1. CASE 205
Denyo Adjoa Zakhia, MD Kristin Hunt Karner, MD Henry Ford Hospital, Detroit, MI

2. CLINICAL HISTORY 61 year-old Caucasian male
Cough, night sweats, low-grade fever
Complete blood count
Hemoglobin – 9.4 gm/dl
White blood cell count – 71.1 K/uL
Platelet count – 135 K/uL
Peripheral blood smear
Leukocytosis with 79% blasts

3. BONE BIOPSY BONE MARROW ASPIRATE Cellularity ->95% Blasts-87% H&E
CD1a

4. FLOW CYTOMETRY
cyto CD3

5. FLOW CYTOMETRY SUMMARY
Positive antigen panel
Negative antigen panel
cytoCD3
cytoTDT
CD2
CD7
CD13
CD15
CD34
CD117
HLA-DR
CD3
CD4
CD8
CD5
CD10
CD11b
CD14
CD16
CD33
CD56
CD61
CD235a
cytoCD79a
cytoMPO

6. CHROMOSOMAL ANALYSIS OF BONE MARROW ASPIRATE
46,XY,del(16)(q13)[6]/46,XY[14]
FISH ANALYSIS
No genetic abnormalities involving:
MYC(8q24)
BCL6(3q27)
IGH-BCL2(14:18)
API2-MALT1(11:18)
BCR-ABL(9:22)
MLL (11q23)
Inv 16

7. WHAT IS THE DIAGNOSIS?
EGIL
WHO

8. Mixed phenotype acute leukemia, favor T/myeloid
EGIL
T-lineage:
Score 3.5
Myeloid:
Score 2.5
Mixed phenotype acute leukemia, favor T/myeloid

9. Acute leukemia of T-cell Lineage with aberrant myeloid differentiation
WHO table (criteria)
Myeloid lineage
Myeloperoxidase (flow cytometry, immunohistochemistry or cytochemistry) Or
Monocytic differentiation (at least too of NSE, CD11c, CD14, CD64, lysozyme)
T lineage
Cytoplasmic CD3 or Surface CD3
B lineage
Strong CD19 with at least one of the following strongly expressed (CD79a, cytoplasmic CD22, CD10) Or
Weak CD19 with at least two of the following strongly expressed (CD79a, cytoplasmic CD22, CD10)
Acute leukemia of T-cell Lineage with
aberrant myeloid differentiation

10. PANEL CONSENSUS DIAGNOSIS
INITIAL PROPOSED DIAGNOSIS
Mixed phenotype acute leukemia, favor T/myeloid
Acute leukemia of T-cell Lineage with aberrant myeloid differentiation
PANEL CONSENSUS DIAGNOSIS
EARLY T-CELL PRECURSOR ALL with MYELOID ANTIGEN EXPRESSION

11. NEED FOR A CONSENSUS IN THE CLASSIFICATION SYSTEM
Provide appropriate treatment
Provide appropriate prognostication

12. Treatment and Outcome Hyper CVAD therapy
Matched unrelated donor stem cell transplant
Complications
DVT
New diagnosis of Hepatitis C infection
Clostridium difficile colitis
Reactivation of EBV and BK virus
Subdural hemorrhage
Patient in remission at day 116+ s/p SCT

13. IMMUNOPHENOTYPE (Adapted from WHO 2008)
CD7
CD1a
CD2/CD5
CD3
Cytoplasmic | Surface
CD4/CD8
CD4+
CD8+
Double +
TdT
T-ALL
Mature
T-ALL/LBL can be stratified into different stages of intra-thymic differentiation according to antigens co-expressed
Pro T-ALL
cCD3, CD7 +
CD2-, CD1a-, cd34+/-
Pre-T
Ccd3+, cd7+, cd2+
Cd1a-
Cd34+/-
Cortical T
Cd3+, cd7+, cd2+, cd1a+,
Cd34-
Medullary
Cd3+, cd7+, cd2+, surface cd3+
Cd1a-, cd34-,
Cd4 and cd8 double negative in pro and pre-T
Cd4 and cd8 co-expression in cortical T
Cd4/cd8 either expression in medullary
Early

14. COMMON DIAGNOSTIC FEATURES OF EARLY T-CELL PRECURSOR ALL (ETP-ALL)
Comprises 85-90% of all lymphoblastic lymphoma
Adolescents > Younger children
15% pediatric ALL
25% adult ALL
Presentation:
Mediastinal mass with pleura effusions
Bone marrow involvement if present <20%
High peripheral blood blast counts

15. CLINICAL SIGNIFICANCE OF ETP-ALL
Clinical, laboratory and biologic characteristics not useful in prognostication
HIGH RISK
INDUCTION FAILURE
EARLY RELAPSE
CNS RELAPSE
Children treated as high risk
75% 5 yr-event free survival rate (similar to pre B-ALL/LBL)
The presence of minimal residual disease following therapy is a strong adverse prognostic indicator.

16. DOES MYELOID ANTIGEN EXPRESSION OFFER ANY CLINICAL SIGNIFICANCE?
Asnafi et al
CD13 and CD33 most frequently expressed myeloid-associated antigens
15% of 91 cases reviewed
MPO – negative or very rarely <3%
CD13/Cd33 expression seen in 19 – 32 5 of T-ALL/LBL
Presence of myeloid markers does not indicate MPAL or exclude diagnosis of T-ALL

17. Uckun et al
Not an adverse prognostic factor in childhood ALL

18. Evaluated c-kit expression in 295 ALL patients and in 977 AML patients
T- ALL, 5.4 % expressed c-kit
In AML 84% expressed c-kit
Concluded
High c-kit expression is an independent predictor of
Lower complete response in ALL
Higher complete response in AML
Not an independent predictor of disease free survival in ALL or AML
T-ALL may benefit from AML type therapy

19. Improved survival rates
Normal karyotype
T(10:14)(q24:q11) HOX11:TCRα
Overexpression of HOX11 gene

20. THANK YOU QUESTIONS???

21. REFERENCES
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