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 .