Department of Medicine, University of Wisconsin-Madison, Madison, WI.
Oncology Genetics, University of Wisconsin Carbone Cancer Center, UWHealth, Madison, WI.
JCO Precis Oncol. 2024 Jun;8:e2300518. doi: 10.1200/PO.23.00518.
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.
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.
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% 14%, = .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.
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.
了解骨髓增生异常综合征（MDS）和急性髓系白血病（AML）的遗传易感性对治疗决策、监测和高危亲属的护理具有重要的临床意义。国家综合癌症网络（NCCN）指南最近根据个人和家族史特征纳入了对 MDS/AML 患者进行种系遗传评估的建议，但这些建议的实施实用性尚未得到研究。
成立了遗传性血液学质量改进（QI）委员会，以在 MDS/AML 患者的前瞻性队列中实施这些指南。建议符合 NCCN 指南标准的患者进行种系基因检测。比较了符合 NCCN 指南标准的患者与 MDS/AML 历史队列的转诊模式和基因评估结果。确定了评估的障碍。
在由 QI 委员会评估的 90 例 MDS/AML 患者中，59 例（66%）符合种系评估标准。QI 委员会的实施导致按照 NCCN 指南更频繁地转诊进行种系评估（31% 比 14%， =.03）。然而，由于医疗急症或在 QI 委员会建议时死亡或在临终关怀中，大多数符合标准的患者从未被转诊。尽管如此，在接受基因检测的 12 名患者中，有 2 名（17%）被诊断为遗传性髓系恶性肿瘤综合征。
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 委员会有助于最初的实施，并适度提高了 NCCN 指南的依从性。然而，MDS/AML 患者的高发病率和死亡率以及住院时间延长挑战了传统的门诊遗传咨询模式。要进一步提高指南的依从性，需要为这一患者群体创新新的遗传咨询和检测模式。
