PMID- 36343892
OWN - NLM
STAT- MEDLINE
DCOM- 20230213
LR  - 20240202
IS  - 2666-6367 (Electronic)
IS  - 2666-6375 (Print)
IS  - 2666-6367 (Linking)
VI  - 29
IP  - 2
DP  - 2023 Feb
TI  - Allogeneic Hematopoietic Cell Transplantation after Chimeric Antigen Receptor T 
      Cell Therapy in Large B Cell Lymphoma.
PG  - 99-107
LID - S2666-6367(22)01740-7 [pii]
LID - 10.1016/j.jtct.2022.10.026 [doi]
AB  - Anti-CD19 chimeric antigen receptor T cell (CAR-T) therapy has transformed the 
      care of patients with relapsed/refractory large B cell lymphoma (LBCL). However, 
      approximately 60% of CAR-T recipients ultimately will experience disease 
      recurrence or progression. Salvage therapies after CAR-T treatment failures are 
      of limited efficacy and have a short duration of response. The objective of the 
      present study was to evaluate the role of allogeneic hematopoietic cell 
      transplantation (allo-HCT) after CAR-T therapy in LBCL patients. This was a 
      multicenter observational study reporting the outcome of 39 adult LBCL patients 
      who underwent allo-HCT following anti-CD19 CAR-T therapy. The median patient age 
      was 47 years (range, 20 to 68 years). HLA-matched sibling, HLA-matched unrelated, 
      and alternative donors were used in 36%, 36%, and 28% of transplantations, 
      respectively. Conditioning regimens were primarily of low or intermediate 
      intensity. Disease status at allo-HCT was complete response in 41%, partial 
      response in 38%, and progressive disease in 21%. Allo-HCT was performed at a 
      median of 127 days (range, 82 to 206 days) after CAR-T therapy. A high incidence 
      of hepatic toxicity (28%), including sinusoidal obstruction syndrome (15.4%; 95% 
      confidence interval; [CI], 6.2% to 28.5%), was observed. The 1-year cumulative 
      incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) 
      was 38.5% (95% CI, 23.2% to 53.6%) and 15.4% (95% CI, 6.1% to 28.5%), 
      respectively. The 2-year cumulative incidence of moderate-severe chronic GVHD was 
      11.1% (95% CI, 3.3% to 24.3%). Overall, 2-year nonrelapse mortality and 
      relapse/progression incidence were 26% (95% CI, 13% to 41%) and 43% (95% CI, 27% 
      to 59%), respectively. With a median follow-up of 32 months, the 2-year overall 
      survival (OS) and progression-free survival (PFS) were 45% (95% CI, 31% to 66%) 
      and 31% (95% CI, 19% to 50%), respectively. In multivariable analyses, pre-HCT 
      elevated lactate dehydrogenase level and transformed lymphoma were predictive of 
      OS and PFS, respectively. Our data suggest that allo-HCT after anti-CD19 CAR-T 
      treatment failure is feasible with a relatively promising efficacy but possibly 
      high toxicity rate.
CI  - Copyright (c) 2022 The American Society for Transplantation and Cellular Therapy. 
      Published by Elsevier Inc. All rights reserved.
FAU - Fried, Shalev
AU  - Fried S
AD  - Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical 
      Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, 
      Tel-Aviv, Israel.
FAU - Shouval, Roni
AU  - Shouval R
AD  - Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan 
      Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New 
      York, New York. Electronic address: shouvalr@mskcc.org.
FAU - Walji, Moneeza
AU  - Walji M
AD  - Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan 
      Kettering Cancer Center, New York, New York.
FAU - Flynn, Jessica R
AU  - Flynn JR
AD  - Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer 
      Center, New York, New York.
FAU - Yerushalmi, Ronit
AU  - Yerushalmi R
AD  - Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical 
      Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, 
      Tel-Aviv, Israel.
FAU - Shem-Tov, Noga
AU  - Shem-Tov N
AD  - Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical 
      Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, 
      Tel-Aviv, Israel.
FAU - Danylesko, Ivetta
AU  - Danylesko I
AD  - Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical 
      Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, 
      Tel-Aviv, Israel.
FAU - Tomas, Ana Alarcon
AU  - Tomas AA
AD  - Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan 
      Kettering Cancer Center, New York, New York; PhD Program in Signals Integration 
      and Modulation in Biomedicine, Cellular Therapy, and Translational Medicine, 
      University of Murcia, Murcia, Spain.
FAU - Fein, Joshua A
AU  - Fein JA
AD  - University of Connecticut Medical Center, Farmington, Connecticut.
FAU - Devlin, Sean M
AU  - Devlin SM
AD  - Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer 
      Center, New York, New York.
FAU - Sauter, Craig S
AU  - Sauter CS
AD  - Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan 
      Kettering Cancer Center, New York, New York; Department of Hematology and Medical 
      Oncology, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
FAU - Shah, Gunjan L
AU  - Shah GL
AD  - Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan 
      Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New 
      York, New York.
FAU - Kedmi, Meirav
AU  - Kedmi M
AD  - Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical 
      Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, 
      Tel-Aviv, Israel; The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan 
      University, Ramat Gan, Israel.
FAU - Jacoby, Elad
AU  - Jacoby E
AD  - Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel; Department of 
      Pediatric Hematology-Oncology, Safra Children's Hospital, Chaim Sheba Medical 
      Center, Tel Hashomer, Israel.
FAU - Shargian, Liat
AU  - Shargian L
AD  - Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel; Institute of 
      Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah-Tikvah, Israel.
FAU - Raanani, Pia
AU  - Raanani P
AD  - Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel; Institute of 
      Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah-Tikvah, Israel.
FAU - Yeshurun, Moshe
AU  - Yeshurun M
AD  - Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel; Institute of 
      Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah-Tikvah, Israel.
FAU - Perales, Miguel-Angel
AU  - Perales MA
AD  - Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan 
      Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New 
      York, New York.
FAU - Nagler, Arnon
AU  - Nagler A
AD  - Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical 
      Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, 
      Tel-Aviv, Israel.
FAU - Avigdor, Abraham
AU  - Avigdor A
AD  - Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical 
      Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, 
      Tel-Aviv, Israel.
FAU - Shimoni, Avichai
AU  - Shimoni A
AD  - Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical 
      Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, 
      Tel-Aviv, Israel.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Observational Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20221105
PL  - United States
TA  - Transplant Cell Ther
JT  - Transplantation and cellular therapy
JID - 101774629
RN  - 0 (Receptors, Chimeric Antigen)
SB  - IM
CIN - Transplant Cell Ther. 2023 Feb;29(2):67-68. PMID: 36759047
MH  - Adult
MH  - Humans
MH  - Young Adult
MH  - Middle Aged
MH  - Aged
MH  - *Receptors, Chimeric Antigen
MH  - Neoplasm Recurrence, Local/complications
MH  - *Hematopoietic Stem Cell Transplantation/adverse effects
MH  - *Graft vs Host Disease/epidemiology/etiology
MH  - *Lymphoma, Large B-Cell, Diffuse/therapy
PMC - PMC10387120
MID - NIHMS1853768
OTO - NOTNLM
OT  - Allogeneic hematopoietic cell transplantation
OT  - Chimeric antigen receptor
OT  - GVHD
OT  - Large B cell lymphoma
OT  - Sinusoidal obstruction syndrome
OT  - Toxicity
COIS- Declaration of Competing Interest R.S. has served as a consultant for Medexus and 
      MyBiotics. M.A.P. has received honoraria from AbbVie, Astellas, Bristol-Myers 
      Squibb, Celgene, Equilium, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi 
      Biotec, MorphoSys, Novartis, Nektar Therapeutics, Omeros, Takeda, VectivBio AG, 
      and Vor Biopharma; has served on data safety and monitoring boards for Cidara 
      Therapeutics, Medigene, Sellas Life Sciences, and Servier and the scientific 
      advisory board of NexImmune; has ownership interests in NexImmune and Omeros; has 
      received research support for clinical trials from Incyte, Kite/Gilead, Miltenyi 
      Biotec, and Novartis; and serves in a volunteer capacity as a member of the Board 
      of Directors of the American Society for Transplantation and Cellular Therapy and 
      Be the Match (National Marrow Donor Program), as well as on the Center for 
      International Blood and Marrow Transplant Research's Cellular Immunotherapy Data 
      Resource executive committee. A.S. has served on scientific advisory boards for 
      Jazz Pharmaceutical, Gilead, Novartis, AbbVie, Bristol-Myers Squibb, and Medac. 
      A.A. reports honoraria from Gilead, Novartis, Takeda, Roche, Bristol-Myers 
      Squibb, and Sanofi. C.S.S. has served as a paid consultant on advisory boards for 
      Juno Therapeutics, Sanofi-Genzyme, Spectrum Pharmaceuticals, Novartis, Genmab, 
      Precision Biosciences, Kite/Gilead, Celgene/BMS, Gamida Cell, Karyopharm, Ono 
      Pharmaceuticals, and GSK and has received research funds for clinical trials from 
      Juno Therapeutics, Celgene/BMS, Bristol-Myers Squibb, Precision Biosciences, 
      Actinium Pharmaceuticals, and Sanofi-Genzyme. G.L.S. has received research 
      funding from Janssen, Amgen, and Beyond Spring.
EDAT- 2022/11/08 06:00
MHDA- 2023/02/14 06:00
PMCR- 2024/02/01
CRDT- 2022/11/07 19:27
PHST- 2022/07/01 00:00 [received]
PHST- 2022/10/20 00:00 [revised]
PHST- 2022/10/31 00:00 [accepted]
PHST- 2022/11/08 06:00 [pubmed]
PHST- 2023/02/14 06:00 [medline]
PHST- 2022/11/07 19:27 [entrez]
PHST- 2024/02/01 00:00 [pmc-release]
AID - S2666-6367(22)01740-7 [pii]
AID - 10.1016/j.jtct.2022.10.026 [doi]
PST - ppublish
SO  - Transplant Cell Ther. 2023 Feb;29(2):99-107. doi: 10.1016/j.jtct.2022.10.026. 
      Epub 2022 Nov 5.