hsct in a patient with hyper igm sy n drome - our recent experience -
DESCRIPTION
HSCT in a patient with hyper IgM sy n drome - our recent experience -. Aleš Janda, Renata Formánková Department of Immunology Clinic of Paediatric Haematology and Oncology 2nd Medical School of Charles University University Hospital Motol, Prague. ONDŘEJ, 8 month old boy. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/1.jpg)
HSCT in a patient with hyper IgM syndrome
- our recent experience -
Aleš Janda, Renata Formánková
Department of Immunology
Clinic of Paediatric Haematology and Oncology 2nd Medical School of Charles University
University Hospital Motol, Prague
![Page 2: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/2.jpg)
ONDŘEJ, 8 month old boy
![Page 3: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/3.jpg)
ONDŘEJ Personal history
vaccinated with BCG in 3 months lymphnode
enlargement in armpit suppuration puncture healing
in 4 months cough runny yellow-green stool longterm
since 2 month of age failure to thrive
![Page 4: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/4.jpg)
ONDŘEJ Growth chart
![Page 5: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/5.jpg)
ONDŘEJ Symptoms at diagnosis
in 8 months thrush in oral cavity
afebrile, weight loss ( 200 g from check-up in 6 months), tachypnoea
sat. O2 80%, leukocytosis 37 x109/l, Hgb 10,4 g/dl, trombocytosis 837x109/l
ESR, CRP
![Page 6: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/6.jpg)
ONDŘEJ Microbial investigation
PCR CMV blood + BAL + PCR Pneumocystis carinii blood + BAL
+ PCR mycobacteria blood - BAL - test of stool on Cryptosporidia negative
![Page 7: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/7.jpg)
ONDŘEJ Immunological investigation
IgG 0,6 g/l [NR 3.6-7.7]IgA < 0.06 g/l [NR 0.1-0.6]IgE < 1 IU/ml [NR 0-30.0]IgM 1,98 g/l [NR 0.3-1.4]
number of lymphocytesfunctional tests
(blastic transformation) (NBT)
normal
![Page 8: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/8.jpg)
ONDŘEJ Flow Cytometry
![Page 9: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/9.jpg)
Mutation in 5th exonu of CD40L geneAminoacid substitution Tre254Met(dr. Genevieve de Saint Basil, Neckar, Pařiž)
Notarangelo, J Allergy Clin Immunol 2006, 117, 855-64
Xq26
Molecular genetics
Mother is carrier
ONDŘEJ
![Page 10: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/10.jpg)
Defects in HIGM
Notarangelo, J Allergy Clin Immunol 2006, 117, 855-64
X
X
XXX
X
![Page 11: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/11.jpg)
Clinical symptoms insufficient antibody production bacterial inf.
defect of cooperation T-DC opportunist, viral inf.
Defect in negative selection of autoreactive clones in thymus autoimmunity
antigenic stimulation (inf.) inaccurate regulation
tumours
![Page 12: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/12.jpg)
HIGM1 Treatment and prognosis
regular IVIG substitution prevention of pneumocystic pneumonia:
cotrimoxazol in case of neutropenia: G-CSF prevention of cryptosporidial infection: hygienic
regime, use of boiled water in case of malabsorbtion: total parenteral nutrition sometimes liver transplantation needed only 40 % of patients reach 25 years of age
HSCT is curativeGennery, Blood 2004,103, 1152-1157
![Page 13: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/13.jpg)
ONDŘEJ Supportive therapy
trimetoprim 20 mg/kg/day ganciclovir for 3 weeks antimycotics (fluconazol) azitromycin to prevent cryptosporidial infection antiTBC drugs (INH, RIF) to prevent BCG infection IVIG 0.5g/kg every 3-4 weeks G-CFS if ANC < 1000
indicated for allogeneic SCT from identical sibling
![Page 14: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/14.jpg)
ONDŘEJ January 2007 – before SCT
no signs of respiratory infection
good oral intake, no diarrhea, but persistent failure to thrive (7,5 kg)
no signs of cryptosporidial infection, normal hepatic function and ultrasound imaging
Chest X-RAY - slight residual interstitial changes
![Page 15: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/15.jpg)
ONDŘEJ Stem cell transplantation I
February 9, 2007 (aged 12,5 months)
Donor: HLA identical sister (16 years) Graft: BM (NC 8,6x108/kg, CD34+ 11,5x106/kg)
Conditioning: Busulfan (20mg/kg)Cyclophosphamide (200mg/kg)
GVHD prophylaxis: Cyclosporine A, Methotrexate
![Page 16: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/16.jpg)
ONDŘEJ Stem cell transplantation II
Engraftment: ANC D+21, Plt D+20
GVHD: gr. II (skin 3, GIT 1) on D+28therapy: corticosteroids 2mg/kg
Complications: febrile neutropenia (D+11)CMV infection (D+32) – GCV
Discharge from SCT unit: D+ 80 (aged 15 months)
![Page 17: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/17.jpg)
ONDŘEJ Hemopoietic chimerism
0
20
40
60
80
100
14 28 42 49 62 73
days after SCT
% o
f allog
en
eic
h
em
op
oie
sis
T-cells 94% T-cells 92%
T-cells 71%
withdrawal of corticosteroids
D+53
withdrawal of CsA D+71
![Page 18: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/18.jpg)
ONDŘEJ 3 months after SCT
without immunosupressive treatment
no GVHD no signs of infection
stable mixed chimerism (50-55% of allogeneic hematopoiesis in PB;90-95% in T-lymphocytes)
![Page 19: HSCT in a patient with hyper IgM sy n drome - our recent experience -](https://reader035.vdocuments.site/reader035/viewer/2022062518/5681454c550346895db21d98/html5/thumbnails/19.jpg)
ONDŘEJ Team work Vlastimil Král Dalibor Jílek
Veronika Skalická Jakub Zieg Květa Bláhová Jan Lebl Renata Formánková Petr Sedláček Jan Starý Aleš Janda Jiřina Bartůňková Anna Šedivá
Genevieve de Saint Basile
Centre of Immunology and MicrobiologyÚstí n. L
Pediatric Clinic
Clinic of Pediatric Haematology and Oncology
Department of ImmunologyUniversity Hospital Motol, Prague
INSERM, Necker, Paříž