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Randomized Controlled Trial
. 2023 Apr;91(4):331-336.
doi: 10.1007/s00280-023-04525-8. Epub 2023 Mar 23.

Impact of pre-hydration duration on high-dose methotrexate induced nephrotoxicity in childhood acute lymphoblastic leukaemia in resource constraint centers: a randomized crossover study

Sanjeev Khera  1 , Deepti Mahajan  2 , Kapil Barbind  3 , Sandeep Dhingra  2
Affiliations
Randomized Controlled Trial

Impact of pre-hydration duration on high-dose methotrexate induced nephrotoxicity in childhood acute lymphoblastic leukaemia in resource constraint centers: a randomized crossover study

Sanjeev Khera et al. Cancer Chemother Pharmacol. 2023 Apr.

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

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

Keywords: Acute lymphoblastic leukaemia; Children; High-dose methotrexate; Low-middle income countries; Methotrexate toxicities; Pre-hydration.

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References

    1. Pui CH, Sandlund JT, Pei D, Campana D, Rivera GK, Ribeiro RC et al (2004) Improved outcome for children with acute lymphoblastic leukemia: results of total therapy study XIIIB at St Jude children’s research hospital. Blood 104(9):2690–2696 - DOI - PubMed
    1. Howard SC, McCormick J, Pui CH, Buddington RK, Harvey RD (2016) Preventing and managing toxicities of high-dose methotrexate. Oncologist 21(12):1471–1482 - DOI - PubMed - PMC
    1. Khera S, Kapoor R, Pramanik SK (2020) Solitary serum methotrexate level 36 hours post high-dose methotrexate: a safe, efficacious, and cost-effective strategy to monitor methotrexate toxicities in childhood leukemia in resource-limited centers. Pediatr Blood Cancer 67(7):e28387 - DOI - PubMed
    1. Vaishnavi K, Bansal D, Trehan A, Jain R, Attri SV (2018) Improving the safety of high-dose methotrexate for children with hematologic cancers in settings without access to MTX levels using extended hydration and additional leucovorin. Pediatr Blood Cancer 65(12):e27241 - DOI - PubMed
    1. Christensen ML, Rivera GK, Crom WR, Hancock ML, Evans WE (1988) Effect of hydration on methotrexate plasma concentrations in children with acute lymphocytic leukemia. J Clin Oncol 6(5):797–801. https://doi.org/10.1200/JCO.1988.6.5.797 . (PMID: 3163362) - DOI - PubMed

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