Not All Therapy-Related Neoplasms are Myeloid: A Case Report of Rare B-ALL With t(5;14) Following Alkylating Agent Treatment

Abstract Introduction/Objective Most therapy-related hematologic neoplasms are myeloid (t-MN). Although not recognized as a distinct entity in the WHO classification of hematologic neoplasms, therapy-related acute lymphoblastic leukemia (t- ALL) cases have been previously reported. ALL incidence increases with any previous malignancy and is higher in those with previous treatment, supporting the concept of therapy-related ALL. B lymphoblastic leukemia/lymphoma (B- ALL) with t(5:14) is a rare subtype of the ALL (<1%) harboring a IL-3/IGH gene translocation. We present the first case of B-ALL with t(5;14) following treatment with alkylating agents for breast carcinoma. Methods/Case Report A 79-year-old female received docetaxel, carboplatin, trastuzumab, pertuzumab, Herceptin and radiotherapy for an invasive ductal breast carcinoma. Two years later, she developed progressive pancytopenia requiring a bone marrow biopsy. Results (if a Case Study enter NA) The bone marrow aspirate smears demonstrated B-ALL with 25% blasts, limited neutrophilic maturation, moderate erythroid dysplasia, and decreased megakaryocytes with occasional atypical forms. On the biopsy, atypical megakaryocytes and lymphoblasts were positive for TP53 immunohistochemical stain. On flow cytometry, blasts were positive for CD19, cCD79a, CD22, CD10, TdT, and HLA-DR and only 6% were positive for CD34. Next generation sequencing showed TP53 and NRAS mutation. Karyotyping revealed 46, XX, t (5;14) (q33; q13) and trisomy 21. Conclusion B-ALL with t (5;14); IGH/IL3 fusion has not been previously reported following treatment with alkylating agents. The presence of morphologic myeloid dysplasia developing after chemotherapy with alkylating agents support causality being therapy related rather than an independent process. The case expands the breadth of known therapy- related hematologic neoplasms and raises questions regarding the mechanisms of leukemogenesis.