1. ¹Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
2. ²Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA
3. ³University of Minnesota Cancer Center, Minneapolis, MN, USA
4. ⁴Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
5. ⁵Department of Public Health Sciences, University of Alberta, Edmonton, AB, Canada
6. ⁶Department of Epidemiology, University of Washington, Seattle, WA, USA

Correspondence: Dr K Robien, Division of Epidemiology and Community Health, University of Minnesota, 1300 S 2nd Street, Suite 300, Minneapolis, MN 55454, USA. E-mails: robien@epi.umn.edu; nulrich@fhcrc.org

Received 13 October 2005; Revised 19 December 2005; Accepted 22 December 2005; Published online 27 February 2006.

Abstract

Methotrexate (MTX) is used as an immunosuppressive agent for acute graft-versus-host disease (GVHD) prophylaxis following hematopoietic cell transplantation (HCT). Concerns that folate intake may impair MTX effectiveness or selectively rescue leukemic cells have led to variations in clinical practice regarding supplemental folic acid during MTX administration. A retrospective, observational study was undertaken to determine the association between folic acid intake (days 0–18 post transplant) and MTX toxicity and efficacy following HCT. The study population consisted of 311 adult patients who received a myeloablative HCT for chronic myelogenous leukemia, all four scheduled doses of MTX, and did not require leucovorin rescue. Multiple linear regression models were used to assess the relationships between folic acid intake (days 0–18 post-HCT) and oral mucositis index (OMI) scores, time to engraftment and risk of detectable acute GVHD. No statistically significant differences in mean OMI scores, time to engraftment, risk of acute GVHD, days to acute GVHD, risk of relapse or survival were observed when comparing patients taking, on average, <400 (14%), 400 (58%) or >400 g (28%) folic acid per day. Our results suggest that concurrent folic acid supplementation does not change MTX effectiveness or toxicity in this patient population.