Prevalence of Multiple Primary Hematologic Malignancies Seen at a Tertiary Care Center
Authors: Cooper Kathrine A , Lattell Jonathan , Gonzalez Beverly , Kliethermes Stephanie , Nand Sucha 
Published: October 2019

Abstract
Background: There is a paucity of data regarding patients who develop multiple unrelated hematologic malignancies. This study aims to determine the prevalence of two or more hematologic malignancies in the same patient at Loyola University Medical Center (LUMC) over a period of 7 years and to explore associations with certain clinical risk factors.
Methods: After obtaining IRB approval, the electronic medical record was queried for various hematologic malignancies according to ICD-9 codes from 2007-2014. Chemotherapy-associated and transformed malignancies were excluded. In addition, the following data were collected: age at first and second diagnoses, gender, ethnicity, HIV, EBV, CMV, hepatitis B or C, JAK2 mutation, or autoimmune disorders. Survival outcomes and presence of coexisting solid tumors were assessed.
Results: Of 5902 patients diagnosed with any hematologic malignancy, 27 were found to have more than one. Two patients had three hematologic malignancies (Hodgkin lymphoma, cutaneous t-cell lymphoma, diffuse large B-cell lymphoma; chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), MALT lymphoma, diffuse large B-cell lymphoma). The most common first hematologic malignancy was CLL/SLL (10) followed by chronic myeloid leukemia (CML) (5) and Hodgkin lymphoma (4). The most common second primary hematologic malignancy was Hodgkin lymphoma (5), followed by multiple myeloma or plasmacytoma (4), acute myeloid leukemia (3) and CLL or monoclonal B-cell lymphocytosis (3). Thirty-seven of all malignancies were lymphoid, 16 myeloid and one Kaposi's sarcoma. Fifteen had both a myeloid and lymphoid malignancy; the remaining 12 patients had either two myeloid or two lymphoid malignancies. Seven cases were diagnosed synchronously and 20 metachronously. The median interval between the first and second diagnosis was 3 years (range: 0.19 - 6.26). The average age at diagnosis of the first and second disease was 62.4 and 67.2 years. Although not tested for statistical differences, the median survival after first and second diagnosis was 4.9 and 0.8 years, respectively. Seven patients also had at least one solid tumor malignancy; three had two different solid tumors. One patient had rheumatoid arthritis and hypothyroidism (SLL followed by Hodgkin lymphoma). Two patients had hypothyroidism, and four had type two diabetes. One patient had hepatitis B, and another had hepatitis B and C. Males were five times more likely to die after the first malignancy diagnosis compared to females, irrespective of the type of malignancy (p=0.04). No association was seen between survival and type of first malignancy or whether the second diagnosis was of lymphoid or myeloid lineage.
Conclusion: These data show that in patients presenting with a hematologic malignancy, the risk of developing a second hematologic malignancy over a 7 year period was low at 0.005% (27 out of 5902). In about half (15 out of 27) the second hematologic malignancy belonged to a separate lineage and about a quarter (7/27) developed solid tumors. About one fourth of the patients (7/27) had an autoimmune disorder. Males in this cohort had a five-fold increased risk of death compared to females. The second hematologic malignancy was an ominous development and was associated with a median survival of 0.8 years. These observations should be confirmed in a prospective study.

Disclosures
No relevant conflicts of interest to declare.