Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in

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 equivalents? Are there abnormal promyelocytes? Are there Auer rods? Is cytochemical MPO positive? Is cytochemical NSE positive? Must send for immunophenotyping. YES? NO? NO? NO? NO?

Cytochemical MPO

Summary Morphology Immunophenotype Myeloid Blasts Strong MPO positive 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 equivalents? Are there abnormal promyelocytes? Are there Auer rods? Is cytochemical MPO positive? Is cytochemical NSE positive? Must send for immunophenotyping. YES? 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. 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. 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. (B) MPO-positive and MPO-negative cup-like blast cells in a patient with AML FAB M1. 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

NPM1 Mutated AML, FAB AML M1 Final Diagnosis NPM1 Mutated AML, FAB AML M1