PMID- 34844022
OWN - NLM
STAT- MEDLINE
DCOM- 20220420
LR  - 20220420
IS  - 2666-6367 (Electronic)
IS  - 2666-6367 (Linking)
VI  - 28
IP  - 2
DP  - 2022 Feb
TI  - Cytokine Release Syndrome Following Peripheral Blood Stem Cell Haploidentical 
      Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide.
PG  - 111.e1-111.e8
LID - S2666-6367(21)01397-X [pii]
LID - 10.1016/j.jtct.2021.11.012 [doi]
AB  - Post-transplantation cyclophosphamide (PTCy) is a safe and efficacious 
      graft-versus-host-disease (GVHD) prophylaxis following hematopoietic cell 
      transplantation (HCT) from a haploidentical (haplo) donor. Cytokine release 
      syndrome (CRS) is a common complication of this platform. Early fever 
      post-haplo-HCT using bone marrow grafts is associated with higher CD3(+) cell 
      dose and CRS. However, the impact of CD3(+) and CD34(+) cell dose on CRS 
      post-haplo-HCT using peripheral blood stem cell (PBSC) grafts is unknown. Our 
      goals were to evaluate the incidence of CRS following PBSC transplantation 
      (PBSCT) and to identify factors that can be modified to prevent the development 
      of severe CRS in this setting. In 271 patients, we investigated factors 
      associated with the development of CRS following haplo-PBSCT and examined the 
      impact of CRS on clinical outcomes. Ninety-three percent of the patients 
      developed CRS of any grade post-haplo-PBSCT. In multivariate analysis, severe CRS 
      (grade 3-4 versus grade 0-1) was associated with higher nonrelapse mortality 
      (hazard ratio [HR], 6.42; 95% confidence interval [CI], 2.68 to 15.39; P < .001), 
      worse 1-year overall survival (HR, 3.40; 95% CI, 1.63 to 7.08; P = .005), and 
      worse disease-free survival (HR, 4.02; 95% CI, 1.99 to 8.08; P < .001). Moderate 
      to severe CRS (grade 2-4) did not impact 1-year relapse or acute GVHD (grade 
      II-IV and III-IV) at 100 days (P = .71 and .19, respectively). Importantly, 
      higher CD3(+) cell dose, but not CD34(+) cell dose, predicted a higher incidence 
      of grade 2-4 CRS (HR, 1.20; 95% CI,1.07 to 1.36; P = .003) and grade 3-4 CRS (HR, 
      1.40; 95% CI, 1.05 to 1.86; P = .022). Both older age (HR, 8.57; 95% CI, 1.73 to 
      42.36; P < .001) and non-total body irradiation-based reduced-intensity 
      conditioning with fludarabine/melphalan (HR, 15.38; 955 CI, 2.06 to 114.67; P < 
      .001) were predictive of grade 3-4 CRS. Overall, we observed that severe CRS 
      (grade 3-4) negatively affected transplantation outcome, and that higher CD3 cell 
      dose was associated with the development of any grade CRS and severe CRS.
CI  - Copyright (c) 2021 The American Society for Transplantation and Cellular Therapy. 
      Published by Elsevier Inc. All rights reserved.
FAU - Otoukesh, Salman
AU  - Otoukesh S
AD  - Department of Hematology and Hematopoietic Cell Transplantation, City of Hope 
      National Medical Center, Duarte, California.
FAU - Elmariah, Hany
AU  - Elmariah H
AD  - Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee 
      Moffitt Cancer Center & Research Institute, Tampa, Florida.
FAU - Yang, Dongyun
AU  - Yang D
AD  - Department of Computational and Quantitative Medicine, Division of Biostatistics, 
      City of Hope National Medical Center, Duarte, California.
FAU - Clark, Mary C
AU  - Clark MC
AD  - Department of Clinical and Translational Project Development, City of Hope 
      National Medical Center, Duarte, California.
FAU - Siraj, Madiha
AU  - Siraj M
AD  - University of South Florida, Tampa, Florida.
FAU - Ali, Haris
AU  - Ali H
AD  - Department of Hematology and Hematopoietic Cell Transplantation, City of Hope 
      National Medical Center, Duarte, California.
FAU - Mogili, Krishnakar
AU  - Mogili K
AD  - Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee 
      Moffitt Cancer Center & Research Institute, Tampa, Florida.
FAU - Arslan, Shukaib
AU  - Arslan S
AD  - Department of Hematology and Hematopoietic Cell Transplantation, City of Hope 
      National Medical Center, Duarte, California.
FAU - Nishihori, Taiga
AU  - Nishihori T
AD  - Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee 
      Moffitt Cancer Center & Research Institute, Tampa, Florida.
FAU - Nakamura, Ryotaro
AU  - Nakamura R
AD  - Department of Hematology and Hematopoietic Cell Transplantation, City of Hope 
      National Medical Center, Duarte, California.
FAU - Pidala, Joseph
AU  - Pidala J
AD  - Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee 
      Moffitt Cancer Center & Research Institute, Tampa, Florida.
FAU - Marcucci, Guido
AU  - Marcucci G
AD  - Department of Hematology and Hematopoietic Cell Transplantation, City of Hope 
      National Medical Center, Duarte, California.
FAU - Forman, Stephen J
AU  - Forman SJ
AD  - Department of Hematology and Hematopoietic Cell Transplantation, City of Hope 
      National Medical Center, Duarte, California.
FAU - Anasetti, Claudio
AU  - Anasetti C
AD  - Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee 
      Moffitt Cancer Center & Research Institute, Tampa, Florida.
FAU - Al Malki, Monzr M
AU  - Al Malki MM
AD  - Department of Hematology and Hematopoietic Cell Transplantation, City of Hope 
      National Medical Center, Duarte, California. Electronic address: 
      malmalki@coh.org.
FAU - Bejanyan, Nelli
AU  - Bejanyan N
AD  - Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee 
      Moffitt Cancer Center & Research Institute, Tampa, Florida.
LA  - eng
PT  - Journal Article
DEP - 20211126
PL  - United States
TA  - Transplant Cell Ther
JT  - Transplantation and cellular therapy
JID - 101774629
RN  - 8N3DW7272P (Cyclophosphamide)
SB  - IM
MH  - Cyclophosphamide/therapeutic use
MH  - Cytokine Release Syndrome
MH  - *Graft vs Host Disease/epidemiology
MH  - *Hematopoietic Stem Cell Transplantation/adverse effects
MH  - Humans
MH  - Neoplasm Recurrence, Local/complications
MH  - *Peripheral Blood Stem Cells
OTO - NOTNLM
OT  - CD3+ cell dose
OT  - CRS
OT  - Cytokine release syndrome
OT  - Halploidentical HCT
OT  - Peripheral blood stem cell
EDAT- 2021/11/30 06:00
MHDA- 2022/04/21 06:00
CRDT- 2021/11/29 20:16
PHST- 2021/09/23 00:00 [received]
PHST- 2021/11/17 00:00 [revised]
PHST- 2021/11/21 00:00 [accepted]
PHST- 2021/11/30 06:00 [pubmed]
PHST- 2022/04/21 06:00 [medline]
PHST- 2021/11/29 20:16 [entrez]
AID - S2666-6367(21)01397-X [pii]
AID - 10.1016/j.jtct.2021.11.012 [doi]
PST - ppublish
SO  - Transplant Cell Ther. 2022 Feb;28(2):111.e1-111.e8. doi: 
      10.1016/j.jtct.2021.11.012. Epub 2021 Nov 26.