Therapy-related acute promyelocytic leukemia during lung cancer treatment

What happened, in summary

A 74-year-old man with lung squamous cell carcinoma was treated beginning in November 2022 with pembrolizumab, carboplatin, and paclitaxel. He then continued pembrolizumab monotherapy until April 2024. In May 2024, he developed progressive pancytopenia. Bone marrow examination showed 85% promyelocytic blasts. Flow cytometry supported acute promyelocytic leukemia, with CD33-positive blasts and negative CD34, CD117, HLA-DR, and CD2. Cytogenetics showed t(15;17)(q24;q21), and PCR confirmed a PML/RARA fusion transcript. He was classified as intermediate-risk therapy-related acute promyelocytic leukemia. Treatment started with all-trans retinoic acid and arsenic trioxide, with prophylactic methylprednisolone and furosemide to reduce differentiation-syndrome risk. On day 6 of induction therapy, he developed diffuse myalgia, aphasia, and loss of consciousness. CT imaging did not show ischemic or hemorrhagic lesions, but endocranial hypertension was indicated and transaminase levels were elevated. He died 6 hours after symptom onset. His lung cancer stage was not reported, and the fatal event was not described as lung cancer progression. The final course was driven by therapy-related acute promyelocytic leukemia after prior chemoimmunotherapy and pembrolizumab maintenance. The case series emphasized that therapy-related APL is uncommon and difficult to manage in patients previously exposed to potent anti-cancer therapy, especially when severe complications occur early during induction. The rapid decline also occurred despite prophylaxis for differentiation syndrome, making the induction course unusually severe. The exact APL biomarkers t(15;17) and PML/RARA defined the diagnosis and supported treatment with all-trans retinoic acid and arsenic trioxide. The final status is In Memory because death occurred during APL induction, not because a later lung cancer response assessment was reported.