Case Presentation: A 25-year-old female with no known significant medical conditions presented with two weeks of vaginal bleeding, generalized body aches, chills, and fever. Blood counts were significant for WBC count 74 K/uL with 9% blasts, platelet count 25 k/uL, and hemoglobin 5.4g/dL. Peripheral smear showed leukocytosis with numerous blasts and occasional Auer rods concerning for APL. Diagnosis of APL with PML-RARa fusion was confirmed by fluorescence in situ hybridization (FISH) with bone marrow biopsy. Fibrinogen was 127mg/dL and INR 1.6 which confirmed clinical DIC. Initial management involved cryoprecipitate and platelet transfusions with close monitoring for bleeding. Due to high presenting WBC and concern for DS, cytoreduction with hydroxyurea and IV cytarabine was initiated and immediately followed by Gemtuzumab-Ozagomycin with ATRA-ATO induction therapy in a sequential manner. Pre-emptive dexamethasone was given for additional prevention of DS. The patient experienced mild transient hypoxia that resolved with supportive care. Vaginal bleeding resolved and fatigue improved with treatment during hospitalization. The remaining course of induction was unremarkable for any complications related to bleeding or severe DS, and she was discharged for outpatient management.
Discussion: Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21) resulting in PML-RARa fusion genes. While APL is highly curable with a long-term overall survival rate over 90% with all-trans retinoic acid (ATRA)-arsenic trioxide (ATO), it must be considered a hematologic emergency due to potential peri-treatment mortality. While early mortality (EM), defined as death occurring within 30 days of diagnosis, reported in clinical trials is 5-10%, several population studies show EM approaching 30% (1,2). Dominant factors contributing to high observed mortality are disseminated intravascular coagulopathy (DIC) and differentiation syndrome (DS) during induction therapy. DS is a potentially fatal cytokine release syndrome that can occur with ATRA-ATO, and risk is determined by several factors including total leukocyte and blast count at presentation, age, and underlying organ dysfunction (3). Here we describe management of a patient with APL presenting with a very high leukocyte count and coagulopathy.
Conclusions: High-risk APL is a hematologic emergency. While leukocytosis > 10k/uL is considered high risk, it is uncommon to encounter an APL with a very high WBC count, as seen in our patient, and can be associated with a greater risk of relapse and treatment related morbidity. Though initiation of ATRA-ATO with any suspicion of APL and coagulopathy correction is strongly recommended as the first step, the importance of anticipating and recognizing impending DS is also paramount. Pre-emptive measures such as aggressive cytoreductive therapy, sequential addition of ATRA-ATO with necessary dose titrations, and steroids are essential to reduce EM. Our case highlights the nuances of risk stratification and need for vigilant monitoring upon diagnosis and initiating chemotherapy.