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Immunosuppressive strategies and infectious risk in hematopoietic stem cell transplantation

Immunosuppressive strategies and infectious risk in hematopoietic stem cell transplantation Andrea Bacigalupo Istituto di Ematologia Fondazione Policlinico Universitario Gemelli IRCCS Universita’ Cattolica del Sacro Cuore Roma Varese, 23 maggio 2019. MTX. Cyclosporin A. CyA+MTX. PTCY.

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Immunosuppressive strategies and infectious risk in hematopoietic stem cell transplantation

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  1. Immunosuppressive strategies and infectious risk in hematopoietic stem cell transplantation Andrea Bacigalupo Istituto di Ematologia Fondazione Policlinico Universitario Gemelli IRCCS Universita’ Cattolica del Sacro Cuore Roma Varese, 23 maggio 2019

  2. MTX Cyclosporin A CyA+MTX PTCY CyA + MMF FK+ Sirolimus TCD ex vivo ex vivoCD34 sel / αβ CD19 dep T CD in vivo (ATG /CAMP) 1970 1980 1990 2000 2010 2017

  3. Post-transplant CY: Three distinct and sequential mechanisms for induction and maintenance of tolerance 3 Intrathymic clonal deletion of donor-derived anti host T cells 1 1anti-host and anti-donor T cells are destroyed in the periphery 2 development of peripheral tolerance Luznik, 2012

  4. Allpatients and year of transplant: acute GvHD II P<0.000001 <2000, n=1062 40% 2001-2010, n=840 20% 12% >2010, n=914

  5. Allpatients and year of transplant: acute GvHD III-IV P<0.000001 <2000, n=1238 13% 2001-2010, n=927 5% >2010, n=961 4%

  6. GvHD prophylaxis 2000-2018 HLA id.sibsCyA MTX UD 8/8 CyA MTX ATG 5 CB (4/6 5/6) CyA MTX ATG 5 HAPLO CyA MMF PT-CY

  7. Pre-engr BSI G+ G- F N=166 (30%) at least 1 BSI 19% 15% Median int from SCT 8 days Year 2010-2012 =29% 18% 14% Year 2013-2016 =31% 20% 16% HLA id SIB 7% 4% UD 7% 16% CB 26% 11% HAPLO 26% 19%

  8. Pre-engr BSI: 7 and 30 day mortality 7d 30d N=166 at least 1 BSI 5% 8% G+ 0% 1% G- 6% 11% Coli (4) 2% 4% Klebsiella (6) 33% 50% Pseudomonas (3) 33% 67% Multiple only G+ (8) 0% 1% G+G- (19) 21% 26%

  9. Pre-engr BSI: Factors predicting IR mortal NRM D 60 BSI YES Etiology G- G- Engraftm no Year >2012 (2.5%)

  10. Pre-engraftmentinfections # predicted by donor type HLA mismatch and/or GvHD proph ? # negative impact on 60-day NRM # caused mainly by carbapenem resistant Gram- pathogens, # particular attention should be given to appropriate empiric therapy and management of patients at high risk for Gram-negative BSI.

  11. Post engraftment infections CMV EBV Aspergillus Bacteria

  12. GvHD prophylaxis HLA id.sibsCyA MTX UD 8/8 CyA MTX ATG 5 CB (4/6 5/6) CyA MTX ATG 5 HAPLO CyA MMF PT-CY

  13. CD4 recoveryafter HSCTmediancounts CsA+MTX CsA+MMF+PTCY CsA+MTX+ATG CsA+MTX+ATG

  14. ChronicGvHD (moderate-severe) Acute GvHD (grade II-IV) P= 0.02 P= 0.003 SIBS ; 29% UD; 31% SIBS ; 31% UD; 21% UCB; 19% UCB; 21% HAPLO; 14% HAPLO; 14% CMV infection TransplantRelatedMortality P= 0.007 UD; 76% HAPLO; 75% UCB; 74% SIBS; 55% UCB; 34% UD; 34% SIB ; 19% HAPLO; 17% P< 0.001 Fig.2

  15. CMV infection after engraftment • # higher risk with HLA mm donors • And treatment?

  16. Cumulative incidence of CMV response P=0.01 84% HAPLO and PT-CY, n=67 59% UD and ATG, n=30 Both HLA mm DifferentGvHDproph Sameincidence of CMV But HAPLO higher CD4

  17. Actuarialsurvival HAPLO and PT-CY, n=67 71% 51% UD and ATG, n=30 P=0.02

  18. Rituximab 200 mg fixed dose Day +5

  19. Infections: • donortype/ diagnosis / ATG/ • HLA mm / GvHDprophylaxis/ • CD4 recovery • Complexinterplay

  20. Infectionsrelateddeath and year of transplant N= 3126 allograftedpatients AGE Alt Don <2000 10% 32yy 22% 2000-2010 12% 42yy 51% 2011-2018 7% 52yy 78% P=0.001

  21. Infectionsrelateddeath and year of transplant N= 3126 allograftedpatients AGE Alt Don <2000 10% 32yy 22% 2000-2010 12% 42yy 51% 2011-2018 7% 52yy 78% (PTCY 65%) P=0.001

  22. Non Infectionrelateddeath and year of transplant N= 3126 allograftedpatients <2000 44% 2000-2010 45% 2011-2018 38% P<0.00001

  23. Non Infectionrelateddeath and year of transplant N= 3126 allograftedpatients (ge-gem) <2000 (n=1236) 45% 2000-2010 (n=927) 42% 2011-2018 (n=963) 54% P<0.00001

  24. Conclusions # BetterGvHDprophylaxis # Better CD4 recovery with PT-CY ascompared to ATG # Improvedsurvival Whatnow?

  25. GvHD proplylaxis <=2018 2019  HLA id.sibsCyA MTX CyA MMF PT-CY UD 8/8 CyA MTX ATG 5 CyA MMF PT-CY CB (4/6 5/6) CyA MTX ATG 5 CyA MMF PT-CY HAPLO CyA MMF PT-CY CyA MMF PT-CY

  26. Commissione Infezioni Corrado Girmenia Genova BMT Unit E Angelucci AM Raiola, F Gualandi, A Dominietto, R Varaldo, M T Van Lint , S Bregante, C di Grazia T Lamparelli Gemelli BMT Unit S Sica, L Laurenti, P Chiusolo, F sora’, S Giammarco, E Metafuni, I Innocenti, F Autore A DiGiovanni E Alma ID Unit GE C Viscoli M Mikulska V del Bono Gemelli ID Unit R Cauda M Tumbarello Microbiology M Sanguinetti Data Manager R Oneto G Conti M Daneri Nursing team

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