A SINGLE-CENTER EXPERIENCE WITH ALLOGENEIC STEM-CELL TRANSPLANTATION FOR SEVERE APLASTIC-ANEMIA IN CHILDHOOD

Background Severe aplastic anaemia (SAA) is a rare disorder which has a fatal course when allogeneic stem cell transplantation (SCT) or an i mmunosuppressive regimen is not applied. Stem cell replacement is the only curative approach for these patients but it is limited by the ava ilability of a compatible donor.Patients Between 1982 and 1993, 18 chi ldren (15 boys, 3 girls) with SAA and HLA identical, MLC negative dono rs underwent SCT in our institution. SAA was preceeded by viral infect ion in 8 patients (3 x hepatitis, 1 x measles, 1 x herpes simplex infe ction and 3 x viral upper respiratory tract infections). It was drug-a ssociated in one and idiopathic in the 9 others. The median age at dia gnosis was 9.7 years (range, 2 months to 16 years). Pretreatments incl uded corticosteroids in 11/18 patients, androgens in 4 patients in add ition, two had received cyclosporin A (CSA.). One patient progressing from Diamond-Blackfan anaemia to SAA had multiple immunosuppressive tr eatment courses over 7 years before his grand-uncle was identified as donor while 4 patients had no treatment prior to SCT. Methods Early SC T (within 90 days after diagnosis) was performed in 9/18 patients and the median intervall 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 sy ngeneic twin in 2 patients, the BM (13 patients) or the cord blood (1 patient) of a sibling whilst it was BM from a HLA-phaenotypical family donor (1 father, 1 granduncle) in two patients. Cyclophosphamide 50 m g/kg on 4 consecutive days was given as preparative regimen to 16 pati ents but not to the two syngeneic twins. Rejection prophylaxis include d total lymphoid irradiation in 5/16 pa tients while in the other 11 p atients donor buffy coat cells were given on days +1 to +4. The syngen eic 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). Prophyla xis 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 r eceived 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 daps 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 ( 1 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 tox icity, 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 afte r 2 transplant procedures in a boy with previ ous platelet transfusion s from his mother. Late mortality occured in 2 patients: one chronic G VHD associated haemorrhage 20 months after SCT and one chronic GVHD as sociated septicaemia 10 years after SCT. Conclusion Although this repo rt reflects patients data accumulated over 15 years. results compare f avourably with more recent survival data, Acute and late transplant re lated toxicity was low in patients undergoing early transplantation wi th adequate prior supportive care. This data confirms that SCT still s hould be the first treatment choice if an HLA identical sibling is ava ilable.