Measurable residual disease at myeloablative allogeneic transplantation in adults with acute lymphoblastic leukemia: a retrospective registry study on 2780 patients from the acute leukemia working party of the EBMT
Measurable residual disease at myeloablative allogeneic transplantation in adults with acute lymphoblastic leukemia: a retrospective registry study on 2780 patients from the acute leukemia working party of the EBMT
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DOI：
10.1186/s13045-019-0790-x
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发表时间：
2019-10-23
影响因子：
28.5
通讯作者：
Mohty, Mohamad
中科院分区：
文献类型：
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作者：
Pavlu, Jiri;Labopin, Myriam;Mohty, Mohamad
背景：可测量残余疾病的评估（MRD）正在迅速改变各种血液系统恶性肿瘤的治疗和预后前景。它在急性淋巴细胞白血病（ALL）中的预后价值已经确立，在诱导结束时测量MRD越来越多地用于指导进一步的治疗。虽然已知在同种异体造血细胞移植（HCT）之前立即检测到MRD与不良结果相关，但尚不清楚不同类型的条件是否或在多大程度上存在差异。方法：在这项回顾性登记研究中，我们探讨了急性淋巴细胞白血病同种异体造血细胞移植（HCT）前可测量的残留病（MRD）是否与基于骨髓清除全身照射（TBI）和基于化疗的治疗的不同结果相关。我们分析了2780例患者（中位年龄38岁，范围18-72岁）的结果，这些患者在2000年至2017年期间使用兄弟姐妹或非亲属供体接受了首次HCT并完全缓解。结果：1816例患者未检出疾病，964例患者MRD阳性。在2122例（76%）移植中，调节是基于tbi的。在整个队列中，MRD阳性是总生存期（OS）和无白血病生存期（LFS）较低以及复发率（RI）较高的重要独立因素，其风险比（HR， 95%置信区间）分别为1.19（1.02-1.39）、1.26（1.1-1.44）和1.51（1.26-1.8）。TBI与较高的OS、LFS和较低的RI相关，HR分别为0.75（0.62-0.90）、0.70（0.60-0.82）和0.60（0.49-0.74）。在MRD状态和条件作用之间没有发现显著的相互作用。当通过多变量分析分别研究MRD对TBI和基于化疗的适应症队列的影响时，我们发现MRD阳性与TBI组较低的OS和LFS以及较高的RI相关，而与化疗组较高的RI相关。基于tbi的调节与mrd阴性和mrd阳性患者的预后改善相关。结论：在这项大型研究中，我们证实在HCT之前mrd阴性的患者获得了更好的结果。如果使用TBI调理，这一点尤其明显。所有急性淋巴细胞白血病患者，无论MRD状态如何，均可从清除骨髓的tbi治疗中获益。
Background: Assessment of measurable residual disease (MRD) is rapidly transforming the therapeutic and prognostic landscape of a wide range of hematological malignancies. Its prognostic value in acute lymphoblastic leukemia (ALL) has been established and MRD measured at the end of induction is increasingly used to guide further therapy. Although MRD detectable immediately before allogeneic hematopoietic cell transplantation (HCT) is known to be associated with poor outcomes, it is unclear if or to what extent this differs with different types of conditioning.Methods: In this retrospective registry study, we explored whether measurable residual disease (MRD) before allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia is associated with different outcomes in recipients of myeloablative total body irradiation (TBI)-based versus chemotherapy-based conditioning. We analyzed outcomes of 2780 patients (median age 38 years, range 18-72) who underwent first HCT in complete remission between 2000 and 2017 using sibling or unrelated donors.Results: In 1816 of patients, no disease was detectable, and in 964 patients, MRD was positive. Conditioning was TBI-based in 2122 (76%) transplants. In the whole cohort MRD positivity was a significant independent factor for lower overall survival (OS) and leukemia-free survival (LFS), and for higher relapse incidence (RI), with respective hazard ratios (HR, 95% confidence intervals) of 1.19 (1.02-1.39), 1.26 (1.1-1.44), and 1.51 (1.26-1.8). TBI was associated with a higher OS, LFS, and lower RI with HR of 0.75 (0.62-0.90), 0.70 (0.60-0.82), and 0.60 (0.49-0.74), respectively. No significant interaction was found between MRD status and conditioning. When investigating the impact of MRD separately in the TBI and chemotherapy-based conditioning cohorts by multivariate analysis, we found MRD positivity to be associated with lower OS and LFS and higher RI in the TBI group, and with higher RI in the chemotherapy group. TBI-based conditioning was associated with improved outcomes in both MRD-negative and MRD-positive patients.Conclusions: In this large study, we confirmed that patients who are MRD-negative prior to HCT achieve superior outcomes. This is particularly apparent if TBI conditioning is used. All patients with ALL irrespective of MRD status benefit from TBI-based conditioning in the myeloablative setting.