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

Slides:



Advertisements
Similar presentations
Minimal Residual Disease in Hematologic Neoplasms Lloyd M. Stoolman, M.D. Professor of Pathology and Director, Clinical and Research Flow Cytometry Laboratories.
Advertisements

TA OGUNLESI (FWACP)1 CHILDHOOD LEUKAEMIA. TA OGUNLESI (FWACP)2 LEUKAEMIA Heterogenous group of malignant disorders Characterised by uncontrolled clonal.
A Hematology Case Study about Leukemia by Sarah Wycoff
Acute leukemia Mohammed Al-matrafi.
LEUKEMIA—HEMATOLOGY {S1}
Acute Lymphoblastic Leukemia Maggie Davis Hovda 5/26/2009.
Acute lymphoblastic leukemia (ALL)
Adult acute lymphocytic leukemia Adult acute lymphocytic leukemia Jaya V.Juturi MD 5/5/2004.
ECSI case Fall 2014 Andrea M. Sheehan, MD Associate Professor of Pathology & Immunology Baylor College of Medicine.
Risk Adapted Therapy for ALL 서울아산병원 내과 이 제 환. (Pui CH et al, N Engl J Med 1998;339:605) St. Jude Children’s Research Hospital, 2255 children with ALL,
Leukemias.
Notch1 and pre-T-cell Acute Lymphoblastic Leukemia (T-ALL) by Lindsey Wilfley.
Acute Leukaemia Dr. Soheir Adam, MRCPath Assistant Professor Department of Haematology, KAUH.
Acute lymphoblastic leukemia (ALL)
Acute myeloid leukemia: morphology and beyond
ACUTE MYELOID LEUKEMIA Irit Avivi
Identification and Diagnosis of the Acute Leukemias
ICCS e-Newsletter CSI Winter 2013
LEUKEMIAS Dr Mehboob Khan Pathologist
Acute leukemia Aggressive malignant hematopoietic disorders
Acute Myeloid Leukemia
Flow Cytometric Abnormalities in Myelodysplastic Syndrome Raida Oudat,MD Consultant Hematopathologist at Princess Iman Research and Laboratory Sciences.
In The name of God.  CD117 is a 145 kD protein tyrosine kinase also known as c- Kit.  Receptor for stem cell factor or c-Kit ligand.  CD117 is expressed.
Clinical Characteristics and Treatment Outcome of Childhood Acute Lymphoblastic Leukemia With the t(4;ll) (q21;q23) By Ching-Hon Pui, Lawrence S. Frankel,
Challenges and Considerations in Linking Adult and Pediatric Leukemias David G. Poplack M.D. Texas Children’s Cancer Center Baylor College of Medicine.
Products of haematopoiesis. Leukaemia, the current hypothesis Defect in maturation of white blood cells-may involve a block in differentiation and/or.
The acute Leukemias are clonal hematopoietic malignant disease that arise from the malignant T r a n s f o r m a t i o n of an early Hematopoietic stem.
Heterogeneity of Abnormal RUNX1 Leading to Clinicopathological Variations in Childhood B-Lymphoblastic Leukemia Xiayuan Liang, MD Department of Pathology.
ICCS e-Newsletter CSI Spring 2015 Prashanti Reddy, M.D., M.S. Senior Staff Hematopathologist Genoptix, Inc., a Novartis company.
Pei Lin, MD Department of Hematopathology UT M.D. Anderson Cancer Center, Houston, TX Monitoring of Minimal Residual Disease Principles and Applications.
Migle Janeliuniene, MD, PhD Lithuania Teaching/research/clinical Associate, Specialist Vilnius University Hospital Santariskiu Klinikos Santariskiu 2 LT
Myeloproliferative Disorders (MPDs)
MOLECULAR GENETICS and LEUKEMIA Clive S. Zent M.D. Division of Hematology/Oncology.
Characteristics Useful for the Diagnosis and Classification of Non-Lymphoid Neoplasms Gross Pathology Counts and Cytology Blood Bone Marrow Lineage Assessment.
4th Year Medical Student KAU
Blood Cancers in older adults Cancer and Older Adults 19 November 2015 Matthew Foster, MD Assistant Professor of Medicine Leukemia, Lymphoma and Myeloma.
Single-Agent Lenalidomide Induces Complete Remission of Acute Myeloid Leukemia in Patients with Isolated Trisomy 13 Fehniger TA et al. Blood 2009;113(5):
MLAB 1415: Hematology Keri Brophy-Martinez
Acute Leukemia Kristine Krafts, M.D..
Case report Sudden blastic transformation in patient with chronic myeloid leukemia treated with imatinib mesylate Mehrdad Payandeh,MD Hematology, Medical.
Case 297 Guilin Tang and Sa A. Wang Department of Hematopathology UT MD Anderson Cancer Center.
Minimal Residual Disease(MRD) detections by Flow Cytometry in Acute Leukemia 혈액학파트 안 미 숙.
Case 251: Clinical Information Raymond E Felgar, MD, PhD University of Pittsburgh, Pittsburgh, PA 45-year-old man with recent history of shingles, night.
Acute lymphoblastic leukemia in children
Case 255 Elizabeth Courville, MD Robert Hasserjian, MD Massachusetts General Hospital Society for Hematopathology/European Association for Haematopathology.
Society for Hematopathology/ European Association for Haematopathology 2013 Workshop Case 145 Nidhi Aggarwal, M.D.; Robert L. Redner, MD; Fiona E. Craig,
Case 398 Submitting Author: Hutchison, Robert E, MD Institution: SUNY Upstate Medical University Additional authors: Constance K. Stein, Ph.D., Theresa.
Society for Hematopathology/European Association for Haematopathology 2013 Case Number 208 Erika Moore, MD; Darshan Roy, MD; Patti Cohen, MD; Adam Bagg,
SH/EAHP Workshop 2013 Case 93 Winnie Wu, M.D. Sheeja Pullarkat, M.D.
SH/EAHP 2013 Workshop Case 285 Sara-Eloína Cuadra-Acree, MD,* Kiran Qidwai, MD,* Brit Shackley, MD,** & Imran N. Siddiqi, MD, PhD* * University of Southern.
CASE 411 Jose Gonzalez-Berjon, MD & Tariq Muzzafar, MD UT M.D. Anderson Cancer Center.
ICCS e-Newsletter CSI Fall 2015 Hywyn R. O. Churchill, MD PhD Division of Hematopathology.
eCSI case Weijie Li, MD Department of Pathology & Laboratory Medicine
Rebecca L. King, Gerald Wertheim, Michele E. Paessler
Acute Leukemia Kristine Krafts, M.D..
eCSI case 2 – November 2016 Jyotinder Nain Punia, MD
CASE SUBMISSION 2016 EAHP BM Workshop
Acute Myeloid Leukemia
CLINICAL PROGRESSION INTRODUCTION METHOD CONCLUSION REFERENCES
Clinical history 30-years-old female
Image 1 Detection of minimal residual disease (MRD) in consecutive bone marrow (BM) samples from a patient with relapse (A) and a patient still in remission.
Early T-Cell Precursor ALL in 5 Year Old Female
Building better therapy for children with acute lymphoblastic leukemia
Leukemia Case 1.
Acute Myeloid Leukemia
IMMUNOPHENOTYPING LEUKEMIAS AND LYMPHOMAS
Diagnostic Hematology
Acute Leukemia Dr. Noha Noufal.
Neoplastic disorder.
RITUXIMAB IN B-LINEAGE ADULT ACUTE LYMPHOBLASTIC LEUKAEMIA
Presentation transcript:

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

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

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

FLOW CYTOMETRY cyto CD3

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

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

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

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

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

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 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

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

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.

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

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

THANK YOU QUESTIONS???

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;21:3616- 3622. 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 antigen positive acute lymphoblastic leukemia: a report from the Children’s Cancer Group. Blood. 1997;90:28-35. 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. Ferrando AA, Neuberg DS, Dodge RK, et al. Prognostic importance of TLX1 (HOX11) oncogene expression in adults with T-cell acute lymphoblastic leukaemia. Lancet. 2004;363:535-536. Schneider NR, Carroll AJ, Shuster JJ, et al. New recurring cytogenetic abnormalities and association of 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. Bene MC, Bernier RO, Casasnovas G, et al. The reliability and specificity of c-kit for the diagnosis of acute myeloid Leukemias and Undifferentiated leukemias. Blood 1998;15:596-599.