1. Successful allogeneic SCT in infant with FHL, dilemmas in using „unaffected“ sibling P.Sedláček, R. Špíšek, et al 2nd Medical School, Charles University, Prague, CZ ESID – May 10.-11. 2004

2. Past Medical History (family) mother HBsAg +, no transf.history father – OK 1st girl – died 32nd gest.week (umb. cord problems) 2nd boy (IVF) – Jakub – alive/well 3rd girl (IVF) - Jana * July 8 th 2003

3. History of Present Illness I – early postnatal pancytopenia (WBC : 4,8, RBC: 3,1, ret.: 0,1%, ANC: <100, Plt 11) allo HLA Ab in mother exchange transfusion (D+9), PRBC, Plt, Fbg HSmegaly, hepatopathy, hypertriglycemia, hyperbilirubinemia hyperferritinemia ( >18 000) DIC, infections, fever and elev. CRP, HBsAg and HBeAg negative (Engerix, Hepatect) Admission to our department at the age of 28 days (Aug.2003)

4. History of Present Illness II Day of admission Aug. 5th 2003 –liver +4cm, spleen +3-4cm bcm, pancytopenia Therapy according to HLH 94 –(VP16, Dexa, CsA) –discontinued for acute sepsis Transfusion history pre SCT –PRBC 13 x (or more) –Plt more than 13

5. Pre-transplant condition HSmegaly, ferritin 3153 antiHBc and antiHBe pos., HBsAg neg. Failure to thrive (bw 3,45 kg; 2,8 kg at birth) normal LFT; Plt 100, WBC and RBC normal brother fully HLA matched, 19kg bw, 3yo ABO incompat. : A+ vs. B- (low titers)

6. Diagnostics-1 FACS analysis of perforin expression in NK cells Exclusion of FHL type 2- perforin deficiency Patient´s NK cells Control 87% of NK cells are perforin + Brother´s NK cells Control

7. Diagnostics-2 Cytotoxic activity of T-lymphoblasts generated from T-cells Target cells: L1210 cells deficient in FAS expression % cytotoxicity patient brother control defective cytotoxic activity of patient´s lymphoblasts normal findings in her brotherdonor of SC X

8. Transplantation 11.9.2003 (* 8.7.2003) Bu(19mgkg) + Cy(200) + rATG(25mg/kg) CsA + MP (MTX not used due to early and severe VOD) BM : NC : 8,9x 10 8 /kg; CD34: 22x10 6 /kg VOD : D+1 (D-3 through D+15 defibrotide) –Bilirubinemia, thrombocytopenia, ascites, ARDS Engraftment :ANC (500) D+19; Plt (20/50) D+22/+26 Chimer. : stable, 95% donor Discharched to outpatient clinic D+34 no aGVHD, no cGVHD so far (~D+240) –continues on CsA, steroids D/C ~D+50 –growth catch-up

10. Acknowledgement Department of Pediatric Hematology and Oncology –HSCT unit; Division of Hematology Institute of Immunology –diagnostics of primary HLH Institute of Hematology and Blood Transfusion –HLA typing