High dose methotrexate in the treatment of children with acute lymphoblastic leukemia

Abstract

Background It has been claimed that around 70% of childhood
acute lymphoblastic leukemia (ALL) can be cured. One of the
important role is high dose methotrexate (HDMTX) administration
during the consolidation therapy.
Objective To determine the safety and effectiveness of HDMTX
in children with ALL.
Methods We reviewed patients with ALL in Pantai Indah Kapuk
Hospital, Jakarta during the period August 2000 through July 2005
with observation time run through September 2006. Only patients
with normal kidney function were allowed to have HDMTX. Besides
good hydration and alkalinization, patients were supported with good
hygiene (mouth, skin and anal area). MTX was given in loading
dose of 10% from the total dose in ½ hour and the rest 23½ hours for
90%. Leucovorin rescue was started 12 hours after discontinuation
of 24 hour MTX IV infusion. Leucovorin was given until the MTX
concentration reached 0.1 uM/L. Patients were stratified to low,
intermediate and high risk groups; 2 gram/m 2 was given to low risk
group and 5 gram/m2 to intermediate and high risk groups.
Results There were 20 patients eligible for study. All methotrexate
steady-state plasma concentrations (MTX Cp ss ) were above 16 uM/
L, and steady state concentration in CSF was always below 0.5 uM/
L for 2 gram/m 2 and above 0.5 uM/L for 5 gram/m 2 doses. All 20
cases went through the procedure with only mild side effects i. e,
mild mucositis, anal furuncle and diarrhea, which recovered 2 weeks
later. Only 1 high risk case with initial WBC 612X10 9 /L, succumbed
after he went through the HDMTX program smoothly and relapsed
subsequently during reinduction phase.
Conclusion HDMTX can be given safely to ALL patients with normal
kidney function with good supportive care. Five gram/m 2 HDMTX
effectively treat the minor disease and/or prevent CNS and testicular
leukemia. This study has also given an impression that HDMTX
may increase event-free survival.