domingo, 29 de mayo de 2016

Evaluation of Patients and Families With Concern for Predispositions to Hematologic Malignancies Within the Hereditary Hematologic Malignancy Clini... - PubMed - NCBI

2016 Apr 27. pii: S2152-2650(16)30044-1. doi: 10.1016/j.clml.2016.04.001. [Epub ahead of print]

Evaluation of Patients and Families With Concern for Predispositions to Hematologic Malignancies Within the Hereditary Hematologic Malignancy Clinic (HHMC).

DiNardo CD1, Bannon SA2, Routbort M3, Franklin A4, Mork M2, Armanios M5, Mace EM6, Orange JS6, Jeff-Eke M7, Churpek JE7, Takahashi K8, Jorgensen JL3, Garcia-Manero G8, Kornblau S8, Bertuch A9, Cheung H10, Bhalla K8, Futreal A10, Godley LA7, Patel KP3.

Author information

Abstract

INTRODUCTION:

Although multiple predispositions to hematologic malignancies exist, evaluations for hereditary cancer syndromes (HCS) are underperformed by most hematologist/oncologists. Criteria for initiating HCS evaluation are poorly defined, and results of genetic testing for hereditary hematologic malignancies have not been systematically reported.

PATIENTS AND METHODS:

From April 2014 to August 2015, 67 patients were referred to the Hereditary Hematologic Malignancy Clinic (HHMC). Referral reasons included (1) bone marrow failure or myelodysplastic syndrome in patients ≤ 50 years, (2) evaluation for germ-line inheritance of identified RUNX1, GATA2, or CEBPA mutations on targeted next-generation sequencing panels, and (3) strong personal and/or family history of malignancy. Cultured skin fibroblasts were utilized for germ-line DNA in all patients with hematologic malignancy.

RESULTS:

Eight patients (12%) were clinically diagnosed with a HCS: 4 patients with RUNX1-related familial platelet disorder (FPD)/acute myeloid leukemia (AML), and 1 patient each with dyskeratosis congenita, Fanconi anemia, germ-line DDX41, and Li-Fraumeni syndrome (LFS). Two patients with concern for FPD/AML and LFS, respectively, had RUNX1 and TP53 variants of unknown significance. Additionally, 4 patients with prior HCS diagnosis (1 LFS, 3 FPD/AML) were referred for further evaluation and surveillance.

CONCLUSION:

In this HHMC-referred hematologic malignancy cohort, HCS was confirmed in 12 patients (18%). HCS identification provides insight for improved and individualized treatment, as well as screening/surveillance opportunities for family members. The HHMC has facilitated HCS diagnosis; with increased clinical awareness of hematologic malignancy predisposition syndromes, more patients who may benefit from evaluation can be identified. Mutation panels intended for prognostication may provide increased clinical suspicion for germ-line testing.