Mahir Khan’s research while affiliated with University of Illinois Chicago and other places

Introduction: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy. Methods: Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors. Results: Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3 months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 - 1.39; targeted therapy OR 1.89, 95% CI 0.64 - 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 - 2.35). Conclusions: Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors.

Background Eligibility assessment of patients with sickle cell disease (SCD) for allogeneic hematopoietic stem cell transplant (HSCT) is a complex yet vital component of pre-transplant evaluation. Psychosocial assessment tools have been modeled after those completed in solid organ transplantation but no studies have validated these tools in this population and therefore a standardized assessment is lacking. Because adult SCD patients face the burdens of chronic disease and racial disparities, we hypothesized that psychosocial frailties would be prevalent in those undergoing HSCT. Methods Adult patients diagnosed with sickle cell disease who received HSCT between 2014 and 2021 and had a documented pre-HSCT social worker semi-structured qualitative interview addressing patient's living arrangement, family structure, education, employment, financial situation, social habits and understanding of the transplant were included. Our goal was to use these interviews to identify domains of psychosocial frailties and to eventually develop a tool in this SCD patient population that could be used pre-HSCT. Interviews. A codebook was developed by the research team consisting of clinical experts and a qualitative expert. This process was repeated to theme saturation, resulting in a RedCap scoring tool with 12 psychosocial frailty domains related to housing, transportation, interpersonal issues with family, marital status, dependency, unemployed work status, mental health diagnosis, dependence on government subsidies, and the presence of a reliable 24-hour caregiver. Two reviewers independently coded the data from notes into Redcap and discrepancies were addressed with the team. Results Of the 65 SCD patients who received HSCT, 40 patients met inclusion criteria. The median age at the time of transplant was 29 (18-55) years and 19 patients (47.5%) were male. 21 (52.5%) patients received a haploidentical HSCT, while 19 (47.5%) received a matched relator donor HSCT. Insurance was either private (n=20, 50%), Medicaid for (n=11, 27.5%), or Medicare/Medicaid (n=5, 12.5%). For marital status, 15 (37.5%) were married and 23 (57.5%) were not married. Most patients had either a high school (n=17, 42.5%) or college (n=13, 32.5%) degree. 40% of patients were unemployed at the time of transplant. We then examined the frequency of individual and total psychosocial frailties experienced within each patient and among the entire cohort. In 40 patients, a total of 150 psychosocial frailties existed. The most frequent psychosocial frailties were related to marital status (n=25), government subsidy dependency (n=18), housing dependency (n=18), financial dependency (n=17), unemployed work status (n=16), and any transportation vulnerability (n=17). The median number of psychosocial vulnerabilities experienced by each patient was 4 (range: 0-9), with 10 (25%) patients having more than 5 vulnerabilities. Specific vulnerabilities are listed in Table 2. After a median follow up of 36.7 (3-101.3) months, there were 3 deaths, with 0, 4, and 9 pre-HSCT psychosocial frailties experienced by each patient. 8 (53%) patients with a psychosocial frailty ≥ 5 were re-hospitalized within 100 days of HSCT. Conclusions Here we report for the first time an analysis of a qualitative dataset to understand and determine the prevalence of psychosocial frailties that adult sickle cell patients experience during allo-HSCT. We observed a very high number of frailties within the entire cohort including financial and housing dependency, not having a 24-hour caregiver after HSCT, and reliance on government subsidies for support. However, despite these psychosocial frailties, HSCT was successfully performed in these patients and based on this, should not be a barrier to receiving this life-saving procedure. Confirming these findings in a larger cohort in order to assess the impact on survival and specific transplant outcomes is warranted.

Importance Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation. Objective To determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer. Design, Setting, and Participants This registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings. Exposures Immunosuppression due to therapy; systemic anticancer therapy (IO or non-IO). Main Outcomes and Measures The primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm. Results The median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79). Conclusions and Relevance This cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm. Trial Registration ClinicalTrials.gov Identifier: NCT04354701

Background: During the COVID-19 pandemic, telehealth rapidly emerged as an essential health care service and became particularly important for patients with cancer and chronic conditions. However, the benefits of telehealth have not been fully realized for some of the most vulnerable populations due to inequitable access to telehealth capable technology. Purpose: This study aimed to assess accessibility and satisfaction with telehealth technology by vulnerable patients with cancer and pulmonary disease. Methodology: A paper survey and internet-based survey were developed and administered to adult (≥18 years) cancer and pulmonary clinic patients (July 1, 2020 to October 30, 2020). Results: Descriptive statistics and Fisher exact test were performed. Two hundred eleven patients completed the survey. Adults ≥50 years old (older) had reduced access to smartphone video capability and internet connection compared with adults less than 50 years old (59% vs. 90%, p < .01). Older adults reported more challenges with telehealth visits compared with younger adults (50.3%, 28.6%; p < .01). No difference in access to technology and preferences for telehealth versus in-person care was found by race, gender, or education level. Conclusions: Nearly all patients (95%) who had a previous experience with a telehealth visit felt confident in the quality of care they received via telehealth. Younger adults preferred video visits compared with older adults (75% vs. 50.6%, p < .01). Older adults were less likely to have access to smartphones with internet access, have more challenges with telehealth visits, and were less likely to prefer audio-video telehealth visits compared with younger adults. Implications: Ensuring equitable access to all health care delivery modalities by telehealth, including audio-only visits for patients across the age continuum, is paramount.

Importance: Non-Hispanic Black individuals experience a higher burden of COVID-19 than the general population; hence, there is an urgent need to characterize the unique clinical course and outcomes of COVID-19 in Black patients with cancer. Objective: To investigate racial disparities in severity of COVID-19 presentation, clinical complications, and outcomes between Black patients and non-Hispanic White patients with cancer and COVID-19. Design, setting, and participants: This retrospective cohort study used data from the COVID-19 and Cancer Consortium registry from March 17, 2020, to November 18, 2020, to examine the clinical characteristics and outcomes of COVID-19 in Black patients with cancer. Data analysis was performed from December 2020 to February 2021. Exposures: Black and White race recorded in patient's electronic health record. Main outcomes and measures: An a priori 5-level ordinal scale including hospitalization intensive care unit admission, mechanical ventilation, and all-cause death. Results: Among 3506 included patients (1768 women [50%]; median [IQR] age, 67 [58-77] years), 1068 (30%) were Black and 2438 (70%) were White. Black patients had higher rates of preexisting comorbidities compared with White patients, including obesity (480 Black patients [45%] vs 925 White patients [38%]), diabetes (411 Black patients [38%] vs 574 White patients [24%]), and kidney disease (248 Black patients [23%] vs 392 White patients [16%]). Despite the similar distribution of cancer type, cancer status, and anticancer therapy at the time of COVID-19 diagnosis, Black patients presented with worse illness and had significantly worse COVID-19 severity (unweighted odds ratio, 1.34 [95% CI, 1.15-1.58]; weighted odds ratio, 1.21 [95% CI, 1.11-1.33]). Conclusions and relevance: These findings suggest that Black patients with cancer experience worse COVID-19 outcomes compared with White patients. Understanding and addressing racial inequities within the causal framework of structural racism is essential to reduce the disproportionate burden of diseases, such as COVID-19 and cancer, in Black patients.

Importance The COVID-19 pandemic has had a distinct spatiotemporal pattern in the United States. Patients with cancer are at higher risk of severe complications from COVID-19, but it is not well known whether COVID-19 outcomes in this patient population were associated with geography. Objective To quantify spatiotemporal variation in COVID-19 outcomes among patients with cancer. Design, Setting, and Participants This registry-based retrospective cohort study included patients with a historical diagnosis of invasive malignant neoplasm and laboratory-confirmed SARS-CoV-2 infection between March and November 2020. Data were collected from cancer care delivery centers in the United States. Exposures Patient residence was categorized into 9 US census divisions. Cancer center characteristics included academic or community classification, rural-urban continuum code (RUCC), and social vulnerability index. Main Outcomes and Measures The primary outcome was 30-day all-cause mortality. The secondary composite outcome consisted of receipt of mechanical ventilation, intensive care unit admission, and all-cause death. Multilevel mixed-effects models estimated associations of center-level and census division–level exposures with outcomes after adjustment for patient-level risk factors and quantified variation in adjusted outcomes across centers, census divisions, and calendar time. Results Data for 4749 patients (median [IQR] age, 66 [56-76] years; 2439 [51.4%] female individuals, 1079 [22.7%] non-Hispanic Black individuals, and 690 [14.5%] Hispanic individuals) were reported from 83 centers in the Northeast (1564 patients [32.9%]), Midwest (1638 [34.5%]), South (894 [18.8%]), and West (653 [13.8%]). After adjustment for patient characteristics, including month of COVID-19 diagnosis, estimated 30-day mortality rates ranged from 5.2% to 26.6% across centers. Patients from centers located in metropolitan areas with population less than 250 000 (RUCC 3) had lower odds of 30-day mortality compared with patients from centers in metropolitan areas with population at least 1 million (RUCC 1) (adjusted odds ratio [aOR], 0.31; 95% CI, 0.11-0.84). The type of center was not significantly associated with primary or secondary outcomes. There were no statistically significant differences in outcome rates across the 9 census divisions, but adjusted mortality rates significantly improved over time (eg, September to November vs March to May: aOR, 0.32; 95% CI, 0.17-0.58). Conclusions and Relevance In this registry-based cohort study, significant differences in COVID-19 outcomes across US census divisions were not observed. However, substantial heterogeneity in COVID-19 outcomes across cancer care delivery centers was found. Attention to implementing standardized guidelines for the care of patients with cancer and COVID-19 could improve outcomes for these vulnerable patients.

Patients with sickle cell disease (SCD) are known to require increased dosing of drugs including opioids due to differences in renal and hepatic metabolism. While it is known that SCD patients require higher opioid doses to achieve the same degree of analgesia, it is not clear if this is associated with a similar increase in drug toxicities. A significant risk of opioid use is respiratory depression, and naloxone is used for rapid reversal of this adverse effect. In the setting of a nationwide opioid shortage in 2018, our institution established a policy requiring the use of patient-controlled analgesia (PCA) rather than intravenous push (IVP) for hospitalized SCD patients. This coincided with a mandate for end tidal carbon dioxide (ETCO) monitoring with PCA use, effectively implementing ETCO in the routine care of this population. In this study, we describe our experience using naloxone for opioid reversal in hospitalized SCD patients. We studied naloxone use in patients admitted to the University of Illinois at Chicago for two 24-month time periods (July 31, 2015 - July 31, 2017 and May 1, 2018 - May 1, 2020). These dates were chosen to compare naloxone use before and after implementation of ETCO monitoring. A pharmacy reporting tool was used to identify every dose of naloxone administered within the hospital during these dates. We isolated patients on the inpatient sickle cell service and compared the proportion of SCD patients between study periods using Fisher's exact test. For SCD patients who received naloxone, we obtained baseline patient characteristics and divided doses into episodes when multiple doses were given within a day. For each episode, we studied analgesic regimens, details of the hospitalization, and laboratory values. Given the small data sample, we used descriptive statistics for analysis. Among 931 total naloxone doses given in the two time periods, 35 were given to SCD patients. Out of 580 total distinct patients, there were 14 patients admitted to the sickle cell service. There were 5 out of 279 (1.8%) SCD patients who received 12 out of 443 (2.7%) doses between July 2015 and July 2017. There were 10 out of 309 (3.2%) SCD patients who received 23 out of 488 (4.7%) doses between May 2018 and May 2020. There was no significant difference in naloxone use by SCD patients before and after implementation of ETCO. For the two time periods combined, there were 14 out of 580 (2.4%) SCD patients who received 35 out of 931 (3.8%) doses. We were able to manually confirm 10 SCD patients and 17 episodes of naloxone use by chart review. Among these, 2 patients who only had 1 episode each received naloxone in the absence of opioid overdose. One patient with multiple episodes had an episode of receiving naloxone for opioid overdose not involving hospital-administered medications. Among the remaining 8 SCD patients who appropriately received naloxone for opioid reversal in the hospital, 100% were black or African American race. Seven (87.5%) out of 8 had Hgb SS genotype, and male-to-female ratio was 1:1. Six out of 14 (42.9%) episodes occurred when patients were not receiving their usual pain regimen. Vaso-occlusive crisis was a diagnosis for 13 out of 14 (92.9%) episodes. A median of 2 doses of naloxone were given per episode. Median creatinine clearance was 20.85 mL/min, and several cases coincided with acute kidney injury. Median sedation scale score prior to naloxone dose was 1 (minimally sedated). One patient was treated with a naloxone continuous infusion. Our study highlights the relatively low use of naloxone in patients with SCD despite generally high usage of opioids. Nearly every patient admitted to the sickle cell service utilizes opioid pain medications, but the proportion of naloxone use in SCD patients is small. There was no significant difference in naloxone use after policy changes instituted the use of ETCO, but this may be due to sample size. The low rates of naloxone use in SCD patients may be related to mechanisms of hyperfiltration that necessitate increased opioid dosing. Our results suggest that the higher observed opioid dosages are not associated with worsened toxicities in SCD patients. With techniques such as ETCO, SCD patients can more safely be treated for pain using opioid medications, and providers should be mindful of pertinent pharmacological factors when caring for this population. Disclosures Saraf: Pfizer: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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 (<50 yrs) treated with pediatric ALL regimens at an urban academic medical center. 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.

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<0.001). 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.

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.