Long Term Survival and Relapse Rate After Transplantation of Highly T and B Cell Depleted Stem Cells From Alternative Donors in Pediatric Patients with Acute Lymphatic Leukemia.
Authors: Lang Peter J. , Mueller Ingo , Teltschik Heiko-Manuel , Schumm Michael , Pfeiffer Matthias , Feuchtinger Tobias , Greil Johann , Bader Peter , Klingebiel Thomas , Handgretinger Rupert 
Published: October 2019

Abstract
Abstract 4333
T cell mediated GvL effects have been shown in particular in adult CML patients. However, those effects are less clear in childhood acute lymphatic leukemias (ALL). Here, we present long term results in 68 pediatric patients with ALL who received highly T and B cell depleted stem cells from matched unrelated (n=17) or full haplotype mismatched related donors (n=51) at the Children's University Hospital Tuebingen. Our aim was to minimize GvHD and to avoid EBV LPD in both matched and mismatched transplantations. Remission status was: CR 1, n=18; CR2, n=23; ≥CR3, n=12; Non remission or second transplant, n=15. Graft manipulation was carried out with immunomagnetic microbeads and the CliniMACSTM device (indirect depletion of T and B cells with CD34+ or CD133+ positive selection (n=50); or direct depletion with anti-CD3/anti-CD19 coated microbeads (n=18)). T and B cell counts were reduced for 4-5 log with median numbers of residual T cells of 15 000/kg bw (positive selection) and 49 000/kg bw (CD3/19 depletion). No pharmacological immune suppression was given after positive selection, whrereas patients with CD3/19 depleted grafts received mycophenolate mofetil. The conditioning regimenn were either TBI or Bu based (n=50) or a toxicity reduced protocol (Flud, TT, Mel) was used (n=18). Rejection prophylaxis was carried out with ATG or OKT3. Primary engraftment occurred in 85% of the patients. After reconditioning, final engraftment was achieved in 98%. GvHD grade 0-1 occurred in 86%. 12% had GvHD grade II, 4% had GvHD grade III. Chronic GvHD occurred in 4 patients. No GvHD related mortality was observed.
Median follow up was 5.9 years. EFS at 1 year was 56% (CR1), 51% (CR2) and 50% (≥CR3); EFS at 5 years was 49% (CR1), 46% (CR2) and 27% (≥CR3). Median survival of patients with active disease was 0.2 years. Relapse rates at 1 year were 0.32 (CR1), 0.47 (CR2) and 0.46 (≥CR3); relapse rates at 5 years were 0.32 (CR1), 0.47 (CR2) and 0.64 (≥CR3). TRM at 1 year was 14%, causes of death remained viral and fungal infections, no EBV LPD occurred.

Conclusions
immunomagnetic selection of progenitor cells or depletion of T and B cells can minimize acute and chronic GVHD in both matched unrelated and mismatched related transplantations and may prevent GvHD related mortality. Lethal infections occurred in 14% of the patients probably due to the delayed recovery of T cells. Despite profound depletion of donor T cells, relapse rates were acceptable and remained on a stable level after the first year in patients with complete remission. Thus, absence of GvHD may not necessarily be associated with high relapse rates in childhood ALL. Apart from T cells, other effector cells like NK cells are likely to exert GvL effects and may contribute to the favorable long term EFS in our patients.

Disclosures:
No relevant conflicts of interest to declare.