Epidemiology of monoclonal gammopathy in Morocco – A hospital‐based study

Abstract Background Monoclonal gammopathies are a group of disorders associated with clonal proliferation of plasma cells that produces a monoclonal protein. Aims The main objective of this study was to describe the epidemiological and immunochemical characteristics of monoclonal gammopathies diagnosed during 19 years in a Moroccan teaching hospital. Materials and Results This retrospective study enrolled 443 Moroccan patients with monoclonal gammopathy, patients meeting the inclusion and exclusion criteria in at the biochemistry department of Military Hospital in Rabat, the capital of Morocco, from January 2000 to August 2019. Of the 443 enrolled patients, 320 (72.23%) were men and 123 (27.77%) were women. All patients were of Caucasian origin, from 12 Moroccan regions. The patient's samples were collected and subjected to serum protein electrophoresis and serum immunofixation electrophoresis to further characterize the monoclonal protein. The mean ± SD age of the 443 participants was 62.24 ± 13.14 years. Reasons for being admitted to the hospital were as follows, bone pain (41.60%), renal failure (19.08%), alteration of the general condition (12.21%), and anemia (10.69). Plasma cell proliferative disorders in our study were as follows, multiple myeloma (MM) (45.65%), Monoclonal gammopathies of undetermined significance (MGUS) (39.05%), Waldenstrom's macroglobulinemia (5.58%), Lymphoma (2.27% + 1.2%), Chronic Lymphocytic Leukemia (2.48%), Plasma cell leukemia (1.86%), Plasmacytoma (0.62%), POEMS syndrome (0.41%), and Amyloidosis (0.84%). The most frequent isotypes in MM were the IgGκ (62) 36.5%, IgGλ (52) 30.6%, IgAκ (27) 15.9%, and the IgAλ (19) 11.2%. It is also worth noting that Free light chain MM represents 20% of all cases of MM. Conclusions We found that monoclonal gammopathies are age‐related and affects men more than women, also the results of this study point to the delayed diagnosis of monoclonal gammopathies, since most of our patients were diagnosed at the MM stage. The most frequent isotypes were the IgGκ and IgGλ in MM and MGUS, in Waldenström macroglobulinemia were IgMκ and IgMλ and the oligoclonal profile represented only 3.70%.

Monoclonal gammopathies of undetermined significance is defined as the production of monoclonal protein without any systemic effect. It represents the early stage of multiple myeloma (MM). MGUS accounts for 3% of MG in patients over 50 years of age. 5 In general, MGUS will progress to MM at a rate of 1% per year. 6 MM represents 10% of hematologic malignancies in general, the median age at diagnosis is estimated to be 70 years, and it affects more men (7 per 100 000) than women (4.5 per 100 000), blacks more than whites, thus, the highest prevalence rate is observed in African Americans, particularly in those aged 80-84 years and older. 2 Some mutations and cytogenetic abnormalities are associated with high-risk MM, such as translocations (t(4;14), t(14;16), t(14;20)), deletions: del (17p), gain 1q, or p53 mutation. 7 The main objective was to describe the epidemiological and immunochemical characteristics of MG diagnosed over 19 years at a Moroccan teaching hospital.

| Patient selection
The study was carried out over 19 Figure 1).

| Methods
Blood samples were collected using serum dry tubes, the samples were left to clot for 1 hour before centrifugation at 1000 RPM for 15 min. Total protein (g/L), C-reactive protein (mg/L), Calcium (mg/L), Immunofixation was performed when an abnormal serum protein electrophoresis was defined by the presence of a quantifiable monoclonal spike, hypogammaglobulinemia, and a fuzzy band.
Patient records have been reviewed for clinical history and the monoclonal protein subtype. The diagnosis of MG is based on the presence of an increase in the number of plasma cells and/or immature and dystrophic plasma cells in the marrow, the presence of F I G U R E 1 Flow chart which represents the study protocol. histological evidence of plasmacytoma, the presence of monoclonal protein in the serum and urine, and/or bone lesions.

| Statistical analysis
The frequencies of clinical signs at admission and types of plasma cell dyscrasias were calculated using the software SPSS 13.0 of IBM for windows. The quantitative variables are presented as mean ± standard deviation (SD).

| RESULTS
The baseline characteristics of the study participants (n = 443) are as follows. The study involved 320 (72.23%) men and 123 (27.77%) women, with mean ± SD age of 62.24 ± 13.14 years. The total protein level is highly increased in patients diagnosed with MM (38.21 g/L ± 23.83), MW (33.31 g/L ± 20.65), and MGUS (11.76 g/L ± 6.96), and low in patients diagnosed with light chain MM. Low albumin concentration was found in patients with MM and plasma cell leukemia.
The isotype repartition by Plasma cell proliferative disorders in this study is given in                      ± SD age at diagnosis of all MG was 62.24 years ±13.14 with a sex ratio male/female of 2.14. Our results are in agreement with the results of international studies confirming that MG is age-related and affects men more than women. [8][9][10] Plasma cell proliferative disorders in our study were as follows,

CONFLICT OF INTEREST STATEMENT
The authors have stated explicitly that there are no conflicts of interest in connection with this article.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are availabe from the corresponding author upon reasonable request.

ETHICS STATEMENT
The