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A Novel Intermediate Intensity Conditioning Regimen Achieves High Rates of Long-Term Outpatient Progression-Free Survival Offsetting the Disadvantage of Early Post-Transplant Complications in Adult Cord Blood (CB) Transplant Recipients

Year: 2017

Type: article

Abstract: Background: The impact of the disease risk index (rDRI) & aaHCT-CI upon PFS & hospitalization burden after CBT is not established. Methods: We analyzed PFS & hospitalization determinants after cyclophosphamide 50 mg/kg, fludarabine 150 mg/m2, thiotepa 5-10 mg/kg, 400 cGy TBI & CSA/MMF-based dCBT for the treatment of adults with acute leukemia/MDS/MPD (≤10% blasts pre-CBT), B-cell NHL or HL. Results: Patients [n = 110, 55% non-European, 62% CMV+, median age 51 years (range 18-65), 83 acute leukemia, 11 MDS/MPD, 14 B-cell NHL & 2 HL] received double (n = 109) or single unit (n = 1) grafts [median 8-allele HLA-match 5/8 (range 2-8); median infused CD34+ dose .95 × 105/kg/unit (range .17-3.72)]. 96% of pts engrafted. Day 180 grades II-IV & III-IV aGVHD were 75% & 21%, respectively; 8% of pts had cGVHD by 1 year. Day 180 TRM incidence was 15% & 10% of pts relapsed by 2 years. With a median 2.7 years (range 6 months-8.5 years) survivor follow-up, 2-year OS is 72% (95%CI: 64-81) & PFS is 69% (95%CI: 61-79). rDRI & aaHCT-CI were significant determinants of 2-year PFS (Figure 1). In multivariate analysis, only aaHCT-CI was significant [HR 2.15 (95%CI: 1.01-4.59) if aaHCT-CI ≥ 3 (P = .047)]. The HR if high-very high rDRI was 2.03 (95%CI: .92-4.48) (P = .079). The median initial length of stay was 37 days (range 14-77) post-CBT. 101/110 (92%) pts survived to first discharge. Within the first 180 days, 60/101 (59%) of these pts were re-admitted [median 1 re-admit/pt, (range 1-9)], most commonly due to infection or aGVHD ± infection. We then examined the determinants of outpatient PFS (a composite endpoint defined as the number of days being free of relapse, death or hospitalization). Low-intermediate rDRI, 0-2 aaHCT-CI, & CMV seronegativity were associated with a higher mean number of outpatient progression-free days in days 0-180, but in multivariate analysis only aaHCT-CI was significant (P = .015). Moreover, only aaHCT-CI was significant in the 2 years post-CBT overall (Table 1). When the distribution of pts who were outpatient/progression-free vs inpatient vs dead/relapsed was analyzed by post-CBT month (Figure 2A,B), high proportions of pts are outpatient & progression-free after 6 months post-CBT regardless of aaHCT-CI, suggesting low rates of late CBT complications. Additionally, pts with aaHCT-CI 0-2 had a low hospitalization burden overall & especially low rates of readmission (<15%) beyond the first 3 months post-CBT (Figure 2A).Table 1Patient Variables Impacting Days Spent Outpatient & Progression-FreeFigure 2Distribution of pt status (outpatient & progression-free vs inpatient vs dead/ relapsed) by post-transplant month in CBT recipients with (A) aaHCT-Cl = 0-2 vs (B) aaHCT-Cl ≥ 3.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Conclusions: 2-year PFS in adult CBT recipients (median 51 years) after Cy/Flu/Thio/TBI is high overall (69%). Pts with 0-2 aaHCT-CI score do especially well (81%) with low hospitalization burden in the first 2 years post-CBT. As with all allograft types, new strategies to reduce CBT complications in pts with high aaHCT-CI are needed. Notably, however, given the very rapid graft availability & high PFS, dCBT should have a high priority in adult pts with low aaHCT-CI & high risk malignancies.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2016.12.292