Nishiwaki Satoshi, Akahoshi Yu, Mizuta Shuichi, Shinohara Akihito, Hirabayashi Shigeki, Noguchi Yuma, Fukuda Takahiro, Uchida Naoyuki, Tanaka Masatsugu, Onizuka Makoto, Ozawa Yukiyasu, Ota Shuichi, Shiratori Souichi, Onishi Yasushi, Kanda Yoshinobu, Sawa Masashi, Tanaka Junji, Atsuta Yoshiko, Kako Shinichi
Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan.
Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan.
Blood Adv. 2021 Jan 26;5(2):584-592. doi: 10.1182/bloodadvances.2020003536.
Although measurable residual disease (MRD) at the time of allogeneic hematopoietic cell transplantation (allo-HCT) has been reported to be an important prognostic factor for Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) during first complete remission (CR1), the prognostic impact of MRD is unclear during second CR (CR2). To clarify the impact of MRD for both CR1 and CR2, we analyzed data from a registry database including 1625 adult patients with Ph+ ALL who underwent first allo-HCT during either CR1 or CR2 between 2002 and 2017. Adjusted overall and leukemia-free survival rates at 4 years were 71% and 64%, respectively, for patients undergoing allo-HCT during CR1 with MRD-, 55% and 43% during CR1 with MRD+, 51% and 49% during CR2 with MRD-, and 38% and 29% during CR2 with MRD+. Although survival rates were significantly better among patients with CR1 MRD- than among patients with CR2 MRD-, no significant difference was observed in survival rate between patients with CR1 MRD+ and CR2 MRD-. Relapse rates after 4 years were 16% in patients with CR1 MRD-, 29% in CR1 MRD+, 21% in patients with CR2 MRD-, and 46% in patients with CR2 MRD+. No significant difference was identified in relapse rate between patients with CR1 MRD- and CR2 MRD-. CR2 MRD- was not a significant risk factor for relapse in multivariate analysis (hazard ratio, 1.26; 95% confidence interval, 0.69-2.29; P = .45 vs CR1 MRD-). MRD at time of allo-HCT was an important risk factor in patients with Ph+ ALL during both CR1 and CR2.
尽管据报道，异基因造血细胞移植（allo-HCT）时的可测量残留病（MRD）是费城染色体（Ph）阳性急性淋巴细胞白血病（ALL）首次完全缓解（CR1）期间的一个重要预后因素，但MRD在第二次缓解（CR2）期间的预后影响尚不清楚。为了阐明MRD对CR1和CR2的影响，我们分析了一个注册数据库中的数据，该数据库包括2002年至2017年间在CR1或CR2期间接受首次allo-HCT的1625例成年Ph+ ALL患者。CR1期间接受allo-HCT且MRD阴性的患者4年调整后的总生存率和无白血病生存率分别为71%和64%，CR1期间MRD阳性的患者为55%和43%，CR2期间MRD阴性的患者为51%和49%，CR2期间MRD阳性的患者为38%和29%。尽管CR1 MRD阴性患者的生存率显著高于CR2 MRD阴性患者，但CR1 MRD阳性患者和CR2 MRD阳性患者的生存率没有显著差异。4年后的复发率在CR1 MRD阴性患者中为16%，CR1 MRD阳性患者中为29%，CR2 MRD阴性患者中为21%，CR2 MRD阳性患者中为46%。CR1 MRD阴性患者和CR2 MRD阴性患者的复发率没有显著差异。在多变量分析中，CR2 MRD阴性不是复发的显著危险因素（风险比，1.26；95%置信区间，0.69-2.29；与CR1 MRD阴性相比，P = 0.45）。allo-HCT时的MRD是Ph+ ALL患者在CR1和CR2期间的一个重要危险因素。
