Allogene Neues vom immunologischen Ctrl-Alt-Del Prof. Dr. med. Wolfgang Bethge
Allogene am ASH Insgesamt 715 Abstracts zum Thema Auswahl: Azacitidine als Überbrückung zu allogenen SZT bei MDS Ergebnis Allo SZT bei Patienten >65 mit MDS RIC vs MAC für MDS/AML Allogene CAR-T cells RIC SZT als Salvage für das rezidivierte hochmaligne NHL Haploidente SZT: was gibt es neben Post SZT Cy Neues? Ruxolitinib für steroidrefraktäre GVHD
Azacitidine und Allo SZT bei MDS #66 Voso et al.
Azacitidine und Allo SZT bei MDS #66 Voso et al.
Allo SZT bei MDS in Patienten über 65 Bis 2010 keine Medicare Übernahme einer SZT >65 Jahre in USA! Prospektives CIBMTR Register #193 Attalha et al.
Allo SZT bei MDS in Patienten über 65 #193 Attalha et al.
RIC versus MAC bei MDS/AML Late-Breaking Scott et al.
RIC versus MAC bei MDS/AML Late-Breaking Scott et al.
Allogene CAR-T Zellen Jacobson et al. Blood 2011 Gamma-retroviraler Vector CD28 Kostimulatorische Domaine Einzelne Infusion von CAR-CD19 Keine Lymphodepletion Maude et al. Blood 2015 #99 Kochenderfer et al.
Allogene CAR-T Zellen Phase I Dosiseskalation Donor CAR-CD19-T Zellen N=20 ORR 40% (6 CR, 2 PR) Keine GVHD Persistenz für etwa 14 Tage Response auch in Patienten ohne Ansprechen auf DLI AEs: Fieber, Tachykardie, Hypotension Patient Number Malignancy 1 CLL Transplant type URD 10/10 HLA match Total T cells infused/kg Anti-CD19 CARexpressing T cells infused/kg Malignancy response at last follow-up (interval from infusion to last follow-up in months) 1x10 6 0.4x10 6 SD (3) 2 DLBCL Sibling 2x10 6 0.7x10 6 SD (1) 3 CLL Sibling 4x10 6 2.4x10 6 PD 4 DLBCL Sibling 4x10 6 2.2x10 6 SD (31+) 5 CLL URD 10/10 HLA match 1.5x10 6 1.0x10 6 CR (30+) 6 MCL Sibling 7x10 6 4.6x10 6 SD (3) 7 CLL URD 10/10 HLA match 1x10 6 0.7x10 6 PD 8 MCL Sibling 7x10 6 3.9x10 6 SD (24+) 9 MCL URD 10/10 HLA match 4x10 6 2.2x10 6 PR (3) 10 MCL Sibling 10x10 6 7.8x10 6 SD (2) 11 CLL URD 9/10 HLA match 5x10 6 3.1x10 6 PR (12+) 12 ALL Ph+ Sibling 7x10 6 5.2x10 6 MRD-negative CR (15+) 13 MCL Sibling 10x10 6 7.1x10 6 SD (9) 14 ALL Ph-neg Sibling 10x10 6 7.0x10 6 MRD-negative CR (5) 15 ALL Ph-neg Sibling 10x10 6 6.9x10 6 MRD-negative CR (3) 16 ALL Ph-neg Sibling 7x10 6 5.6x10 6 PD 17 DLBCL Sibling 10x10 6 8.2x10 6 CR (6+) 18 DLBCL Sibling 10x10 6 3.1x10 6 SD (2) 19 FL URD 10/10 transformed HLA match to DLBCL 5x10 6 4.3x10 6 PD 20 ALL Ph-neg URD 9/10 HLA match 5x10 6 4.2x10 6 MRD-negative CR (3+)^ #99 Kochenderfer et al.
Salvage RIC Allo für Relapsed DLBCL #197 Fenske et al.
Salvage RIC Allo für Relapsed DLBCL Tübingen #197 Fenske et al.
Haplo SZT: nur noch Post-Cy? Retrospektiver Vergleich Familienspender/Fremdspender/Haplo TCRαβ 2010-2014 Sibling (n=41) MUD (n=51) Haplo (n=80) Sex M 27 32 55 F 14 19 25 p=0.77 cgvhd TRM Age at Transplantation (years) 10.6 9.4 9.7 p=0.20 Disease ALL 34 35 56 AML 7 16 24 Disease status at Transplantation CR1 20 30 30 CR2 21 20 47 CR3 0 1 3 p=0.23 p=0.13 Relapse CMV serology (Donor/Recipient) neg/neg 8 5 6 neg/pos 8 21 7 pos/neg 1 4 11 pos/pos 24 21 56 Source of Stem Cells BM 40 40 0 PBSC 1 11 80 Conditioning regimens TBI-based 26 29 60 non TBI-based 15 22 20 p=0.001 p<0.0001 p=0.10 EFS #195 Bertaina et al.
Ruxolitinib für steroidrefraktäre GVHD #858 Zeiser et al.
Ruxolitinib für steroidrefraktäre GVHD #858 Zeiser et al.
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Wichtige Studien Tübingen Allo-SZT Phase I/II safety and feasibility study using CliniMACS TCR-α/β and CD19 depleted stem cell grafts from haploidentical donors for haematopoietic progenitor cell transplantation in children and adults (Miltenyi Studie) Evaluation of the impact of remission induction chemotherapy prior to allogeneic stem cell transplantation in relapsed and poor-response patients with AML (ETAL3-ASAP) Prophylactic application of escalating doses of donor-derived central memory T lymphocytes (Tcm) after allogeneic hematopoetic progenitor cell transplantation (HPCT) to prevent infectious complications: A Prospective, first in man, open Phase I/IIa Clinical Trial (PACT-DZIF) Clinical phase III trial to compare Treosulfan-based conditioning therapy with Busulfanbased reduced-intensity conditioning (RIC) prior to allogeneic haematopoietic stem cell transplantation in patients with AML or MDS considered ineligible to standard conditioning regimens (Medac Studie) Weitere Studien unter www.onkologie-tuebingen.de Ansprechpartner: Prof. Dr. Wolfgang Bethge