B-Lymphoblastic Leukemia Presenting with Eosinophilia: A Case Report and Review
Authors: Shabsovich David , Maranzano Michael J. , Said Jonathan , Ku Nam , Pullarkat Sheeja , Schiller Gary J. 
Published: December 2023

B-lymphoblastic leukemia (B-ALL) presenting with eosinophilia represents a rare entity. In particular, the unique clinical manifestations as well as the genetic and molecular pathogenesis of the associated eosinophilia have been topics of debate and investigation. Herein, we present a case of B-ALL presenting with concomitant eosinophilia and a review of the published cases, including 120 additional cases.
The patient, at presentation, was a 20-year-old female who presented with cardiac, neurologic, and cutaneous signs of eosinophilia and with leukocytosis (WBC 51, 40% eosinophils, 0% blasts), anemia, and thrombocytopenia. Imaging revealed multi-focal brain infarcts, pulmonary infiltrates, and myocarditis. Empiric steroids, colchicine, and intravenous immunoglobulin were initiated. One week after presentation, bone marrow biopsy revealed a hypercellular (&gt;95%) marrow with 50% blasts and marked eosinophilia, which on later review revealed an immunophenotype most consistent with B-ALL (positive for Pax5, CD10, CD19, CD20, cCD22, CD34, CD45, CD79a, HLA-DR, and TdT and negative for MPO and CD117). Conventional cytogenetic analysis of the bone marrow was unable to be performed. Fluorescence in situ hybridization (FISH) revealed an IGH rearrangement in 10.5% of nuclei analyzed. After three weeks of treatment with steroids and resolution of symptomatic organ involvement, a repeat bone marrow biopsy did not show any evidence of malignancy or genetic abnormalities. The patient was continued on a steroid taper, did not initiate further antileukemic therapy, and was lost to follow up.
Ten weeks after initial presentation and after completing a steroid taper, the patient presented with diffuse bone pain. Repeat bone marrow biopsy showed B-ALL with 64% blasts and increased eosinophils, normal conventional cytogenetics and hematologic malignancy sequencing panel, and FISH with gain of Xp in 20.5% of nuclei analyzed; a lumbar puncture did not detect blasts in the cerebrospinal fluid. The patient began induction therapy with aBFM, rituximab, PEG-asparaginase, and intrathecal cytarabine. A bone marrow biopsy performed four months after her initial presentation revealed a mildly hypocellular marrow with 3% B-lymphoblasts and no eosinophilia, suggesting residual disease, with no evidence of cytogenetic or molecular genetic abnormalities. As a result, therapy with blinatumomab was initiated. A follow up bone marrow biopsy performed six months after her initial presentation revealed a hypocellular marrow with multilineage maturation and no excess blasts with normal cytogenetic and molecular genetic studies.
A literature review identified 120 additional cases of ALL with eosinophilia. In summary, it tends to present in adolescent males, often with mild anemia and thrombocytopenia and no peripheral blasts, which can lead to a delay in diagnosis of ALL. The eosinophilia is often symptomatic, with cardiopulmonary involvement being the most common, and can lead to rapid mortality in a substantial number of cases. A significant proportion of cases of ALL with eosinophilia involve t(5;14)(q31;q32), leading to overexpression of IL-3, which was not definitively found in this patient; however, there are numerous other recurrent abnormalities that may be contributing to the pathogenesis, both concurrently with and in the absence of this translocation, including other rearrangements of IGH as well as IKZF1 and CDKN2A abnormalities. Prompt diagnosis, now commonly using sensitive molecular diagnostic assays, and initiation of glucocorticoids for symptom control and subsequent antileukemic therapy, are essential to avoiding complications of eosinophilia in such patients.