Roy Moulik Nirmalya, Keerthivasagam Swaminathan, Chatterjee Gaurav, Agiwale Jayesh, Rane Pallavi, Dhamne Chetan, Chichra Akanksha, Srinivasan Shyam, Mohanty Purvi, Jain Hemani, Shetty Dhanlaxmi, Rajpal Sweta, Tembhare Prashant, Patkar Nikhil, Narula Gaurav, Subramanian Papagudi G, Banavali Shripad
Tata Memorial Hospital, Pediatric Oncology, Mumbai, India.
Homi Bhabha National Institute, Mumbai, India.
Am J Hematol. 2025 Feb;100(2):210-217. doi: 10.1002/ajh.27528. Epub 2024 Nov 20.
Pediatric chronic myeloid leukemia (pCML) is a rare childhood malignancy, representing 2%-3% of all childhood leukemia. Tyrosine kinase inhibitors (TKIs) have greatly improved survival but pose challenges due to their long-term effects on growth and bone health in children. We prospectively studied treatment-free remission (TFR) in 45 children with pCML in chronic phase on imatinib. Eligibility criteria were as per current NCCN guidelines, with a less stringent qPCR monitoring scheduled every 3 months. TFR was successful in 71.1% (32 out of 45) of patients after a median follow-up of 25 (range: 6-42) months. The TFR rates at 12 and 24 months were 70% and 66%, respectively. Children under 5 years had a TFR rate of 88.9%, compared to 61.8% in those over 5 years (p = 0.18). Eleven of the 13 patients who lost MMR did so within 6 months of discontinuation. The cumulative incidence of loss in MMR at 6, 12, and 24 months was 26.4%, 27%, and 33%, respectively. Ten out of 13 (76.9%) patients with discontinuation failure (DF) regained MMR within 3 (2-20) months of restarting imatinib. A significant correlation was found between higher T-regulatory cell levels at baseline and DF (p = 0.005). More than half patients showed improved bone mineral density after 2 years of TFR. Our findings suggest that high TFR rates can be attained in pCML, with added benefits for bone health. Less frequent molecular monitoring was not associated with adverse outcomes and there seems to be a role of the immune system in sustaining TFR. The study is registered in the Clinical Trials Registry-India (CTRI/2020/11/029199).
小儿慢性髓性白血病(pCML)是一种罕见的儿童恶性肿瘤,占所有儿童白血病的2%-3%。酪氨酸激酶抑制剂(TKIs)显著提高了生存率,但因其对儿童生长和骨骼健康的长期影响而带来挑战。我们对45例处于慢性期且接受伊马替尼治疗的pCML患儿进行了无治疗缓解(TFR)的前瞻性研究。入选标准按照当前美国国立综合癌症网络(NCCN)指南执行,qPCR监测计划每3个月进行一次,要求相对宽松。中位随访25(范围:6-42)个月后,71.1%(45例中的32例)的患者实现了TFR。12个月和24个月时的TFR率分别为70%和66%。5岁以下儿童的TFR率为88.9%,而5岁以上儿童为61.8%(p = 0.18)。13例失去微小分子学缓解(MMR)的患者中有11例在停药后6个月内发生。6个月、12个月和24个月时MMR丧失的累积发生率分别为26.4%、27%和33%。13例停药失败(DF)的患者中有10例(76.9%)在重新开始使用伊马替尼后的3(2-20)个月内恢复了MMR。发现基线时较高的调节性T细胞水平与DF之间存在显著相关性(p = 0.005)。超过半数的患者在TFR 2年后骨矿物质密度有所改善。我们的研究结果表明,pCML可实现较高的TFR率,且对骨骼健康有益。分子监测频率降低与不良结局无关,免疫系统似乎在维持TFR中发挥作用。该研究已在印度临床试验注册中心(CTRI/2020/11/029199)注册。