Background: The introduction of all-transretinoic acid (ATRA) and arsenic trioxide (ATO) has radically improved the prognosis of acute promyelocytic leukemia (APL), with cure rates above 80%. While relapse occurs in less than 20% of cases, addressing this issue remains challenging. Identifying effective salvage therapies for relapsed APL is crucial to improve patient outcomes. Methods: A retrospective analysis was performed on a multicentric cohort of 67 APL patients in first relapse, treated in three Italian hematology centers from June 1981 to November 2021. The overall survival (OS) and cumulative incidence of relapse (CIR) were calculated, and predictive factors were assessed using Cox regression models. Results: Overall, 61 patients (91%) received ATO ± ATRA (40.3%), chemo-based regimens (40.3%), or ATRA ± Gemtuzumab ozogamicin (GO) (10.4%). Complete remission (CR) was achieved in 98.2% of patients (molecular CR, n = 71.4%). With a median follow-up time of 54.5 months, the 5-year OS was 73% in the ATO ± ATRA group, 44% in the chemo-based group, and 29% in the ATRA ± GO group (p= 0.035). The 5-year OS rate was also higher for transplant recipients vs. non-recipients within the chemo-based cohort (50% vs. 33%,p= 0.017), but not in the ATO-based cohort (p= 0.12). ATO-based salvage therapy resulted in better OS in both univariate (p= 0.025) and multivariate analyses (p= 0.026). The 2-year CIR was higher in patients without molecular CR vs. patients in molecular CR (66% vs. 24%,p= 0.034). Molecular CR was a significant predictor of second relapse in both univariate (p= 0.035) and multivariate analyses (p= 0.036). Conclusions: Our findings support the efficacy of ATO-based therapies in first relapse of APL and confirm the achievement of molecular remission as an independent outcome predictor in both first and second APL relapse.
背景：全反式维甲酸（ATRA）与三氧化二砷（ATO）的应用已显著改善急性早幼粒细胞白血病（APL）的预后，治愈率超过80%。尽管复发率低于20%，应对复发仍是临床挑战。明确有效的复发APL挽救治疗方案对改善患者结局至关重要。方法：本研究对1981年6月至2021年11月期间意大利三家血液中心收治的67例首次复发APL患者进行多中心回顾性队列分析。计算总生存期（OS）与累积复发率（CIR），并通过Cox回归模型评估预后因素。结果：总体而言，61例患者（91%）接受了ATO±ATRA（40.3%）、化疗方案（40.3%）或ATRA±吉妥珠单抗奥佐米星（GO）（10.4%）治疗。完全缓解（CR）率达98.2%（分子学CR率为71.4%）。中位随访54.5个月后，ATO±ATRA组、化疗组及ATRA±GO组的5年OS率分别为73%、44%和29%（p=0.035）。在化疗亚组中，移植受者较非受者5年OS率更高（50% vs. 33%，p=0.017），但ATO亚组中无显著差异（p=0.12）。单因素（p=0.025）与多因素分析（p=0.026）均显示ATO挽救治疗可获得更优OS。未达分子学CR患者的2年CIR显著高于分子学CR患者（66% vs. 24%，p=0.034）。单因素（p=0.035）与多因素分析（p=0.036）均证实分子学CR是预测二次复发的独立因素。结论：本研究证实ATO方案在APL首次复发治疗中的有效性，并明确分子学缓解状态是首次及二次APL复发的独立预后预测指标。
Response Rates and Transplantation Impact in Patients with Relapsed Acute Promyelocytic Leukemia
肿瘤(癌症)患者之家