Research Article: Frequency of hematologic and solid malignancies in the family history of 50 patients with acute myeloid leukemia – a single center analysis

Date Published: April 18, 2019

Publisher: Public Library of Science

Author(s): Anne-Sophie Sandner, Ramona Weggel, Yasmin Mehraein, Stephanie Schneider, Wolfgang Hiddemann, Karsten Spiekermann, Amanda Ewart Toland.

http://doi.org/10.1371/journal.pone.0215453

Abstract

The revised World Health Organization classification of 2016 for myeloid neoplasms and acute leukemia added a section of myeloid neoplasms with germline predisposition. The main objective of our study was to evaluate the frequency of hematologic and solid malignancies in the family history of patients with acute myeloid leukemia (AML) by using a systemic pedigree interview. The family history was taken of 50 patients between 24 and 80 years.

8/50 (16%) patients with AML had family members with hematologic malignancies. 2/50 (4%) patients had family members of first degree with hematologic malignancies. Furthermore in 42/50 (84%) of AML patients solid malignancies were documented in family members of any degree and in 31/50 (62%) in family members of first degree. The most commonly occurring malignancies in our cohort were breast and colorectal cancer. We analyzed the pedigrees for cancer syndromes that can be associated with acute leukemia like Li-Fraumeni syndrome, Lynch syndrome and hereditary breast cancer. 2/50 (4%) patients fulfilled the criteria for familial breast and ovarian cancer from the German consortium and 1/50 (2%) patients fulfilled the Bethesda Guidelines criteria for hereditary nonpolyposis colorectal cancer. No pedigree met the criteria for Li-Fraumeni syndrome. In 29 cases we compared the patient history obtained in the routine work-up with our data. The accuracy of the obtained family history was 23%, outlining that in the clinical routine information about family histories often escapes notice.

Our study shows that though generally considered a sporadic disease, the presence of hematologic and solid malignancies in the family history of AML patients is relatively high. One should keep in mind that cancer syndromes like hereditary breast cancer are associated with a higher incidence of leukemia. These data are relevant in the context of family donor search for allogeneic stem cell transplantation, genetic counseling and testing as well as cancer prevention.

Partial Text

Myeloid neoplasms have long been considered to be sporadic diseases. In recent studies it could be demonstrated that there are several germline mutations that lead to a familial predisposition for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) [1–3]. Many germline mutations are already defined, for example germline mutations in the RUNX1, CEBPA and GATA2 gene. These findings have led to the implementation of a new category in the revised World Health Organization (WHO) classification of 2016 for myeloid neoplasms and acute leukemia namely myeloid neoplasms with germline predisposition as well as in the recent European Leukemia Network (ELN) classification named familial myeloid neoplasms. [4, 5]

From January 2016 until September 2017 we asked 50 unselected AML patients (de-novo-AML and secondary AML) older than 18 years to take approximately 30 minutes to obtain a detailed family cancer history. All patients were treated in our clinical center and signed informed consent. A comprehensive at least three-generation pedigree was obtained as broad as it was remembered by the patient. First-degree family relationships were parents, siblings and children. Second-degree relationships were uncles/aunts, nephews/nieces, grandparents/grandchildren and half-siblings and third-degree relationships were cousins. The definition of family relationship grades was applied according to the American Society of Oncology. [6] The pedigrees encompassed 3 to 5 generations and 6 to 47 family members per pedigree.

We analyzed the pedigrees of 50 AML patients from 24 to 80 years. Median age was 59.5 years, 32% of the patients were female. 72% of the patients were diagnosed with de-novo AML. Secondary AML arising from a myelodysplastic or myeloproliferative syndrome was diagnosed in 28% of the patients. [Table 1]

The aim of obtaining the family history of oncological patients is to identify patients with a genetic predisposition or patients at risk of second malignancies. The method of a pedigree interview is easy to apply, but typically taking 15–30 minutes it is not always feasible in the routine clinical practice. [19]

 

Source:

http://doi.org/10.1371/journal.pone.0215453

 

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