Acute Promyelocytic Leukemia Following Myelodysplastic Neoplasm in an Octogenarian Patient: a Case Report
Year: 2026
Type: article
Study design: Case Report
Abstract: Background The development of Acute Myeloid Leukemia (AML) from antecedent Myelodysplastic Neoplasm (MDS) is well recognized, arising from progressive acquisition and selection of genetic and epigenetic alterations. Progression to Acute Promyelocytic Leukemia (APL), however, is uncommon, as this entity is defined by the PML::RARA rearrangement — t(15;17). We report a case of low-risk MDS evolving to intermediate-risk APL in an octogenarian. Case report An 86-year-old woman with chronic neutropenia presented with progressive worsening of cytopenias. Bone marrow evaluation in March 2026 showed granulocytic maturation arrest and 1.07% anomalous myeloid precursor cells, leading to a diagnosis of low-risk MDS. During hospitalization for acute abdomen, she developed severe anemia and thrombocytopenia, progressive leukocytosis, and circulating blasts. Repeat immunophenotyping identified 86.81% immature myeloid cells, negative for HLA-DR, CD34, CD11b, and CD117, with aberrant CD2 and CD15 expression. FISH confirmed PML::RARA fusion in 158/200 nuclei, establishing intermediate-risk APL. Despite treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), she developed Differentiation Syndrome, dialysis-dependent Acute Kidney Injury, Acute Coronary Syndrome, and Subdural Hemorrhage, and died in June 2026. Discussion Secondary APL is a rare entity, most often reported after cytotoxic or radiation exposure, defining therapy-related APL. In these cases, leukemogenesis is thought to follow a topoisomerase II-mediated mechanism favoring recurrent breakpoints that generate the PML::RARA fusion, typically within one to three years of exposure. However, the patient had no prior cytotoxic exposure. Unlike most secondary AMLs arising from MDS, which typically evolve through stepwise accumulation of complex karyotypic and molecular abnormalities, APL is characteristically driven by a single reciprocal translocation. The immunophenotype CD34, HLA-DR, CD11b, and CD117 negativity with aberrant CD2 and CD15 expression matched the classic hypogranular APL pattern and prompted FISH confirmation, enabling timely ATRA-based therapy, critical given the risk of early hemorrhagic death in APL. The chemotherapy-free ATRA-ATO combination is now standard of care for low- and intermediate-risk, offering excellent outcomes with reduced hematologic toxicity compared with anthracycline-based regimens. Reports of secondary APL suggest response to ATRA-based induction is generally comparable to de novo disease, reinforcing that etiology alone should not preclude standard first-line therapy. Early mortality in APL, driven by coagulopathy, differentiation syndrome, and infectious or cardiovascular complications, remains disproportionately high in older patients. Despite prompt ATRA-ATO initiation, the patient developed differentiation syndrome and a cascade of severe complications, including dialysis-dependent renal failure, acute coronary syndrome, and fatal subdural hemorrhage. Early corticosteroid prophylaxis, close hemodynamic monitoring, and aggressive correction of coagulopathy are essential, yet may still be insufficient in the most vulnerable patients. Conclusion Post-MDS APL is uncommon in hematologic practice. Although it generally remains responsive to standard APL therapy. Frail elderly patients require rapid diagnosis, early treatment, and intensive monitoring to mitigate disease- and treatment-related complications.
Institution: Hospital Santa Izabel
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7223152396