Abstract • 154

The presence of severe organ dysfunction prior to Bone marrow transplant (BMT) significantly reduces the chance of successful outcome using conventional preparative regimens. Five boys of median age 10.4 years (range 3.7 -18.3) with severe organ dysfunction underwent unrelated donor [n=4] or matched sibling donor [n=1] BMT following a non-myeloablative regimen consisting of fludarabine 30mg/kg × 5, melphelan 140 mg/kg and anti-thymocyte globulin (ATG) 2.5mg/kg × 5. Diagnoses included: 2 cases of CD 40 ligand deficiency complicated by severe sclerosing cholangitis and in one chronic cryptosporidiosis (in one case BMT was performed 5 weeks after elective orthotopic liver transplant); one boy with X linked lymphoproliferative syndrome with haemophagocytic lymphohistiocytosis and pneumonitis; one boy with a combined immunodeficiency of unknown type with sclerosing cholangitis and bronchiectasis; and a child with moderate neuro-developmental delay with hepatitis induced MDL progressing to AML with monosomy 7. Unrelated marrows were A,B,C (serological) DRB1,DQB1 matched. All children received whole marrow with cyclosporin A and prednisolone as graft versus host disease (GVHD) prophylaxis. At follow-up of between 59 - 136 days, all patients show >95% engraftment of donor cells. Neutrophil counts reached 0.5 × 109/L by a median of day 13 (range 9 - 16). No GVHD greater than grade 1 occured. 4/5 patients had transient worsening of liver function, but significant morbidity was seen in only one patient with seizures and bilateral hip fractures. In conclusion, this conditioning permits rapid engraftment of related and unrelated donor marrow with minimal toxicity even in the presence of severe organ dysfunction. If prolonged follow-up confirms the stability of the grafts, then the potential for reduced late effects of this type of BMT is considerable.