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巴西成人急性淋巴细胞白血病患者异基因造血干细胞移植后的预测因素和结果。

Predictive Factors and Outcomes after Allogeneic Stem Cell Transplantation for Adults with Acute Lymphoblastic Leukemia in Brazil.

机构信息

Discipline of Hematology, Hospital das Clínicas from Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, SP, Brasil.

Discipline of Hematology, Hospital das Clínicas from Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, SP, Brasil.

出版信息

Transplant Cell Ther. 2022 Nov;28(11):763.e1-763.e7. doi: 10.1016/j.jtct.2022.07.025. Epub 2022 Jul 30.

Abstract

Allogeneic stem cell transplantation (HSCT) remains a potentially curative approach for acute lymphoblastic leukemia (ALL), especially for high-risk patients and those with relapsed/refractory disease, although its efficacy is offset by a not-negligible toxicity. Adult patients with ALL fare worse in developing countries, with little data about the HSCT in this setting. In this study, we aimed to describe outcomes and examine risk factors for overall survival (OS), leukemia-free survival (LFS), cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), and graft-versus-host disease (GVHD) after HSCT for ALL in Brazilian centers. This retrospective registry study included patients with ALL or ambiguous lineage leukemia age >16 years who underwent a first HSCT at 5 Brazilian centers between January 2007 and December 2017. A total of 275 patients were included, with a median age of 31 years (range, 16 to 65 years). Thirty-five percent were Philadelphia chromosome-positive. A matched sibling donor was used in 53%, a matched unrelated donor (MUD) in 19%, a mismatched unrelated donor in 9%, a haploidentical donor in 19%, and umbilical cord blood in 5%. The engraftment failure rate was 1.5%. The 5-year cumulative incidence of acute grade II-IV was 54.2%, and that of chronic GVHD was 26.2%. Five-year CIR and NRM were 28.1% and 34.1%, respectively. Central nervous system involvement at diagnosis (hazard ratio [HR], 2.2) and disease status (HR, 1.8 for second or later complete response and 7.9 for refractory) were associated with increased relapse incidence, whereas the use of peripheral blood graft (HR, .51) and a haploidentical donor (HR, .4) significantly decreased relapse incidence. Five-year OS and LFS were 40.7% (95% confidence interval [CI], 35.1-47.1) and 37.8% (95% CI, 32.3-44.1), respectively. Patient age, donor age, and disease status were independently associated with OS and LFS. Pre-HSCT positivity of minimal residual disease (>.01%) was associated with worse LFS (HR, 1.47) in available cases. This is the largest series of adults with ALL undergoing HSCT from Brazil reported to date. Although OS and LFS were similar to data reported in the literature, NRM was higher. Patient age and donor age outweighed donor type or graft source in our analysis. Interestingly, haploidentical HSCT was associated with lower CIR, whereas the use of MUDs was associated with higher NRM and GVHD rates. These results impact donor selection strategy in Brazil with the aim of offering timely HSCT for high-risk ALL patients in our setting.

摘要

异基因造血干细胞移植(HSCT)仍然是治疗急性淋巴细胞白血病(ALL)的一种潜在治愈方法,特别是对于高危患者和复发/难治性疾病患者,尽管其疗效因不可忽视的毒性而受到影响。在发展中国家,ALL 成年患者的预后较差,关于该地区 HSCT 的资料很少。在这项研究中,我们旨在描述巴西中心 ALL 患者 HSCT 后的总生存(OS)、无白血病生存(LFS)、累积复发率(CIR)、非复发死亡率(NRM)和移植物抗宿主病(GVHD)的结果,并探讨其危险因素。这项回顾性登记研究纳入了 2007 年 1 月至 2017 年 12 月期间在巴西 5 个中心接受首次 HSCT 的年龄>16 岁的 ALL 或不确定谱系白血病患者。共纳入 275 例患者,中位年龄 31 岁(范围,16 至 65 岁)。35%的患者存在费城染色体阳性。53%的患者使用了同胞供体,19%使用了匹配的无关供体(MUD),9%使用了不匹配的无关供体,19%使用了半相合供体,5%使用了脐带血。植入失败率为 1.5%。5 年急性Ⅱ-Ⅳ级累积发生率为 54.2%,慢性 GVHD 发生率为 26.2%。5 年 CIR 和 NRM 分别为 28.1%和 34.1%。诊断时中枢神经系统受累(风险比[HR],2.2)和疾病状态(HR,第二次或以后完全缓解为 1.8,难治为 7.9)与复发发生率增加相关,而外周血移植物(HR,.51)和半相合供体(HR,.4)的使用显著降低了复发率。5 年 OS 和 LFS 分别为 40.7%(95%置信区间[CI],35.1-47.1)和 37.8%(95% CI,32.3-44.1)。患者年龄、供者年龄和疾病状态与 OS 和 LFS 独立相关。在可评估的病例中,HSCT 前微小残留病(>0.01%)阳性与较差的 LFS 相关(HR,1.47)。这是迄今为止报告的巴西接受 HSCT 的 ALL 成年患者最大系列。尽管 OS 和 LFS 与文献报道的数据相似,但 NRM 更高。在我们的分析中,患者年龄和供者年龄比供者类型或移植物来源更重要。有趣的是,半相合 HSCT 与较低的 CIR 相关,而 MUD 的使用与较高的 NRM 和 GVHD 发生率相关。这些结果影响了巴西的供者选择策略,目的是为我们地区的高危 ALL 患者提供及时的 HSCT。

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