Citations

Background: Prepectoral implant-based reconstruction reemerged as a viable approach following recent advances in reconstructive techniques and technology. To achieve successful outcomes, careful patient selection is critical. Obesity increases the risk of complications and has been suggested as a relative contraindication for prepectoral breast reconstruction. Methods: Retrospective chart review of patients who underwent immediate two-stage implant-based reconstruction at the authors’ institution was performed. Only women having a body mass index of 30 kg/m2 or greater were included. Patient demographics, operative details, and surgical outcomes of prepectoral and subpectoral reconstruction were compared. Results: One hundred ten patients (189 breasts) who underwent prepectoral and 83 (147 breasts) who underwent subpectoral reconstruction were included. Complications were comparable between the two groups. Twelve devices (6.4 percent), including implants and tissue expanders, required explantation in the prepectoral group, and 12 devices (8.2 percent) required explantation in the subpectoral group (p =0.522). Final implant-based reconstruction was achieved in 180 breasts (95.2 percent) in the prepectoral group and 141 breasts (95.9 percent) in the subpectoral group. Regardless of type of reconstruction (prepectoral or subpectoral), for each point increase in body mass index, the odds of complications and device explantation increased by 3.4 percent and 8.6 percent, respectively; and the optimal cutoff to predict higher complications and explantation rates was a body mass index of 34.8 kg/m2 and 34.1 kg/m2, respectively. Conclusions: Obesity increases complications and failure rates in a positive correlation; however, complications and final reconstruction rates are comparable between the prepectoral and subpectoral groups. The authors believe that obesity should not be a contraindication for prepectoral breast reconstruction but that care should be taken in patients with a body mass index above 35 kg/m2. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Background Past research has shown how fires, heat and hot substances are important causes of health loss globally. Detailed estimates of the morbidity and mortality from these injuries could help drive preventative measures and improved access to care. Methods We used the Global Burden of Disease 2017 framework to produce three main results. First, we produced results on incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years from 1990 to 2017 for 195 countries and territories. Second, we analysed these results to measure mortality-to-incidence ratios by location. Third, we reported the measures above in terms of the cause of fire, heat and hot substances and the types of bodily injuries that result. Results Globally, there were 8 991 468 (7 481 218 to 10 740 897) new fire, heat and hot substance injuries in 2017 with 120 632 (101 630 to 129 383) deaths. At the global level, the age-standardised mortality caused by fire, heat and hot substances significantly declined from 1990 to 2017, but regionally there was variability in age-standardised incidence with some regions experiencing an increase (eg, Southern Latin America) and others experiencing a significant decrease (eg, High-income North America). Conclusions The incidence and mortality of injuries that result from fire, heat and hot substances affect every region of the world but are most concentrated in middle and lower income areas. More resources should be invested in measuring these injuries as well as in improving infrastructure, advancing safety measures and ensuring access to care.

PURPOSETo estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized.METHODSWe analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes.RESULTSWe found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10−76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10−3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10−3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 × 10−2). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age ( P for trend = 2.0 × 10−3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies ( P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer.CONCLUSIONThese results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.

Objectives/HypothesisCreate a competency‐based assessment tool for pediatric tracheotomy.Study DesignBlinded, modified, Delphi consensus process.MethodsUsing the REDCap database, a list of 31 potential items was circulated to 65 expert surgeons who perform pediatric tracheotomy. In the first round, items were rated as “keep” or “remove,” and comments were incorporated. In the second round, experts were asked to rate the importance of each item on a seven‐point Likert scale. Consensus criteria were determined a priori with a goal of 7 to 25 final items.ResultsThe first round achieved a response rate of 39/65 (60.0%), and returned questionnaires were 99.5% complete. All items were rated as “keep,” and 137 comments were incorporated. In the second round, 30 task‐specific and seven previously validated global rating items were distributed, and the response rate was 44/65 (67.7%), with returned questionnaires being 99.3% complete. Of the Task‐Specific Items, 13 reached consensus, 10 were near consensus, and 7 did not achieve consensus. For the 7 previously validated global rating items, 5 reached consensus and two were near consensus.ConclusionsIt is feasible to reach consensus on the important steps involved in pediatric tracheotomy using a modified Delphi consensus process. These items can now be considered to create a competency‐based assessment tool for pediatric tracheotomy. Such a tool will hopefully allow trainees to focus on the important aspects of this procedure and help teaching programs standardize how they evaluate trainees during this procedure.Level of Evidence5 Laryngoscope, 130:2700–2707, 2020

Introduction: Despite advances in treatment strategy, multiple myeloma (MM) remains a challenging, incurable disease as patients (pts) often relapse. Here we describe preclinical data of a novel cereblon (CRBN) E3 ligase modulatory compound (CELMoD), iberdomide (IBER; CC-220), as well as clinical and translational data from a current phase 1/2 clinical trial (NCT02773030). These data support a differentiated profile for IBER from immunomodulatory agents (IMiD agents), and development of IBER as a foundation of combination therapy for the treatment of relapsed/refractory MM (RRMM). Methods: Preclinical analyses were performed on pomalidomide (POM)-sensitive and acquired-resistant MM cell lines and peripheral blood mononuclear cells from healthy volunteers. Eligible pts enrolled on the clinical trial had RRMM and had received ≥ 2 prior regimens, containing at least an IMiD agent and proteasome inhibitor (PI), and had experienced disease progression within 60 days of last MM therapy. Escalating doses of IBER were given on Days 1-21, in combination with dexamethasone (DEX; 40 mg; 20 mg in pts aged > 75 years) on Days 1, 8, 15, and 22, of each 28-day cycle. Immunohistochemistry (IHC) data on CRBN, Ikaros, Aiolos, and ZFP91 expression was obtained from pt bone marrow specimens at screening and at Cycle 2, Day 15. Immune profiling was evaluated by flow cytometry of peripheral blood at Cycle 1, Day 1 and Cycle 2, Day 15. Primary objectives were to evaluate maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety, and preliminary efficacy. Results: Preclinically, IBER exhibited potent tumoricidal anti-MM and immunostimulatory activity. IBER was more potent than lenalidomide (LEN) or POM in overcoming the immunosuppressive activity of bortezomib (BORT), inducing a more than twofold increase in T cell proliferation in the presence of BORT. IBER also enhanced the antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity of daratumumab (DARA), leading to deeper responses than combinations with LEN or POM. Further differentiating from both LEN and POM, IBER showed activity alone and in combination with BORT or DARA in POM-resistant MM cell lines. As of June 28, 2019, 69 pts with RRMM had received IBER + DEX. Median age was 65 years (range 33-80), and median number of prior regimens was 5 (range 2-12). Prior therapies included autologous stem cell transplantation (80%), LEN (100%), POM (70%), PIs (100%), DARA (71%) and anti-BCMA (6%), including CAR T cells. Clinical activity was observed across all dose levels with an overall response rate (ORR) of 29%, clinical benefit rate of 45%, and disease control rate of 80%. ORR was 30%, 28% and 29% in IMiD agent-refractory, DARA-refractory and Quad-class (IMiD agents/PIs/steroids/CD-38 antibodies)-refractory pts, respectively. IBER + DEX showed a favorable safety profile, with grade 3-4 neutropenia, infections, and thrombocytopenia, occurring in 29%, 25%, and 12% of pts, respectively. To date, IBER doses range from 0.3 to 1.3 mg and the MTD/RP2D has not yet been reached. Pharmacodynamic immunophenotyping changes were dose-dependent. Treatment with IBER (at doses > 0.75mg) + DEX doubled the percentage of proliferating T cells and NK cells (P < 0.001 for each) and increased activated and effector memory CD8+ and CD4+ T cells by > 50% (P < 0.01 for each subset). Pharmacodynamic changes in pt bone marrow by quantitative IHC scoring showed significant degradation of substrates (Ikaros, P = 0.006; Aiolos, P < 0.001; ZFP91, P < 0.001) and downregulation of c-myc (P = 0.027), including in pts refractory to POM and with low CRBN expression. Conclusions: IBER + DEX has shown notable clinical activity and favorable tolerability in heavily pretreated pts with RRMM, including pts refractory to prior IMiD therapy. Preclinical and translational data suggest a differentiated profile of IBER from IMiD agents in regard to activity in POM-resistant models, potency in combination with BORT and DARA, and by inducing changes in CD4+ T cells that were not observed in pts treated with POM from prior studies. Taken together, these data support a differentiated profile for IBER from IMiD agents, and the clinical development of IBER as a foundation of combination therapy for the treatment of RRMM. This study is ongoing, and includes cohorts evaluating the combinations of IBER + DEX with DARA, BORT, and carfilzomib. Updated results will be presented at the meeting. Disclosures Lonial: Karyopharm: Consultancy; GSK: Consultancy; Takeda: Consultancy, Research Funding; Celgene Corporation: Consultancy, Research Funding; Amgen: Consultancy; Genentech: Consultancy; Janssen: Consultancy, Research Funding; BMS: Consultancy. Amatangelo:Celgene Corporation: Employment, Equity Ownership. Popat:Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel, accommodations, expenses; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria; Takeda: Honoraria, Other: travel, accommodations, expenses; Janssen: Honoraria, Other: travel support to meetings. Minnema:Gilead: Honoraria; Celgene Corporation: Honoraria, Research Funding; Amgen: Honoraria; Servier: Honoraria; Jansen Cilag: Honoraria. Zonder:Alnylam: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Intellia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Caelum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Larsen:Janssen Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Oriol Rocafiguera:Celgene Corporation: Consultancy, Speakers Bureau; Janssen: Consultancy; Amgen: Consultancy, Speakers Bureau. Rodriguez Otero:Celgene Corporation: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria; Takeda: Consultancy; BMS: Honoraria; Kite Pharma: Consultancy. Badros:Celgene Corporation: Consultancy; Amgen: Consultancy. Siegel:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Jagannath:Bristol-Myers Squibb: Consultancy; Janssen Pharmaceuticals: Consultancy; Karyopharm Therapeutics: Consultancy; AbbVie: Consultancy; Merck & Co.: Consultancy; Celgene Corporation: Consultancy. Bringhen:Bristol-Myers Squibb: Honoraria; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy. Gironella:Amgen: Honoraria; Janssen: Honoraria; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kaiser:Takeda, Janssen, Celgene, Amgen: Honoraria, Other: Travel Expenses; Abbvie, Celgene, Takeda, Janssen, Amgen, Abbvie, Karyopharm: Consultancy; Celgene, Janssen: Research Funding. Cook:Janssen, Takeda, Sanofi, Karyopharm, Celgene: Consultancy, Honoraria, Speakers Bureau; Amgen, Bristol-Myers Squib, GlycoMimetics, Seattle Genetics, Sanofi: Honoraria; Celgene, Janssen-Cilag, Takeda: Honoraria, Research Funding. Gamberi:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sonneveld:SkylineDx: Research Funding; Takeda: Honoraria, Research Funding; Karyopharm: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; BMS: Honoraria; Amgen: Honoraria, Research Funding. Nguyen:Celgene Corporation: Employment, Equity Ownership. Chen:Celgene Corporation: Employment, Equity Ownership. Homan:Celgene Corporation: Employment. Bjorklund:Celgene Corporation: Employment, Equity Ownership. Wang:Celgene Corporation: Employment, Equity Ownership. Pierceall:Celgene Corporation: Employment, Equity Ownership. Bensmaine:Celgene Corporation: Employment, Equity Ownership. Thakurta:Celgene: Employment, Equity Ownership. Peluso:Celgene Corporation: Employment. Van De Donk:Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier: 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, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; AMGEN: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees.

Background With the exception of therapy related MDS due to treatment with alkylating agents and/or radiation or with a topoisomerase II inhibitor, little is known about the etiology of myelodysplastic syndromes (MDS). A few studies have evaluated pre-existing medical conditions as risk factors for MDS, with evidence suggesting that autoimmune disease is associated with an increased risk of MDS. Here, we evaluated associations between history of autoimmune disease, overall and by individual disease subtype, and risk of MDS in a population-based case control study. Methods MDS cases were identified by rapid case ascertainment through the population-based Minnesota Cancer Surveillance System (MCSS). Participants were recruited if they were diagnosed with MDS between April 1, 2010 and October 31, 2014. Eligibility criteria included residence in Minnesota, age at diagnosis between 20 and 85 years, and ability to understand English or Spanish. Centralized pathology and cytogenetics review were conducted to confirm diagnosis and classify by subtypes. Controls were identified through the Minnesota State driver's license/identification card list. History of autoimmune disease was reported using a self-administered questionnaire; proxy interviews were not conducted. Unconditional logistic regression with adjustment for age, sex and confounders (education, NSAID use, benzene exposure, BMI) was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CI) for autoimmune disease and MDS. Results A total of 399 cases with a confirmed diagnosis of MDS and 1399 controls were included. Cases were significantly more likely to report a diagnosis of any autoimmune disease when compared with controls (OR=1.49, 95% CI 1.13-1.97). As illustrated in Figure 1, specific associations were observed for hypothyroidism (OR=2.07, 95% CI 1.39-3.08), ulcerative colitis (OR=2.26, 95% CI 1.09-4.69), Crohn's disease (OR=3.88, 95% CI 1.23-12.2), and systemic lupus erythematosus (SLE; OR=7.52, 95% CI 1.98-28.6). Autoimmune conditions were more commonly reported in both female cases and female controls when compared with males; however, associations for hypothyroidism and ulcerative colitis were significantly associated with MDS in males in an analysis stratified by sex. Associations between autoimmune disease and MDS remained statistically significant after exclusion of therapy-related MDS cases. Discussion Our results validate previous findings of an association between autoimmune disease and MDS risk from population-based registry studies and case-control studies. In addition, our results provide additional evidence to suggest that this association is largely driven by hypothyroidism, inflammatory bowel disease, and SLE. This increased MDS risk following a diagnosis for an autoimmune condition is hypothesized to be due to shared genetic or environmental risk factors, treatment for autoimmune diseases, altered immune surveillance or damage to the bone marrow caused by the autoimmune condition. Further studies are required to confirm which of these is the most plausible explanation. Disclosures No relevant conflicts of interest to declare.

Background MDS is a heterogeneous disease and the revised International Prognostic Scoring System (IPSS-R) is utilized in prognostication. The percentage (%) of blasts in the bone marrow is determined in the aspirate morphologically. Though the former is the standard of care the blast percentage is also reported by flow cytometry and biopsy which can many times be inconsistent. We previously presented the utilization of biopsy based blast percentage which showed meaningful prognostic groups compared to aspirate. In this study we compare the blasts as reported by the aspirate and flow cytometry in MDS-EB in calculating IPSS-R. Methods The MDS database was reviewed for cases of MDS-EB after due IRB approval at the Mayo clinic. We calculated IPSS-R scores based on the aspirate blast % (IPSS-RAsp) and flow blast% (IPSS-Rfl). The aspirate blast percentage was reported morphologically. Suboptimal aspirates were excluded from the study. The flow blast percentage was determined by immunophenotyping. The overall survival (OS) was determined by IPSS-RAsp and IPSS-RFl. OS estimates were calculated by Kaplan-Meier curves and log-rank testing using JMP v.13. Uno's concordance statistic was used to compare the 2 risk scoring systems. Results Of 1322 patients, 431 (33%) cases were identified with MDS-EB out of which 120 (29%) cases had blasts reported in the aspirate and flow. Based on aspirate MDS EB1: 54% (n=65), MDS EB2 46% (n=55). The hematological, cytogenetic and R-IPSS categories were compared between MDS-EB1 and MDS- EB 2. The blast percentage and hemoglobin levels was significantly different between MDS-EB1 and EB2 as seen in table 1, however the IPSS-R risk groups were not significantly different. The flow cytometry was concordant with aspirate in 66/120 (55%) cases. Out of the dis-concordant cases only 20% (11/54) was upstaged by flow cytometry with most of the patients being down staged as expected by the techniques used in processing the blood and hence not reliable when reported low (Figure 1). The OS outcomes based on the IPSS- R asp, IPSS-Rfl areshown in figure 2A,2B .The p value with aspirate based R-IPSS was more significant than flow cytometry based R-IPSS (p= 0.0007 vs 0.0174). We compared the two models for observed OS differences using the Uno model which was not statistically significant. (p= 0.6) Conclusions Both models did not show a difference which is likely due to the very small sample size. However flow cytometry did down stage more patients when disconcordant and may have less value in that setting. It would be ideal to compare all 3 models aspirate, biopsy and flow cytometry however we did not have enough number of patients to do the comparison. Disclosures Patnaik: Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees. Al-Kali:Astex Pharmaceuticals, Inc.: Research Funding.

Introduction: Whereas morphological assessment and cytogenetics have been the cornerstone for the diagnosis of myelodysplastic syndrome (MDS), flow cytometry and mutational analyses are novel, evolving techniques. These diagnostic procedures play a role in identifying pre-MDS cases including idiopathic cytopenia of undetermined significance (ICUS) and clonal cytopenia of undetermined significance (CCUS). Aim: To assess flow cytometric findings in ICUS and CCUS and their correlation with progression to MDS or myeloid neoplasm (MN), concurrent genetic aberrations, and underlying pathological evolution. Methods: Patients (Pts) who had undergone evaluation to rule out MDS and had retrospectively undergone flow cytometry, cytogenetic, mutational and morphological assessment were included. Flow cytometry results were classified as normal (no abnormality or 1 equivocal result), abnormal (2 abnormalities or at least 1 abnormality and 1 equivocal result), or atypical (1 abnormality or 2-3 equivocal results). Next generation sequencing included mutation analysis of: ASXL1, BCOR, BRAF, CALR, CBL, CEBPA, CSF3R, DNMT3A, ETV6, EZH2, FLT3, GATA1, GATA2, IDH1, IDH2, JAK2, KIT, KRAS, MPL, MYD88, NOTCH1, NPM1, NRAS, PHF6, PTPN11, RUNX1, SETBP1, SF3B1, TERT, TET2, TP53, U2AF1, WT1, ZRSR2. Results: A) Characteristics: 229 pts were assessed (median age 60 and 69% were males). Based on pathologist interpretation, 87 (38%) pts met diagnostic criteria of MDS, 106 (46%) pts had normal/reactive bone marrow (BM), and 36 (16%) pts had BM findings suspicious for MDS. Median time to follow-up was 24 months for MDS pts, and 32 months for pts with cytopenias. B) Morphology: Pts who had a BM biopsy that was suspicious for MDS by pathologist interpretation were more likely to develop MDS compared to pts with normal/reactive pathology report with an incidence rate (IR) of 16% versus 0.9% (p= .0005). Pts who were suspicious for MDS based on the BM biopsy were more likely to have underlying mutations compared to pts with normal/reactive BM (IR 83% versus 69%, p= .2). C) Flow cytometry: In the non-MDS cohort, 96 (67%) pts had normal flow results, 29 (20%) pts had atypical flow, and 17 (12%) pts had abnormal flow results compared to 16 (18%) pts, 18 (21%) pts, and 53 (61%) pts in the MDS cohort, respectively. Of the pts who had normal flow result (n=112), 16 were MDS, 16 were suspicious for MDS/MN, and 80 were normal/reactive. Pts who had biopsy interpretation suspicious for MDS/MN were more likely to have abnormal flow cytometry compared to normal/reactive BM biopsy (IR 55% versus 24%, p=.0003). IR of MDS was 4% in normal flow, 3% in atypical flow, and 12% in abnormal flow (p= .5). Likewise, IR of MN was 4% in normal flow, 20% in atypical flow, and 30% in abnormal flow (p= .1). D) Genetics (cytogenetics and mutation profiling): Cytogenetics was normal in 123 (86%) pts and abnormal in 19 (13%) pts. Pts who had abnormal cytogenetics were more likely to develop MN (IR 57% versus 5%, p= .002). Out of the 50 non-MDS pts tested for NGS, 38 (76%) were positive for mutations. 15 (39%) pts had 1 mutation, 8 (21%) pts had 2, 3 (8%) pts had 3, 6 (16%) pts had 4, 2 (5%) pts had 5, 1 (3%) pt had 7, and 1 (3%) pt had 8 mutations (61% had >1 mutation). Pts with positive mutations were more likely to develop MDS during follow-up compared to pts who did not have mutations (IR 16% versus 0%, p=.06). Additionally, flow cytometric aberrations significantly correlate with the number of mutations (p= .03). MN correlated significantly with BCOR mutation and RUNX1 (IR 60% (p= .008) and 50% (p=.02), respectively. E) Interaction between variables: In pts with positive mutations, flow cytometry did not correlate with progression to MDS with an IR of 17% of MDS in normal flow, 11% in atypical flow, and 17% in abnormal flow, (p= .9). There was no impact on overall survival neither in pts with abnormal flow results vs normal nor in pts with positive mutations vs wild type. Conclusion: Conventional diagnostic techniques remain the cornerstone of MDS diagnosis with flow cytometry and NGS arising as novel techniques that correlate significantly with progression of pre-MDS pts to MDS. Flow had an impact on pathology final interpretation but did not add value in pt with a positive mutation analysis. Larger studies are needed to confirm our findings. Disclosures Patnaik: Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees. Al-Kali:Astex Pharmaceuticals, Inc.: Research Funding.