Occurrence of Extramedullary Relapses in Pediatric Acute Lymphoblastic Leukemia After Treatment With Blinatumomab

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We report a retrospective single-center analysis of pediatric patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia focusing on relapses outside of the typical locations, bone marrow, central nervous system, or testes. The purpose of the analysis was to describe the relapse patterns after immunotherapy with the bispecific antibody blinatumomab. The cohort includes 90 patients suffering a total of 167 relapses. The majority of relapses, 103/167 (61.7%), were isolated bone marrow relapses, while 34/167 (20.4%) were combined bone marrow and extramedullary relapses (EMR), and 30/167 (18.0%) were classified as isolated extramedullary relapses (IEMR). EMR included 36/64 (56.3%) central nervous system relapses, 10/64 (15.6%) testicular relapses, and 18/64 (28.1%) relapses occurred in other extramedullary sites (OEMR). Seven in 64 (4.2%) of these OEMR presented as isolated OEMR without bone marrow involvement at the time of diagnosis. Multivariate analyses did not show significant differences in EMR rates for patients undergoing hematopoietic stem cell transplantation, patients receiving total body irradiation or patients suffering acute or chronic graft-versus-host disease. Blinatumomab treatment, however, displayed a significant association with OEMR (HR 3.169; 95% CI [1.032-9.728], p = 0.044) and an increased risk for isolated OEMR (HR 13.322; 95% CI [2.276-77.989], p = 0.004) in univariate and multivariate analyses. These results suggest a higher rate of OEMR after treatment with blinatumomab in pediatric ALL, and require confirmation by prospective trials as well as consented diagnostic and therapeutic algorithms.

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