Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Leukemia. 2023 Sep;37(9):1782-1791. doi: 10.1038/s41375-023-01992-z. Epub 2023 Aug 5.
Polyethylene glycol (PEG)-asparaginase (pegaspargase) is a key agent in chemotherapy for acute lymphoblastic leukemia (ALL), but recipients frequently experience allergic reactions. We hypothesized that by decreasing antibody-producing CD20-positive B cells, rituximab may reduce these reactions. Children and adolescents (aged 1-18 years) with newly diagnosed B-ALL treated on the St. Jude Total XVII study were randomized to induction therapy with or without rituximab on day 3 (cohort 1) or on days 6 and 24 (cohort 2). Patient clinical demographics, CD20 expression, minimal residual disease (MRD), rituximab reactions, pegaspargase allergy, anti-pegaspargase antibodies, and pancreatitis were evaluated. Thirty-five patients received rituximab and 37 did not. Among the 35 recipients, 16 (45.7%) experienced a grade 2 or higher reaction to rituximab. There were no differences between recipients and non-recipients in the incidence of pegaspargase reactions (P > 0.999), anti-pegaspargase antibodies (P = 0.327), or pancreatitis (P = 0.480). CD20 expression on day 8 was significantly lower in rituximab recipients (P < 0.001), but there were no differences in MRD levels on day 8, 15, or at the end of induction. Rituximab administration during induction in pediatric patients with B-ALL was associated with a high incidence of infusion reactions with no significant decrease in pegaspargase allergies, anti-pegaspargase antibodies, or MRD.
聚乙二醇(PEG)-天冬酰胺酶(pegaspargase)是急性淋巴细胞白血病(ALL)化疗的关键药物,但受者常发生过敏反应。我们假设通过减少产生抗体的 CD20 阳性 B 细胞,利妥昔单抗可能会降低这些反应。在圣裘德全十七期研究中,新诊断为 B-ALL 的儿童和青少年(年龄 1-18 岁)被随机分配至第 3 天(队列 1)或第 6 天和第 24 天(队列 2)接受利妥昔单抗诱导治疗或不接受利妥昔单抗。评估了患者的临床特征、CD20 表达、微小残留病(MRD)、利妥昔单抗反应、pegaspargase 过敏、抗 peg 天冬酰胺酶抗体和胰腺炎。35 例患者接受了利妥昔单抗治疗,37 例未接受。在接受利妥昔单抗治疗的 35 例患者中,有 16 例(45.7%)发生了 2 级或更高级别的利妥昔单抗反应。接受者与未接受者之间的 peg 天冬酰胺酶反应发生率(P > 0.999)、抗 peg 天冬酰胺酶抗体(P = 0.327)或胰腺炎(P = 0.480)无差异。利妥昔单抗组第 8 天的 CD20 表达明显低于未接受者(P < 0.001),但第 8、15 天或诱导结束时的 MRD 水平无差异。在儿童 B-ALL 患者诱导治疗期间给予利妥昔单抗与输注反应发生率高相关,与 peg 天冬酰胺酶过敏、抗 peg 天冬酰胺酶抗体或 MRD 无显著降低相关。