Comparable outcome after haploidentical and HLA-matched allogeneic stem cell transplantation for high-risk acute myeloid leukemia following sequential conditioning-a matched pair analysis.

In acute myeloid leukemia (AML), primary refractory or relapsed disease, secondary AML, and leukemia with unfavorable genetics are considered high-risk AML (hrAML), with allogeneic stem cell transplantation (SCT) representing the standard treatment. Sequential conditioning has been successfully used for SCT in hrAML in HLA-matched transplants, and found its way into HLA-haploidentical SCT (haplo-SCT) later on. Hence, sequential conditioning had become standard for all patients with hrAML in our two centers, regardless of donor type. Thereby, HLA-matched family or unrelated transplants were first/second choice, post-transplant cyclophosphamide (PTCY)-based haplo-SCT was chosen in patients missing matched donors or requiring urgent transplantation. To compare the outcome after HLA-matched and haplo-SCT for hrAML following sequential conditioning, we performed a retrospective, matched-pair comparison, using disease stage, genetic subgroups and age as matching criteria. Thirty-four well-matched pairs were identified. At SCT, patients (median age 54 years) were untreated (9%), had remission (13%), or active disease (78%). Three-year overall and leukemia-free survival (OS/LFS) of the entire cohort was 56 ± 7%/49 ± 7%, without significant differences between donor types (OS after HLA-matched/haplo-SCT 62 ± 10%/52 ± 9% (p = 0.21), LFS 53 ± 10%/46 ± 9% (p = 0.26)). Similarly, the cumulative incidence of relapse, non-relapse-mortality and chronic GvHD, as well as GvHD-free, relapse-free survival (GRFS), and chronic GvHD-free, relapse-free survival (cGRFS), were comparable. However, a higher incidence of acute GvHD ≥ II° was observed after HLA-matched SCT (15 ± 1% versus 50 ± 2%, p = 0.001). In conclusion, sequential conditioning SCT achieved remarkable results in hrAML, independently from donor type. PTCY-based haplo-SCT produced results that were comparable to HLA-matched SCT and can be used as an alternative option.

Nurse-like cells show deregulated expression of genes involved in immunocompetence.

Chronic lymphocytic leukaemia (CLL) cells convert CD14(+) cells from patients into 'nurse-like' cells (NLCs). CLL cells can also convert CD14(+) peripheral blood mononuclear cells (PBMCs) from healthy donors into cells with morphological similarities to NLCs (CD14(CLL) -cells). However it is unclear whether only CLL cells induce this conversion process. This study showed that CD14(+) PBMCs from healthy donors could also be converted into differentiated cells (CD14(B) -cells) by non-malignant B-cells. In order to identify changes specifically induced by CLL cells, we compared gene expression profiles of NLCs, CD14(CLL) -cells and CD14(B) -cells. CD14(+) cells cultured with CLL cells were more similar to NLCs than those cultured with non-malignant B-cells. The most significant changes induced by CLL cells were deregulation of the antigen presentation pathway and of genes related to immunity. NLCs had reduced levels of lysozyme activity, CD74 and HLA-DR in-vitro while expression of inhibitory FCGR2B was increased. These findings suggest an impaired immunocompetence of NLCs which, if found in-vivo, could contribute to the immunodeficiency in CLL patients.