Efficacy and Long-Term Remission Following Haploidentical HSCT for Therapy-Related Acute Myelomonocytic Leukemia with Plasmacytoid Dendritic Cells Post-FCR Therapy for CLL: A Case Report

<b>Introduction:</b> 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. <b>Case Presentation:</b> 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. <b>Conclusions:</b> 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.