Search

Introduction: Pediatric or pediatric-inspired regimens are used in the treatment of adolescent or young adult (AYA) patients with acute lymphoblastic leukemia (ALL). While overall survival is improved with these regimens, hepatotoxicity and metabolic complications are common adverse events related to the increased dosages of asparaginase and steroids used vs adult ALL regimens. Among ethnicities, prevalence of metabolic syndrome and hepatic steatosis is highest in the Hispanic population, which comprises ~20% of the US population and carries an increased risk of ALL. Surprisingly, there is limited literature describing hepatotoxicity in this at-risk population. Herein we describe our experience with this adverse effect in AYA Hispanic patients ( Methods: Single-center retrospective chart review of patients with ALL treated from January 1, 2010 to May 30, 2021 at the University of Illinois at Chicago. Patients with an associated ALL diagnosis were identified through an internal pathology database. Demographic information, clinical characteristics, treatment history and complications [grade 3/4 transaminitis, development of non-alcoholic fatty liver (NAFLD) on imaging, non-alcoholic steato-hepatitis (NASH)/fibrosis/cirrhosis on biopsy, pancreatitis, treatment change or drug discontinuation secondary to hepatotoxicity] were abstracted from the EMR. Descriptive statistics were used to determine outcome frequencies. Results: We identified 33 Hispanic (n= 20) and Non-Hispanic White (NHW; n = 13) patients with either B-ALL or T-ALL, with each demographic stratified by pediatric or adult regimen therapy (Table 1). Pediatric regimens include Children's Oncology Group protocols and E1910; the adult regimen was HyperCVAD. Of 16 Hispanic patients who received pediatric regimens, 7 (44%) had pre-existing diabetes, 1 had fatty liver on baseline imaging and 1 biopsy-confirmed NASH. During treatment, 12/16 (75%) developed grade 3/4 hepatotoxicity, 11 (69%) developed mild-severe NAFLD on imaging, 2 additional patients developed cirrhosis, and 4 (25%) pancreatitis. Treatment-related adverse events prompted therapy change or drug discontinuation in 25%. Hispanic patients, (n = 4), on adult and NHW patients, (n = 7), on pediatric regimens had low rates of pre-existing comorbidities, but of the older NHW patients, (n = 6), on an adult regimen, 4/6 (67%) and 1/6 had underlying diabetes or NAFLD, respectively. We found similar high rates of grade 3/4 hepatotoxicity in Hispanics on an adult regimen (100%) and NHW patients on either a pediatric (71%) or adult regimen (50%). However, fewer patients developed NAFLD (4/17, 24%), only 1 (Hispanic) patient developed fibrosis, and none developed pancreatitis. There was no difference in mean BMI between Hispanic and NHW patients. Conclusions: While grade 3/4 transaminitis is described during ALL treatment, in this retrospective analysis we observed that Hispanic AYA patients treated on pediatric protocols frequently develop more serious complications including hepatic steatosis, cirrhosis or pancreatitis. Co-existing metabolic syndrome is associated with a higher incidence of simple steatosis (SS; 70% in obesity, 90% in diabetes), and Hispanic patients have a higher baseline SS incidence (45% in Hispanics vs 33% in NHW), which in the context of use of higher doses of steroids and asparaginase may explain their increased frequency of progression to NASH and fibrosis. As few underwent biopsy, the true incidence is likely underrepresented. Additionally, Hispanics treated on a pediatric regimen more frequently developed pancreatitis than NHW patients on the same regimen. SS is related to the accumulation of hepatic free fatty acids and triglycerides, thus patients with SS or at risk may have impaired free fatty acid metabolism that predisposes to pancreatitis with asparaginase use. Limitations of this study include a small sample size, partial availability of baseline imaging, and non-standardized radiographic interpretations of the degree of steatosis. However, our findings suggest further investigation is warranted and a multi-center study is in progress. Our study highlights the need for closer monitoring of Hispanic patients to mitigate the risk of serious liver disease with the use of curative pediatric regimens for ALL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Opioid analgesics are used to treat cancer-related pain and improve quality of life, however overuse of these high-risk drugs has been associated with significant public health implications as exhibited by the national attention received during the opioid pandemic. In addition, pain associated with hematologic malignancies is frequent yet not well understood. There is no data examining opioid use and outcomes in patients with hematologic malignancies and recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, we sought to describe chronic opioid use (COU) and its impact on long-term outcomes in patients undergoing allo-HSCT. We analyzed outcomes of adult patients ≥ 18 years (n=159) diagnosed with hematologic malignancies (n=151) or benign hematologic disorders (n=8) (excluding sickle cell disease) who received allo-HSCT between 2012 and 2019 at a single urban medical center. COU was defined as having a documented active prescription for 3 consecutive months. Daily opioid doses were converted to morphine milligram milliequivalents (MME) using standard conversion factors. Among the entire cohort, the median age was 55.4 (19.4-74.3) years, 94 (59.1%) were male, 70 (44%) were White, 42 (26.4%) were Hispanic, and 26 (16.4%) were Black. The majority of patients were diagnosed with acute leukemia, with 89 (56%) having AML and 16 (10%) having ALL patients. Of the remaining patients, 14 (8.8%) were CML-BP or CML-AP, 16 (10%) NHL/HD, and 15 (9.4%) MPDs. 33.5% of patients were found to have high or very high DRI prior to allo-HSCT. Most patients received either a myeloablative (n=102, 64.2%) or reduced-intensity (n=55, 34.6%) conditioning regimen. At baseline (immediately prior to allo-SCT), COU was observed in 38 (23.9%) patients, 20 (52.6%) of which were diagnosed with AML. Only 23 (60.5%) patients with COU had a documented indication for opioid analgesia. The baseline median MME per day was 23.5mg (range: 2-150). In logistic regression analysis including demographic and social factors such as insurance type (i.e. Medicare, Medicaid, private payer), education level, smoking, alcohol, illicit drug and/or benzodiazepine use, and employment status, only older age (RR 0.97, 95% CI 0.94-0.99; p=0.026) was associated with a lower likelihood of baseline COU. In total, 149 (93.7%) patients received opioids during the allo-HSCT admission, while 45 (28.3%) were discharged on opioids. The reason for being discharged on opioids was related to musculoskeletal pain (n=19), residual mucositis-related pain (n=7), and headache (n=3). This was found to persist over time, with 35 (92.1%) of the 45 patients discharged on opioids remaining on opioids at 180 days after allo-HSCT thus meeting the definition for COU. The only factor found to predict for COU at 6 months was discharge from initial transplant hospitalization with an opioid (RR 2.24, 95% CI 1.16-4.32, p=0.016). Not only did a significant number of post-transplant survivors meet the definition for COU, but the MME was found to be relatively high with a median of 50mg (range: 10-540) at discharge and 30mg (range: 4.5-202) on days +30, 90, 180 as well as at 1 and 5 years after allo-HSCT. In a multivariable modified Poisson regression with robust standard errors for binary outcomes, when adjusted for established prognostic characteristics (i.e., disease, DRI, HCT-CI), we found that COU prior to admission strongly predicted for worse overall survival (HR 2.99, 95% CI 1.59-5.64; p=0.001), progression free survival (HR 2.72, 95% CI 1.48-4.99), and GVHD free, relapse-free survival (HR 1.78, 95% CI 1.05-3.03; p=0.033). This study is the first to describe patterns of COU, an important public health problem, among patients undergoing allo-HSCT, and in particular in long term survivors. We demonstrate high rates of baseline COU in patients undergoing allo-HSCT as well as persistent long term COU, which is linked to prescribing patterns after the initial transplant hospitalization. In addition, we show the negative impact of baseline COU on overall survival, even when adjusted for disease- and transplant-related factors. These data highlight the need to improve understanding and management of pain in hematologic malignancies as well as to reinforce the need for continuous reassessment of the use of opioids prior to and after allo-HSCT. Disclosures Calip: Flatiron Health: Current Employment; Roche: Current equity holder in publicly-traded company; Pfizer: Research Funding. Rondelli: Vertex: Membership on an entity's Board of Directors or advisory committees. Patel: Celgene: Consultancy.

Background Vaccine hesitancy, defined as the delay in acceptance or refusal of safe vaccines, remains a challenge in the general population. Given that patients with hematologic malignancies frequently encounter healthcare professionals and are at high risk of severe COVID-19 infection, their attitudes towards vaccines may differ from other patient groups. We therefore performed a survey-based study to investigate vaccine hesitancy within an ethnically diverse group of patients diagnosed with hematologic malignancies. Methods We administered a 122-item questionnaire from December 2020 to January 2021 (prior to commercial availability of the COVID-19 vaccines) to 60 patients with hematologic malignancies. Questions were separated into the following categories: demographic and socioeconomic data; personal impact of COVID-19 infection; COVID-19 pandemic experience; COVID-19 infection perceptions; COVID-19 vaccine perceptions; and baseline COVID-19 vaccine knowledge. Results The majority of patients were Black (n=33, 55%) or Hispanic (n=11, 18.3%) and were undergoing active treatment (n=43, 71.7%) or had received prior hematopoietic stem cell transplantation (n=9, 15%). Eight (13.3%) patients had prior COVID-19 infection. Sixteen (26.7%) patients reported infection in an immediate family member while 15 (25%) reported infection in a friend. 20 of these cases were moderate in severity requiring healthcare interaction, and 17 of these cases were reported to result in severe infection (n=7, 9.6%) or death (n=10, 13.7%). Only 16 (29.6%) patients perceived themselves to be at high or very high risk of COVID-19 infection. The COVID-19 pandemic was reported to moderately or severely affect employment/income in 10 (22.8%) patients and led to worse mental health in 10 (22.3%) patients. However, the majority of patients reported no negative impact on their cancer treatment (n=37, 88.1%) or prognosis (n=45, 93.8%). Of the 60 patients, 22 (40.7%) reported that if a COVID-19 vaccine was made publicly available in the next 30 days, they would not vaccinate themselves, either due to safety concerns (n=4, 20%) or indifference (n=6, 30%). Despite this, 43 (78.2%) patients stated that vaccination was an important tool in ending the pandemic. More patients agreed to accept the vaccine if it was made available in 6 months from the time of survey (n=40, 76.9%). Only 32 (59.3%) patients were extremely or very likely to accept a yearly vaccine. In terms of perception on cancer outcomes, 31 (62%) patients were uncertain if the vaccine would interact negatively with their current chemotherapy treatment, while 27 (52.9%) believed the vaccine would make their cancer worse. The biggest fear patients had about COVID-19 vaccines were side effects or death (n=15, 38.5%) and complications to cancer/cancer therapy (n=5, 12.8%). Only 6 (15.4%) patients stated they had no fears related to COVID-19 vaccination. In fact, only 21 (39.6%) patients agreed or strongly agreed that the side effects of most vaccines outweigh the benefits. In a modified (age- and sex-adjusted) Poisson regression model (Table 1) that included baseline demographics and answers to select survey questions, older age was associated with a stronger likelihood of vaccine acceptance (RR 1.73, 95% CI 1.11-2.71; p=0.016), while female gender was associated with less likelihood to accept the vaccine (RR 0.58, 95% CI 0.37-0.90; p=0.016). Patients reported as "other" race (e.g., Asian) were more inclined to accept the vaccine (RR. 2.21, 95% CI 1.16-4.20; p=0.016) compared to White patients. Finally, when compared to patients who receive information primarily from medical professionals, those patients who received their information from social media or friends were far less likely to accept the vaccine (RR 0.02, 95% CI 0.01-0.04; p Conclusion This is the first study to report that although patients with hematologic malignancies experienced significant medical and social burdens from the COVID-19 pandemic and have frequent interaction with healthcare professionals, a high rate of COVID-19 vaccine hesitancy still exists. We provide in depth information on the potential reasons for vaccine refusal in a diverse patient population and highlight potential areas for improvement in patient education. In particular, we show that vaccine disinformation received from friends and social media is a significant reason for vaccine refusal. Figure 1 Figure 1. Disclosures Calip: Pfizer: Research Funding; Roche: Current equity holder in publicly-traded company; Flatiron Health: Current Employment. Rondelli: Vertex: Membership on an entity's Board of Directors or advisory committees. Patel: Celgene: Consultancy.