PMID- 33290545
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20231110
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 4
IP  - 23
DP  - 2020 Dec 8
TI  - High progression-free survival after intermediate intensity double unit cord 
      blood transplantation in adults.
PG  - 6064-6076
LID - 10.1182/bloodadvances.2020003371 [doi]
AB  - Cord blood transplantation (CBT) after high intensity or nonmyeloablative 
      conditioning has limitations. We investigated cyclosporine-A/mycophenolate 
      mofetil-based intermediate intensity (cyclophosphamide 50 mg/kg, fludarabine 150 
      mg/m2, thiotepa 10 mg/kg, total body irradiation 400 cGy) unmanipulated 
      double-unit CBT (dCBT) with prioritization of unit quality and CD34+ cell dose in 
      graft selection. Ninety adults (median age, 47 years [range, 21-63]; median 
      hematopoietic cell transplantation comorbidity index, 2 [range, 0-8]; 61 [68%] 
      acute leukemia) received double-unit grafts (median CD34+ cell dose, 1.3 x 105/kg 
      per unit [range, 0.2-8.3]; median donor-recipient human leukocyte antigen (HLA) 
      match, 5/8 [range 3-7/8]). The cumulative incidences of sustained CB engraftment, 
      day 180 grade III-IV acute, and 3-year chronic graft-versus-host disease were 
      99%, 24%, and 7%, respectively. Three-year transplant-related mortality (TRM) and 
      relapse incidences were 15% and 9%, respectively. Three-year overall survival 
      (OS) is 82%, and progression-free survival (PFS) is 76%. Younger age and higher 
      engrafting unit CD34+ cell dose both improved TRM and OS, although neither 
      impacted PFS. Engrafting unit-recipient HLA match was not associated with any 
      outcome with a 3-year PFS of 79% in 39 patients engrafting with 3-4/8 HLA-matched 
      units. In 52 remission acute leukemia patients, there was no association between 
      minimal residual disease (MRD) and 3-year PFS: MRD negative of 88% vs MRD 
      positive of 77% (P = .375). Intermediate intensity dCBT is associated with high 
      PFS. Use of highly HLA mismatched and unmanipulated grafts permits wide 
      application of this therapy, and the low relapse rates support robust 
      graft-versus-leukemia effects even in patients with MRD.
CI  - (c) 2020 by The American Society of Hematology.
FAU - Barker, Juliet N
AU  - Barker JN
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
FAU - Devlin, Sean M
AU  - Devlin SM
AD  - Department of Epidemiology and Biostatistics.
FAU - Naputo, Kristine A
AU  - Naputo KA
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
FAU - Skinner, Kelcey
AU  - Skinner K
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
FAU - Maloy, Molly A
AU  - Maloy MA
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
FAU - Flynn, Lisa
AU  - Flynn L
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
FAU - Anagnostou, Theodora
AU  - Anagnostou T
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
FAU - Avecilla, Scott T
AU  - Avecilla ST
AD  - Department of Laboratory Medicine, and.
FAU - Scaradavou, Andromachi
AU  - Scaradavou A
AD  - Stem Cell Transplantation and Cellular Therapies, MSK Kids, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Pediatrics, Weill Cornell Medical College, New York, NY; and.
FAU - Cho, Christina
AU  - Cho C
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
FAU - Dahi, Parastoo B
AU  - Dahi PB
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
FAU - Giralt, Sergio A
AU  - Giralt SA
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
FAU - Gyurkocza, Boglarka
AU  - Gyurkocza B
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
FAU - Hanash, Alan M
AU  - Hanash AM
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
FAU - Hsu, Katharine
AU  - Hsu K
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
FAU - Jakubowski, Ann A
AU  - Jakubowski AA
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
FAU - Papadopoulos, Esperanza B
AU  - Papadopoulos EB
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
FAU - Peled, Jonathan U
AU  - Peled JU
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
FAU - Perales, Miguel-Angel
AU  - Perales MA
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
FAU - Sauter, Craig S
AU  - Sauter CS
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
FAU - Shah, Gunjan L
AU  - Shah GL
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
FAU - Shaffer, Brian C
AU  - Shaffer BC
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
FAU - Tamari, Roni
AU  - Tamari R
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
FAU - Young, James W
AU  - Young JW
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
FAU - Roshal, Mikhail
AU  - Roshal M
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
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.
AD  - Department of Pediatrics, Weill Cornell Medical College, New York, NY; and.
FAU - Ponce, Doris M
AU  - Ponce DM
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
FAU - Politikos, Ioannis
AU  - Politikos I
AD  - Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
LA  - eng
GR  - K08 HL143189/HL/NHLBI NIH HHS/United States
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
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
SB  - IM
MH  - Adult
MH  - *Cord Blood Stem Cell Transplantation
MH  - *Graft vs Host Disease
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Middle Aged
MH  - Progression-Free Survival
MH  - Transplantation Conditioning
MH  - Young Adult
PMC - PMC7724901
COIS- Conflict--interest disclosure: J.N.B. has received clinical trial funding from 
      Angiocrine Bioscience and an unrestricted educational grant from Merck. S.T.A. 
      has received honoraria from Abbott Laboratories. A.S. was the Medical Director of 
      the National Cord Blood Program until 1/2020 and serves as a consultant at the 
      Scientific Advisory Board of ExCellThera. S.A.G. has served as a consultant for 
      Amgen, Actinium, Celgene, Johnson & Johnson, Jazz Pharmaceutical, Takeda, 
      Novartis, Kite, and Spectrum Pharma and has received research funding from Amgen, 
      Actinium, Celgene, Johnson & Johnson, Miltenyi, and Takeda. J.U.P. reports 
      research funding, intellectual property fees, and travel reimbursement from Seres 
      Therapeutics and consulting fees from DaVolterra. M.-A.P. has received honoraria 
      from Abbvie, Bellicum, Bristol-Myers Squibb, Incyte, Kite (Gilead), Merck, 
      Novartis, Nektar Therapeutics, and Takeda; serves on data and safety monitoring 
      boards for Servier, Cidara Therapeutics and Medigene; serves on 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, and GSK, and has received research funds for 
      clinical trials from Juno Therapeutics, Celgene, Bristol-Myers Squibb, Precision 
      Biosciences, and Sanofi-Genzyme. R.J.O. receives royalties from Atara 
      Biotherapeutics. I.P. has received research funding from Merck and serves as a 
      member on a data and safety monitoring board for ExcellThera. The remaining 
      authors declare no competing financial interests.
EDAT- 2020/12/09 06:00
MHDA- 2021/05/15 06:00
PMCR- 2020/12/08
CRDT- 2020/12/08 17:18
PHST- 2020/09/08 00:00 [received]
PHST- 2020/10/26 00:00 [accepted]
PHST- 2020/12/08 17:18 [entrez]
PHST- 2020/12/09 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/12/08 00:00 [pmc-release]
AID - S2473-9529(20)32033-4 [pii]
AID - 2020/ADV2020003371 [pii]
AID - 10.1182/bloodadvances.2020003371 [doi]
PST - ppublish
SO  - Blood Adv. 2020 Dec 8;4(23):6064-6076. doi: 10.1182/bloodadvances.2020003371.