Arsenic trioxide and thalidomide combination produces multi-lineage hematological responses in myelodysplastic syndromes patients, particularly in those with high pre-therapy EVI1 expression

Raza, Azra; Buonamici, Silvia; Lisak, Laurie; Tahir, Sarah; Li, Donglan; Imran, Mehnaz; Chaudary, Nusrat Ijaz; Pervaiz, Hassan; Gallegos, J.Alejandro; Alvi, M.Imran; Mumtaz, Muhammad; Gezer, Sefer; Venugopal, Parameswaran; Reddy, Poluru; Galili, Naomi; Candoni, Anna; Singer, Jack; Nucifora, Giuseppina

doi:10.1016/j.leukres.2003.11.018

« Previous Next »Leukemia Research
Volume 28, Issue 8 , Pages 791-803, August 2004

Arsenic trioxide and thalidomide combination produces multi-lineage hematological responses in myelodysplastic syndromes patients, particularly in those with high pre-therapy EVI1 expression

Azra Raza
- Section of Myeloid Diseases and MDS Center, Rush University, Rush-Presbyterian-St. Luke’s Medical Center, 2242 West Harrison Street, Suite 108, Chicago, IL 60612-3515, USA
- Corresponding author. Tel.: +1-312-563-4500; fax: +1-312-563-4170.
Silvia Buonamici
- Department of Pathology, University of Illinois, Chicago, IL, USA
Laurie Lisak
- Section of Myeloid Diseases and MDS Center, Rush University, Rush-Presbyterian-St. Luke’s Medical Center, 2242 West Harrison Street, Suite 108, Chicago, IL 60612-3515, USA
Sarah Tahir
- Section of Myeloid Diseases and MDS Center, Rush University, Rush-Presbyterian-St. Luke’s Medical Center, 2242 West Harrison Street, Suite 108, Chicago, IL 60612-3515, USA
Donglan Li
- Section of Myeloid Diseases and MDS Center, Rush University, Rush-Presbyterian-St. Luke’s Medical Center, 2242 West Harrison Street, Suite 108, Chicago, IL 60612-3515, USA
Mehnaz Imran
- Section of Myeloid Diseases and MDS Center, Rush University, Rush-Presbyterian-St. Luke’s Medical Center, 2242 West Harrison Street, Suite 108, Chicago, IL 60612-3515, USA
Nusrat Ijaz Chaudary
- Section of Myeloid Diseases and MDS Center, Rush University, Rush-Presbyterian-St. Luke’s Medical Center, 2242 West Harrison Street, Suite 108, Chicago, IL 60612-3515, USA
Hassan Pervaiz
- Section of Myeloid Diseases and MDS Center, Rush University, Rush-Presbyterian-St. Luke’s Medical Center, 2242 West Harrison Street, Suite 108, Chicago, IL 60612-3515, USA
J.Alejandro Gallegos
- Section of Myeloid Diseases and MDS Center, Rush University, Rush-Presbyterian-St. Luke’s Medical Center, 2242 West Harrison Street, Suite 108, Chicago, IL 60612-3515, USA
M.Imran Alvi
- Section of Myeloid Diseases and MDS Center, Rush University, Rush-Presbyterian-St. Luke’s Medical Center, 2242 West Harrison Street, Suite 108, Chicago, IL 60612-3515, USA
Muhammad Mumtaz
- Section of Myeloid Diseases and MDS Center, Rush University, Rush-Presbyterian-St. Luke’s Medical Center, 2242 West Harrison Street, Suite 108, Chicago, IL 60612-3515, USA
Sefer Gezer
- Section of Myeloid Diseases and MDS Center, Rush University, Rush-Presbyterian-St. Luke’s Medical Center, 2242 West Harrison Street, Suite 108, Chicago, IL 60612-3515, USA
Parameswaran Venugopal
- Section of Myeloid Diseases and MDS Center, Rush University, Rush-Presbyterian-St. Luke’s Medical Center, 2242 West Harrison Street, Suite 108, Chicago, IL 60612-3515, USA
Poluru Reddy
- Section of Myeloid Diseases and MDS Center, Rush University, Rush-Presbyterian-St. Luke’s Medical Center, 2242 West Harrison Street, Suite 108, Chicago, IL 60612-3515, USA
Naomi Galili
- Section of Myeloid Diseases and MDS Center, Rush University, Rush-Presbyterian-St. Luke’s Medical Center, 2242 West Harrison Street, Suite 108, Chicago, IL 60612-3515, USA
Anna Candoni
- Section of Myeloid Diseases and MDS Center, Rush University, Rush-Presbyterian-St. Luke’s Medical Center, 2242 West Harrison Street, Suite 108, Chicago, IL 60612-3515, USA
Jack Singer
- Cell Therapeutics Inc., Seattle, Washington, USA
Giuseppina Nucifora
- Department of Pathology, University of Illinois, Chicago, IL, USA

Abstract

Twenty-eight myelodysplastic syndromes (MDS) patients were treated with arsenic trioxide (ATO) and thalidomide. Seven patients responded including one complete hematologic and cytogenetic response and one with regression in spleen size. Two trilineage responses were seen in patients with inv(3)(q21q26.2). Three of five patients who had high pre-therapy EVI1 levels showed unexpectedly good responses while two died early in the first cycle. In vitro studies using 32Dcl3 cells forced to express EVI1 confirmed increased sensitivity of these cells to ATO. Both low/high risk MDS may benefit significantly from therapy with ATO/thalidomide, and those with high pre-therapy EVI1 expression may be uniquely sensitive.

Keywords: Asenic trioxide, Talidomide, Melodysplastic syndromes, EVI1, Agiogenesis, Aoptosis