Graft-versus-host disease, a major complication after stem cell transplantation – home care for prevention and stromal cells for therapy

Abstract

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic haematopoietic stem cell transplantation (HSCT). Although severe acute GVHD is associated with a high mortality, chronic GVHD is associated with a strong anticancer effect. Patients suffering from leukaemia who undergo HSCT have a reduced risk of recurrent disease if they develop chronic GVHD. During the neutropenic phase after HSCT, patients are isolated in the hospital, sometimes in laminar airflow rooms. We challenged this by allowing patients to be treated at home. A nurse from the unit visited and checked the patient daily. Compared with hospital controls, home-care patients had a decreased risk of acute GVHD, which was associated with number of days treated at home during neutropenia. Home care did not affect chronic GVHD or relapse and, therefore, home-care patients had a trend for better survival than those treated in the hospital. Stromal cells such as mesenchymal stem cells (MSCs) or placenta-derived decidual stromal cells suppress alloantigen-induced T-cells in vitro. This effect was seen despite HLA incompatibility between MSCs and stimulatory or allo-reactive cells in vitro, enabling the use of third-party stromal cells in the clinic. Because stromal cells home to target organs of tissue toxicity, and have low immunogenicity, they may be useful in regenerative medicine such as acute and chronic GVHD, haemorrhages and tissue toxicity. I was the first to use MSCs for life-threatening acute GVHD with miraculous response in some, although not all, patients. Clinically, MSCs were found to completely reverse severe acute GVHD in approximately 50% of patients. Among patients with chronic GVHD, the complete response rate was approximately 25%. Stromal cells interfere with coagulation and reversed haemorrhagic cystitis and may stop major haemorrhages in patients who have undergone HSCT. In addition to GVHD and haemorrhages, stromal cells may be used for treatment of graft failure and allograft rejection in organ transplant patients, for tissue toxicity in cancer patients and to treat autoimmune disorders. To conclude, GVHD is a limiting severe side-effect of HSCT which may be decreased by home care. Stromal cells have potential in regenerative medicine and have healed severe GVHD, although improvements are warranted.