Relapse/refractory paediatric B-ALL case with CD19 - phenotype switching indicating the importance of appropriate diagnostics approach and targeted treatment adjustment – case report

Background: The case reported presents a rare CD19 − phenotype shift of acute lymphoblastic leukaemia clone during the course of relapse/refractory ALL in a paediatric patient. We explore possible reasons promoting CD19 negative cell selection, including discrete mutations and anti-CD19 treatment, which is gaining importance as targeted therapies such as blinatumomab enter standard treatment protocols. Case presentation: A 9-year-old male patient was admitted to the Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, Poland with fatigue, anaemia and hepatosplenomegaly, and was subsequently diagnosed with B lymphocyte acute lymphoblastic leukaemia. Initial standard genetic analysis did not show significant chromosomal aberrations, and the patient underwent chemotherapy in line with the intermediate-risk protocol. After initially achieving remission, the disease relapsed, and the patient required hematopoietic stem cell transplantation (HSCT). In-depth retrospective microarray analysis performed at this point revealed additional risk factors including hyperdiploidy. After staying in remission for several months, a second recurrence was diagnosed which prompted targeted treatment application (Blinatumomab) and subsequent HSCT. The third leukemic relapse diagnosed shortly after second HSCT limited treatment options to last-resort CAR T cell therapy in Germany. Subsequent immunophenotyping revealed lack of CD19 expression by ALL clones and disqualified the patient from treatment. The patient died in October 2019 from disease progression. Conclusions: The case we report highlights the importance of in-depth molecular diagnostics and monitoring of relapse/recurrent ALL cases in order to identify and manage as many potential risk factors as possible during treatment. This gain importance as selective targeted treatments use increases, as antigenic phenotype and its changes directly influence the efficacy of such treatments, and therefore patients’ prognosis.