Abstract Types

CRA
Clinical Review Abstract

LBA
Late-Breaking Abstract

TPS
Trials in Progress Abstract

e
Abstracts selected for publication but not presentation at the Annual Meeting

^
Abstracts granted an exception in accordance with ASCO's Conflict of Interest Policy



Frequency of rare cytogenetic abnormalities at relapse in acute myeloid leukemia (AML) with FLT3 internal tandem duplication (ITD) and normal karyotype at diagnosis: Evidence for genomic instability?

Sub-category:
Leukemia

Category:
Leukemia, Myelodysplasia, and Transplantation

Meeting:
2013 ASCO Annual Meeting

Abstract No:
7049

Citation:
J Clin Oncol 31, 2013 (suppl; abstr 7049)

Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2013 Annual Meeting but not presented at the Meeting, can be found online only.

Author(s): Theodore Stewart Gourdin, Yi Ning, Feyruz Rassool, Michael Tidwell, Vu Duong, Ashkan Emadi, Maria R. Baer; University of Maryland, Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD

Abstract Disclosures


Abstract:

Background: FLT3-ITD mutations are present in AML in 30% of patients, most commonly with a normal karyotype, and are associated with short disease-free survival. In vitro and in vivo studies of FLT3-ITD cell lines and patient samples have demonstrated DNA double-strand break repair by an alternative highly error-prone form of non-homologous end-joining (ALT NHEJ), resulting in illegitimate ligation of non-contiguous DNA breaks, causing DNA deletions and translocations that may contribute to disease progression. To look for clinical evidence of genomic instability, we reviewed cytogenetic changes at relapse. Methods: Charts of patients with cytogenetically normal AML with FLT3-ITD treated at the University of Maryland Greenebaum Cancer Center were reviewed along with metaphase analysis results at diagnosis and relapse. Results: Cytogenetic data were available from first and, when applicable, subsequent relapses for 12 patients with cytogenetically normal AML with FLT3-ITD who relapsed, including 5 following allogeneic hematopoietic stem cell transplantation (allo HSCT). Ten patients acquired cytogenetic changes, many of them rare translocations and inversions (Table). Conclusions: AML with FLT3-ITD and normal karyotype at diagnosis has a high frequency of rare cytogenetic abnormalities at relapse, providing clinical evidence for genomic instability. These data may support the potential therapeutic role of inhibitors of ALT NHEJ repair proteins, such as PARP1 and DNA ligase IIIa, in AML with FLT3-ITD.

Karyotypes at relapse (*after allo HSCT).
46,XY,t(2;14)(p23;q24)[2]/46,XY[18]
46,XX,t(4;4)(q21;q35)[7]/46,XX[13]
46,XX,t(5;13)(q31;q12)[20]*
46,XX,inv(9)(q22q32)[20]
46,XY,t(9;22)(q34;q11.2)[4]/46,XY[8]
46,XY,inv(10)(p11.2q21.2)[12]/46,XY[8]*
46,XY,t(10;13)(q10;q10)[9]/46,XY[9]//46,XX[2]*
47,XY,+21[10]/46,XY[10]*
46,X,t(X;10)(q13;q24),t(3;14)(p21;q11.2),t(12;17)(p12;q12)[15]//46,XY[5]*
45,XX,der(2)t(2;?)(q21;?),del(3)(q12),der(6)t(6;?)(p22;?),der(7)t(7;?)
(p15;?),-17,-22,+mar[19]/46,XX[1]

 

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2. Final results of a phase I study of idelalisib (GSE1101) a selective inhibitor of PI3Kδ, in patients with relapsed or refractory CLL.

Meeting: 2013 ASCO Annual Meeting Abstract No: 7003 First Author: J. R. Brown
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3. Obinutuzumab (GA101) plus chlorambucil (Clb) or rituximab (R) plus Clb versus Clb alone in patients with chronic lymphocytic leukemia (CLL) and preexisting medical conditions (comorbidities): Final stage 1 results of the CLL11 (BO21004) phase III trial.

Meeting: 2013 ASCO Annual Meeting Abstract No: 7004 First Author: V. Goede
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