Case Presentation: In 2000, a 32-year-old female without significant medical history was diagnosed with Acute promyelocytic leukemia (APL) after evaluation for fatigue, easy bruising, and menorrhagia. Labs revealed pancytopenia, bone marrow biopsy demonstrated extensive infiltration by promyelocytes with Auer rods, and Fluorescence in Situ Hybridization (FISH) confirmed t(15;17). She achieved hematologic remission after All-Trans Retinoic Acid (ATRA) and daunorubicin. Twenty-five years later, she presented with 1–2 weeks of vague memory issues and right-sided deficits. MRI showed multifocal acute infarcts in the left MCA territory. She was not eligible for tPA due to delayed presentation. Because the stroke occurred while on Eliquis, malignancy-associated hypercoagulability was suspected. A CT scan revealed a new lytic lesion at T8. Four days after admission, the patient developed acute right upper-extremity weakness and became obtunded. CT head revealed a left frontal intraparenchymal hemorrhage concerning for hemorrhagic conversion. Coagulation studies were notable for INR 1.66, aPTT 37.6 seconds, platelet count 80 K/µL, and fibrinogen 75 mg/dL. She received Kcentra and desmopressin, then underwent an urgent craniotomy for hemorrhage evacuation. Post-operatively, she continued to exhibit laboratory features of disseminated intravascular coagulation (DIC) including markedly elevated D-dimer (>35.20 mg/L FEU). A peripheral smear showed new promyelocytes concerning for relapsed APL so reinduction with ATRA was promptly initiated. Positive FISH-RARA and bone marrow biopsy confirmed relapsed APL, so arsenic trioxide (ATO) was added per the Lo-Coco trial. Repeat workup a month later showed no residual APL. The patient has remained in complete remission (CR) since and is expected to complete one year of ATRA maintenance therapy in eight months.
Discussion: APL is an aggressive subtype of Acute Myeloid Leukemia (AML) characterized by a block in differentiation at the promyelocyte stage. Historically, APL carried a high fatality rate due to its fulminant course and profound coagulopathy; however, the introduction of targeted differentiation therapies, particularly ATRA and ATO, dramatically improved outcomes. Both interventions have transformed APL into one of the most curable leukemias, with survival rates exceeding 90%. This case underscores the diagnostic challenges of extremely late relapse of APL due to its rarity and nonspecific presentation. Clinicians should maintain vigilance and notably, these findings must be recognized by hospital medicine physicians as DIC and other life-threatening complications can present while patients are being treated for other chief concerns. Early diagnosis and initiation of ATRA/ATO prevent the otherwise high morbidity and mortality of APL and complications such as DIC. While relapse occurs in approximately 10–15% of patients, the vast majority occur within the first three years after CR. Only six cases of relapse beyond ten years have been described. Our case presents one of the longest relapse intervals at 25 years.
Conclusions: Prompt workup should be pursued in patients with even a remote history of APL now found to have cytopenias or coagulopathy. Standard monitoring is for five years; however, some experts recommend continuing surveillance for longer. Future studies can further elucidate risk factors for extremely late APL relapse and evaluate whether longer surveillance would significantly benefit outcomes.