Arsenic trioxide and thalidomide combination produces multi-lineage hematological responses in myelodysplastic syndromes patients, particularly in those with high pre-therapy EVI1 expression.
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.
Raza
Azra
A
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. azra_raza@rush.edu
Buonamici
Silvia
S
Lisak
Laurie
L
Tahir
Sarah
S
Li
Donglan
D
Imran
Mehnaz
M
Chaudary
Nusrat Ijaz
NI
Pervaiz
Hassan
H
Gallegos
J Alejandro
JA
Alvi
M Imran
MI
Mumtaz
Muhammad
M
Gezer
Sefer
S
Venugopal
Parameswaran
P
Reddy
Poluru
P
Galili
Naomi
N
Candoni
Anna
A
Singer
Jack
J
Nucifora
Giuseppina
G
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000473:pathology; D010087:Oxides / Q000627:therapeutic use*; D011519:Proto-Oncogenes; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D013792:Thalidomide / Q000627:therapeutic use*; D014157:Transcription Factors; D016335:Zinc Fingers
D000970:Antineoplastic Agents; D001152:Arsenicals; D004268:DNA-Binding Proteins; D007166:Immunosuppressive Agents; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D010087:Oxides; D014157:Transcription Factors; D013792:Thalidomide; D000077237:Arsenic Trioxide