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

来源：

LEUKEMIA | 2000年 / 14卷 / 08期

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

页码：1362 / 1370

页数：9