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
Year: 2019
Type: article
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 7 /kg/unit & median infused viable CD34+ cell dose of 1.1 (range 0.1-3.1) x 10 5 /kg/unit with a median 5/8 (range 2-7) unit-recipient HLA-allele match. Haplo grafts [median infused CD34+ dose 5.2 × 10 6 /kg (range 1.1-16.8), median infused CD3+ dose 1.6 × 10 3 /kg (range 0.3-13.7), 61 (78%) 4/8 & 17 (22%) 5-7/8 HLA-matched to the pt] were from children (46%), siblings (31%), parents (13%) or extended family (10%). In 77 evaluable pts, 75 had sustained CB engraftment with either an optimal haplo-bridge (Gp. 1, 34/77, 44%), a transient bridge with a 2nd nadir preceding CB engraftment (Gp. 2, 20/77, 26%), no bridge (Gp. 3, 21/77, 27%) or CB/ haplo graft failure (Gp. 4, 2/77, 3%) ( Table 1 ). Similar to dCBT alone, sustained engraftment in haplo-dCBT was mediated by a "winning" CB unit [median winning CB unit-haplo 8-allele HLA-match 3/8 (range 1-7/8)] & was heralded by winning unit-derived T-cells as early as day +28. In univariate analysis, higher haplo CD34+ dose/kg, > 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.
Authors: Ioannis Politikos, Sean M. Devlin, Christopher Mazis, Molly A. Maloy, Kristine Naputo, Aishat Afuye, Scott T. Avecilla, Hugo Castro-Malaspina, Parastoo B Dahi, Sergio A. Giralt, Craig S. Sauter, Michael Scordo, Brian C. Shaffer, Gunjan L. Shah, Roni Tamari, Miguel-Angel Perales, Andromachi Scaradavou, Richard J. O'Reilly, Christina Cho, Boglarka Gyurkocza, Katharine C. Hsu, Ann A. Jakubowski, Esperanza B. Papadopoulos, Marcel R.M. van den Brink, James W. Young, Doris M. Ponce, Juliet N. Barker
Institutions: Memorial Sloan Kettering Cancer Center, New York Blood Center
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W2914818251