Lineage Specific Chimerism Analysis Reveals That Mixed Donor T-Cell Chimerism Is Common in the Early Post-Transplant Period Following Myeloablative Allotransplants from HLA-Matched but Not HLA-Haploidentical Donors: A Multivariable Analysis of Allografted Patients from a Single Center

Failure to achieve complete donor T-cell chimerism in the early post-transplant period may impair the graft-versus malignancy effect and contribute to a higher risk of disease relapse. Lineage specific chimerism analysis (LSCA) of T-lymphocytes versus myeloid cells is routinely performed following reduced-intensity or non-myeloablative hematopoietic cell allografts. However, many centers do not perform LSCA following myeloablative conditioning. We performed LSCA in all consecutive patients receiving a first T-replete allotransplant using myeloablative conditioning as defined by the CIBMTR (Giralt 2009 BBMT 15;367) between 2/2006 and 2/2015 (n=232; patient characteristics: median age 49 (18-73); Female 50%, Black 19%, Asian 3% white 78%; donor MRD 41%, MUD 39%, Haploidentical 20%; graft PBSC 88%, BM 11.5%, both 0.5%; diagnosis AML 52%, ALL 18%, MDS 11%, CML 11%, NHL 4% MPS1%, CLL1%, HL 1%; DRI low 10%, intermediate 51%, high 29%, very high 10%. Our objectives were to determine the rate of full-donor and mixed T-cell chimerism in the early post-transplant period (d 30 and d 90) , to determine the association of T-cell chimerism with patient, disease and regimen specific factors, and to determine whether early mixed chimerism impacts post-transplant outcomes following myeloablative conditioning. LSCA was performed on peripheral blood using a RoboSep instrument for automated sorting of CD3-positive T-cells and CD33 positive myeloid cells to 96.5-100% and 98.3-100% purity respectively, and short tandem repeat analysis by PCR. Full donor chimerism was defined as > 90% donor derived cells. Probability of achieving full donor T-cell chimerism in evaluable patients on d 30 and d 90 post transplant were 55% and 71%. In contrast the probabilities of achieving full-donor myeloid chimerism were 99.5% and 93.5% respectively. On univariate analysis the following factors were significantly associated with achievement of full-donor T-cell chimerism on d 30: donor type (haploidentical 100%, MRD 39%, MUD 47%, p 50% or to administer DLI (starting at 1 x 10e6 CD3+ cells/kg) for patients with CD3 chimerism Disclosures No relevant conflicts of interest to declare.