关键词: TTMV::RARA融合基因, 急性早幼粒细胞白血病, 儿童

Abstract:

Objective To summarize the diagnosis and treatment process of a pediatric patient with rare TTMV::RARA fusion gene-positive acute promyelocytic leukemia (APL), and to explore the disease's clinical characteristics, treatment, and prognosis. Methods A retrospective analysis was conducted on the clinical data of a child with TTMV::RARA fusion gene-positive APL admitted in January 2024, and the relevant literature was reviewed. Results The patient, a 13-year-old girl, initially presented with abnormal hematopoiesis (white blood cell count 20.29×10⁹/L, hemoglobin 76 g/L, platelet count 76×10⁹/L) and bone pain. A diagnosis of APL with TTMV::RARA fusion positivity accompanied by an SF3B1 mutation was confirmed via MICM (Morphology, Immunology, Cytogenetics, Molecular biology) classification. The patient received personalized intensive therapy, which consisted of induction with all-trans retinoic acid (ATRA) combined with arsenic trioxide (ATO), along with intensified chemotherapy including cytarabine (Ara-C) and mitoxantrone (MTZ). Subsequently, autologous peripheral blood hematopoietic stem cell transplantation (APBSCT) was performed during consolidation chemotherapy, and multiple cycles of maintenance treatment were received after the transplantation. As of July 2025 (11 months post-transplant), the patient remains in sustained molecular remission (TTMV::RARA digital PCR-negative), with a disease-free survival (DFS) of 14 months. This article includes 9 cases from literature reports and 1 case from the current study, totaling 10 cases. There were 5 boys and 5 girls, with a median age of 7.5 (2 to 17) years. These children showed initial sensitivity to the treatment regimen of ATRA combined with ATO. The outcomes of the 10 pediatric patients were as follows: The patient did not undergo transplantation, remained in remission for 6 months after chemotherapy, but subsequently experienced two relapses and ultimately succumbed to disease progression; one patient underwent APBSCT during the first complete remission (CR1) and remained in continuous remission; four patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after achieving CR1, among whom two remained in continuous remission, one experienced relapse, and one died (due to non-relapse causes); four patients received allo-HSCT during the second complete remission (CR2) after relapse, among whom two remained in continuous remission, one experienced relapse, and one died. Conclusions For patients with morphologically consistent APL who test negative for both PML::RARA and its variant fusions, rare fusion genes such as TTMV should be screened as early as possible using techniques like transcriptome sequencing (RNA-seq). TTMV::RARA fusion gene positive APL usually indicates a poor prognosis. It is recommended to use ATRA+ATO combined intensive chemotherapy and perform allo-HSCT as soon as possible. For those who do not have the conditions, APBSCT can be considered to achieve deep and sustained remission.

Key words: TTMV::RARA, acute promyelocytic leukemia, child