接受酪氨酸激酶抑制剂治疗的成人费城染色体阳性急性淋巴细胞白血病是否仍需要干细胞移植？：系统评价和荟萃分析。

Is stem cell transplantation still needed for adult Philadelphia chromosome-positive acute lymphoblastic leukemia receiving tyrosine kinase inhibitors therapy?: A systematic review and meta-analysis.

机构信息

Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

出版信息

PLoS One. 2021 Jun 28;16(6):e0253896. doi: 10.1371/journal.pone.0253896. eCollection 2021.

BACKGROUND

Hematopoietic stem cell transplantation (HSCT) is the current mainstay treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). However, tyrosine kinase inhibitors (TKI) also play a significant role in the treatment of these patients. We conducted this systematic review and meta-analysis to compare the efficacy of allogeneic (allo-) HSCT, autologous (auto-) HSCT, and chemotherapy (CMT) alone-all in combination with TKIs in adult Ph+ ALL patients.

MATERIALS AND METHODS

This systematic review identified studies from the EMBASE and MEDLINE databases from inception to April 2021 using search terms related to "ALL" and "HSCT." Eligible studies could be randomized controlled trials or cohort studies that included adult Ph+ ALL patients who received a TKI and either allo-HSCT, auto-HSCT, or CMT alone, and that reported the number of patients in each group for each of our primary outcomes of interest: overall survival (OS) or disease-free survival (DFS). Point estimates and associated 95% confidence intervals (CI) from each study were combined using the Hantel-Maenszel method.

RESULTS

After two rounds of review, 26 cohort studies were determined to be eligible for the meta-analysis. Adult Ph+ ALL patients who received HSCT had better survival outcomes than those who did not receive any HSCT (pooled odds ratio [OR] for OS of 1.61, 95%CI: 1.08-2.40; I2 = 59%, and for DFS of 3.23, 95%CI: 2.00-5.23; I2 = 62% for allo-HSCT; and, pooled OR for OS of 7.04, 95%CI: 1.97-25.15; I2 = 0%, and for DFS of 5.78, 95%CI: 1.04-32.19; I2 = 42% for auto-HSCT). Allo-HSCT recipients had comparable OS and DFS, but lower relapse rate compared to auto-HSCT recipients. Funnel plot generally demonstrated no presence of publication bias.

CONCLUSIONS

This systematic review and meta-analysis demonstrated superior results of HSCT in Ph+ ALL patients compared to CMT alone. Moreover, auto-HSCT could be implemented with comparable survival outcomes to allo-HSCT in patients with no available donor or when haploidentical HSCT is not feasible.

背景

造血干细胞移植（HSCT）是目前治疗费城染色体阳性急性淋巴细胞白血病（Ph+ ALL）的主要方法。然而，酪氨酸激酶抑制剂（TKI）在这些患者的治疗中也发挥着重要作用。我们进行了这项系统评价和荟萃分析，比较了异基因（allo-）HSCT、自体（auto-）HSCT 和单独化疗（CMT）联合 TKI 在成人 Ph+ ALL 患者中的疗效。

材料和方法

本系统评价从 EMBASE 和 MEDLINE 数据库中检索了从成立到 2021 年 4 月与“ALL”和“HSCT”相关的研究。合格的研究可以是随机对照试验或队列研究，纳入接受 TKI 治疗且接受 allo-HSCT、auto-HSCT 或 CMT 单独治疗的成人 Ph+ ALL 患者，并报告了每组患者的数量每个研究的我们主要关注的结果：总生存率（OS）或无病生存率（DFS）。使用 Hantel-Maenszel 方法组合每个研究的点估计值和相关的 95%置信区间（CI）。

结果

经过两轮审查，确定了 26 项符合荟萃分析条件的队列研究。接受 HSCT 的成人 Ph+ ALL 患者的生存结果优于未接受任何 HSCT 的患者（OS 的合并优势比[OR]为 1.61，95%CI：1.08-2.40；I2=59%，DFS 的合并 OR 为 3.23，95%CI：2.00-5.23；I2=62%，allo-HSCT；OS 的合并 OR 为 7.04，95%CI：1.97-25.15；I2=0%，DFS 的合并 OR 为 5.78，95%CI：1.04-32.19；I2=42%，auto-HSCT）。与 auto-HSCT 相比，allo-HSCT 患者的 OS 和 DFS 结果相似，但复发率较低。漏斗图普遍表明不存在发表偏倚。