Case Report: Persistent severe thrombocytopenia after adjuvant ado-trastuzumab emtansine with sequential bone marrow...

Ado-trastuzumab emtansine (T-DM1) remains an established adjuvant option for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer and residual invasive disease after neoadjuvant treatment. Severe, persistent thrombocytopenia deviating from the usual cyclic pattern is uncommon and clinically challenging. We report a 50-year-old woman who developed sustained grade 4 thrombocytopenia after three cycles of adjuvant T-DM1, following prior platinum-based chemotherapy and during adjuvant radiotherapy. The thrombocytopenia was refractory to recombinant human thrombopoietin and hetrombopag. Additional evaluations found no evidence of splenomegaly, peripheral platelet destruction, clonal hematologic disease, or a localized radiation effect on the sampled marrow. Sequential marrow evaluations supported megakaryocytic maturation impairment, with initial depletion followed by quantitative recovery but persistently few platelet-producing forms, without dysplasia or fibrosis. Platelet counts repeatedly declined after romiplostim interruption and recovered after reintroduction, allowing long-term stabilization with a threshold-based intermittent regimen. Following multidisciplinary discussion, further anti-HER2 therapy was withheld because of the severely compromised thrombopoietic reserve. As adjuvant antibody-drug conjugate (ADC) strategies continue to evolve, this case suggests that severe non-cyclic thrombocytopenia may occur early during HER2-directed ADC therapy. It supports the value of sequential marrow assessment in selected refractory cases and provides clinical context for individualized romiplostim support in prolonged thrombocytopenia.