Reduced dose of MTX for GVHD prophylaxis promotes engraftment and decreases non-relapse mortality in umbilical cord blood transplantation.

Abstract

Although a combination of calcineurin inhibitor and methotrexate (MTX) is used for graft-versus-host disease (GVHD) prophylaxis in umbilical cord blood transplantation (CBT), optimal dose of MTX for CBT remains to be determined.We conducted a retrospective study to evaluate the safety and efficacy of standard-dose MTX (St-MTX, 15 mg/m2 on day 1 and 10 mg/m2 on days 3 and 6) and mini-dose MTX (Mini-MTX, 5 mg/m2 on days 1, 3 and 6) for GVHD prophylaxis in patients who underwent single unit CBT against hematological malignancies.Thirty-two and 26 patients received St-MTX and Mini-MTX, respectively. Cumulative incidence of neutrophil engraftment was significantly higher in the Mini-MTX group than in the St-MTX group (88.5% vs 65.6%, P = 0.00448). Cumulative incidences of grade II to IV and grade III to IV of acute graft-versus-host disease (GVHD) were 34.4% and 6.2% in the St-MTX group, and 34.6% and 7.7% in the Mini-MTX group with no statistical significance. One-year non-relapse mortality (NRM) was significantly lower in the Mini-MTX group compared to the St-MTX group (31.2% vs 3.8%, P = 0.00938), whereas relapse rate was not different between the groups. Multivariate analysis also indicated that Mini-MTX significantly improved engraftment (HR, 0.5359; 95% CI, 0.3082 to 0.9318; P = 0.0270) and reduced NRM (HR, 0.117; 95% CI, 0.0151 to 0.9067; P = 0.040).Our study suggests that GVHD prophylaxis using Mini-MTX in CBT is feasible and associated with improvement of engraftment and reduction in NRM.

• Authors: Souichi Shiratori, Hiroyuki Ohigashi, Shuichiro Takahashi, Takahide Ara, Hideki Goto, Masao Nakagawa, Junichi Sugita, Masahiro Onozawa, Kaoru Kahata, Tomoyuki Endo, Daigo Hashimoto, Takanori Teshima, North Japan Hematology Study Group (NJHSG)
• Journal: Annals of hematology (Ann Hematol) Vol. 99 Issue 3 Pg. 591-598 (Mar 2020) ISSN: 1432-0584 [Electronic] Germany
• PMID: 32006152 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Methotrexate

Topics

• Adolescent
• Adult
• Aged
• Allografts
• Cord Blood Stem Cell Transplantation
• Disease-Free Survival
• Female
• Graft Survival (drug effects)
• Graft vs Host Disease (mortality, prevention & control)
• Hematologic Neoplasms (mortality, therapy)
• Humans
• Male
• Methotrexate (administration & dosage)
• Middle Aged
• Retrospective Studies
• Survival Rate