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
Sanjeev Khera, Rajan Kapoor, Suman Pramanik
Abstract
Abstract Background The standard practice during high‐dose methotrexate (HD‐MTX) in acute lymphoblastic leukemia (ALL) to mitigate toxicity is to serially monitor levels till serum MTX < 0.01 μmol/L. Most resource‐limited centers lack in‐house access to MTX levels, and therefore repeated monitoring is costly and cumbersome. We studied the efficacy and safety of “solitary 36 hours post HD‐MTX levels (MTX 36 ).” Procedure This prospective observational study consecutively enrolled children with ALL receiving HD‐MTX. Cycles with unavailable MTX 36 and MTX 36 > 10 μmol/L were excluded. HD‐MTX was administered over 24 hours (BFM‐2009 protocol) with 12 hours of prehydration. MTX 36 were performed at other centers. Leucovorin was given in six hourly doses 36 hours post HD‐MTX. Hydration was continued until the last dose of leucovorin. MTX toxicities, including change of creatinine from baseline at 36 hours (∆Cr 36 ), were noted. Two groups depending on MTX 36 (≤1 μmol/L vs > 1 μmol/L) received six versus eight doses of leucovorin, and toxicities were compared. Results Twenty‐nine children with median age five years (1‐11) who received 100 HD‐MTX cycles with a median MTX dose of 3 g/m 2 (2‐5) were analyzed. The median MTX 36 level was 1.165 μmol/L (0.1‐7.32). Toxicities of HD‐MTX (CTCAE‐4.0): transaminitis‐22%; creatinine elevation ≥ 1.25 times baseline‐24%; cytopenias‐16%; mucositis‐17%; acute kidney injury (AKI)‐6%. All toxicities were ≤CTCAE grade 3. Creatinine elevation, AKI, and mucositis were significantly higher in the group with higher MTX 36 . There was no correlation ( r = 0.3) between ∆Cr 36 and MTX 36 . MTX 36 was thrice more economical than the standard protocol. Conclusion MTX 36 is a potential cost‐effective, efficacious, and safe limited sample strategy to monitor HD‐MTX, particularly in centers where in‐house MTX levels are unavailable.