Bone Marrow Transplantation (2001) 27, 107–109  2001 Nature Publishing Group All rights reserved 0268–3369/01 $15.00 www.nature.com/bmt Case report Acute heart failure after allogeneic blood stem cell transplantation due to massive myocardial infiltration by cytotoxic T cells of donor origin U Platzbecker 1 , K Klingel 2 , C Thiede 1 , J Freiberg-Richter 1 , D Schuh 3 , G Ehninger 1 , R Kandolf 2 and M Bornha ¨user 1 1 Medical Clinic I, 3 Institute of Pathology, University Hospital, Dresden; and 2 Institute of Pathology, University Hospital, Tu ¨bingen, Germany Summary: A 17-year-old male with AML FAB M4 relapsed 4 months after myeloablative conditioning and peripheral blood stem cell transplantation (PBSCT) from an HLA- identical unrelated donor. A second PBSC harvest was infused 2 days after completion of cytoreductive therapy with mitoxantrone 7 mg/m 2 /day i.v. for 3 days (total dose 21 mg/m 2 ), fludarabine 30 mg/m 2 /day i.v. for 6 days (total dose 180 mg/m 2 ) and Ara-C 125 mg/m 2 /day i.v. for 5 days (total dose 625 mg/m 2 ). Neutrophil recovery occurred on day + 10 and was associated with GVHD grade III of the skin which was treated with cyclosporin A (CsA) and prednisone. Because of fever of unknown origin and progressive fatigue combined with hypoten- sion on day + 15 after second PBSCT, echocardiography was performed which revealed a dramatic decrease in systolic function compared to the status pre-transplant. On the same day acute heart failure with consecutive ventricular fibrillation occurred. Although resuscitation was performed immediately the patient died. The auto- psy revealed massive infiltration by donor CD8-positive lymphocytes with concomitant extensive damage of the heart tissue. Acute myocarditis of viral origin was excluded by in situ hybridization and nested PCR tech- niques. In this patient, myocardial involvement by acute GVHD seems to have triggered a fatal arrhythmia and heart failure. Bone Marrow Transplantation (2001) 27, 107–109. Keywords: GVHD; heart; HHV-6 Recurrence of disease is a frequent complication in patients with advanced leukemia receiving allogeneic blood stem cell transplantation. In relapsed AML patients intensive chemotherapy is needed for induction of remission. Second transplantation for recurrent acute leukemia is associated Correspondence: Dr U Platzbecker, Medical Clinic I, University Hospital Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany; platz- beckeroncocenter.de Received 24 July 2000; accepted 4 October 2000 with a procedure-related mortality of up to 50% in the first 100 days after BMT. Remission induction can be achieved by omitting GVHD prophylaxis, thus maximizing GVL effects. Nevertheless, GVHD remains one of the persistent problems of allogeneic blood stem cell transplantation mostly affecting the skin, gut and the liver. To our knowl- edge, there is only one report in the literature suggesting an acute GVHD of the heart with reversible complete heart block. 1 We report a case of allogeneic unrelated PBSC transplan- tation in a patient with AML which relapsed early after first transplant. Acute GVHD occurred and the patient died due to acute heart failure on day + 15 after a second PBSCT. Histological and immunohistochemical investigations of the heart provided evidence of irreversible heart damage caused by massive infiltration by CD8-positive lympho- cytes, thus suggesting acute GVHD of the heart. Case report A 17-year-old male with AML FAB M4 (46 XY) diagnosed 1 year previously was admitted to our hospital. Initial treat- ment had included two cycles of idarubicine 12 mg/m 2 once daily i.v. for 3 days (total dose 72 mg/m 2 ) plus Ara-C 1000 mg/m 2 by continuous infusion on 6 consecutive days (total dose 12 g/m 2 ) and one cycle of mitoxantrone 7 mg/m 2 /day i.v. for 3 days (total dose 21 mg/m 2 ) plus Ara-C 1000 mg/m 2 (total dose 6 g/m 2 ) by continuous infusion on 6 con- secutive days. The patient relapsed 2 months later. A second remission was induced with one cycle of mitoxan- trone 7 mg/m 2 /day i.v. for 3 days (total dose 21 mg/m 2 ), fludarabine 30 mg/m 2 /day i.v. for 6 days (total dose 180 mg/m 2 ) and Ara-C at a dose of 125 mg/m 2 /day for 5 days (total dose 500 mg/m 2 ) intravenously. Two months later an allogeneic peripheral blood stem cell transplant from an HLA-identical unrelated donor was performed. Echocardiography pre-transplant showed an ejection fraction of more than 60% and normal cardiac parameters. Both donor and host were CMV-negative and CMV-negative blood products were given. The first con- ditioning regimen consisted of busulfan (total dose 13.2 mg/kg), etoposide (total dose 30 mg/kg), cyclophosphamide