Bassan R, Battista R, Viero P, d'Emilio A, Buelli M, Montaldi A, Rambaldi A, Tremul L, Dini E, Barbui T
Division of Hematology, Ospedali Riuniti, Bergamo, Italy.
Leukemia. 1995 Feb;9(2):238-43.
A high hemorrhagic risk and a complete response to the differentiative agent all-trans-retinoic acid (ATRA) are the main clinical features of acute promyelocytic leukemia (APL), two distinct subtypes of which have been recognized, the common hypergranular leukopenic form (M3) and a microgranular hyperleukocytic variant (M3v). We analyzed, with emphasis on both disease- and therapy-related prognostic factors, the results from a 9-year trial in 65 adults with M3 and M3v APL, treated homogenously with a short-term therapy (STT) program excluding maintenance. STT comprised a maximum of six courses with doxorubicin, cytosine arabinoside (ara-C), and 6-thioguanine. Sixty-five APL patients formed the study group, M3v accounting for 25% of cases. In M3v, the absolute blast cell count was significantly higher (p < 0.0001) and early hemorrhagic deaths were more frequent (p = 0.05). The blast count correlated inversely with the probability of remission (p = 0.005), poor-risk patients being those with > 10 x 10(9)/l blast cells. During the study, the median survival improved from 0.1 to 2.7 years (p = < 0.005). In first place, response to chemotherapy increased from 42 to 84% (p = 0.006), by giving daily prophylactic platelet transfusions (to > 30 x 10(9)/l) and no heparin (course I), and by avoiding too toxic high-dose ara-C and deferring treatment in infected/neutropenic patients showing the atypical differentiative bone marrow pattern (course II). Secondly, the probability of first unmaintained remission differed significantly between patients given intentionally more than four total chemotherapy courses or intermediate/high-dose ara-C consolidation (0.59 at 5 years) and those treated less intensively (0.21) (p < 0.005). Intensive STT was very effective for the management of adult APL patients at standard hemorrhagic risk and receiving optimal supportive care. In high-risk patients with hyperleukocytosis and M3v, induction results could be improved by the concomitant use of ATRA. M3v in adults must be recognized promptly because of the very high early hemorrhagic risk.
高出血风险以及对分化剂全反式维甲酸（ATRA）的完全反应是急性早幼粒细胞白血病（APL）的主要临床特征，已识别出其两种不同亚型，即常见的高颗粒白细胞减少型（M3）和微颗粒高白细胞变异型（M3v）。我们重点分析了疾病和治疗相关的预后因素，这些结果来自一项针对65例M3和M3v型APL成年患者的9年试验，采用不包括维持治疗的短期治疗（STT）方案进行统一治疗。STT最多包括六个疗程的阿霉素、阿糖胞苷（ara - C）和6 - 硫鸟嘌呤。65例APL患者组成研究组，M3v占病例的25%。在M3v中，原始细胞绝对计数显著更高（p < 0.0001），早期出血死亡更频繁（p = 0.05）。原始细胞计数与缓解概率呈负相关（p = 0.005），高危患者是那些原始细胞>10×10⁹/L的患者。在研究期间，中位生存期从0.1年提高到2.7年（p = < 0.005）。首先，通过每日预防性输注血小板（至>30×10⁹/L）且不使用肝素（疗程I），以及避免使用毒性过大的高剂量ara - C并推迟对显示非典型分化骨髓模式的感染/中性粒细胞减少患者的治疗（疗程II），化疗反应率从42%提高到84%（p = 0.006）。其次，故意接受超过四个总化疗疗程或中/高剂量ara - C巩固治疗的患者（5年时为0.59）与治疗强度较低的患者（0.21）首次未维持缓解的概率有显著差异（p < 0.005）。强化STT对于标准出血风险且接受最佳支持治疗的成年APL患者的管理非常有效。在伴有高白细胞血症和M3v的高危患者中，联合使用ATRA可改善诱导结果。由于早期出血风险非常高，必须迅速识别成人M3v。
