Sri Ram Cancer Center, Mahatma Gandhi Medical College Hospital, Jaipur, Rajasthan, India.
Fred Hutch, Seattle, WA; and.
Hematology Am Soc Hematol Educ Program. 2019 Dec 6;2019(1):433-442. doi: 10.1182/hematology.2019000050.
Subsequent to the development and global availability of BCR/ABL-targeted tyrosine kinase inhibitors (TKIs), the prognosis of patients with chronic myeloid leukemia (CML), at least those in the chronic phase, has markedly improved, and in the developed world, the average lifespan of these patients is now close to that of age- and sex-matched subjects without the disease. However, the situation in low- and middle-income countries (LMICs) may not be so rosy. Many important differences in hematological cancers, including CML, have been highlighted in various publications in LMICs vs developed countries. These include differences in incidence and prevalence rates, age and stage of disease at diagnosis, response rates, and survival. Some of the possible reasons proposed for these are varying socioeconomic milieu (impacting availability of effective drugs and essential monitoring), environmental factors (mainly exposure to viral infections and pesticides), nutritional factors with interplay of malnutrition and diet on drug absorption and blood levels, and possible unknown genetic factors. Although generic first-generation TKIs (imatinib) are available in many parts of the world, several challenges remain in providing optimal treatment to patients with CML in resource-poor countries. Some of these include availability of optimal and high-quality BCR/ABL testing, availability and expense related to use of second- and third-generation TKIs (nilotinib, dasatinib, bosutinib, and ponatinib) and hematopoietic stem cell transplantation, issues with compliance and toxicities of drugs, and ensuring a minimal standard-of-care treatment and monitoring for every patient diagnosed with CML. For the purpose of this article, the more objective country label-LMIC-coined by the World Bank will be used (gross national income per capita between $1026 and $3995; World Bank, June 2019). Some of these issues will be discussed in this article in greater detail by experts in the field in 3 different but interconnected sections.
在 BCR/ABL 靶向酪氨酸激酶抑制剂 (TKI) 开发和全球应用之后,慢性髓性白血病 (CML) 患者的预后明显改善,至少在慢性期患者中是这样,在发达国家,这些患者的平均寿命现在已接近无该病的年龄和性别匹配人群。然而,在中低收入国家 (LMIC) 的情况可能并非如此乐观。在 LMIC 与发达国家的各种出版物中,已经强调了包括 CML 在内的血液系统癌症的许多重要差异。这些差异包括发病率和患病率、诊断时的年龄和疾病分期、反应率和生存率。对于这些差异,有人提出了一些可能的原因,包括不同的社会经济环境(影响有效药物的供应和必要的监测)、环境因素(主要是病毒感染和农药暴露)、营养因素(营养不良和饮食对药物吸收和血药浓度的相互作用)以及可能未知的遗传因素。尽管在世界许多地方都可以获得第一代通用 TKI(伊马替尼),但在资源匮乏的国家为 CML 患者提供最佳治疗仍存在一些挑战。其中一些包括提供最佳和高质量的 BCR/ABL 检测、与使用第二代和第三代 TKI(尼洛替尼、达沙替尼、博舒替尼和帕纳替尼)以及造血干细胞移植相关的可用性和费用、药物的依从性和毒性问题,以及确保每个被诊断为 CML 的患者都能接受最低标准的治疗和监测。出于本文的目的,将使用世界银行提出的更客观的国家标签-LMIC(人均国民总收入在 1026 美元至 3995 美元之间;世界银行,2019 年 6 月)。本文将由该领域的专家在三个不同但相互关联的部分中更详细地讨论其中的一些问题。