In contrast to standard myeloablative allo-SCT, the kinetic of lineage-specific chimerism of donor origin is an important issue after RIC-allo-SCT, because of its major impact on transplant-related events and outcome. Predictive factors for full CD3+ T cell LC are not yet well defined in this setting. Here, we investigated the impact of different factors on the establishment of full LC after RIC-allo-SCT. 102 patients from a single center receiving allo-SCT from an HLA-identical sibling were analyzed. Patients and graft characteristics are: age 49 y. (range, 18–67), diagnoses: 41 myeloid malignancies (40%), 43 lymphoid malignancies (42%) and 18 metastatic solid tumors (18%). 83 patients (81%) were considered as high risk. 65 patients (64%) received a fludarabine, busulfan and ATG-based RIC, while 36 pts (36%) received a low dose irradiation-based RIC. All patients received a PBSC graft, with 55 (54%) receiving CSA alone for GVHD prophylaxis and 47 (46%) receiving CSA and MMF. Chimerism of immunomagnetically CD3+ T cells was assessed by VNTR at day 30, 60, 90 and >90 after allo-SCT. Full LC was defined as >95% of CD3+ sorted T cells of donor origin. At day 30, only 30% (95%CI, 21–39%) of patients achieved a full donor LC, and this increased to 50% (95%CI, 40–60%) by day 60. At day 90, a majority of 77% of the patients (95%CI, 69–85%) had a full donor LC. In this series, none of the patients’, graft, RIC regimen or disease characteristics could be predictive of establishment of a full LC at day 30 after allo-SCT. When looking for predictive factors for full donor LC at day 90, univariate analysis including patients and disease characteristics, RIC type and GVHD prophylaxis regimen, PBSC graft composition (CD34+, CD4+, CD8+, CD19+, NK cells), and early transplant-related events such as acute GVHD and time to engraftment, showed that a female donor, diagnosis (lymphoid malignancy or solid tumor vs. myeloid malignancy), CD34+ stem cell dose, and CD4+ T cell dose infused with the graft, were significantly associated with the establishment of full LC by day 90. In the multivariate analysis, a diagnosis other than a myeloid malignancy, was the strongest parameter significantly predictive of establishment of full LC at day 90 after RIC-allo-SCT (P=0.007; OR=3.82; 95%CI, 1.4–10.1). Overall, these results suggest that graft composition may represent an attractive tool towards harnessing chimerism of donor origin after RIC allo-SCT. Most importantly, disease-related features (type, previous courses of chemotherapy, previous autologous transplantation,≡) are the strongest predictors of the kinetic of donor LC that may impact transplant-related events after RIC allo-SCT.