PMID- 32555371
OWN - NLM
STAT- MEDLINE
DCOM- 20210322
LR  - 20210617
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 35
IP  - 3
DP  - 2021 Mar
TI  - Engraftment kinetics after transplantation of double unit cord blood grafts 
      combined with haplo-identical CD34+ cells without antithymocyte globulin.
PG  - 850-862
LID - 10.1038/s41375-020-0922-x [doi]
AB  - 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 x 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 x 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.
FAU - Politikos, Ioannis
AU  - Politikos I
AUID- ORCID: 0000-0002-2854-8751
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY, USA. politiki@mskcc.org.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY, USA. 
      politiki@mskcc.org.
FAU - Devlin, Sean M
AU  - Devlin SM
AD  - Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer 
      Center, New York, NY, USA.
FAU - Arcila, Maria E
AU  - Arcila ME
AD  - Diagnostic Molecular Pathology, Department of Pathology, Memorial Sloan Kettering 
      Cancer Center, New York, NY, USA.
FAU - Barone, Jonathan C
AU  - Barone JC
AD  - Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New 
      York, NY, USA.
FAU - Maloy, Molly A
AU  - Maloy MA
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY, USA.
FAU - Naputo, Kristine A
AU  - Naputo KA
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY, USA.
FAU - Ruiz, Josel D
AU  - Ruiz JD
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY, USA.
FAU - Mazis, Christopher M
AU  - Mazis CM
AUID- ORCID: 0000-0002-7490-2395
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY, USA.
FAU - Scaradavou, Andromachi
AU  - Scaradavou A
AD  - Stem Cell Transplantation and Cellular Therapies, MSK Kids, Memorial Sloan 
      Kettering Cancer Center, New York, NY, USA.
AD  - Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA.
FAU - Avecilla, Scott T
AU  - Avecilla ST
AUID- ORCID: 0000-0003-0661-9704
AD  - Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New 
      York, NY, USA.
FAU - Dahi, Parastoo B
AU  - Dahi PB
AUID- ORCID: 0000-0002-0794-3226
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY, USA.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
FAU - Giralt, Sergio A
AU  - Giralt SA
AUID- ORCID: 0000-0003-1944-5053
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY, USA.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
FAU - Hsu, Katherine C
AU  - Hsu KC
AUID- ORCID: 0000-0003-2827-5324
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY, USA.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
FAU - Jakubowski, Ann A
AU  - Jakubowski AA
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY, USA.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
FAU - Papadopoulos, Esperanza B
AU  - Papadopoulos EB
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY, USA.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
FAU - Perales, Miguel A
AU  - Perales MA
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY, USA.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
FAU - Sauter, Craig S
AU  - Sauter CS
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY, USA.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
FAU - Tamari, Roni
AU  - Tamari R
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY, USA.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
FAU - Ponce, Doris M
AU  - Ponce DM
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY, USA.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
FAU - O'Reilly, Richard J
AU  - O'Reilly RJ
AD  - Stem Cell Transplantation and Cellular Therapies, MSK Kids, Memorial Sloan 
      Kettering Cancer Center, New York, NY, USA.
AD  - Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA.
FAU - Barker, Juliet N
AU  - Barker JN
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY, USA. barkerj@mskcc.org.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY, USA. 
      barkerj@mskcc.org.
LA  - eng
GR  - P01 CA023766/CA/NCI NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20200618
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antigens, CD34)
RN  - 0 (Antilymphocyte Serum)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antigens, CD34/*metabolism
MH  - *Antilymphocyte Serum
MH  - Clinical Trials, Phase II as Topic
MH  - Donor Selection
MH  - Female
MH  - Fetal Blood/*transplantation
MH  - Follow-Up Studies
MH  - Graft vs Host Disease/*prevention & control
MH  - HLA Antigens/immunology
MH  - Haplotypes
MH  - Hematologic Neoplasms/pathology/*therapy
MH  - Hematopoietic Stem Cell Transplantation/*methods
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Transplantation Conditioning
MH  - Young Adult
PMC - PMC7746597
MID - NIHMS1602688
COIS- Conflict-of-Interest disclosure: I.P. has received research funding from Merck 
      and serves on a Data and Safety Monitoring Board (DSMB) for ExCellThera. A.S. 
      serves on a DSMB for ExcellThera and is the medical director of the New York 
      Blood Center/ National Cord Blood Program. S.T.A. has received honoraria from 
      Abbott Laboratories. S.A.G. has served as a consultant for Amgen, Actinium, 
      Celgene, Johnson & Johnson, Jazz pharmaceutical, Takeda, Novartis, Kite, Spectrum 
      Pharma and has received research funding from Amgen, Actinium, Celgene, Johnson & 
      Johnson, Miltenyi, Takeda. M.A.P. has received honoraria from Abbvie, Bellicum, 
      Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, and Takeda; 
      serves on DSMBs for Servier and Medigene, and the scientific advisory boards of 
      MolMed and NexImmune; and has received research support for clinical trials from 
      Incyte, Kite (Gilead) and Miltenyi Biotec. C.S.S. has served as a paid consultant 
      on advisory boards for Juno Therapeutics, Sanofi-Genzyme, Spectrum 
      Pharmaceuticals, Novartis, Genmab, Precision Biosciences, Kite, a Gilead Company, 
      Celgene, Gamida Cell, Pfizer, and GSK, and has received research funding for 
      clinical trials from Juno Therapeutics, Celgene, Precision Biosciences and 
      Sanofi-Genzyme. R.J.O.R. receives royalties from Atara Biotherapeutics. J.N.B. 
      has received research funding from Angiocrine Bioscience, Gamida Cell and Merck. 
      The authors have no other relevant conflicts of interest to declare.
EDAT- 2020/06/20 06:00
MHDA- 2021/03/23 06:00
PMCR- 2021/03/06
CRDT- 2020/06/20 06:00
PHST- 2020/03/16 00:00 [received]
PHST- 2020/06/09 00:00 [accepted]
PHST- 2020/06/07 00:00 [revised]
PHST- 2020/06/20 06:00 [pubmed]
PHST- 2021/03/23 06:00 [medline]
PHST- 2020/06/20 06:00 [entrez]
PHST- 2021/03/06 00:00 [pmc-release]
AID - 10.1038/s41375-020-0922-x [pii]
AID - 10.1038/s41375-020-0922-x [doi]
PST - ppublish
SO  - Leukemia. 2021 Mar;35(3):850-862. doi: 10.1038/s41375-020-0922-x. Epub 2020 Jun 
      18.