肝移植术后新发急性早幼粒细胞白血病的诊断和治疗

目的探讨肝移植术后新发急性早幼粒细胞白血病(acute promyelocytic leukemia,APL)的诊断和治疗方法。方法 2003年10月至2012年12月在中山大学附属第三医院肝移植中心定期随访的肝移植患者中发现1例APL患者,回顾性分析该例患者的临床表现、诊断、治疗和预后情况。检索Pubmed、万方医学数据库等国内外数据库,分析肝移植术后白血病患者,特别是APL患者的年龄、性别、原发病、免疫抑制方案、术后发病时间、白血病分类、染色体变异类型、治疗、预后及死因等特点。结果本例患者于肝移植术后52个月门诊随访时发现外周血白细胞减少,无明显症状和体征,无感染与出血倾向,重组人粒细胞集落刺激因子治疗无效,经骨髓穿刺检查诊断为急性髓细胞白血病(acute myeloid leukemia,AML)-M3型,即APL。经维A酸和复方黄黛片(主要化学成份为二硫化二砷)联合治疗,患者获得完全缓解。检索文献共报道肝移植术后白血病34例(包括本例),其中22例诊断为AML(成人18例,儿童4例),术后发病时间中位数为26个月(38d至8年)。18例AML中,以APL最多见(8/18,44%)且伴有异常染色体核型t(15;17),治疗采用维A酸、三氧化二砷及联合柔红霉素、阿糖胞苷等化学药物治疗(化疗)药物。22例AML死亡13例(59%),主要死于弥散性血管内凝血(disseminated intravascular coagulation,DIC)、感染、肝衰竭和心力衰竭。APL和非APL患者中分别有2例(2/8)和11例死亡(79%,11/14),两组差异有统计学意义(P<0.05)。APL患者中6例化疗后完全缓解,另2例死于DIC和败血症。结论肝移植术后新发AML总体预后不佳,其中APL的预后好于非APL。早期诊断、早期治疗是提高肝移植术后APL疗效的关键措施。

Diagnosis and treatment of de novo acute promyelocytic leukemia after liver transplantation

Objective To investigate the diagnosis and treatment of de novo acute promyelocytic leukemia （APL） after liver transplantation. Methods One case developed APL among patients who were regularly followed up after liver transplantation in the Third Affiliated Hospital of Sun Yat-sen University from October 2003 to December 2012. Clinical dam of the patient, including clinical manifestations, diagnosis, treatment and prognosis, were retrospectively analyzed. A scientific literature search was undertaken in thedomestic and foreign medical databases, like Pubmed and Wanfang Medical Database. Clinical characteristics of patients with leukemia especially APL patients after liver transplantation were analyzed, such as age, gender, primary disease, the immunosuppression regimen, the postoperative elapsed time, the types of leukemia, the types of chromosome mutations, treatment, prognosis and the cause of death. Results At 52 months afler liver transplantation, the patient was found a reduction in the number of peripheral white blood ceils in the follow-up clinic, without any sign, symptom, infection or bleeding tendency. After the failure of treatment of recombinant human granulocyte colony-stimulating factor, the diagnosis of acute myeloid leukemia （AML） type M3 （APL） was confirmed by bone marrow biopsy. After combined treatment of vitamin A acid and compound realgar natural indigo tablet （main chemical component was arsenic disulfide ）, the patient achieved complete remission. There were 34 reported cases of leukemia after liver transplantation in the literature including this case. Among them, there were 22 cases of AML including 18 adults and 4 children. The median of postoperative elapsed time was 26 months （range from 38 d to 8 years）. The most common AML subtype was APL （8/18, 44% ） and all accompanied with abnormal karyotype t （15; 17）. Therapeutic regimen consisted of vitamin A acid, arsenic trioxide and chemotherapy drugs like daunorubicin or cytarabine. The overall mortality of AML patients was 59% （13/22） and the main causes of death included disseminated intravascular coagulation （DIC）, infection, liver failure and heart failure. The deaths included 2 cases （2/8） of APL and 11 cases （79% , 11/14 ） of the other types of AML, where significant difference was observed （ P 〈 0. 05 ）. Six APL patients achieved complete remission and the other two died of DIC and sepsis respectively. Conclusions The general prognosis of de novo AML after liver transplantation is not good but the prognosis of APL patients is better than that of the other types of AML. Early diagnosis and timely treatment is the key to improve the prognosis of APL after liver transplantation.