Biphenotypic Acute Leukemia with t(15;17) Lacking Promyelocytic-retinoid Acid Receptor α Rearrangement
A 55-year old Japanese woman was referred to our hospital with elevated white blood cell (WBC) counts with blasts. Her laboratory data on admission showed rising WBC counts (13.4×109/L; 76% blasts, 1% band, 6% segmented, 16% lymphocytes, 1% monocytes) with anemia and thrombocytopenia (hemoglobin 9.3 g/dL and platelets 110×109/L). Coagulation studies were normal. Lactate dehydrogenase was slightly raised to 367 IU/L (normal range 120-245). Bone marrow aspiration revealed replacement of normal marrow by blasts (94%). We detected differences in the size of the blasts, corresponding to an abnormal lymphocyte-like cell population with a high nuclear/cytoplasmic (N/C) ratio, but without granules in the cytoplasm (). These blasts were negative for myeloperoxidase (MPO) and esterase. Morphological findings were compatible with acute lymphoblastic leukemia (ALL-L2, FAB classification).\nImmunophenotype with double-color flow cytometry showed positivity (>30%) for CD19 (90.8%), CD22 (45.4%), CD79a (92.4%), CD13 (40.9%), CD33 (94.6%), CD34 (95.8%) and HLA-DR (93.8%). MPO was negative (2.0%). Double staining for CD19xCD33 was strongly positive (96.6%). The use of the EGIL scoring system revealed 5 points for B-lymphoid lineage and 2 points for myeloid lineage. The immunophenotype analysis was conclusive for a diagnosis of BAL.\nChromosomal analysis with G-banded karyotype of the bone marrow cells showed 46, XX, t(4;12)(q21;p11), t(15;17)(q22;q12) in all 24 metaphase spreads (). Fluorescence in situ hybridization (FISH) performed on interphase nuclei using an LSI PML/RARα dual color, dual fusion translocation probe (Vysis, USA) showed two separate PML and RARα signals () in 1000 interphase nuclei and all metaphases analyzed. No PML/RARα fusion signal was identified.\nThe patient was initially treated with the Japan Adult Leukemia Study Group (JALSG)-ALL202 chemotherapy protocol () and induction for ALL treatment was completed. The bone marrow aspirate at the end of the induction phase revealed hematologic complete remission (CR). After the consolidation phase I (with a high dose of cytarabine), the patient experienced the complication of septic shock with acute phlegmonous gastritis. Thereafter, we administered a single dose (9 mg/m2) of gemtuzumab ozogamicin (GO), an anti-CD33 antibody conjugate, independent of the JALSG protocol, and subsequently, completed the course until consolidation phase V. Furthermore, we continued maintenance phase therapy using the JALSG protocol until two years after the onset of disease, during which time we administered GO (6 mg/m2) twice. At present, 1.7 years after the end of chemotherapy, the patient has remained in hematologic first CR during the over 3.7 years follow up.