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Life sciences · Journal article
Annals of Hematology · September 25, 2026
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Cancer therapy-induced thrombocytopenia (CTIT) is a common hematologic toxicity in patients with solid tumors. It often results in bleeding, delays or reductions in cancer treatment, and worsening prognosis. This study evaluated the efficacy and safety of all-trans retinoic acid (ATRA) administered in combination with thrombopoietin receptor agonists (TPO-RAs) for refractory CTIT in patients with solid tumors. We retrospectively analyzed patients with refractory CTIT (grade ≥ 2 thrombocytopenia per CTCAE v5.0 after TPO-RA therapy) who received oral ATRA at 25 mg/m² daily for six weeks in combination with continued TPO-RA therapy at Peking University People’s Hospital between August 2023 and May 2025. A total of 28 refractory CTIT patients were included. The baseline median platelet count was 13 × 10⁹/L (range: 2–69). Platelet counts increased progressively from baseline after treatment initiation, the median platelet elevations were + 17 × 10⁹/L (Day 14 vs. baseline, P = 3.05 × 10⁻⁵), + 36 × 10⁹/L (Day 28 vs. baseline, P = 9.54 × 10⁻⁷), and + 59 × 10⁹/L (Day 42 vs. baseline, P = 7.45 × 10⁻⁹). Complete response (CR) was achieved in 12 patients (42.9%), and partial response (PR) was achieved in 7 patients (25.0%). The median time to CR was 31 days (range: 12–40 days). Overall response rate (ORR) was 67.9% (19/28 patients). Within the female cohort, patients with female reproductive system (FRS) tumors had a significantly poorer response compared to those with non-FRS tumors (ORR: 57.1% vs. 100.0%, P = 0.038; CR: 0% vs. 70.0%, P = 0.008). History of radiotherapy and paclitaxel treatment showed trends toward inferior CR rates ( P = 0.057 and P = 0.054, respectively). Patients with higher baseline megakaryocyte counts (≥ 5 per high-powered field) exhibited a higher ORR trend compared to those with lower counts (76.5%vs. 54.5%, P = 0.41). This combination therapy was well tolerated: four patients (14.3%) developed elevated liver enzymes (three with grade 1 and one with grade 2), while three patients (10.7%) experienced nausea (grade 1); no grade ≥ 3 events, thrombotic events, or differentiation syndrome were observed. ATRA combined with TPO-RAs was associated with encouraging platelet recovery and a favorable safety profile in refractory CTIT patients.