Different Effects of Pre-transplantation Measurable Residual Disease on Outcomes According to Transplant Modality in Patients With Philadelphia Chromosome Positive ALL
Different Effects of Pre-transplantation Measurable Residual Disease on Outcomes According to Transplant Modality in Patients With Philadelphia Chromosome Positive ALL
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费城染色体阳性 ALL 患者移植前可测量残留疾病对不同移植方式结果的不同影响
DOI：
10.3389/fonc.2020.00320
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发表时间：
2020-03-17
影响因子：
4.7
通讯作者：
Chang, Ying-Jun
中科院分区：
文献类型：
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作者：
Li, Si-Qi;Fan, Qiao-Zhen;Chang, Ying-Jun
背景资料：本研究比较了费城染色体（Ph）阳性ALL患者行人类白细胞抗原匹配的同胞供者移植（MSDT）或接受未经操作的单倍相合SCT（haplo-SCT）后，移植前可测量残留疾病（pre-MRD）对预后的影响。结果：在总病例组中，前MRD阳性者的4年累积复发率（CIR）高于前MRD阴性者（26.1% vs. 12.1%，P = 0.009）;然而，非复发死亡率（NRM）的累积发生率（7. 4% vs. 15.9%，P = 0.148）、无白血病生存率（LFS）（66. 3% vs. 71.4%，P = 0.480）和总生存率（OS）（68. 8% vs. 76.5%，P = 0.322）具有可比性。在MSDT组中，与前MRD阴性的患者相比，前MRD阳性的患者4年CIR增加（56.4% vs. 13.8%，P < 0.001），4年LFS减少（35.9% vs. 71.0%，P = 0.024）和OS减少（35.9% vs. 77.6%，P = 0.011）。在单倍SCT设置中，4年CIR（14.8% vs. 10.7%，P = 0.297），NRM（7.3% vs. 16.3%，P = 0.187）和4年OS概率MRD前阳性组和阴性组之间的LFS（77.7% vs. 72.3%，P = 0.804）和LFS（80.5% vs. 75.7%，P = 0.660）相当。在pre-MRD阳性的亚组患者中，与MSDT相比，haplo-SCT的4年CIR（14.8% vs. 56.4%，P = 0.021）较低，4年LFS（77.7% vs. 35.9%，P = 0.036）和OS（80.5% vs. 35.9%，P = 0.027）较高。多因素分析显示，单倍体SCT与低CIR相关（HR，0.288; P = 0.031），上级LFS（HR，0.283; P = 0.019）和OS（HR，0.252; P = 0.013）。结论：我们的研究结果表明，根据移植方式，阳性pre-MRD对Ph阳性ALL患者结局的影响是不同的。对于Ph阳性且pre-MRD阳性的病例，单倍SCT可能具有较强的移植物vs.白血病（GVL）的影响。
Background: This study compared the effects of pre-transplantation measurable residual disease (pre-MRD) on outcomes in Philadelphia chromosome (Ph)-positive ALL patients who underwent human leukocyte antigen-matched sibling donor transplantation (MSDT) or who received unmanipulated haploidentical SCT (haplo-SCT).Methods: A retrospective study (n = 202) was performed. MRD was detected by RT-PCR and multiparameter flow cytometry.Results: In the total patient group, patients with positive pre-MRD had a higher 4-year cumulative incidence of relapse (CIR) than that in patients with negative pre-MRD (26.1% vs. 12.1%, P = 0.009); however, the cumulative incidence of non-relapse mortality (NRM) (7.4% vs. 15.9%, P = 0.148), probability of leukemia-free survival (LFS) (66.3% vs. 71.4%, P = 0.480), and overall survival (OS) (68.8% vs. 76.5%, P = 0.322) were comparable. In the MSDT group, patients with positive pre-MRD had increased 4-year CIR (56.4% vs. 13.8%, P < 0.001) and decreased 4-year LFS (35.9% vs. 71.0%, P = 0.024) and OS (35.9% vs. 77.6%, P = 0.011) compared with those with negative pre-MRD. In haplo-SCT settings, the 4-year CIR (14.8% vs. 10.7%, P = 0.297), NRM (7.3% vs. 16.3%, P = 0.187) and the 4-year probability of OS (77.7% vs. 72.3%, P = 0.804) and LFS (80.5% vs. 75.7%, P = 0.660) were comparable between pre-MRD positive and negative groups. In subgroup patients with positive pre-MRD, haplo-SCT had a lower 4-year CIR (14.8% vs. 56.4%, P = 0.021) and a higher 4-year LFS (77.7% vs. 35.9%, P = 0.036) and OS (80.5% vs. 35.9%, P = 0.027) than those of MSDT. Multivariate analysis showed that haplo-SCT was associated with lower CIR (HR, 0.288; P = 0.031), superior LFS (HR, 0.283; P = 0.019) and OS (HR, 0.252; P = 0.013) in cases with a positive pre-MRD subgroup.Conclusions: Our results indicate that the effects of positive pre-MRD on the outcomes of patients with Ph-positive ALL are different according to transplant modality. For Ph-positive cases with positive pre-MRD, haplo-SCT might have strong graft-vs.-leukemia (GVL) effects.