A single centre experience with allogeneic stem cell transplantation for severe aplastic anaemia in childhood.

BACKGROUND: Severe aplastic anaemia (SAA) is a rare disorder which has a fatal course when allogeneic stem cell transplantation (SCT) or an immunosuppressive regimen is not applied. Stem cell replacement is the only curative approach for these patients but it is limited by the availability of a compatible donor.

PATIENTS: Between 1982 and 1993, 18 children (15 boys, 3 girls) with SAA and HLA identical, MLC negative donors underwent SCT in our institution. SAA was preceded by viral infection in 8 patients (3x hepatitis, 1x measles, 1x herpes simplex infection and 3x viral upper respiratory tract infections). It was drug-associated in one and idiopathic in the 9 others. The median age at diagnosis was 9.7 years (range, 2 months to 16 years). Pretreatments included corticosteroids in 11/18 patients, androgens in 4 patients in addition, two had received cyclosporin A (CSA). One patient progressing from Diamond- Blackfan anaemia to SAA had multiple immunosuppressive treatment courses over 7 years before his grand-uncle was identified as donor while 4 patients had no treatment prior to SCT.

METHODS: Early SCT (within 90 days after diagnosis) was performed in 9/18 patients and the median interval between diagnosis and SCT was 2.6 months (range, 0.5 to 7 years). The stem cell source was the bone marrow (BM) of a syngeneic twin in 2 patients, the BM (13 patients) or the cord blood (1 patient) of a sibling whilst it was BM from a HLA-phenotypical family donor (1 father, 1 grand-uncle) in two patients. Cyclophosphamide 50 mg/kg on 4 consecutive days was given as preparative regimen to 16 patients but not to the two syngeneic twins. Rejection prophylaxis included total lymphoid irradiation in 5/16 patients while in the other 11 patients donor buffy coat cells were given on days +1 to +4. The syngeneic twins had no need for either approach. Patients received a median number of 3.7 x 10(8)/kg nucleated cells (range, 2.6 to 6.7). Prophylaxis of graft versus host disease (GVHD) was carried out with MTX alone (n = 12), with CSA alone (n = 2) or with both (n = 4). All patients received standard supportive care.

RESULTS: The overall survival is 89% at the median observation time of 100 months. The median time to reach 500 granulocytes was 24 days (range, 15 to 40). Median time to become transfusion independent after BMT was 30 days for platelets (range, 2 to 111) and was 28 days for packed red blood cells (range, 6 to 128). Acute GVHD was observed in 10/18 patients and involved only skin in 6 patients, skin and liver or gut in two patients and all 3 organs in another two patients. Seven of 10 patients had grade 1 to 2 a GVHD toxicity, whereas 3 patients experienced grade 3 to 4 acute GVHD. Chronic GVHD developed in 5 patients. Acute transplant related mortality was 5.5%. Cause of death was persisting non engraftment till day +180 after 2 transplant procedures in a boy with previous platelet transfusions from his mother. Late mortality occurred in 2 patients: one chronic GVHD associated haemorrhage 20 months after SCT and one chronic GVHD associated septicaemia 10 years after SCT.

CONCLUSION: Although this report reflects patients data accumulated over 15 years, results compare favourably with more recent survival data. Acute and late transplant related toxicity was low in patients undergoing early transplantation with adequate prior supportive care. This data confirms that SCT still should be the first treatment choice if an HLA identical sibling is available.