PMID- 38066845
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20240215
IS  - 1520-4383 (Electronic)
IS  - 1520-4391 (Print)
IS  - 1520-4383 (Linking)
VI  - 2023
IP  - 1
DP  - 2023 Dec 8
TI  - Chronic GVHD: review advances in prevention, novel endpoints, and targeted 
      strategies.
PG  - 164-170
LID - 10.1182/hematology.2023000427 [doi]
AB  - Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative therapy 
      for many malignant and non-malignant hematologic disorders. Chronic 
      graft-versus-host (cGVHD) disease remains a significant hurdle for long-term 
      survival in patients post allo-HCT, and it remains the leading cause of late 
      non-relapse mortality. The risk factors for development of cGVHD include degree 
      of human leukocyte antigen (HLA) disparity, increasing recipient age, use of 
      peripheral blood stem cells as a source, myeloablative conditioning regimens, 
      prior acute GVHD (aGVHD), and female donor to male recipient. Our biological 
      understanding of cGVHD is mostly derived from transplantation mouse models and 
      patient data. There are three distinct phases in the development of cGVHD. 
      Approaches to prevent GVHD include pharmacologic strategies such as calcineurin 
      inhibitors (cyclosporine, tacrolimus) combined with methotrexate or mTOR 
      inhibitors (sirolimus), and IMP dehydrogenase inhibitors (mycophenolate mofetil). 
      Increasingly, posttransplant cyclophosphamide is emerging as a promising strategy 
      for GVCHD prevention especially in a setting of reduced intensity conditioning. 
      Other approaches include serotherapy (ATG, Campath) and graft manipulation 
      strategies. A significant obstacle to evaluating the response of novel 
      GVHD-directed therapies has been standardized response assessments. This has 
      functioned as a barrier to designing and interpreting clinical trials that are 
      structured around the treatment of cGVHD. Novel endpoints including failure-free 
      survival, Graft-versus-host disease-free, relapse-free survival (GRFS), and 
      current GVHD-free, relapse-free survival (CGRFS) may create a clearer picture for 
      post-HCT outcomes. Targeted therapies including Bruton's tyrosine kinase 
      inhibition, JAK1/2 inhibition, and ROCK2 inhibitors have improved cGVHD therapy, 
      especially in the steroid refractory setting. Continued improvement in 
      prophylactic strategies for cGVHD, identification of accurate cGVHD treatment 
      endpoints, and access to novel therapeutic agents are expected to improve cGVHD 
      outcomes.
CI  - Copyright (c) 2023 by The American Society of Hematology.
FAU - Amanam, Idoroenyi
AU  - Amanam I
AD  - City of Hope National Medical Center, Duarte, CA.
FAU - Otoukesh, Salman
AU  - Otoukesh S
AD  - City of Hope National Medical Center, Duarte, CA.
FAU - Al Malki, Monzr M
AU  - Al Malki MM
AD  - City of Hope National Medical Center, Duarte, CA.
FAU - Salhotra, Amandeep
AU  - Salhotra A
AD  - City of Hope National Medical Center, Duarte, CA.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Hematology Am Soc Hematol Educ Program
JT  - Hematology. American Society of Hematology. Education Program
JID - 100890099
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - WM0HAQ4WNM (Tacrolimus)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Humans
MH  - Male
MH  - Female
MH  - *Graft vs Host Disease/prevention & control/etiology
MH  - Cyclosporine
MH  - Tacrolimus
MH  - Mycophenolic Acid
MH  - Methotrexate
MH  - *Hematopoietic Stem Cell Transplantation/adverse effects
MH  - Transplantation Conditioning
PMC - PMC10727045
COIS- Idoroenyi Amanam: no competing financial interests to declare. Salman Otoukesh: 
      no competing financial interests to declare. Monzr M. Al Malki: no competing 
      financial interests to declare. Amandeep Salhotra: no competing financial 
      interests to declare.
EDAT- 2023/12/09 10:43
MHDA- 2023/12/17 09:44
PMCR- 2024/12/08
CRDT- 2023/12/09 01:01
PHST- 2024/12/08 00:00 [pmc-release]
PHST- 2023/12/17 09:44 [medline]
PHST- 2023/12/09 10:43 [pubmed]
PHST- 2023/12/09 01:01 [entrez]
AID - 506393 [pii]
AID - 2023000427 [pii]
AID - 10.1182/hematology.2023000427 [doi]
PST - ppublish
SO  - Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):164-170. doi: 
      10.1182/hematology.2023000427.