Pediatric Oncology Research Laboratory, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Eur J Haematol. 2022 Feb;108(2):109-117. doi: 10.1111/ejh.13711. Epub 2021 Sep 30.
Explore patient adherence and physician compliance to protocol guidelines during maintenance therapy, including the association with survival in adults with acute lymphoblastic leukemia (ALL).
Blood counts, aminotransferase levels and prescribed 6-mercaptopurine (6MP)/methotrexate (MTX) doses were compared with the protocol guidelines to assess compliance. Non-adherence to the prescribed medication was confirmed in patients with unmeasurable 6MP metabolite levels and suspected in patients with low 6MP metabolites concurrent with aminotransferase and white blood cell count within normal ranges, while potential intermittent non-adherence was defined by >1.9 fold fluctuating 6MP metabolites.
Physicians' non-compliance with insufficient dose increments of 6MP/MTX despite white blood cell counts above the target level comprised a median of 20.1% (interquartile range 9.7-39.3%) of the observed time in maintenance therapy, yet no association to relapse was found (P = .17). Non-adherence to 6MP was confirmed in 9.8% (5 of 51 patients), suspected in an additional 9.8% (5 of 51 patients), and intermittent non-adherence was suspected in 52.6% (20 of 38 patients).
Although no association between non-compliance and leukemic relapse was found, likely due to lack of power, increased attention to this phase of ALL therapy is indicated.
探讨急性淋巴细胞白血病（ALL）成人患者在维持治疗期间对方案指南的患者依从性和医生依从性，包括与生存的相关性。
将血细胞计数、氨基转移酶水平和规定的 6-巯基嘌呤（6MP）/甲氨蝶呤（MTX）剂量与方案指南进行比较，以评估依从性。在无法测量 6MP 代谢物水平的患者中确认未按规定服药，在氨基转移酶和白细胞计数均在正常范围内但 6MP 代谢物水平较低的患者中怀疑未按规定服药，而潜在的间歇性不依从则定义为 6MP 代谢物波动超过 1.9 倍。
尽管白细胞计数高于目标水平，但医生仍未遵守 6MP/MTX 剂量不足的增加规定，这在维持治疗期间占观察时间的中位数为 20.1%（四分位距 9.7-39.3%），但与复发无关（P=.17）。9.8%（51 例中的 5 例）的患者确认存在 6MP 不依从，另有 9.8%（51 例中的 5 例）的患者疑似存在不依从，52.6%（38 例中的 20 例）的患者疑似存在间歇性不依从。
尽管未发现不依从与白血病复发之间存在关联，可能是由于缺乏效力，但需要对 ALL 治疗的这一阶段给予更多关注。
