Extramedullary relapse and discordant CD19 expression between bone marrow and extramedullary sites in relapsed acute lymphoblastic leukemia after blinatumomab treatment.
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| Abstract |
Blinatumomab, a bispecific T-cell engager antibody construct targeting CD19, has been shown to improve the outcome in patients with relapsed and/or refractory B-cell acute lymphoblastic leukemia. Treatment with blinatumomab demonstrated significant survival benefit over chemotherapy, supporting its use as a bridge therapy to allogeneic hematopoietic stem cell transplantation. Unfortunately, following initial response, approximately 50% of responding patients eventually relapse. At the time of failure, the majority of patients have CD19-positive blasts, yet a concerning number of CD19-negative relapses has been reported. In the data reported herein, we present an interesting case of a 42-year-old patient with primary refractory B-cell acute lymphoblastic leukemia who achieved complete morphologic remission after one cycle of blinatumomab as a single agent. Notably, and in the absence of extramedullary disease history, the response in marrow coincided with the emergence of CD19-positive extramedullary relapse including sites of previous punctures for blood and bone marrow samples, as confirmed by biopsy, as well as parenchymal organs (eg breast and lung). During the second cycle of blinatumomab, a CD19-negative morphological relapse emerged. The loss of CD19 was a transient event, as leukemic cells partially regained it after chemotherapy. This study illustrates a challenging situation of relapsed and refractory acute lymphoblastic leukemia complicated with extramedullary disease after exposure to a bispecific T-cell engager antibody, such as blinatumomab. Physicians should maintain a high level of suspicion for the evolution of extramedullary leukemia. This pattern of resistance and/or relapse to blinatumomab resembles the graft-versus-leukemia effect after allogeneic transplantation (stronger in blood and marrow than in other tissues). Mechanisms of resistance to blinatumomab are not yet clear. Combination treatments for refractory patients and those at high risk for exramedullary disease may warrant future assessment.
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| Authors | Christos Demosthenous, Chrysavgi Lalayanni, Michalis Iskas, Vassiliki Douka, Nikoleta Pastelli, Achilles Anagnostopoulos |
| Journal | Current problems in cancer (Curr Probl Cancer) Vol. 43 Issue 3 Pg. 222-227 (06 2019) ISSN: 1535-6345 [Electronic] United States |
| PMID | 29895435 (Publication Type: Case Reports, Journal Article) |
| Copyright | Copyright © 2018. Published by Elsevier Inc. |
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