NEW YORK (Reuters Health) Apr 06 - For kids with acute lymphoblastic leukemia (ALL), faster infusions of high-dose methotrexate (MTX) might seem like a good way to spare them from an overnight hospital stay -- but in fact the shorter infusion times present a serious problem, a new study shows.
With infusions cut from 24 to 4 hours, less of the drug accumulates in leukemia cells, decreasing its antileukemic effects, the researchers say.
"Making changes in the administration of cancer chemotherapy so that it can be delivered more easily and perhaps cheaply in the outpatient clinic may have serious adverse consequences on treatment response ... and in our case, it would," Dr. William E. Evans, Director and CEO of St. Jude Children's Research Hospital in Memphis, Tennessee, told Reuters Health.
Dr. Evans and colleagues describe their randomized trial involving 356 children with newly diagnosed ALL who were about to receive intravenous high-dose MTX, at 1 g/m�. The children were randomly assigned to receive just the first dose as either a 24-hour infusion (200 mg/m� over 5 minutes then 800 mg/m� over the next 23 hours 55 minutes) or a 4-hour constant infusion.
As reported in the Journal of Clinical Oncology online March 28, the 24-hour infusion produced significantly higher amounts of active methotrexate polyglutamates in bone marrow leukemia cells compared to the 4-hour infusion (P = 0.0059) and "better antileukemic effects," determined by measuring circulating ALL cells over 3 days.
Low accumulation of MTX polyglutamates in ALL cells was associated with a greater than 3-fold higher risk of relapse when compared to intermediate or high accumulation of active drug.
"For most subtypes of childhood ALL, it is best to not shorten the infusion time to avoid hospitalization, etc.," Dr. Evans said.
An exception, the researchers note in their report, may be ALL with the t(12;21)/(ETV6-RUNX1) chromosome translocation. For this subtype, infusion duration had no significant impact on MTX accumulation or antileukemic effect in their study.
In comments to Reuters Health, Dr. Evans emphasized that giving only one dose as a 4-hour infusion had no adverse consequences in this study. All other doses were given as a 24-hour infusion.
With infusions cut from 24 to 4 hours, less of the drug accumulates in leukemia cells, decreasing its antileukemic effects, the researchers say.
"Making changes in the administration of cancer chemotherapy so that it can be delivered more easily and perhaps cheaply in the outpatient clinic may have serious adverse consequences on treatment response ... and in our case, it would," Dr. William E. Evans, Director and CEO of St. Jude Children's Research Hospital in Memphis, Tennessee, told Reuters Health.
Dr. Evans and colleagues describe their randomized trial involving 356 children with newly diagnosed ALL who were about to receive intravenous high-dose MTX, at 1 g/m�. The children were randomly assigned to receive just the first dose as either a 24-hour infusion (200 mg/m� over 5 minutes then 800 mg/m� over the next 23 hours 55 minutes) or a 4-hour constant infusion.
As reported in the Journal of Clinical Oncology online March 28, the 24-hour infusion produced significantly higher amounts of active methotrexate polyglutamates in bone marrow leukemia cells compared to the 4-hour infusion (P = 0.0059) and "better antileukemic effects," determined by measuring circulating ALL cells over 3 days.
Low accumulation of MTX polyglutamates in ALL cells was associated with a greater than 3-fold higher risk of relapse when compared to intermediate or high accumulation of active drug.
"For most subtypes of childhood ALL, it is best to not shorten the infusion time to avoid hospitalization, etc.," Dr. Evans said.
An exception, the researchers note in their report, may be ALL with the t(12;21)/(ETV6-RUNX1) chromosome translocation. For this subtype, infusion duration had no significant impact on MTX accumulation or antileukemic effect in their study.
In comments to Reuters Health, Dr. Evans emphasized that giving only one dose as a 4-hour infusion had no adverse consequences in this study. All other doses were given as a 24-hour infusion.
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