Statistical analysis
The statistical analysis was carried out by a software SPSS 13.0 of IBM for windows. the continuous parameters, the results were expressed by the Mean ± standard deviation (SD).
RESULTS
The baseline characteristics of the study participants are as follow. The study included 374 (68.6%) men and 171 (31.4%) women, the mean ±SD ages were 62.24±13.14 years. The mean ±SD years age for the MM, MGUS, WM, LLMM, KLMM and the POEMS (Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome) were respectively of 61.70± 11.66, 63.64± 13.66, 61.71± 13.35, 60.57± 10.90, 56.50± 12.83 and 45.50 ± 2.12. regarding ethnic origin, all patients were of Caucasian origin, from the twelve regions of the Kingdom of Morocco. The most frequent reasons for admission were the bone pain (41,60%), the renal failure (19.08%), the alteration of the general condition (12.21%) and anaemia (10.69) (Table1). Plasma cell proliferative disorders in our study were as follow, MM (45.65%), Monoclonal gammopathies of undetermined significance (MGUS) (39.05%), Waldenstrom’s macroglobulinemia(5.58%), Lymphoma (2.27%+1.2%), Chronic Lymphocytic Leukaemia (2.48%), Plasma cell leukaemia (1.86%), Plasmacytoma (0.62%), POEMS syndrome (0.41%), and Amyloidosis (0.84%) (Table 2).
The estimated glomerular filtration rate (eGFR) in patients with MM was low compared to other monoclonal gammopathies, but the lowest eGFR were in patients with Free light chain MM, with more cases with kappa versus lambda light chain myeloma myeloma. The frequency of hypercalcemia was very high in patients with multiple myeloma and plasma cell leukaemia compared to other gammopathies. The kappa/Lambda ratio was highly elevated in patients with MM, plasma cell leukaemia, and plasmacytoma in comparison to the other MG. Even in patients with MGUS, the kappa/Lambda ratio was elevated.
The total protein level is highly increased in patients diagnosed with MM and WM and low in patients diagnosed with light chain MM. Low albumin concentration was found in patients with MM and plasma cell leukaemia. The SRFH was very high in patients with WM and MM. Furthermore, monoclonal protein levels were higher in patients with MM (38.21±23.83), MW (33.31±20.65) and MGUS (11.76±6.96).
Concentrations of parameters used in the prognostic evaluation of monoclonal gammopathies ( β2- microglobulin, CRP and LDH) were higher in patients with MM and MGUS respectively. Anaemia was more profound in patients with multiple myeloma in general (9.76±2.21), and in patients with free light chains MM ( LLMM (7.76±1.12), KLMM (9.07±1.81)), and Waldenstrom’s macroglobulinemia (9.29±2.15) (Table 3).
The isotype repartition by Plasma cell proliferative disorders in this study is given in table 4. The most frequent monoclonal proteins 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 worthy of note, that Free light chain MM represents 20% of all cases of MM.
For the MGUS, the most frequent isotypes were the IgGκ (87) 46.27%, IgGλ (61)32.44%, IgAκ(4)2.13%, IGAλ (9)4.78% , IgMλ (5)2.66% and IgMκ(9)4.78%. Finally, the most frequent isotypes in Waldenström’s macroglobulinemia were IgMκ (19)70.37%, IgMλ (7)25.93%, and an oligoclonal profil (1)3.70% (Table 4).
DISCUSSION
The study was carried out over a period of 19 years, between January 2000 and August 2019. The patients who were included in this study were 545 patients. To describe the epidemiological and immunochemical characteristics of monoclonal gammopathies diagnosed during a nineteen-year period in a Moroccan teaching hospital was the main objective of this study. The results of this study point to the need for an early diagnosis of monoclonal gammopathies in the Moroccan population. The mean±SD age at diagnosis of all MG was 62.24±13.14 years, and with a sex ratio male/female of 2.14. Our results are in agreement with the results of international studies confirming that GM is age-related and affects men more than women 1–3 .
Plasma cell proliferative disorders in our study were as follow, MM 45.65% (n=221), MGUS 39.05% (n=189), WM 5.58% (n=27), plasmacytomas 5.58% (n=27), plasma cell leukaemia 0.62% (n=3). The most frequent diagnosis of MG in the European and American studies was MGUS9,10 . In contrast, the most frequent diagnosis of monoclonal gammopathies in our study and the studies from Maghreb countries (Algeria and Tunisia) was MM 11,12 . This is due to the delay in diagnosis and the lack of serum protein electrophoresis in most of the hospitals in Maghreb countries. In a cross-sectional study Gupta et al have reported a low incidence of MGUS in Indians compared to blacks and whites populations13 . This study included 3429 patients, only 49 (1.43%) had a diagnosis of MGUS at the time of diagnosis13.
In this study, the POEMS syndrome was diagnosed only in 2 patients (0.41%), POEMS syndrome is relatively rare, in a mayo clinic study only 99 cases were diagnosed 14 .
The κ/λ ratio was very high in patients with MM (25.04), plasma cell leukaemia (26.67), MGUS (2.06) and plasmacytoma (19.00). Indeed, in patient with MM, Belouni et al, Mseddi et al and the Mayo clinic 10–12 have found the kappa/Lambda ratio respectively of 14.9, 14.13 and 16. Nevertheless, normal κ/λ ratio does not exclude the presence of a monoclonal gammopathy according to Singh et al, and false negatives rates associated with lambda chain are higher than those for lesions with kappa chains 15 .
The mean concentrations of monoclonal peak were MM (38.21±23.83), MW (33.31±20.65) and MGUS (11.76±6.96), these results are very far from the means noted in the patients included in the Algerian study of Belouni et al (22.19±20.19 g/l) 11 and in the majority of the other series, this can be explained by the late diagnosis of the monoclonal gammopathies in our country, and the high frequency of MM in our study in comparison of the international studies9,10. Furthermore, Monoclonal protein concentration was elevated in patients diagnosed with MW or MM compared to MGUS.
Anaemia was more profound in patients with free light chain MM, LLMM (7.76±1.12), KLMM (9.07±1.81). This may be explained by the high frequency of free light chain MM, and the delay in the diagnosis of our patients with MM.
The isotype repartition by plasma cell proliferative disorders is given in table 4. The most frequent monoclonal proteins in the group of patients with MM were the IgGκ (62) 36.5%, IgGλ(52)30.6%, IgAκ(27)15.9% and the IgAλ (19)11.2%. Regarding the MGUS group, the most frequent isotypes were the IgGκ (87) 46.27%, IgGλ (61)32.44%, IgAκ(4)2.13%, IgAλ (9)4.78%, IgMλ (5)2.66% and IgMκ(9)4.78%. The same results were reported in the study of Landgren et al, the most frequent isotypes by race/ethnicity were IgG %(n) 76.1 (71), IgA 5.2 (5), IgM 2.7 (3) in black, IgG 68.1 (150), IgA 9.7 (12), IgM 15.4 (34) in whites and IgG 63.1 (29) IgA 16.7(8) IgM 7.4 (6) in Mexican Americans16 .
Finally, the most frequent isotypes in Waldenström’s macroglobulinemia were IgMκ (19)70.37%, IgMλ (7)25.93%. These results are consistent with the results of studies from the Maghreb countries, in which the most common isotypes were the Ig G followed by the Ig A and the IgM in the studies of Mseddi et al in Tunisia, and Belouni et al in Algeria11,12 .