Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation.
Saad A, Lamb L, Wang T, Hemmer MT, Spellman S, Couriel D, Alousi A, Pidala J, Abdel-Azim H, Agrawal V, Aljurf M, Beitinjaneh AM, Bhatt VR, Buchbinder D, Byrne M, Cahn JY, Cairo M, Castillo P, Chhabra S, Diaz MA, Farhan S, Floisand Y, Frangoul HA, Gadalla SM, Gajewski J, Gale RP, Gandhi M, Gergis U, Hamilton BK, Hematti P, Hildebrandt GC, Kamble RT, Kanate AS, Khandelwal P, Lazaryn A, MacMillan M, Marks DI, Martino R, Mehta PA, Nishihori T, Olsson RF, Patel SS, Qayed M, Rangarajan HG, Reshef R, Ringden O, Savani BN, Schouten HC, Schultz KR, Seo S, Shaffer BC, Solh M, Teshima T, Urbano-Ispizua A, Verdonck LF, Vij R, Waller EK, William B, Wirk B, Yared JA, Yu LC, Arora M, and Hashmi S. Impact of T-cell dose on the outcome of T-cell replete HLA matched allogeneic peripheral blood stem cell transplantation. Biol Blood Marrow Transplant 2019; Epub ahead of print.
Biology of blood and marrow transplantation
BACKGROUND: Data on whether T-cell dose of allogeneic peripheral blood stem cell (PBSC) product influences transplant outcome are conflicting. METHODS: Using CIBMTR database, we identified 2,736 adult patients who underwent first allogeneic peripheral blood stem cell (PBSC) transplant for acute leukemia (AML, ALL) or myelodysplastic syndrome (MDS) between 2008-2014 using an HLA-matched sibling donor (MSD) or 8/8-matched unrelated donor (MUD). We excluded ex-vivo and in-vivo T-cell depleted transplants. Correlative analysis was performed between CD3+ T-cell dose and risk of graft-versus-host-disease (GVHD), relapse, non-relapse mortality (NRM), disease free survival (DFS) and overall survival (OS). RESULTS: Using maximum likelihood estimation method, we identified CD3+ T-cell cell dose cutoff that separated risk of acute GVHD (aGVHD) grade II-IV in both MSD and MUD groups. A CD3+ T-cell dose cutoff of 14x10(7) cells/kg identified MSD/low CD3+ (n=223) and MSD/high CD3+ (n=1214), and a dose of 15x10(7) cells/kg identified MUD/low CD3+ (n=197) and MUD/high CD3+ (n=1102). With univariate analysis, MSD/high CD3+ group had higher cumulative incidence of day 100 aGVHD grade II-IV of 33% vs 25% when compared to MSD/low CD3+ group (P value =0.009). There was no other difference between both groups in engraftment rate, risk of aGVHD grade III-IV or chronic GVHD (cGVHD), NRM, relapse, DFS, or OS. MUD/high CD3+ group had higher cumulative incidence of day 100 aGVHD grade II-IV of 49% vs 41% when compared to MUD/low CD3+ group (P value =0.04). There was no other difference between both groups in engraftment rate, risk of severe aGVHD or cGVHD, NRM, relapse, DFS, or OS. Multivariate analysis of MSD and MUD groups failed to show an association between CD3+ T-cell dose and risk of either aGVHD grade II-IV (p value =0.1 and 0.07 respectively) or cGVHD (p value=0.8 and 0.3 respectively). Sub-analysis of CD4, CD8 and CD4/CD8 ratio failed to identify cutoff values predictive of transplant outcome. Using log-rank test, the sample size was, however, suboptimal to identify difference at these cutoff cell dose. CONCLUSION: In this registry study, CD3+ T-cell dose of PBSCT product did not influence risk of aGVHD or cGVHD or other transplant outcomes when using HLA-matched sibling or 8/8 unrelated donors. Subset analysis of CD4+ and CD8+ T-cell dose was not possible for small sample size.
ePub ahead of print