ALBERT

Description: Isoprene-derived secondary organic aerosol (iSOA) is a significant contributor to organic carbon (OC) in some forested regions, such as tropical rainforests and the Southeastern US. However, its contribution to organic aerosol in urban areas that have high levels of anthropogenic pollutants is poorly understood. In this study, we examined the formation of anthropogenically influenced iSOA during summer in Beijing, China. Local isoprene emissions and high levels of anthropogenic pollutants, in particular NOx and particulate SO42-, led to the formation of iSOA under both high- and low-NO oxidation conditions, with significant heterogeneous transformations of isoprene-derived oxidation products to particulate organosulfates (OSs) and nitrooxy-organosulfates (NOSs). Ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry was combined with a rapid automated data processing technique to quantify 31 proposed iSOA tracers in offline PM2.5 filter extracts. The co-elution of the inorganic ions in the extracts caused matrix effects that impacted two authentic standards differently. The average concentration of iSOA OSs and NOSs was 82.5 ng m−3, which was around 3 times higher than the observed concentrations of their oxygenated precursors (2-methyltetrols and 2-methylglyceric acid). OS formation was dependant on both photochemistry and the sulfate available for reactive uptake, as shown by a strong correlation with the product of ozone (O3) and particulate sulfate (SO42-). A greater proportion of high-NO OS products were observed in Beijing compared with previous studies in less polluted environments. The iSOA-derived OSs and NOSs represented 0.62 % of the oxidized organic aerosol measured by aerosol mass spectrometry on average, but this increased to ∼3 % on certain days. These results indicate for the first time that iSOA formation in urban Beijing is strongly controlled by anthropogenic emissions and results in extensive conversion to OS products from heterogenous reactions.

Description: Gas-phase oxidation pathways and products of anthropogenic volatile organic compounds (VOCs), mainly aromatics, are the subject of intensive research, with attention paid to their contributions to secondary organic aerosol (SOA) formation and potentially new particle formation (NPF) in the urban atmosphere. In this study, a series of OH-initiated oxidation experiments of trimethylbenzene (TMB, C9H12) including 1,2,4-TMB, 1,3,5-TMB, 1,2,3-TMB, and 1,2,4-(methyl-D3)-TMBs (C9H9D3) were investigated in an oxidation flow reactor (OFR) in the absence and presence of NOx. Products were measured using a suite of state-of-the-art instruments, i.e. a nitrate-based chemical ionization–atmospheric pressure interface time-of-flight mass spectrometer (nitrate CI-APi-TOF), an iodide-adduct chemical ionization time-of-flight mass spectrometer (iodide CI-TOF) equipped with a Filter Inlet for Gases and AEROsols (FIGAERO), and a Vocus proton-transfer-reaction mass spectrometer (Vocus PTR). A large number of C9 products with 1–11 oxygen atoms and C18 products presumably formed from dimerization of C9 peroxy radicals were observed, hinting at the extensive existence of autoxidation and accretion reaction pathways in the OH-initiated oxidation reactions of TMBs. Oxidation products of 1,2,4-(methyl-D3)-TMBs with deuterium atoms in different methyl substituents were then used as a molecular basis to propose potential autoxidation reaction pathways. Accretion of C9 peroxy radicals is the most significant for aromatics with meta-substituents and the least for aromatics with ortho-substituents if the number and size of substituted groups are identical. The presence of NOx would suppress the formation of highly oxygenated molecules (HOMs) of C18 and enhance the formation of organonitrates and even dinitrate organic compounds. Our results show that the oxidation products of TMB are much more diverse and could be more oxygenated than the current mechanisms predict.

Description: Multicenter large collaborative research groups have been the cornerstone for advances that have been made in multiple disciplines in medicine. These collaborative groups are specifically useful in situation where no single center based dataset is large enough to effectively address biological and clinical relevant questions that could advance the field. Most such collaborative groups exist in the developed countries and have contributed significantly to the development of the current standards of care in leukemia. The challenges in the developing countries or low middle income countries (LMIC) are distinctly different and often algorithms that have evolved in the developed world may not be applicable, relevant or accessible in the LMIC. It is imperative that these challenges be addressed through large multicenter studies that are located within the LMIC and appropriate local data driven solutions be implemented in response. The 'Hematological Cancer Consortium' is a collaborative group from India currently compromising twelve institutions spread across the country that have come together to collaborate in the field of leukemia. As an initial exercise, to establish denominators a retrospective data analysis was undertaken (Indian acute leukemia research database [INwARD]). Here we present the retrospective analysis of the acute myeloid leukemia (AML) data. Retrospective data from January 2013 to December 2017 was collected from 10 large tertiary centers from across the country (in one center data was available only from January 2017). A central online data capture and management system was in place which was independent of all the participating centers (Clinical Data Management Center [CDMC], Vellore, which is compliant with standard ICH-GCP regulations). In this initial phase some centers contributed data offline to the data management center. A total of 3848 were confirmed to have had a diagnosis of AML in this period of which it was noted that 1766 (46%) received definitive treatment (Fig 1 a). The median age of the patients was 40 years (range: 0-89) and there were 59% males. The age distribution of patients by each decade is illustrated in Fig 1b. 399 (10.4%) were ≤ 18 years). A sample for karyotyping was sent in 2609 (68%) however of these an evaluable karyotype was noted in only 1477 (57%) (Fig 1c), the reasons for lack of evaluable metaphases was not clear. A FLT3 and NPM1 mutation status was evaluated in 1338 (35%) and 1401 (36%) respectively. Of the evaluated patients 20.6% and 21.9% had FLT3-ITD and NPM1 mutated respectively (Fig 1d). Of the 1766 patients that were treated 858 (48.6%) received a conventional 7/3 induction, 170 (9.6%) received hypo-methylating agents while the rest received various abbreviated dose regimens and a small proportion (2.8%) received high dose cytosine based regimens as induction therapy. Antifungal prophylaxis was used by 82% of patients that received therapy. Of those that received induction therapy there were 18% induction deaths and 12.9% subsequently received an allogeneic SCT as part of their consolidation therapy (Fig 1a). The 5 year KM estimate for overall and event free survival for the patient that received treatment was 56.2±2.6% and 33.8±2.4% respectively. The data illustrates significant challenges and opportunities with the management of AML in India. A significant proportion of cases do not receive definitive therapy nor do they have conventional tests such as karyotyping or molecular tests done as part of the baseline diagnostic tests, various social and financial constraints could contribute to these and these need to be evaluated in more detail. Strategies to increase access to care and laboratory facilities along with an effort to reduce early induction deaths need relatively urgent attention. The relatively young age of the cohort and large number of cases would allow us to address relevant biological and clinically challenges effectively, in the future, in this cooperative setting. Disclosures No relevant conflicts of interest to declare.

Description: Background: To fully evaluate the potential benefit of novel agents for the treatment of patients with multiple myeloma (MM) who are heavily pretreated and refractory, it is important to understand the outcomes of this patient population based on current real-world experience. An International Myeloma Working Group study determined that the median overall survival (OS) of patients refractory to bortezomib (proteasome inhibitor, PI) and at least 1 immunomodulatory drug (IMiD) was 9 months (Kumar S et al. Leukemia 2012; 26: 149). Since then, other therapies have been approved for relapsed and refractory MM in the United States (US), including pomalidomide (IMiD) and carfilzomib (PI). In this analysis, real-world data were used to define the treatment landscape and outcomes of patients with MM refractory to PIs and IMiDs or who had received ³3 prior lines of therapy (LOT; including a PI and an IMiD) and provide context to results from the single-agent daratumumab phase 2 study MMY2002 (Sirius) recently presented at ASCO 2015 (Lonial S. J Clin Oncol 33, 2015 suppl; abstr LBA8512). Methods: Two independent databases were analyzed.TheIMS LifeLink: IMS Oncology Electronic Medical Records (EMR) Database (IMS Health Incorporated, Danbury, CT) and the OPTUM Database (OPTUM, Inc., Eden Prairie, MN) both comprised US patients only. For the IMS LifeLink database, patient records from the index period of 2000-2011 were screened. For the OPTUM database, the indexing period was 2007-2014. Median OS was assessed for cohorts that met the criteria of disease that was double refractory to a PI and IMiD (Criteria 1) or had been treated with ³3 LOT including a PI and IMiD and showed disease progression within 60 days on completion of last regimen (Criteria 2). Patients who met Criteria 1 could have received ³3 prior LOT, however those who met Criteria 2 only did not meet the double refractory criteria. Subgroup analyses of the eligible population were conducted on those who were only double refractory and triple/quadruple refractory. Results: For the IMS LifeLink database, 4,030 patients with MM were screened, approximately 90% of patients were diagnosed with MM in 2006 or later, and 500 met the criteria for the target population. Of the 500 patients, 323 patients met Criteria 1 and 177 patients only met Criteria 2. For the OPTUM database, 3,837 patients with MM were screened, approximately 90% of patients were diagnosed after 2009, and 162 met the criteria for the target population, 120 of whom met Criteria 1 and 42 of whom only met Criteria 2. In the total eligible populations, median OS was 239 days in the IMS LifeLink dataset compared with 240 days in the OPTUM dataset (P = 0.5358). Among patients that were only double refractory (triple/quadruple refractory patients excluded), median OS was 228 days (n = 253) in the IMS LifeLink dataset compared with 259 days (n = 97) in the OPTUM dataset (P = 0.8052). In triple/quadruple refractory patients, median OS was 154 days (n = 70) in the IMS LifeLink dataset and 95 days (n = 23) in the OPTUM dataset (P = 0.6675). The results from both databases were consistent, hence the data were pooled for further analyses; the pooled analyses indicated that the median OS was 240 days for the eligible population (n = 662), 237 days for patients who were only double refractory (n = 350), and 154 days for patients who were triple/quadruple refractory (n = 93). A naïve comparison of the OS curves from the MMY2002 study and the pooled analysis suggests a survival benefit with daratumumab versus the real-world historical control (Figure). Conclusions: Analyses of real-world data from two independent US patient databases indicated that outcomes remain poor among patients with MM who are heavily pretreated and/or highly refractory despite the availability and use of newer PIs and IMiDs, such as carfilzomib and pomalidomide. Median OS of approximately 8 months was observed in patients with ≥3 LOT (including a PI and IMiD) or refractory to a PI and IMiD. These data not only highlight the critical need for new MM treatments for patients with advanced MM, but also provide a point of reference against which novel agents such as daratumumab could be evaluated. Disclosures Usmani: Onyx: Consultancy, Honoraria, Research Funding; Janssen: Research Funding; Celgene Corporation: Consultancy, Honoraria. Ahmadi:Janssen: Employment. Ng:Janssen: Employment. Lam:Janssen: Employment. Potluri:Smart Analyst: Employment. Mehra:Janssen: Employment.

Description: Introduction: Myelofibrosis (MF) is a myeloproliferative neoplasm with profound negative effects on quality of life and survival. MF is characterized by clonal myeloproliferation, ineffective erythropoiesis, bone marrow stromal changes, hepatosplenic extramedullary hematopoiesis, and aberrant cytokine expression. Patients (pts) with MF may present with splenomegaly, constitutional symptoms, anemia, thrombocytopenia, or leukocytosis. Presentation may be primary (PMF), secondary following transformation from polycythemia vera or essential thrombocythemia (post-PV/ET sMF), or secondary from diseases such as myelodysplastic syndrome, leukemia, or lymphoma (Other sMF). Management options include allogeneic stem cell transplantation (the only potentially curative treatment), hydroxyurea, interferon alpha, alkylating agents, splenectomy, splenic radiotherapy, and the JAK1/2 inhibitor ruxolitinib. The present analysis was conducted to characterize disease, treatment patterns, and outcomes in pts with MF using 2 US health insurance claims databases. Methods: The Truven Health Analytics MarketScan® (Commercial Claims and Encounters and Truven Medicare) and Optum™ integrated virtual electronic health records and claims databases were retrospectively analyzed to identify pts with MF diagnosed between 2006 and 2015. Pts aged ≥ 18 years with ≥ 1 month of medical history prior to diagnosis were included. Pts were categorized as PMF, post-PV/ET sMF, or Other sMF based on earliest MF International Classification of Diseases, 9th revision diagnosis code. Demographic characteristics, constitutional symptoms, platelet counts, and treatment patterns were summarized. A treatment line was considered ended if followed by a treatment gap of ≥ 60 days. Kaplan-Meier analysis was performed to determine overall survival (OS). The effects of specific covariates on OS were analyzed using a Cox proportional hazards model. Results: 6,982 pts in the Truven and Optum databases met the inclusion criteria. Median age at diagnosis was 66 years (interquartile range, 58-78 years); 52.3% (n = 3,650) were aged 〉 65 years. More than half of pts were male (52.6%; n = 3,673). Overall, 23.5% (n = 1,637), 13.7% (n = 956), and 62.9% (n = 4,389) of pts had PMF, post-PV/ET sMF, and Other sMF, respectively. At the time of index diagnosis (± 90 days), 10.7% (n = 749) of pts had splenomegaly; an additional 3.3% (n = 227) developed splenomegaly 〉 90 days following index diagnosis, and a total of 17.8% (n = 1,239) had splenomegaly at any time. Among 112 pts with available baseline platelet counts (-90 to +180 days of index MF diagnosis) most had 〉 100,000/μL (77.7%; n = 87); 1.8% (n = 2) had 75,000-100,000/μL, 11.6% (n = 13) had 50,000-75,000/μL, and 8.9% (n = 10) had 〈 50,000/μL. Overall, 56.6% (n = 3,950) of pts received frontline treatment or supportive care, and 18.7% (n = 1,305) received second-line treatment or supportive care. Among pts receiving frontline and second-line treatment/supportive care, respectively, the most common approaches were steroids alone (26.7% [n = 1,053] and 26.7% [n = 348]) and hydroxyurea alone (20.5% [n = 811] and 21.1% [n = 276]). Ruxolitinib, ± other treatments, was given frontline to 12.4% (n = 488) of pts and second-line to 12.0% (n = 157) of pts. Median OS for pts who received frontline ruxolitinib was 30 months compared with 22 months for pts receiving other treatments (hazard ratio [HR] = 0.7; 95% confidence interval, 0.6-0.8; Figure 1A). Of the 488 pts who received frontline ruxolitinib, 23.0% (n = 112) went on to receive ≥ 1 further treatment; in 43.8% (n = 49) of these pts, the latter regimen also included ruxolitinib. Median OS among pts (n = 430) who failed or discontinued frontline ruxolitinib was 7 months (Figure 1B); this was not affected by sex (HR = 1.03; P = 0.85), age (〈 65 vs ≥ 65 years; HR = 0.88; P = 0.50), or the presence of splenomegaly (-90 days before index diagnosis to any point after index diagnosis; HR = 0.87; P = 0.48). Conclusions: Most pts diagnosed with MF were aged ≥ 65 years and had neither splenomegaly nor thrombocytopenia at baseline. In the present database analysis, slightly more than half of pts received any treatment or supportive care. Although only a fraction of pts received ruxolitinib, treatment with ruxolitinib was associated with favorable median OS. However, median OS was greatly reduced once pts failed or discontinued ruxolitinib; additional treatment options for these pts are needed. Disclosures Mehra: Janssen: Employment, Equity Ownership. Potluri:Janssen Research & Development, LLC: Other: Contracted to perform research; SmartAnalyst, Inc.: Employment. He:Janssen Global Services, LLC: Employment, Equity Ownership. Wang:Janssen Research & Development, LLC: Employment, Equity Ownership. Mundle:Janssen Research & Development, LLC: Employment, Equity Ownership. Bussolari:Janssen Research & Development, LLC: Employment, Equity Ownership.

Description: Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in Western countries with a median age of 72 years at diagnosis. Data from recent randomized clinical trials of novel agents, such as ibrutinib, have shown significant improvements in overall survival (OS) among older CLL patients. Prior to the introduction of kinase inhibitor therapies, chemoimmunotherapy combinations were the mainstay treatment. However, older individuals and/or those with co-morbid conditions may be less likely to tolerate standard CLL chemoimmunotherapy. While we await real-world outcomes data on how novel agents have continued to change the CLL landscape, little is known about the management and survival among older CLL patients prior to the availability of novel agents in clinical practice. Our study uses comprehensive prescription and medical insurance claims linked with registry data to describe the time to treatment initiation, front line therapy, and survival outcomes in older adults with CLL between 2007-2013--an era that predates the approvals of ibrutinib, idelalisib and obinutuzumab. Methods: The study used the 2007 to 2013 SEER-Medicare linked database. The sample included patients with first primary tumor site as CLL or SLL (ICD-O histology codes 9670 and 9823) diagnosed between 2007 and 2011. This date of first diagnosis of CLL or SLL defines the index date. Patients aged 〉 65 years with Medicare fee-for-service coverage in the 12 months pre-index and Medicare fee-for-service and prescription drug coverage in the 6-months post-index period or until death were included. Study outcomes included time to first treatment since CLL/SLL diagnosis, type of treatment initiated, and OS since first treatment. The first treatment type was classified into 6 groups (rituximab monotherapy, chlorambucil monotherapy, rituximab + bendamustine, rituximab + fludarabine +/- other treatment, rituximab + other chemotherapy, and other chemotherapy without rituximab). Logistic regression examined factors associated with receiving any treatment within 1- and 2-years of diagnosis. Cox regression examined factors associated with OS. Covariates in both sets of models included age, gender, race, region, low-income subsidy status, anemia/thrombocytopenia at diagnosis, comorbidities, disability status, and year of diagnosis. Cox regressions also included covariates for time to treatment and type of first treatment. Results: We identified 3,214 newly diagnosed CLL/SLL patients. Our sample had a mean age of 78 years (SD: 8), 49% were male, and 30% had anemia and/or thrombocytopenia at diagnosis. Nearly 33% of the patients received at least one CLL treatment over a median follow-up of 1,099 days (IQR: 834-1735 days) from the date of diagnosis. The most common treatments were rituximab monotherapy (26%), fludarabine + rituximab +/- other treatment (23%), and chlorambucil monotherapy (16%). Among those who initiated treatment, the median time to initiation was 791 days (IQR: 127-1344 days) from diagnosis. Logistic regressions indicated that patients aged 75-79 years old (vs. 80+ year olds) and those with anemia and/or thrombocytopenia at diagnosis were significantly more likely to initiate treatment within 1- and 2-years of diagnosis. The median OS from treatment initiation among the 1,047 treated patients was 52.4 months (Figure 1). The estimated 1-year and 2-year OS since treatment initiation was 81% and 69%, respectively. The OS at 2 years was 68% for rituximab monotherapy, 73% for fludarabine + rituximab +/- other treatment, and 59% for chlorambucil monotherapy. Cox regressions showed older age, male gender, disability, higher comorbidity scores, and type of first treatment (chlorambucil monotherapy vs. rituximab as monotherapy or in combination with chemotherapies) to be significantly associated with lower OS. Discussion: About one-third of older individuals who were newly diagnosed with CLL initiated treatment over a median follow-up of 3 years. This real world study shows modest 2-year OS in older CLL patients after initiating treatment in the pre-novel therapy era. While available clinical trials suggest novel CLL agents offer significant improvements in survival for older adults with CLL, future studies should examine CLL outcomes in real world settings to correlate how results obtained in recent landmark clinical trials translate into clinical practice. Disclosures Mato: Abbvie, Acerta Pharma, Gilead Sciences, ProNAi, TG Therapeutics, Theradex: Research Funding; Abbvie, Gilead Sciences, Pharmacyclics, TG Therapeutics: Consultancy. Mehra:Janssen: Employment, Equity Ownership. Mahler:Janssen Research & Development: Employment. Huntington:Johnson & Johnson: Consultancy; Celgene: Consultancy, Honoraria; Oncosec Medical: Equity Ownership; Geron: Equity Ownership; Pharmacyclics: Honoraria; Exelixis: Equity Ownership. Doshi:Pfizer Inc.: Other: Spouse owns stock in company, Research Funding; Forest Labs: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding; Amgen: Research Funding; Janssen: Research Funding; PhRMA: Research Funding; National Pharmaceutical Council: Research Funding; Humana: Research Funding; Merck & Co., Inc.: Membership on an entity's Board of Directors or advisory committees, Other: Spouse owns stock; Shire: Membership on an entity's Board of Directors or advisory committees; Alkermes: Membership on an entity's Board of Directors or advisory committees.

Description: Background: Anemia in pregnancy increases the need for blood transfusion during and after delivery and is associated with an increased risk of maternal and fetal mortality, therefore preventing maternal anemia may improve outcomes. Iron deficiency is the most common pathologic cause of anemia in pregnancy and is estimated to affect about 30% of pregnant women in the third trimester in the US. The baseline peripartum blood transfusion rate at our institution is 3.2%. Historically, patients who may have benefited from intravenous (IV) iron were continued on oral iron and subsequently delivered with persistent iron deficiency anemia. If identified to need IV iron, these patients were usually referred to a hematologist. However, in the absence of a structured protocol, referral was provider-dependent. Objective: We formed a multidisciplinary work group consisting of members from the departments of Hematology, Obstetrics, Pharmacy, Nursing, and Blood Bank to reduce peripartum blood transfusions by developing a process to manage pregnant patients with iron deficiency anemia. The treatment algorithm utilized at our institution was adapted from "How I treat anemia in pregnancy: iron, cobalamin, and folate" (Achebe & Gafter-Gvili, 2017), which recommends IV iron for hemoglobin less than 11 g/dL and ferritin less than 30 µg/dL in the third trimester and for hemoglobin less than 10.5 g/dL and ferritin less than 30 µg/dL in the second trimester along with recommendations for iron repletion in the first trimester. The primary endpoint was the utilization of blood transfusion. Secondary endpoints included an increase in maternal hemoglobin after treatment and evaluating the safety of IV ferric carboxymaltose as measured by side effects and frequency of hypophosphatemia. Five months after initiation of the IV iron recommendations, we performed an audit to assess its use. Methods: A retrospective IRB-approved chart review of anemic, iron-deficient pregnant women who received IV ferric carboxymaltose from 1/30/19 - 6/30/19 was performed. Thirty-six patients were identified and their charts were reviewed to determine the hemoglobin and ferritin levels prior to IV iron, the number of IV iron infusions received with any side effects, phosphorus levels on days of IV iron, hemoglobin level after IV iron, and need for peripartum blood transfusion. Results: Of the 36 patients who received IV iron for anemia in pregnancy, post-IV iron hemoglobin and blood transfusion information was only available for 26 patients. The remaining 10 patients had not delivered as yet or had delivered at another institution so data were not available. Of these 26 patients, the median age was 26.0 years and all received IV iron during their third trimester. No patients required a blood transfusion peripartum. The average hemoglobin prior to IV iron was 9.3 g/dL and the average hemoglobin after 1-2 IV iron infusions was 11.3 g/dL, an increase of 2.0 g/dL across the total group (Figure 1) (p

Description: Introduction Alemtuzumab is a monoclonal anti-CD52 antibody, a pan-lymphodepleting immunosuppressive agent in common use as part of conditioning for allogeneic stem cell transplantation (Allo-HSCT) in United Kingdom and many other centres across the globe, with benefits related to reduced graft versus Host disease (GVHD) and lower non-relapse mortality (NRM). However, evidence for effective dose schedule in Allo-HSCT remains debatable with some concerns related to delayed immune reconstitution and increased relapses with higher dosages; but increased risk of acute and chronic GVHD observed with lower doses. We present a large single-centre UK experience evaluating differential dosage effect of Alemtuzumab on HSCT outcomes. Methods: We retrospectively evaluated 330 patients undergoing Allo-HSCTs for myeloid malignancies (AML/MDS/MPNs) during a 10-year period (Jan 2010 to April 2019) at King's College Hospital, London. Two dosage schedules of Alemtuzumab based T-cell deplete conditioning regimen using 100mg (n-96) were compared to those receiving 60mg (n-234;

Description: Introduction Telomere length is shortened in patients with idiopathic aplastic anemia (AA) and other bone marrow failure disorders (BMFD) and predicts risk of clonal evolution (CE), relapse and overall survival (OS). Telomereopathies predominantly cause bone marrow failure, are multi-systemic disorders with variable penetrance, and may involve inter-play of other factors in disease manifestation and organ affliction. Telomere length (TL) in AA and other hypocellular BMFD, independent of mutations in telomere genes (TGC), has not been studied as a scoring tool, as well predicting the risk of affliction of other organ/systems in these disorders. We systematically review a large cohort of 472 patients in a single centre with AA/BMFD using TL and TGC analysis as a discriminator, to study risk of CE and OS, manifesting with liver/lung and skin complications, cancer predisposition and likelihood of a family member presenting with cytopenias. Methods We screened 1060 consecutive patients at a single centre from the years 2011-18, with AA or unexplained cytopenias for telomere length (TL) analysis using a multiplex qPCR methodology as described by Cawthon et al. 472 (44.5%) patients had TL less than the 25th centile, of whom 243 had

Description: Introduction: The treatment of acute myeloid leukaemia (AML) with intensive induction regimens remains a challenge in low and middle incomes countries. Early induction related deaths particularly due to infectious complications are a major problem. This is in stark contrast to high-income countries where induction mortality has declined significantly over the last 2 decades with improved antibiotic use and supportive care. In this study we assess induction mortality (all cause and infection related) in AML patients who received intensive induction therapy in a tertiary cancer centre in India over a 10-year period (2008-2017). Methods: We included patients with newly diagnosed AML treated at Cancer Institute, Chennai in South India who received intensive induction therapy. Intensive therapy was defined as use of any anthracycline with cytarabine (3+7/ADE/others). We assessed baseline demographics including age, gender, cytogenetic risk status, and type of induction regimen used. We also assessed key clinical outcomes including patterns of antimicrobial prophylaxis and treatment, infectious complications, cause of death, ICU stay, and length of hospital stay. Induction mortality was defined as deaths occurring within 45 days of initiating treatment for AML or start of 2nd induction. Results: Between January 2008 and December 2017, 510 patients with AML were evaluated at Cancer Institute, Chennai and accepted for treatment. Excluding 51 patients with APML and 55 patients who were unfit for intensive induction, 404 patients received treatment with an intensive induction regimen. Median age was 23 years (Range: 1-74 years) and 219 (54.2%) were male patients. 165(40.8%) patients were less than 18 years of age. Among those who had cytogenetic and/ molecular data for risk stratification [N=341 (84.7%)], 101 (29.6%) were low risk, 166 (48.7%) intermediate risk and 74 (21.7%) high risk. Therapy details: 318 (78.7%) patients received daunorubicin and cytarabine ('3+7'), 52 (12.9%) received ADE, and 38 (8.4%) received other combinations ofdaunorubicin and cytarabine. 87(21.5%) of the cases had infection at the time of presentation. 389(96.8%) had an episode of febrile neutropenia with 184(45.5%) requiring management in Intensive Care Unit (ICU). Focus of infection could be identified in 294(72.7%) of the patients with 207(51.2%) having a positive culture. The overall incidence of induction mortality over the entire study period was 15.6%(n=63)and 14.8% for the most recent year included (2017). The majority of the deaths (n=53; 84.1%) were due to infectious complications (fig1). Median time to death from start of induction was 19 days. The incidence of fungal pneumonia significantly reduced since 2012 when thethe antifungal prophylaxis was switched from fluconazole to voriconazole (p=0.03). Starting in 2012, an increase in the incidence of multi-drug resistance (MDR) gram negative septicaemia and mortality (MDR: carbapenem resistant enterobacteriacea sensitive only to colistin and tigecycline) was noted. This led to proactive use of colistin in patients with febrile neutropenia and septic shock, a GI focus or baseline stool colonisation by MDR gram negative organisms.Despite this, during the last 4 years(2014-2017), there has been a significant rise in the incidence of sepsis and death due to MDR gram negative organisms (fig2). The proportion of deaths attributable to MDR sepsis is 23.8%. The early use of colistin, tigecycline and carbapenems did not significantly decrease the mortality. Conclusions: The induction mortality remains high at 15.6% and is in contrast to the declining induction mortality in high-income countries. While the morbidity and mortality due to specific infections (specifically fungal pneumonia) have changed over time, there is no signfiicant decline in infectious or all cause induction mortality over the 10 years. In the last four years, MDR gram negative sepsis has been a major cause of morbidity and mortality. The early and increased use of broad spectrum antibiotics like tigecycline, colistin and carbapenems has not led to a decrease in MDR gram negative sepsis. Overall, despite improvements in supportive care and early use of broad spectrum antimicrobial agents, infection related morbidity and mortality remains a substantial challenge in treating acute myeloid leukaemia in low- and middle-income countries. Disclosures No relevant conflicts of interest to declare.