Treatment of HIV and EBV associated lymphoma by allogenic CCR5 32 - - PowerPoint PPT Presentation

treatment of hiv and ebv associated lymphoma by allogenic
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Treatment of HIV and EBV associated lymphoma by allogenic CCR5 32 - - PowerPoint PPT Presentation

Treatment of HIV and EBV associated lymphoma by allogenic CCR5 32 blood stem cell transplantation AREVIR-Meeting 2019 - Viral load below detection limit what is next Marek Widera The 1 st Essener Patient Folie 2 Titel Treatment of HIV and


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Treatment of HIV and EBV associated lymphoma by allogenic CCR5Δ32 blood stem cell transplantation

AREVIR-Meeting 2019 - Viral load below detection limit – what is next Marek Widera

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The 1st Essener Patient

Treatment of HIV and EBV associated lymphoma by allogenic CCR5Δ32 blood stem cell transplantation

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The 2nd Essener Patient

Treatment of HIV and EBV associated lymphoma by allogenic CCR5Δ32 blood stem cell transplantation

Male, 38 years Primary disease: EBV associated non-Hodgkin plasmobl. B-cell lymphoma, 08.10.17 Herpes zoster, Candida albicans 08.12.17 Jaw: Sinusitis maxillaris, Epulis granulomatose 12.12.17 Dissection of the jaw-tumor (V.a. Burkitt-Lymphoma) HIV diagnosis: 12.12.2017, 148/µl (CDC 3, WHO IV). Treatment TAF/FTC+RAL since 21.12.2017 12.01.18 Immunesuppressive therapy (Prednisolon) 17.01.18 Chemotherapy 10.04.18 Histological diagnosis: plasmobl. aggressive B-cell lymphoma 24.05.18 Relapse-Chemotherapy 06/18 partial remission 02.07.18 autological stem cell transplantation 08-09/18 radiotherapy, jawbone 09/18 chemotherapy and autological stem cell transplantation 11/18 complete remission of the B-cell lymphoma University Hospital Essen, allogenic CCR5Δ32 blood stem cell transplantation

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Before HSCT coreceptor-usage was predicted as R5-tropic (NGS: 0.1% X4 at 3.75% FPR, geno2pheno). Co-Receptor-prediction reveals the presence of R5-tropic viruses No resistance mutations in PR/ RT / IN

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HLA/CCR5 of the stem cell donor

permissive mismatch

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Transition from CCR5 wt/wt to CCR5 Δ32/Δ32 status

Treatment of HIV and EBV associated lymphoma by allogenic CCR5Δ32 blood stem cell transplantation

bp 300 200 CCR5 wt CCR5 Δ32 Transplantation

6%PAA

Transplantation: 31.01.2019

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Before HSCT

Treatment of HIV and EBV associated lymphoma by allogenic CCR5Δ32 blood stem cell transplantation

PBMC derived DNA samples were analysed by qPCR: 39 HIV DNA cps/1x106 PBMCs Samples were send for T-cell responses determination (T. Harrer). Anti-CMV IgG: positive Anti-EBV-EBNA IgG: positive Anti-HSV IgG: positive Anti-HIV-1/-2 inkl. p24 Ag: positive Anti-VZV IgG: positive Anti-CMV IgM: negative Anti-EBV-VCA IgG: positive Anti-HBc negativ Anti-HBs negativ Anti-HCV negativ Anti-HAV IgG negativ Anti-HAV IgM negativ HBs-Ag negativ Negative for Influenza A/B, HSV1/2 CMV-DNA (Vollblut) : <65 (positiv) EBV-DNA (Vollblut) 26,254 HIV pVL. <40

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Transplantation

ART: TAF/FTC+RAL

Virological features before and after HSCT

<40 <40 <40 <40 <40 <40 <40 <40 Proviral DNA load pro 1x106 PBMCs (Analyzed PBMC-count)

39.0 / 2,8x105

293 245

99,3% chimersim.

69.2 / 2,1x105 <LOD / 4,5x106 <LOD / 3,9x106 1.4 / 1,8x106

HIV pVL

CD4+/µL GvHD TAC/MMF

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BKPyV- Reactivation Transplantation

ART: TAF/FTC+RAL

Virological features before and after HSCT

<40 <40 <40 <40 <40 <40 <40 <40 Proviral DNA load pro 1x106 PBMCs (Analyzed PBMC-count)

39.0 / 2,8x105

293 245

99,3% chimersim.

69.2 / 2,1x105 <LOD / 4,5x106 <LOD / 3,9x106 1.4 / 1,8x106

HIV pVL

CD4+/µL GvHD TAC/MMF

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HIV Immunoblot analysis before and after HSCT

Treatment of HIV and EBV associated lymphoma by allogenic CCR5Δ32 blood stem cell transplantation

Immunoblot analysis: sgp120+, gp41+, p31+, p24+, p17+

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05.11.2018 Ficoll 04.02.2019 Ficoll 07.02.2019 Ficoll 11.02.2019 Ficoll 14.02.2019 Ficoll 18.02.2019 Ficoll 21.02.2019 Ficoll 25.02.2019 Ficoll 22.03.2019 Ficoll 25.03.2019 Ficoll 04.04.2019 Ficoll 08.04.2019 Ficoll 15.04.2019 Ficoll 16.04.2019 Ficoll 23.04.2019 Ficoll 24.04.2019 Ficoll 24.04.2019 Ficoll

More samples…

04.02.2019 Plasma 07.02.2019 Plasma 11.02.2019 Plasma 13.02.2019 Plasma 14.02.2019 Plasma 18.02.2019 Plasma 21.02.2019 Plasma 26.02.2019 Plasma 26.02.2019 Plasma 27.03.2019 Plasma 24.04.2019 Plasma

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Acknowledgements

HIV/HPSTD-Studienambulanz Stefan Esser Institute for Virology Ulf Dittmer Barbara Bleekmann Olympia Anastasiou Miriam Dirks Helene Sertznig Tyärk Rütten Seq-IT, Kaiserslautern Martin Däumer Alexander Thielen University of Cologne, Virology Rolf Kaiser Veronica di Cristanziano Elena Knops Eva Heger University of Düsseldorf, Virology Nadine Lübke HMT Transplantationsambulanz Rudolf Trenschel University Hospital Erlangen Thomas Harrer University Hospital Hamburg-Eppendorf Johanna Eberhard