All-trans retinoic acid for refractory cancer therapy-induced thrombocytopenia: A new option beyond TPO-ras?

Abstract Background: 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 investigates the potential of all-trans retinoic acid (ATRA) as a novel treatment option for CTIT. Methods: We aimed to assess the efficacy and safety of ATRA in refractory CTIT patients after solid tumor. We retrospectively analyzed refractory CTIT patients after solid tumor therapy using ATRA at Peking University People's Hospital between August 2023 and May 2025. Refractory CTIT was defined as grade ≥2 thrombocytopenia according to CTCAE v5.0 after TPO-RA therapy. Refractory CTIT patients received oral ATRA at 25 mg/m² daily for six weeks. Complete Response (CR) was defined as achievement of a platelet count ≥100×10⁹/L (or return to individual baseline level if pre-treatment values were <100×10⁹/L) sustained for ≥7 consecutive days in the absence of platelet transfusions. Concurrently, patients must have demonstrated no clinically significant bleeding events (WHO bleeding scale grade ≤1) throughout the response period. Partial Response (PR) was defined as a ≥2-grade improvement in platelet count severity (CTCAE v5.0) from nadir sustained for ≥7 days without transfusion support while not meeting CR criteria. Overall Response Rate (ORR) included both CR and PR. Results: A total of 28 refractory CTIT patients after solid tumor using ATRA were included. The baseline median platelet count at 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). CR was achieved in 12 patients (42.9%), with a median time to CR of 31 days (range: 12-40 days). The ORR among patients was 67.9% (19/28 patients). During the treatment, four patients (14.3%) developed elevated liver enzymes (three with grade 1 and one with grade 2 toxicity), while three patients (10.7%) experienced nausea (grade 1, manifested solely as decreased appetite). Conclusion: ATRA may serve as a potential therapeutic alternative for CTIT patients refractory to TPO-RAs.