Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic leukemia. German AML Cooperative Group.
A prospective multicenter study was performed to investigate the clinical and molecular results of intensified double induction therapy including high-dose cytarabine (ara-C) in combination with ATRA in newly diagnosed acute promyelocytic leukemia (APL), followed by consolidation and 3 years maintenance therapy. Fifty-one patients, diagnosed and monitored from December 1994 to June 1999, were evaluated. The median age was 43 (16-60) years. The morphologic diagnosis was M3 in 40 (78%) and M3v in 11 (22%) patients. In 15 (30%) patients the initial white blood cell counts were > or =5 x 10(9)/l. The cytogenetic or molecular proof of the translocation t(15;17) was a mandatory prerequisite for eligibility. The diagnosis was confirmed by karyotyping in 46 and by RT-PCR of the PML/RARalpha transcript in 45 cases. The rate of complete hematological remission was 92% and the early death rate 8%. Monitoring of minimal residual disease by RT-PCR of PML/RARalpha (sensitivity 10(-4)) showed negativity in 29 of 32 (91%) evaluable cases after induction, in 23 of 25 (92%) after consolidation, and in 27 of 30 (90%) during maintenance, after a median time of 2, 4 and of 18 months after diagnosis, respectively. After a median follow-up of 27 months, the estimated actuarial 2 years overall and event-free survival were both 88% (79, 97), and the 2 years relapse-free survival 96% (90, 100). The high antileukemic efficacy of this treatment strategy is demonstrated by a rapid and extensive reduction of the malignant clone and by a low relapse rate. The results suggest that the intensity of the induction chemotherapy combined with ATRA is one of the factors which may have a critical influence on the outcome of APL. A randomized trial should assess the value of an induction therapy including ATRA and high-dose ara-C in comparison to standard-dose ara-C.
Lengfelder
E
E
III. Medizinische Klinik Mannheim, University of Heidelberg, Germany.
Reichert
A
A
Schoch
C
C
Haase
D
D
Haferlach
T
T
Löffler
H
H
Staib
P
P
Heyll
A
A
Seifarth
W
W
Saussele
S
S
Fonatsch
C
C
Gassmann
W
W
Ludwig
W D
WD
Hochhaus
A
A
Beelen
D
D
Aul
C
C
Sauerland
M C
MC
Heinecke
A
A
Hehlmann
R
R
Wörmann
B
B
Hiddemann
W
W
Büchner
T
T
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001483:Base Sequence; D003561:Cytarabine / Q000008:administration & dosage; D017931:DNA Primers; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014212:Tretinoin / Q000008:administration & dosage
D017931:DNA Primers; D003561:Cytarabine; D014212:Tretinoin