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
J. Hu et al., 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, INT J HEMAT, 70(4), 1999, pp. 248-260
Objective: All-trans-retinoic acid (ATRA), chemotherapy, and arsenic trioxi
de (As2O3) have been found to be effective in the treatment of acute promye
locytic leukemia (APL). Here we present a single institutional retrospectiv
e study with longterm 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.
Patients and methods: Newly diagnosed patients with APL entering complete r
emission were followed up for 3 to 95 months (n = 120). Univariate and mult
ivariate analyses were performed to identify potential prognostic factors,
including age and sex; initial white blood cell (WBC) count and peak WBC le
vel of hyperleukocytosis during induction therapy; dose of ATRA in inductio
n; days from induction therapy to remission; postremission therapy, type of
PML-RAR alpha isoform; and follow-up of reverse transcription-polymerase c
hain reaction (RT-PCR).
Results: The median relapse-free survival (RFS) was 26 months, and median o
verall 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 gr
eater than or equal to 20 X 10(9)/l), peak level of WBC during induction: a
nd type of postremission therapy were significantly related to survival. Ou
r multivariate study showed that only peak level of WBC count during induct
ion 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 ente
ring remission and survival after relapse.
Conclusion: Through this retrospective study with long term follow-up, some
conclusions can be drawn: I) 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 chemoth
erapy and ATRA is better than chemotherapy or ATRA alone as postremission t
herapy, 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. (C) 1999 The
Japanese Society of Hematology.