Detection of non-CLL-like monoclonal B cell lymphocytosis increases dramatically in the very elderly, while detection of CLL-like populations varies by race: findings in a multiethnic population-based cohort of elderly women.

Monoclonal B cell lymphocytosis (MBL) is both a marker of immune senescence and a potential precursor of B cell malignancy. Most MBL populations have a chronic lymphocytic leukemia-like (CLL-like) immunophenotype, but those that are CD5-negative (non-CLL-like) are also recognized and may represent a distinct diagnostic entity. To date, MBL studies have taken place in relatively homogenous populations, although risk of CLL varies across racial groups and geographic regions. We report flow cytometry data from 597 ethnically diverse 64-94-year-old women from across the USA who are participants in the Women's Health Initiative (WHI) Long-Life Study (LLS). Overall, MBL was detected in 26 % of the participants and included 20.9 % with a CLL-like immunophenotype, 5 % with a non-CLL-like immunophenotype, and 1.3 % with both. White and Hispanic women were more than twice as likely to have a CLL-like MBL population detected than African American women, corrected for age (P = 0.003). By contrast, detection of non-CLL-like MBL did not vary significantly by race, but did increase markedly with advancing age, being present in 12.7 % of those aged 85 and older. We provide new evidence that rates of detection of CLL-like MBL are lower in African Americans, and further suggest that non-CLL-like clonal expansions should be regarded as distinct from CLL-like MBL.

Predictors of plasma cell disorders among African American patients: a community practice perspective.

African Americans have two- to three-fold higher incidence of multiple myeloma and MGUS compared to other ethnic groups in the USA. Some physicians often perform diagnostic evaluations for plasma cell disorders (PCD) in African American patients on the basis of hematological abnormalities (thrombocytopenia, leucopenia, etc.) even in the absence of traditional triggers such as anemia, renal impairment, hypercalcemia, hyperglobulinemia, and lytic bone disease. Whether these nontraditional triggers have any significant association with PCD in African American population is not known. In addition, whether this approach could detect more asymptomatic PCD than black population prevalence is questionable. Moreover, the association between traditional triggers and PCD particularly in blacks has not been clearly delineated. Hence, we have carried out a retrospective study in an attempt to answer these questions. Two hundred fifty-four patients were eligible. Multiple myeloma workup based on parameters other than traditional triggers did not detect more asymptomatic PCD than what is expected of black population prevalence (p = 0.19). Of traditional triggers, the finding of only anemia or hyperglobulinemia seemed to be nonspecific in black population (p = 0.17 and 0.85, respectively). However, the presence of serum creatinine >2 mg/dL or corrected serum calcium >10.5 mg/dL or a combination of traditional triggers appeared to be strongly predictive of PCD (odds ratio of 6.9, 4.2, and 3, respectively). The number of trigger variables was positively correlated with the likelihood of PCD (p < 0.001). Light-chain-only PCD, renal disease, and abnormal free light chain ratio seemed to be higher in black patients than their white counterparts.

Higher prevalence of monoclonal gammopathy of undetermined significance in African Americans than whites--the unknown role of underlying HIV infection.

The age-adjusted prevalence rate of monoclonal gammopathy of undetermined significance (MGUS) is three-fold higher in African Americans than whites. Similarly, there is a higher preponderance of multiple myeloma (MM) in African-American patients. Since the risk of progression of MGUS to MM is equal in both races, identification of exogenous and genetic risk factors of MGUS [such as genetic pre-disposition; diet; and chronic antigenic exposure related to sexually transmitted diseases, including human immunodeficiency virus (HIV) infection] is essential for unraveling the etiology of the racial disparity for MM. HIV infection, a well-documented risk factor for MGUS, is more frequent in African-American patients. Future epidemiologic studies dealing with plasma cell disorders should carefully examine the relationship between race, HIV infection status, prevalence of MGUS and its ultimate progression to MM.

Deletion of genetic material from a poly(ADP-ribose) polymerase-like gene on chromosome 13 occurs frequently in patients with monoclonal gammopathies.

Recently, by using a probe for the nuclear DNA repair enzyme poly(ADP-ribose) polymerase gene, a pseudogene was found on the long arm of chromosome 13. RFLP analysis demonstrates the presence of a common "A" allele and a rare "B" allele, which has a deletion of approximately 200 bp. This deletion occurs more frequently in blacks than in whites in the United States. In two B-cell malignancies, Burkitt's and follicular lymphomas, there is a marked increased frequency of the expression of the B allele. Thus, we have analyzed the frequency of this allele in another B-cell malignancy, multiple myeloma (MM), which is also more frequently observed in blacks. We studied 97 patients with MM (41 black and 56 white patients) and 30 patients with the related disorder monoclonal gammopathy of undetermined significance (MGUS; 13 black and 17 white patients). The results demonstrate that the overall frequency of B allele expression (37%) is higher than in a noncancer control population (23%; P < 0.01). This difference is mainly due to the much higher frequency of B expression in black patients (52 versus 35% in black controls; P < 0.01), whereas there is no significant difference in white patients (18 versus 14% in white controls). Overall, B allelic frequency is similar in patients with MM and MGUS. Matched germline and tumor DNA show identical patterns of expression of these alleles. These results suggest germline B allelic expression predisposes one to MM and MGUS.

Racial differences in the prevalence of monoclonal gammopathy in a community-based sample of the elderly.

PURPOSE: To determine if there is an increased prevalence of monoclonal gammopathy in elderly blacks compared with whites, analogous to the difference in incidence of multiple myeloma reported for the two racial groups and to confirm age and gender relationships. PATIENTS AND METHODS: Subjects were from the Duke Established Populations for the Epidemiologic Study of the Elderly, selected on the basis of stratified random household sampling. Blacks were oversampled to allow for increased statistical precision in racial comparisons. In all, 1,732 subjects (aged > 70 years) consented to blood drawing and constitute the sample for this study. Monoclonal immunoglobulins were determined by agarose gel electrophoresis and immunofixation. RESULTS: One hundred six subjects (6.1%) had a monoclonal gammopathy. There was a greater than twofold difference in prevalence between blacks (8.4%) and whites (3.8%) (P < 0.001); monoclonal gammopathy prevalence increased with age, and was greater in men than women. Those with monoclonal gammopathy did not differ from those without in socioeconomic status, urban/rural residence, or education. The presence of monoclonal gammopathy was not associated with any specific diseases nor with impaired functional status. There was a slight increase in serum creatinine levels and decrease in hemoglobin and albumin levels in patients with monoclonal gammopathy, but no difference in interleukin-6 (IL-6) levels. Moreover, IL-6 levels were not correlated significantly with the level of monoclonal protein. CONCLUSION: Prevalence of monoclonal gammopathy is significantly greater among blacks than whites in a community-based sample, in approximately the same ratio that multiple myeloma has been reported in the two groups. Given the absence of correlation with environmental factors, there may be a biological racial difference in susceptibility to an early event in the carcinogenic process leading to multiple myeloma.

Assessment of serum-mediated neurotoxicity in Navajo neuropathy.

Navajo neuropathy is a unique sensorimotor neuropathy which is geographically restricted to Navajo children living on the Navajo Reservation. Affected patients present with weakness, loss of sensation in extremities, corneal ulcerations, and a high incidence of childhood infections. Metabolic complications, such as severe liver disease, may further contribute to peripheral nerve injury in affected patients. In this study, serum-mediated injury to rat peripheral nerve was critically assessed. Serum samples from affected Navajo patients were tested in vivo for effects on peripheral nerve function. Injection of serum from affected Navajo patients into rat sciatic nerve produced a modest slowing of nerve conduction velocity without effecting evoked-compound muscle action potential (CMAP) amplitudes. By comparison, injection of serum from patients with MGUS neuropathy, an immune-mediated disorder, diminished evoked-CMAP amplitudes by approximately 70%. Navajo neuropathy sera had no effect in vitro on the neurite outgrowth of developing dorsal root ganglia neurons. The results argue against serum-mediated toxic injury to peripheral nerves in Navajo neuropathy.

Racial disparities in the prevalence of monoclonal gammopathies: a population-based study of 12,482 persons from the National Health and Nutritional Examination Survey.

Multiple myeloma (MM) incidence is markedly higher in blacks compared with whites, which may be related to a higher prevalence of monoclonal gammopathy of undetermined significance (MGUS). Our objective was to define the prevalence and risk factors of MGUS in a large cohort representative of the US population. Stored serum samples from the National Health and Nutritional Examination Survey (NHANES) III or NHANES 1999-2004 were available for 12,482 individuals of age ⩾50 years (2331 'blacks', 2475 Hispanics, 7051 'whites' and 625 'others') on which agarose-gel electrophoresis, serum protein immunofixation, serum-free light-chain assay and M-protein typing were performed. MGUS was identified in 365 participants (2.4%). Adjusted prevalence of MGUS was significantly higher (P<0.001) in blacks (3.7%) compared with whites (2.3%) (P=0.001) or Hispanics (1.8%), as were characteristics that posed a greater risk of progression to MM. The adjusted prevalence of MGUS was 3.1% and 2.1% for the North/Midwest versus South/West regions of the United States, respectively (P=0.052). MGUS is significantly more common in blacks, and more often has features associated with higher risk of progression to MM. A strong geographic disparity in the prevalence of MGUS between the North/Midwest versus the South/West regions of the United States was found, which has etiologic implications.

Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis.

Monoclonal gammopathy of undetermined significance (MGUS) is one of the most common premalignant disorders in Western countries. Recent studies show that almost every multiple myeloma (MM) case is preceded by an MGUS stage. Interestingly, prevalence and incidence patterns for MGUS and MM show striking disparity patterns across ethnic/racial groups, most notably the two- to threefold increase in both these disorders in African Americans compared with Caucasians. In contrast, studies on Asian patients show lower prevalence/incidence for MGUS/MM compared with Caucasians. Familial aggregation for both MGUS and MM has been observed; the risk for MGUS or MM in family members with these disorders is increased about two- to three fold compared with the general population. Although underlying mechanisms remain unclear, there is evidence of heterogeneity among MGUS patients from different ethnic/racial groups. For example, compared with Caucasians, African-American and African MGUS patients have reportedly lower rates of immunoglobulin M (IgM) MGUS (versus IgG/IgA MGUS) and higher rates of unquantifiable immunoglobulins (Igs). This review focuses on racial disparity and familial aggregation patterns for MGUS and MM and discusses how these observations provide novel clues with regard to pathogenesis.

The POEMS syndrome among Chinese: association with Castleman's disease and some immunological abnormalities.

POEMS or Crow-Fukase syndrome is a multisystemic, clinically malignant disorder of obscure etiology. Peripheral neuropathy and plasma cell dyscrasia are central features. The authors now report 7 Chinese patients with this syndrome in which PCD or paraproteinemia were absent in 6, and 2 had a lymph node histology resembling that of hyaline-vascular Castleman's disease. Immunological abnormalities consisted of either increased or decreased numbers of B- and T-cells in 2 cases, and an elevated OKT4/OKT8 ratio with paradoxical dissociation of the lymphocyte transformations to various concentrations and types of mitogens in 1 case. This suggests that the underlying abnormalities of POEMS syndrome are heterogeneous and that it may be an immunologically related syndrome of varying etiology.