disease with WBC at diagnosis 〉30,000/uL; high-risk cytogenetics including t(9;22), t(4;11), other 11q23 abnormalities, or monosomy 7; or primary refractory disease. Peripheral hematopoietic cell mobilization consisted of cytarabine 2000mg/m2 IV every 12 hours (16,000mg/m2 cumulative) concurrent with etoposide 40mg/kg cumulative by continuous IV infusion over 4 days. The autoHCT conditioning consisted of 1320cGy total body irradiation (TBI) given in 11 fractions from day -8 to -5, etoposide 60mg/kg IV on day -4, and cyclophosphamide 100mg/kg IV on day -2. Tyrosine kinase inhibitors (TKI) were allowed for patients with Philadelphia chromosome-positive (Ph+) B-ALL. Seven patients (22%) participated in a multi-institutional trial in which the PBPC graft underwent ex vivo complement-mediatedpurging using monoclonal antibodies against CD9/CD10/CD19/CD20 for patients with B-lineage disease, or against CD2/CD3/CD4/CD5/CD8 for patients with T-lineage disease. Kaplan-Meier curves were generated using GraphPad Prism (GraphPad Software, La Jolla, CA) and statistical differences assessed via Log-Rank and Wilcoxon analyses, with a p-value of

Description: Approximately 40% of patients (pts) with newly diagnosed (AML) either fail to achieve complete remission with intensive induction therapy or experience disease recurrence after a short remission duration (〈 6 months). These pts, herein considered to have primary refractory disease, are an extremely challenging population to treat, with only 14% achieving remission following conventional chemotherapy and with subsequent salvage attempts being nearly universally ineffective (1). Increased immune infiltration of the tumor microenvironment (TME) and high CD123 expression on AML blasts have been associated with primary induction failure and poor prognosis (2, 3). Flotetuzumab (FLZ), a CD123 x CD3 bispecific DART molecule, is currently being tested in a phase 1/2 study in pts with either relapsed or refractory (R/R) AML. We have previously reported FLZ activity in primary refractory AML (4); herein, we provide additional scientific rationale supporting the investigation of FLZ in this patient population. The recommended Phase 2 dose (RP2D) of FLZ identified in an ongoing Phase 1/2 study is 500 ng/kg/day administered as a 7 -day/week continuous infusion. Pts receive a lead-in dose during week (W) 1, followed by 500 ng/kg/day during W2-4 of Cycle 1, and a 4-day on/3-day off schedule for Cycle 2 and beyond. Disease status was assessed by modified IWG criteria; bone marrow (BM) samples were collected to investigate biomarkers, including CD123 receptor density (RD), and gene expression profiling using the NanoString PanCancer IO 360™ panel, which measures the expression of 770 genes, including 14 immune cell types and 32 immuno-oncology biological signatures. Gene expression comparisons are presented at fold change (FC) and a t-test was used for statistical analysis. Fifty pts with R/R AML received FLZ at the RP2D. Thirty (60%) pts had primary refractory AML: 24 failed ≥2 induction attempts and 6 recurred after remission of

Description: Background: Patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs) have high symptom burdens that negatively impact quality of life, including risk for developing chronic pain and psychosocial complications. The NCCN guidelines recommended the use of the MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) starting in 2017 to assess symptom burden. Our primary aim was to determine if the MPN-SAF TSS has been incorporated into patient care, and if not, how well BCR-ABL-negative MPN symptoms are captured by review of systems (ROS). Our secondary aim was to evaluate the prevalence of anxiety, depression, chronic pain, and opiate use in our patient population. Methods: We performed a single-center, cross-sectional study of all active BCR-ABL-negative MPN patients in the UCSF Hematology Clinic between January 2017 and March 2019. We reviewed all hematology visits for completion of the MPN-SAF TSS, and the most recent visit for the number symptoms from the MPN-SAF TSS explicitly captured in ROS or problem list and relevant medications. Descriptive statistics were used to summarize the data. Patients whose disease transformed into acute leukemia or were post-allogeneic stem cell transplantation were excluded. Results: Of 299 patients with BCR-ABL-negative MPN diagnoses, the median age was 66 (range 20-98) with an equal number of males (n=150) and females (n=149). Essential thrombocythemia (ET) was the most common diagnosis (n=109; 37%), followed by polycythemia vera (PV) (n=90; 30%), primary myelofibrosis (MF) (n=49; 16%), post-PV or post-ET MF (n=29; 10%), and MPN-Unclassifiable or overlap (n=22; 7%). Most were JAK2 V617F positive (n=213; 71%) and high-risk (n=148; 49.5%) by clinical criteria, IPSET-thrombosis, and DIPSS-plus. Nearly all were on active treatment (91%), with aspirin (n=205; 69%), hydroxyurea (n=130; 43.5%), phlebotomy (n=61; 20%), and ruxolitinib (n=37; 12%) being the most frequent treatments. Significant disease-related vascular complications were documented in 20.7% of patients. The 299 patients were evaluated by 22 hematology providers. The MPN-SAF TSS was formally documented in 1 patient (0.3%). Of the 10 symptoms in the MPN-SAF TSS, the median number documented as positive or negative on ROS was 3 (range 0-8), with 0 or 1 symptoms documented in 82 patients (27.4%). The mean number of positive symptoms was 0.7 (range 0-4) with at least 1 positive symptom reported by 44.7%. The most frequently charted symptoms were fever (n=182; 60.9%), unintentional weight loss (n=137; 45.8%), abdominal pain (n=137; 45.8%), and night sweats (n=130; 43.5%). More unique MPN symptoms were documented less frequently, including pruritis (n=89; 29.8%), early satiety (n=56; 18.7%), bone pain (n=28; 9.4%), and problems with concentration (n=3; 1%). The most common positive symptoms were fatigue (n=90; 73%), pruritis (n=30; 33.7%) and bone pain (n=9; 32%). Pain and psychological symptoms were infrequently charted in hematology clinic. Pain medications were used by 20.4% with nearly half (48%) on opiates, but chronic pain was on the provider problem list for only 5.7% of patients. Anxiety/depression medications were used by 20.4%, but anxiety/depression was on the provider problem list in only 4% of patients. Conclusions: To our knowledge, this is the first study to assess the implementation of the MPN-SAF TSS into clinical practice since the NCCN recommendations went into effect. The MPN-SAF TSS is not being utilized in regular practice at our site and a low number of disease-related symptoms are documented in clinic notes. Fatigue is the predominant symptom in our patients, which is similar to previously published studies. The discrepancy between medications taken and symptoms documented suggests that patients have a higher symptom burden than reported. Implementing a standardized way of consistently capturing patients' MPN-related symptoms in hematology practice will be explored in future quality improvement research. Disclosures Damon: Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Logan:Incyte: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Research Funding; Kite: Research Funding; Kadmon: Research Funding; Pharmacyclics: Research Funding; Novartis: Consultancy; TeneoBio: Consultancy; Kiadis: Consultancy; Astellas: Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Mannis:Jazz: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Abbvie/Genentech: Membership on an entity's Board of Directors or advisory committees; Forty Seven: Membership on an entity's Board of Directors or advisory committees; Curis: Membership on an entity's Board of Directors or advisory committees. Olin:Spectrum: Research Funding; Novartis: Research Funding; Mirati Therapeutics: Research Funding; MedImmune: Research Funding; Ignyta: Research Funding; Clovis: Research Funding; Daiichi Sankyo: Research Funding; Astellas: Research Funding; Genentech: Consultancy, Research Funding; Pfizer: Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria; Revolution Medicine: Consultancy; AstraZeneca: Research Funding. Shah:Bristol-Myers Squibb: Research Funding. Atreya:Immunotherapeutics: Honoraria; Guardant Health: Research Funding; Novartis: Research Funding; Merck: Research Funding; Kura Oncology: Research Funding; Array Biopharma: Honoraria; Pionyr: Honoraria; Bristol-Meyers Squibb: Research Funding. Smith:Astellas Pharma: Research Funding; Abbvie: Research Funding; fujiFilm: Research Funding; Revolution Medicines: Research Funding.

Description: Introduction Arsenic trioxide (ATO)-based therapy for acute promyelocytic leukemia (APL) is highly effective and has been incorporated into standard therapeutic algorithms for patients with newly diagnosed and relapsed disease. Therapy for patients with high-risk or relapsed APL also includes high-dose chemotherapy with autologous stem cell transplantation (autoSCT). Both treatments have independently been demonstrated to improve long-term disease-free survival; however, the use of ATO prior to autoSCT has not been well studied. We sought to determine whether use of ATO prior to autologous stem cell collection impacts hematopoietic recovery following autoSCT. Methods Clinical histories of 31 consecutive patients undergoing autoSCT for APL at our institution since 1994 were reviewed. Viable CD34-positive cell recovery from cryo-preserved autograft products was assessed by pre- and post-thaw 7-amino-actinomycin D (7-AAD) staining. Student's t-tests and chi-squared tests were used for statistical analyses. Results A total of 32 autoSCTs were performed in this population. Twenty-four transplants (75.0%) were performed for patients in first complete remission (CR1) versus 8 transplants (25.0%) for patients in second complete remission (CR2). Seven of the 32 transplants (21.8%) were performed for patients who received ATO therapy prior to autologous stem cell collection. One patient received ATO with initial induction and consolidation therapy, 1 patient received ATO with initial consolidation therapy only, and 5 patients received ATO with re-induction therapy for relapsed disease. A significantly higher proportion of patients who received ATO were transplanted in CR2 (71.5% vs 12.0%, p10,000/uL at presentation (28.6% vs 45.8%, p=0.42), mean CD34-positive cells collected (94.5 x106/kg vs 69.9x106/kg, p=0.35), or mean CD34-positive cells infused (41.4x106/kg vs 39.7x106/kg, p=0.90). Four cases (12.5%) of delayed hematopoietic recovery were identified, defined as requiring 〉16 days after stem cell infusion to recover an absolute neutrophil count (ANC) 〉1,000/uL. Three of 7 patients (43%) who received prior ATO had delayed hematopoietic recovery, compared with 1 of 24 patients (4.2%) not previously treated with ATO (p

Description: Abstract 962 Most patients with relapsing-remitting multiple sclerosis (RRMS) do not achieve a sustained remission after disease-modifying therapy. A phase II clinical trial of high-dose immunochemotherapy (HDIT; BCNU, etoposide, ara-C, melphalan and antithymocyte globulin) and autologous hematopoietic cell transplantation (HCT) was conducted in patients with highly active RRMS who had failed conventional therapy to assess if a high rate of sustained remission could be induced. Eligibility required an EDSS of 3.0 (moderate disability, fully ambulatory) to 5.5(severe disability, ambulatory only 100 meters without aids) and 〉2 relapses on treatment in previous 18 months. Treatment-failure was defined as a composite endpoint including 1) mortality 2) relapse 3) new MRI lesions or 4) disability increase 〉0.5 EDSS points. Adverse events (AE) were recorded according to NCI-CTCAE v3.0. 25 patients at a median age of 38(27-53) years were treated with G-CSF to mobilize the autograft; prednisone was given at the same time to prevent MS flares. The autograft was CD34-selected (Baxter, Isolex). One patient withdrew after mobilization secondary to HIT/pulmonary embolus. 24 patients had HDIT/HCT according to protocol. Median follow-up was 131 (52, 282) weeks. After initially stabilizing, one patient died from progressive loss of neurological function at 32 months. No patient had delayed recovery of blood counts. In the 1st year after HDIT, there were 42 grade 3 and 6 grade 4 non-hematopoietic AE. Grade 4 AE included: one suicide attempt (with 3 grade 4 AE); hyperuricemia; hypokalemia; and elevated ALT. In the 2ndyear, there were 13 grade 3 and 1 grade 4 non-hematopoietic AE. The 1-year and 2-year probabilities of event-free survival (i.e. without treatment-failure) were 95.8% (90% CI: 80.2%-99.2%) and 82.8% (90% CI: 65.0%-92.0%), respectively. Progression-free and relapse-free survival at 1 year were 100% (90% CI: 100%-100%) and 95.8% (90% CI: 80.2%-99.2%) and at 2 years were 91.7% (90% CI: 75.7%-97.3%) and 91.7% (90% CI: 75.7%-97.3%), respectively. The probability of freedom from disease activity detected by brain MRI was 95.8% (90% CI: 80.2%-99.2%) at both year 1 and 2. In comparison, a randomized clinical trial of placebo vs natalizumab (Havrdova E et al, Lancet Neurology, 2009) showed that 7% and 37% of RRMS patients were free of disease activity (i.e. progression, relapse and MRI) at 2 years, respectively. T2-weighted MRI scans measure disease burden from MS. T2 lesion volume was significantly reduced by 6 months and was sustained at 2 years (Table 1). T1 lesion volume was increased at 1 year. There was a significant loss of brain volume at 6 months but stabilized after this time point. Flow cytometry of peripheral blood was done at baseline and at 1, 2, 6 and 12 months. There was near complete depletion of naïve CD4 and CD8 T cells (CD45RA+) at 1 month. Memory CD4 and CD8 T cells (CD45RO+) were not completely eliminated from the blood after in vivo depletion from HDIT. Within 2 months of transplant, there was rapid expansion of memory CD8 T cells. The numbers of CD4 naïve and memory T cells were not recovered at 1 year. CD4 and CD8 recent thymic emigrants (CD45RA+, CD31+) were increased at 1 year compared to the nadir at 1 month but did not completely recover. Recovery of naïve and memory B cells was complete between months 6 and 12. HDIT/HCT for highly active RRMS resulted in profound immunosuppression and induced a high rate of sustained remissions at 2 years. The small increase in T1-weighted lesion volume in the absence of persistent brain inflammation may have resulted from damage due to previous brain injury. No further loss in brain volume was observed after 6 months. Follow-up is planned through 5 years. Table 1: Brain MRI: Changes after HDIT/HCT as compared to baseline* or screening**. Disclosures: No relevant conflicts of interest to declare.