Long-term survival and prognostic study in acute promyelocytic leukemia treated with all-trans-retinoic acid, chemotherapy, and As2O3: an experience of 120 patients at a single institution.
OBJECTIVE
All-trans-retinoic acid (ATRA), chemotherapy, and arsenic trioxide (As2O3) have been found to be effective in the treatment of acute promyelocytic leukemia (APL). Here we present a single institutional retrospective study with long-term follow-up to better define the prognostic factors and a rationale for the use of ATRA, chemotherapy, and As2O3 in the treatment of newly diagnosed and relapsed APL patients.


METHODS
Newly diagnosed patients with APL entering complete remission were followed up for 3 to 95 months (n = 120). Univariate and multivariate analyses were performed to identify potential prognostic factors, including age and sex; initial white blood cell (WBC) count and peak WBC level of hyperleukocytosis during induction therapy; dose of ATRA in induction; days from induction therapy to remission; postremission therapy; type of PML-RAR alpha isoform; and follow-up of reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
The median relapse-free survival (RFS) was 26 months, and median overall survival (OS) was still not reached. The estimated 5-year RFS and OS were 34.0% +/- 6.0% and 52.5% +/- 7.9%, respectively. Initial WBC count (> or = 20 x 10(9)/l), peak level of WBC during induction, and type of postremission therapy were significantly related to survival. Our multivariate study showed that only peak level of WBC count during induction therapy and type of postremission therapy were associated with RFS and that initial WBC count was associated with OS. In relapsed patients, As2O3 was very effective and remained as the most important factor for their entering remission and survival after relapse.


CONCLUSIONS
Through this retrospective study with long-term follow-up, some conclusions can be drawn: 1) Low-dose ATRA is as effective as the standard dose in terms of survival; 2) Initial and peak levels of WBC count during induction therapy are associated with survival; 3) A combination of chemotherapy and ATRA is better than chemotherapy or ATRA alone as postremission therapy; 4) Patients with the long form of PML-RAR alpha tend to have a more favorable OS but not RFS when compared with patients with the short form; 5) Persistent negative RT-PCR in remission is associated with favorable RFS and OS; 6) As2O3 is an effective agent for relapsed patients.
Hu
J
J
Shanghai Institute of Hematology, Department of Hematology, RuiJin Hospital, Shanghai Second Medical University, People's Republic of China.
Shen
Z X
ZX
Sun
G L
GL
Chen
S J
SJ
Wang
Z Y
ZY
Chen
Z
Z
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000008:administration & dosage; D015514:Oncogene Proteins, Fusion / Q000008:administration & dosage; D010087:Oxides / Q000008:administration & dosage; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014212:Tretinoin / Q000008:administration & dosage
D001152:Arsenicals; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D010087:Oxides; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin; D000077237:Arsenic Trioxide