Higher Total Nucleated Cell Dose, but Not CD3+, 4+, 8+, or 34+ Cell Dose, Is Associated with Better Overall and Progression-Free Survival after Allogeneic Peripheral Blood Hematopoietic Cell Transplantation (AlloPBHCT) with TBI-Based Conditioning Regimens

AlloPBHCT compared to bone marrow transplants have a decreased time to engraftment due to higher levels of CD34+ cells in the graft.  However, the correlation of CD34+, CD3+, CD4+, CD8+ and total nucleated cell (TNC) dose with outcomes after alloPBHCT have been inconsistent. We retrospectively analyzed graft cell composition, focusing on conditioning regimen intensity +/- total body irradiation (TBI), in 254 consecutive first alloPBHCT patients from 1/2001 to 9/2012. Patient characteristics are: 58% male, 76% ≥40 years, 56% related/44% unrelated donor, 44% AML, 18% MDS/MPD, 13% ALL, 13% NHL, 12% other diseases, 49% in CR pre-PBHCT. 94 patients had myeloablative (MA) conditioning with (n=53) or without (n=41) TBI. 160 patients had reduced intensity conditioning (RIC) with (n=40) or without (n=120) TBI. CD3+, CD4+ and CD8+ doses were analyzed above vs. below the median dose.  TNC dose was analyzed < vs ≥ 8 x 10⁸ cells/kg; CD34+ was analyzed < vs ≥ 4 x 10⁶ cells/kg. The median (range) follow-up was 3.2 (<0.1-11) years. Time to neutrophil engraftment was shorter in patients with ≥ 4 x 10⁶ CD34+ cells/kg (14 vs 15 days, P=.051), but was only significant in TBI-based conditioning (P=.007 TBI, P=NS no TBI). Time to platelet engraftment was also significantly shorter in patients with ≥ 4 x 10⁶ CD34+ cells/kg (17 vs 21 days, P=.004); but was only significant in the MA+TBI (P=.001) and RIC-noTBI (P=.023) subgroups. CD34+ dose was not associated with overall survival (OS) (Figure, Table), progression free survival (PFS, Table) or development of acute GVHD (grade II-IV or III-IV), either in the entire cohort or in any conditioning subgroups. CD3+, CD4+ and CD8+ cell doses were not associated with any outcomes in the entire cohort or in any conditioning subgroups. OS and PFS were both improved for patients receiving either a MA or RIC TBI-based regimen and a TNC ≥8 x 10⁸ cells/kg (Figure, Table). The TNC dose did not correlate with CD34+ dose and is therefore an independent predictor of outcomes. Our study suggests that understanding blood graft cell composition is needed, and that conditioning regimen may influence the desired cell dose. Further study may allow us to identify which cell population in the TNC is associated with outcomes.