Comparison of Melphalan Dose in Patients with Myelodysplastic Syndrome Undergoing Allogeneic Transplantation with
Shuhei Kurosawa1, Yoshimitsu Shimomura2, Hidehiro Itonaga3
1Department of Hematology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan.
Abstract:
The present study compared lower-dose melphalan (80 mg/m2, FM80) and higher-dose melphalan (140 mg/m2, FM140) when administering reduced-intensity conditioning with fludarabine in adult patients with myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed nationwide registry data (2006 to 2019) and compared transplant outcomes between the 2 groups. Ninety-two patients (median age, 61 [interquartile range, 56 to 65] years) were assigned to the FM80 and FM140 groups by propensity score matching. The 3-year overall survival (OS) rate in the FM140 group (63.9%; 95% confidence interval [CI], 52.9% to 73.0%) was significantly higher than that in the FM80 group (54.2%; 95% CI, 37.1% to 52.1%) (P = .038). The FM140 group had a nonsignificantly (P = .095) lower 3-year cumulative incidence of relapse (15.5%; 95% CI, 8.9% to 23.8% versus 26.0%; 95% CI, 17.3% to 35.5%). The 3-year cumulative incidences of nonrelapse mortality were 22.3% (95% CI, 14.1% to 31.8%) and 23.7% (95% CI, 15.4% to 33.2%) in the FM80 and FM140 groups, respectively (P = .49). The beneficial effect of FM140 was more evident in patients with a poor cytogenetic risk. Our findings suggest the superiority of FM140 in patients with MDS undergoing allo-HSCT, especially in high-risk patients.
Insights
Higher-dose melphalan (FM140) improved overall survival in myelodysplastic syndrome (MDS) patients undergoing allogeneic stem cell transplant compared to lower-dose melphalan (FM80). FM140 also reduced relapse rates, particularly in high-risk MDS patients.
Area of Science:
- Hematology
- Oncology
- Transplantation Medicine
Background:
- Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders.
- Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for MDS.
- Reduced-intensity conditioning regimens are commonly used in older patients or those with comorbidities.
Purpose of the Study:
- To compare the efficacy and safety of lower-dose melphalan (FM80) versus higher-dose melphalan (FM140) combined with fludarabine as reduced-intensity conditioning for adult MDS patients undergoing allo-HSCT.
- To evaluate the impact of melphalan dose on overall survival, relapse rates, and nonrelapse mortality.
Main Methods:
- Retrospective analysis of nationwide registry data from 2006 to 2019.
- Propensity score matching was used to compare 92 adult patients with MDS undergoing allo-HSCT, divided into FM80 and FM140 groups.
- Key outcomes assessed included overall survival, cumulative incidence of relapse, and cumulative incidence of nonrelapse mortality.
Main Results:
- The 3-year overall survival rate was significantly higher in the FM140 group (63.9%) compared to the FM80 group (54.2%) (P = .038).
- The FM140 group showed a trend towards a lower 3-year cumulative incidence of relapse (15.5% vs. 26.0%, P = .095).
- There was no significant difference in 3-year nonrelapse mortality between the two groups (22.3% vs. 23.7%, P = .49).
- The benefit of FM140 was more pronounced in patients with poor cytogenetic risk.
Conclusions:
- Higher-dose melphalan (FM140) appears superior to lower-dose melphalan (FM80) for reduced-intensity conditioning in adult MDS patients undergoing allo-HSCT.
- FM140 may improve survival outcomes and reduce relapse rates, especially in high-risk MDS patients.
- Further prospective studies are warranted to confirm these findings.
