ALBERT

Description: PNH, a rare disease in children, is caused by an acquired somatic mutation of the phosphatidyl-inositol glycan (GPI)class A (PIG-A) gene, followed by a survival-advantage of the PNH clone. This results in a deficiency of GPI-anchored proteins on the hematopoietic cells, making them more susceptible for attacks of the complement system, causing hemolysis and pancytopenia. Binding-impairment of coagulation-system-regulators increases thrombosis-risk. Until now, world-wide only 40 cases of pediatric PNH have been reported. Clinical data from Dutch cases from 1983–2003 were collected nation-wide and studied retrospectively. Diagnosis was confirmed by a decrease of GPI-linked anchor proteins on granulocytes and/or erythrocytes (CD24, CD66b/67, CD59, CD16). All 11 PNH patients (4 boys, 7 girls), with a median age of 11 years (range 6–14 years) presented with pancytopenia-related symptoms. Two cases showed clinical hemoglobinuria, and one developed thrombosis during the course of the disease. BM biopsies showed hypoplasia/aplasia (AA)(n=7) or MDS (n=4). All cases showed decreased percentages of the GPI-linked proteins, 3/8 showed positive acid-Ham tests, 5/6 showed positive sucrose-lysis tests. Seven patients received prednisolone, in 5 combined with androgens and in 4 with ATG. After initial treatment, 3 patients reached complete remission (CR), and 2 showed partial response (PR), 1 subsequently relapsed and was transplanted. Three died of disease related mortality, one showed spontaneous recovery of blood counts.In total 5 patients underwent BMT (5MUD/2MSD). Conditioning regimens were Busulphan/Melphalan/Cyclophosphamide (n=2) in MDS, and Cyclophosphamide/ low dose TBI (n=3) in AA. Three patients received additional anti-Tcell antibody therapy. Of the 5 BMT patients 4 in CCR (median follow-up: 6 years, 10 months (range 7 months-14 years)). One patient died post-BMT of intracranial hemorrhage. PNH, a rare but serious disease in children, should be considered in every child with aplastic anemia/hypoplastic MDS. Hemoglobinuria is not an obligatory presenting symptom. GPI-linked anchor protein analysis provides the most reliable diagnostic tool. If prednisolone/ATG/androgens is not effective, BMT should be considered even if no matched sibling donor is available.