Evidence of myeloid differentiation in non-M3 acute myeloid leukemia treated with the retinoid X receptor agonist bexarotene.
All-trans-retinoic acid has dramatically changed the treatment paradigm for acute promyelocytic leukemia, however, it has no significant activity in non-M3 acute myeloid leukemia (AML). In vitro, bexarotene, a retinoid X receptor agonist inhibits the proliferation of non-M3 AML cell lines and induces differentiation of leukemic blasts from patients. We hypothesized that there may be similar activity in patients with AML. We report on two patients with relapsed or refractory non-M3 AML treated with bexarotene monotherapy. After initiating treatment, both patients showed leukemic differentiation in their peripheral blood and reduction in bone marrow blasts to less than 5%. One patient had a significant improvement in her platelet count with loss of platelet transfusion needs. Differentiation syndrome occurred in one patient and was successfully treated with steroids and discontinuation of bexarotene. These data suggest that bexarotene has clinical activity in non-M3 AML and may be able to induce myeloid differentiation in vivo.
Tsai
Donald E
DE
Hematology-Oncology Division, Department of Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, USA. detsai@mail.med.upenn.edu
Luger
Selina M
SM
Kemner
Allison
A
Swider
Cezary
C
Goradia
Ami
A
Tomczak
Ewa
E
DiPatri
Doris
D
Bagg
Adam
A
Nowell
Peter
P
Loren
Alison W
AW
Perl
Alexander
A
Schuster
Stephen
S
Thompson
James E
JE
Porter
David
D
Andreadis
Charlambos
C
Stadtmauer
Edward A
EA
Goldsteini
Steven
S
Ghalie
Richard
R
Carroll
Martin
M
D000208:Acute Disease; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000077610:Bexarotene; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects; D047488:Retinoid X Receptors / Q000819:agonists*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene