Summary.We report the case of an 11-year-old boy who underwent allogeneic bone marrow transplantation (BMT) for relapsed acute lymphoblastic leukaemia. Despite adequate engraftment, on day 45 he developed marrow aplasia with haemophagocytosis. HHV-6 was detected in blood and bone marrow by nested PCR. Retrospective testing showed that viraemia had started on day 24. Following therapy with foscarnet and ganciclovir, viral load declined to undetectable levels and his donor marrow recovered contemporaneously. This case suggests that HHV-6 may be a treatable cause of graft failure following BMT and provides clinical and virological evidence for the anti-HHV-6 activity of ganciclovir and foscarnet.Keywords: HHV-6, bone marrow transplantation, graft failure, ganciclovir, foscarnet. CASE REPORTAn 11-year-old boy underwent unrelated bone marrow transplantation (BMT) in his third complete remission of acute lymphoblastic leukaemia (ALL) L1. The transplant was allele mis-matched at HLA class I (split of B41), DRB4 and C. Both he and his donor were CMV sero-negative. The patient received immunosuppressive conditioning with Campath 1G (10 mg/d for 5 d), TNI (9 Gy in six fractions), cyclophosphamide 120 mg/m 2 , single fraction TBI (7·5 Gy) and cyclosporin from day ¹1.Donor marrow was re-infused following in vitro T-cell depletion with Campath 1-M and complement. The final product contained 1·8 × 10 8 /kg mononuclear cells, 6·2 × 10 6 /kg CD34 þ and 6·2 × 10 6 /kg CD3 þ cells. From day 10 he received antimicrobial prophylaxis with aciclovir (10 mg/kg t.d.s. i.v. until day 25 and then 400 mg orally t.d.s.), nebulized pentamidine, oral ciprofloxacin, oral itraconazole and routine mouthcare.The early post-transplant period was uncomplicated apart from a febrile illness for which no cause was found. Neutrophil engraftment occurred on day 18 and the patient was discharged on day 34 with a white cell count (WCC) of 1·9 × 10 9 /l and a neutrophil count of 1·4 × 10 9 /l, remaining, however, platelet and red cell transfusion dependent.A bone marrow aspirate was performed on day 45 to investigate trilineage graft failure which had developed over the preceding 3 d; the WCC had declined from 2·0 to 0·4 × 10 9 /l; platelets from 71 to 41 × 10 9 /l and Hb from 9·8 to 7·5 g/dl. The aspirate was aplastic with evidence of haemophagocytosis. At this time he was not receiving myelosuppressive drugs and showed no clinical evidence of sepsis. In addition his blood was negative for both CMV and parvovirus DNA by PCR and dot-blot hybridization respectively. Cytogenetic analysis showed 100% donor (female) chimaeric status.Treatment was instituted with i.v. G-CSF (10 mg/kg/d), aciclovir (10 mg/kg t.d.s.), meropenem, immunoglobulin and high-dose methylprednisolone to treat possible infective and immunological causes of graft failure. On day 50 i.v. foscarnet (180 mg/kg/d) was added empirically to broaden antiviral cover. A repeat bone marrow aspirate on day 52 was still aplastic. This bone marrow and a peripheral blood sample were tested for the pres...
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