Low-dose decitabine plus all-trans retinoic acid in patients with myeloid neoplasms ineligible for intensive chemotherapy.
In our previous in vitro trials, decitabine and all-trans retinoic acid (ATRA) demonstrated synergistic effects on growth inhibition, differentiation, and apoptosis in SHI-1 cells; in K562 cells, ATRA enhanced the effect of decitabine on p16 demethylation, and the combination of the two drugs was found to activate RAR-β expression (p16 and RAR-β are two tumor suppressor genes). On the rationale of our in vitro trials, we used low-dose decitabine and ATRA to treat 31 myeloid neoplasms deemed ineligible for intensive chemotherapy. The regimen consisted of decitabine at the dose of 15 mg/m(2) intravenously over 1 h daily for consecutive 5 days and ATRA at the dose of 20 mg/m(2) orally from day 1 to 28 except day 4 to 28 in the first cycle, and the regimen was repeated every 28 days. After 6 cycles, decitabine treatment was stopped, and ATRA treatment was continued for maintenance treatment. Treated with a median of 2 cycles (range 1-6), 7 patients (22.6 %) achieved complete remission (CR), 7 (22.6 %) marrow CR (mCR), and 4 (12.9 %) partial remission (PR). The overall remission (CR, mCR, and PR) rate was 58.1 %, and the best response (CR and mCR) rate was 45.2 %. The median overall survival (OS) was 11.0 months, the 1-year OS rate was 41.9 %, and the 2-year OS rate was 26.6 %. In univariate analyses, age, performance status, comorbidities, white blood cell counts and platelets at diagnosis, percentage of bone marrow blasts, karyotype, and treatment efficacy demonstrated no impacts on OS (P > 0.05, each). Main side effects were tolerable hematologic toxicities. In conclusion, low-dose decitabine plus ATRA is a promising treatment for patients with myeloid neoplasms judged ineligible for intensive chemotherapy.
Department of Hematology, The Third Affiliated Hospital of Suzhou University, The First People's Hospital of Changzhou, Changzhou, Jiangsu Province, People's Republic of China, 213003.
Wei
W
Wu
Department of Hematology, The Third Affiliated Hospital of Suzhou University, The First People's Hospital of Changzhou, Changzhou, Jiangsu Province, People's Republic of China, 213003.
Yan
Y
Lin
Department of Hematology, Xuzhou Central Hospital, Xuzhou, Jiangsu Province, People's Republic of China, 221009.
Lili
L
Xiang
Department of Hematology, The Third Affiliated Hospital of Suzhou University, The First People's Hospital of Changzhou, Changzhou, Jiangsu Province, People's Republic of China, 213003.
Weimin
W
Dong
Department of Hematology, The Third Affiliated Hospital of Suzhou University, The First People's Hospital of Changzhou, Changzhou, Jiangsu Province, People's Republic of China, 213003.
Xiaoying
X
Hua
Department of Hematology, The Third Affiliated Hospital of Suzhou University, The First People's Hospital of Changzhou, Changzhou, Jiangsu Province, People's Republic of China, 213003.
Yun
Y
Ling
Department of Hematology, The Third Affiliated Hospital of Suzhou University, The First People's Hospital of Changzhou, Changzhou, Jiangsu Province, People's Republic of China, 213003.
Haiqian
H
Li
Department of Hematology, The Third Affiliated Hospital of Suzhou University, The First People's Hospital of Changzhou, Changzhou, Jiangsu Province, People's Republic of China, 213003.
Feng
F
Yan
Department of Hematology, The Third Affiliated Hospital of Suzhou University, The First People's Hospital of Changzhou, Changzhou, Jiangsu Province, People's Republic of China, 213003. czxxb1098@163.com.|Department of Hematology, The First People's Hospital of Changzhou, Third Affiliated to Suzhou University, Changzhou, 213003, China. czxxb1098@163.com.
Xiaobao
X
Xie
Department of Hematology, The Third Affiliated Hospital of Suzhou University, The First People's Hospital of Changzhou, Changzhou, Jiangsu Province, People's Republic of China, 213003. guweiying2001@163.com.|Department of Hematology, The First People's Hospital of Changzhou, Third Affiliated to Suzhou University, Changzhou, 213003, China. guweiying2001@163.com.
Weiying
W
Gu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy*; D014212:Tretinoin / Q000008:administration & dosage*
D000964:Antimetabolites, Antineoplastic; D014212:Tretinoin; D000077209:Decitabine; D001374:Azacitidine
Acute myeloid leukemia; All-trans retinoic acid; Decitabine; Myelodysplastic syndromes