针对急性髓系白血病残留病阳性患者缓解后治疗的优化

Toward optimization of postremission therapy for residual disease-positive patients with acute myeloid leukemia.

作者信息

Maurillo Luca, Buccisano Francesco, Del Principe Maria Ilaria, Del Poeta Giovanni, Spagnoli Alessandra, Panetta Paola, Ammatuna Emanuele, Neri Benedetta, Ottaviani Licia, Sarlo Chiara, Venditti Daniela, Quaresima Micol, Cerretti Raffaella, Rizzo Manuela, de Fabritiis Paolo, Lo Coco Francesco, Arcese William, Amadori Sergio, Venditti Adriano

机构信息

Hematology, Policlinico Tor Vergata and Ospedale S Eugenio, Rome, Italy.

出版信息

J Clin Oncol. 2008 Oct 20;26(30):4944-51. doi: 10.1200/JCO.2007.15.9814. Epub 2008 Jul 7.

DOI:10.1200/JCO.2007.15.9814

PMID:18606980

Abstract

PURPOSE

Despite the identification of several baseline prognostic indicators, the outcome of patients with acute myeloid leukemia (AML) is generally heterogeneous. The effects of autologous (AuSCT) or allogeneic stem-cell transplantation (SCT) are still under evaluation. Minimal residual disease (MRD) states may be essential for assigning patients to therapy-dependent risk categories.

PATIENTS AND METHODS

By multiparametric flow cytometry, we assessed the levels of MRD in 142 patients with AML who achieved complete remission after intensive chemotherapy.

RESULTS

A level of 3.5 x 10(-4) residual leukemia cells (RLCs) after consolidation therapy was established to identify MRD-negative and MRD-positive cases, with 5-year relapse-free survival (RFS) rates of 60% and 16%, respectively (P < .0001) and overall survival (OS) rates of 62% and 23%, respectively (P = .0001). Of patients (n = 77) who underwent a transplantation procedure (56 AuSCT and 21 SCT procedures); 42 patients (55%) were MRD positive (28 patients who underwent AuSCT and 14 patients who underwent SCT) and 35 patients (45%) were MRD negative (28 patients who underwent AuSCT and seven who underwent SCT). MRD-negative patients had a favorable prognosis, with only eight (22%) of 35 patients experiencing relapse, whereas 29 (69%) of 42 MRD-positive patients experienced relapse (P < .0001). In this high-risk group of 42 patients, we observed that 23 (82%) of 28 of those who underwent AuSCT experienced relapse, whereas six (43%) of 14 who underwent SCT experienced relapse (P = .014). Patients who underwent SCT also had a higher likelihood of RFS (47% v 14%).

CONCLUSION

A threshold of 3.5 x 10(-4) RLCs postconsolidation is critical for predicting disease outcome. MRD-negative patients have a good outcome regardless of the type of transplant they receive. In the MRD-positive group, AuSCT does not improve prognosis and SCT represents the primary option.

摘要

目的

尽管已确定了多种基线预后指标，但急性髓系白血病（AML）患者的预后总体上仍存在异质性。自体造血干细胞移植（AuSCT）或异基因造血干细胞移植（SCT）的效果仍在评估中。微小残留病（MRD）状态对于将患者归入依赖治疗的风险类别可能至关重要。

患者与方法

通过多参数流式细胞术，我们评估了142例接受强化化疗后达到完全缓解的AML患者的MRD水平。

结果

确定巩固治疗后残留白血病细胞（RLC）水平为3.5×10⁻⁴可区分MRD阴性和MRD阳性病例，5年无复发生存率（RFS）分别为60%和16%（P<0.0001），总生存率（OS）分别为62%和23%（P = 0.0001）。在接受移植手术的77例患者中（56例AuSCT和21例SCT手术）；42例患者（55%）为MRD阳性（28例接受AuSCT，14例接受SCT），35例患者（45%）为MRD阴性（28例接受AuSCT，7例接受SCT）。MRD阴性患者预后良好，35例患者中只有8例（22%）复发，而42例MRD阳性患者中有29例（69%）复发（P<0.0001）。在这42例高危患者中，我们观察到接受AuSCT的28例中有23例（82%）复发，而接受SCT的14例中有6例（43%）复发（P = 0.014）。接受SCT的患者无复发生存的可能性也更高（47%对14%）。