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This case study presents a 50-year-old male with acute myeloid leukemia (AML) refractory to induction chemotherapy. The diagnosis, clinical presentation, cytogenetic studies, and classification of Acute Megakaryoblastic Leukemia (AMKL) are discussed.
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CASE 411 Jose Gonzalez-Berjon, MD & Tariq Muzzafar, MD UT M.D. Anderson Cancer Center
CLINICAL PRESENTATION • 50 year old gentleman • No significant past medical history • Two week history of constitutional symptoms • Diagnosed with acute myeloid leukemia • Refractory to induction chemotherapy • Presented to UT M.D. Anderson Cancer Center
CBC • Hgb 9.1 g/dL • WBC 4.0 K /UL • Platelet 3 K/UL • Neutrophils 28% • Lymphocytes 63% • Monocytes 2% • Eosinophils 1% • Bands 1% • Unclassified cells 5%
Flow Cytometry SSC CD 45
CD 13 CD 64 CD 117 CD34 CD41 HLA DR CD 9 CD 7 CD34 CD 33 MPO
Cytogenetic & Molecular Studies Karyotype: • 46,XY,del(9)(q22)[17] • 46,XY,del(9)(q22)[cp2] • 46,XY[1] NEGATIVE for • PML-RARA;short or long form • RUNX1T1/RUNX1 [t(8;21)] • CBFB-MYH11 [inv(16)] • FLT3 mutation (ITD or codon 835/836) • Krasand Nras mutations (codons 12, 13 and 61)
Submitted DiagnosisAcute megakaryoblasticleukemia(Acute myeloid leukemia not otherwise specified)
Panel Consensus DiagnosisAcute megakaryoblasticleukemia(Acute myeloid leukemia not otherwise specified)
ACUTE MEGAKARYTOBLASTIC LEUKEMIA (AMKL) per WHO • Acute myeloid leukaemia (megakaryoblastic) with t(1;22)(p13;q13); RBM15-MKL1 • <3 years • Myeloid leukemia associated with Down syndrome • + 21 • GATA mutations • Acute megakaryoblasticleukemia (acute myeloid leukemia, not otherwise specified) • Adults and children
AMKL (ADULTS) • Rare • WHO definition: • ≥ 20% blasts • ≥ 50% of blasts must be of megakaryocytic lineage • Morphologically: • Primitive blasts (like our case); some may be called AML with minimal differentiation • Large blasts; spectrum of forms • Megakaryocytes: small & dysplastic • Fibrosis often present
AMKL: PITFALLS Fibrosis • Aspirate blast count not reliable • Flow: not sufficient cells to analyze Solution • High index of suspicion • Immunohistochemistry on core biopsy • CD34, CD61, Factor VIII • Flow cytometry: • Blasts (subset) have CD41, CD42b, CD61, CD36 • HLA-DR often negative • CD34 may be positive on megakaryoblasts
AMKL & OTHER MYELOID NEOPLASMS MPN MDS AMKL AML-MRC MRC: myelodysplasia related changes
AMKL: UT M.D. ANDERSON EXPERIENCE • 53 cases diagnosed as AMKL (01/1994 to 08/2012) • Excluded cases < 18 years of age • Reassessed diagnosis using WHO criteria • Largest reported series
AML; therapy related Prior chemo / radiation AML with MRC Karyotype = MDS BCR-ABL 1 CML; blast phase inv(3) AML with inv(3)
AMKL: 53 CASES PER WHO 4 (7) 18 (34) 5 (9) 3 (6) 12 (23) 11 (21)) number of cases (% of cases)
AMKL: 53 CASES PER WHO 4 (7) 18 (34) 5 (9) 3 (6) 12 (23) 11 (21)) 4 cases: clinical information or cytogenetic results not available Classified as AMKL based solely on morphologic / immunohistochemical features
AMKL: 53 CASES PER WHO • Median survival: 26 weeks • Complex karyotype predicts adverse prognosis (p < 0.01) • No statistical significance: • History of chemo and / or radiation therapy • Pre - existing MDS or MPN • Blast percentage in peripheral blood
CONCLUSIONS • 9% of cases with megakaryocytic differentiation (morphologic / immunophenotypic) classified as AMKL per WHO • Megakaryoblastic differentiation occurs in spectrum of myeloid neoplasms • Most cases of AMKL fulfill diagnostic criteria for AML with myelodysplasia-related changes per WHO • 23% cases evolved from pre-existing MPN not commonly emphasized
What is “Acute megakaryoblastic leukemia NOS”? Prior chemo / radiation BCR-ABL 1 AML; therapy related Karyotype = MDS AML with MRC CML; blast phase inv(3) AML with inv(3) MPN MPN; blast phase
What is “Acute megakaryoblasticleukemia NOS”? • 18 years in busiest leukemia center on the planet • 5 cases only as defined by WHO • AMKL NOS is an exceedingly rare entity
What is “Acute megakaryoblasticleukemia NOS”? AMKL NOS is an exceedingly rare entity per WHO Should morphology and immunophenotype determine the entity of AMKL? OR Should clinical history of a prior myeloid neoplasm and karyotype determine what gets called AMKL? What determines disease classification & nomenclature?