Andrea Bacigalupo Istituto di Ematologia

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Presentation transcript:

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

PTCY CyA+MTX MTX Cyclosporin A TCD ex vivo 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

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 1 anti-host and anti-donor T cells are destroyed in the periphery 2 development of peripheral tolerance Luznik, 2012

All patients and year of transplant: acute GvHD II 40% 2001-2010, n=840 20% 12% >2010, n=914

All patients and year of transplant: acute GvHD III-IV 13% 2001-2010, n=927 5% >2010, n=961 4%

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

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%

Pre-engr BSI: 7 and 30 day mortality 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%

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

Pre-engraftment infections # 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.

Post engraftment infections CMV EBV Aspergillus Bacteria

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

CD4 recovery after HSCT median counts CsA+MTX CsA+MMF+PTCY CsA+MTX+ATG CsA+MTX+ATG

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

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

Cumulative incidence of CMV response 84% HAPLO and PT-CY, n=67 59% UD and ATG, n=30 Both HLA mm Different GvHD proph Same incidence of CMV But HAPLO higher CD4

Actuarial survival HAPLO and PT-CY, n=67 71% 51% UD and ATG, n=30 P=0.02

Rituximab 200 mg fixed dose Day +5

Infections: donor type/ diagnosis / ATG/ HLA mm / GvHD prophylaxis/ CD4 recovery Complex interplay

Infections related death and year of transplant N= 3126 allografted patients AGE Alt Don <2000 10% 32yy 22% 2000-2010 12% 42yy 51% 2011-2018 7% 52yy 78% P=0.001

Infections related death and year of transplant N= 3126 allografted patients AGE Alt Don <2000 10% 32yy 22% 2000-2010 12% 42yy 51% 2011-2018 7% 52yy 78% (PTCY 65%) P=0.001

Non Infection related death and year of transplant N= 3126 allografted patients <2000 44% 2000-2010 45% 2011-2018 38% P<0.00001

Non Infection related death and year of transplant N= 3126 allografted patients (ge-gem) <2000 (n=1236) 45% 2000-2010 (n=927) 42% 2011-2018 (n=963) 54% P<0.00001

Conclusions # Better GvHD prophylaxis # Better CD4 recovery with PT-CY as compared to ATG # Improved survival What now?

GvHD proplylaxis <=2018 2019  HLA id.sibs CyA MTX CyA MMF PT-CY <=2018 2019  HLA id.sibs CyA 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

Nursing team Genova BMT Unit Gemelli BMT Unit ID Unit GE 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 Commissione Infezioni Corrado Girmenia Data Manager R Oneto G Conti M Daneri Nursing team