Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre [email protected] History • 59 year old female, easy fatiguability • Leucocytosis, decrease in platelets – TLC:90,000/mm3 – Platelet counts: 54,000/mm3 • Suspected to have acute leukemia and referred to TMH Questions to ask when faced with acute leukemia • Is there an increase in blasts or blast YES? equivalents? • Are there abnormal promyelocytes? • Are there Auer rods? • Is cytochemical MPO positive? • Is cytochemical NSE positive? • Must send for immunophenotyping. NO? NO? NO? NO? Cytochemical MPO Summary • Morphology – Myeloid Blasts – Strong MPO positive • Immunophenotype – CD34 Negative – HLA-DR Negative – CD13,CD33positive, CD117 dim-negative DIAGNOSIS? Questions to ask when faced with acute leukemia • Is there an increase in blasts or blast YES? equivalents? • Are there abnormal promyelocytes? • Are there Auer rods? • Is cytochemical MPO positive? • Is cytochemical NSE positive? • Must send for immunophenotyping. NO? NO? NO? NO? Is this acute promyelocytic leukemia? Yes / No Is this distinction important? How urgent is the report ? APL with t(15;17)(q22;q12); PML-RARA How does this determine treatment? • AML with t(15;17) – Treated with • All Trans Retinoic Acid • Or Arsenic Trioxide – Excellent survival – High mortality if not detected early & treated correctly • DIC and bleeding complications eg intracranial bleeding – Practical working algorithm in a pathology lab • AML M3 or non M3 AML Overall survival (top) and disease-free survival (bottom) curves of 14 relapsed APL patients after As2O3-induced CR. Shen Z et al. Blood 1997;89:3354-3360 ©1997 by American Society of Hematology Cup Shaped Blasts Cytochemical MPO Positive Typical morphology of myeloid blasts with cup-like nuclear invagination in AML. (A) The “cup” seems to be a part of the nucleus in Pappenheim staining, however it is positive for myeloperoxidase (MPO) in reactive blasts. Kroschinsky F P et al. Haematologica 2008;93:283-286 ©2008 by Ferrata Storti Foundation Cup shaped blasts are often associated with NPM1 Mutations NPM WT 169bp NPM Mutant 173 bp FLT3-WT 330bp Final Diagnosis NPM1 Mutated AML, FAB AML M1