T- Cell Depleted Peripheral Blood Stem Cell (TCD-PBSC) Transplants Secure Consistent Engraftment with Low Risk of Acute or Chronic Gvhd and Favorable Disease Free Survival (DFS) and Overall Survival (OS) for Pediatric Patients (<21 years) with AML in CR1 or CR2 or MDS Including tMDS/AML

Higher cGVHD, TRM and treatment failure following sibling donor unmanipulated allogeneic PBSCT compared to BMT in children and adolescents has been reported by the IBMTR (Eapen M et al, J Clin Oncol, 2004). To determine the effect of T cell depletion (TCD) of PBSC on outcome for pediatric patients with AML or MDS, we reviewed our results with 49 patients (pts) with AML-1CR (n=18), AML-CR2 (n=11), MDS (n=10) and tAML/MDS (n=8/2) following allogeneic TCD-PBSCT transplanted between June 2003 and January 2015. Median age in this cohort was 13.9yrs (range 1.9 - 20.4) with 27 males and 19pts CMV seropositive at time of PBSCT. Donors were related HLA identical (14siblings, 1uncle), unrelated HLA 10/10 matched (n=14) or unrelated HLA mismatched (n=20: 9/10 n=12: 8/10 n=8). Cytoreduction consisted of a HFTBI containing regimen (n=14) with thiotepa and cyclophosphamide (n=12) or thiotepa and fludarabine (n=2). Alternatively, 35 pts received chemotherapy alone: BU/MEL/FLU (n=31) or other (n=4). ATG provided graft rejection prophylaxis for 43 pts either pre (n=37) or post (n=6) infusion. Six young pts with sibling donors did not receive ATG. No pt received additional GVHD prophylaxis. PBSC were CD34+ selected using ISOLEX 300i Magnetic Cell Selection System, followed by sheep erythrocyte rosetting (n=25) or CD34+ selected with Miltenyi CliniMACS device (n=24). The median CD34+ cells/Kg was 10.5x10⁶ (range 3.3 - 33.4x10⁶) and CD3+ cells/kg was 2.4x10³ (range 0 - 29x10³).

All pts engrafted neutrophils and platelets at a median of 11 days (range 9 - 14 days) and 26 days (range 13 - 182 days), respectively. 42pts had platelet recovery by day 40. One patient who had late graft failure (GF) at 3.5 mos engrafted with a subsequent unmanipulated PBSCT. Seven pts developed Grade II or III aGVHD of skin or GI. No pt had Gr IV aGVHD. Six pts responded to treatment. Only 1pt developed limited cGVHD of the skin. No pt who was CMV seronegative developed CMV viremia. 7 of 19 CMV seropositive pts developed CMV viremia. Nine pts received rituximab for EBV viremia. No pt died of CMV disease or EBV-LPD. Five pts received defibrotide for treatment of VOD.

With a median follow-up of 36.3 mos the DFS and OS at for the entire cohort at 3 yrs is 72.3% and 87.7%, respectively. Although the DFS for pts with AML-CR1 is 75.6%, 3 of 4 pts are in CR2 post a second BMT for OS of 94.4%. The 4 pts with AML-CR2 who relapsed died of disease. In this series of 49 pts, 6pts died of disease, 1 pt died of aGVHD and 1 pt (Down Syndrome) died of MOF (VOD). Thus, in young pts (< 21 yrs) TCD-PBSCT is associated with low risk of acute and chronic disease, no increment in relapse and a highly favorable DFS and OS. The data support the inclusion of pediatric pts in BMT CTN 1301 trial (NCT02345850): a Randomized, Multi-Center, Phase III Trial of Calcineurin Inhibitor-Free Interventions for Prevention of Graft-versus-Host Disease.