Double-Unit Cord Blood (CB) Transplantation (dCBT) Supplemented with Haplo-Identical CD34+ Cells May be Associated with Enhanced Neutrophil Recovery but Successful Myeloid Bridging Is Strongly Influenced By Haplo CD34+ Cell Dose and Haplo-Winning CB Unit HLA-Match

Abstract

Background While dCBT is associated with high rates of sustained donor engraftment, delayed neutrophil recovery is frequent. Methods We investigated the addition of CD34+ selected haplo-identical PBSC to double unit CB grafts (haplo-dCBT) in patients (pts) undergoing ablative dCBT with the aim to provide a myeloid bridge prior to CB engraftment. ATG was not used due to its adverse effects on immune recovery & potential to increase relapse risk. Results 78 adult pts [median 48.5 years (range 21-68), median 82 kgs (range 48-138), 3 with prior allografts, 54 (69%) acute leukemias or 10 (13%) MDS/ MPN (all 4/8 haplo-recipient HLA-match & ≥ 3/8 winning unit-haplo HLA-match were associated with higher likelihood of bridging (Table 2). Haplo CD34+ dose & winning unit-haplo HLA-match remained significant in multivariate analysis. While there was no difference in the day 100 TRM in the 34 optimal bridge pts vs others [9% (95%CI 2-21) vs 15% (95%CI 6-27), p = 0.388], optimal bridge pts had earlier hospital discharge [28.5 (range 20-60) vs 36 days (range 28-98)]. Conclusions ATG-free haplo-dCBT can speed neutrophil recovery but this benefit is highly variable, and a successful myeloid bridge is not guaranteed due to early haplo rejection. For these reasons our data does not support pursuit of haplo-dCBT. It is likely that similar limitations will also apply to ATG-free single CB unit-haplo transplants. Our findings also have significance for strategies that combine unmanipulated CB with third-party or ex vivo expanded T-cell depleted products given higher CD34+ cell dose & better HLA-match to the unmanipulated CB unit could improve successful bridging.