The delicate balance of graft versus leukemia and graft versus host disease after allogeneic hematopoietic stem cell transplantation

ABSTRACT

Introduction

The curative basis of allogeneic hematopoietic stem cell transplantation (HSCT) relies in part upon the graft versus leukemia (GvL) effect, whereby donor immune cells recognize and eliminate recipient malignant cells. However, alloreactivity of donor cells against recipient tissues may also be deleterious. Chronic graft versus host disease (cGvHD) is an immunologic phenomenon wherein alloreactive donor T cells aberrantly react against host tissues, leading to damaging inflammatory symptoms.

Areas Covered

Here, we discuss biological insights into GvL and cGvHD and strategies to balance the prevention of GvHD with maintenance of GvL in modern HSCT.

Expert Opinion/Commentary

Relapse remains the leading cause of mortality after HSCT with rates as high as 40% for some diseases. GvHD is a major cause of morbidity after HSCT, occurring in up to half of patients and responsible for 15–20% of deaths after HSCT. Intriguingly, the development of chronic GvHD may be linked to lower relapse rates after HSCT, suggesting that GvL and GvHD may be complementary sides of the immunologic foundation of HSCT. The ability to fine tune the balance of GvL and GvHD will lead to improvements in survival, relapse rates, and quality of life for patients undergoing HSCT.

KEYWORDS:

• Chronic graft versus host disease
• relapse
• GvHD
• GvL
• HSCT

Article highlights

• Nearly half of patients may relapse with their original disease and is the major cause of mortality after HSCT. Chronic graft versus host disease (cGvHD) is a leading contributor to morbidity in long-term survivors after HSCT

• GvL and cGvHD are closely-related immunologic phenomena after HSCT both likely dependent upon activity of alloreactive donor immune cell subsets, though the precise mechanisms driving both are likely multifactorial and poorly defined

• Although there have been recent advances in strategies for prevention and treatment of cGvHD, there is an urgent need for improved understanding of GvL

Declaration of interest

R Soiffer serves on the board of directors for BeThe Match/National Marrow Donor Program; provided consulting for Astellas, Neovii, Jasper, Smart Immune, and Vor Biopharma, and is on the Data Safety Monitoring board for BMS. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was funded by the National Institute of Health (NCI P01CA229092).