Annals of Hematology

, Volume 95, Issue 12, pp 2009–2015 | Cite as

Hypoalbuminemia is significantly associated with increased clearance time of high dose methotrexate in patients being treated for lymphoma or leukemia

  • Samantha N. ReissEmail author
  • Larry W. Buie
  • Nelly Adel
  • Debra A. Goldman
  • Sean M. Devlin
  • Dan Douer
Original Article


As a weak acid, methotrexate (MTX) is bound to serum albumin and has variable protein binding. The purpose of this study was to assess serum albumin’s relationship with MTX pharmacokinetics by comparing MTX clearance and toxicities between patients with normal serum albumin to those with hypoalbuminemia. This single-center retrospective study included adult patients with leukemia or lymphoma who received their first MTX at a dose ≥1 g/m2. Hypoalbuminemia was defined as serum albumin ≤3.4 g/dL. MTX clearance was defined as the first documented time the MTX level ≤0.05 μM. Fisher’s exact tests and Wilcoxon rank sum tests were used to examine differences in toxicities, and Cox proportional hazard regression was used to assess relationship with time to clearance. Of 523 patients identified, 167 patients were evaluable. One hundred thirty-five patients had normal serum albumin and 32 had hypoalbuminemia. Hypoalbuminemia was associated with a higher proportion of patients experiencing edema, ascites or pleural effusions (34 vs. 12 %, p = 0.006), and the concomitant use of nephrotoxic agents (41 vs. 20 %, p = 0.021). Hypoalbuminemia was associated with a significantly longer time to MTX clearance (median 96 vs. 72 h, p = 0.004). In addition, patients with hypoalbuminemia had a higher proportion of hyperbilirubinemia and significantly longer hospitalization (median 14 vs. 5 days, p < 0.001). In conclusion, hypoalbuminemia was associated with increased time to MTX clearance and increased length of hospitalization. High dose MTX is safe to administer in patients with low albumin levels, with appropriate leucovorin rescue, and good supportive care.


Methotrexate Hypoalbuminemia Pharmacokinetics Toxicity Clearance Albumin Leukemia Lymphoma High dose methotrexate 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Memorial Sloan Kettering Cancer CenterNew YorkUSA
  2. 2.Memorial Sloan Kettering Cancer CenterNew YorkUSA

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