目的:了解骨髓增生异常综合征(MDS)和AML的遗传易感性对治疗决策具有重要的临床意义,监视,和照顾有风险的亲戚。国家综合癌症网络(NCCN)指南最近纳入了根据个人和家族史特征对MDS/AML患者进行种系遗传评估的建议。但是尚未研究实施这些建议的实用性。
方法:成立了遗传性血液学质量改善(QI)委员会,以在诊断为MDS/AML的患者的前瞻性队列中实施这些指南。对于符合NCCN指南标准的患者,建议转诊进行种系基因检测。将转诊模式和遗传评估结果与MDS/AML患者的历史队列进行比较。确定了评估的障碍。
结果:在QI委员会评估的90例MDS/AML患者中,59(66%)符合种系评估标准。QI委员会的实施导致根据NCCN指南(31%v14%,P=.03)。然而,在QI委员会提出建议时,大多数符合标准的患者从未因医学敏锐度高或死亡或临终关怀而被转诊.尽管如此,接受基因检测的12例患者中有2例(17%)被诊断为遗传性髓系恶性肿瘤综合征.
结论:目前的NCCN指南导致三分之二的MDS/AML患者符合种系评估标准。以遗传性血液学为重点的QI委员会为初步实施提供了帮助,并适度改善了NCCN指南的依从性。然而,与MDS/AML相关的高发病率和高死亡率以及住院时间延长对传统的门诊遗传咨询模式提出了挑战.指南依从性的进一步改善需要为该患者群体创新遗传咨询和测试的新模式。
OBJECTIVE: Knowledge of an inherited predisposition to myelodysplastic syndrome (MDS) and AML has important clinical implications for treatment decisions, surveillance, and care of at-risk relatives. National Comprehensive Cancer Network (NCCN)
guidelines recently incorporated recommendations for germline genetic evaluation of patients with MDS/AML on the basis of personal and family history features, but the practicality of implementing these recommendations has not been studied.
METHODS: A hereditary hematology quality improvement (QI) committee was formed to implement these guidelines in a prospective cohort of patients diagnosed with MDS/AML. Referral for germline genetic testing was recommended for patients meeting NCCN
guideline criteria. Referral patterns and genetic evaluation outcomes were compared with a historical cohort of patients with MDS/AML. Barriers to evaluation were identified.
RESULTS: Of the 90 patients with MDS/AML evaluated by the QI committee, 59 (66%) met criteria for germline evaluation. Implementation of the QI committee led to more referrals for germline evaluation in accordance with NCCN guidelines (31% v 14%, P = .03). However, the majority of those meeting criteria were never referred due to high medical acuity or being deceased or in hospice at the time of QI committee recommendations. Despite this, two (17%) of the 12 patients undergoing genetic testing were diagnosed with a hereditary myeloid malignancy syndrome.
CONCLUSIONS: Current NCCN
guidelines resulted in two thirds of patients with MDS/AML meeting criteria for germline evaluation. A hereditary hematology-focused QI committee aided initial implementation and modestly improved NCCN
guideline adherence. However, the high morbidity and mortality and prolonged inpatient stays associated with MDS/AML challenged traditional outpatient genetic counseling models. Further improvements in
guideline adherence require innovating new models of genetic counseling and testing for this patient population.