Search

Few studies have evaluated diagnostic yield of small volume biopsies (SVB) for the diagnosis and management of follicular lymphoma (FL).The authors performed a multi-institutional retrospective analysis of SVBs including fine-needle aspiration (FNA) and needle core biopsy (NCB) for initial FL diagnosis and suspected recurrence or transformation of FL. A total of 676 workups beginning with SVB were assessed for the mean number of biopsies per workup, the proportion of workups requiring multiple biopsies, and the proportion with a complete diagnosis including grade, on initial biopsy.Compared to workups performed for question transformation/recurrence, those done for initial FL diagnosis were significantly more likely to require multiple biopsies (p .01), had a higher mean number of biopsies per workup (1.7 vs. 1.1, absolute standardized difference = 1.1), and a lower complete diagnosis rate at initial biopsy (39% vs. 56%). At initial FL diagnosis, NCB +/- FNA was associated with fewer biopsies per workup compared to FNA +/- CB (1.2 vs. 1.9), fewer workups requiring multiple biopsies (23% vs. 83%), and a higher complete diagnosis rate (71% vs. 18%). In contrast, during assessment for transformation/recurrence, NCB and FNA showed a similar mean number of biopsies per workup (1.2 vs. 1.2) and few workups required multiple biopsies (6% vs. 19%).SVB at initial FL diagnosis often required additional biopsies to establish a complete diagnosis. In contrast, when assessing for transformed/recurrent FL, additional biopsies were generally not obtained regardless of SVB type, suggesting that in these clinical settings SVB may be sufficient for clinical decision-making.

Background/aims This article describes the proposed design of a phase I study evaluating the safety of ceramide nanoliposome and vinblastine among an initial set of 19 possible dose combinations in patients with relapsed/refractory acute myeloid leukemia and patients with untreated acute myeloid leukemia who are not candidates for intensive induction chemotherapy. Methods Extensive collaboration between statisticians and clinical investigators revealed the need to incorporate several adaptive features into the design, including the flexibility of adding or eliminating certain dose combinations based on safety criteria applied to multiple dose pairs. During the design stage, additional dose levels of vinblastine were added, increasing the dimension of the drug combination space and thus the complexity of the problem. Increased complexity made application of existing drug combination dose-finding methods unsuitable in their current form. Results Our solution to these challenges was to adapt a method based on isotonic regression to meet the research objectives of the study. Application of this adapted method is described herein, and a simulation study of the design’s operating characteristics is conducted. Conclusion The aim of this article is to bring to light examples of novel design applications as a means of augmenting the implementation of innovative designs in the future and to demonstrate the flexibility of adaptive designs in satisfying changing design conditions.

Acute myeloid leukemia has recently undergone a significant transition into identifying and successfully inhibiting driver mutations leading to disease. One of the most common mutations in acute myeloid leukemia involves the protein FMS-like tyrosine kinase 3 (FLT3), which leads to ligand-independent activation of intracellular signaling cascades leading to the survival and proliferation of the acute leukemia blast cell. Preclinical studies have demonstrated the presence of two dominant types of mutations of this protein: internal tandem duplication and tyrosine kinase domain mutations. Successful inhibition of this protein has proven to be challenging. While FLT3 has been shown to be successfully inhibited and shown to improve overall survival in the frontline therapy of acute myeloid leukemia in combination with cytarabine and anthracycline, relapsed and refractory (R/R) patients have not been shown to be a successful population until recently. A phase III trial (ADMIRAL trial) demonstrated significant overall survival benefit in patients receiving gilteritinib compared to patients receiving salvage chemotherapy. This review will provide an overview of the preclinical, clinical, and practical use of gilteritinib in the treatment of patients with relapsed and refractory acute myeloid leukemia with FLT3 mutation.

PURPOSE: Mucosal barrier injury (MBI) occurs during periods of prolonged neutropenia in patients receiving cytotoxic chemotherapy for hematologic malignancies. This can lead to laboratory-confirmed bloodstream infections (LCBIs) and subsequent complications, including sepsis, organ failure, and possible death. There are no published prevention strategies for MBI. The purpose of our proposal was to decrease our MBI-LCBI events per month by 25%. METHODS: A multidisciplinary team was assembled to achieve this proposal. Cause-and-effect diagrams in addition to Pareto charts were used to investigate potential interventions. Using Plan-Do-Study-Act (PDSA) cycles, multiple tests of change were designed over the course of 3 years. RESULTS: The number of baseline events per month for MBI-LCBIs was 1.1. With the completion of the first PDSA cycle, the MBI-LCBI events dropped to 1.0 event per month. A second PDSA cycle involving implementation of an oral care kit improved to 0.35 events per month. This unfortunately was not sustained, and a root cause analysis demonstrated that physician noncompliance with ordering the oral kit was the main reason. After the change of a physician-driven protocol to a nurse-driven protocol, the third PDSA cycle resulted in a decrease in MBI-LCBI events to 0.89 events per month. CONCLUSION: To our knowledge, this is the first published report of an intervention to prevent MBI-LCBI events. Through a multidisciplinary approach and with quality improvement tools, we were able to demonstrate a significant reduction in MBI-LCBI events.

Prophylaxis is commonly used to prevent central nervous sy stem (CNS) relapse in diffuse large B-cell lymphoma (DLBCL), with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013 and 2019. Prophylaxis was administered intrathecally(IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). Sixty-four patients (5.7%) had CNS relapse after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4% vs 6.8%, P = .4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected vs observed CNS relapse rates were nearly identical (5.8% vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors. This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated, and reconsideration of prophylaxis strategies in DLBCL is of critical need.

Diagnosis of histologic transformation (HT) of follicular lymphoma (FL) requires tissue biopsy. While surgical biopsy represents the gold standard, less invasive procedures such as fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) are frequently performed. In this retrospective multi-institutional study including 269 patients with FL and suspected HT, the median time from initial clinical suspicion to final diagnostic biopsy was similar whether the workup began with FNAB, CNB, or surgical biopsy (4, 9, and 6 days, respectively

Cytomegalovirus (CMV) reactivation remains a serious complication after allogeneic hematopoietic cell transplantation (HCT) occurring in approximately 60-70% of CMV-seropositive HCT recipients. CMV reactivation leads to adverse outcomes including end-organ damage, graft-versus-host disease, and graft failure.Ganciclovir was administered pretransplant at 5 mg/kg twice daily intravenously from the start of conditioning to Day T-2 to CMV-seropositive patients receiving their first allogeneic HCT. CMV DNA was monitored weekly until at least Day 100 posttransplant.A total of 109 consecutive patients were treated, median age 57 (range 20-73) years. Of these, 36 (33%) patients had a CMV reactivation within the first 105 days posttransplant with a median time of reactivation of 52.5 (range 36-104) days posttransplant. The cumulative incidence of CMV reactivation at Day 105 posttransplant was 33.1% (95% confidence interval: 24.4-42.0). One patient developed CMV disease.The use of pretransplant ganciclovir was associated with low incidence of CMV reactivation and disease. These data suggest that pretransplant ganciclovir with preemptive therapy for viral reactivation may be a useful strategy to reduce CMV reactivation. Future prospective trials are needed to compare strategies for CMV prophylaxis.

Daniel R Reed,1 Eric J Pierce,2 Jeremy M Sen,3 Michael K Keng11Division of Hematology/Oncology, Department of Medicine, University of Virginia, Charlottesville, VA, USA; 2Department of Medicine, University of Virginia, Charlottesville, VA, USA; 3Department of Pharmacy Services, University of Virginia, Charlottesville, VA, USACorrespondence: Michael K KengUniversity of Virginia, Department of Medicine, Division of Hematology/Oncology, 1300 Jefferson Park Avenue, West Complex, Room 6009, Charlottesville, VA 22908, USATel +1 434 924 4257Fax +1 434 244 7534Email mk2pv@virginia.eduPurpose: Intravenous (IV) sodium bicarbonate is typically used in alkalization regimens for the safe use of the chemotherapeutic agent high-dose methotrexate (HDMTX). Urine parameters including urine output and pH are important in order to minimize the risk of kidney injury, which increases adverse effects and hospital length of stay following HDMTX. IV sodium bicarbonate has been on shortage, and there are limited literature describing the safety of alternative regimens.Patients and methods: A single institution, prospective analysis of non-Hodgkin’s lymphoma and acute lymphoblastic leukemia patients receiving HDMTX for central nervous system (CNS) prophylaxis or disease. Patients received an oral (PO) regimen of sodium bicarbonate and acetazolamide to achieve a urine pH >7. This cohort was compared to a subsequent IV sodium bicarbonate control cohort. Multiple co-primary safety outcomes assessed the incidences of acute kidney injury and delayed methotrexate clearance as well as change in liver function tests. Secondary outcomes included time to urine pH, time to urine output, and length of stay.Results: A total of 126 encounters were studied for the primary safety outcome. There was no difference between AKI incidence in patients receiving the PO alkalization regimen compared to patients receiving IV sodium bicarbonate (14.5% vs 9.3%, respectively, P=0.41). There was no difference in methotrexate clearance between the PO and IV groups (26.5% vs 37.2%, respectively, P=0.21). The use of PO alkalization regimen is estimated to have saved 2002 vials of IV sodium bicarbonate and was approximately US$226 less expensive per encounter.Conclusion: This analysis supports the use of PO regimens to achieve urine alkalization necessary for safe administration of HDMTX during periods of IV sodium bicarbonate shortage. Further studies may determine optimal dosing strategies that decrease length of stay and ensure noninferiority of efficacy outcomes with PO regimens for urine alkalization with HDMTX.Keywords: non-Hodgkin’s lymphoma, acute lymphoblastic leukemia, oral alkalization, alkalization, high-dose methotrexate, chemotherapy administration

Recently there has been a significant progression in the understanding of molecular mutations driving biochemical and cellular signaling changes leading to survival and proliferation of leukemia cells in patients with acute myeloid leukemia (AML). Preclinical studies have demonstrated a mutated enzyme in the citric acid cycle, isocitrate dehydrogenase (IDH), leads to the production of an oncogenic metabolite R-2-hydroxy-glutarate (R-2-HG). This causes the arrest in the differentiation of hematopoietic stem cells leading to the promotion of leukemia. Inhibitors of the IDH enzyme have been shown in preclinical studies to reduce the production of R-2-HG, resulting in terminal differentiation of leukemia blast cells. In recent phase I and II trials, the IDH2 inhibitor enasidenib has shown clinical activity in patients with relapsed and refractory (R/R) AML. This review will describe the preclinical and clinical developments of enasidenib and its Food and Drug Administration approval in R/R AML, treatment recommendations and management will be outlined.

Background Acute myeloid leukemia, the most common acute leukemia in adults, has a poor overall survival. Studies have suggested that certain socioeconomic factors such as living in a rural or farming area are associated with worse outcomes. Since 42% of acute myeloid leukemia patients seen in our academic center reside in a rural area, we have a unique opportunity to study outcomes of patients in rural versus urban settings. Aim This analysis evaluates the effect of geography and socioeconomic factors on the biology, treatment, and overall survival of patients with acute myeloid leukemia, with the goal of understanding health care disparities. Methods and results Patient characteristics, cytogenetic data, treatment history, and overall survival were collected and analyzed to identify differences between urban and rural residency. This cohort included 42% of patients who resided in a rural area at the time of acute myeloid leukemia diagnosis. There was no difference in overall survival between the cohorts. The 1 year overall survival for the entire cohort was 47.9%. There was no difference detected in rates of adverse cytogenetics between the rural and urban cohorts. Similar numbers of patients received induction chemotherapy or proceeded to allogeneic stem cell transplant between the cohorts. Conclusions This study highlights that similar outcomes can be achieved in rural and urban patients, suggesting that intensive efforts at telehealth, education, and collaboration with local oncology practices may be beneficial.

Introduction: New treatment strategies with low intensity therapy have emerged for acute myeloid leukemia (AML) patients who are not candidates for intensive therapy. To date, there is limited data on the frequency of invasive fungal infections (IFIs) in patients treated with low intensity regimens, and there is no consensus on the most appropriate prophylactic antifungal agent to use in either the newly diagnosed or relapsed/refractory setting. At our institution, fluconazole is the prophylactic antifungal agent of choice for neutropenic patients receiving low intensity therapy, however the appropriateness of fluconazole is being questioned due to the depth and duration of neutropenia observed in these patients. Rates of breakthrough IFIs need to be better characterized to optimize antifungal prophylaxis in this patient population. Methods: This is a retrospective review of AML patients treated with low intensity therapy from January 2017 through May 2020 for both newly diagnosed and relapsed/refractory disease. Patients were included if they received fluconazole as prophylaxis during periods of neutropenia and received at least two cycles of low intensity treatment. Low intensity regimens included hypomethylating agent (HMA) monotherapy or a combination of venetoclax with either a HMA or low dose cytarabine (LDAC). Any patient with a contraindication to fluconazole or those who received prophylaxis with an alternative antifungal agent (i.e. posaconazole, voriconazole, isavuconazole, and micafungin), history of previous IFI, or history of a stem cell transplant were excluded. The primary objective was to determine the incidence of breakthrough IFIs. The secondary objective was to further characterize IFI occurrences as possible, probable or proven using criteria defined by the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC). An occurrence of IFI was defined as receipt of any systemic antifungal agent, aside from fluconazole, for four or more days for suspected IFI. Patients were evaluated for antifungal escalation from the time of low intensity treatment initiation through 30 days after treatment discontinuation. Results: Eighty encounters were included for analysis. The median age of the cohort was 73 years (interquartile range [IQR] 67 - 80) and 70% of patients were newly diagnosed (n = 56). HMA/venetoclax was the most commonly utilized regimen (66%, n = 53) followed by HMA monotherapy (29%, n = 23) and LDAC/venetoclax (5%, n = 4). The median number of treatment cycles was 5 (IQR 3 - 9). Nineteen IFI occurrences (24%) were documented, with ten in the newly diagnosed population (18%, n = 10/56) and nine in relapsed/refractory patients (38%, n = 9/24). There were no proven, four probable and fourteen possible IFIs. Of the four probable infections, three were in relapsed/refractory patients. Median times to IFI onset from low intensity treatment initiation were 82 and 80 days for the newly diagnosed and relapsed/refractory populations, respectively. Of the patients with an IFI, 15/19 (79%) were neutropenic at IFI onset. Conclusions: IFIs are a serious complication of AML as these infections are associated with significant morbidity and mortality. With 24% of patients requiring antifungal escalation, our study demonstrates that breakthrough IFIs remain a concern for patients receiving low intensity therapy and fluconazole prophylaxis. Incidence of IFI was higher in the relapsed/refractory setting, which is an expected finding as these patients are typically subjected to multiple lines of therapy, leading to poor hematopoietic reserves and more prolonged periods of profound neutropenia. Additional analysis is needed for determination of risk factors, beyond relapsed/refractory disease, to potentially identify subsets of patients at highest risk of developing IFIs as these patients may benefit from closer monitoring and longer durations of prophylaxis. Given these findings, it is reasonable to consider prophylaxis with an extended spectrum antifungal agent against molds for patients receiving low intensity therapy. Figure 1 Figure 1. Disclosures Ellis: Rafael Pharmaceuticals: Consultancy. Pardee: Karyopharm Pharmaceuticals: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Rafael Pharmaceuticals: Consultancy, Research Funding; Genetech: Membership on an entity's Board of Directors or advisory committees; BMS: Speakers Bureau; Pharmacyclics: Speakers Bureau.

Introduction Assessment of frailty is central to medical decision-making for older adults with newly diagnosed acute myeloid leukemia (AML), but validated frailty tools used at the point of care are lacking in this setting. An electronic frailty index (eFI), based on the theory of deficit accumulation, has been developed from routinely collected outpatient primary care data and embedded in the electronic health record (EHR) at Wake Forest Baptist Health (WFBH). The embedded eFI predicts hospitalization and mortality for older adults in a primary care cohort but has yet to be assessed for older adults with AML. The objectives of this analysis were to evaluate this tool among a cohort of newly diagnosed older adults with AML by determining the percent with available data to calculate a score, assessing the distribution of eFI categories (fit, pre-frail, and frail) at the time of treatment by therapy type, and exploring an association of eFI categories with survival. Methods Participants in this retrospective cohort study were adults aged ≥ 60 years with newly diagnosed AML from January 2018 - October 2020 who received treatment at WFBH. Patients with acute promyelocytic leukemia (APL) were excluded. Calculation of the EHR embedded eFI requires at least two ambulatory visits over a 2-year period. The eFI comprises demographic information, vital signs, smoking status, ICD-10 diagnosis codes, select outpatient laboratory measurements, and functional information (if available from past Medicare Annual Wellness Visits) during the 2 years prior to diagnosis. For this analysis, eFI was derived using date of treatment initiation as the reference date. Frailty status is categorized as fit (eFI ≤0.10), pre-frail (0.100.21) based on the proportion of deficits present over the total number evaluated. Intensive therapy is defined as receipt of anthracycline-based chemotherapy. Less-intensive therapy includes hypomethylating agents, low dose cytarabine, and/or venetoclax. The association of eFI category to therapy type was evaluated using a chi square test. Median survival was estimated using the Kaplan-Meier method and compared using log-rank tests. Results Among N=163 older adults treated for non-APL AML, 78 (43.3%) had a calculable eFI score. Among those with a calculable score, average age was 74.7 years (range 60 to 90), 68% were male, 90% were white, and average hematopoietic cell transplantation-comorbidity index (HCT-CI) score was 3.5 ± 2.7. Approximately 17% had favorable, 23% had intermediate, and 59% had unfavorable cytogenetics; 54% had secondary AML. Among those with a calculable eFI, 38.5% were classified as fit, 48.7% as pre-frail, and 12.8% as frail. For those who received intensive therapy (N=35), the majority were classified as fit (60%) and the remaining were pre-frail (40%); none were frail. The distribution of eFI categories differed for patients who received less-intensive therapies (N=43), with the majority classified as pre-frail (56%), a smaller proportion classified as fit (21%), and almost one-quarter as frail (23 %) (p Conclusions The embedded eFI derived from a longitudinal primary care population was not calculable using available data for most older adults with AML. This may reflect a skewed population referred to a Comprehensive Cancer Center that has higher-risk cytogenetics and/or does not receive primary care through the academic medical center. Among those with a calculable eFI, frailty categories significantly differed by treatment type. There was no association between survival and eFI category within treatment type in exploratory analyses. Our observations highlight the opportunity to adapt the EHR embedded eFI data capture process, including incorporation of inpatient labs, to the AML setting to effectively test the utility of a cancer-adapted passive digital marker for frailty. Disclosures Pardee: Rafael Pharmaceuticals: Consultancy, Research Funding; Karyopharm Pharmaceuticals: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genetech: Membership on an entity's Board of Directors or advisory committees; BMS: Speakers Bureau; Pharmacyclics: Speakers Bureau.

BackgroundImmune checkpoint inhibitors (ICIs) have become the backbone of treatment for most driver-mutation negative, advanced non-small cell lung cancers. ICIs have been approved both as monotherapy and in combination with chemotherapy for front line management. While ICIs are generally regarded as well-tolerated, an unintended activation of the immune system can result in a variety of immune-related adverse events (irAEs), which can limit their use in severe cases. In patients with NSCLC treated with ICI monotherapy, the occurrence of an irAE and the development of multisystem irAEs have been associated with improved clinical outcomes, suggesting irAE occurrence could have prognostic implications.1–4 However, in patients treated with combination immunotherapy plus chemotherapy, the correlation between irAEs and survival has not been completely elucidated.MethodsWe conducted a retrospective chart review of 94 patients with advanced NSCLC treated with a combination of ICI plus chemotherapy between 2015 and 2021 to evaluate for a correlation between irAE occurrence and overall survival (OS). Patients were divided into two groups: those who experienced at least one irAE and those who did not experience an irAE. To account for immortal time bias, we conducted landmark analyses at 12 and 24 weeks. We additionally investigated the impact of multisystem irAEs on clinical outcomes and described the profile of irAEs observed at our institution.ResultsAmong the 94 evaluable patients identified in our population, 43.6% experienced at least one irAE. Of those patients who experienced an irAE, 26 (63.4%) experienced a single irAE, 9 (22.0%) experienced 2 irAEs, and 6 (14.6%) experienced 3 or more irAEs. The most commonly observed irAEs were dermatitis followed by pneumonitis and colitis. In our cohort, patients with at least one irAE had significantly longer median OS (16.8 mos vs 9.8 mos) compared to those who did not experience an irAE (HR 0.51, 95% CI 0.43–0.76, p=0.011) (figure 1). Landmark survival analyses at 12 and 24 weeks continued to support significant differences in median OS based on presence or absence of an irAE (HR 0.49, 95% CI 0.24–0.46, and HR 0.45, 95% CI 0.21–0.60 respectively). Among patients with at least one irAE, the subset of patients who experienced multiple irAEs had further improved median OS compared to those with a single irAE.ConclusionsIn patients with advanced NSCLC treated with combination ICI plus chemotherapy, the occurrence of an irAE is associated with improved overall survival.ReferencesTeraoka S, Fujimoto D, Morimoto T, et al. Early Immune-related adverse events and association with outcome in advanced non-small cell lung cancer patients treated with Nivolumab: a prospective cohort study. Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer 2017;12(12):1798–1805. doi:10.1016/j.jtho.2017.08.022.Ricciuti B, Genova C, De Giglio A, et al. Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with nivolumab: long-term outcomes from a multi-institutional analysis. Journal of Cancer Research and Clinical Oncology 2019;145(2):479–485. doi:10.1007/s00432-018-2805-3.Toi Y, Sugawara S, Kawashima Y, et al. Association of immune-related adverse events with clinical benefit in patients with advanced non-small-cell lung cancer treated with nivolumab. The Oncologist. 2018;23(11):1358–1365. doi:10.1634/theoncologist.2017-0384.Shankar B, Zhang J, Naqash AR, et al. Multisystem immune-related adverse events associated with immune checkpoint inhibitors for treatment of non-small cell lung cancer. JAMA Oncol 2020;6(12):1952–1956. doi:10.1001/jamaoncol.2020.5012Ethics ApprovalThis research study obtained ethics approval by the institutional review board at the University of Virginia, IRB# 19083.Abstract 803 Figure 1Overall Survival by presence or absence of an irAE in patients with advanced lung cancer treated with immune checkpoint inhibitors plus chemotherapy

Introduction Relapses involving the central nervous system (CNSrel) occur in ~5% of patients (pts) with aggressive non-Hodgkin lymphoma (NHL) in the rituximab era (Ghose et al, Clin LML 2015) with rates exceeding 10% in high risk groups (Villa et al, Ann Onc 2010; Schmitz et al, JCO 2016). CNSrel are generally thought to occur in the first 4-6 months from diagnosis. Prophylaxis (PPx) administration, route, and frequency are not standardized, and the impact of PPx on CNSrel risk is incompletely understood. Methods We performed a multicenter retrospective analysis of pts with aggressive NHL (excluding Burkitt's) without known CNS involvement (inv) who received single-route CNS PPx with during front-line (FL) anthracycline-based therapy (tx) from 2013-2019 across 19 US academic institutions. Recipients of chemotherapy for prior CLL or indolent NHL were ineligible. Method, frequency, and outcomes of CNS PPx administration were evaluated, with significance assessed by various statistical methods via two-tailed P Results 1030 patients were identified who met eligibility criteria. Clinical features included median age 61 years (yrs; range 16-86), 40.9% female, ECOG PS 0-1 82.8%, elevated LDH 65.3%, >1 extranodal (EN) site 42.3%, stage 3/4 disease 79.2%. NHL histologies included diffuse large B cell (DLBCL; 75.2%), high grade B cell (16.3%), transformed follicular lymphoma (5.6%) and 3% other; among pts with DLBCL, 46.4% had germinal center (GCB) subtype and 40.5% had non-GCB. 26.2% (n=210) of evaluable pts had double-hit lymphoma (DHL). Among pts with known HIV status, 7.2% (n=65) were HIV-positive. 85.7% had EN inv; common sites included bone (35.4%), liver (13.7%), gastrointestinal (12.7%), lung (11.8%), and marrow (11.5%). FL regimens included RCHOP (45.9%), REPOCH (46.5% total; 79.1% with dose-adjustment), 7.6% other. PPx was given intravenously (IV) in 20% of pts vs 77% intrathecally (IT), over a median 2.9 vs 4.1 doses respectively; see Table 1 for factors associated with PPx route. PPx was generally well-tolerated, with 10.7% PPx-related toxicity reported; see Table 2. CNSrel after FL tx was 5.3% overall without significant difference by PPx route (7% IV vs 5% IT, p=0.178). This lack of difference between PPx routes was observed in all subgroup analyses performed, including by: age, stage, histology, number of EN sites, individual EN site inv, elevated LDH, CNS-IPI, DHL status, HIV status, FL regimen, number of PPx doses. There was no significant difference in anatomic site(s) of CNSrel by PPx route. CNSrel occurred bimodally: 24% by end of FL tx vs 76% delayed (average 2.3 yrs, range 0.4-5.2 yrs). Rates of CNSrel were significantly higher with CNS-IPI high vs moderate risk (8.3 vs 4.1%, p=0.03; Figure 1), elevated LDH (6.9 vs 2.6%, p=0.007) and multiple inv EN sites (7.5% for 2+ vs 4% for 0-1, p=0.01); each additional EN site further increased risk (p=0.03 for trend; Figure 2). Increased CNSrel was noted in pts with testis (13.7 vs 5%, p=0.004) and liver inv (11.1 vs 4.6%, p=0.002) vs those without inv at respective sites. No significant difference was noted at other EN sites, including renal/adrenal (4.8 vs 5.6%, p=0.71), marrow (8.9 vs 5.1%, p=0.09), or lung (8.6 vs 5.1%, p=0.12). All EN site-CNSrel correlations were unchanged when accounting for PPx route. With median follow-up of 2.3 yrs, median PFS and OS for the overall group have not been reached; 2-yr PFS and OS were 70 and 85% respectively. PFS and OS were each predicted by CNS-IPI (p Conclusion Use of single-route ppx demonstrated similar CNSrel vs established outcomes for this population in the rituximab era, with no difference by PPx route. CNSrel remains a rare but devastating complication, with greater risk even after single-route PPx in those with higher EN burden and inv of key EN sites. Disclosures Kahl: Acerta: Consultancy, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy; Pharmacyclics LLC: Consultancy; Genentech: Consultancy; Celgene Corporation: Consultancy; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy. Spinner:Notable Labs: Honoraria. Advani:Celgene, Forty Seven, Inc., Genentech/Roche, Janssen Pharmaceutical, Kura, Merck, Millenium, Pharmacyclics, Regeneron, Seattle Genetics: Research Funding; Astra Zeneca, Bayer Healthcare Pharmaceuticals, Cell Medica, Celgene, Genentech/Roche, Gilead, KitePharma, Kyowa, Portola Pharmaceuticals, Sanofi, Seattle Genetics, Takeda: Consultancy. Voorhees:AstraZeneca: Research Funding. Grover:Genentech: Research Funding; Tessa: Consultancy. Huntington:Genentech: Consultancy; Novartis: Consultancy; Celgene: Consultancy, Research Funding; TG Therapeutics: Research Funding; Pharmacyclics: Honoraria; Bayer: Consultancy, Honoraria; DTRM: Research Funding; Astrazeneca: Honoraria; AbbVie: Consultancy. Spurgeon:Beigene: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Bristol-Myers Squibb: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy, Research Funding; VelosBio: Consultancy, Research Funding; Cardinal Health: Honoraria; Verastem: Research Funding; Genmab: Research Funding; AstraZeneca: Research Funding; Acerta: Research Funding. Olszewski:Spectrum Pharmaceuticals: Research Funding; Genentech, Inc.: Research Funding; Adaptive Biotechnologies: Research Funding; TG Therapeutics: Research Funding. Landsburg:Seattle Genetics: Speakers Bureau; Morphosys: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Curis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Triphase: Research Funding. Kamdar:Roche: Research Funding. Caimi:Kite Pharma: Other: Advisory Board; ADC Therapeutics: Other: Advisory Board, Research Funding; Verastem: Other: Advisory Board; Amgen: Other: Advisory Board; Bayer: Other: Advisory Board; Celgene: Speakers Bureau. Karmali:Takeda: Research Funding; BeiGene: Speakers Bureau; AstraZeneca: Speakers Bureau; Karyopharm: Honoraria; Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau; BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau. Stephens:Pharmacyclics: Consultancy; Innate: Consultancy; Verastem: Research Funding; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy; Gilead: Research Funding; Arqule: Research Funding; Juno: Research Funding; MingSight: Research Funding; Acerta: Research Funding; Beigene: Consultancy. Smith:Genentech/Roche: Consultancy, Other: Support of parent study and funding of editorial support, Research Funding; TG Therapeutics: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy; BMS: Consultancy; Karyopharm: Consultancy, Research Funding; FortySeven: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding. Khan:Celgene: Research Funding; Pharmacyclics: Honoraria; Seattle Genetics: Research Funding; Bristol Myers Squibb: Research Funding; Janssen: Honoraria. Cohen:Genentech, BMS, Novartis, LAM, BioInvent, LRF, ASH, Astra Zeneca, Seattle Genetics: Research Funding; Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo: Consultancy. Portell:Bayer: Consultancy; Xencor: Research Funding; BeiGene: Consultancy, Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding; Amgen: Consultancy; Janssen: Consultancy; Pharmacyclics: Consultancy; AbbVie: Research Funding; TG Therapeutics: Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding.

Mantle cell lymphoma is an aggressive and rare type of non-Hodgkin’s lymphoma that is considered incurable. It is a heterogeneous disease with diverse clinical presentations and complex treatment courses. In this chapter, the presentation, diagnosis, and conventional treatment will be discussed and outlined for the frontline setting in both young fit adults and the elderly. This will be followed by an in-depth analysis regarding exciting novel therapies and combinations being investigated, from early stage development to ongoing clinical trials. We will finish with a recommended treatment algorithm for frontline and relapsed disease.

Introduction: Cytogenetics and next generation sequencing (NGS) have become standard of care for initial diagnosis for patients (pts) with acute myeloid leukemia (AML). Obesity rates in the United States continue to rise and the relationship of obesity to outcomes and NGS results in AML is not well defined. This study analyzed if body mass index (BMI) at diagnosis was correlated with the number or type of myeloid mutations seen on initial NGS and whether obesity influenced outcomes stratified by individual mutations. Methods: Adult pts newly diagnosed with AML at the University of Virginia from 3/2015 to 4/2020 who had cytogenetics and NGS panel completed prior to initiation to therapy were included. Pts without initial diagnostic information or incomplete diagnostic information were excluded. AML disease characteristics, treatment type, and comorbidities were assessed including weight, height, BMI (categories defined per CDC) at the time of diagnosis. The primary aim of this analysis was to test the association of BMI with the number and type of mutations on NGS panel at diagnosis. A logistic regression model was used to explore the relationship between 9 mutations of interest including NPM1, FLT3, TP53, RUNX1, ASXL1, IDH1,IDH2, TET2, and DNMT3A. Spearman's rank correlation test was used to investigate impact of BMI on number of mutations found on NGS. Non parametric tests using Mann-Whitney-U to explore the relationship between type of mutation and BMI. An alpha level ≤ 0.05 was used to determine significance. Relapse free survival (RFS) was estimated for the different BMI groups by the Kaplan-Meier method. Results: 176 AML pts met inclusion criteria with a median age of 66 (range 18-95) and 60.2% (n=106) were male. The median weight was 83.6 kg and median BMI at diagnosis was 28 kg/m2 (range 18.1-52.4). There were 54 pts in the normal or underweight category (30.7%), 59 pts in the overweight category (33.5%), 63 pts in the obese class (35.8%). By ELN criteria, 10.2% pts were favorable (n=18), 42% pts were intermediate (n=74), and 47.7% pts were adverse (n=84). The majority of pts received induction with anthracycline and cytarabine (66.5%, n=117), 21% patients received a hypomethylating agent (HMA) (n=37), and 12.5% of patients received palliative care or low intensity treatment (n=22).)There was no difference in the median number of mutations across BMI groups with a spearman correlation of -0.1 (p value 0.2, Figure 1) with a median number of 2 mutations across all weight groups. Patients in underweight or normal weight groups were more likely to have a TP53 mutation than patients in higher weight classes HR 3.5 (95% CI 1.7-7.3; p = 0.04, Figure 1). BMI did not predict presence of the other 8 mutations. TP53 mutation status was associated with decreased RFS and OS as expected, specifically there was no protective effect of BMI on TP53. However, obese and overweight TP53 negative patients trended better with improved RFS and OS compared to the lower weight classes (Figure 2). When risk stratified for BMI alone, patients with higher BMIs had an improved trend in RFS and OS (Figure 3). Conclusion: BMI in pts with newly diagnosed AML does not appear to predict for the gross number of NGS mutations. However, TP53 mutations occurred more often in patients with low or normal BMI compared to overweight patients. Obese and overweight patients trended with improved RFS and OS compared to the lower weight classes. Prospective and larger retrospective studies are needed to expand on the findings that BMI may have unexplored potential in stratifying AML pts at diagnosis. Figure 1 Disclosures Keng: Agios: Other.

Background: Rural communities may not have access to adequate health care, but the effect of geographic residence on patient outcomes and molecular characteristics of acute myeloid leukemia (AML) is poorly understood. Several studies have investigated the effect of various demographics (such as race, gender, zip code) and environmental exposures on the development and outcome of AML. Evidence is lacking to suggest a link between genetic abnormalities and residence. Methods: A single center, retrospective chart review was conducted on patients with AML diagnosed between 9/2015 and 8/2018. Consecutive patients with a new diagnosis of AML and a clinical next generation sequencing panel (Illumina TruSight Myeloid 54 gene panel) performed during their initial leukemia workup were included. Patients were excluded if they had APML or CML in blast crisis. Data collected included demographic information (including zip code), smoking history, BMI, cytogenetic data, treatment regimen, and overall survival. Patients were grouped into urban and rural subsets based on their county of residency as described in the National Center for Health Statistics 2013 Urban-Rural Classification Scheme for Counties. Zip codes were used to extrapolate socioeconomic data including education and income level. Cytogenetic data was used to risk stratify patients per ELN criteria. Mutational profile, cytogenetics and overall survival (OS) were compared between the groups. Mutations analyzed were limited to ASXL1, DNMT3A, FLT3, IDH1, IDH2, NPM1, NRAS, TET2, and TP53, as these are often used in medical decision making. Multivariate logistic regression was conducted to evaluate differences between the groups. Time to event data were analyzed using log-rank tests, Kaplan-Meier method, and Cox proportional hazard regression model. Results: 113 patients were included in this study. Median age of the entire cohort was 66.3 years old. 59% (n = 67) were male. 24% (n = 27) of patients were from a rural area; 76% (n = 86) were from an urban area. There was no difference in median age, race, prior MDS or MPN, number of patients who underwent chemotherapy or number of patients who underwent allogeneic stem cell transplant (ASCT) as demonstrated in Table 1. Patients from both cohorts also had similar risk cytogenetics (urban cohort: favorable: n = 5, 5.8%; intermediate: n = 35; 40.7%; adverse: n=46; 53.5%; rural cohort: favorable: n = 3, 11.1%; intermediate: n = 14; 51.9%; adverse: n = 10, 37%; p = 0.282). In the rural cohort, 15% of patients reported income below the poverty level; in the urban cohort, 10.2% reported income below the poverty level (p < 0.0001). Fewer patients in the rural cohort were high school graduates as compared to the urban cohort (82.7% versus 87.8%, p < 0.0001). Rural patients traveled an average of 145 miles for treatment; urban patients traveled 57 miles (p < 0.0001). Mutation frequency is described in Table 2. ASXL1 mutation was more frequent in the urban cohort as compared to the rural cohort (p = 0.032). There was no difference in frequency of other mutations between the cohorts. The 2 year survival rate was 46% (n = 52) for the cohort; 2 year survival rate for the rural cohort was 70% (n = 19) and for the urban cohort was 38% (n = 33) (p = 0.011; Figure 1). 53 patients (urban: n =39, 66.1%; rural: n = 14, 77.8%; p = 0.35) underwent induction chemotherapy. Rural patients who underwent induction chemotherapy had an improved OS as compared to urban patients who underwent induction chemotherapy (p = 0.005). Conclusion: In this single center retrospective study, our data demonstrates: 1. Urban patients had an increased frequency of ASXL1 mutations; 2. Rural patients were more likely to live below the poverty level and not graduate high school; 3. Rural patients traveled a greater distance for treatment; 4. OS was improved in rural patients in this limited cohort. Our rural patients may have improved OS due to our close co-management with rural centers. These studies suggest that the biology of the AML is not worse in the rural cohort and intensive efforts at access, remote monitoring, and communication with local physicians may result in outcomes similar to urban patients. Further studies will be investigating improving access to leukemia and transplant care for patients with AML. Disclosures Balkrishnan: Merck and Company: Consultancy. Keng:Agios: Membership on an entity's Board of Directors or advisory committees.

Introduction Cytomegalovirus (CMV) reactivation remains a serious complication after allogeneic hematopoietic stem cell transplantation (HCT) occurring in 35-55% of HCT recipients. CMV reactivation can lead to adverse outcomes including end-organ damage and graft failure. Objective To reduce the incidence of CMV reactivation and disease by using prophylactic ganciclovir pretransplant. Methods We conducted a retrospective analysis of all recipient or donor CMV seropositive patients who received their first allogeneic HCT between 2012 and 2017. Ganciclovir was administered pretransplant (5 mg/kg twice daily IV from day −8 to day −2). Patients received valacyclovir or acyclovir starting day 0 until one-year posttransplant. Patients were monitored weekly with serum CMV PCR through Day 100 posttransplant. CMV reactivation was defined as a CMV viral load of more than 135 IU/ml, and was treated with preemptive therapy. All patients received GVHD prophylaxis with calcineurin inhibitor. Results Seventy-nine consecutive patients were treated. The median age was 58 years (range 20 to 72). The most common diagnoses were acute myeloid leukemia (49%) and acute lymphocytic leukemia (14%). Graft sources were matched related donor (30%), matched unrelated donor (35%), haploidentical (5%) and cord blood (29%). 43 patients (55%) received myeloablative conditioning. 36 patients (45%) received fludarabine based reduced intensity/nonmyeloablative conditioning. 24 patients (30%) had CMV reactivation with median time of reactivation of 47 days posttransplant (range 27 to 229). 22 out of the 24 (88%) patients required treatment for CMV reactivation with a median treatment duration of 37 days (range 14 to 315) and were treated with ganciclovir or foscarnet. The cumulative incidence of CMV reactivation at day 100 posttransplant was 27% with a 95% CI (18%-37%) depicted in Figure 1. There were no patients with biopsy proven CMV disease or deaths attributed to CMV reactivation or disease. The median time-to neutrophil recovery (≥500 K/ul) was 18 days and the median time to platelet recovery (≥20,000 K/ul) was 19 days. The incidence of acute GVHD Grades II-IV was 25 %. The incidence of significant kidney injury (Creatinine >2.5 mg/dL) was 2.4%. Conclusions The incidence of CMV reactivation, in this high-risk patient population, by day 100 of 27% with pretransplant ganciclovir may be improved compared to historical controls of 35-55%. The use of pretransplant ganciclovir was associated with no CMV disease and was safe, with low incidence of kidney damage. These data suggest that pretransplant ganciclovir with preemptive therapy for viral reactivation should be considered regardless of graft source. Future prospective randomized trials are needed to evaluate strategies for CMV prophylactic regimens.

Essentials The safety of apixaban in patients on dialysis is currently debated.Bleeding events were retrospectively compared for dialysis patients on warfarin vs apixaban.Overall bleeding events were significantly less frequent in apixaban group compared to warfarin group.Apixaban appears to be a safe and effective choice for anticoagulation in patients on dialysis. Background The use of apixaban for stroke prophylaxis or for the treatment of venous thromboembolism in end stage renal disease (ESRD) patients maintained on dialysis is based on one single‐dose pharmacokinetic study. There is a deficiency of clinical evidence supporting safety in this population. Objective The purpose of this study was to determine the safety and efficacy of apixaban compared with warfarin in dialysis patients. Patients/methods This is a retrospective cohort study conducted at the University of Virginia Medical Center. A total of 124 ESRD patients maintained on dialysis who either received apixaban (n = 74) or warfarin (n = 50) between January 1, 2014 and October 31, 2016 were included in the study. We used multivariable logistic regression to compare the likelihood of patients experiencing a bleeding event based on anticoagulant therapy. Results The apixaban group experienced fewer overall bleeding events than the warfarin group (18.9% vs 42.0%; P = .01); this significant difference persisted in adjusted analysis (OR = 0.15; 95% CI = 0.05‐0.46; P = .001). Major bleeding events were less frequent in the apixaban group compared with patients on warfarin (5.4% vs 22.0%; P = .01). There were no recurrent ischemic strokes in either groups. A lower, non‐significant, incidence of recurrent VTE was found in patients on apixaban compared with warfarin (4.4% vs 28.6%; P = .99). Conclusion Compared to warfarin, our findings suggest that apixaban is a safe and effective alternative in patients with ESRD maintained on dialysis, with apixaban patients experiencing fewer bleeding events than warfarin patients.

83 Background: Concurrent chemotherapy (CTX) with checkpoint inhibitors (CPI) has become a new standard of care for treatment naïve stage IV non-small cell lung cancer (NSCLC). Little is known about the timing and pattern of immune-related adverse events (irAEs) when CTX and CPI are combined. We sought to characterize irAEs and determine if combination CTX+CPI affects time to first irAE in comparison to patients (pts) receiving CPI alone. Methods: Advanced NSCLC patients who received at least one dose of a CPI at our institution between 2015 and 2018, either alone or with CTX, were identified. Retrospective review for occurrence of irAEs and clinical outcomes was performed. Proportional hazards models were used to assess time to first irAE for CPI vs CTX+CPI and overall survival (OS) for CPI alone. Results: 149 pts were identified. 112 pts received CPI alone and 37 received CTX+CPI. The proportion of pts with at least 1 irAE was higher in the combination therapy group than the monotherapy group (59% vs 34% of patients). Time to any grade first irAE was shorter with CTX+CPI vs CPI alone (6.0 m vs 36.7 m, HR 1.8, p = 0.0304). Among pts treated with CPI alone, OS was significantly longer with any irAE (38.0 m vs 11.4 m, HR 2.9, p = 0.0026). While there were more irAEs in the CTX+CPI cohort, the frequency of irAEs by organ system was similar to previous reports. Conclusions: For patients receiving CTX+CPI, there is an increased risk of irAEs and a significantly shorter time to first irAE occurrence compared to CPI alone. Among patients receiving CPI alone, the presence of irAE was associated with a 3-fold improvement in OS. Further analysis of OS for the CTX+CPI group is planned with additional follow-up. [Table: see text]

Introduction: Cytomegalovirus (CMV) reactivation remains one of the most serious complications after allogeneic hematopoietic stem cell transplantation (HSCT) occurring in up to 30-50% of HSCT recipients. CMV reactivation can lead to adverse outcomes including end-organ damage and graft failure. Prevention of CMV infection may improve outcomes of HSCT recipients; however, CMV reactivation can still occur in HSCT recipients despite receiving prophylactic acyclovir. In this study, we used prophylactic ganciclovir pre-transplant to reduce the incidence of CMV reactivation and CMV disease. Methods: To reduce the incidence of CMV reactivation and disease, ganciclovir was administered before transplantation (5 mg/kg twice daily intravenously from day −8 to day −2) for all donor and recipient seropositive allogeneic HSCT. This was followed by high dose valacyclovir or acyclovir starting day 0 until one year post-transplant. Patients were monitored weekly with serum CMV PCR through Day 100 post transplantation. Preemptive therapy was started for an elevated CMV viral load. CMV reactivation was defined as a CMV viral load of more than 135 IU/ml. Over the course of the analysis period, two different PCR methods were used for CMV viral load; since 2015 Roche Cobas AmpliPrep/Cobas TaqMan CMV test was implicated. CMV disease was defined as detection of CMV by one of the following diagnostic tests including: culture, immunohistochemistry staining, or histopathology examination accompanied by documentation of disease signs and symptoms of the affected organ. Statistical analysis was performed using SAS version 9.4. Logistic regression models were explored to assess the association of age, graft source, and disease type on CMV reactivation. We performed a retrospective analysis of all recipient or donor CMV seropositive patients who received their first allogeneic HSCT at the University of Virginia between 2012 and 2017. Results: Seventy-nine consecutive patients were treated. The median age was 58 years (range 20 to 72). The most common diagnoses were acute myeloid leukemia (n=39, 49%) and acute lymphocytic leukemia (n=11, 14% ). Graft sources were matched related donor, (n=24, 30%), matched unrelated donor, (n=28, 35%), haploidentical (n=4, 5%) and cord blood (n=23, 29%). 43 patients (55%) received myeloablative (CyTBI, BuCy and FluBu) conditioning. 36 patients (45%) received reduced intensity/nonmyeloablative conditioning (Flu/Cy/TBI+/- ATG, Flu/Cy/ATG ,Flu Mel, Flu Bu and Cy ATG). All patients received calcineurin inhibitor based prophylactic immunosuppressive therapy for GVHD prevention. 24 patients (30%) had CMV reactivation with median time of reactivation of 47 days post-transplant (range 27 to 229). 22 out of the 24 (88%) patients required treatment for CMV reactivation with a median treatment duration of 37 days (range 14 to 315). Patients were treated with either ganciclovir or foscarnet, as clinically indicated. The cumulative incidence of CMV reactivation at day 100 post-transplant was 27% with a 95% CI (18%-37%). The median highest viral load was 2130 copies/ml (range 151 to 3,250,000 copies/ml). There were no patients with biopsy proven CMV disease. There were no deaths attributed to CMV reactivation or disease. The median time-to neutrophil recovery (ANC > 500 k/uL) was 18 days and the median time to platelet count greater than 20,000 k/ul unsupported was 19 days. The incidence of acute GVHD (Grades II-IV) was 25 %. The incidence of significant acute kidney injury defined by serum creatinine of more than 2.5 mg/dL was 2.4 %. 1 year overall survival estimate was 54% with 95% CI (42-65%). In multivariate analysis, patients who received cord blood transplants, were approximately 4 times more likely to have a CMV reactivation (Odds Ratio 3.9 with a 95% CI(1.4-10.9)), p= 0.01, than those who did not. Conclusions:The incidence of CMV reactivation by day 100 of 27% with pre-transplant ganciclovir may be improved compared to historical controls of 30-50%.The use of pre-transplant ganciclovir was associated with no CMV disease, in this single center study.The use of pre-transplant ganciclovir is safe, with low incidence of kidney damage. These data suggest that pre-transplant ganciclovir with Preemptive therapy for viral reactivation should be considered regardless of graft source. Future prospective randomized trials are needed to evaluate strategies for CMV prophylactic regimens. Disclosures No relevant conflicts of interest to declare.

Introduction: Thrombotic events are a frequent complication in patients with malignancy due to increased tissue factor expression and activation of hemostatic mechanisms by both host cells and cancer tissues. Patients with acute myeloid leukemia (AML) are at risk of venous thromboembolism (VTE) not only because of their malignancy but also because of prolonged hospitalizations, immobility, and the need for central venous access. Profound thrombocytopenia is an expected complication, due to myelosuppressive chemotherapy as well as from underlying marrow-infiltrative disease. This results in difficult prophylactic and treatment decisions where providers must carefully balance the risk of thrombosis and bleeding. There are no published consensus guidelines regarding appropriate use of prophylaxis in patients with leukemia. Methods: A retrospective chart review was completed on AML patients receiving induction or consolidation chemotherapy or treatment for relapsed disease admitted to the University of Virginia from October 2011 through September 2017. Patients with acute promyelocytic leukemia were excluded. Clinical data from 142 patients over a total of 667 hospital admissions were reviewed. The following data was collected: demographics (including age, sex, and race), clotting events, clot location, type of line placed, treatment of clot, and bleeding events. Bleeding events were defined according to International Thrombosis and Hemostasis criteria. χ2 analysis was performed to compare categorical values. Results: Twenty-nine of 142 (20.4%) AML patients were diagnosed with VTE. None of the patients had a prior history of clot or diagnosis of clotting disorder. Thrombosis occurred more commonly during induction therapy, 13 of the 29 events (45%), compared to other stages in their treatment (p value=0.37). Of the thromboses occurring during induction, 14 clotting events (48%) were central line associated, 4% (5/125) of thrombosis occurred in peripherally inserted central lines, 10% (5/51) in temporary internal jugular central lines and 2% (4/165) in tunneled central lines (p value=0.99). The average platelet count at the time of clot was 61 K/µl. Most patients were not on prophylaxis at the time of their clotting event (93.1% vs 6.9%; p value= Patients who received therapeutic anticoagulation had a comparable rate of bleeding compared to patients who were not on anticoagulation (31.6% vs 40.8%; p value= 0.44). Patients who were treated for VTE (n=19) had 2 major bleeds and 4 clinically relevant non-major bleeds. Patients who did not receive treatment for their VTE event (n=10) had 1 major bleed and 3 minor bleeding events. Conclusion: Our study identified a 20.4% incidence of VTE in AML patients, occurring more frequently during induction chemotherapy and in patients without prior thrombotic history.The clots were most commonly catheter associated and the highest rate of clot occurred with temporary internal jugular lines. Importantly, we found that when patients were treated with anticoagulation, their incidence of bleed did not exceed the general incidence of bleeding (43%) seen during the time period of the analysis. Average platelet count at VTE diagnosis was 61 K/µL, which is above most institutions' thresholds for use of pharmacologic VTE prophylaxis including patients with acute leukemia. Given that only two patients in our study were receiving prophylaxis at the time of VTE and that bleeding rates were similar with full therapeutic anticoagulation, this suggests prophylaxis is important, safe, and is potentially neglected in patients with acute leukemia. This highlights an area of potential improvement in decreasing VTE in patients that can safely receive prophylaxis and is the basis for future prospective safety trials exploring the use of prophylaxis in this patient population. Disclosures No relevant conflicts of interest to declare.

Background: High dose methotrexate (MTX) is an important agent in the prevention and treatment of cancer in the central nervous system. Administration of this drug requires alkalization of the urine, which traditionally includes the use of intravenous (IV) sodium bicarbonate (bicarb). In May 2017, IV bicarb was on national shortage; at the University of Virginia, pharmacists and physicians designed an oral (PO) regimen using bicarb and acetazolamide to ensure patients could continue receiving MTX. As there are limited published data, we aimed to assess the safety and the impact on time to start of MTX. Methods: Retrospective chart review was done 5/2016-4/2017 to establish a baseline time to methotrexate. In a prospective analysis, data was collected from May 2017 to May 2018 on all patients who received MTX. For patients receiving the PO regimen, bicarb 2,600 mg PO 6 times daily and acetazolamide 250 mg PO every 6 hours were the initial doses and titrated to maintain a urine pH greater than or equal to 7. The primary endpoint was time to MTX for patients with planned admissions who start MTX upon meeting urine pH and output parameters. Secondary endpoints included incidence of acute kidney injury (AKI) and delayed methotrexate clearance for all patient encounters. AKI was defined using Kidney Disease Improving Global Outcomes criteria. Delayed MTX clearance was defined based on failure to meet goal levels based on published chemotherapy protocols. χ2 analysis was completed on categorical variables. A statistical process control chart (p-chart) depicted time to MTX. Results: A total of 162 patient encounters were included in the analysis. The median age of patients receiving oral bicarb was 51 years (range 21-69) and was 51 years (range 21-63) for patients receiving IV bicarb. Eighty-six encounters were planned admissions that started MTX when urine parameters were met and received either IV (n=32) or PO bicarb (n=54). In these patients median time from admission to MTX was 8.4 vs 7.9 hours, respectively. Figure 1 shows consecutive patients receiving MTX prior to, during, and after resolution of the IV bicarb shortage; there is less variability and fewer outliers in the MTX start time when exclusively administering the PO regimen during the shortage. For the secondary analysis an additional 76 encounters with either unplanned admissions or predetermined MTX start time on subsequent day to admission were analyzed for safety outcomes. The rate of AKI was 14.5% vs 8.9% in the PO vs IV groups, respectively (p=0.28). There was no difference in incidence of delayed methotrexate clearance with 26.5% of patients in PO group vs 25.3% patients in IV group (p=0.87). Length of stay was slightly increased in patients who received PO vs IV alkalization (3.78 vs 3.15 days). Conclusion: Our alternative oral bicarb and acetazolamide urine alkalization regimen appears safe in patients receiving MTX and allowed for continued treatment of patients during a national IV bicarb shortage. Time to start of MTX was decreased with implementation of PO regimen, and there appeared to be a more predictable start time for MTX. While not significant, the higher incidence of AKI in PO group warrants further analysis. Future efforts include using oral outpatient alkalization prior to inpatient admission to work towards improving length of stay. Disclosures No relevant conflicts of interest to declare.

Introduction: A dangerous consequence of chemotherapy used to treat patients with hematologic malignancy is the breakdown of intestinal and oral mucosa known as MBI (mucosal barrier injury). In the setting of neutropenia, this can lead to life-threatening laboratory confirmed blood stream infections (LCBI) from translocation of bacteria. This results in increased length of stay, ICU admissions, and decreased quality of life for patients. Sparse evidence exists to guide clinicians on interventions to help prevent and treat MBI and reduce its complications. Methods: In an attempt to reduce MBI-LCBI events, a multidisciplinary team including oncology physicians, nurses, and pharmacists was assembled. A retrospective chart review from 1/2015 to 12/2015 was completed to establish a baseline for MBI-LCBI rate. This rate was calculated by dividing the number of MBI-LCBI events by total number of patients on the malignant hematology wards receiving inpatient chemotherapy treatment. The average MBI-LCBI rate was 0.01. While there is no published national average MBI-LCBI rate, we aimed to decrease this rate by 75%. LEAN principles were applied to approach the problem. A statistical process chart (p-chart) was used to depict rates of MBI-LCBI in baseline cohort and intervention groups. Results: The baseline MBI-LCBI rate was found to be 0.01. Through LEAN methodology with analysis of an A3 and outlining "5 whys," a number of root causes leading to increased MBIs were identified. These included: accessibility of necessary supplies needed for compliance with standard work, availability of the oral care kits, importance of on-going education related to appropriate care and maintenance practices. The multidisciplinary team focused on 2 main interventions to improve MBI-LCBI rate. One Plan Study Do Act (PDSA) cycle was completed and post intervention data was analyzed. In March of 2016 the first intervention implemented was a robust education plan for nursing, including instructions for grading mucositis based on WHO criteria and completing through oral assessments marking the first PDSA cycle. Through further analysis of an A3, oral care was identified as a potential intervention in decreasing MBIs. A second intervention of oral care bundle, consisting of sodium bicarbonate mouth wash, artificial saliva, scheduled nursing oral assessments and teeth brushing, was implemented on May of 2016. After one year of implementation of PDSA cycle 1 the MBI rate (0.003 MBI-LCBIs per month) was reduced by 70% from baseline (Figure 1). This was not sustainable and ultimately after completion of first cycle in March of 2018 the average MBI-LCBI rate was found to be 0.009 which was still reduced from the baseline event rate of 0.01 MBI-LCBI per month. Conclusions: Through a multidisciplinary effort, the rate of MBI-LCBIs were able to be reduced through interventions in both education of nursing and physician staff and focus on oral care in patients. While there was initially significant success, it is apparent towards the end of PDSA cycle 1 there was difficulty with sustainability. There was a reduction in the number of oral care bundle ordered and therefore currently a second PDSA cycle is underway with a nurse driven oral care order set. Further focus in prevention, sustainability support structures (nurse driven protocol implementation) and reducing MBI rate is important in decreasing morbidity and mortality in this patient population. Disclosures No relevant conflicts of interest to declare.

e18804Background: High-dose methotrexate (MTX), used in protocols for treatment and prevention of central nervous system disease in multiple types of cancer, requires intravenous (IV) hydration and...

Importance Tadalafil is used to treat erectile dysfunction after prostate cancer treatment, but its role as a preventive agent is undefined. Objectives To determine primarily whether tadalafil preserved erectile function in men treated with radiotherapy for prostate cancer, and secondarily to determine whether participant- or partner-reported overall sexual function and sexual and marital satisfaction were affected. Design, Setting, and Participants Stratified, placebo-controlled, double-blind, parallel-group study with 1:1 randomization at 76 community-based and tertiary medical sites in the United States and Canada. Two hundred forty-two participants with intact erectile function scheduled to receive radiotherapy for prostate cancer were recruited between November 2009 and February 2012 with follow-up through March 2013. Interventions One hundred twenty-one participants were assigned 5 mg of tadalafil daily and 121 were assigned placebo for 24 weeks starting with external radiotherapy (63%) or brachytherapy (37%). Participant-reported International Index of Erectile Function response before radiotherapy and at weeks 2 and 4, between weeks 20 and 24, between weeks 28 and 30, and 1 year thereafter. Participants and partners could respond also to the Sexual Adjustment Questionnaire and to the Locke Marital Adjustment Test before radiotherapy, between weeks 20 and 24 and weeks 28 and 30, and at 1 year. Main Outcomes and Measures Primary outcome was off-drug spontaneous erectile function 28 to 30 weeks after radiotherapy started. Secondary end points were spontaneous erection at 1 year; overall sexual function and satisfaction; marital adjustment; and partner-reported satisfaction and marital adjustment at 28 to 30 weeks and 1 year, predictors of tadalafil response; and adverse events. Results Among 221 evaluable participants, 80 (79%; 95% CI, 70%-88%) assigned to receive tadalafil retained erectile function between weeks 28 and 30 compared with 61 (74%; 95% CI, 63%-85%) assigned to receive placebo ( P = .49); an absolute difference of 5% (95% CI, −9% to 19%). A significant difference was also not observed at 1 year (72%; 95% CI, 60%-84% vs 71%; 95% CI, 59%-84%; P = .93). Tadalafil was not associated with significantly improved overall sexual function or satisfaction; a significant difference was not observed in any domain subscale. Partners of men assigned tadalafil noted no significant effect on sexual satisfaction, and marital adjustment was not significantly improved in participants or partners. Conclusions and Relevance Among men undergoing radiotherapy for prostate cancer, daily use of tadalafil compared with placebo did not result in improved erectile function. These findings do not support daily use of tadalafil to prevent erectile dysfunction in these patients. Trial Registration clinicaltrials.gov Identifier:NCT00931528

9525 Background: Determine if prophylactic tadalafil maintains spontaneous (off-drug) erectile function (EF) compared to placebo in patients (pts) treated with radiotherapy (RT) for prostate cancer. Methods: Double-blind 1:1 randomization to tadalafil 5mg daily for 6 mos vs placebo starting with RT. Primary outcomes measured by International Index of Erectile Function (IIEF). Eligibility included pre-RT IIEF Question [Q] 1 response “sometimes/most times/always” able to get an erection. Ps treated with hormones were excluded. Primary outcome was response to IIEF Q1 at 30 wks (6 wks off drug). Pts were stratified by RT modality (external vs. brachytherapy) and age (≤65 vs. >65 years). 182 pts were needed in an intent-to-treat analysis to show a difference from 20% responders with placebo to 40% with tadalafil based on a 2-sided Fishers exact test with α=0.05 and 80% power. Results: We report on 155/222 analyzable/eligible pts. Median age was 63 years, white (73%), and external RT (63%). Mean total dose for external RT was 77.23 Gy and 136.74 Gy for brachytherapy with penile bulb D50 of 24.46 Gy and 31.24 Gy respectively. Most pts completed treatment per protocol (84% tadalafil, 70% placebo). Spontaneous EF at 30 wks from drug start was not different (p=0.99) between arms based on IIEF Q1 response, total IIEF score (52.5 drug vs 52.8 placebo), or score change from baseline (-8.0 drug vs -8.8 placebo). No difference in these outcomes was noted at 1 year. Non-responders at 30 wks were likely to be older (age≥65; p=0.432), but there were no significant predictors at 1 year. About 80% of pts maintained spontaneous EF in both arms. Conclusions: Low-dose daily tadalafil did not preserve EF within the first year of RT for prostate cancer. If tadalafil positively influences delayed RT-induced vasogenic injury, additional time may be needed to observe a benefit to tadalafil as a preventive agent. Alternatively, tadalafil dose modification or altered dosing schedules may be needed to demonstrate a protective effect of this agent when used with RT. Clinical trial information: NCT00951184.