Cardiac Effects of Chronic Graft-versus-Host Disease after Stem Cell Transplantation

Chronic graft-versus-host disease (GVHD) develops as a result of the immunologic response that donor T-lymphocytes generate against host tissue after allogeneic stem cell transplantation. We tried to elucidate the contribution of cardiac dysfunction to the high morbidity and mortality rates observed after GVHD.Forty patients who had undergone bone marrow transplantation were enrolled in this prospective study: 14 patients who had been diagnosed with chronic GVHD (manifestations beyond day 100 after hemopoietic cell transplantation) and 26 patients who had not. All patients had undergone baseline echocardiography before bone marrow transplantation and were monitored. After the expected period of time had elapsed for GVHD after transplantation, these patients were divided into 2 groups in accordance with whether or not they developed chronic GVHD.No significant differences were observed before bone marrow transplantation in the 2 groups'' broad attributes or in their laboratory and echocardiographic findings (P >0.05). After transplantation, high-sensitivity C-reactive protein levels and erythrocyte sedimentation rates were significantly higher in the chronic GVHD group (P < 0.001 and P=0.01, respectively). Mean left ventricular mass was 227 ± 32.3 g in the GVHD group and 149.3 ± 27.4 g in the non-GVHD group (P < 0.001). The E/A flow rate was significantly higher in the non-GVHD group.This study shows that chronic GVHD increases left ventricular mass and impairs left ventricular diastolic function in patients who have developed chronic GVHD. In addition, it shows that inflammatory markers increase to higher levels in these patients. Comprehensive studies with larger samples are needed to more fully elucidate the cardiac effects of this disease.Key words: Bone marrow transplantation, C-reactive protein, diastole, left ventricular, graft vs host disease/prevention & control, hematopoietic stem cell transplantation/adverse effectsStem cell transplantation is acknowledged as the basic treatment approach in many hematologic diseases. In patients who receive allogeneic bone marrow transplantation (BMT), graft-versus-host disease (GVHD) is the leading cause of morbidity and death. Graft-versus-host disease is a result of immunologic responses to the host''s tissues by the donor''s T-lymphocytes.^1–5 Because the host''s immune system is suppressed, it is less resistant to the donor''s lymphocytes.^6,7The organs that are most commonly affected by GVHD are the liver, lungs, skin, gastrointestinal system, and lymphoid tissues. The risk of developing GVHD is higher in elderly hosts than in younger hosts and in older hosts whose donors are young. The incidence of GVHD after BMT is approximately 35% to 50%. The clinical manifestation of chronic GVHD often differs from that of acute GVHD. Mostly mesenchymal tissues are affected in chronic GVHD.^8,9 The diagnostic and therapeutic approaches to diffuse organ involvement are well known for both acute and chronic GVHD, but the body of knowledge on cardiac involvement is more limited.After the 2005 National Institutes of Health (NIH) Consensus Development Project on Chronic GVHD, major changes in the diagnosis, classification, and grading of chronic GVHD were proposed. Rather than focus on the customary 100 days post–bone marrow transplantation as the dividing line between acute and chronic GVHD in regard to the continued manifestation of symptoms, the proposed NIH Consensus Criteria invoke the diagnostic characteristics of the syndromes in order to classify them. Accordingly, those manifestations (dermal, oral, hepatic, ocular, respiratory, and gastrointestinal) occurring beyond day 100 are considered diagnostic of classic chronic GVHD. A revised scheme for grading the severity of GVHD assigns a score for each involved organ with attention to functional impairment and provides a global summary score (mild, moderate, or severe) that takes into account the number of organs involved and the severity of the condition of those organs.¹⁰Yet we still define classic chronic GVHD as manifestations beyond day 100 after allogeneic hemopoietic cell transplantation. According to this older criterion, 14 patients were in our classic chronic GVHD group. The other 26 patients had neither chronic nor acute GVHD.The purpose of this prospective study was to find out whether there are cardiac effects in patients who develop GVHD after receiving BMT and to determine their extent.