Download 205 - SH/EAHP

Denyo Adjoa Zakhia, MD
Kristin Hunt Karner, MD
Henry Ford Hospital, Detroit, MI
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
BONE MARROW ASPIRATE
Cellularity ->95%
Blasts-87%
BONE BIOPSY
H&E
CD1a
FLOW CYTOMETRY
cyto CD3
FLOW CYTOMETRY SUMMARY
Positive antigen panel
Negative antigen panel
cytoCD3
CD3
cytoTDT
CD4
CD2
CD8
CD7
CD5
CD13
CD10
CD15
CD11b
CD34
CD14
CD117
CD16
HLA-DR
CD33
CD56
CD61
CD235a
cytoCD79a
cytoMPO
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
WHAT IS THE DIAGNOSIS?
EGIL
WHO
EGIL
T-lineage:
Score 3.5
Myeloid:
Score 2.5
-
Mixed phenotype acute leukemia, favor T/myeloid
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
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
*NEED FOR A CONSENSUS IN
THE CLASSIFICATION SYSTEM
*Provide appropriate treatment
*Provide appropriate prognostication
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
IMMUNOPHENOTYPE (Adapted from WHO 2008)
CD7
CD1a
CD2/CD5
CD3
CD4/CD8
Cytoplasmic |
Double +
Surface
CD4+
CD8+
TdT
T-ALL
Early
Mature
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
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)
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%
•Uckun et al
•Not an adverse prognostic factor in childhood ALL
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
•Improved survival rates
•Normal karyotype
•T(10:14)(q24:q11) HOX11:TCRα
•Overexpression of HOX11 gene
*
REFERENCES
•Goldberg JM, Silverman LB, Levy DE, et al. Childhood T-cell acute lymphoblastic leukemia: the Dana-
Farber Cancer Institute acute lymphoblastic leukemia consortium experience. J Clin Oncol. 2003;21:36163622.
•Onciu M, Lai R, Vega F, et al. Precursor T-cell acute lymphoblastic leukemia in adults: age-related
immunophenotypic, cytogenetic, and molecular subsets. Am J Clin Pathol. 2002;117:252-258.
•Brunning R, Borowitz M, Matutes E, et al. Precursor B-cell and T-cell neoplasms. In: Jaffe ES, Harris NL,
Stein H, et al, eds. Pathology and Genetics of Tumors of Hematopoietic and Lymphoid Tissues. Lyon,
France: IARC Press; 2001:109-117. World Health Organization Classification of Tumors.
•Thalhammer-Scherrer R, Mitterbauer G, Simonitsch I, et al. The immunophenotype of 325 adult acute
leukemias’: relationship to morphologic and molecular classification and proposal for a minimal screening
program highly predictive for lineage discrimination. Am J Clin Pathol. 2002;117:380-389.
•Asnafi V, Beldjord K, Libura M, et al. Age-related phenotypic and oncogenic differences in T-cell acute
lymphoblastic leukemias may reflect thymic atrophy. Blood. 2004;104:4173-4180.
•Asnafi V, Buzyn A, Thomas X, et al. Impact of TCR status and genotype on outcome in adult T-cell acute
lymphoblastic leukemia: a LALA-94 study. Blood. 2005;105:3072-3078.
•Uckun FM, Sather HN, Gaynon PS, et al. Clinical feature and treatment outcome of children with myeloid
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•Tsao AS, Kantarjian H, Thomas D, et al. C-kit receptor expression in acute leukemias: association with
patient and disease characteristics and with outcome. Leuk Res. 2004;28:373-378.
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blast cell karyotypes with prognosis in childhood T-cell acute lymphoblastic leukemia: a Pediatric
Oncology Group report of 343 cases. Blood. 2000;96:2543-2549.
•X Han, CE Bueso-Ramos. Precursor T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma and
acute biphenotypic leukemias. Am J of clin pathol 2007;127:528-544.
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acute myeloid Leukemias and Undifferentiated leukemias. Blood 1998;15:596-599.