Ratio of methotrexate to folate uptake by lymphoblasts in children with B-lineage acute lymphoblastic leukemia: a pilot study.
OBJECTIVE
Methotrexate (MTX) remains one of the most effective drugs for the treatment of children with acute lymphoblastic leukemia (ALL). Because MTX and 5-methyltetrahydrofolate (5CH3THF) share uptake and metabolic pathways, the efficacy of MTX is likely to depend not only on its metabolism but also on how well folate is accumulated by lymphoblasts. The authors' goal was to compare in vitro folate and antifolate uptake in B-lineage lymphoblasts from patients who remained in continuous complete remission (CCR) and those in whom relapse occurred.


METHODS
Twenty-four children with B-lineage ALL were studied at diagnosis (n = 20) or relapse (n = 4). Lymphoblasts obtained by bone marrow aspiration were incubated for 24 hours in vitro with 0.05 microM 5CH3[3H]THF or 1 microM [3H]MTX.


RESULTS
As of July 1999, 16 patients studied at diagnosis remained in CCR at a median follow-up of 45 months after achieving remission. Two of the patients studied at relapse are in second CCR; the remaining two died from progressive disease. The median uptake of neither [3H]MTX nor 5CH3[3H]THF differed significantly between the 16 patients in first CCR studied at diagnosis and the 4 patients studied at relapse. However, the median ratio of [3H]MTX:5CH3[3H]THF uptake differed significantly for patients who remained in first CCR versus patients studied at relapse.


CONCLUSIONS
The uptake of [3H]MTX in relation to 5CH3[3H]THF by leukemic lymphoblasts in vitro may correlate positively with treatment outcome in children with B-lineage ALL. A larger study of homogeneously treated patients is necessary to confirm these results.
Mantadakis
E
E
Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, USA.
Smith
A K
AK
Kamen
B A
BA
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001853:Bone Marrow / Q000473:pathology; D002051:Burkitt Lymphoma / Q000453:epidemiology / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D005492:Folic Acid / Q000493:pharmacokinetics*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008727:Methotrexate / Q000493:pharmacokinetics*; D010865:Pilot Projects; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D017211:Treatment Failure
D000970:Antineoplastic Agents; D005492:Folic Acid; D008727:Methotrexate