MPN-188: Myeloablative Fludarabine and Busulfan Regimen in Myelofibrosis (MF): Long-Term Outcomes and Analysis of Prognostic Factors
2020
Context: Standard scoring systems prognosticate outcomes of MF at diagnosis and at allogeneic transplantation. Thorough evaluation of pre-transplant characteristics can point to appropriate mitigation strategies to improve outcomes. Objective: To evaluate the impact of individual components of standard scoring systems, along with factors previously reported in the literature, on transplant outcomes in patients with MF. Design: 65 consecutive patients transplanted for MF with a myeloablative regimen (details below) during 2007-2019 at the MD Anderson Cancer Center, were identified; associations between factors of interest and outcomes were evaluated. Median follow-up for survivors was 35.6 months. Patients: At transplant, median age was 61 years (range, 27-73); 42% were transfusion-dependent; 31% had secondary MF; and 53% of the patients were intermediate-2 while 42% were high-risk by DIPSS-plus. Interventions: Conditioning was Fludarabine 40 mg/m2 daily for 4 days, each dose followed by one daily dose of PK-guided IV Busulfan to an average daily AUC of 4,000 μM-min, or total course AUC of 16,000 μM-min. GvHD prophylaxis was tacrolimus and mini-methotrexate, patients with an unrelated donor received rabbit-antithymocyte globulin at a dose of 4-7.5 mg/kg. Outcomes: Overall survival (OS), non-relapse mortality (NRM), and cumulative incidence of relapse. Results: One-year and 3-year rates for OS were 78% and 65%, for relapse were 21% and 27%, and for NRM were 16% and 20%, respectively. Multivariable analysis (HR [95%CI]) showed a significant increase in risk of death for time from diagnosis to transplantation > 12 months (vs. ≤12 months; 3.01 [1.05-8.60], p=0.040), HCT-CT ≥ 3 (vs. 12 months (vs. ≤12 months; 7.20 [0.96-53.94], p=0.055). Increased risk of relapse was associated with age > 65 years at transplant (vs. ≤65 years; 2.77 [1.05-7.31], p=0.039), with a trend towards higher risk of relapse for patients with time to transplantation > 12 months (vs. ≤12 months; 4.50 [0.91-22.18], p=0.06). Conclusions: Time from diagnosis to transplant > 12 months was associated with worse OS with a trend towards worse NRM and relapse. Among DIPSS-components, only age and peripheral blood blasts ≥ 1 were associated with worse outcomes in this study. Analyses supported in part by the Cancer Center Support Grant (NCI Grant P30 CA016672)
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