European Association for Haematopathology 2013 Workshop Case 145 Nidhi Aggarwal MD Robert L Redner MD Fiona E Craig MD University of Pittsburgh Medical Center Clinical History 73 yearold male with history of a highgrade sarcoma of the thigh diagnosed January 2012 status post ID: 649291
Download Presentation The PPT/PDF document "Society for Hematopathology/" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Society for Hematopathology/ European Association for Haematopathology 2013 Workshop Case 145
Nidhi Aggarwal, M.D.; Robert L. Redner, MD; Fiona E. Craig, M.D.
University of Pittsburgh Medical CenterSlide2
Clinical History73 year-old male with history of a high-grade sarcoma of the thigh diagnosed January 2012, status post chemotherapy [Adjuvant Adriamycin (Doxorubicin) and Ifosfamide). Acute myeloid leukemia diagnosed November 2012.
Enrolled in phase 1 trial ATRA plus Dasatinib (UPCI 08-160).
Bone marrow obtained day 28 status post chemotherapy .Slide3
Peripheral smear
Patient
value
Reference
range
WBC
0.5X10^9/l
3.8-10.6
Hemoglobin
9.7g/dl
12.9-16.9
Platelet
9X10^9/l
156-369
Polys
16% (0.08X10^9/l)
2.24-7.68
Lymphocytes
82% (0.41X10^9/l)
0.8-3.65
Monocytes
2% (0.01X10^9/l)
0.3-0.9Slide4
Bone marrow aspirate: 84% blastsSlide5
CD14 -
CD36,CD64 +
CD15,CD33 +
HLA-DR +
CD117 -
CD34 -
SSC
CD4 +
MPO +Slide6
Butyrate esterase
Butyrate esterase with fluorideSlide7
t(8;16)(p11;p13)Slide8
Bone marrow biopsy
day 28 status post therapy
Bone marrow biopsy
at the start of therapySlide9
SH/ EAHP Case 145:Persistent therapy-related AML with t(8;16) (p11;p13).Receiving novel therapy (protocol UPCI 08-160) with ATRA and escalating doses of Dasatinib
Started on Decitabine therapy on 01/28/2013
The patient died on 03/11/2013.
Follow-up:Slide10
AML with t(8;16) (p11;p13)Rare distinct subtype of AML (<1% of all AML).
Atlas of Genetic and
C
ytogenetics
in Oncology and
Haematology
Translocation inhibits
RUNX1 regulated transcription,
leading
to differentiation block
.
Chr
8: MYST3
/
MOZ
Chr
16: CERBBP
/
CBP Slide11
Younger patients including infants More common in women (?)More frequent in therapy related AML than de novo AMLShort latency (6-23months)Absence of preceding
MDS
Extramedullary
disease especially skin
may precede
bone marrow
involvement.
Relatively
high rate of
DIC
Extremely
poor
prognosis
Disease
free survival very short ~3-4 months & overall survival 8-9
months
Rare spontaneous remission in infants
AML with t(8;16) - Clinical featuresSlide12
AML with t(8;16) - Pathologic featuresMonocytoid/ myelomonocytoid differentiationMorphologic features can overlap with Acute promyelocytic leukemia
Erythrophagocytosis
Immunophenotype
shows myeloid and monocytic markers, and usually CD34 negative and CD117 negative
A few
known collaborating somatic genetic alterations.
J
Clin
Oncol
(1993)11:2370-2379;
Leukemia
Research (
2013
)
37:
32-36; Leukemia (2009) 23:934–943Slide13
ATRA classically used to induce differentiation in APL EGFR inhibitors (Erlotinib/ Gefitinib) combined with naturally occurring pro-differentiation agents (ATRA or Vitamin D) helps differentiation of AML [Cell Cycle. 2013;(12):18].
Epigenetic modification
[
Clin
Epigenetics.
2013;5(1
):
12]
Histone
deacetylase
inhibitor:
Valproic
acid
DNA methylation inhibitors
Furazolidone
has been investigated as a differentiation agent for
AML
[
PLoS One. 2013;8(8):e72335. doi: 10.1371/ journal.pone.0072335.
eCollection 2013].
Therapeutic induction of differentiation .Slide14
Patient with AML-M5
CD11b: Marker for differentiation
Induction of differentiation
with
ATRA
&
Dasatinib
Src
family kinase
(SFK), overexpressed in AML, is a negative regulator of ATRA-induced differentiation
Dasatinib
inhibits ABL and
Src
family kinase (SFK)Slide15
UPCI 08-160 protocol: Dasatinib and All-Trans Retinoic Acid for Relapsed/Refractory and/or Elderly Patients with Acute Myeloid Leukemia (AML)Non induction candidate elderly male (>65yrs).Relapsed/Refractory AML:Failed 2 inductions, or relapsed within 6months. If relapse after >6 months - failed 2 inductions.
AML after MDS/
MPN
and after chemotherapy also considered).
Fixed dose ATRA with escalating doses of Dasatinib.Slide16
DiagnosisProposed DiagnosisPersistent acute myeloid leukemia with monocytic differentiation and t(8;16), likely therapy related. Consensus DiagnosisTherapy-related myeloid leukemia, acute myeloid leukemia (
monocytic
) with t(8;16)(p11;p13)