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BACKGROUND Maintenance therapy with proteasome inhibitors (PIs) can improve outcomes of multiple myeloma (MM) patients, however, the neurotoxicity and parenteral route of bortezomib limit its long-term use. An efficacious, tolerable, and convenient PI option is needed. METHODS In this single-center, real-world study, we retrospectively analyzed the outcome and safety profile of ixazomib-based maintenance therapy in patients who plateaued with the responses of steady disease or better after bortezomib-based induction therapy in MM patients not undergoing transplantation. RESULTS Of all the 71 patients, 37 cases (52.1%) were newly diagnosed MM (NDMM) and 34 cases (47.9%) were relapsed and/or refractory MM (RRMM). The overall response rate (ORR) was 81.7%, including 34 patients (47.9%) with a very good response rate or better (≥VGPR) after a median of nine cycles (6-14) of bortezomib-based induction therapy. Then the ORR was transformed to 74.6% including 39 patients of ≥VGPR (54.9%) after a median of six courses (2-25) of ixazomib-based maintenance therapy. Of these, 18 patients (25.4%) exhibited responses deepened. With 26.5 months median follow-up, median progression-free survival (PFS) was 28.4 and 16.5 months from the start of bortezomib and 16.2 and 10.0 months from the initiation of ixazomib in NDMM and RRMM group, respectively. Moreover, responses deepened during the maintenance phase (hazard ratio: 0.270, p = 0.007), and responses of ≥VGPR during the induction phase (hazard ratio: 0.218, p

Aplastic anemia (AA) is a T cell–mediated autoimmune disorder of the hematopoietic system manifested by severe depletion of the hematopoietic stem and progenitor cells (HSPCs). Nonetheless, our understanding of the complex relationship between HSPCs and T cells is still obscure, mainly limited by techniques and the sparsity of HSPCs in the context of bone marrow failure. Here we performed single-cell transcriptome analysis of residual HSPCs and T cells to identify the molecular players from patients with AA. We observed that residual HSPCs in AA exhibited lineage-specific alterations in gene expression and transcriptional regulatory networks, indicating a selective disruption of distinct lineage-committed progenitor pools. In particular, HSPCs displayed frequently altered alternative splicing events and skewed patterns of polyadenylation in transcripts related to DNA damage and repair, suggesting a likely role in AA progression to myelodysplastic syndromes. We further identified cell type–specific ligand-receptor interactions as potential mediators for ongoing HSPCs destruction by T cells. By tracking patients after immunosuppressive therapy (IST), we showed that hematopoiesis remission was incomplete accompanied by IST insensitive interactions between HSPCs and T cells as well as sustained abnormal transcription state. These data collectively constitute the transcriptomic landscape of disrupted hematopoiesis in AA at single-cell resolution, providing new insights into the molecular interactions of engaged T cells with residual HSPCs and render novel therapeutic opportunities for AA.