肿瘤细胞治疗研究
英文原题：Development of ALL-Hematotox: predicting post-CAR T-cell hematotoxicity in B-cell acute lymphoblastic leukemia.
Development of ALL-Hematotox: predicting post-CAR T-cell hematotoxicity in B-cell acute lymphoblastic leukemia.
在一项纳入 156 例复发/难治性 B-ALL 儿童与年轻成人患者的队列中，重度中性粒细胞减少（ANC <500/ L）的中位持续时间为 13 天（95% 置信区间，10-16 天），其中 83 例（53%）发生 3 级 ICAHT。
免疫效应细胞相关血液毒性（ICAHT）是靶向B细胞嵌合抗原受体（CAR）T细胞治疗的一种主要毒性。尽管大B细胞淋巴瘤（LBCL）、套细胞淋巴瘤（MCL）和多发性骨髓瘤（MM）中ICAHT的发生率和严重程度已有记录，但B细胞急性淋巴细胞白血病（B-ALL）中的ICAHT尚未得到描述。类似地，CAR-HEMATOTOX（CAR-HT）模型旨在预测重度长期中性粒细胞减少（绝对中性粒细胞计数〔ANC〕<500/μL，持续≥14天），已在LBCL、MCL和MM中验证，但尚未在B-ALL中验证。由于B-ALL骨髓（BM）浸润可能影响血细胞减少，我们旨在描述B-ALL中的ICAHT，并评估CAR-HT对血液毒性的预测能力。在156例复发/难治性B-ALL儿童和青年患者队列中，重度中性粒细胞减少（ANC<500/μL）持续时间中位数为13天（95%置信区间10至16天），83例（53%）发生3级ICAHT。使用CAR-HT评分后，近90%的患者被归为高危，区分能力有限，因此需进一步优化。根据我们发现的骨髓疾病负荷与输注后中性粒细胞减少之间的相关性（r=0.64，P<0.0001），我们开发ALL-Hematotox（ALL-HT）评分，以骨髓疾病负荷替代CAR-HT中的铁蛋白。ALL-HT评分与重度长期中性粒细胞减少相关（曲线下面积=0.84，P<0.0001），并能恰当地识别高危患者（47%）；该组中性粒细胞减少累计天数更多（26天对4天；P<0.0001）、完全缓解率较低（88%对98%；P=0.03），总生存期中位数更短（9.8对24个月；log-rank P=0.0002）。ALL-HT也在两个独立队列中得到验证。ALL-HT评分完善了广泛接受的输注后血液毒性预测模型，可用于B-ALL患者。
Immune effector cell-associated hematotoxicity (ICAHT) is a major B-cell targeted chimeric antigen receptor (CAR) T-cell related toxicity. Although ICAHT incidence and severity is documented in large B-cell lymphoma (LBCL), mantle cell lymphoma (MCL), and multiple myeloma (MM), ICAHT has not been described in B-cell acute lymphoblastic leukemia (B-ALL). Similarly, the CAR-HEMATOTOX (CAR-HT) model, designed to predict severe prolonged neutropenia ( 14 days of absolute neutrophil count [ANC] <500/ L), has been validated in LBCL, MCL, and MM, but not in B-ALL. As B-ALL bone marrow (BM) infiltration can impact cytopenias, we sought to describe ICAHT and assess CAR-HT for predicting hematotoxicity in B-ALL. In a cohort of 156 children and young adults with relapsed/refractory B-ALL, the median duration of severe neutropenia (ANC <500/ L) was 13 days (95% confidence interval, 10-16 days), with 83 (53%) experiencing grade 3 ICAHT. Applying CAR-HT, nearly 90% were classified as high risk, demonstrating limited discriminative power and prompting further development. Using the association identified between BM disease burden and postinfusion neutropenia (r = 0.64, P < .0001), we developed the ALL-Hematotox (ALL-HT) score, which substitutes BM disease burden for ferritin in CAR-HT. The ALL-HT score associated with severe prolonged neutropenia (area under the curve = 0.84, P < .0001), and appropriately discriminated high-risk patients (47%) who had more cumulative days of neutropenia (26 vs 4 days; P < .0001), fewer rates of complete response (88% vs 98%; P = .03), and shorter median overall survival (9.8 vs 24 months; log-rank P = .0002). ALL-HT was also validated in 2 independent cohorts. The ALL-HT score refines a widely accepted predictive model of postinfusion hematotoxicity, which is applicable in B-ALL.
MEMBER ACCOUNT
登录成功会直接打开下一页。
