Pretransplant Characteristics Could Predict Full Donor Chimerism on Day +90 and Day +180 and Outcomes in Reduced Intensity Alemtuzumab Conditioning Allogeneic Transplantation Can Be Influenced by Chimeric Status
Authors: Nikolousis Emmanouil , Craddock Charles F. , Paneesha Shankaranarayana , Tauro Sudhir , Mahendra Prem , Cook Mark , Clark Fiona , Lovell Richard , Chaganti Sridhar , Milligan Donald , Mcmullan Dominique , Griffiths Mike , Robinson Stephen P 
Published: April 2020

Abstract
The use of reduced intensity conditioning transplants gained momentum over the last 10 years enabling older patients with haematological malignancies to go through a potentially curative treatment option. This is based on the premise of graft versus leukaemia effect with low toxicity of conditioning therapy as older patients have other co morbidities. Full donor chimerism is the optimal desired result of transplantation. We have analysed here whether pretransplant characteristics could predict full donor chimerism on whole blood and T-cell fraction on day +90 and +180 and also the effect of the chimeric status on the transplant outcomes. This study included 70 patients with lymphoid (n=43) and myeloid (n=27) malignancies with a median age of 47 years (9–63). Median follow up was 22.3 months (range 2.2 – 49.6 months). Pretransplant baseline characteristics included age, sex, donor type, previous stem cell transplant, CD34 cell dose, CD3 cell dose, disease status at the time of transplant, alemtuzumab dose (50 vs. 100mg) and conditioning regimen. Multivariate logistic regression showed CD34 cell count was significant in predicting full donor T cell chimerism at 90 days (p=0.05). High CD3 cell dose (median 20.5 vs. 2.4; p=0.01) predicted full donor whole blood chimerism at 90 days. High CD34 cell count (median 6.0 vs. 5.0, p=0.02) and type of donor (Unrelated vs. sibling: 45% vs. 13%; p=0.003) were predictors for full donor chimerism at 180 days. Full donor T cell chimerism at 180 days was predicted by high CD34 cell count (median 6.0 v. 5.0, p=0.02) and type of donor (Unrelated vs. sibling: p=0.006). Donor type (unrelated vs. sibling; 68% vs. 33%: p=0.01), high CD3 cell dose (median 130 vs. 2, p=0.0001) and dose of alemtuzumab (high vs. low; 74% vs. 33%, p=0.006) were predictors for full whole blood chimerism at 180 days. Full donor and mixed T cell chimerism at 90 days did not impact on overall survival (OS), disease free survival (DFS), relapse free survival (RFS) and chronic graft versus host disease (GvHD). Full as compared to mixed donor chimerism at 90 days (74% vs.27%, p=0.001) was associated with acute GvHD. T cell mixed chimerism as compared to full at 180 days was a predictor for relapse (HR=7.6, p=0.02). Full donor chimerism at 180 days was a predictor for both acute (OR=3.3, p=0.04) and chronic GvHD (OR=4.6, p=0.02). Whole blood chimerism at 180 days did not impact OS, DFS, RFS and acute or chronic GvHD, but it appeared to show a trend for increased relapse (HR=2.52, p=0.05). Our study revealed CD3 & CD34 cell dose along with unrelated donor type were predictors for whole blood & T cell chimerism at days +90 and +180 in reduced intensity alemtuzumab conditioning transplantation. Our study also showed donor chimerism may be a predictor for GvHD. More studies are warranted to understand the predictors for donor chimerism. This will enable to establish optimal transplant strategies.