All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results.
All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results.
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DOI：
10.1182/blood.v76.9.1704.bloodjournal7691704
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发表时间：
1990-11
期刊：
影响因子：
20.3
通讯作者：
S. Castaigne;C. Chomienne;Danielson Mt;P. Ballerini;R. Berger;P. Fenaux;L. Degos
中科院分区：
文献类型：
--
作者：
S. Castaigne;C. Chomienne;Danielson Mt;P. Ballerini;R. Berger;P. Fenaux;L. Degos
用全反式维甲酸（RA，45 mg/m2/d）治疗急性早幼粒细胞白血病22例，疗程90天。在这22名患者中，4名患者以前未经治疗，2名患者在常规化疗后耐药，16名患者首次（n = 11）、第二次（n = 4）或第三次（n = 1）复发。我们观察到14例完全缓解、4例短暂缓解、1例失败和3例早期死亡。完全应答者的住院时间和输血次数显著减少。纠正凝血障碍和白细胞增加是全反式RA疗效的第一个迹象。在第0、15、30、45、60和90天进行的形态学分析显示，获得了完全缓解，没有骨髓（BM）发育不全。成熟细胞中存在奥尔杆证实了处理的分化效果。在缓解期，t（15;17）最初存在于20例患者中未发现。体外研究显示，在18例受试病例中，16例存在全反式RA分化。体外对全反式RA无应答者在体内无应答。RA治疗的副作用-皮肤和粘膜干燥，高甘油三酯血症，肝转氨酶升高-经常被注意到。我们还观察到11例患者的骨痛和4例患者的高白细胞血症。无论维持治疗包括低剂量化疗或全反式RA，观察早期复发。5例患者在4至13个月时仍处于完全缓解（CR）状态。我们的研究证实了全反式RA在M3中的主要疗效，即使在复发患者中也是如此。通过分化过程获得缓解。
Twenty-two patients with acute promyelocytic leukemia were treated with all-trans retinoic acid (RA, 45 mg/m2 per day) for 90 days. Of the 22, four patients were previously untreated, two were resistant after conventional chemotherapy, and 16 were in first (n = 11), second (n = 4), or third (n = 1) relapse. We observed 14 complete response, four transient responses, one failure, and three early deaths. Length of hospitalization and number of transfusions were notably reduced in complete responders. Correction of coagulation disorders and an increase of WBCs were the first signs of all-trans RA efficacy. Morphologic analysis performed at days 0, 15, 30, 45, 60, and 90 showed that complete remissions were obtained without bone marrow (BM) hypoplasia. Presence of Auer rods in the maturing cells confirmed the differentiation effect of the treatment. At remission, the t(15;17) initially present in 20 patients was not found. The in vitro studies showed a differentiation in the presence of all-trans RA in 16 of the 18 tested cases. The single nonresponder to all trans RA in vitro did not respond in vivo. Adverse effects of RA therapy--skin and mucosa dryness, hypertriglyceridemia, and increase of hepatic transaminases--were frequently noted. We also observed bone pain in 11 patients and hyperleukocytosis in four patients. Whether maintenance treatment consisted of low-dose chemotherapy or all-trans RA, early relapses were observed. Five patients are still in complete remission (CR) at 4 to 13 months. Our study confirms the major efficacy of all-trans RA in M3, even in relapsing patients. Remissions are obtained by a differentiation process.