PMID- 33570626
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20211204
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 5
IP  - 1
DP  - 2021 Jan 12
TI  - Immune reconstitution and infectious complications following axicabtagene 
      ciloleucel therapy for large B-cell lymphoma.
PG  - 143-155
LID - 10.1182/bloodadvances.2020002732 [doi]
AB  - Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has significantly 
      improved outcomes in the treatment of refractory or relapsed large B-cell 
      lymphoma (LBCL). We evaluated the long-term course of hematologic recovery, 
      immune reconstitution, and infectious complications in 41 patients with LBCL 
      treated with axicabtagene ciloleucel (axi-cel) at a single center. Grade 3+ 
      cytopenias occurred in 97.6% of patients within the first 28 days postinfusion, 
      with most resolved by 6 months. Overall, 63.4% of patients received a red blood 
      cell transfusion, 34.1% of patients received a platelet transfusion, 36.6% of 
      patients received IV immunoglobulin, and 51.2% of patients received growth factor 
      (granulocyte colony-stimulating factor) injections beyond the first 28 days 
      postinfusion. Only 40% of patients had recovered detectable CD19+ B cells by 1 
      year, and 50% of patients had a CD4+ T-cell count <200 cells per muL by 18 months 
      postinfusion. Patients with durable responses to axi-cel had significantly longer 
      durations of B-cell aplasia, and this duration correlated strongly with the 
      recovery of CD4+ T-cell counts. There were significantly more infections within 
      the first 28 days compared with any other period of follow-up, with the majority 
      being mild-moderate in severity. Receipt of corticosteroids was the only factor 
      that predicted risk of infection in a multivariate analysis (hazard ratio, 3.69; 
      95% confidence interval, 1.18-16.5). Opportunistic infections due to Pneumocystis 
      jirovecii and varicella-zoster virus occurred up to 18 months postinfusion in 
      patients who prematurely discontinued prophylaxis. These results support the use 
      of comprehensive supportive care, including long-term monitoring and 
      antimicrobial prophylaxis, beyond 12 months after axi-cel treatment.
CI  - (c) 2021 by The American Society of Hematology.
FAU - Baird, John H
AU  - Baird JH
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA; and.
FAU - Epstein, David J
AU  - Epstein DJ
AD  - Division of Infectious Diseases and Geographic Medicine, Department of Medicine.
FAU - Tamaresis, John S
AU  - Tamaresis JS
AD  - Department of Biomedical Data Science, and.
FAU - Ehlinger, Zachary
AU  - Ehlinger Z
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA; and.
FAU - Spiegel, Jay Y
AU  - Spiegel JY
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA; and.
FAU - Craig, Juliana
AU  - Craig J
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA; and.
FAU - Claire, Gursharan K
AU  - Claire GK
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA; and.
FAU - Frank, Matthew J
AU  - Frank MJ
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA; and.
FAU - Muffly, Lori
AU  - Muffly L
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA; and.
FAU - Shiraz, Parveen
AU  - Shiraz P
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA; and.
FAU - Meyer, Everett
AU  - Meyer E
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA; and.
FAU - Arai, Sally
AU  - Arai S
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
FAU - Brown, Janice Wes
AU  - Brown JW
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Division of Infectious Diseases and Geographic Medicine, Department of Medicine.
FAU - Johnston, Laura
AU  - Johnston L
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
FAU - Lowsky, Robert
AU  - Lowsky R
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
FAU - Negrin, Robert S
AU  - Negrin RS
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
FAU - Rezvani, Andrew R
AU  - Rezvani AR
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
FAU - Weng, Wen-Kai
AU  - Weng WK
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
FAU - Latchford, Theresa
AU  - Latchford T
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
FAU - Sahaf, Bita
AU  - Sahaf B
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA; and.
FAU - Mackall, Crystal L
AU  - Mackall CL
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA; and.
AD  - Division of Hematology/Oncology, Department of Pediatrics, Stanford University 
      School of Medicine, Stanford, CA.
FAU - Miklos, David B
AU  - Miklos DB
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA; and.
FAU - Sidana, Surbhi
AU  - Sidana S
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA; and.
LA  - eng
GR  - KL2 TR003143/TR/NCATS NIH HHS/United States
GR  - P01 CA049605/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
RN  - 0 (Antigens, CD19)
RN  - 0 (Biological Products)
RN  - U2I8T43Y7R (axicabtagene ciloleucel)
SB  - IM
MH  - Antigens, CD19/therapeutic use
MH  - Biological Products
MH  - Humans
MH  - *Immune Reconstitution
MH  - Immunotherapy, Adoptive
MH  - *Lymphoma, Large B-Cell, Diffuse
PMC - PMC7805341
COIS- Conflict-of-interest disclosure: P.S. has received research support from Kite 
      Pharma-Gilead. A.R.R. has received research support from Pharmacyclics/AbbVie; 
      has served on ad hoc scientific advisory boards for Nohla Therapeutics and 
      Kaleido; has served as an expert witness for US Department of Justice; and his 
      brother works for Johnson & Johnson. T.L. has been a member of the speaker's 
      bureau for Kite Pharma-Gilead. C.L.M. has acted as a consultant for Lyell, 
      NeoimmuneTech, Nektar Therapeutics, and Apricity Therapeutics; has received 
      royalties from the National Institutes of Heath and Juno Therapeutics for 
      CD22-CARl and has equity in Lyell and Allogene Therapeutics. D.B.M. has acted as 
      a consulting for Kite Pharma-Gilead, Juno Therapeutics-Celgene, Novartis, Janssen 
      Pharmaceuticals, and Pharmacyclics and has received research support from Kite 
      Pharma-Gilead, Allogene Therapeutics, Pharmacyclics, Miltenyi Biotec, and 
      Adaptive Biotechnologies. S.S. has acted as a consultant for Janssen 
      Pharmaceuticals. The remaining authors declare no competing financial interests.
EDAT- 2021/02/12 06:00
MHDA- 2021/05/15 06:00
PMCR- 2021/01/05
CRDT- 2021/02/11 12:10
PHST- 2020/06/19 00:00 [received]
PHST- 2020/10/30 00:00 [accepted]
PHST- 2021/02/11 12:10 [entrez]
PHST- 2021/02/12 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2021/01/05 00:00 [pmc-release]
AID - S2473-9529(21)00009-4 [pii]
AID - 2020/ADV2020002732 [pii]
AID - 10.1182/bloodadvances.2020002732 [doi]
PST - ppublish
SO  - Blood Adv. 2021 Jan 12;5(1):143-155. doi: 10.1182/bloodadvances.2020002732.