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Antimetabolite Dose Intensity and Adverse Outcomes in Children with Acute Lymphoblastic Leukemia: A COG-AALL03N1 Report.
Wadhwa, Aman; Chen, Yanjun; Hageman, Lindsey; Angiolillo, Anne; Dickens, David; Neglia, Joseph P; Ravindranath, Yaddanapudi; Termuhlen, Amanda; Wong, F Lennie; Landier, Wendy; Bhatia, Smita.
Afiliación
  • Wadhwa A; University of Alabama at Birmingham, Birmingham, Alabama, United States.
  • Chen Y; University of Alabama at Birmingham, Birmingham, Alabama, United States.
  • Hageman L; University of Alabama at Birmingham, Birmingham, Alabama, United States.
  • Angiolillo A; Servier Pharmaceuticals, Boston, Massachusetts, United States.
  • Dickens D; University of Iowa, United States.
  • Neglia JP; University of Minnesota School of Medicine, Minneapolis, Minnesota, United States.
  • Ravindranath Y; Wayne State University School of Medicine, Detroit, Michigan, United States.
  • Termuhlen A; University of Minnesota, Grosse Pointe Farms, Michigan, United States.
  • Wong FL; City of Hope, Duarte, California, United States.
  • Landier W; University of Alabama at Birmingham, Birmingham, Alabama, United States.
  • Bhatia S; University of Alabama at Birmingham, Birmingham, Alabama, United States.
Blood ; 2024 Aug 27.
Article en En | MEDLINE | ID: mdl-39190431
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 context of antimetabolite adherence. Using COG-AALL03N1 data, we examined the association between high DI during the first four study months and (i) treatment-related toxicities during the subsequent two 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 four study months, or 6-MPDI or MTXDI 100%-110% at study enrollment and ≥25% increase over the four study months) and normal DI phenotype (all others). Only patients with wildtype 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 non-adherent (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%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 non-adherers (2.1-fold, 95%CI=0.4-10.1).. While 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 non-adherent 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Blood Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Blood Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos