Submitting Author: Muzzafar, Tariq, MD
Institution: UT MD Anderson Cancer Center
Additional authors:Sa Wang, MD
Session: Acute leukemias of ambiguous lineage

38 year old male presents to UTMDACC with fever and high WBC (2/2010)

WBC 204.2 Hgb 8.1, MCV 89, Platelet 73, Neutrophils 1%, Lymphs 4% Blasts 94%

Bone marrow work up was performed.

Peripheral blood: Blasts are intermediate in size, with round nuclear contours, moderately dispersed chromatin, prominent "punched out" nucleoli, and scant amounts of basophilic cytoplasm, some with sparse granules. Additional findings: pancytopenia

Bone marrow aspiration and biopsy Site: posterior iliac crest Procedure - Formalin fixed biopsy after decalcification

Core biopsy: 100% cellularity; sheets of blasts represent almost entire marrow cellularity; blasts are small to intermediate in size, with round nuclear contours, moderately dispersed chromatin, conspicuous nucleoli, scant to intermediate amounts of cytoplasm

Aspirate smears: Blasts small to intermediate in size, have high nuclear: cytoplasmic ratio, round nuclear contours, moderately dispersed chromatin, one to two prominent nucleoli, scant to small amounts of basophilic cytoplasm; subset of cells contain fine cytoplasmic granules

Myeloperoxidase (cytochemistry): Blasts are negative

Flow cytometry:

96% blasts

POSITIVE: CD34, HLA-DR, CD7, CD33 (partial, dim), CD38 (partial, dim), CD9 (partial, dim), CD52, CD58, CD81, CD49b, CD184 (partial, dim)

NEGATIVE: CD19, CD20, CD22, cyto CD79a, CD10, sIg, CD1, CD2, CD3, cyto CD3, CD4, CD8, CD5, CD25, CD56, TdT, CD13, CD14, CD15, CD41, CD64, CD117 and myeloperoxidase

KARYOTYPE: Insufficient yield of analyzable metaphases 45-46,XY[cp2]

FISH: NEGATIVE for BCR-ABL1 rearrangement

Multiplex leukemia translocation assay:

Negative for b3a2, b2a2 and e1a2 transcripts of bcr-abl/ t(9;22)(q34;q11), the short and long forms of PML-RARA/ t(15;17)(q22;q21), the A and D forms of CBFb-MYH11/inv(16), AML1-ETO/t(8;21)(q22;q22), E2A-PBX-1/t(1;19)(q23;p13), MLL-AF4/t(4;11)(q12;q23) and TEL-AML1/ t(12;21)(p12;q22)

NEGATIVE for BCR-ABL fusion transcript, monoclonal T-cell receptor beta chain gene rearrangements, monoclonal T-cell receptor gamma chain gene rearrangements

Patient was treated with hyper CVAD chemotherapy with no response; subsequently with fludarabine, idarubicin, cytarabine and Myelotarg with complete remission. He underwent 1-antigen mismatched unrelated donor transplant for in 08/2010. Last follow up was in 11/2012 with complete remission

Acute undifferentiated leukemia is a rare entity; hence genomic aberrations are not well characterized. Whole genome sequencing may be helpful in elucidating pathogenesis and suggest drug targets.

Anecdotal reports mention poor prognosis. Patient was initially treated with hyper CVAD (directed against high grade lymphoid neoplasms) with no response. However, he achieved complete response to FLAG protocol (including fludarabine, cytarabine, idarubicin. Mylotarg was added since blasts expressed CD33. Since disease was high risk and patient was young and he underwent stem cell transplant.

Treatment planning is problematic since there are no standard protocols for this entity. Antibody based immunotherapy may be considered if blasts express relevant antigens like CD33 in this case.

Stem cell transplant should be considered if patient is a candidate in view of the poor prognosis.

Acute undifferentiated leukemia

Acute myeloid leukemia with minimal differentiation

Case 396