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4CPS-014 Comparison of two protocols for the administration of leucovorin rescues after high dose methotrexate infusion of 24 hours
  1. A Escolà Rodríguez,
  2. N Arranz Pasqual,
  3. C Bastida,
  4. M Albanell,
  5. I Monge Escartín,
  6. P Maté Arbaiza,
  7. S Ruiz Boy,
  8. E Carcelero San Martín,
  9. D Soy Muner
  1. Pharmacy Service, Division of Medicines, Clinic Barcelona – University of Barcelona, Barcelona, Spain


Background and Importance Therapeutic drug monitoring (TDM) of methotrexate (MTX) in plasma is a standard procedure to early identify patients with delayed drug elimination and adjust leucovorin dose. Adequate leucovorin rescues (LR) should start within 42-48h of the beginning of high dose (HD)-24h-MTX infusion to avoid MTX toxicity but extending LR more than needed can reduce MTX antitumour effect. Before implementation of new PETHEMA-2019 protocol at our hospital, standard LR were prescribed and MTX plasma concentration was determined 48h after infusion completion. Following new protocol recommendations, pharmacists started TDM.

Aim and Objectives To assess whether the implementation of the new protocol allowed reducing the total leucovorin dose administered after HD-24h-MTX infusion. Secondary outcomes: compare the incidence of toxicity and the level of compliance of appropriate MTX sampling times and LR between both protocols

Material and Methods Retrospective observational study conducted at a university tertiary hospital. Adults treated with a HD-24h-MTX infusion as treatment for acute lymphoblastic leukaemia (ALL) and Burkitt lymphoma from May 2019 to June 2022 were included. Patients were stratified (1:1) according to the protocol followed. Data collected were: age, sex, haematology malignancy, MTX dose, LR and serum creatinine.

Results Fifty-eight HD-24h-MTX infusions were analysed corresponding to 20 patients for the new protocol (75% males; mean ± SD age 49 ± 15 years; 7 with lymphoma, 11 ALL-B, 2 ALL-T) and to 20 for the original (65% male; mean ± SD age 49 ± 16 years; 10 lymphoma; 7 ALL-B, 3 ALL-T). The median [interquartile range] leucovorin dose administered per cycle following the original protocol was an 87% higher than the dose administered with the new protocol (597 mg/m2 [475,700] vs 75 mg/m2 [45,180], p<0,001). Nephrotoxicity incidence (increase of 0,3 mg/dl from basal creatinine) was 21% in the original protocol vs 19% in the new one (p=0,84). Sample extractions for TDM were correctly drawn in 93% of the cases and LR were correctly administered in 76% of the cases when using the new protocol, in comparison with 97% and 55% when using the original protocol).

Conclusion and Relevance Implementation of the new protocol allows a significant reduction of the leucovorin dose by 87% without an increase in nephrotoxicity. Measures to increase adherence to the new protocol may be implemented hereafter.

Conflict of Interest No conflict of interest

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