12-Month Full Donor Chimerism Is Associated with Low-Grade Acute Graft Versus Host Disease (aGVHD) and Predicts Superior Outcomes in Reduced Intensity (RIC) Alemtuzumab-Based Transplants for MDS and AML

Introduction

Reduced intensity (RIC) Alemtuzumab conditioned allogeneic stem cell transplants have enabled a successful graft versus leukaemia effect while GvHD rates were low. The impact of chimerism on outcome has scarcely been studied in RIC, Alemtuzumab-based transplants.

Patient characteristics

Retrospective analysis of 50 patients with high risk MDS (n=14) and AML (n=36) undergoing RIC-Alemtuzumab transplant in our center since 2006. Median age was 62 years (range 51-72) and there were 33 male and 17 female recipients. All donors were fully (10/10) matched in HLA-loci. 11 patients had a sibling donor while 39 had a matched unrelated donor. 29 patients were conditioned with fludarabine, melphalan and alemtuzumab while 21 patients received fludarabine, busulphan and alemtuzumab.

Results

The median follow-up of patients was 18.2 months (range 15-90). Median overall survival was 27.4 months and median progression free survival 33 months. At 3 months post-HSCT 72% (n=36) and 18% (n=9) of patients were full and mixed chimeras respectively. At 12 months post-HSCT n=19 and n=10 of patients were full and mixed donor respectively. 14 patients (28%) developed grade 1-2 GvHD while only 1 (2%) grade 3-4 GvHD. Patients who attained 12-month full donor chimerism in whole blood (WB), had a mean PFS of 85 months as compared to 81.5 months for mixed chimeras (p= 0.04). In 3-months, those who were full donor in WB had a mean PFS 95 months compared to 33 for mixed chimeras in WB (p= 0.016). 3, 12 -month T-cell chimerism did not influence OS and PFS. The presence of grade I-II GVHD was significantly associated with 12-month full donor chimerism in both WB and T-cells (p<0.05).

Conclusion

In our series of AML/MDS patients who received RIC Campath-based allografts, full donor chimerism is a surrogate marker for progression free and overall survival. All grade I/II aGVHD patients achieved full donor chimerism in whole blood.