The prognosis of adult patients with acute lymphoblastic leukemia (ALL) has improved with the incorporation of pediatric-inspired regimens that contain PEGylated asparaginase (PEG-Asp). However, PEG-Asp administration is associated with an increased rate of thrombosis. Data regarding the benefits of antithrombin (AT) repletion and prophylactic anticoagulation in adults receiving PEG-Asp-based regimens are limited. We performed a retrospective study to evaluate the rates of induction thrombosis and bleeding among adults receiving ALL therapy containing Asp at 6 academic centers in the United States. Of 233 patients who met the inclusion criteria, 98.3% received PEG-Asp. Ninety-six patients (41.2%) had their AT levels monitored, 58 patients (24.9%) received AT repletion, and 41 patients (17.6%) received prophylactic anticoagulation. Thirty-two patients (13.7%) experienced thrombotic events, with half (53.1%) being line-associated thromboses. In multivariate analysis, the odds of thrombosis did not differ between patients who received AT monitoring, AT repletion, or prophylactic anticoagulation. The odds of thrombosis were 4 times higher for patients with peripherally inserted central catheters than for those with other types of central lines (odds ratio, 4.112; 95% confidence interval, 1.622-10.427; P = .01). Thrombotic risk did not differ based on age, cumulative Asp dose, type of steroid administered, or whether transfusions were performed. Bleeding occurred in 12 patients (5.2%), and major bleeding occurred in 8 patients (3.4%). The odds of bleeding did not increase in the patients who received prophylactic anticoagulation. Our study brings into question whether prophylactic AT repletion and anticoagulation are beneficial strategies for reducing PEG-Asp-associated thrombosis, and large randomized prospective studies are needed.

Allogeneic hematopoietic cell transplantation (allo-HCT) represents an important and potentially curative treatment option for adult patients with acute lymphoblastic leukemia. Relapse continues to remain the most important factor influencing overall survival post allo-HCT. We discuss early identification, clinical manifestations, and management of relapsed disease. Routine evaluation of measurable residual disease (MRD) and change in donor chimerism play a crucial role in early detection. Pivotal clinical trials have led to FDA approval of multiple novel agents like blinatumomab and inotuzumab. Combining targeted therapy with cellular immunotherapy serves as the backbone for prolonging overall survival in these patients. Donor lymphocyte infusions have traditionally been used in relapsed disease with suboptimal outcomes. This review provides insight into use of cellular therapy in MRD positivity and decreasing donor chimerism. It also discusses various modalities of combining cellular therapy with novel agents and discussing the impact of chimeric antigen receptor T-cell therapy in the setting of post allo-HCT relapse both as consolidative therapy and as a bridge to second transplant.

BACKGROUND:The goal of therapy for many patients with advanced stage malignancies, including those with metastatic gastric and esophageal cancers, is to extend overall survival while also maintaining quality of life. After weighing the risks and benefits of treatment with palliative chemotherapy (PC) with non-curative intent, many patients decide to pursue treatment. It is known that a subset of patients who are treated with PC experience significant side effects without clinically significant survival benefits from PC.METHODS:We use data from 150 patients with stage-IV gastric and esophageal cancers to train machine learning models that predict whether a patient with stage-IV gastric or esophageal cancers would benefit from PC, in terms of increased survival duration, at very early stages of the treatment.RESULTS:Our findings show that machine learning can predict with high accuracy whether a patient will benefit from PC at the time of diagnosis. More accurate predictions can be obtained after only two cycles of PC (i.e., about 4 weeks after diagnosis). The results from this study are promising with regard to potential improvements in quality of life for patients near the end of life and a potential overall survival benefit by optimizing systemic therapy earlier in the treatment course of patients.

PURPOSE OF REVIEW:Measurable residual disease (MRD) is an important monitoring parameter that can help predict survival outcomes in acute lymphoblastic leukemia (ALL). Identifying patients with MRD has the potential to decrease the risk of relapse with the initiation of early salvage therapy and to help guide decision making regarding allogeneic hematopoietic cell transplantation. In this review, we discuss MRD in ALL, focusing on advantages and limitations between MRD testing techniques and how to monitor MRD in specific patient populations.RECENT FINDINGS:MRD has traditionally been measured through bone marrow samples, but more data for evaluation of MRD via peripheral blood is emerging. Current and developmental testing strategies for MRD include multiparametric flow cytometry (MFC), next-generation sequencing (NGS), quantitative polymerase chain reaction (qPCR), and ClonoSeq. Novel therapies are incorporating MRD as an outcome measure to demonstrate efficacy, including blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor T (CAR-T) cell therapy. Understanding how to incorporate MRD testing into the management of ALL could improve patient outcomes and predict efficacy of new therapy options.

e19016 Background: The standard remission induction regimen for medically fit patients with AML consists of a backbone of cytarabine & an anthracycline (“7+3” therapy). However, the choice & dose of the anthracycline varies between institutions & practitioner preference, particularly in patients with favorable risk cytogenetics. Gemtuzumab ozogamicin (GO) may improve outcomes in this patient population but is associated with increased toxicities. Methods: We performed a retrospective analysis on medically fit patients ≥ 18 yo with favorable risk AML from 2015-2020 treated with 7+3 at the University of Virginia. Patients were stratified based on standard dose (45 or 60 mg/m2 daunorubicin) (SD) vs higher dose (90 mg/m2 daunorubicin or 12 mg/m2 idarubicin) (HD) of anthracycline vs the addition of GO. Measures included rates of remission, EFS, RFS, and OS as well as rates of treatment-related complications. Results: In total, 58 patients were identified, of which 33 received induction with SD, 19 received HD, & 6 received GO. The majority (75%) of patients were < 60 years old & 93% had de novo AML. The rates of complete remission in the SD, HD & GO groups were 90.9%, 89.5% & 100%, respectively (p = 0.57). EFS at 2-years was 43.9%, 36.7%, & 66.7%, respectively (p = 0.85). RFS at 2-years was 53.0%, 39.0%, & 100%, respectively (p = 0.18). OS at 2-years was similar between all groups (58.9%, 56.9%, & 66.7%, p = 0.92). The rate & duration of cytopenias after induction were similar among all groups (median duration 29 days), however cytopenias were more common in the GO group following consolidation. The rates of major bleeding, admission to the intensive care unit (ICU), and new onset cardiomyopathy (EF < 50%) were higher in the GO group (major bleeding: 0% in SD, 5.3% in HD, 33.3% in GO; ICU admission: 12.1% in SD, 21.1% in HD, 33.3% in GO; cardiomyopathy: 12.1% in SD, 26.3% in HD, 33.3% in GO). The rate of infection, liver dysfunction, & acute renal injury were similar among all groups. No patients developed veno-occlusive disease. Conclusions: Patients receiving GO had a trend toward improved EFS & RFS, however with a similar OS at the expense of higher rates of cytopenias, major bleeding, ICU admission, & cardiotoxicity. Patients receiving HD had a trend toward worse outcomes than those who received SD. A major limitation of our study is the small sample size & single institution experience, however multi-institutional analysis is ongoing for further investigation.[Table: see text]

6561 Background: Hospital readmissions are associated with increased health care utilization and unfavorable patient outcomes. Oncology patients have an increased risk of hospital readmission compared to the general patient population. The 30-day readmission rate for cancer patients at our institution is 27.7% which is higher than the reported national average of 20.2%. We sought to reduce 30-day hospital readmission rates by 25% for solid tumor oncology patients through a prospective integrated multidisciplinary discharge approach. Methods: Hospital readmissions for adult patients with a known solid tumor cancer diagnosis admitted to the oncology service at UVA from Jan 2019 – Apr 2019 were identified. Baseline information on tumor type, reason for readmission, interventions, length of stay (LOS), and inpatient morbidity and mortality (including ICU admission and transition to hospice) were collected via retrospective review. Qualitative and quantitative tools including process maps, cause-and-effect diagrams, Pareto charts, and priority matrix were used to identify potential areas for intervention. Two PDSA cycles were implemented: daily multidisciplinary discharge rounds with physicians, nursing, social work, case management, and PT/OT (PDSA1), and a templated discharge email to patients’ primary oncology team including attending oncologist, mid-level providers, nurse coordinator, pharmacist, and urgent care team (PDSA2). An SPC chart with 3-σ limits and t-test of unequal variance with 2-sided p-value was used to evaluate impact on readmission rates from baseline to PDSA2. Results: Following PDSA1 (May 2019 – Oct 2019), the 30-day readmission was 25.7%; PDSA2 was postponed due to COVID-19, however the 30-day readmission rate remained stable during the pandemic. Following PDSA2 (Sept 2021 – Dec 2021), the 30-day readmission rate was 18.2% corresponding to an absolute decrease of 34.3% which was statistically significant (p≤0.05). This was associated with a trend towards increased LOS, rate of ICU admission, and case-mix severity index although not statistically significant. There was no significant difference in inpatient mortality or transition to hospice (Table). Conclusions: Implementation of multidisciplinary discharge rounds and templated discharge communication resulted in a significant decrease in rate of 30-day readmissions for solid tumor oncology patients. There was a trend towards increased LOS and ICU admissions without increased inpatient mortality. Improvement in discharge email compliance and implementation of an urgent symptom clinic may further reduce the 30-day readmission rate. [Table: see text]

e19015 Background: The prognosis of adult patients with acute lymphoblastic leukemia (ALL) has improved with the adoption of pediatric-inspired chemotherapy regimens. PEGylated asparaginase (PEG-Asp) is essential to these regimens. Although PEG-Asp is associated with an increased risk of coagulopathy, venous thromboembolism, and depletion of antithrombin III (AT3), there is limited data evaluating the risk of thrombosis and bleeding and optimal antithrombotic interventions in these patients are unknown. Methods: We performed a single-center retrospective study of patients ≥ 18 years-old who received PEG-Asp for B- or T-ALL at the University of Virginia between 2015 and 2020. The primary outcomes were the incidence of thrombosis and bleeding events. All patients received prophylactic AT3 repletion for activity level <60% & cryoprecipitate for fibrinogen <100mg/dL. None received prophylactic anticoagulation. All received prednisone during induction at a median daily dose of 1 mg/kg. Results: We identified 57 patients who received PEG-Asp for ALL. Median age was 32 years (range 18-63). Five patients (8.8%) had a thrombotic event during induction versus five (16%) during post-induction. Four patients (7%) had a bleeding event during induction versus five (10%) during post-induction. The most common type of thrombosis was deep venous thrombosis, with the majority being catheter-associated. Pulmonary embolism and CNS thrombosis were less common. During induction, the median time to thrombotic event was 18 days after last PEG-Asp administration. 60% and 80% of patients received AT3 and cryoprecipitate, respectively. During post-induction, the median time to thrombotic event was 58 days after last PEG-Asp administration. 38% and 63% of the patients received AT3 and cryoprecipitate, respectively. There was one episode of major bleeding during induction and six during post-induction. Conclusions: Though the increase in thrombotic risk in adult patients receiving PEG-Asp is well-characterized, rates of reported thromboses vary widely. Studies examining bleeding risk associated with PEG-Asp regimens are even scarcer and with variable outcomes. There was a significant occurrence of both thrombotic and bleeding events associated with administration of PEG-Asp. More investigation into the relative thrombotic and bleeding risks associated with PEG-Asp is needed to determine optimal antithrombotic interventions in adult patients with ALL.[Table: see text]