successful allogeneic sct in infant with fhl, dilemmas in using „unaffected“ sibling
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, CZ. ESID – May 10.-11. 2004. Past Medical History (family). mother HBsAg +, no transf.history father – OK - PowerPoint PPT PresentationTRANSCRIPT
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