Abstract 5098

Military Service in Vietnam/Korea and Serum Dioxin Levels Do Not Affect the Outcomes of Patients Diagnosed with Plasma Cell Dyscrasias.

Background:

Exposure to dioxin, a contaminant found in herbicides has been associated with increased risk of cancers including multiple myeloma and postulated to cause poorer survival in the exposed population. Military personnel, especially those who had served in Vietnam and Korea have an increased risk of dioxin (which contaminated the herbicide Agent Orange which was sprayed during these wars) exposure. We looked at the impact of dioxin exposure and blood levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) which is the most toxic of the poly-chlorinated dioxins on the survival outcomes of military veterans diagnosed with plasma cell dyscrasias (PCD).

Methods:

A prospective analysis of newly diagnosed and existing myeloma patients was done. Information regarding the patient and disease characteristics, the military record, and outcomes were collected. Approximately 60 ml of heparinised peripheral blood was collected and immediately frozen at −20 degrees. These samples were shipped to Eurofins Laboratory, Hamburg, Germany for dioxin level measurement. Patients' blood lipid levels were also measured and the dioxin toxic equivalent (Teq) was calculated. Overall survival (OS) was calculated from the date of diagnosis till death (Kaplan Meier method). Cox regression and log rank analysis were used to look for prognostic variables.

Results:

Fifty two (52) patients of PCD were available for analysis. Majority had a diagnosis of multiple myeloma. Forty one underwent treatment including stem cell transplant in 16 (Table 1 shows the patient characteristics, laboratory results and treatment outcomes). During a median follow up of 54 months (2–348), 21 patients died (progressive myeloma: 12(23%), cardiac failure: 3 (5.7%), infections: 1 (1.9%), acute myeloid leukemia: 1 (1.9%), pulmonary embolism: 1 (1.9%) and unknown: 3 (5.7%). The median OS was 111 mos (95% CI 56–155) and the estimated survival at 5 yrs was 69.5% (+/− SE 0.067). The 5 yr OS was negatively impacted by abnormal cytogenetics (40.3 % vs. 75.5%; p=0.012), and service in the army (non-army vs. army: 83% vs. 40%; p=0.032). Patients who had served in Vietnam had outcomes similar to others; Korean War veterans had a poorer OS, but this was not statistically significant (5 yr OS 68% vs. 48%; p=0.1). There was no association between TCDD levels or the Teq with OS. Abnormal cytogenetics was the only significant factor on multivariate analysis.

Table 1

Characteristics of the patients and treatment outcomes(n=52)

ParameterN (%Median (range)
Male sex 51 (98)  
Age  65 (33–86) 
Diagnosis and Salmon Durie Stage 
    • MM 46 (82.5)  
    • MGUSàMM 5 (9.5)  
    • MGUS 3 (6)  
    • Amyloidosis 1 (2)  
    • Stage I 15 (29)  
    • Stage II 11 (21)  
    • Stage III 25 (48)  
Military serviceain the armyb 25 (48)  
    • Vietnam service 10 (19)  
    • Korean service 10 (19)  
Smokersc 18 (34)  
Alcoholism 20 (38)  
Hypothyroidism 16 (31)  
Diabetes 17 (32)  
Hyperlipidemia 30 (57)  
Bone lesions 29 (55)  
Plasmacytomas 6 (11.5)  
Weight at diagnosis  90.3 (50–144) 
M spike present 47 (91)  
    • Heavy chain IgG 40 (76)  
    • Heavy chain IgA 7 (13)  
    • Light chain kappa 30 (59)  
    • Light chain lambda 22 (41)  
Bone marrow plasma cell%  30 (0–97) 
Elevated calcium 5 (10)  
Calcium level (mg/dL)  9.4 (7.5–14.1) 
Renal dysfunction 16 (31)  
Anemia (hemoglobin <120g/L) 32 (61.5)  
Hemoglobin (g/L)  109 (49–161) 
Serum cholesterol (mg/dL)  152 (87–415) 
Serum Triglycerides (mg/dL)  121 (36–438) 
Serum Albumin (g/dL)  3.9 (2.4–4.6) 
Beta2microglobulin (X103μg/L)  3.7 (1.7–50) 
Abnormal cytogenetics 25 (48)  
Serum TCDD levels (ppt)  2.65 (0–10) 
Serum Teq (ppt)  20.5 (2–54) 
Number who were treated 41 (79)  
Stem cell transplantation done 16 (31)  
Treatment outcome ≥PR 26 (50)  
Relapse after intital treatment 28 (54)  
ParameterN (%Median (range)
Male sex 51 (98)  
Age  65 (33–86) 
Diagnosis and Salmon Durie Stage 
    • MM 46 (82.5)  
    • MGUSàMM 5 (9.5)  
    • MGUS 3 (6)  
    • Amyloidosis 1 (2)  
    • Stage I 15 (29)  
    • Stage II 11 (21)  
    • Stage III 25 (48)  
Military serviceain the armyb 25 (48)  
    • Vietnam service 10 (19)  
    • Korean service 10 (19)  
Smokersc 18 (34)  
Alcoholism 20 (38)  
Hypothyroidism 16 (31)  
Diabetes 17 (32)  
Hyperlipidemia 30 (57)  
Bone lesions 29 (55)  
Plasmacytomas 6 (11.5)  
Weight at diagnosis  90.3 (50–144) 
M spike present 47 (91)  
    • Heavy chain IgG 40 (76)  
    • Heavy chain IgA 7 (13)  
    • Light chain kappa 30 (59)  
    • Light chain lambda 22 (41)  
Bone marrow plasma cell%  30 (0–97) 
Elevated calcium 5 (10)  
Calcium level (mg/dL)  9.4 (7.5–14.1) 
Renal dysfunction 16 (31)  
Anemia (hemoglobin <120g/L) 32 (61.5)  
Hemoglobin (g/L)  109 (49–161) 
Serum cholesterol (mg/dL)  152 (87–415) 
Serum Triglycerides (mg/dL)  121 (36–438) 
Serum Albumin (g/dL)  3.9 (2.4–4.6) 
Beta2microglobulin (X103μg/L)  3.7 (1.7–50) 
Abnormal cytogenetics 25 (48)  
Serum TCDD levels (ppt)  2.65 (0–10) 
Serum Teq (ppt)  20.5 (2–54) 
Number who were treated 41 (79)  
Stem cell transplantation done 16 (31)  
Treatment outcome ≥PR 26 (50)  
Relapse after intital treatment 28 (54)  

MM: multiple myeloma, MGUS: Monoclonal gammopathy of undetermined significance, TCDD: 2,3,7,8-tetrachlorodibenzo-p-dioxin, Teq: toxic equivalent, PR: Partial response

a.

Median duration of service 3 years (1–23)

b.

Non-army service: Navy 11, marines 5, coastguard 1, air force 9

c.

Median of 40 pack years among smokers

Conclusions:

We did not find an association between military service in Korea/Vietnam or serum dioxin levels and poor survival in military veterans diagnosed with Plasma cell dyscrasias. However, a study of a larger sample of myeloma patients with similar service and exposure histories maybe warranted.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.

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