Nabhan C, Mehta J, Tallman M S
Division of Hematology-Oncology, Department of Medicine, Northwestern University Medical School, Robert H Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA.
Bone Marrow Transplant. 2001 Aug;28(3):219-26. doi: 10.1038/sj.bmt.1703119.
Acute promyelocytic leukemia (APL) is characterized by a specific gene rearrangement and the generation of the PML-RARalpha fusion transcript which results from a translocation between chromosomes 15 and 17. Targeted therapy with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy results in an apparent cure in 70-80% of patients. Both allogeneic (ALLO) and autologous (AUTO) hematopoietic stem cell transplantation (HSCT) are effective in acute myeloid leukemia (AML), but their role in APL is not clear given the excellent outcome with ATRA and chemotherapy. Several retrospective studies have analyzed the outcome of patients undergoing AUTO or ALLO-HSCT in first (CR1) or second (CR2) complete remission. Most of these studies have shown significant transplant-related mortality (TRM) with ALLO-HSCT, but a reduction in relapse rate compared with AUTO-HSCT. The high TRM with ALLO-HSCT and the excellent outcome with ATRA and chemotherapy do not justify recommending this procedure for the majority of patients in CR1. The role of AUTO-HSCT in CR1 also is unclear. A small subset of patients at high risk of relapse, possibly identifiable by a high white blood cell count at presentation may benefit from HSCT. Most patients with relapsed disease achieve CR2 with ATRA, arsenic trioxide, or combination therapy. However, it is not known if these responses are sustained or if consolidation with HSCT has a place in this setting. The outcome of AUTO-HSCT in CR2 using stem cells that are negative for PML-RARalpha is excellent. It is unclear whether ALLO-HSCT from an HLA-identical sibling is superior to AUTO-HSCT with PML-RARalpha-negative cells in CR2 since the former would be associated with graft-versus-leukemia effects and the latter with lower TRM. Alternatively, arsenic trioxide or re-treatment with ATRA, followed by intensive chemotherapy may also be effective. A randomized prospective clinical trial, or a retrospective analysis of the available data would be useful in answering this critical question.
急性早幼粒细胞白血病（APL）的特征是特定的基因重排以及15号和17号染色体易位产生的PML-RARα融合转录本。全反式维甲酸（ATRA）和蒽环类化疗药物的靶向治疗可使70-80%的患者明显治愈。异基因（ALLO）和自体（AUTO）造血干细胞移植（HSCT）在急性髓系白血病（AML）中均有效，但鉴于ATRA和化疗的良好效果，它们在APL中的作用尚不清楚。多项回顾性研究分析了在首次（CR1）或第二次（CR2）完全缓解期接受AUTO或ALLO-HSCT的患者的预后。这些研究大多显示，ALLO-HSCT有显著的移植相关死亡率（TRM），但与AUTO-HSCT相比，复发率有所降低。ALLO-HSCT的高TRM以及ATRA和化疗的良好效果并不足以证明对大多数处于CR1期的患者推荐该治疗方法是合理的。AUTO-HSCT在CR1期的作用也不清楚。一小部分复发风险高的患者，可能在初诊时通过高白细胞计数得以识别，可能会从HSCT中获益。大多数复发患者通过ATRA、三氧化二砷或联合治疗实现CR2。然而，尚不清楚这些缓解是否能持续，以及在这种情况下HSCT巩固治疗是否有作用。使用PML-RARα阴性干细胞进行CR2期AUTO-HSCT的预后良好。尚不清楚在CR2期，来自HLA匹配同胞的ALLO-HSCT是否优于PML-RARα阴性细胞的AUTO-HSCT，因为前者会有移植物抗白血病效应，而后者TRM较低。或者，三氧化二砷或再次使用ATRA，随后进行强化化疗也可能有效。一项随机前瞻性临床试验或对现有数据的回顾性分析将有助于回答这个关键问题。
