Allogeneic stem cell transplantation (ASCT) has improved leukemia-free survival (LFS) in many but not all patients with acute leukemia. This is an eight-year followup to our previous study showing a survival advantage to patients with an increased cd T cells following ASCT. cd T cell levels were collected prospectively in 153 patients (acute lymphoblastic leukemia (ALL) n ¼ 77; acute myelogenous leukemia (AML) n ¼ 76) undergoing partially mismatched related donor ASCT. Median age was 22 years (1-59), and 62% of the patients were in relapse at transplant. Patient-donor human leukocyte antigen (HLA) disparity of three antigens was 37% in the graft-versushost disease (GvHD) and 29% in the rejection directions. All patients received a partially T cell-depleted graft using T10B9 (n ¼ 46) or OKT3 (n ¼ 107). Five years LFS and overall survival (OS) of patients with increased cd compared to those with normal/decreased numbers were 54.4 vs 19.1%; Po0.0003, and 70.8 vs 19.6% Po0.0001, respectively, with no difference in GvHD (P ¼ 0.96). In a Cox multivariate analysis, normal/decreased cd (hazard ratio (HR) 4.26, P ¼ 0.0002) and sex mismatch (HR 1.45 P ¼ 0.049) were associated with inferior LFS. In conclusion, cd T cells may facilitate a graft-versus-leukemia (GvL) effect, without causing GvHD. Further evaluations of this effect may lead to specific immunotherapy for patients with refractory leukemia.

Human antibody-secreting cells (ASC) in peripheral blood are found after vaccination or infection but rapidly apoptose unless they migrate to the bone marrow (BM). Yet, elements of the BM microenvironment required to sustain long-lived plasma cells (LLPC) remain elusive. Here, we identify BM factors that maintain human ASC > 50 days in vitro. The critical components of the cell-free in vitro BM mimic consist of products from primary BM mesenchymal stromal cells (MSC), a proliferation-inducing ligand (APRIL), and hypoxic conditions. Comparative analysis of protein–protein interactions between BM-MSC proteomics with differential RNA transcriptomics of blood ASC and BM LLPC identify two major survival factors, fibronectin and YWHAZ. The MSC secretome proteins and hypoxic conditions play a role in LLPC survival utilizing mechanisms that downregulate mTORC1 signaling and upregulate hypoxia signatures. In summary, we identify elements of the BM survival niche critical for maturation of blood ASC to BM LLPC.