۱- BACKGROUND

۲- IN VIVO T‐ CELL DEPLETION: ALEMTUZUMAB AND ANTI‐THYMOCY TE GLOBULIN

۳- COSTIMUL ATORY BLOCK ADE: ABATACEPT AND ALEFACEPT

۴- PROTE A SOME INHIBITORS: BORTEZOMIB AND IXAZOMIB

۶- B‐ CELL MODUL ATION: RITUXIMAB, OFATUMUMAB, BTK /ITK , AND SYK INHIBITORS

۷- JANUS KINA SE INHIBITORS: RUXOLITINIB, BARICITINIB, AND ITACITINIB

۸- INDUC TION OF IMMUNE TOLER ANCE: E X TR ACORPORE AL PHOTOPHERESIS AND INTERLEUKIN‐۲

۹- CELLULAR THERAPIES

۱۰- HOW TO MANAGE CGVHD

۱۱- CONCLUSION

۱۲- FUTURE PERSPECTIVE

REFERENCES

Abstract

Chronic Graft Versus Host Disease (cGVHD) occurs in over 50‐۷۰% of patients un‐ dergoing hematopoietic stem‐cell transplantation (HSCT) and is the leading cause of late non‐relapse mortality. cGVHD typically has insidious multi‐organ involvement and has been associated with a worse quality of life, functional status, and increased risk of subsequent comorbidities. The last several years have seen advances in the understanding of the disease, which provided a framework for the design of transla‐ tional and clinical studies with newer agents currently at different phases which that may hopefully change the course of the disease. This review provides an overview of more commonly used and newer second line options for the management of cGVHD.

BACKGROUND

Chronic Graft‐Versus‐Host Disease (cGVHD) occurs in over 30%‐۷۰% of patients undergoing hematopoietic stem‐cell transplan‐ tation (HSCT)1 and is the leading cause of late nonrelapse mortality.2 Furthermore, cGVHD has been associated with a worse quality of life, functional status, and increased risk of subsequent comorbidi‐ ties. Unfortunately, advances in the practice of HSCT over the last several years have not decreased the incidence or severity of this complication.3 This is thought to be at least in part due to increased survival after HSCT and the use of pooled peripheral blood mono‐ nuclear cells. Thus, although many GVHD prevention regimens have reduced the incidence of acute graft‐versus‐host disease (aGVHD), cGVHD has been less affected.4 Chronic GVHD typically has insidious multi‐organ involvement, predominantly of mucocutaneous tissues. This defines two different and typical clinical presentations: lichen planus‐like or lichenoid and sclerodermatous. The lichenoid form resembles lichen planus, with a similar pattern of involvement of cutaneous and mucosal tissues. Sclerodermatous cGVHD is a fibroproliferative disease that when severe can involve the joints with potentially severe impact on mo‐ bility.