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

被引:116
作者
Lengfelder, E
Reichert, A
Schoch, C
Haase, D
Haferlach, T
Löffler, H
Staib, P
Heyll, A
Seifarth, W
Saussele, S
Fonatsch, C
Gassmann, W
Ludwig, WD
Hochhaus, A
Beelen, D
Aul, C
Sauerland, MC
Heinecke, A
Hehlmann, R
Wörmann, B
Hiddemann, W
Büchner, T
机构
[1] Heidelberg Univ, Med Klin Mannheim 3, D-68305 Mannheim, Germany
[2] Univ Munster, Dept Hematol Oncol, D-4400 Munster, Germany
[3] Univ Munich, Dept Hematol Oncol, Munich, Germany
[4] Univ Gottingen, Dept Hematol Oncol, D-3400 Gottingen, Germany
[5] Univ Kiel, Dept Hematol Oncol, Kiel, Germany
[6] Univ Cologne, Dept Hematol Oncol, Cologne, Germany
[7] Univ Dusseldorf, Dept Hematol Oncol, D-4000 Dusseldorf, Germany
[8] Univ Vienna, Inst Med Biol, A-1010 Vienna, Austria
[9] Univ Essen Gesamthsch, Klin Knochenmarktransplantat, D-4300 Essen 1, Germany
[10] Humboldt Univ, Robert Rossle Med Ctr, Dept Hematol Oncol, Berlin, Germany
[11] Univ Munster, Dept Biostat, D-4400 Munster, Germany
关键词
acute promyelocytic leukemia; all-trans retinoic acid; high-dose ara-C; double induction; molecular monitoring by RT-PCR;
D O I
10.1038/sj.leu.2401843
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 greater than or equal to 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/RAR alpha 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/RAR alpha (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 followup 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.
引用
收藏
页码:1362 / 1370
页数:9
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