First clinical results with ±²+ T-cell depleted haploidentical stem cells in children...

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Transcript of First clinical results with ±²+ T-cell depleted haploidentical stem cells in children...

  • Slide 1
  • First clinical results with + T-cell depleted haploidentical stem cells in children Childrens University Hospital, Tbingen, Germany P Lang, T Feuchtinger, HM Teltschik, P Schlegel, M Schumm, P Schwarze, M Pfeiffer, K Schilbach, R Handgretinger
  • Slide 2
  • Haploidentical donors : T cell depletion mandatory 1.CD34+ Selection pure stem cells 2. CD3/19 Depletion Stem cells + effectors (NK cells) 3. TCR/CD19 Depletion Stem cells + effectors (NK cells + T cells) 4. Antigen- specific T cells + + 1995 2011
  • Slide 3
  • The anti-leukemic activity of gamma/delta T-cells Otto M. et al: Human T cells from G-CSF mobilized donors retain strong tumoricidal activity and produce immunostimulatory cytokines after clinical scale isolation. J Immunotherapy 2005: 28: 73 Godder et al., Long term disease-free survival in acute leukemic patients recovering with increased T cells after partially mismatched related donor bone marrow transplantation. BMT 2007; 39,751-757.
  • Slide 4
  • magnet waste ( T cells) 1. biotin-anti- mAb 2. microbeads with anti-biotin mAb graft T-cells CD34+ and CD34- progenitors NK cells dendritic cells Strategy for depletion of + T-cells Chaleff S. et al.: A large scale method for the selective Depletion of / T-lymphocytes from PBSC for allogeneic Transplantation. Cytotherapy, 2007
  • Slide 5
  • TCR depletion: Efficacy of procedure n = 9BeforeAfterLog Depletion Percent TCR 29.2 6.40.0015 0.0008 absolute TCR + 1.4 0.52 x10 10 0,38 0.22 x10 6 4.6 0.3 absolute CD3+ 1.4 0.44 x10 10 3.5 1.8 x10 8 1.6 0.2 absolute CD19+ 2.7 1.4 x10 9 5.3 5.8 x10 6 3.9 0.6
  • Slide 6
  • n=49 Comparative analysis of the efficacy of T-cell depletion CD34+ selection vs CD3- vs TcR -depletion 4.6 log
  • Slide 7
  • Graft composition after TCR /CD19 depletion (n=24 patients) CD34+ x10 6 /kg CD3+ x106/kg CD19+ x10 3 /kg CD56+ x10 6 /kg CD14+ x10 6 /kg aTcR+ x10 3 /kg TcR+ x10 6 /kg min54.646353511.65 max3841.8528192.281146.430 median1213.6110107.461818.911
  • Slide 8
  • Patients (pediatric, n=24) Diagnosisn= ALL12 AML/MDS/JMML7 Nonmalignant4 Solid tumors1 Disease statusn= CR2-CR68 (35%) NR/active disease11 (48%) 2 nd /3 rd SCT16 (70%)
  • Slide 9
  • ATG-F (15 mg/kg) 1mg4 mg5 mg -1211109876543+1210 Fludarabin (mg/m) or Clofarabin 40mg Thiotepa (mg/kg) 10mg Melphalan (mg/m) 70mg TCR /CD19 depleted cells days from transplantation Conditioning regimen (2) n=12 steroids MMF, if >25.000 residual abT cells
  • Slide 10
  • TCR /CD19 Depletion: Engraftment
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  • TCR /CD19 Depletion: residual T-cells do not cause GvHD (22/24 patients without pharmacological immune suppression) acute GvHD graden=% no GvHD521 11250 2312 3312 414
  • Slide 12
  • TCR /CD19 Depletion: Outcome Alive: 17 out of 24 patients (70%) Median Follow up: 0.5 (0.06-1.4) years
  • Slide 13
  • Comparison of CD3+ recovery: CD3/19 vs TCR /CD19 Depletion
  • Slide 14
  • Comparison of CD3+ recovery at day +30 p