Approach to Acute Leukemia

Dr. Nikhil PatkarClinician Scientist & Asst Professor

Hematopathology LaboratoryTata Memorial Centrepatkarnv@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– 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 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.

Shen Z et al. Blood 1997;89:3354-3360

©1997 by American Society of Hematology

Cup Shaped BlastsCytochemical 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 WT169bp

NPM Mutant173 bp

FLT3-WT330bp

Final Diagnosis

NPM1 Mutated AML, FAB AML M1