Multiple Myeloma and Its Precursor Disease Among Firefighters Exposed to the World Trade Center Disaster

Ola Landgren,Lakshmi Ramanathan,Malin Hultcrantz,Hillel W Cohen,George Nwankwo,Rachel Zeig‐Owens ,Theresa Schwartz,Ulrich Steidl,Katie L Thoren ,Laura Crowley,Amit Verma,Ahmet Doğan ,Mayris P Webber,Charles B Hall,Nadia Jaber,Kith Pradhan,Michael Crane,Kaznouri Murata,Shani Irby,Orsi Giricz ,David J Prezant

doi:10.1001/jamaoncol.2018.0509

Abstract

The World Trade Center (WTC) attacks on September 11, 2001, created an unprecedented environmental exposure to known and suspected carcinogens suggested to increase the risk of multiple myeloma. Multiple myeloma is consistently preceded by the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS, detectable in peripheral blood. To characterize WTC-exposed firefighters with a diagnosis of multiple myeloma and to conduct a screening study for MGUS and light-chain MGUS. Case series of multiple myeloma in firefighters diagnosed between September 11, 2001, and July 1, 2017, together with a seroprevalence study of MGUS in serum samples collected from Fire Department of the City of New York (FDNY) firefighters between December 2013 and October 2015. Participants included all WTC-exposed FDNY white, male firefighters with a confirmed physician diagnosis of multiple myeloma (n = 16) and WTC-exposed FDNY white male firefighters older than 50 years with available serum samples (n = 781). WTC exposure defined as rescue and/or recovery work at the WTC site between September 11, 2001, and July 25, 2002. Multiple myeloma case information, and age-adjusted and age-specific prevalence rates for overall MGUS (ie, MGUS and light-chain MGUS), MGUS, and light-chain MGUS. Sixteen WTC-exposed white male firefighters received a diagnosis of multiple myeloma after September 11, 2001; median age at diagnosis was 57 years (interquartile range, 50-68 years). Serum/urine monoclonal protein isotype/free light-chain data were available for 14 cases; 7 (50%) had light-chain multiple myeloma. In a subset of 7 patients, myeloma cells were assessed for CD20 expression; 5 (71%) were CD20 positive. In the screening study, we assayed peripheral blood from 781 WTC-exposed firefighters. The age-standardized prevalence rate of MGUS and light-chain MGUS combined was 7.63 per 100 persons (95% CI, 5.45-9.81), 1.8-fold higher than rates from the Olmsted County, Minnesota, white male reference population (relative rate, 1.76; 95% CI, 1.34-2.29). The age-standardized prevalence rate of light-chain MGUS was more than 3-fold higher than in the same reference population (relative rate, 3.13; 95% CI, 1.99-4.93). Environmental exposure to the WTC disaster site is associated with myeloma precursor disease (MGUS and light-chain MGUS) and may be a risk factor for the development of multiple myeloma at an earlier age, particularly the light-chain subtype.

Highlights

Environmental exposure to the World Trade Center (WTC) disaster site is associated with myeloma precursor disease (MGUS and light-chain monoclonal gammopathy of undetermined significance (MGUS)) and may be a risk factor for the development of multiple myeloma at an earlier age, the light-chain subtype
Evidence from a large, prospective, population-based cancer screening trial shows that IgH-secreting and light-chain– secreting multiple myeloma are consistently preceded by their respective precursor states, monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS, which can be detected in peripheral blood.[5]
A high proportion of patients with multiple myeloma had CD20expressing plasma cells, which is a characteristic associated with a poorer prognosis.[5,21]

Summary

Methods

Multiple Myeloma Case Series Population and Case Information Through the WTC Health Program, FDNY WTC-exposed firefighters (N = 12 942) receive comprehensive physical and mental health services. Male firefighters with a post9/11 diagnosis of multiple myeloma (n = 16) in the FDNY WTC Health Program as of July 1, 2017, were included in the case series population (Figure 1A). All active FDNY firefighters are required to live in New York City or neighboring New York state counties of Westchester, Rockland, Orange, Nassau, or Suffolk; (2) via FDNY WTC Health Program medical assessments/records reviewed by an experienced clinician (N.J.).[13] Using medical records from the time of diagnosis, we extracted information on age at diagnosis, bone marrow aspirate and biopsy reports, and serum and urine protein testing. We performed complete case analysis when outcome data were missing

Results

Discussion

Conclusion