不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel:ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
肿瘤细胞治疗研究
英文原题:A Risk Model Using Refined Disease Risk Index and 1-Month NK-Cell Count for Relapse in Children and Adults with T-ALL/LBL After Myeloablative Umbilical Cord Blood Transplantation.
A Risk Model Using Refined Disease Risk Index and 1-Month NK-Cell Count for Relapse in Children and Adults with T-ALL/LBL After Myeloablative Umbilical Cord Blood Transplantation.
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复发仍是 T-ALL/LBL 患者接受 UCBT 后治疗失败的主要原因。
评估T细胞急性淋巴细胞白血病/淋巴瘤(T-ALL/LBL)患者接受脐带血移植(UCBT)后的移植结局,并确定与复发相关的因素。
我们回顾性分析了2014年1月至2024年6月在本中心接受单份脐带血作为首次移植的105例T-ALL/LBL患者(年龄2–53岁)。评估全队列移植结局。在具备移植后1个月外周血自然杀伤(NK)细胞测定结果的亚组中(58/105,55.2%),采用Fine-Gray竞争风险回归识别复发相关因素。根据分析队列的中位数,将1个月NK细胞计数二分。基于最终多变量模型建立简化风险评分,并通过时间依赖性曲线下面积(AUC)和校准分析评估模型表现。
全队列3年总生存率、无进展生存率和无GVHD无复发生存率分别为57.3%(95% CI,46.9%–66.4%)、54.9%(95% CI,44.9%–63.9%)和49.3%(95% CI,39.5%–58.5%);3年复发累积发生率为34.5%(95% CI,25.5%–43.6%)。在NK细胞检测亚组中,多变量Fine-Gray分析确定较高的精细疾病风险指数(R-DRI)(sHR=4.561;95% CI,1.662–12.51;P=0.003)和较低的移植后1个月NK细胞计数(<0.165×10^9/L)(sHR=6.175;95% CI,1.711–22.280;P=0.005)为与复发独立相关的因素。2分风险评分将患者分为低、中和高危组,3年复发率分别为0、43.5%(95% CI,23.3%–62.1%)和89.7%(95% CI,48.6%–98.4%)(P<0.001)。表观3年AUC为0.539(95% CI,0.255–0.823),乐观校正后AUC为0.523。
复发仍是T-ALL/LBL患者UCBT后治疗失败的重要原因。较高R-DRI和较低的移植后1个月NK细胞计数与复发独立相关,并可在开发队列中进行表观风险分层。这一探索性双因素模型可为未来纳入早期免疫重建指标的复发评估研究提供依据。
To assess transplant outcomes after umbilical cord blood transplantation (UCBT) in patients with T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) and identify factors associated with relapse.
We retrospectively analyzed 105 patients with T-ALL/LBL (age, 2-53 years), who underwent single-unit UCBT as their first transplant at our center between January 2014 and June 2024. Transplant outcomes were assessed in the overall cohort. Relapse-associated factors were identified using Fine-Gray competing-risk regression in the subgroup with available 1-month peripheral blood natural killer (NK) cell measurements (58/105, 55.2%). The 1-month NK-cell count was dichotomized based on the median number in the analyzed cohort. A simplified risk score was derived from the final multivariable model. Model performance was assessed using time-dependent area under the curve (AUC) and calibration analysis.
In the overall cohort, the 3-year overall survival, progression-free survival, and GVHD-free relapse-free survival were 57.3% (95% CI, 46.9-66.4%), 54.9% (95% CI, 44.9-63.9%), and 49.3% (95% CI, 39.5-58.5%), respectively, and the 3-year cumulative incidence of relapse was 34.5% (95% CI, 25.5-43.6%). In the NK-measured subgroup, multivariable Fine-Gray analysis identified high refined Disease Risk Index (R-DRI) (sHR, 4.561; 95% CI, 1.662-12.51; P = 0.003) and low 1-month NK-cell count (< 0.165 10 9 /L) (sHR, 6.175; 95% CI, 1.711-22.280; P = 0.005) as independent factors associated with relapse. A 2-point score stratified patients into low-, intermediate-, and high-risk groups with 3-year relapse incidences of 0, 43.5% (95% CI, 23.3-62.1%), and 89.7% (95% CI, 48.6-98.4%), respectively ( P < 0.001). The apparent 3-year AUC was 0.539 (95% CI, 0.255-0.823), and the optimism-corrected AUC was 0.523.
Relapse remains a major cause of treatment failure after UCBT in T-ALL/LBL. High R-DRI and low 1-month NK-cell count were independently associated with relapse and allowed apparent risk stratification in the development cohort. This exploratory 2-factor model may provide a basis for future studies of relapse assessment incorporating early immune recovery.
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