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Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic leukemia

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 mainten...

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Main Authors: Lengfelder, Eva (Author) , Reichert, A. (Author) , Haferlach, Claudia (Author) , Haase, D. (Author) , Haferlach, T. (Author) , Löffler, H. (Author) , Staib, P. (Author) , Heyll, A. (Author) , Seifarth, Wolfgang (Author) , Saußele, Susanne (Author) , Fonatsch, C. (Author) , Gassmann, Winfried (Author) , Ludwig, Wolf-Dieter (Author) , Hochhaus, Andreas (Author) , Beelen, D. (Author) , Aul, C. (Author) , Sauerland, M.-C. (Author) , Heinecke, A. (Author) , Hehlmann, Rüdiger (Author) , Wörmann, B. (Author) , Hiddemann, W. (Author) , Büchner, T. (Author)
Format: Article (Journal)
Language:English
Published: 04 August 2000
In: Leukemia
Year: 2000, Volume: 14, Issue: 8, Pages: 1362-1370
ISSN:1476-5551
DOI:10.1038/sj.leu.2401843
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/sj.leu.2401843
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/2401843
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Author Notes:E. Lengfelder, A. Reichert, C. Schoch, D. Haase, T. Haferlach, H. Löffler, P. Staib, A. Heyll, W. Seifarth, S. Saussele, C. Fonatsch, W. Gassmann, W.-D. Ludwig, A. Hochhaus, D. Beelen, C. Aul, M.-C. Sauerland, A. Heinecke, R. Hehlmann, B. Wörmann, W. Hiddemann, T. Büchner
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Summary: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 ⩾5 × 109/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/RARα 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/RARα (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.
Item Description:Gesehen am 13.04.2022
Physical Description:Online Resource
ISSN:1476-5551
DOI:10.1038/sj.leu.2401843

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