Relationship of iothalamate clearance and NRM in patients receiving fludarabine and melphalan reduced-intensity conditioning

Abstract

The reduced-intensity conditioning regimen, fludarabine and melphalan, is frequently used in allogeneic hematopoietic stem cell transplantation (HSCT). Melphalan and the active metabolite of fludarabine, F-ara-A, are excreted via the kidneys. Existing methods to assess clearance in this setting are based on serum creatinine, which has known limitations for glomerular filtration rate (GFR) estimation in patients with malignancy. Measured GFR (mGFR) may better predict drug dosing to mitigate toxicity and increase the chances of successful engraftment. The primary objective of this study was to assess the association between mGFR and risk for non-relapse mortality (NRM) in allogeneic HSCT patients receiving conditioning with fludarabine and melphalan. In the 109 included patients, mGFR < 65 ml/min/1.73m2 predicted a significantly higher rate of overall NRM (HR 2.13, 95% CI, 1.03-4.35, P = 0.04) and 1-year incidence of infection (HR 2.63, 95% CI, 1.54-4.55, P < 0.001) in addition to a significantly lower 2-year survival (P = 0.019). Kidney function estimated via eGFR and eCrCl did not correlate with post-transplant outcomes. These results suggest that mGFR is a promising approach for assessing clearance in allogeneic HSCT patients and may be preferred to standard creatinine-based eGFR strategies.