Leucovorin Following Methotrexate Graft-Vs-Host Disease Prophylaxis Shortens the Duration of Mucositis, Time to Neutrophil Engraftment and Length of Hospitalization in Myeloablative Allogeneic Hematopoietic Transplantation

• Published in: Biology of blood and marrow transplantation 2019-03, Vol.25 (3), p.S283-S283
• Main Authors: Freyer, Craig, Ganetsky, Alex, Timlin, Colleen, Babushok, Daria, Frey, Noelle V., Gill, Saar I., Hexner, Elizabeth O., Loren, Alison W., Mangan, James, Martin, Mary Ellen, McCurdy, Shannon R., Perl, Alexander E., Smith, Jacqueline, Luger, Selina M., Stadtmauer, Edward A., Porter, David L.
• Format: Article
• Language: English
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2018.12.355

Grade (gr) 2-4 mucositis complicates myeloablative (MAC) allogeneic hematopoietic transplantation (HCT) in 90% of patients. Methotrexate (MTX) GVHD prophylaxis (ppx) contributes to mucositis and delays engraftment. Severe mucositis increases patient-controlled analgesia (PCA) and TPN (total parenteral nutrition) use, length of stay (LOS) and precludes completion of post HCT MTX. Leucovorin (LCV) following MTX is controversial. To address exacerbation of mucositis by MTX, we implemented routine LCV post MAC alloHCT and compared outcomes with historical controls. The primary endpoint was the duration of gr 2-4 mucositis. Secondary endpoints were the incidence of gr 3-4 mucositis, time to engraftment, TPN and PCA use, LOS, incidence of GVHD and relapse. Thirty-two consecutive adults received MAC alloHCT and MTX ppx with LCV 15 mg PO q6h x 4 doses, 12 h post d+3, +6, and +11 MTX and were compared to 33 consecutive historical controls. Controls did not receive routine LCV, but may have received ≥ 1 dose post d+6 or +11 MTX at physician discretion. Baseline characteristics were similar between the groups. All patients received tacrolimus and MTX GVHD ppx, most with Cy/TBI conditioning. Forty percent received peripheral blood stem cells and 60% had a matched unrelated donor. The median age was 46 y and 50% had AML. Thirty percent of controls received ≥ 1 LCV dose (most post d+11 MTX). The mean duration of gr 2-4 mucositis was shorter with LCV vs. control (7.4 vs. 11 d, p = 0.02). A trend towards lower incidence of gr 3-4 mucositis was observed with LCV (34% vs. 58%, p = 0.08). TPN use was similar between groups (25% vs. 36%, p = 0.4), however duration was shorter with LCV (8.6 vs. 21 d, p = 0.02). A trend towards less frequent PCA use was observed with LCV (34% vs. 58%, p = 0.08). Neutrophil engraftment was faster with LCV (17.6 vs. 20 d, p = 0.04) and a trend towards faster platelet engraftment was observed (15 vs. 20 d, p = 0.06). LOS was shorter with LCV (27 vs. 33 d, p = 0.01). LCV did not impact the incidence of GVHD. Relapse was less common in the LCV group (3% vs. 27%, p = 0.01) albeit with a shorter follow up (mean 202 d vs. 560 d). Routine LCV addition to MAC alloHCT with MTX ppx shortened the duration of gr 2-4 mucositis, expedited neutrophil engraftment, shortened TPN and LOS and showed trends towards reduction in clinically important endpoints related to mucositis incidence, severity and associated supportive care. Our small sample size and non-random