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Engraftment kinetics after transplantation of double unit cord blood grafts combined with haplo-identical CD34+ cells without antithymocyte globulin.
Leukemia. 2020 Jun 18 [Online ahead of print]L

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 antithymocyte globulin, ATG). CB units (median CD34+ dose 1.1 × 105/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 × 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.

Authors+Show Affiliations

Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. politiki@mskcc.org. Department of Medicine, Weill Cornell Medical College, New York, NY, USA. politiki@mskcc.org.Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.Diagnostic Molecular Pathology, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.Stem Cell Transplantation and Cellular Therapies, MSK Kids, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA.Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Department of Medicine, Weill Cornell Medical College, New York, NY, USA.Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Department of Medicine, Weill Cornell Medical College, New York, NY, USA.Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Department of Medicine, Weill Cornell Medical College, New York, NY, USA.Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Department of Medicine, Weill Cornell Medical College, New York, NY, USA.Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Department of Medicine, Weill Cornell Medical College, New York, NY, USA.Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Department of Medicine, Weill Cornell Medical College, New York, NY, USA.Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Department of Medicine, Weill Cornell Medical College, New York, NY, USA.Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Department of Medicine, Weill Cornell Medical College, New York, NY, USA.Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Department of Medicine, Weill Cornell Medical College, New York, NY, USA.Stem Cell Transplantation and Cellular Therapies, MSK Kids, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA.Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. barkerj@mskcc.org. Department of Medicine, Weill Cornell Medical College, New York, NY, USA. barkerj@mskcc.org.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32555371

Citation

Politikos, Ioannis, et al. "Engraftment Kinetics After Transplantation of Double Unit Cord Blood Grafts Combined With Haplo-identical CD34+ Cells Without Antithymocyte Globulin." Leukemia, 2020.
Politikos I, Devlin SM, Arcila ME, et al. Engraftment kinetics after transplantation of double unit cord blood grafts combined with haplo-identical CD34+ cells without antithymocyte globulin. Leukemia. 2020.
Politikos, I., Devlin, S. M., Arcila, M. E., Barone, J. C., Maloy, M. A., Naputo, K. A., Ruiz, J. D., Mazis, C. M., Scaradavou, A., Avecilla, S. T., Dahi, P. B., Giralt, S. A., Hsu, K. C., Jakubowski, A. A., Papadopoulos, E. B., Perales, M. A., Sauter, C. S., Tamari, R., Ponce, D. M., ... Barker, J. N. (2020). Engraftment kinetics after transplantation of double unit cord blood grafts combined with haplo-identical CD34+ cells without antithymocyte globulin. Leukemia. https://doi.org/10.1038/s41375-020-0922-x
Politikos I, et al. Engraftment Kinetics After Transplantation of Double Unit Cord Blood Grafts Combined With Haplo-identical CD34+ Cells Without Antithymocyte Globulin. Leukemia. 2020 Jun 18; PubMed PMID: 32555371.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Engraftment kinetics after transplantation of double unit cord blood grafts combined with haplo-identical CD34+ cells without antithymocyte globulin. AU - Politikos,Ioannis, AU - Devlin,Sean M, AU - Arcila,Maria E, AU - Barone,Jonathan C, AU - Maloy,Molly A, AU - Naputo,Kristine A, AU - Ruiz,Josel D, AU - Mazis,Christopher M, AU - Scaradavou,Andromachi, AU - Avecilla,Scott T, AU - Dahi,Parastoo B, AU - Giralt,Sergio A, AU - Hsu,Katherine C, AU - Jakubowski,Ann A, AU - Papadopoulos,Esperanza B, AU - Perales,Miguel A, AU - Sauter,Craig S, AU - Tamari,Roni, AU - Ponce,Doris M, AU - O'Reilly,Richard J, AU - Barker,Juliet N, Y1 - 2020/06/18/ PY - 2020/03/16/received PY - 2020/06/09/accepted PY - 2020/06/07/revised PY - 2020/6/20/entrez JF - Leukemia JO - Leukemia N2 - 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 × 105/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 × 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. SN - 1476-5551 UR - https://www.unboundmedicine.com/medline/citation/32555371/Engraftment_kinetics_after_transplantation_of_double_unit_cord_blood_grafts_combined_with_haplo-identical_CD34+_cells_without_antithymocyte_globulin L2 - http://dx.doi.org/10.1038/s41375-020-0922-x DB - PRIME DP - Unbound Medicine ER -
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