Pediatric Oncology Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), NIH, Bethesda, Maryland, USA.
Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA.
Pediatr Blood Cancer. 2023 Jan;70(1):e30062. doi: 10.1002/pbc.30062. Epub 2022 Nov 12.
An adequate absolute lymphocyte count (ALC) is an essential first step in autologous chimeric antigen receptor (CAR) T-cell manufacturing. For patients with acute myelogenous leukemia (AML), the intensity of chemotherapy received may affect adequate ALC recovery required for CAR T-cell production. We sought to analyze ALC following each course of upfront therapy as one metric for CAR T-cell manufacturing feasibility in children and young adults with AML.
ALC data were collected from an observational study of patients with newly diagnosed AML between the ages of 1 month and 21 years who received treatment between the years of 2006 and 2018 at one of three hospitals in the Leukemia Electronic Abstraction of Records Network (LEARN) consortium.
Among 193 patients with sufficient ALC data for analysis, the median ALC following induction 1 was 1715 cells/μl (interquartile range: 1166-2388), with successive decreases in ALC with each subsequent course. Similarly, the proportion of patients achieving an ALC >400 cells/μl decreased following each course, ranging from 98.4% (190/193) after course 1 to 66.7% (22/33) for patients who received a fifth course of therapy.
There is a successive decline of ALC recovery with subsequent courses of chemotherapy. Despite this decline, ALC values are likely sufficient to consider apheresis prior to the initiation of each course of upfront therapy for the majority of newly diagnosed pediatric AML patients, thereby providing a window of opportunity for T-cell collection for those patients identified at high risk of relapse or with refractory disease.
足够的绝对淋巴细胞计数(ALC)是自体嵌合抗原受体(CAR)T 细胞制造的第一步。对于急性髓系白血病(AML)患者,接受的化疗强度可能会影响 CAR T 细胞生产所需的足够 ALC 恢复。我们旨在分析每位患者的初始治疗后 ALC,作为评估儿童和年轻 AML 患者 CAR T 细胞制造可行性的指标之一。
从 LEARN 联盟的三家医院之一在 2006 年至 2018 年期间接受治疗的年龄在 1 个月至 21 岁之间的新诊断为 AML 的患者的观察性研究中收集 ALC 数据。
在 193 名具有足够分析 ALC 数据的患者中,诱导 1 后 ALC 的中位数为 1715 个细胞/μl(四分位距:1166-2388),随后每个疗程的 ALC 均降低。同样,随着每个疗程的进行,达到 ALC>400 个细胞/μl 的患者比例逐渐降低,从第 1 疗程的 98.4%(190/193)到第 5 疗程的 66.7%(22/33)。
随着后续化疗疗程的进行,ALC 恢复呈连续下降趋势。尽管存在这种下降,但对于大多数新诊断的儿科 AML 患者,在开始每轮初始治疗之前,ALC 值很可能足以考虑进行单采,从而为那些复发风险高或患有难治性疾病的患者提供收集 T 细胞的机会。