Case report and review of TTMV::RARA-positive APL with spinal cord compression in a child

This case report describes a 9-year-old boy with TTMV::RARA-positive acute promyelocytic leukemia (APL) presenting with spinal cord compression due to vertebral destruction, a manifestation not previously documented in the literature. Through a systematic review of 11 published cases (2020–2024), we identified both shared and distinctive features of this ultra-rare entity. The patient presented with a 2-year history of progressive hip pain, culminating in neurogenic claudication and urinary retention. Diagnostic evaluation revealed APL-like morphology and immunophenotype (CD33+, MPO+, CD34−, HLA-DR−), negative PML::RARA fluorescence in situ hybridization (FISH), and a high burden of TTMV::RARA fusion detected by RNA sequencing (81,142 copies). Treatment with all-trans retinoic acid (ATRA) plus an oral arsenic compound showed an insufficient response; however, the addition of venetoclax achieved molecular remission, which was maintained through 10 months of follow-up. Magnetic resonance imaging (MRI) documented resolution of spinal compression with fatty marrow replacement post-treatment. The literature review reveals recurring patterns: frequent extramedullary involvement (7/12 cases) and diagnostic challenges with conventional testing (6/10 cases FISH/reverse transcription-polymerase chain reaction (RT-PCR) negative). While limited by a single-case observation and heterogeneous reported data that preclude statistical analysis, this report expands the recognized clinical spectrum of TTMV::RARA APL and documents three previously unreported observations: spinal cord compression as the initial presentation, venetoclax-induced remission, and oral arsenic compound utilization. These findings suggest RNA-based fusion testing may be informative for PML::RARA-negative suspected APL with atypical presentations, although optimal diagnostic and therapeutic approaches await validation through collaborative studies.