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Early Predictors of Severe Cytopenia Post CAR-T for Identification of Patients for Potential Stem Cell Collection
Corraes, Andre De Menezes Silva , Bansal, Radhika , Brunaldi, Larissa, Khurana, Arushi , Hampel, Paul J. , Hayman, Suzanne R. , Kapoor, Prashant , Kourelis, Taxiarchis , Warsame, Rahma , Johnston, Patrick B. , Ansell, Stephen M. , Kumar, Shaji , Ailawadhi, Sikander , Durani, Urshila , Dingli, David , Wang, Yucai , Binder, Moritz , Kenderian, Saad S. , Bennani, N. Nora , Gertz, Morie A. , Fonseca, Rafaël , Bergsagel, P. Leif , Parrondo, Ricardo D , Chhabra, Saurabh , Lin, Yi

Mayo Clinic

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 6927-6927

10.1182/blood-2023-189683 Get It

Background: Cytopenias are a common complication of and prolonged (beyond month 3 post CAR-T infusion), severe (grade 3 or higher) cytopenias can be difficult to manage. Stem cell boosts have been reported to restore hematopoiesis; however, stem cells would need to be available prior to CAR-T therapy for potential use post CAR-T. Most lymphoma patients and limited number of myeloma patients may have pre-collected stem cells in storage. Identifying patients at high risk for prolonged and severe cytopenia post CAR-T at the time of CAR-T evaluation (baseline), before leukapheresis, can help identify the patients for coordination of stem cell collection during CAR-T manufacturing and increase the likelihood that the collected stem cells would be used. In this study, we aim to identify clinical variables at the time of CAR-T evaluation, prior to leukapheresis, that are associated with severe cytopenias at month 3 post CAR-T infusion and identify patients who could be considered for pre-emptive stem cell collection prior to CAR-T therapy. Methods: We conducted a retrospective analysis of patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) who received CAR-T products at Mayo Clinic from 01/2016 to 06/2022. Patients with progressive disease in the first year post CAR-T were excluded from the analysis. Baseline (at CAR-T evaluation, prior to leukapheresis) variables were compared between those with and without severe cytopenia at month 3 post CAR-T. Severe cytopenias were defined as hemoglobin (Hg) < 8 g/dL, absolute neutrophil count (ANC) < 0.5 x 10 9/L, and/or platelet count (PLT) < 50 x 10 9/L. Statistically significant variables (p<0.05) by analysis were examined for statistical significance in multivariate analysis (MVA). Results: Among the 166 patients who received CAR-T (88 NHL, 78 MM) during the study period, 31 (18.67%) had a severe cytopenia at month . Twenty baseline variables were examined; HGB, PLT, ANC, and c-reactive protein (CRP) We devised a cytopenia risk score using 1 point each for Hg<10 or PLT<100k at baseline, with a range of 0 to 2. Demographics and clinical outcome by cytopenia risk score is shown in Table 1B. A higher percentage of patients with a score of 1 or 2 had a severe cytopenia at month 3 (Figure 1). In particular, there was a . In addition Conclusion: Baseline cytopenias before leukapheresis may identify patients with increased risk for severe cytopenias at month 3 post CAR-T. These patients can have continued slow hematopoietic recovery in the first year. Stem cell collection, if feasible, could be considered before CAR-T to alleviate post-CAR-T severe prolonged cytopenias.
Transplacental Transfer of Emicizumab: Experience with Emicizumab in a Pregnant Female with Severe Hemophilia Α and an Inhibitor
Kharel, Zeni , Pruthi, Rajiv K. , Reid, Robin, Kouides, Peter A. , Reid, Robin

Mayo Clinic

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 5492-5492

10.1182/blood-2023-190012 Get It

Introduction: Severe hemophilia A (HA) in females is incredibly rare particularly if complicated by a high-titer factor VIII (FVIII) inhibitor. We report, to the best of our knowledge, the first-of-its-kind use of emicizumab (emi) ante/post-partum, its effect on the newborn, and its excretion in breast milk. Baseline details: 29-year-old-female was diagnosed with severe HA at age 1 following prolonged bleeding from a venipuncture site. She had no family history of HA. One stage FVIII activity (OSA) was less than 1%. She was compound heterozygous for F8 type 1 and type 2 intron 22 inversions. At 21 months of age, she developed a high-titer inhibitor (peak: 35 Bethesda unit[BU]). She was not treated with immune tolerance induction and had remained on factor eight inhibitor bypassing activity (FEIBA) as prophylaxis until transferring to our center. She was transitioned to monthly emi prophylaxis and recombinant FVIIa (rFVIIa, NovoSeven) for breakthrough bleeding at age 26. She was medically advised against pregnancy due to unclear safety profile of emi in pregnancy and theoretical concerns for an increased risk of bleeding and thrombotic complications associated with the use of bypassing agents in the peripartum setting. Nevertheless, she desired pregnancy and continued on emi prophylaxis every 4 weeks during her pregnancy. Clinical course in pregnancy: She had an uncomplicated antepartum course and did not require rFVIIa for breakthrough bleeds. Blood emi levels and FVIII inhibitor levels were measured in each trimester of pregnancy (Table 1). Her labor was induced with oxytocin while on rFVIIa and tranexamic acid (TXA) support. She had a spontaneous, unassisted vaginal delivery immediately complicated by post-partum hemorrhage resulting in estimated blood loss of 1100cc. She did not require blood transfusion. She continued on 90 mcg/kg rFVIIa support every 2 hours, gradually prolonging the dosing interval by 2 hours every 24 hours (q2, q4, q6, etc.), and experienced no further in-hospital bleeding. She delivered a healthy female newborn. The infant developed cephalhematoma but transcranial ultrasound was negative for intracranial bleeding. Cord blood was collected at the time of delivery and sent for emi level, FVIII activity and FVIII inhibitor titer (Table 2). FVIII inhibitor assay with bovine reagent (CBU) was performed using chromogenic substrate assay (CSA) after pre-analytical heat-inactivation of patient plasma. The infant's CSA FVIII level was measured using a bovine chromogenic FVIII assay, and FVIII was also assayed using a one-stage APTT-based assay. Mother opted to breast-feed the infant. Emi level was measured in breast milk (Table 1). Conclusion: In this highly unusual case, we demonstrate that emi crossed the placenta and is excreted in breast milk. We also demonstrate that the maternal FVIII inhibitor did not cross the placenta into the newborn. Drawing conclusions on the safety of emi despite placental and breast milk transmission and transmissibility of inhibitor based on a single case would be premature. The conglomeration of several rarities in a single case renders our report unique and insightful and provides a baseline experience for future cases.
Experience with Gray Zone Lymphoma (GZL) at Mayo Clinic: A Review of Clinical Characteristics and Treatment Outcomes
Ghorab, Ahmad , Ghorab, Ahmad , Mosalem, Osama , Baidoun, Firas , Tun, Han W. , Moustafa, Muhamad Alhaj

Mayo Clinic

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 6317-6317

10.1182/blood-2023-191074 Get It

Introduction: Gray zone lymphoma (GZL) is a rare lymphoid neoplasm exhibiting features intermediate between diffuse large B-cell lymphoma and Hodgkin lymphoma. Due to its rarity and relatively recent recognition by the World Health Organization in 2008, the natural history, clinical behavior, and best treatment strategies are still evolving. We present a retrospective review of GZL patients diagnosed and managed at the Mayo Clinic. This study aims to explore the clinical characteristics, treatment modalities, and outcomes of this poorly understood disease. Methods: After reviewing the electronic medical records of patients presented to the Mayo Clinic Cancer Center between March 2012 and July 2022 at the Mayo Clinic, we identified the patients who were diagnosed with GZL. Clinicopathological characteristics, disease features, treatment modalities, and outcomes were analyzed. The Kaplan-Meier method was utilized to assess survival outcomes. Results: Six patients (n=6) with GZL, all Caucasian and predominantly male 4/6 (67%), were identified. The median age at diagnosis was 37 years (range 24-57). Disease characteristics included high rates of mediastinal involvement 5/6 (83%) and bulky disease 4/6 (67%), with various stages of Ann Arbor classification represented. First-line treatment regimen varied between R-CHOP, ABVD, and DA R-EPOCH. The R-CHOP regimen was received in 3/6 patients (50%); the first patient achieved Complete Remission (CR), then managed with R-ICE, followed by consolidative autologous stem cell transplantation (auto-SCT) when relapsed. The second patient had Partial Response (PR) to R-CHOP and required consolidative radiotherapy to achieve CR, and the third R-CHOP patient achieved CR however, after multiple disease progressions that were managed with multiple regimens including R-ICE, R-CODOX-M/IVAC regimen, Nivolomab/Ipilumuab, consolidative radiotherapy, and Brentuximab vedotin. The ABVD regimen was received by 2/6 patients (33%). The first patient had CR, and the second patient had disease progression, which required treatment with R-ICE, followed by consolidative radiotherapy and auto-SCT. One patient (17%) received the DA R-EPOCH regimen and achieved CR, consolidated with auto-SCT. The median follow-up for our cohort is nine years (range, 5-13). All six GZL patients are alive and in CR (since 2019 or before) at the time of the study analysis, with an excellent flat overall survival curve. For this reason and due to the small patient sample, we could not calculate the progression-free survival data. Conclusions: Our Mayo Clinic review provides unique insights into managing Gray Zone Lymphoma (GZL), a rare disease. We reported 100% survival and remission in six GZL patients using diverse treatment strategies, contrasting with varied outcomes from other institutions. This underscores the potential of individualized treatments for GZL and the need for further, broader studies to validate our findings and refine optimal treatment approaches for this rare disease entity.
IPSS-M - Use for Predicting Survival and Progression in Patients with Ccus - a Retrospective Multi-Institutional Study
Nanaa, Ahmad , Al‐Kali, Aref , Nguyen, Phuong L., He, Rong , Patnaik, Mrinal M. , Mangaonkar, Abhishek A. , Anderson, Julia , Chen, Weina , Weinberg, Olga K. , Chung, Stephen S. , Jevremović, Dragan , Greipp, Patricia T. , Alkhateeb, Hassan B. , Madanat, Yazan F.

Mayo Clinic

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 4590-4590

10.1182/blood-2023-191048 Get It

Background: Clonal cytopenia of undetermined significance (CCUS) is characterized by the presence of a clone with somatic mutations in genes associated with myeloid neoplasms (MN) or abnormal cytogenetics, along with unexplained and persistent cytopenias in the absence of significant marrow dysplasia. CCUS is considered a premalignant state with a risk of progression to MN. The clinical outcomes of patients (pts) with high risk CCUS (Weeks et al, NEJM Evidence 2023) may be similar that of some patients with myelodysplastic syndromes (MDS). This study aims to predict the outcomes of CCUS patients using the molecular international prognostic scoring system (IPSS-M) developed for MDS. Methods: A retrospective analysis was conducted in patients diagnosed with CCUS between 2015 and 2023, we included patients harboring pathogenic mutations (MUT) identified through next-generation sequencing (NGS) testing at two institutions: Mayo Clinic and the University of Texas Southwestern Medical Center, Dallas, TX, USA were included. Progression was considered present if patients with CCUS progressed into myeloid neoplasm at follow up. Statistical analysis was performed using JMP® 17.1.0 Software. IPSS-M risk scores were calculated via the IPSS-M Risk Calculator (mds-risk-model.com). Results: A total of 103 patients were included in the study. The median age was 72 years, the majority were male patients (73%), and the median bone marrow blast % at the time of NGS was 1%. Forty-five % had an isolated mutation in a single gene, and 55% had co-mutations in ≥1 gene. The median number of mutations was 2 (range 1 - 5), occurring across 43 different genes. The most common mutations were in TET2 (N=28; 27%), ASXL1 (N=21; 20%), SRSF2 (N=21; 20%), U2AF1 (N=18; 17%), DNMT3A (N=16; 16%), and TP53 (N=12; 12%). Additionally, 25% of patients had an abnormal karyotype. Hematologic and genetic characteristics are summarized in (Table 1A). The median IPSS-M score was -0.9 (-3 to +2.34) and the median IPSS- Revised (R) score was 2 (0 - 6). The majority of patients had low (L) IPSS-M risk category (53%), followed by moderate low (ML) (19%) and very low (VL) (17%). Per IPSS-R, the majority had low-risk category (47%), followed by VL (38%) and intermediate (14%). Overall, 26 (25%) pt died after a median follow-up of 34 months and 21% progressed to MN (MDS 14 & CMML 8), and 1 patient with MDS and 1 with CMML progressed to secondary AML (2%). The median overall survival (mOS) was not reached, with a 2-year estimated (YE) OS and leukemia-free survival (LFS) of 80%. Predictive Power: When utilizing the IPSS-M risk category ( L, M, H) * by combining the risk categories into L *(L+VL), M * (ML+MH), and H *(H+VH) to overcome the low sample size limitation, it significantly predicted OS (p < .0001) ( Figure 1A) and median MN-free survival (FS) (p < .0001) ( Figure 1B). The 2YE-OS rates by IPSS-M risk category were as follows: VL - 93%, L - 87%, ML - 75%, high (H) - 25%, very high (VH) - 0% and the 2YE-OS rates by IPSS-M ( L, M, H) are summarized in Table 1B. IPSS-M hazard ratio (HR) for OS was 1.6 for ( M*) compared to 25 for ( H *) risk category (p < .0001). The ( L *) category, being the largest, was used as the reference level. Conclusion: This study provides the first real-world experience of using the IPSS-M and a modified version of the IPSS-M ( L, M, H) * risk category model to predict survival and progression into MN in CCUS (MUT) pt. The IPSS-M risk category was found to be a significant predictor of OS and MN-free survival. We propose that larger cohorts are needed to validate our findings.
Trend in Von Willebrand Factor Profile in Women With Von Willebrand Disease During Pregnancy and Postpartum
Albusoul, Linda, Vuyyala, Sowjanya, Otrock, Zaher K. , Kuriakose, Philip , Shahid, Muhammad Furqan

Mayo Clinic

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 5499-5499

10.1182/blood-2023-188011 Get It

Introduction: Pregnancy is considered a hypercoagulable state, with levels of multiple coagulation factors including Factor VIII (FVIII) and von Willebrand Factor (VWF), progressively increasing throughout, reaching their peak levels during the third trimester. However, in women with von Willebrand disease (VWD), these changes are variable and could be blunted or absent due to the wide heterogeneity of phenotypes and pathophysiological mechanisms linked to this disorder, posing a significant clinical challenge. This study aims to describe the trend in the VWF profile in women with VWD during each trimester of pregnancy and in the postpartum period. Methods: This is a retrospective single-center study that included adult pregnant women diagnosed with VWD, who were followed at Henry Ford Health between 03/2012 and 11/2022. Patients with other bleeding disorders were excluded from the study. Data on baseline characteristics, including age, race, age at childbirth, and parity were collected. Additional data collected included VWF antigen (VWF:Ag) level, FVIII activity level, and VWF ristocetin cofactor (VWF:Rco) activity during the first, second, and third trimesters, as well as in the postpartum period. Results: A total of 33 cases were included in our study. At baseline, the mean VWF:Ag level in our patients was 50.5% (reference range 50%-150%). Compared to baseline, the VWF:Ag level increased by 48.71% in the first trimester, 80.59% in the second trimester, and 168.71% in the third trimester. Postpartum, the VWF:Ag level decreased by 51.29% compared to the third trimester; however, it remained 30.89% higher than baseline levels. While the FVIII level (reference range 50%-150%) was an average of 64.8% at baseline, it increased by 21.91% in the first trimester, 74.23% in the second trimester, and 143.67% in the third trimester, compared to baseline. Postpartum, the FVIII level decreased by 48.45% from the third trimester but remained 25.62% higher than baseline. Additionally, the VWF:Rco level was an average of 44.3% (reference range 51%-215%) at baseline. Compared to baseline, the VWF:Rco level increased by 61.85% in the first trimester, 90.52% in the second trimester, and 142.66% in the third trimester. It decreased by 49.12% postpartum compared to the third trimester but remained 23.48% higher than baseline. Conclusion: In women with VWD, VWF:Ag level, FVIII level, and VWF:Rco levels steadily increase during pregnancy, reaching their maximum levels during the third trimester. All three levels decreased in the postpartum period; however, they remain higher compared to baseline at a median follow up of 105 days after delivery.
Unraveling the Link: Cannabis Use Disorder and Pulmonary Embolism-Related Hospital Outcomes in Female Breast Cancer Survivors
Katukuri, Nishanth , James, Alpha , Kadiyala, Avinash , Vutukuru, Sai Diksha , Tajdin, Borzoo, Nalla, Akhila , Kotharu, Devi Meghana, Keesari, Praneeth Reddy , Kanagala, Sai Gautham , Ghadge, Nitin , Vegivinti, Charan Thej Reddy , Jain, Akhil , Desai, Rupak

Mayo Clinic

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 7322-7322

10.1182/blood-2023-190618 Get It

Background: The use of cannabis in cancer patients has gained significant attention due to its analgesic properties, which help alleviate cancer-related pain. Studies have also shown the interference of cannabis with the coagulation system. We aimed to study the impact of cannabis use disorder (CUD) and Pulmonary embolism (PE) on outcomes in female breast cancer survivors, considering reports suggesting significant overlap between recreational and medicinal use. Our objective was to compare outcomes in CUD+ (with cannabis use disorder) and CUD- (without cannabis use disorder) cohorts to gain critical insights into this group and understand the impact of CUD on PE-related hospitalization and outcomes. Methods: National Inpatient Sample (NIS) data from 2020 was utilized in order to analyze inpatient cohorts of PE hospitalizations. The International Classification of Diseases 10 (ICD 10) codes for pulmonary embolism, cannabis use disorder, and female breast cancer were utilized to classify cohorts. All cases of female breast cancer and pulmonary embolism with an age >18 years were included in the final analysis. The primary outcome was the impact of CUD on PE-related hospitalizations in female breast cancer survivors. We also compared demographic correlations and comorbidities affecting outcomes between cohorts. Results: This study included a total of 508065 admissions among breast cancer survivors, with a median age of 74 years for the entire cohort. The prevalence of PE admissions was lower in CUD+ cohort compared to CUD- cohort (1.3% vs. 2.1%). The CUD+ cohort was relatively younger (median 66 vs 74 years, p<0.001). Overall, admission rates were higher among white patients (77%) and this trend was statistically significantly higher in the 76-100 th percentile household income group (p<0.002) compared to CUD+(50%) and CUD-(26.5%). Most admissions were non-elective (95.4%), with no statistical significance between CUD- and CUD+ patients (p=0.16). The majority of readmissions occurred in urban teaching hospitals (75.5%), with no significant difference observed between CUD- and CUD+ patients (p=0.111). Regionally, the South had a higher admission rate (37.2%) compared to other regions and this difference was statistically significant (p<0.001) between CUD- and CUD+ patients. Among the coexisting comorbidities, hypertension showed a significant difference between CUD- (70%) and CUD+(37.5%) patients (p<0.001). Alcohol use disorder (p<0.001) and cancer (p<0.001) had significant associations with CUD+, along with prior myocardial infarction (p=0.005) and drug use (p<0.001) were significantly associated with CUD+.Furthermore, there was difference in routine patient disposition between between CUD-(45.3%) and CUD+(37.5%),(p=0.033) and length of stay (4 VS 2 days), (p=0.033) and cost of stay (47033 vs 27668 $), (p=0.017). The multivariable logistic regression analysis showed that the odds of PE-related hospitalization in CUD+ vs CUD- cohorts among female breast cancer survivors were not statistically significant, with an OR of 0.79 (CI: 0.38-1.62, p=0.512). Subgroup analysis by age demonstrated no statistically significant differences in odds for PE-related hospitalization between CUD+ and CUD- cohorts. For the age group of 18-44 years, the OR was 1.37 (CI: 0.18-10.60, p=0.762). In the 45-64 years age group, the OR was 0.48 (CI: 0.15-1.53, p=0.215), and for those aged ≥65 years, the OR was 1.32 (CI: 0.48-3.67, p=0.590). Furthermore, the analysis by race indicated that the odds of PE-related hospitalization did not reach statistical significance in both white and black female breast cancer survivors with CUD. For white patients, the OR was 0.64 (CI: 0.23-1.73, p=0.375), while for black patients, the OR was 1.15 (CI: 0.38-3.46, p=0.804). Conclusion: Among female breast cancer survivors, the presence of CUD did not show a statistically significant impact on the odds of PE-related hospitalization. Subgroup analysis by age and race also revealed no significant differences in the odds of PE-related hospitalization between CUD+ and CUD- cohorts. These findings underscore the importance of considering CUD when managing pulmonary embolism in breast cancer survivor females and emphasize the need for further research to understand the complex interplay between these factors.
Variations in Complete Blood Count Reference Limits Among Hospitals in the US and Their Clinical Significance
Go, Lucas T, Go, Lewis T , Gunaratne, Madugodaralalaage DSK, Abeykoon, Jithma P. , Gunaratne, M

Mayo Clinic

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 3701-3701

10.1182/blood-2023-182994 Get It

Background Complete blood count (CBC) is the most common hematology test performed. Reference limits, aka normal values, are known to vary from one hospital to another. However, little is known about the values of the upper (UL) and lower (LL) limits of common elements reported in the CBC and how they differ among facilities. The objectives of our study were to report the UL and LL of CBC elements from various hospitals in the US, analyze the variances, and describe their clinical significance. Methods This study was approved by the Mayo Clinic institutional review board. We obtained the reference limits of CBCs from various hospitals using the Epic electronic medical records Care Everywhere health information exchange. CBCs from 2020-2023 were included. We included the following CBC elements: hemoglobin (Hgb; male and female), mean cell volume (MCV), white blood cell count (WBC), and platelet count (PLT). We performed descriptive statistics and calculated the coefficients of variation (COVs). In addition, we analyzed the data for clinical context using: A) World Health Organization (WHO) major criterion for polycythemia vera of Hgb >16.5 g/dL and >16.0 g/dL for males and females, respectively; B) WHO major criterion for essential thrombocytosis of PLT >450 x109/L; and C) common textbook reference limits for MCV (80-100 fL) and WBC (5-10 x109/L). Results We collected CBC reference limits from 143 hospitals across 43 states and 99 cities. Most (54.5%) hospitals were community-based, while the rest (45.5%) were academic. The statistics are shown in the Table. In general, there was minimal variance in the UL and LL of CBC elements, with COVs mostly under 8.0%. The one exception was WBC LL, in which the COV was 10.5%. There was no significant difference in the CBC reference limits between academic and community hospitals. The median Hgb UL and LL for males were 17.5 (range, 16.3-18.1) and 13.5 (range, 12.0-14.3), respectively. Similarly, the median Hgb UL and LL for females were 15.7 g/dL (range, 14.6-16.3) and 12.0 g/dL (range, 11.0-12.5), respectively. Majority (93.5%) of the hospitals' male Hgb UL exceeded 16.5 g/dL. In contrast, only few (3.6%) of the hospitals' female Hgb UL exceeded 16.0 g/dL (Figure A). The median MCV UL and LL were 99.0 fL (range, 92.2-103.0) and 80.0 fL (range, 77.0-88.0), respectively. A substantial minority (19.6%) of the hospitals' MCV UL exceeded 100 fL (Figure B). The median WBC UL and LL were 10.8 x109/L (range, 8.9-13.0) and 4.0 x109/L (range, 3.1-5.4), respectively. Most (80.4%) hospitals' WBC UL exceeded 10 x109/L (Figure C). The median PLT UL and LL were 400 x109/L (range, 317-500) and 150 x109/L (range, 125-172), respectively. Over a quarter (27.5%) of the hospitals' PLT UL were at or exceeded 450 x109/L (Figure D). Conclusions: There was minimal variance in CBC reference limits across hospitals in the US with WBC LL having the highest COV. Most MCV UL and WBC UL exceeded common textbook reference limits. Almost all male Hgb UL and over a quarter of PLT UL exceed the WHO major criteria of polycythemia vera and essential thrombocytosis, respectively. Since our findings suggest that there could be a risk of underdiagnosing these myeloproliferative neoplasms due to the commonly used reference limits, clinical context must be used when interpreting normal CBC results, especially when there is a suspicion of polycythemia vera or essential thrombocytosis.
Advancing Collaboration across the Multiple Myeloma Treatment Journey from Oncology Clinic to CAR T-Cell Center: A Paired Center Transformative Quality Improvement Initiative
Sullivan, Shelby , Carter, Jeffrey, Heggen, Cherilyn, Ailawadhi, Sikander , Sullivan, Shelby

Mayo Clinic

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 5074-5074

10.1182/blood-2023-173042 Get It

Background Treating patients with multiple myeloma (MM) is a complex endeavor that requires effective clinical decision-making from a team of specialists and supporting clinicians. Additionally, treatment with chimeric antigen receptor (CAR) T-cell therapy presents unique challenges, requiring communication and collaboration between the oncology clinic and CAR T-cell treatment centers. To improve collaborative MM care, we conducted a quality improvement (QI) study, bringing together community and academic oncology centers to assess current practice patterns and develop strategies to overcome barriers in the treatment of patients with MM across the continuum of care. Methods This QI initiative is comprised of baseline provider surveys (Community n = 21; Academic n = 18) and pre- and post-surveys of providers (n = 31) participating in small-group, team-based audit-feedback (AF) sessions (Table 1). Survey questions were designed to assess knowledge, confidence, and experiences in keeping up with the latest clinical evidence and guideline recommendations and collaboration and communication practices between centers. Care teams from each clinic, along with a nationally renowned expert MM physician, participated in audit and feedback sessions to (a) assess system-specific practice gaps identified via the provider surveys, (b) prioritize areas for improvement, and (c) develop action plans for addressing root causes. Results Provider Surveys: When asked their top challenge encountered in managing patients with MM, community-based providers reported keeping up with clinical evidence for new and emerging therapies (48%), whereas academic-based providers reported knowing how to optimally sequence therapies (50%). Further differences between community and academic clinicians were evident in their self-reported confidence in their ability to stay up-to-date with new data on CAR T-cell therapies and other MM treatment (high/very high confidence: 84% academic; 24% community; p < .001), ability to align clinical practices with evidence-based guidelines (high/very high confidence: 72% academic; 34% community; p = .018), and ability to sequence lines of therapy and differentiate between novel therapies for MM (high/very high confidence: 72% academic; 29% community; p = .007). Despite these differences, care teams from both settings reported low percentages of eligible patients have received CAR T-cell therapy for MM, citing patient resistance, cost and difficulty gaining insurance approval as top barriers (Figure 1). When asked to rate the level of communication and collaboration between academic and community centers, 44% of academic providers and 35% of community providers rated very good/excellent. The top barrier among providers not indicating very good/excellent communication from both settings was lack of time for our clinic's staff to communicate. AF Sessions: Providers participating in the small group AF sessions reported gaining access to newer therapies (55%) as their biggest challenge regarding MM management. Clinicians indicated gains in moderate/high/very high confidence in their ability to align treatment decisions with guidelines and clinical evidence for MM (78% to 92%) and ability to sequence treatment options across multiple lines of therapy for patients with MM (80% to 100%). Care teams set goals to enhance knowledge of clinical efficacy and safety of new and emerging therapies for MM. Action plans to achieve these goals include developing a hematology disease specific tumor board to collaborate on patient care plans, further train designated staff members focused on CAR T-cell/MM, discuss relevant new data to improve the team's confidence in therapy sequencing and early referrals to CAR T-cell centers. Conclusions Through this QI initiative, clinical teams identified barriers to optimal MM care, creating and implementing specific action plans to increase knowledge of current and emerging therapies for MM to enhance individualized treatment plans. While meaningful confidence gains were demonstrated, these data underscore clinical practice gaps to address in future initiatives to support evidence-based, collaborative care plans for patients with MM. Study Sponsor Statement The study reported in this abstract was funded by educational grants from Bristol Myers Squibb. The grantors had no role in the study design, execution, analysis, or reporting.
Survey of Pulmonary Embolism Risk Stratification Methods in the Emergency Department and Barriers to Electronic Health Record Documentation
Keenan, Megan , Dykhoff, Hayley J. , Hall, Marie Boas, Campbell, Kyle N., Cahill, Emily , Balgord, Sarah , Aranda, J. A. Veloz, Rubin, Jonathan M. , Heaton, Heather A. , Thompson, Kristine M., Rosovsky, Rachel , Houghton, Damon E. , Hall, Marie, Raja, Ali S , Kreuziger, Lisa Baumann

Mayo Clinic

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 3746-3746

10.1182/blood-2023-181446 Get It

Introduction Pulmonary Embolism (PE) is a major cause of morbidity and mortality worldwide. Diagnosis is essential as untreated PE has a 30% mortality rate. Currently, computer tomography pulmonary angiogram (CTPA) is the standard of care to diagnose PE. However, this modality is expensive, exposes patients to radiation and increases risk of contrast induced nephropathy. Furthermore, only 5% of CTPAs performed are positive for PE signifying that many unnecessary tests are being performed. To address this gap, Pre-Test Probability (PTP) tools have been developed to safely exclude patients with low risk of PE and limit iatrogenic harm from over testing. Despite the tools being developed over 20 years ago, they are not widely available in electronic health record (EHR) systems and even when they are built in, uptake remains low. Methods Three large integrated health systems using Epic EHR systems across five states (MA, WI. MN, AZ, FL) built electronic PTP assessments into their EHR systems to safely exclude patients with low risk of PE and limit over testing. Two sites made the PTP optional, and one site made it a forced function (providers were forced to complete PTP prior to ordering CTPA unless a D-dimer result was present in the prior 48 hours). To assess the usability of these EHR tools, the team conducted a survey with ED clinicians across the three test sites. The survey was created to identify which PE risk stratification methods were employed by ED clinicians (EHR embedded PTP tool, apps on their phone, web applications like MDcalc, calculations from memory, or if they relied on clinical gestalt), and to identify barriers to using the EHR embedded PTP. Results Site 1 had 47 respondents, Site 2 had 94 respondents, and Site 3 had 16 respondents. Two key findings emerged from the survey (Figure 1). First, clinicians used a variety of risk stratification approaches and few of them documented their risk assessments in structured fields in the medical record. Second, clinical gestalt was the most used PE risk stratification approach, and this was true across all three test sites. In addition, the health system with a PTP prompt before clinicians could proceed with CTPA orders (Site 3) did not have a higher percentage of clinicians who reported using the EHR embedded tool than sites that did not prompt clinicians to fill in the PTP. Clinicians cited a variety of different barriers to using the EHR embedded PTP tool (Table 1). Conclusion While many clinicians indicated intermittent use of PTP criteria to aid in the diagnosis of PE, risk factors and scores from phone apps, web tools, and calculations from memory are unlikely to be documented in the patient's medical record, which means that they are not accessible to all members of the ED care team and cannot be used for electronic clinical quality measure. The biggest hurdles to increasing the use of structured PTP assessments in the ED setting to safely exclude PE and limit iatrogenic harm from over testing are (1) obtaining buy-in from ED clinicians that the PTP tools provide value over clinical gestalt, at least for a subset of patients who could most benefit, and (2) identifying best practices for incorporating PTP tools into EHR systems that make the tools easier to access and use 3) developing and implementing effective education and awareness programs around the PTP tools. This survey adds to the body of literature on PTP assessments in the ED setting and can help inform further research that is needed to continue to improve the diagnosis of PE. Funding: This project is funded in part by the Gordon and Betty Moore Foundation through Grant GBMF10778 to the American Society of Hematology.
Clinical and Epidemiological Characteristics of Patients Admitted with Acute Chest Syndrome on a National Scale and Factors Affecting Clinical Outcomes in Inpatient Setting
Labban, Mohamad El , Yadav, Sumeet Kumar, Hussein, Guleid , Khan, Syed Anjum , Usama, Syed Muhammad, Seegobin, Karan

Mayo Clinic

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 3892-3892

10.1182/blood-2023-181043 Get It

Introduction Acute chest syndrome (ACS) is a clinical presentation of fever, chest pain, pulmonary symptoms, and new infiltrates on lung imaging. It affects nearly 50% of patients with sickle cell disease during their lifetime and often leads to hospitalization. The mortality rate is variable ranging from 3 to 9 %. and depends on several factors. We aimed to identify the clinical and epidemiological characteristics of patients admitted with ACS on a national scale and factors affecting clinical outcomes in inpatient setting. Methods: We utilized the National Inpatient Sample (NIS) database 2019 for the purpose of this study. Using this database, we identified patients with a principle diagnosis of ACS using International Classification of Diseases (ICD-10) codes. Data on demographic characteristics such as age, sex, race, insurance type were collected. Additionally, we selected clinically significant medical comorbidities such as asthma, chronic obstructive pulmonary disease (COPD), coronary artery disease (CAD), chronic kidney disease (CKD), heart failure, hypertension, diabetes mellitus (DM), sepsis, obesity, and others. The primary endpoint of this study was to identify factors influencing all-cause mortality, while the secondary endpoint was to identify factors influencing mechanical intubation, in-patient blood transfusion, and length of stay. We used multivariate logistic regression analysis to adjust for confounders. A p value of ≤0.05 considered statistically significant. Results: Baseline Characteristics Our analysis consisted of 22,459 patients who were admitted with principal diagnosis of ACS. 49.5% were female and 50.5% were male. Mean age was 30.5 years. African American race was predominant (92%) with sickle cell Hb-SS disease (87%). Major insurance payer was Medicaid (47%) followed by Medicare (27%) and then private insurance (21%). Asthma was the most common comorbidities (24%) and majority of patient had Charlson Comorbidity Index (CCI) score of zero (55%). The details of clinical and epidemiological characteristics are shown in Table 1. Clinical outcomes and factors influencing mortality Only 0.89% patient died of ACS. Average length of stay was 6.86 days. 34% of the patient required packed red blood cell (pRBC) transfusion. 3.2% needed mechanical ventilation. In multivariate analysis, factors associated with mortality included age of patient, CCI and sepsis. Younger patient had higher odds of mortality however this was not statistically significant. There was no difference in mortality with sex, race and insurance status of the patients. Factors affecting inpatient transfusion, mechanical ventilation and length of stay Female, higher CCI score and sepsis on admission were associated with higher needs of inpatient pRBC transfusion. Within race, White (OR 3.16, CI 1.44-6.93, P <0.01) and Hispanics (OR 2.68, CI 1.59-4.51, P<0.01) had higher odds of receiving transfusion compared to African Americans (OR 1.84, CI: 1.17-2.89, P <0.01). Similarly patient with sepsis, supraventricular tachycardia had more odds of needing mechanical ventilation. Patient's insurance status was also related to increased odds of intubation. Comorbidities such as asthma and CAD were not associated with need of mechanical ventilation and in fact our study shows they had less odd of needing mechanical ventilation. Length of stay was influenced by several of epidemiological and clinical comorbidities. Females had less odds of longer length of stay compared to male (OR: 0.65, P <0.01). Comorbidities such as asthma, heart failure, CAD, DM2 and hypertension did not increase the length of stay while patients with sepsis and high CCI score had higher odds of hospitalization for extended period of time. The details are in Table 2. Conclusion We found mortality was 0.89% in patients admitted with ACS compared to 3 to 9% previously reported. Sepsis and CCI were one of the predictors for odds of having higher mortality, need of blood transfusion, mechanical ventilation and increased length of stay in patient with ACS. Female, White and Hispanic had higher odds of needing transfusion then African Americans. Comorbidities such as asthma, heart failure, CAD, DM 2 and hypertension did not increase the odds of prolonged hospital stay.