Risk of relapse in childhood acute lymphoblastic leukemia is related to RBC methotrexate and mercaptopurine metabolites during maintenance chemotherapy. Nordic Society for Pediatric Hematology and Oncology
| Autor: | Anders Glomstein, Henrik Daa Schrøder, Kjeld Schmiegelow, Toivo T. Salmi, Lars Wranne, Garan Gustafsson, Jon Kristinsson |
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| Rok vydání: | 1995 |
| Předmět: |
musculoskeletal diseases
Oncology Male Risk Cancer Research medicine.medical_specialty Erythrocytes Time Factors Adolescent medicine.drug_class medicine.medical_treatment Administration Oral Antimetabolite chemistry.chemical_compound Pharmacokinetics Recurrence Internal medicine Acute lymphocytic leukemia medicine Humans Child Childhood Acute Lymphoblastic Leukemia Chemotherapy business.industry Mercaptopurine Remission Induction Infant Precursor Cell Lymphoblastic Leukemia-Lymphoma Thionucleotides medicine.disease Prognosis Guanine Nucleotides Methotrexate chemistry Polyglutamic Acid Child Preschool Antifolate Regression Analysis Female business medicine.drug Follow-Up Studies |
| Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 13(2) |
| ISSN: | 0732-183X |
| Popis: | PURPOSE During maintenance chemotherapy for childhood acute lymphoblastic leukemia (ALL), the cytotoxic metabolites of methotrexate (MTX polyglutamates) and mercaptopurine (6MP) (thioguanine nucleotides [6TGN]) accumulate intracellularly, including in erythrocytes (E-MTX and E-6TGN) with large interindividual variations. In the present Nordic Society for Pediatric Hematology and Oncology (NOPHO) study, the relation of E-MTX and E-6TGN to relapse risk was explored. PATIENTS AND METHODS Two hundred ninety-seven patients with non-B-cell ALL, aged 1 to 14 years, on oral MTX and 6MP had E-MTX and E-6TGN levels measured three to 35 (median, eight) and three to 75 (median, nine) times, respectively. For each patient, a mean of all E-MTX (mE-MTX) and E-6TGN (mE-6TGN) measurements was calculated, as well as the product of mE-MTX and mE-6TGN (mE-MTX-6TGN), since MTX and 6MP may have synergistic action. RESULTS For patients in remission, the median mE-MTX and mE-6TGN values were 4.7 nmol/mmol hemoglobin (Hgb) (range, 0.4 to 10.3) and 173 nmol/mmol Hgb (range, 58 to 846). With a median follow-up duration of 66 months for patients in remission, 64 patients relapsed. Cox regression analysis identified mE-MTX-6TGN and sex to be the most significant parameters to predict relapse (global P = .001). Factors that predicted a better prognosis were high mE-MTX 6TGN and female sex. Patients who had a mE-MTX-6TGN less than the product of the median mE-MTX and median mE-6TGN (813 [nmol/mmol Hgb]2) had a significantly poorer event-free survival (EFS) than did patients with higher values (5-year probability of EFS [pEFS5y], 0.70 v 0.86; P = .001). CONCLUSION The pharmacokinetics of MTX and 6MP may have significant influence on the risk of relapse. The value of dose adjustments by E-MTX and E-6TGN remains to be determined. |
| Databáze: | OpenAIRE |
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