Higher total nucleated cell dose, but not CD3+, CD4+, CD8+, or CD34+ cell dose, is associated with better overall survival and progression free survival after allogeneic peripheral blood transplant with TBI-based conditioning regimens
Burns, Michael William, Jr.
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Background: In the last twenty years, there has been an increase in the number of peripheral blood hematopoietic cell transplants (PBHCT) as a result of improved time to engraftment compared to bone marrow transplants. The increased cell counts that can be achieved by PBHCT raised questions as to whether the increased doses of certain cell subsets could affect certain post-transplant outcomes. This study analyzed the effect of different CD34+, CD3+, CD4+, CD8+, and total nucleated cell (TNC) doses on post-transplant outcomes in patients receiving either myeloablative or reduced intensity conditioning, with or without the use of total body irradiation (TBI). Methods: This retrospective cohort study included 254 patients receiving a primary allogeneic PBHCT. All patients were T-cell replete and were HLA-matched with their donor. Forty-one patients received myeloablative conditioning without TBI, 53, myeloablative with TBI, 120, reduced intensity conditioning without TBI, and 40, reduced intensity with TBI. Cell doses were analyzed in relation to patient's time to neutrophil engraftment, time to platelet engraftment, overall survival, progression free survival, and development of acute Graft-versus-Host Disease (GvHD). Results: Neutrophil engraftment times were significantly faster in patients receiving TBI-containing reduced intensity conditioning regimens and > 4 x 10 6 CD34+ cells/kg (15 vs. 18 days, P=.014). Faster platelet engraftment times were seen in all patients receiving > 4 x 10 6 CD34+ cells/kg (16 vs. 20 days, P=.001). Both overall survival (OS) (P=.007) and progression free survival (PFS) (P=.010) were significantly better in those patients receiving reduced intensity with TBI and a TNC dose > 8 x 10 8 cells/kg. Those patients receiving a myeloablative with TBI conditioning regimen and a TNC dose > 8 x 10 8 cells/kg saw an increased risk of grade II-IV acute GvHD (P=.021). Conclusion: This study showed that a CD34+ dose > 4 x 10 6 cells/kg significantly improved time to engraftment, but did not improve PFS or OS. Additionally, CD3+, CD4+, and CD8+ cell doses were not found to influence PFS or OS. However, a higher TNC dose led to improved PFS and OS in patients receiving TBI, specifically those receiving reduced intensity conditioning with TBI. This suggests that TBI may alter the method of tumor kill and should be compared to non-TBI containing regimens in a prospective manner. The association of TNC dose with outcome suggests that one or more immune cell subsets that may predict for and result in improved PFS and OS.