Sequential Philadelphia-Positive Pre-B Acute Lymphoblastic Leukemia and Chronic Myeloid Leukemia With Distinct BCR::ABL1 Fusion Transcripts

Background

The sequential emergence of chronic myeloid leukemia (CML) following Philadelphia-positive acute lymphoblastic leukemia (ALL) is exceedingly rare, and its biological basis remains uncertain. Case: We report a 15-year-old boy initially diagnosed at age 4 with Philadelphia-positive pre-B ALL expressing p190 BCR::ABL1. He achieved deep molecular remission following chemotherapy per the COG AALL0232-based high-risk B-ALL protocol plus imatinib. Approximately 5 years after his last documented follow-up, he re-presented with splenomegaly, leukocytosis, anemia, and thrombocytosis. Bone marrow findings supported chronic-phase CML, confirmed by detection of BCR::ABL1 p210 (b2a2 and b3a2) with no detectable p190. Responses to imatinib and dasatinib were suboptimal, and kinase-domain analysis identified a rare ABL1 c.1159T>A (p.Leu387Met) variant. He subsequently underwent matched-related allogeneic hematopoietic stem cell transplantation and remains BCR::ABL1-negative on nilotinib.