Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S244 correlated with poor outcomes and reduced survival. Objective: To determine whether high expression of CRLF2 as a single factor or coexistence of other molecular rearrangements and activation of the JAK/STAT signaling pathway is responsible for poor prognosis in BCP-ALL patients. Design and Setting: Since June 2021, all newly diagnosed patients with ALL from 16 Pediatric Oncology Centers in Poland, treated according to the clinical AIEOP BFM 2017 Poland clinical trial, were enrolled in our study. Patients: Patients from the AIEOP BFM 2017 Poland clinical trial who underwent advanced molecular diagnostics were analyzed (n=426). Patients with the expression of the CRLF2 detected by flow cytometry (FC) were distinguished (n=21). Expression was assessed as positive if >50% (strong) or dim if 10-50%. Gene fusions and point mutations found by fluorescence in situ hybridization (FISH) and RNA nextgeneration sequencing (RNA-seq) with TruSight RNA Pan-Cancer Panel were assessed. Main Outcome Measures: In ALL patients with the expression of CRLF2, evaluation of other molecular rearrangements and clinical features was performed, and they were subjected to consider applying targeted therapy with JAK/STAT inhibitors (ruxolitinib). Results: The study group consisted of patients with BCP-ALL in which expression of CRLF2 was found. Seventeen patients had strong, and 4 had a dim expression of CRLF2. In 18 patients, gene fusions as CRLF2::P2RY8, CRLF2::IGH, and NUP214::ABL1 were detected. Point mutations in CRLF2 and JAK2 were identified in 3 and 6 patients, respectively. In 10 patients, more than one rearrangement was noticed, and in 4 patients, neither gene fusion nor point mutations responsible for positive expression of CRLF2 were found. Additionally, 4 patients harbored IKZF1 deletion. Patients were stratified into standard (n=7; 33,3%), medium (n=8; 38,1%), and high (n=6; 28,6%) risk groups. Five patients with poor responses to the standard treatment received targeted therapy (ruxolitinib). Conclusions: In patients with CRLF2 expression, other molecular rearrangements should be searched to determine the proper risk group. Keywords: ALL, CRLF2 expression, JAK/STAT signaling pathway, targeted treatment, ruxolitinib ALL-287 T Cells Under the Influence of Blinatumomab Masquerading as Blasts Fajer Alsejari PharmD1, Fatma Khadadah Consultant hematologist2, Ahmed Absi Assistant professor3, Marwa Seif Hematologist2, Yasser Akbar Medical doctor2, Ayesha Aljassar Cytology2, Ahmed Alhuraiji Consultant hematologist2, Ramesh Pandita Consultant hematologist2 1Kuwait University, Jabriya, Kuwait. 2Kuwait Cancer Center, Shuwaikh, Kuwait. 3Princess Noorah Oncology Center, Jeddah, Saudi Arabia A 47-year-old female with newly diagnosed Philadelphianegative, CD20+ B-acute lymphoblastic leukemia (B-ALL) was started on R-HyperCVAD. Post-induction, she had an open thigh wound following debridement of skin infection and 15% marrow blasts. She was switched to blinatumomab. She experienced grade 2 neurological adverse events (NAEs) with persistent headaches and tremors starting D2 and no other neurological complications. These symptoms continued for the duration of blinatumomab use. D18 lumbar puncture with intrathecal (IT) chemotherapy showed WBC 0, RBC 75, and blasts positive for CD19 and TDT. She received twice weekly IT chemotherapy until resolution of cerebrospinal fluid (CSF) blasts. Post cycle 1, she was in a flow negative remission. During cycle 2 of blinatumomab, the same neurological manifestations reoccurred. D18 CSF cytology revealed blasts, but flow was negative. CSF cultures and virology were also negative. Flow examination of the CSF samples demonstrated a CD3-positive T-cell population whose expansion dynamics perfectly mirrored blinatumomab use. Her neurological symptoms resolved on completion of blinatumomab, and her T cell population dropped from 79% to 26% on chemotherapy (pre-blinatumomab baseline 22%). Blinatumomab is a bispecific T cell engager that significantly improves overall and relapse-free survival for both frontline and relapsed-refractory B-ALL. It is associated with NAEs, including seizures and encephalopathy, independently of disease burden. T cell activation by blinatumomab is a target-cell-dependent effect involving upregulating cell adhesion molecules, cytokine release, and T cell proliferation. This is also seen with other T cell therapies, such as CAR-T, associated with neurotoxicity, possibly through endothelial activation. One theory supported by laboratory evidence is that blinatumomab causes increased T cell adhesion to the endothelium of the blood-brain barrier. In the presence of CD19+ cells, T cells transmigrate to the central nervous system, causing further inflammation, edema, and hypoxia, leading to neurological symptoms. Our case perfectly illustrates this model for NAE-related to blinatumomab; the T-cell population’s dynamics strengthen this association. Given >10% Grade 3 or 4 NAEs with cellular therapies, interruption of T cell adhesion to the CSF may be a strategy worth exploring to minimize future NAEs. Keywords: ALL, blinatumomab, T cells, neurotoxicity, case ALL-296 Results of Treatment of Children With Philadelphia Chromosome‑Positive Acute Lymphoblastic Leukemia With Low‑Dose Chemotherapy Without Bone Marrow Transplantation in Uzbekistan Rahmatulla Hadiyev, Ibragimova Sapura MD Center for Pediatric Hematology Oncology and Clinical Immunology, Tashkent, Uzbekistan Introduction: Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is rare in children, but outcomes are still poor. With the introduction of tyrosine kinase inhibitors into the practice, the results of treatment have improved significantly. Objectives: Our study aimed to analyze cases of toxicity and treatment outcomes in children with Ph+ ALL who received treatment per the ALL-MB-2015 protocol in Tashkent, Uzbekistan, from 2015 to 2022. Materials and Methods: 46 patients aged 1 to 18 years with Ph+ ALL who received treatment according to the ALLMB + Imat-2015 protocol between 2015-2022. The average age of patients was 8.3±1.3; the median follow-up was 5 years. All patients with t(9;22) Ph+ ALL from the 15th day of induction received
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