Impact of pre-hydration duration on high-dose methotrexate induced nephrotoxicity in childhood acute lymphoblastic...

Hydration before starting high-dose methotrexate (HD-MTX) ensures good renal perfusion and alkaline urinary pH. The duration of pre-hydration is not uniform across protocols. We compared 6-h versus 12-h of pre-hydration for HD-MTX therapy in childhood acute lymphoblastic leukaemia (ALL) at our centre where serial MTX level monitoring is not feasible.

This randomised cross-over study consecutively enrolled children  < 12 years with ALL receiving HD-MTX. Children with pre-existing renal disease or those exposed to nephrotoxic drugs were excluded. Two groups receiving 6-h versus 12-h pre-hydration on alternate basis in same patient (each exposed to four cycles of 2-5 g/m² of HD-MTX) were compared for HD-MTX induced nephrotoxicity (primary outcome) and other HD-MTX toxicities (HMT) as per common terminology criteria for adverse events (CTCAE-4.0). HD-MTX was administered over 24 h as per BFM-protocol-2009. Solitary MTX levels at 36-h (MTX36) were outsourced and leucovorin (LV) was started at 36 h at 15 mg/m²/dose for 6-8 doses 6-hourly depending on MTX36. Hydration fluid was dextrose normal saline with sodium-bicarbonate and administered till last LV dose.

Total 136 HD-MTX cycles in 34 patients (age range 5-144 months) were evaluated. Nephrotoxicity [2/68 (2.9%) in 6-h versus 1/68 (1.5%) in 12-h] and HMT incidence was comparable in two pre-hydration groups. Median MTX36 levels were not affected by duration of hydration irrespective of administered dose of HD-MTX. Median serum creatinine at baseline, post-pre-hydration and at 36-h post start of HD-MTX were comparable.

Reduction of pre-hydration duration does not affect HD-MTX induced nephrotoxicity and MTX36 levels in children < 12 years.