Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic Leukemia

被引：1285

作者：

Lo-Coco, F. ^{[1
,3
]}

Avvisati, G. ^{[4
]}

Vignetti, M. ^{[5
]}

Thiede, C.

Orlando, S. M.

Iacobelli, S. ^{[2
]}

Ferrara, F.

Fazi, P. ^{[5
]}

Cicconi, L. ^{[1
]}

Di Bona, E. ^{[8
]}

Specchia, G. ^{[9
]}

Sica, S. ^{[10
]}

Divona, M. ^{[11
]}

Levis, A.

Fiedler, W. ^{[27
]}

Cerqui, E. ^{[12
]}

Breccia, M. ^{[13
]}

Fioritoni, G. ^{[14
]}

Salih, H. R. ^{[28
]}

Cazzola, M. ^{[7
,15
]}

Melillo, L. ^{[16
]}

Carella, A. M. ^{[17
]}

Brandts, C. H. ^{[29
]}

Morra, E. ^{[18
]}

von Lilienfeld-Toal, M. ^{[30
]}

Hertenstein, B. ^{[31
]}

Wattad, M. ^{[32
]}

Luebbert, M. ^{[33
]}

Haenel, M. ^{[34
]}

Schmitz, N. ^{[35
]}

Link, H. ^{[36
]}

Kropp, M. G. ^{[19
]}

Rambaldi, A. ^{[20
]}

La Nasa, G. ^{[21
]}

Luppi, M. ^{[22
]}

Ciceri, F. ^{[23
]}

Finizio, O. ^{[24
]}

Venditti, A. ^{[1
]}

Fabbiano, F. ^{[25
]}

Doehner, K. ^{[37
]}

Sauer, M. ^{[26
]}

Ganser, A. ^{[38
]}

Amadori, S. ^{[1
]}

Mandelli, F. ^{[5
,6
]}

Doehner, H. ^{[37
]}

Ehninger, G. ^{[26
]}

Schlenk, R. F. ^{[37
]}

Platzbecker, U. ^{[26
]}

机构：

[1] Univ Roma Tor Vergata, Dipartimento Biomed Prevenzione, Rome, Italy

[2] Univ Roma Tor Vergata, Ctr Biostat Bioinformat, Rome, Italy

[3] Santa Lucia Fdn, Rome, Italy

[4] Univ Campus Biomed, Dipartimento Ematol, Rome, Italy

[5] GIMEMA Data Ctr, Orlando, FL USA

[6] Hlth Outcomes Res Unit, Rome, Italy

[7] Dipartimento Ematol & Trapianto Cellule Staminali, Naples, Italy

[8] Osped S Bortolo, Unita Operat Ematol, Dipartimento Terapie Cellulari Ematol, Vicenza, Italy

[9] Univ Bari, Dipartimento Ematol, Bari, Italy

[10] Univ Cattolica Sacro Cuore, Ist Ematol, Rome, Italy

[11] Policlinico Univ Tor Vergata, Rome, Italy

[12] Spedali Civil Brescia, Dipartimento Ematol, I-25125 Brescia, Italy

[13] Univ Roma La Sapienza, Dipartimento Biotecnol Cellulari Ematol, Rome, Italy

[14] Osped Civile, Dipartimento Ematol, Pescara, Italy

[15] Univ Pavia, Dipartimento Ematol Oncol, IRCCS, I-27100 Pavia, Italy

[16] Osped Casa Sollievo Sofferenza, Div Ematol Trapianto Cellule Staminali, San Giovanni Rotondo, Italy

[17] AOU San Martino IST, IRCCS, UOC Ematologia 1, Genoa, Italy

[18] Ospedale Niguarda Ca Granda, Dipartimento Ematol, Milan, Italy

[19] Azienda Ospedaliera Pugliese Ciaccio, Catanzaro, Italy

[20] USC Ematol Azienda Ospedaliera Papa Giovanni XXII, Bergamo, Italy

[21] Univ Cagliari, Osped R Binaghi, Ctr Trapianti Midollo Osseo, Dipartimento Sci Med, Cagliari, Italy

[22] Univ Modena & Reggio Emilia, Dept Med & Surg Sci, Modena, Italy

[23] Ist Sci San Raffaele, Dipartimento Ematol Trapianto Midollo, Milan, Italy

[24] Osped Cardarelli, Div Ematol TERE, Naples, Italy

[25] Ospedali Riuniti Villa Sofia Cervello, Div Ematol Unita Trapianti Midollo Osseo, Palermo, Italy

[26] Universitatsklin Carl Gustav Carus, Dresden, Germany

[27] Univ Med Ctr Hamburg Eppendorf, Hubertus Wald Univ Canc Ctr, Dept Hematol & Oncol, Hamburg, Germany

[28] Univ Tubingen, Abteilug Hamatol Onkol Rheumatol Immunol & Pulmol, Tubingen, Germany

[29] Goethe Univ Frankfurt, Dept Med Hematol Oncol, D-60054 Frankfurt, Germany

[30] Univ Hosp Bonn, Dept Internal Med 3, Bonn, Germany

[31] Klinikum Bremen Mitte, Med Klin 1, Bremen, Germany

[32] Kliniken Essen Sud, Essen, Germany

[33] Univ Hosp Freiburg, Dept Internal Med 1, Freiburg, Germany

[34] Klinikum Chemnitz, Chemnitz, Germany

[35] Asklepios Klin St Georg Hamburg, Abt Hamatol Onkol & Stammzelltransplantat, Hamburg, Germany

[36] Kaiserslautern, Westpfalzklinikum, Dept Med 1, Kaiserslautern, Germany

[37] Univ Ulm, D-89069 Ulm, Germany

[38] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2013年 / 369卷 / 02期

关键词：

POLYMERASE-CHAIN-REACTION; MINIMAL-RESIDUAL-DISEASE; FUSION GENE TRANSCRIPTS; FRONT-LINE THERAPY; CONSOLIDATION THERAPY; CHEMOTHERAPY; ANTHRACYCLINE; RELAPSE; TRIAL; RISK;

D O I：

10.1056/NEJMoa1300874

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

BACKGROUND All-trans retinoic acid (ATRA) with chemotherapy is the standard of care for acute promyelocytic leukemia (APL), resulting in cure rates exceeding 80%. Pilot studies of treatment with arsenic trioxide with or without ATRA have shown high efficacy and reduced hematologic toxicity. METHODS We conducted a phase 3, multicenter trial comparing ATRA plus chemotherapy with ATRA plus arsenic trioxide in patients with APL classified as low-to-intermediate risk (white-cell count, <= 10x10(9) per liter). Patients were randomly assigned to receive either ATRA plus arsenic trioxide for induction and consolidation therapy or standard ATRA-idarubicin induction therapy followed by three cycles of consolidation therapy with ATRA plus chemotherapy and maintenance therapy with low-dose chemotherapy and ATRA. The study was designed as a noninferiority trial to show that the difference between the rates of event-free survival at 2 years in the two groups was not greater than 5%. RESULTS Complete remission was achieved in all 77 patients in the ATRA-arsenic trioxide group who could be evaluated (100%) and in 75 of 79 patients in the ATRA-chemotherapy group (95%) (P = 0.12). The median follow-up was 34.4 months. Two-year event-free survival rates were 97% in the ATRA-arsenic trioxide group and 86% in the ATRA-chemotherapy group (95% confidence interval for the difference, 2 to 22 percentage points; P<0.001 for noninferiority and P = 0.02 for superiority of ATRA-arsenic trioxide). Overall survival was also better with ATRA-arsenic trioxide (P = 0.02). As compared with ATRA-chemotherapy, ATRA-arsenic trioxide was associated with less hematologic toxicity and fewer infections but with more hepatic toxicity. CONCLUSIONS ATRA plus arsenic trioxide is at least not inferior and may be superior to ATRA plus chemotherapy in the treatment of patients with low-to-intermediate-risk APL.

引用

页码：111 / 121

页数：11

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