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

Treatment of HIV and EBV associated lymphoma by allogenic CCR5 Δ 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 EBV associated lymphoma by allogenic CCR5 Δ32 blood stem cell transplantation

The 2 nd Essener Patient 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 CCR5 Δ32 blood stem cell transplantation Folie 3 Titel Treatment of HIV and EBV associated lymphoma by allogenic CCR5 Δ32 blood stem cell transplantation

Co-Receptor-prediction reveals the presence of R5-tropic viruses No resistance mutations in PR/ RT / IN Before HSCT coreceptor-usage was predicted as R5-tropic (NGS: 0.1% X4 at 3.75% FPR, geno2pheno). Folie 4 Titel

HLA/CCR5 of the stem cell donor permissive mismatch Folie 5 Titel

Transition from CCR5 wt/wt to CCR5 Δ 32/ Δ 32 status Transplantation: 31.01.2019 bp 300 CCR5 wt CCR5 Δ 32 200 6%PAA Transplantation Folie 6 Titel Treatment of HIV and EBV associated lymphoma by allogenic CCR5 Δ32 blood stem cell transplantation

Before HSCT PBMC derived DNA samples were analysed by qPCR: 39 HIV DNA cps/1x10 6 PBMCs Samples were send for T-cell responses determination (T. Harrer). Anti-HAV IgG negativ Negative for Influenza A/B, HSV1/2 Anti-CMV IgG: positive Anti-CMV IgM: negative Anti-HAV IgM negativ CMV-DNA (Vollblut) : <65 (positiv) Anti-EBV-EBNA IgG: positive HBs-Ag negativ EBV-DNA (Vollblut) 26,254 Anti-EBV-VCA IgG: positive Anti-HBc negativ HIV pVL. <40 Anti-HSV IgG: positive Anti-HBs negativ Anti-HIV-1/-2 inkl. p24 Ag: positive Anti-HCV negativ Anti-VZV IgG: positive Folie 7 Titel Treatment of HIV and EBV associated lymphoma by allogenic CCR5 Δ32 blood stem cell transplantation

Virological features before and after HSCT 245 293 CD4+/µL ART: TAF/FTC+RAL <40 <40 <40 <40 <40 <40 <40 <40 HIV pVL 99,3% chimersim. TAC/MMF GvHD Transplantation 39.0 / 69.2 / <LOD / <LOD / 1.4 / 2,8x10 5 2,1x10 5 4,5x10 6 3,9x10 6 1,8x10 6 Folie 8 Titel Proviral DNA load pro 1x10 6 PBMCs (Analyzed PBMC-count)

Virological features before and after HSCT 245 293 CD4+/µL ART: TAF/FTC+RAL <40 <40 <40 <40 <40 <40 <40 <40 HIV pVL BKPyV- Reactivation 99,3% chimersim. TAC/MMF GvHD Transplantation 39.0 / 69.2 / <LOD / <LOD / 1.4 / 2,8x10 5 2,1x10 5 4,5x10 6 3,9x10 6 1,8x10 6 Folie 9 Titel Proviral DNA load pro 1x10 6 PBMCs (Analyzed PBMC-count)

HIV Immunoblot analysis before and after HSCT … Immunoblot analysis: sgp120+, gp41+, p31+, p24+, p17+ Folie 10 Titel Treatment of HIV and EBV associated lymphoma by allogenic CCR5 Δ32 blood stem cell transplantation

More samples… 05.11.2018 Ficoll 04.02.2019 Ficoll 07.02.2019 Ficoll 04.02.2019 Plasma 11.02.2019 Ficoll 07.02.2019 Plasma 14.02.2019 Ficoll 11.02.2019 Plasma 18.02.2019 Ficoll 13.02.2019 Plasma 21.02.2019 Ficoll 14.02.2019 Plasma 25.02.2019 Ficoll 18.02.2019 Plasma 22.03.2019 Ficoll 21.02.2019 Plasma 25.03.2019 Ficoll 26.02.2019 Plasma 04.04.2019 Ficoll 26.02.2019 Plasma 08.04.2019 Ficoll 27.03.2019 Plasma 15.04.2019 Ficoll 24.04.2019 Plasma 16.04.2019 Ficoll 23.04.2019 Ficoll 24.04.2019 Ficoll 24.04.2019 Ficoll Folie 11 Titel

Acknowledgements Institute for Virology HMT Transplantationsambulanz Ulf Dittmer Rudolf Trenschel Barbara Bleekmann Olympia Anastasiou HIV/HPSTD-Studienambulanz Miriam Dirks Stefan Esser Helene Sertznig Tyärk Rütten University of Cologne, Virology University of Düsseldorf, Virology University Hospital Erlangen Rolf Kaiser Nadine Lübke Thomas Harrer Veronica di Cristanziano Elena Knops University Hospital Hamburg-Eppendorf Seq-IT, Kaiserslautern Eva Heger Johanna Eberhard Martin Däumer Folie 12 Titel Alexander Thielen