Mismatched bone marrow transplantation for severe aplastic anaemia after liver transplantation for associated acute liver failure.

Case Report A previously well 10-year-old Vietnamese boy with exanthematous fever, jaundice (Alanine aminotransferase 688 U/L, Aspartate aminotransferase 340 U/L) and pancytopoenia (Haemoglobin 4.2 g/dL, WBC 1.7 x 109/L, and platelets < 20 x 109/L) developed grade 4 hepatic encephalopathy at 10 weeks of illness. Extensive workup failed to reveal the aetiology. At 11 weeks of illness, a liver transplantation (LT) (segments 5 to 8) was performed, mother being the donor. Histology of the native liver showed massive necrosis. The liver function normalised but there was persistent febrile neutropoenia (ANC 0.07 x 109/L, RBC 2.27 x 1012/L, and platelets 28 x 109/L) (Fig. 1) due to severe AA (marrow cellularity <5%). The treatment of such hepatitis-associated AA (HAA) using immunotherapy entails a time lag (median 60 to 80 days) to myeloid response, even with accelerated regimes. There is also a higher risk of relapse, bone marrow aplasia, clonal disorders and, if the conditioning includes irradiation, secondary malignancies.1,2 Therefore, an urgent bone marrow transplant (BMT) was planned. With no available matched sibling or unrelated donor, we pursued a partial matched BMT from the mother (homozygous mismatch at HLA A, antigen mismatch at HLA B); there being a lower risk of post-BMT red cell aplasia due to identical ABO match. A reduced-intensity, liver-protective preparative regimen [fl udarabine (120 mg/m2), cyclophosphamide (10 mg/kg), anti-thymocyte globulin (ATG) (90 mg/kg) and rituximab (375 mg/ m2)] with subsequent ex-vivo T-cell depleted donor bone marrow (CD34 3.4 x 106/kg; CD3 0.1 x 106/kg) was administered. Graft versus host disease (GVHD) prophylaxis consisted of methotrexate (10 mg/m2 day+1, 5 mg/m2 on day+6 and day+11 after BMT) in addition to post-LT immunosuppression. Although there was initial myeloid engraftment (day 14, 100% donor chimerism), the bone marrow graft was eventually rejected (day 20) with subsequent spontaneous myeloid recovery (32 to 41 days following BMT) (3% donor chimerism). Cytomegalovirus (CMV) reactivation on day 52 following BMT was treated by oral valganciclovir (450 mg bid) for 4 weeks until seronegative. Tacrolimus was continued at a dose of 2 mg bid for a year whereas prednisolone was tapered from 15 mg to 10 mg daily. There was no liver allograft morbidity related to the BMT regimes. Follow-up revealed peripheral donor chimerism (3%) at 9 months and normal blood pressure, neurology, liver