Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S332 on quantitative polymerase chain reaction analysis for BCR-ABL1 p210 transcript (e13/e14 a2), which was expressed in amplified RNA extract at 728.55% IS. The patient was started on imatinib 400 mg/d and after 6 months, BCR-ABL1 p210 was 12.8% IS. Consequently, the treatment was declared a failure and the patient was shifted to nilotinib. A month after treatment, he developed grade III lower limb edema, scrotal edema, and proteinuria (1350 g/24h, range 42-225). Antinuclear and antimitochondrial antibody tests were negative and C3 and C4 were within normal range. Albumin/creatinine ratio was 7099.21 mg/g of creatinine (clinical albuminuria: >300). Both of the patient’s kidneys were of average size, with increased cortical echogenicity (grade I). There were no gross stones or changes in back pressure. Interventions: Renal biopsy was negative for Congo red staining (no amyloid deposits). There were no kappa, lambda, C3, or immunoglobulin A or immunoglobulin G deposits. Biopsy also revealed minimal change as a result of the CML, and nephrotic syndrome. Nilotinib was discontinued and the patient was commenced on corticosteroids, diuretics, statins, and apixaban. Main Outcome Measures: The patient’s symptoms improved; however, on re-evaluation of CML, bone marrow aspirate showed 74% blast cells and flow cytometry was positive for CD34, CD33, HLA-DR, CD117, myeloperoxidase, and CD13. These findings suggested myeloblastic crisis; BCR-ABL1 was 42% IS. Results: The patient achieved complete remission after standard induction chemotherapy in combination with dasatinib. Conclusion: TKI-related renal AEs are uncommon; they are usually observed in case reports and most of them have been associated with dasatinib. TKIs tend to induce fluid retention. Recently a nilotinibinduced acute interstitial nephritis has been reported. TKI-induced nephropathy is a topic worthy of further investigation. Keywords: CML, proteinuria, nephrotic syndrome, myeloblastic crisis, case CML-062 Define the Vulnerable ‑ Social Determinants of Health Impact on Hematological Malignancies Affecting Children, Adolescents, and Young Adults: Systematic Review and Meta‑Analysis Muhannad Sharara MD1, Kellen Cristine Tjioe PhD, MSc, DDS1, Marisol Miranda Galvis PhD, MSc, DDS1, Gagan Agrawal MS, PHD2, Andrew Balas MD, PhD3, Jorge Cortes MD1 1Georgia Cancer Center, Augusta University, USA. 2School of Computer and Cyber Sciences, August, USA. 3Institute of Public and Preventive Health, Augusta, USA Context: Defining vulnerable patients with the highest risk may improve their survival expectations. Objective: To identify and analyze the impact of the social determinants of health (SDH) on hematologic malignancies treatment outcomes in children, adolescents, and young adults. Methods: This systematic review and meta-analysis were registered at the Prospective Register of Systematic Reviews (PROSPERO) (CRD42022346854). We performed a comprehensive search using six databases including articles from January 2002 to September 2022. We included studies held in the US evaluating patients younger than 40 years and evaluating survival outcomes according to any SDH. Results: We identified nineteen studies for qualitative analysis and ten for meta-analysis. This review covered nine SDH variables. The most studied factors were health insurance status (n=13, 68%) and neighborhood socioeconomic status (nSES) (n=9, 47%). Other variables investigated were poverty level (n=3, 15%), median income (n=4, 20%), marital status (n=3, 15%), location of care (n=3, 15%), education level (n=2, 10.5%), distance traveled to treatment facility (n=1, 5%), and unemployment (n=1, 5%). The primary outcome evaluated was overall survival (OS) (n=18) followed by cancer-specific survival (n=5). Most of the studies showed that having low nSES, being uninsured or having public insurance are associated with lower OS. In addition, unmarried patients showed a lower OS compared to those married but data did not show the same when investigators did age stratification. Using databases retrospectively has limited the investigators to use the same variables used for adults. Our meta-analysis demonstrated that patients at the lowest nSES, evaluated through Yost index, exhibited worse OS (HR: 1.40, 95% CI: 1.13–1.73). Health insurance coverage also impacted treatment outcomes; uninsured patients and Medicaid/low public insurance patients show significantly lower OS (HR: 1.35, 95% CI: 1.17–1.55), (HR: 1.21, 95% CI: 1.16– 1.26) respectively, compared to the private insurance as a reference point for both. Conclusion: Our analysis indicates that the most SDH variables evaluated are health insurance coverage and nSES. We identified a significant impact of insurance status and nSES on patients’ survival. Determining vulnerable patients is important to develop public policies to improve their cancer outcomes. This includes assessing SDH in all patients prospectively. Keywords: social determinants of health, pediatric, hematologic malignancies, adolescents, survival CML-076 The Downregulation of Both Large E3 Ubiquitin Ligases, HERC1 and HERC2, is a Common and Unambiguous Feature of Chronic Myeloid Leukemia Muhammad Shahzad Ali PhD1, Zunaira Munir PhD2, Cristina Panuzzo PhD1, Nabeel Ashraf MD1, Stefano Magnati BS1, Barbara Pergolizzi PhD1, Enrico Bracco PhD2, Giuseppe Saglio MD PhD1 1University of Turin, Department of Clinical and Biological Sciences, Turin, Italy. 2University of Turin, Department of Oncology, Turin, Italy Context: Protein degradation by the ubiquitin-proteasome system (UPS) has been shown to regulate hematopoietic stem cell (HSC) self-renewal, differentiation, and survival. The balance between HSC self-renewal and differentiation is critical to maintaining hematopoiesis and its dysregulation is often associated with malignancies, including chronic myeloid leukemia (CML). Objective: Large HERC E3 ligase family members, HERC1 and HERC2, are staggeringly complex proteins that can intervene in a wide range of physiological processes, such as cell proliferation, DNA repair, neurodevelopment, and inflammation. Therefore,
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