Wang Xiaoxue, Wang Jing, Zhang Lijun
Department of Hematology, The First Hospital, China Medical University, Shenyang , China.
Medicine (Baltimore). 2019 May;98(19):e15537. doi: 10.1097/MD.0000000000015537.
The vast majority of acute promyelocytic leukemia (APL) is characterized with a specific chromosomal translocation t (15, 17) (q22, q21), which fuses PML-RARα leading to a good response to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). However, there are few cases of atypical APL, including PLZF-RARα, F1P1L1-RARα, STAT5b-RARα, et al. Neither PLZF-RARα nor STAT5b-RARα are sensitive to ATRA and ATO, and the prognosis is poor.
Here we have 3 cases (PLZF-RARα, n = 2; STAT5b-RARα, n = 1). Case A, A 53-year-old Chinese female had suffered ecchymosis in both legs for 3 days. Case B, A 44 years old male suffered pain from lower limbs and hip. Case C, 52-year-old male patient presented with fever for 3 weeks invalid to antibiotics and gingival bleeding for 1 week.
With RT-PCR and karyotype, Case A is diagnosed with STAT5b-RARα-positive APL.Case B, C are diagnosed with PLZF-RARα-positive APL.
In case A, ATO, and ATRA were used for induction treatment. In Case B, ATO, and chemotherapy with DA were given in the first induction treatment. In Case C, ATRA, and ATO were used immediately, subsequently, chemotherapy was added with DA, ATRA, and CAG combination treatment, and medium-dose cytarabine with daunorubicin were given regularly.
In Case A, the patient refused the following treatment and discharged on day 25. In Case B, the patient got the disseminated intravascular coagulation (DIC).In Case C, the patient has survived for 7 months and remains CR.
Both STAT5b-RARα-positive APL and PLZF-RARα-positive APL appear to be resistant to both ATRA and ATO, so combined chemotherapy and allo-HSCT should be considered. Since the prognosis and long-term outcome are poor, more clinical trials, and researches should be taken.
绝大多数急性早幼粒细胞白血病（APL）的特征是具有特定的染色体易位t（15；17）（q22；q21），该易位使PML-RARα融合，从而对全反式维甲酸（ATRA）和三氧化二砷（ATO）产生良好反应。然而，存在少数非典型APL病例，包括PLZF-RARα、FIP1L1-RARα、STAT5b-RARα等。PLZF-RARα和STAT5b-RARα对ATRA和ATO均不敏感，预后较差。
我们这里有3例病例（PLZF-RARα，2例；STAT5b-RARα，1例）。病例A，一名53岁的中国女性双下肢瘀斑3天。病例B，一名44岁男性下肢及臀部疼痛。病例C，一名52岁男性患者发热3周，抗生素治疗无效，牙龈出血1周。
通过逆转录聚合酶链反应（RT-PCR）和核型分析，病例A被诊断为STAT5b-RARα阳性APL。病例B、C被诊断为PLZF-RARα阳性APL。
病例A采用ATO和ATRA进行诱导治疗。病例B首次诱导治疗采用ATO及DA方案化疗。病例C立即使用ATRA和ATO，随后加用DA、ATRA及CAG联合化疗，并定期给予中剂量阿糖胞苷联合柔红霉素。
病例A患者拒绝后续治疗，于第25天出院。病例B患者发生弥散性血管内凝血（DIC）。病例C患者存活7个月，仍处于完全缓解（CR）状态。
STAT5b-RARα阳性APL和PLZF-RARα阳性APL似乎对ATRA和ATO均耐药，因此应考虑联合化疗和异基因造血干细胞移植（allo-HSCT）。鉴于预后和长期结局较差，应开展更多的临床试验和研究。
