Treatment of relapsing acute promyelocytic leukemia by all-trans retinoic acid therapy followed by timed sequential chemotherapy and stem cell transplantation
X. Thomas et al., Treatment of relapsing acute promyelocytic leukemia by all-trans retinoic acid therapy followed by timed sequential chemotherapy and stem cell transplantation, LEUKEMIA, 14(6), 2000, pp. 1006-1013
The purpose of this study was to assess the safety and efficacy of stem cel
l transplantation (SCT) mainly autologous SCT as consolidation therapy in A
PL patients who relapsed and achieved a second complete remission (CR2). Fi
fty adult patients with a first relapsed APL, of whom 39 had been previousl
y treated with ATRA, entered a multicenter trial of oral ATRA until complet
e remission (CR) achievement followed by timed sequential chemotherapy (EMA
combining etoposide 200 mg/m(2)/day for 3 days, mitoxantrone 12 mg/m(2)/da
y for 3 days, and cytarabine 500 mg/m(2)/day for two sequences of 3 days).
EMA was started either after CR achievement, or on day 1 of ATRA because of
initial white blood cell (WBC) counts >5 x 10(9)/l, or rapidly added to AT
RA in order to prevent ATRA syndrome because WBC count increased under ATRA
, Forty-five patients (90%, 95% CI 78%-97%) were in CR after induction ther
apy. Five patients died from infection during aplasia following EMA chemoth
erapy. Eleven patients who achieved CR had a familiar HLA-identical donor a
nd were allografted. The median disease-free survival (DFS) of allografted
patients was 8.2 months. The 34 other CR patients were scheduled for autolo
gous peripheral blood (PB) SCT (intent-to-treat group). Actually, autologou
s transplantation was only carried out in 22 patients (65%) (17 PBSCT and f
ive autologous bone marrow transplantation (BMT)). Reasons for not autograf
ting were early relapse (three patients), severe toxicity of EMA chemothera
py (six patients), and refusal or failure of stem cell harvest (three patie
nts). The 3-year DFS rate of patients actually autografted was 77%. Among t
he 17 autografted patients still in CR2, nine patients have already reached
a longer CR2 than first CR (CR1), Results of detection of PML/RAR alpha by
RT-PCR after autologous transplantation show negative findings in eight of
the nine patients tested. We conclude that (1) ATRA combined to EMA chemot
herapy is effective in the treatment of relapsed APL; (2) allogeneic BMT ma
y be too toxic after salvage treatment including EMA intensive chemotherapy
; (3) clinical outcome of autografted patients and preliminary molecular re
sults regarding detection of PRL/RAR alpha after autologous PBSCT are encou
raging.