Transplantation and cellular therapy · 2025
Optimizing MMF Dosing for GVHD Prophylaxis in Umbilical Cord Blood Transplantation: A Retrospective Study in Non-Remission Myeloid Malignancies.
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Yamamoto Jotaro, Yamamoto Hisashi, Kuno Mika, Watanabe Otoya, Yamaguchi Kyosuke, Kageyama Kosei, Kaji Daisuke, Taya Yuki, Nishida Aya, Takagi Shinsuke, Yamamoto Go, Asano-Mori Yuki, Wake Atsushi, Taniguchi Shuichi, Uchida Naoyuki
Аннотация
BACKGROUND: Umbilical cord blood transplantation (UCBT) is a valuable treatment option with the potential for curative outcomes in patients with myeloid malignancies in non-remission status, but relapse and early non-relapse mortality (NRM) remain significant barriers. Tacrolimus and mycophenolate mofetil (MMF) are widely used as graft-versus-host disease (GVHD) prophylaxis in UCBT, but there is no consensus on the appropriate MMF dose for GVHD prophylaxis.
OBJECTIVES: We conducted a retrospective analysis to investigate the impact of MMF dose on outcomes in patients undergoing UCBT at our institution.
STUDY DESIGN: We reviewed patients with myeloid malignancies who received their first single UCBT in non-remission status at our center, administered tacrolimus and MMF for GVHD prophylaxis. The initial MMF dose was divided into three groups: MMF-Low (<17 mg/kg), MMF-Int (17-23 mg/kg), and MMF-High (≥23 mg/kg).
RESULT: A total of 574 patients were enrolled, median age 63 years (range 16-79). MMF groups: 95 patients (16.6%) in MMF-Low, 358 (62.4%) in MMF-Int, and 121 (21.1%) in MMF-High. MMF administration began the day before transplantation, median duration 41 days. The MMF-Low group included significantly younger patients and more frequently received myeloablative conditioning (P < .001). Although univariable analysis showed better outcomes in the MMF-Low group-including 2-year DFS of 48.9%, 35.8%, and 33.9% (P = .03) and OS of 53.0%, 37.9%, and 34.2% (P = .02) in the MMF-Low, MMF-Int, and MMF-High groups, respectively-these differences were not significant in multivariable analysis. NRM rates were 31.2%, 44.6%, and 45.2%, respectively, with no statistically significant difference among groups (P = .07). Relapse rates were comparable across groups (19.8%, 19.6%, and 20.8%; P = .77). Similarly, the cumulative incidence of grade II-IV acute GVHD was not significantly different among the groups (69.5%, 63.5%, and 62.8%; P = .176). Importantly, the cumulative neutrophil engraftment rate by day 42 was significantly lower in the MMF-High group (85.1%) compared to the MMF-Low group (96.8%) (P = .048). The incidence of bacterial infections by day 28 was significantly higher in the MMF-Higher group (75.0%) than in MMF-Low (56.2%) groups (P = .011). Consequently, day 28 NRM was significantly higher in the MMF-High group (12.4%) compared to the MMF-Low (2.1%) and MMF-Int (4.7%) groups (P = .002). In multivariable analysis, MMF-High emerged as a significant risk factor for impaired engraftment and early NRM.
CONCLUSION: MMF doses ≥23 mg/kg/day were associated with increased risk of engraftment failure and early mortality, primarily due to bacterial infection. Careful optimization of MMF dosing may improve early transplant outcomes in patients undergoing UCBT for advanced myeloid malignancies.
OBJECTIVES: We conducted a retrospective analysis to investigate the impact of MMF dose on outcomes in patients undergoing UCBT at our institution.
STUDY DESIGN: We reviewed patients with myeloid malignancies who received their first single UCBT in non-remission status at our center, administered tacrolimus and MMF for GVHD prophylaxis. The initial MMF dose was divided into three groups: MMF-Low (<17 mg/kg), MMF-Int (17-23 mg/kg), and MMF-High (≥23 mg/kg).
RESULT: A total of 574 patients were enrolled, median age 63 years (range 16-79). MMF groups: 95 patients (16.6%) in MMF-Low, 358 (62.4%) in MMF-Int, and 121 (21.1%) in MMF-High. MMF administration began the day before transplantation, median duration 41 days. The MMF-Low group included significantly younger patients and more frequently received myeloablative conditioning (P < .001). Although univariable analysis showed better outcomes in the MMF-Low group-including 2-year DFS of 48.9%, 35.8%, and 33.9% (P = .03) and OS of 53.0%, 37.9%, and 34.2% (P = .02) in the MMF-Low, MMF-Int, and MMF-High groups, respectively-these differences were not significant in multivariable analysis. NRM rates were 31.2%, 44.6%, and 45.2%, respectively, with no statistically significant difference among groups (P = .07). Relapse rates were comparable across groups (19.8%, 19.6%, and 20.8%; P = .77). Similarly, the cumulative incidence of grade II-IV acute GVHD was not significantly different among the groups (69.5%, 63.5%, and 62.8%; P = .176). Importantly, the cumulative neutrophil engraftment rate by day 42 was significantly lower in the MMF-High group (85.1%) compared to the MMF-Low group (96.8%) (P = .048). The incidence of bacterial infections by day 28 was significantly higher in the MMF-Higher group (75.0%) than in MMF-Low (56.2%) groups (P = .011). Consequently, day 28 NRM was significantly higher in the MMF-High group (12.4%) compared to the MMF-Low (2.1%) and MMF-Int (4.7%) groups (P = .002). In multivariable analysis, MMF-High emerged as a significant risk factor for impaired engraftment and early NRM.
CONCLUSION: MMF doses ≥23 mg/kg/day were associated with increased risk of engraftment failure and early mortality, primarily due to bacterial infection. Careful optimization of MMF dosing may improve early transplant outcomes in patients undergoing UCBT for advanced myeloid malignancies.