Prognostic impact of the dosage of methotrexate combined with tacrolimus for graft-versus-host disease prophylaxis after cord blood transplantation

• Published in: International journal of hematology Vol. 114; no. 2; pp. 252 - 262
• Main Authors: Adachi, Miwa, Yokota, Daisuke, Hirata, Hiroya, Koyauchi, Katsumi, Dohtan, Satoshi, Oka, Shinichiro, Sakamoto, Nami, Takaba, Masamitsu, Takemura, Tomonari, Nagata, Yasuyuki, Naito, Kensuke, Ono, Takaaki
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01-08-2021; Springer Nature B.V
• Subjects: Blood; Cord blood; Disease prevention; Dosage; Graft rejection; Graft versus host disease; Graft-versus-host reaction; Grafting; Grafts; Hematology; Leukocytes (neutrophilic); Medicine; Medicine & Public Health; Methotrexate; Multivariate analysis; Neutrophils; Oncology; Original Article; Prophylaxis; Survival; Tacrolimus; Transplantation; Tacrolimus; Methotrexate; GVHD prophylaxis; Cord blood transplantation
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-021-03161-3

The optimal dosage of methotrexate (MTX) for graft-versus-host disease (GVHD) prophylaxis after cord blood transplantation (CBT) has not been well elucidated. Therefore, we conducted a retrospective study comparing a mini-MTX group (5 mg/m
2
on day 1, 3 and 6) to a short-MTX group (10 mg/m
2
on day 1 and 7 mg/m
2
on day 3 and 6) after CBT. Sixty-three patients were classified as the mini-MTX group and 20 as the short-MTX group. The median time and cumulative incidence of neutrophil engraftment did not vary between the two groups. The cumulative incidence of grade 2–4 and grade 3–4 acute GVHD was similar in both groups. Overall survival in the mini-MTX group was significantly lower than in the short-MTX group (46.9% vs. 88.7% at 1 year,
p
 < 0.01), contributing to higher non-relapse mortality (NRM) in the mini-MTX group (32.0% vs. 5.0% at 1 year,
p
 = 0.02). In multivariate analysis, the mini-MTX regimen was the most powerful prognostic factor for OS (hazard ratio 4.11;
p
 = 0.03). Although the reduced dosage of MTX had no effect on neutrophil engraftment, increased NRM due to higher incidence of infection, graft failure, and severe acute GVHD resulted in a lower survival rate in the mini-MTX group after CBT.