Engraftment Kinetics after Transplantation of Double Unit Cord Blood Grafts Combined with Haplo-identical CD34+ Cells without Anti-thymocyte Globulin

Ioannis Politikos, Sean M Devlin, Maria E Arcila, Jonathan C Barone, Molly A Maloy, Kristine A Naputo, Josel D Ruiz, Christopher M Mazis, Andromachi Scaradavou, Scott T Avecilla, Parastoo B Dahi, Sergio A Giralt, Katherine C Hsu, Ann A Jakubowski, Esperanza B Papadopoulos,

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AUTHORSHIP

Contribution: J.N.B. and R.J.O.R designed the clinical trial (NCT01682226). I.P. and J.N.B. assembled and analyzed the data, and wrote the manuscript. S.M.D. and I.P. performed the statistical analysis. M.A.M., K.A.N., J.D.R. and C.M.M. maintained the patient database and procured data for the study. M.E.A., J.C.B. and S.T.A. were responsible for the whole blood and white cell subset chimerism assays. I.P., P.D., S.A.G, A.J., E.B.P., M.A.P., C.S.S., R.T., D.M.P., J.N.B. provided patient care. I.P, S.M.D., J.C.B., A.S., S.T.A., P.D., S.A.G, K.C.H., A.J., E.B.P., M.A.P., C.S.S., R.T., D.M.P., R.J.O.R. and J.N.B. interpreted the data, reviewed and edited the manuscript. All authors have approved the submitted version of the manuscript.

https://doi.org/10.1038/s41375-020-0922-x, Volume: 35, Issue: 3, Pages: 850-862

Article Type: research-article Article History

Publisher: None

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Table of Contents

INTRODUCTION
METHODS
RESULTS
DISCUSSION
Supplementary Material

Abstract

Double unit cord blood (dCB) transplantation (dCBT) is associated with high engraftment rates but delayed myeloid recovery. We investigated adding haplo-identical CD34+ cells to dCB grafts to facilitate early haplo-identical donor-derived neutrophil recovery (optimal bridging) prior to CB engraftment. Seventy-eight adults underwent myeloablation with cyclosporine-A/mycophenolate mofetil immunoprophylaxis (no anti-thymocyte globulin, ATG). CB units (median CD34+ dose 1.1 × 10⁵/kg/unit) had a median 5/8 unit-recipient HLA-match. Haplo-identical grafts had a median CD34+ dose of 5.2 × 10⁶/kg. Of 77 evaluable patients, 75 had sustained CB engraftment that was mediated by a dominant unit and heralded by dominant unit-derived T-cells. Optimal haplo-identical donor-derived myeloid bridging was observed in 34/77 (44%) patients (median recovery 12 days). Other engrafting patients had transient bridging with second nadir preceding CB engraftment [20/77 (26%), median first recovery 12 and second 26.5 days] or no bridge [21/77 (27%), median recovery 25 days]. The 2 (3%) remaining patients had graft failure. Higher haplo-CD34+ dose and better dominant unit-haplo-CD34+ HLA-match significantly improved the likelihood of optimal bridging. Optimally bridged patients were discharged earlier [median 28 versus 36 days]. ATG-free haplo-dCBT can speed neutrophil recovery but successful bridging is not guaranteed due to rapid haplo-identical graft rejection.

Keywords

Cord blood transplantation, haplo-identical transplantation, engraftment, chimerism, anti-thymocyte globulin