Successful Haplo-Hematopoietic Stem Cell Transplantation for Juvenile Myelomonocytic Leukemia in a Child With Underlying Thrombocytopenia-Absent Radius Syndrome: A Unique Case.

[BACKGROUND] Thrombocytopenia-absent radius (TAR) syndrome is a rare congenital disorder characterized by bilateral radial aplasia with preserved thumbs and early-onset thrombocytopenia. While hematologic and skeletal abnormalities define the condition, its association with hematologic malignancies is extremely rare, with only a few reported cases of leukemia. Juvenile myelomonocytic leukemia (JMML) is an uncommon pediatric myelodysplastic/myeloproliferative neoplasm frequently linked to RAS pathway mutations. To our knowledge, JMML has not previously been reported in association with TAR syndrome.

[CASE PRESENTATION] We report the case of a male infant diagnosed with TAR syndrome based on clinical features and molecular confirmation of a homozygous RBM8A c.-21G>A variant. The patient presented initially with persistent thrombocytopenia, skeletal deformities, and neonatal sepsis-like manifestations. At 2 years of age, he developed pancytopenia and progressive splenomegaly. Bone marrow evaluation and molecular testing confirmed JMML harboring a pathogenic NF1 mutation. He underwent successful haploidentical hematopoietic stem cell transplantation (HSCT) from a sibling donor, following a conditioning regimen of melphalan, treosulfan, cyclophosphamide, and anti-thymocyte globulin. The patient achieved full donor chimerism and hematologic remission with stable engraftment.

[CONCLUSION] This case represents, to our knowledge, one of the very few-if not the first-reported instances of successful HSCT for JMML in a patient with TAR syndrome. It underscores the importance of vigilant surveillance in TAR patients for potential malignant transformation and demonstrates the curative potential of HSCT in rare congenital-hematologic overlap syndromes.