Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S248 Hunan Julhakyan MD, PhD1, Andrey Sudarikov MD, PhD1, Elena Parovichnikova MD, PhD1 1National Medical Research Center for Hematology, Moscow, Russian Federation. 2I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation Context: Tumor cells of the patients with Ph - negative acute lymphoblastic leukemia (ALL) may have a variety of genetic lesions. New diagnostic methods, such as chromosomal microarray analysis (CMA), allow searching for new molecular factors related to pathogenesis and associated with the disease prognosis. Objective: To appreciate the landscape of tumor molecular karyotypes in a diagnosis of Ph-negative B-ALL. Design: CMA (GeneChip System 3000) of the tumor cells was performed for the patients with de novo Ph-negative B-ALL, admitted to the National Medical Research Center for Hematology (Moscow, Russia) from 2021 to 2023. Patients: The study included 21 patients, median age was 34 years, gender distribution was as follows: 10 (48%) male/11 female (53%). All patients received treatment under the same clinical protocol RALL-2016. Results: Of 21 patients, only 3 had a normal molecular karyotype. Eleven (53%) showed signs of tumor heterogeneity (5 (24%) patients had multiple duplications, 2 (10%) had deletions, and 4 (19%) had both deletions and duplications). Homozygous deletion of 9p21.3 (CDKN2A gene) was established for 4 patients. Early lethality was noted for 1 patient with multiple losses and gains. Two patients (both with chLOH, one with deletion of 9p21.3) had a refractory disease course. After 2 induction courses according to the protocol, of 18 patients: 12 (66%) had minimal residual disease (MRD)- remission and 6 (33%) MRD + remission. Tumor heterogeneity was found in 2 (33%) of 6 patients from the MRD + group vs 8 (66%) of 12 in the MRD - group. However, statistical significance was not reached (P=0.18). Conclusion: Thus, in 53% of patients, tumor heterogeneity was established at the onset of the disease. When comparing groups of patients with and without signs of tumor heterogeneity, there were no significant differences in achieving MRD- remission. However, all patients who did not achieve remission of the disease had changes in DNA copy number. The significance of the identified changes is to be assessed with a longer follow-up. Funding: The research was supported by Russian Science Foundation (RSF project No. 23-25-00490) Keywords: ALL, molecular karyotype, tumor cells, Ph-negative B- acute lymphoblastic leukemia ALL-351 Inotuzumab Ozogamicin in the Treatment of Relapsed/Refractory (R/R) Ph‑Positive Acute Lymphoid Leukemia (ALL) With Extramedullary Disease: Our Experience Maria Dragoescu MD1, Alexandra Ghiaur MD1, Daniel Coriu PhD1,2 1Center of Haematology and Bone Marrow Transplant, Fundeni Clinical Institute, Bucharest, Romania. 2Carol Davila University of Medicine and Pharmacy, Bucharest, Romania Context: At disease recurrence, a significant proportion of patients with B-ALL present with extramedullary involvement. Inotuzumab ozogamicin (IO) is a calicheamicin-based antibody-drug conjugate targeting CD22 that is a valuable asset in the management of R/R B-ALL. Case Presentation: We present 2 cases of relapsed Ph-positive B-ALL with non-CNS extramedullary disease treated with IO. Case 1: 32-year-old woman, diagnosed with Ph-positive B-ALL, with early relapse after hematopoietic stem cell transplantation (HSCT), for which she received ponatinib and steroids, with achievement of minimal residual disease (MRD) negativity both by polymerase chain reaction and flow cytometry. She refused a second HSCT and continued maintenance with ponatinib. Four months after the initial HSCT, she relapsed with extramedullary involvement of the breast and uterus. She was treated with one course of methotrexate and cytarabine-based chemotherapy, with progressive disease. Therefore, she received 6 cycles of IO with complete metabolic response. Case 2: 24-year-old man with Ph-positive B-ALL treated by GRAAPH-2005 (with imatinib) protocol with complete remission who refused HSCT. He experienced medullary relapse 13 months after the initial diagnosis and the tyrosine kinase inhibitor imatinib was switched to dasatinib and then, due to disease progression, to ponatinib, administered in conjunction with steroids. He achieved complete response with MRD negativity after 1 cycle of ponatinib+steroids. After 3 months, extramedullary relapse occurred in the right femur. The patient then received 2 cycles of IO with complete metabolic response and agreed to proceed to HSCT. Conclusion: These 2 cases underscore the potential benefits of IO in Ph-positive advanced B-ALL with extramedullary involvement in comparison with classical chemotherapy. Although notable adverse events can occur during treatment with this novel agent, it was well tolerated by our patients, with only grade 1 hepatotoxicity by elevated alanine aminotransaminase and aspartate transaminase in our male patient. Keywords: inotuzumab ozogamicin, acute lymphoblastic leukemia, extramedullary disease, case ALL-352 Exploring DUX4‑Rearranged B‑ALL in India: Incidence, Molecular Pathways, and Potential Biomarkers Mercilena Benjamin MSc1, Jay Singh PhD1, Avanish Kumar Pandey MSc1, Neha Thukral PhD1, Sarita Kumari PhD1, Sameer Bakhshi DM2, Amitabh Singh MD3, Jayanth Kumar Palanichamy MD4, Inder Kumar Singh PhD5, Rachna Seth DM6, Anita Chopra DM1 1Laboratory Oncology,All India Institute of Medical Sciences, New Delhi, India. 2Department of Medical Oncology, All India Institute Of Medical Sciences, New Delhi, India. 3Department of Pediatrics, VMMC & Safdarjung Hospital, New Delhi, India. 4Department of Biochemistry, All India Institute Of Medical Sciences, New Delhi, India. 5Department of Neurology, All India Institute Of Medical Sciences, New Delhi, India. 6Department of Pediatrics, All India Institute Of Medical Sciences, New Delhi, India Context: DUX4-rearranged B-ALL (DUX4-r), characterized by cryptic DUX4-rearrangements, has not been investigated in Indian
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