The JAK/STAT signaling pathway contributes to the immune response which causes GvHD1
GvHD is the primary immunological complication to allogeneic HSCT , it is the second leading cause of death in patients undergoing allogeneic HSCT, behind only mortality from primary disease2.
There are two types of GvHD3
- Acute GvHD
- Chronic GvHD
Symptoms of aGvHD include
Skin
- Maculopapular rash5
- Blistering and ulceration in severe cases5
GI
- Nausea5
- Anorexia5
- Vomiting5
- Watery Diarrhea5
- Positive Histological Findings5
Liver
- Bile duct destruction5
- Elevated serum bilirubin levels5
Clear goals for better outcomes
Treatment goals
Achieving a higher Overall Response without the requirement of additional systemic therapies 6
Achieving failure free survival6
Reduction of average steroid dose7
Reducing the risk of relapse, disease recurrence, or death caused by the underlying condition6
Guidelines Recommendation
2024 EBMT Guidelines: Ruxolitinib is a recommended therapy for SR-GvHD (acute and chronic)8
2025 NCCN Guidelines®: Ruxolitinib is recommended as a category I treatment option for SR-GvHD (acute and chronic)9
References
Heine A, Held SA, Daecke SN, Wallner S, Yajnanarayana SP, Kurts C, Wolf D, Brossart P. The JAK-inhibitor ruxolitinib impairs dendritic cell function in vitro and in vivo. Blood, The Journal of the American Society of Hematology. 2013 Aug 15;122(7):1192-202.
McDonald-Hyman C, Turka LA, Blazar BR. Advances and challenges in immunotherapy for solid organ and hematopoietic stem cell transplantation. Science translational medicine. 2015 Mar 25;7(280):280rv2-.
Garnett C, Apperley JF, Pavlů J. Treatment and management of graft-versus-host disease: improving response and survival. Therapeutic advances in hematology. 2013 Dec;4(6):366-78.
Zeiser R, Blazar BR. Acute graft-versus-host disease—biologic process, prevention, and therapy. New England Journal of Medicine. 2017 Nov 30;377(22):2167-79.
Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. The Lancet. 2009 May 2;373(9674):1550-61.
Zeiser R, von Bubnoff N, Butler J, Mohty M, Niederwieser D, Or R, Szer J, Wagner EM, Zuckerman T, Mahuzier B, Xu J. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. New England Journal of Medicine. 2020 May 7;382(19):1800-10.
Zeiser R, Polverelli N, Ram R, Hashmi SK, Chakraverty R, Middeke JM, Musso M, Giebel S, Uzay A, Langmuir P, Hollaender N. Ruxolitinib for glucocorticoid-refractory chronic graft-versushost disease. New England Journal of Medicine. 2021 Jul 15;385(3):228-38.
Penack O, Marchetti M, Aljurf M, Arat M, Bonifazi F, Duarte RF, Giebel S, Greinix H, Hazenberg MD, Kröger N, Mielke S. Prophylaxis and management of graft-versus-host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation. The Lancet Haematology. 2024 Feb 1;11(2):e147-59.Available at https://linkinghub.elsevier.com/retrieve/pii/S2352-3026(23)00342-3 [Last accessed: 06/10/2025].
(NCCN Guidelines®) for Hematopoietic Cell Transplantation (HCT).V.2.2025. Available at https://www.nccn.org/guidelines/guidelines-detail?category=3&id=1501. [Last accessed: 06/10/2025].
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