1 / 18

Donor lymphocyte infusion as a treatment of a complete DiGeorge syndrome

Donor lymphocyte infusion as a treatment of a complete DiGeorge syndrome. K.Zdráhalová 2 , E.Mejstříková 1,2 ,T.Kalina 1,2 ,P.Sedláček 2 , A. Janda 1 , H.Žižková 3 , Z.Sieglová 3 ,A.Šedivá 1 , J.Bartůňková 1 , J.Starý 2 , P.Kobylka 3 , P.Hubáček 2,4 , O.Hrušák 1,2

kemal
Download Presentation

Donor lymphocyte infusion as a treatment of a complete DiGeorge syndrome

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Donor lymphocyte infusion as a treatment of a complete DiGeorge syndrome K.Zdráhalová2, E.Mejstříková1,2,T.Kalina1,2,P.Sedláček2, A. Janda1, H.Žižková3, Z.Sieglová3,A.Šedivá1, J.Bartůňková1, J.Starý2, P.Kobylka3 , P.Hubáček 2,4, O.Hrušák1,2 2Department of Pediatric Hematology and Oncology, 1Department of Immunology, 3Institute of Hematology and Blood Transfusion, 4Department of Pediatrics, Prague, Czech Republic

  2. Introduction - DiGeorge syndrome • the most common deletion syndrome in humans – • monoallelic microdeletion of 22q11.2 (DiGeorge • and velo-cardio-facial sy, conotruncal anomaly) • variable phenotype even in pts with the same deletion • manifestation:("CATCH22") • mainly heart defects; hypoparathyroidism • thymic hypoplasia  immunodeficiency, facialdysmorphism, developmental and behavioral problems • Deletion or interstitial deletion of 10p13 - other rare cause of DiGeorge sy (type II)

  3. Patient: male, born June 18th 2004, now 10 months • Family history: healthy parents, 0 siblings • Personal history: 1st pregnancy, polyhydramnios  amniocentesis  normal karyotype 46, XY • term delivery, fetal hypoxia  Cesarian section, • resuscitation, intubation, artificial ventilation • esophageal atresia + tracheoesophageal fistula: • D+2 operation • bilateral choanal atresia: D+5 operation • congenital heart defects: D+13 operation

  4. Stigmatisation: • face • genitals • eyes • CNS • CHARGE association • (Coloboma, Heart disease, Atresia choanae, Retarded growth + • development and/or CNS anomalies, Genital anomalies and/or • hypogonadism, Ear anomalies and/or deafness) • Problems: • recurrent infections, septicemias • recurrent respiratory distress  ventilation • apneas, irritability, states of altered consciousness

  5. Immunology: • lymphocyte subsets in 2 months of age: • CD3+ 0% • NK 40% • CD4+ 0% • CD8+ 0% • CD19+ 58% • absent T cells • response to mitogens: absent • MRI -absent thymus at 12.8.04 prior DLI 16.12.05 10 CD4 (10^9/L) 1 CD8 (10^9/L) CD3 (10^9/L) CD19 (10^9/L) 0,1 NK (10^9/L) 0,01 0,001 0,0001

  6. Complete DiGeorge Syndrome • (diagnosis at 2 months) • microdeletion 22q11 not found • prophylaxis started : • cotrimoxazole + itraconazole + IVIG

  7. 2 months of age

  8. 1st donor lymphocyte infusion age 6 months unrelated donor from register, 8/10 (B, Cw) no conditioning no GVHD prevention 1x 106/kg CD3+; 0.2x 106/kg CD34+ due to mistake non irradiated blood products administered (7 times prior 1st DLI, 1 time after 1st DLI)

  9. 1st donorlymphocyteinfusion(cont.) Between 1st and 2nd DLI • Complications:D+10: • isolated skin • aGVHD • (stage 3, grade II) • sepsis • cardiopulmonary • instability • capillary leak sy 10 after ATG 8 10 days post 1st DLI 0 1 CD3 (10^9/L) CD4 (10^9/L) 0,1 CD8 (10^9/L) 0,01 0,001 Chimerism: D+10 donordetected 0,0001 after ATG

  10. aGVHD, Capillary leak sy

  11. Immunosupressive therapy: • rATG Fresenius(25mg/kg 3x D+10, D+12, D+14) • CsA • corticosteroids- MP (2mg/kg) • GVHD resolved • corticosteroids - 2 weeks 2 mg/kg, 1 week 1 mg/kg, • 1 week 0.5 mg/kg, then tapered (D+35) • CsA continued • ***** • D+33 last extubation! - aged 7 months

  12. 2nd donor lymphocyte infusion age 7 months, D+36 after 1st DLI the same donor no conditioning prevention of GVHD: CsA (continued) 0.89x 106/kg CD3+

  13. 2nd donor lymphocyte infusion (cont.) EBV • Complications: • D+27EBV infection: • (B cell proliferation, • oligoclonality, IgM; • no clinical • manifestation) • withdrawal of CsA • Rituximab(375 mg/m2) • proliferation of • CD8+ activated T • cells started 10 rituximab CD3 CD8 10^9/L CD4 1 0 27 days post 2nd DLI 0,1 0,01 0,001 0 CD19

  14. Chimerism after 1st and 2nd DLI chimerism in FACSorted T lymphocytes CD3+ (D+41 and D+55 CD4+ and CD8+): mainly donor chimerism in non separated blood: recipient mainly, donor detected proliferation of activated T cells, severe liver GVHD acute GVHD 1st DLI 2nd DLI d 0 d 8 d 19 d 10 d 25 d 10 d 34 d 41 d 55 last non irradiated trf EBV infection and prior rituximab No proof of engraftment of non irradiated blood transfusions

  15. D+34:jaundice - bilirubin 4 mg/dL • dif.dg.: • hepatic GVHD • EBV lymphoproliferation(EBV in blood 0; in organs?) • hepatic infection- not found • ********* • D+352nd Rituximab(375 mg/m2) • D+41 corticosteroids(MP 1 mg/kg) hepatic aGVHD • neutropenia - granulo 215! • D+55 preventive ATB, antimycotics

  16. D+45 - D+49: agranulocytosis (0 granulo) •  corticosteroids(MP 2 mg/kg) • CsA • G-CSF5x • D+52: granulo 3000 • bilirubin 13.7 mg/dL •  isolated liver GVHD stage 3, grade III

  17. D+56: rATG Fresenius 1 dose, 25mg/kg • D+57:  bilirubin 23.8 mg/dL •  isolated liver GVHD stage 4, grade IV • ********* •  corticosteroids (D+63 1.5 mg/kg, D+83 1 mg/kg) • CsA continues • Current status: • D+108 after 2nd DLI, age 10 months •  bilirubin 7.6 mg/dL • CD8 activated T cells absolutely decreased • slight gradual psychomotor development

  18. Patient aged 10 months Thank you.

More Related