How we treat chronic graft-versus-host disease

Abstract

Chronic graft-versus-host disease (GVHD) remains a common and potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (HCT). The 2-year cumulative incidence of chronic GVHD requiring systemic treatment is ~30% to 40% by National Institutes of Health criteria. The risk of chronic GVHD is higher and the duration of treatment is longer after HCT with mobilized blood cells than with marrow cells. Clinical manifestations can impair activities of daily living and often linger for years. Hematology and oncology specialists who refer patients to centers for HCT are often subsequently involved in the management of chronic GVHD when patients return to their care after HCT. Treatment of these patients can be optimized under shared care arrangements that enable referring physicians to manage long-term administration of immunosuppressive medications and supportive care with guidance from transplant center experts. Keys to successful collaborative management include early recognition in making the diagnosis of chronic GVHD, comprehensive evaluation at the onset and periodically during the course of the disease, prompt institution of systemic and topical treatment, appropriate monitoring of the response, calibration of treatment intensity over time in order to avoid overtreatment or undertreatment, and the use of supportive care to prevent complications and disability.

Figure 1

The frequency of involvement by chronic GVHD varies across organs and sites and is higher after HCT with mobilized blood cells as compared with marrow. (A) The most frequently involved organs and sites are the skin, mouth, eyes, gastrointestinal tract, and liver. (B) Chronic GVHD can affect all layers of the skin. Photographs of each manifestation in italic may be found in the supplemental Data, available on the Blood Web site. Artwork by Delilah Cohn, MFA, CMI, used with permission.

Figure 2

Appropriate management of chronic GVHD requires continuous recalibration of immunosuppressive treatment in order to avoid overtreatment or undertreatment. The intensity of treatment required to control the disease decreases across time. Manifestations of chronic GVHD improve or are absent when the intensity of treatment is above the threshold shown as the orange curve, and they worsen or recur when the intensity of treatment is below the threshold. The slope of the threshold varies among patients and can be determined only by serial attempts to decrease the intensity of treatment. Clinical tolerance is defined by the ability to withdraw all systemic treatment without recurrence of chronic GVHD.