Journal Article

Engraftment kinetics after transplantation of double unit cord blood grafts combined with haplo-identical CD34+ cells without antithymocyte globulin

Ruiz, Josel D., Hsu, Katherine C., Dahi, Parastoo B., Scaradavou, Andromachi, Arcila, Maria E., Perales, Miguel A., Papadopoulos, Esperanza B., Naputo, Kristine A., Sauter, Craig S., Giralt, Sergio A., Barone, Jonathan C., Jakubowski, Ann A., Maloy, Molly A., O’Reilly, Richard J., Avecilla, Scott T., Barker, Juliet N., Mazis, Christopher M., Tamari, Roni, Politikos, Ioannis, Devlin, Sean M., Ponce, Doris M.

2021

Overview

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 antithymocyte globulin, ATG). CB units (median CD34+ dose 1.1 × 10 5 /kg/unit) had a median 5/8 unit-recipient human leukocyte antigen (HLA)-match. Haplo-identical grafts had a median CD34+ dose of 5.2 × 10 6 /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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/250/1854/2812 / 631/250/1904 / 692/700/565/2319 / Adult / Aged / Antigens / Antigens, CD34 - metabolism / Antilymphocyte Serum / Blood / Cancer / Cancer Research / Care and treatment / CD34 antigen / Clinical Trials, Phase II as Topic / Cord blood / Critical Care Medicine / Cyclosporins / Donor Selection / Engraftment / Female / Fetal blood / Fetal Blood - transplantation / Follow-Up Studies / Globulins / Graft rejection / Graft vs Host Disease - prevention & control / Grafting / Grafts / Haplotypes / Hematologic Neoplasms - pathology / Hematologic Neoplasms - therapy / Hematology / Hematopoietic Stem Cell Transplantation - methods / Histocompatibility antigen HLA / HLA Antigens - immunology / Humans / Immune response / Immunoprophylaxis / Intensive / Internal Medicine / Leukocytes / Leukocytes (neutrophilic) / Lymphocytes / Lymphocytes T / Male / Medicine / Medicine & Public Health / Middle Aged / Mycophenolate mofetil / Mycophenolic acid / Neutrophils / Observations / Oncology / Oncology, Experimental / Optimization / Prognosis / Recovery / Thymocytes / Transplantation / Transplantation Conditioning / Young Adult