PMID- 36499545
OWN - NLM
STAT- MEDLINE
DCOM- 20221216
LR  - 20221222
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 23
DP  - 2022 Dec 2
TI  - Anti-Thymocyte Globulin (ATG)-Free Nonmyeloablative Haploidentical PBSCT Plus 
      Post-Transplantation Cyclophosphamide Is a Safe and Efficient Treatment Approach 
      for Pediatric Acquired Aplastic Anemia.
LID - 10.3390/ijms232315192 [doi]
LID - 15192
AB  - Most cases of acquired aplastic anemia (AA) arise from autoimmune destruction of 
      hematopoietic stem and progenitor cells. Human leukocyte antigen 
      (HLA)-haploidentical nonmyeloablative hematopoietic stem cell transplantation 
      (HSCT) plus post-transplantation cyclophosphamide (PTCy) is increasingly applied 
      to salvage AA using bone marrow as graft and anti-thymocyte globulin (ATG) in 
      conditioning. Herein, we characterize a cohort of twelve AA patients clinically 
      and molecularly, six who possessed other immunological disorders (including two 
      also carrying germline SAMD9L mutations). Each patient with SAMD9L mutation also 
      carried an AA-related rare BCORL1 variant or CTLA4 p.T17A GG genotype, 
      respectively, and both presented short telomere lengths. Six of the ten patients 
      analyzed harbored AA-risky HLA polymorphisms. All patients recovered upon 
      non-HSCT (n = 4) or HSCT (n = 8) treatments. Six of the eight HSCT-treated 
      patients were subjected to a modified PTCy-based regimen involving freshly 
      prepared peripheral blood stem cells (PBSC) as graft and exclusion of ATG. All 
      patients were engrafted between post-transplantation days +13 and +18 and quickly 
      reverted to normal life, displaying a sustained complete hematologic response and 
      an absence of graft-versus-host disease. These outcomes indicate most AA cases, 
      including of the SAMD9L-inherited subtype, are immune-mediated and the modified 
      PTCy-based regimen we present is efficient and safe for salvage.
FAU - Chen, Rong-Long
AU  - Chen RL
AUID- ORCID: 0000-0003-0290-9886
AD  - Department of Pediatric Hematology and Oncology, Koo Foundation Sun Yat-sen 
      Cancer Center, Taipei 11259, Taiwan.
FAU - Ip, Peng Peng
AU  - Ip PP
AD  - Institute of Molecular Biology, Academia Sinica, Taipei 115024, Taiwan.
FAU - Shaw, Jy-Juinn
AU  - Shaw JJ
AD  - School of Law, National Yang Ming Chiao Tung University, Hsinchu City 30093, 
      Taiwan.
FAU - Wang, Yun-Hsin
AU  - Wang YH
AD  - Department of Chemistry, Tamkang University, Tamsui, New Taipei City 251301, 
      Taiwan.
FAU - Fan, Li-Hua
AU  - Fan LH
AD  - Department of Pharmacy, Koo Foundation Sun Yat-sen Cancer Center, Taipei 11259, 
      Taiwan.
FAU - Shen, Yi-Ling
AU  - Shen YL
AD  - Institute of Molecular Biology, Academia Sinica, Taipei 115024, Taiwan.
FAU - Joseph, Nithila A
AU  - Joseph NA
AD  - Institute of Molecular Biology, Academia Sinica, Taipei 115024, Taiwan.
FAU - Chen, Tsen-Erh
AU  - Chen TE
AD  - Institute of Molecular Biology, Academia Sinica, Taipei 115024, Taiwan.
FAU - Chen, Liuh-Yow
AU  - Chen LY
AUID- ORCID: 0000-0002-9857-068X
AD  - Institute of Molecular Biology, Academia Sinica, Taipei 115024, Taiwan.
LA  - eng
GR  - FACSI 211001/Family Association for Children with Serious Illness, Taiwan/
PT  - Journal Article
DEP - 20221202
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antilymphocyte Serum)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Humans
MH  - Child
MH  - Antilymphocyte Serum/therapeutic use
MH  - *Anemia, Aplastic/genetics/therapy
MH  - Transplantation Conditioning
MH  - *Graft vs Host Disease/etiology
MH  - Cyclophosphamide/therapeutic use
MH  - *Hematopoietic Stem Cell Transplantation/adverse effects
MH  - HLA Antigens
MH  - Retrospective Studies
PMC - PMC9739033
OTO - NOTNLM
OT  - SAMD9L variant
OT  - anti-thymocyte globulin
OT  - nonmyeloablative haploidentical peripheral blood stem cell transplantation
OT  - post-transplantation cyclophosphamide
OT  - severe aplastic anemia
COIS- The authors declare no conflict of interest.
EDAT- 2022/12/12 06:00
MHDA- 2022/12/15 06:00
PMCR- 2022/12/02
CRDT- 2022/12/11 01:21
PHST- 2022/10/24 00:00 [received]
PHST- 2022/11/29 00:00 [revised]
PHST- 2022/11/30 00:00 [accepted]
PHST- 2022/12/11 01:21 [entrez]
PHST- 2022/12/12 06:00 [pubmed]
PHST- 2022/12/15 06:00 [medline]
PHST- 2022/12/02 00:00 [pmc-release]
AID - ijms232315192 [pii]
AID - ijms-23-15192 [pii]
AID - 10.3390/ijms232315192 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Dec 2;23(23):15192. doi: 10.3390/ijms232315192.