Antimetabolite dose intensity and adverse outcomes in children with acute lymphoblastic leukemia: a COG-AALL03N1 report.

IF 21 1区 医学 Q1 HEMATOLOGY
Blood Pub Date : 2024-11-28 DOI:10.1182/blood.2024024455
Aman Wadhwa, Yanjun Chen, Lindsey Hageman, Anne Angiolillo, David S Dickens, Joseph P Neglia, Yaddanapudi Ravindranath, Amanda Termuhlen, F Lennie Wong, Wendy Landier, Smita Bhatia
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引用次数: 0

Abstract

Abstract: The association between antimetabolite dose intensity (DI) and adverse events among children receiving maintenance therapy for acute lymphoblastic leukemia (ALL) remains unclear, especially in the context of antimetabolite adherence. Using Children's Oncology Group AALL03N1 data, we examined the association between high DI during the first 4 study months and (i) treatment-related toxicities during the subsequent 2 study months; and (ii) relapse risk. Patients were classified into a high DI phenotype (either 6-mercaptopurine [6-MP] or methotrexate [MTX] DI ≥110% during the first 4 study months, or 6-MPDI or MTXDI 100%-110% at study enrollment and ≥25% increase over the 4 study months) and normal DI phenotype (all others). Only patients with wild-type TPMT and NUDT15 were included. 6-MP adherence data were available for 63.7% of study participants and used to stratify as adherent (median adherence ≥85%) and nonadherent (median adherence <85%) participants. Multivariable analyses were adjusted for sociodemographic and clinical prognosticators. Of the 644 patients, 29.3% were exposed to high DI. High DI was associated with a 2.1-fold greater odds of hematologic toxicity (95% confidence interval [CI] = 1.4-3.1; reference: normal DI) in the entire cohort and 2.9-fold higher among adherers (95% CI = 1.6-5.1); odds were comparable among nonadherers (2.1-fold; 95% CI = 0.4-10.1). Although high DI was not associated with relapse in the entire cohort (adjusted hazard ratio [aHR] = 1.4; 95% CI = 0.8-2.4), it was associated with a greater hazard of relapse among adherent participants (aHR = 2.4; 95% CI = 1.0-5.5) but not among nonadherent participants (aHR = 0.9; 95% CI = 0.2-3.8). Dose escalation above protocol doses during maintenance therapy for ALL should be done cautiously after assessing adherence to prescribed therapy.

急性淋巴细胞白血病患儿的抗代谢药物剂量强度与不良后果:COG-AALL03N1 报告。
在接受急性淋巴细胞白血病(ALL)维持治疗的儿童中,抗代谢药物剂量强度(DI)与不良事件之间的关系仍不清楚,尤其是在抗代谢药物依从性方面。利用 COG-AALL03N1 数据,我们研究了前四个研究月中高 DI 与(i)随后两个研究月中治疗相关毒性;以及(ii)复发风险之间的关联。患者被分为高DI表型(在前四个月中,6-巯基嘌呤[6-MP]或甲氨蝶呤[MTX]DI≥110%,或在入组时,6-MPDI或MTXDI为100%-110%,且在四个月中增加≥25%)和正常DI表型(所有其他患者)。仅纳入野生型 TPMT 和 NUDT15 患者。63.7% 的研究参与者可获得 6-MP 依从性数据,并将其分为依从(依从性中位数≥85%)和非依从(依从性中位数≥85%)两类。
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来源期刊
Blood
Blood 医学-血液学
CiteScore
23.60
自引率
3.90%
发文量
955
审稿时长
1 months
期刊介绍: Blood, the official journal of the American Society of Hematology, published online and in print, provides an international forum for the publication of original articles describing basic laboratory, translational, and clinical investigations in hematology. Primary research articles will be published under the following scientific categories: Clinical Trials and Observations; Gene Therapy; Hematopoiesis and Stem Cells; Immunobiology and Immunotherapy scope; Myeloid Neoplasia; Lymphoid Neoplasia; Phagocytes, Granulocytes and Myelopoiesis; Platelets and Thrombopoiesis; Red Cells, Iron and Erythropoiesis; Thrombosis and Hemostasis; Transfusion Medicine; Transplantation; and Vascular Biology. Papers can be listed under more than one category as appropriate.
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