Wood, Chanel

Abstract INTRODUCTION: Significant burden of pain syndromes are reported in patients with hematological malignancies undergoing HSCT mostly due to underlying disease and associated treatments. Opioid analgesics and benzodiazepines are routinely used for symptomatic management in this patient population. The use of narcotic analgesics and benzodiazepines in non-transplant hospitalized patients has been shown to adversely affect health related outcomes such as length-of-stay (LOS), falls and other complications. However, there is a significant knowledge gap regarding the patterns of opioid and benzodiazepine use and their impact on health outcomes in HSCT patients. METHODS: We identified 275 patients from the year 2015-2018 who underwent HSCT (allogeneic and autologous transplants) at our center for a variety of hematological malignancies. Opioid exposure was defined in three groups of patients 1) Opioid naïve: those did not report prior use of opioid at admission and who were not prescribed opioid during hospitalization, 2) Previous Opioid users: those who reported active use of opioid at admission and continued during hospitalization 3) New Opioid users: Patients who did not report opioid use at admission but were prescribed opioid during hospitalization. Multivariable analysis was performed to identify differences in opioid status, opioid use, benzodiazepine use, disease diagnosis, Karnofsky score, gender, age, race, and marital status with associated complications (Poisson regression), emergency department visits (Logistic Regression) and length of stay (Ordinal Logistic Regression) Figure 1 and Figure 2. RESULTS: The median age of patients was 59 (range: 25-74 ) years with slight male predominance (57%). Patients undergoing autologous transplants for multiple myeloma (MM) comprised 48% of the population. The majority (72 %) were exposed to opioid during hospitalization. Ninety two percent of the opioid naïve population (28% of the total population) underwent autologous transplant. Conversely, 36% of patients undergoing autologous transplants never received opiates during hospitalization as compared to 7% of those who received an allogeneic transplant. Median morphine milligram equivalent daily dose was 3.1 mg. Median diazepam equivalent daily dosage in patients that were opiate exposed was 2.07 milligram. Of the total transplant population, 55% received benzodiazepine concurrently with opiates during hospitalization. 76 % of the population was exposed to both opioid and benzodiazepine. Twenty five percent of those who were exposed to opioid did not receive benzodiazepines. Sixty four percent of the MM patients were exposed to opioid of which majority (59%) were previous opioid users. Of the non-MM patients undergoing HSCT, 80% were exposed to opioid of which 36% were previous opioid users and 64% were new users. A wide range of complications from neutropenic fever to death, were seen in 89% of all patients (opioid users and non-users) but all the falls occurred in patients who were on opioid medications. Autologous transplant recipients had higher odds of having a greater number of complications compared to Allogeneic transplant patients (OR 1.25, 95% CI: 1.01 - 1.55, p=0.04), as well as a reduced odds of having a medium or high length of stay (OR 0.03, 95% CI: 0.02 - 0.07). Of the opioid naïve patients, 6% presented to the ED within 30 days of discharge versus 15% of those that were exposed to opiates during hospitalization. Benzodiazepine use at admission for HSCT was associated with greater odd of presenting to ED within 30 days of discharge (OR 3.94, 95% CI: 1.55-10.04) and this was more significant in patients with MM (OR 4.08, 95% CI: 1.01-16.44). Finally, we also saw a trend towards longer stay in patients who were exposed to opioids as compared to opioid naïve (40% vs. 17%). CONCLUSION: Our study, albeit limited due to its retrospective design, is among the first to report the patterns of use and the impact of opioids and benzodiazepines in patients undergoing HSCT. Our results indicate that the use of these medications is frequent in this population and as in the non-transplant hospitalized patients and is associated with more emergency room visits post discharge, along with other potentially adverse outcomes. Disclosures Kharfan-Dabaja: Incyte Corp: Speakers Bureau; Seattle Genetics: Speakers Bureau; Alexion Pharmaceuticals: Speakers Bureau. Ailawadhi:Amgen: Consultancy; Pharmacyclics: Research Funding; Celgene: Consultancy; Takeda: Consultancy; Janssen: Consultancy.

Abstract INTRODUCTION: Patients undergoing HSCT are reported to have a high prevalence of depression and anxiety. These comorbid mood disorders have been known to be associated with alteration in pain perception in patients without hematological malignancies. Pharmacological compounds such as opioid and benzodiazepines are frequently used to manage patient symptomology including pain and anxiety. Patients undergoing HSCT are a unique population where the impact of depression and anxiety on opioid and benzodiazepine use has not been well studied. METHODS: The study population consisted of patients who underwent HSCT at a single center for a variety of hematological malignancies from 2015-2018. Opioid and benzodiazepine exposure and dosage was defined in a) Patients who were exposed to opioid including those who were previously exposed and those who were exposed during hospitalization for HSCT b) Patients who were neither exposed to opioid previously, nor during the hospitalization for HSCT. Depression and Anxiety was defined as per PHQ-9 and GAD-7 scales prior to hospital admission. Multivariable analysis was performed to identify differences in opioid status, previous benzodiazepine use, transplant type, Karnofsky score, gender, age, race, and marital status with associated Diazepam Equivalent Daily Dosage (DEDD) (Negative Binomial Regression), and Morphine Milligram Equivalent Daily Dosages (MMEDD) (Logistic and Zero Truncated Negative Binomial Regression). RESULTS: A total of 275 patients underwent HSCT including autologous and allogeneic from 2015-2018. Anxious or depressed HSCT recipients had an increased incidence of higher DEDD with an IRR of 1.69 (95% CI: 1.15, 2.49) compared to those who were neither depressed nor anxious (Figure 1). However, patients who reported anxiety and depression did not have a different DEDD than those not anxious nor depressed. In addition, patients who were not naïve to benzodiazepine use prior to admission had an increased incidence of a higher DEDD [IRR of 2.23 (95% CI: 1.61, 3.05)]. Patients undergoing autologous stem cell transplant had a decreased incidence of receiving a higher DEDD [IRR of 0.65 (95% CI: 0.47-0.90)]. African American and other populations had a decreased incidence of receiving a higher DEDD [IRR of 0.40 (95% CI: 0.27, 0.59)]. Patients receiving higher MMEDD had a higher DEDD incidence [IRR of 1.01 (95% CI: 1.01, 1.02)]. Patients who were both anxious and depressed had increased odds of receiving an opioid [OR of 3.35 (95% CI: 1.62, 6.94)] compared to patients who were neither depressed nor anxious. However, patients who were either depressed or anxious did not have different odds of receiving an opioid compared to those who were neither depressed nor anxious. Patients undergoing autologous stem cell transplant had reduced odds of receiving an opioid [OR of 0.17 (95% CI: 0.07, 0.40)]. Patients with less than normal Karnofsky performance status (<90 on scale of 1-100) had an increased incidence of receiving a higher MMEDD [IRR of 2.34 (95% CI: 1.07, 5.12)] when modeled by Zero Truncated Negative Binomial Regression. Finally, HSCT recipients who were both anxious and depressed had reduced odds of being naïve to opioids [OR0.31 (95% CI: 0.15, 0.67)] compared to recipients who were neither depressed nor anxious. New opioid users had reduced odds of receiving a greater MMEDD [OR of 0.98 (95% CI: 0.96, 0.99)] when compared to previous users. In addition, autologous stem cell transplant recipients had reduced odds of receiving greater MMEDD compared to allogeneic transplant recipients (OR 0.33, 95% CI: 0.16, 0.66). CONCLUSION: Comorbid depression and /or anxiety impact opioid and benzodiazepine use in patients undergoing HSCT. The presence of these comorbid conditions and their association with increased use of opioids and benzodiazepines can also affect various health related outcomes. Larger studies are needed to fully understand the potential impact of this association on health related outcomes. Figure 1. Figure 1. Disclosures Kharfan-Dabaja: Incyte Corp: Speakers Bureau; Alexion Pharmaceuticals: Speakers Bureau; Seattle Genetics: Speakers Bureau. Ailawadhi:Amgen: Consultancy; Pharmacyclics: Research Funding; Celgene: Consultancy; Janssen: Consultancy; Takeda: Consultancy.