Post on 08-Jan-2016
description
Successful allogeneic SCT in infant with FHL,
dilemmas in using „unaffected“ sibling
P.Sedláček, R. Špíšek, et al
2nd Medical School,
Charles University, Prague, CZESID – May 10.-11. 2004
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 8th 2003
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)
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
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)
Diagnostics-1FACS analysis of perforin expression in NK cellsExclusion of FHL type 2- perforin deficiency
100 101 102 103 104
FL2-H: PERFORIN
0
20
40
60
80
100
% o
f Ma
x
100 101 102 103 104
FL2-H: PERFORIN
0
20
40
60
80
100
% o
f Ma
x
Patient´s NK cellsControl
87% of NK 87% of NK cells are cells are perforin +perforin +
87% of NK 87% of NK cells are cells are perforin +perforin +
Brother´s NK cells
Control
Diagnostics-2• Cytotoxic activity of T-lymphoblasts generated from T-cells• Target cells: L1210 cells deficient in FAS expression
0
10
20
30
40
50
60
70
80
60:1 30:1 6:1 1,2:1 0,2:1
% c
ytot
oxic
ity
patient
brother
control
• defective cytotoxic activity of patient´s lymphoblasts
• normal findings in her brother donor of SCX
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 108/kg; CD34: 22x106/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
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