- Title
- All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4)
- Creator
- Iland, Harry J.; Bradstock, Ken; Reynolds, John; Di Iulio, Juliana; Tiley, Campbell; Taylor, Kerry; Filshie, Robin; Seldon, Michael; Taper, John; Szer, Jeff; Moore, John; Bashford, John; Supple, Shane G.; Seymour, John F.; Catalano, Alberto; Collins, Marnie; Hertzberg, Mark; Browett, Peter; Grigg, Andrew; Firkin, Frank; Hugman, Amanda
- Relation
- Blood Vol. 120, Issue 8, p. 1570-1580
- Publisher Link
- http://dx.doi.org/10.1182/blood-2012-02-410746
- Publisher
- American Society of Hematology
- Resource Type
- journal article
- Date
- 2012
- Description
- The treatment of acute promyelocytic leukemia has improved considerably after recognition of the effectiveness of all-trans-retinoic acid (ATRA), anthracycline-based chemotherapy, and arsenic trioxide (ATO). Here we report the use of all 3 agents in combination in an APML4 phase 2 protocol. For induction, ATO was superimposed on an ATRA and idarubicin backbone, with scheduling designed to exploit antileukemic synergy while minimizing cardiotoxicity and the severity of differentiation syndrome. Consolidation comprised 2 cycles of ATRA and ATO without chemotherapy, followed by 2 years of maintenance with ATRA, oral methotrexate, and 6-mercaptopurine. Of 124 evaluable patients, there were 4 (3.2%) early deaths, 118 (95%) hematologic complete remissions, and all 112 patients who commenced consolidation attained molecular complete remission. The 2-year rate for freedom from relapse is 97.5%, failure-free survival 88.1%, and overall survival 93.2%. These outcomes were not influenced by FLT3 mutation status, whereas failure-free survival was correlated with Sanz risk stratification (P[trend] = .03). Compared with our previously reported ATRA/idarubicin-based protocol (APML3), APML4 patients had statistically significantly improved freedom from relapse (P = .006) and failure-free survival (P = .01). In conclusion, the use of ATO in both induction and consolidation achieved excellent outcomes despite a substantial reduction in anthracycline exposure.
- Subject
- acute promyelocytic leukemia; all-trans-retinoic acid (ATRA); anthracycline-based chemotherapy; arsenic trioxide (ATO)
- Identifier
- http://hdl.handle.net/1959.13/1325497
- Identifier
- uon:25283
- Identifier
- ISSN:0006-4971
- Language
- eng
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