393 ALPHA/Beta T- CELL Depleted Allogeneic STEM CELL Transplantation from Matched Related and Unrelated DONOR Grafts in Patients with Poor Risk Leukemia

Track: Poster Abstracts
Saturday, February 14, 2015, 6:45 PM-7:45 PM
Grand Hall CD (Manchester Grand Hyatt)
Moniek de Witte, MD, PhD , Department of Hematology, University Medical Center Utrecht, Utrecht, Netherlands
Lotte van der Wagen, MD , Department of Hematology, University Medical Center Utrecht, Utrecht, Netherlands
Ineke Slaper-Cortenbach, PhD , 5Gene and Cell Therapy Facility, UMC Utrecht, Utrecht, Netherlands
Jurgen Kuball, MD, PhD , Blood and Marrow Transplantation Program, University Medical Center Utrecht, Utrecht, Netherlands
Presentation recording not available for download or distribution as requested by the presenting author.
Introduction: The outcome of allo-SCT in patients with poor risk leukemia is still hampered by GVHD and relapse. The innate immune system has been reported to contribute to tumor control, with lower incidence of GVHD. Specific depletion of αβ T- cells – key players in the development of GVHD – will render NK cells and gd T cells within the allograft. Recently reported results have shown the great promise of this approach in haploindentical transplantations. Within this study, we aim to extend αβT- cell depleted allo-SCT to patients with a MRD or MUD.

Methods: Patients with either ‘poor-risk’ or ‘very poor-risk’ leukemia were included in this phase I study. Either HLA matched siblings (MRD) or HLA matched (9 or 10/10) unrelated donors (MUD) were eligible. abT-cell reduction was performed by negative selection with anti-abTCR antibodies in combination with magnetic microbeads, using the automated CliniMACS device (Miltenyi Biotec, Bergisch Gladbach, Germany). The maximal contamination with abT-cells for all dose levels was 5x105/kg. The conditioning regimen consisted of: ATG (Genzyme®) 4 or 6 mg/m2 + fludarabine 120 mg/m2 + busilvex AUC=90 followed by αβT- cell depleted grafts from matched related or unrelated donors. No additional immune suppression was given after allo-SCT.

Results: Products for 15 patients have been successfully processed and used for αβT-cell depleted allo-SCT between 2013 and 2014. A ~4 log depletion of αβT-cells has been observed in the product with a recovery of ~75% of CD34+ cells. The combination of ATG/fludarabine/busilvex was well tolerated with a hematological recovery within 3 weeks. Primary engraftment (chimerism > 95%) was observed in all patients. Immune reconstitution primarily consisted of innate cells (NK cells and gd T cells) the first 6 months post transplantation. In addition, no increase in CMV or EBV reactivations has been observed so far under the profound “innate control”. Up to date, none of the patients developed aGVHD > grade II.

Conclusion: ATG Busulfan Fludarabine is a low toxicity platform for abTCR-depleted transplantations, resulting in a swift reconstitution of innate cells (NK cells and gd T cells) the first 6 months post transplantation. This transplantation strategy can serve as a tool for future immunological interventions such as a pre-emptive DLI or transfer of genetically modified T cells. 

Disclosures:
Nothing To Disclose