Background/Objectives: Light-chain amyloidosis (AL Amyloidosis) is a rare systemic plasma cell disorder in which misfolded light chains form amyloid fibrils that damage vital organs. Diagnosis is often delayed because of variable presentation and overlap with other plasma cell diseases. Methods: We retrospectively analyzed 23 patients diagnosed between 2022 and 2025 at the Fundeni Clinical Institute. All cases underwent free light-chain testing, serum immunofixation, immunohistochemistry, and bone marrow analysis. Since 2022, next-generation flow cytometry (NGF) has been applied to detect clonal plasma cells and characterize their immunophenotype. Results: NGF confirmed clonality in 21 of 23 patients (91.3%), including two cases undetected by conventional assays. Serum immunofixation was positive in 69.6% and immunohistochemistry in 78.3%. Among clonal cases, λ restriction predominated (71.4%). Detection was highest when NGF was combined with standard methods, especially in patients with dFLC < 100, where negative immunofixation was more frequent (p = 0.027). Conclusions: Multiparameter flow cytometry (MFC) provides highly sensitive detection of small clonal plasma cell populations often missed by standard assays, offering a valuable tool for early and accurate diagnosis of low-burden plasma cells in AL amyloidosis. Integrating MFC into routine evaluation improves diagnostic accuracy, identifies overlooked clonal populations, and supports earlier, more informed clinical decisions.

Bone marrow hemodilution could compromise next generation flow cytometry based measurable residual disease evaluation in multiple myeloma and may cause false negative results. This review summarizes definitions, markers, indices, mitigation strategies, and current challenges in standardization.

Introduction: Chronic lymphocytic leukemia (CLL) is a common adult leukemia often treated with fludarabine, cyclophosphamide, and rituximab (FCR). While effective, FCR can lead to therapy-related myeloid neoplasms (t-MN), including aggressive therapy-related acute myeloid leukemia (t-AML). Stem cell transplantation offers the best chance for long-term remission in these cases. Here, we report a rare case of t-AML with plasmacytoid dendritic cells (pDC-AML) developing after FCR treatment for CLL that was successfully treated with haplotransplantation. Case Presentation: A 57-year-old woman with CLL-B was treated with six cycles of FCR, achieving a complete response. Six years later, at age 63, she developed t-AML with a rare morphophenotypic subtype: acute myelomonocytic leukemia with plasmacytoid dendritic cells (pDC-AML) and monosomy 8. Diagnostic challenges included distinguishing this subtype from blastic plasmacytoid dendritic cell neoplasm (BPDCN). She was treated with high-dose cytarabine followed by haploidentical stem cell transplantation from her son. Haploidentical transplantation was prioritized due to the urgent clinical need in a patient with high-risk acute leukemia (therapy-related leukemia secondary to prior chemoimmunotherapy and failure to achieve complete remission following the standard 3 + 7 induction protocol). In this critical setting, the patient’s son was immediately available as an HLA-haploidentical donor. Prior to the performance of the haploidentical stem cell transplant from her son, no HLA-matched unrelated donor (MUD) could be identified. Another viable alternative would have been the utilization of umbilical cord blood-derived stem cells harvested from the patient’s twin granddaughters. She was closely monitored post-transplant for potential complications, including graft-versus-host disease (GVHD), post-transplant lymphoproliferative disorder, and thyroid dysfunction, all of which were ruled out during follow-up. The patient remains in complete remission 15 years after her initial CLL diagnosis and 8 years after the t-AML diagnosis and haplotransplantation. Notably, no residual CLL clone was detected at the time of t-AML development, and a benign polyclonal lymphocytosis observed between 2018 and 2020 spontaneously resolved without intervention. Conclusions: This case illustrates the potential for long-term survival in high-risk patients with therapy-related AML developed after cytotoxic treatment for lymphoid malignancies. Haplotransplantation from a semi-identical Human Leukocyte Antigen (HLA) donor proved to be a viable and effective treatment option despite the patient’s age and dual hematologic malignancies.