HSCT Engraftment Kinetics: Differences in Chimerism between Haploidentical (HI) and Matched Related (MR) Transplant Recipients (HSCT) after the 2 Step Approach

Cyclophosphamide (CY) toleration has been associated with low rates of graft versus host disease (GVHD) and non-relapse mortality after both HI and MR HSCT. At Jefferson, both recipient types undergo a 2 step approach to HSCT in which after myeloablative (MYA) or reduced intensity (RIC) conditioning, patients receive a fixed dose of 2 x 108/kg donor CD3+ T cells (DLI), followed 2 days later by CY daily x 2 for bidirectional tolerization. A CD34-selected stem cell product containing Data for 292 consecutive patients (232 HI, 60 MR) treated on a 2-step trial were evaluated for incorporation into this analysis. To be included, patients were required to be in remission for 3 months post HSCT and have available d+28 and d+90 peripheral blood T cell chimerism data. Seven HI patients with graft rejection, 5/232 with early (2%-all MYA) and 2/232 with late (0.1%-1 MYA and 1 RIC), were not included in the analysis. No MR patients developed graft rejection. Days to ANC > 500 cells x 103/ul, CD3/4 and CD3/8 counts at d+28 and d+90, peak fever after DLI infusion as a rough measure of alloreactivity, and number of patients requiring post HSCT donor lymphocytes for mixed chimerism were also examined. Independent samples T test was used for chimerism and peak fever comparisons. The final study group contained 201 patients treated on a 2 step MYA [12 Gy total body irradiation (TBI)] or RIC (fludarabine/TBI based) regimen. Patients had various hematological malignancies and 6 had aplastic anemia. Data is contained in the table. Mean T cell chimerism was higher in HI versus MR recipients at d+28 and d+90 (p= 0.001 both time points). In 3 MR recipients, donor T cell chimerism was The data presented here supports the concept that MHC mismatching in HI HSCT is associated with a higher frequency of alloreactive T cells in the DLI which more efficiently eliminate residual host lymphocytes prior to CY administration resulting in more complete donor lymphoid chimerism. Interestingly, further support for this notion was provided by the MR recipient data where higher fevers, a surrogate for more robust immunologic activation, translated into the more rapid achievement of full donor chimerism. This finding was potentially due to higher alloreactivity between some MR recipient/donor pairs from non-MHC polymorphisms. Persistence of small numbers of host lymphocytes, which have also been rendered tolerant by CY administration, does not, in and of itself, lead to graft failure/rejection. However, concerns that low degree of chimerism might contribute to higher risk of relapse led to administration of post-transplant DLIs to push donor lymphoid chimerism closer to 100%. The impact if any, of delayed complete chimerism on GVHD and relapse requires further evaluation and may dictate changes to the 2 step regimen for the MR group. Disclosures Porcu:Innate Pharma: Consultancy.