Favorable outcome of haploidentical hematopoietic stem cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia: a multicenter study in Southwest China.
Favorable outcome of haploidentical hematopoietic stem cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia: a multicenter study in Southwest China.
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单倍相合造血干细胞移植治疗费城染色体阳性急性淋巴细胞白血病的良好结果：中国西南地区的一项多中心研究。
DOI：
10.1186/s13045-015-0186-5
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发表时间：
2015-07-26
影响因子：
28.5
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Gao L;Zhang C;Gao L;Liu Y;Su Y;Wang S;Li B;Yang T;Yuan Z;Zhang X
自联合化疗方案中引入酪氨酸激酶抑制剂（TKI）以来，大多数新诊断的费城染色体阳性急性淋巴细胞白血病（Ph+ ALL）患者已达到完全缓解（CR）。然而，如果没有异基因造血干细胞移植（HSCT），成人的长期结果仍然不令人满意。事实上，单倍体相合HSCT已成为缺乏HLA匹配供体的成人患者的常见治疗方法，尽管关于单倍体相合HSCT在Ph+ ALL患者中的疗效的数据有限。我们分析了82例Ph+ ALL患者的临床结局，这些患者接受了单倍体相合HSCT（n = 47）或HLA匹配HSCT（n = 35）。进行实时定量逆转录聚合酶链反应（qRT-PCR）以评估BCR-ABL表达。所有患者在接受HSCT前均接受以伊马替尼为基础的方案治疗。在移植后检测BCR-ABL转录本后，患者重新开始伊马替尼治疗。除5例患者在植入前死亡外，所有患者均实现了中性粒细胞和血小板植入。与HLA匹配的HSCT相比，半相合HSCT与更高的急性移植物抗宿主病（GVHD）（51.1 vs. 25.7%，p < 0.05）和慢性GVHD（48.9 vs. 25.7%，p < 0.05）发生率相关，但在III-IV级急性GVHD或广泛慢性GVHD的发生率方面没有差异。半相合造血干细胞移植组巨细胞病毒感染率明显高于HLA相合造血干细胞移植组（38.3% vs.14.3%，p < 0.05）。与HLA匹配的HSCT相比，单倍体相合的HSCT与显著较低的复发率相关（44.8%对19.1%，p < 0.05）。在接受HLA匹配HSCT和接受单倍体相合HSCT的患者之间，无复发死亡率（NRM）、无白血病生存期（LFS）或总生存期（OS）无差异。我们的数据表明，HSCT后NRM的发病率是谁接受HLA匹配的供体细胞和那些谁接受单倍体相合的供体细胞和HSCT降低复发率的患者之间是相似的。对于缺乏合适HLA匹配供体的Ph+ ALL患者，单倍相合HSCT是一种令人鼓舞的治疗选择。
Since the introduction of tyrosine kinase inhibitors (TKIs) into combination chemotherapy regimens, the majority of newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) patients have achieved complete remission (CR). However, without allogeneic hematopoietic stem cell transplantation (HSCT), long-term outcomes in adults remain unsatisfactory. Indeed, haploidentical HSCT has become a common treatment for adult patients who lack an HLA-matched donor, though limited data are available on the efficacy of haploidentical HSCT in Ph+ ALL patients. We analyzed the clinical outcomes of 82 Ph+ ALL patients who underwent haploidentical HSCT (n = 47) or HLA-matched HSCT (n = 35). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to assess BCR-ABL expression. All of the patients were treated with an imatinib-based regimen before undergoing HSCT. Imatinib treatment was resumed in the patients’ posttransplantation following detection of BCR-ABL transcripts. All of the patients achieved neutrophil and platelet engraftment, with the exception of five patients who died prior to engraftment. Haploidentical HSCT was associated with higher incidences of acute graft-versus-host disease (GVHD) (51.1 vs. 25.7 %, p < 0.05) and chronic GVHD (48.9 vs. 25.7 %, p < 0.05) compared with HLA-matched HSCT, but there was no difference in the incidence of either grades III–IV acute GVHD or extensive chronic GVHD. The incidence of cytomegalovirus (CMV) infection was significantly higher in the patients treated with haploidentical HSCT than in those treated with HLA-matched HSCT (38.3 vs. 14.3 %, p < 0.05). Haploidentical HSCT was associated with a significantly lower relapse rate compared with HLA-matched HSCT (44.8 vs. 19.1 %, p < 0.05). There were no differences in non-relapse mortality (NRM), leukemia-free survival (LFS), or overall survival (OS) between the patients who received HLA-matched HSCT and those who underwent haploidentical HSCT. Our data indicate that the incidence of NRM after HSCT is similar between the patients who receive HLA-matched donor cells and those who receive haploidentical donor cells and that haploidentical HSCT reduces the relapse rate. Haploidentical HSCT represents an encouraging treatment option for Ph+ ALL patients who lack a suitable HLA-matched donor.