الفهرس 
Title pageOnly 14 pages are availabe for public view
 |  | from | 213 |  |  |
| | | from | 213 | | |
Abstract
MM is part of a group of disorders called plasma cell dyscrasias. It is a diverse
disease in which some patients progress rapidly despite therapy while others continue to
stay asymptomatic for years.
Despite advances in MM treatment, methods to evaluate the disease status have not
managed to keep up with this rapidly growing profile. Therefore, defining more precise
and fast methods to monitor and predict the outcome in these patients is now becoming
highly important.
BCMA is a member of the TNF receptor family, whose role has been involved in B-
cell malignancies. BCMA is essential for B-cell proliferation, survival, and differentiation
into plasma cells. This protein, in particular, has been linked to immunodeficiency, which
is a hallmark of MM.
Importantly, because BCMA is known to have a considerably shorter serum half-life
(24–36 hours) than M-protein (3–4 weeks), physicians may be able to quickly assess the
effectiveness of a treatment protocol, in addition to monitoring and evaluating the
therapeutic response. This is particularly crucial for patients who are progressing rapidly.
CD56 is a neural cell adhesion molecule, which plays a role in the adhesion of
myeloma cells to the bone marrow matrix. The lack of CD56 expression on the surface
of myeloma cells reduces their adhesion to the BM matrix and is linked to higher BM
infiltration, as well as an increased risk of renal impairment, extramedullary disease, Bence
Jones protein, and evolving into plasma cell leukemia.
Markers of inflammation are particularly important. Systemic inflammation is related
to alterations in leukocytic count, which is reflected by the NLR. Neutrophilia can suppress
the cytotoxic activity of T cells, thereby inhibiting the immune system and hastening tumor
progression. Lymphopenia is linked to the immune escape of tumor cells. As a result,
increased NLR creates an immune microenvironment that facilitates vascular invasion and
host immune suppression. Accordingly, NLR represents the balance of pro-tumor and anti-
tumor status and may be a useful index for predicting the prognosis of MM patients.
The primary aim of this research was to assess the role of serum BCMA as a new
prognostic marker in MM patients and to investigate the relationship between it and other
known prognostic markers. Furthermore, the study assessed the significance of CD56
expression and NLR in MM patients, in addition to, their prognostic influence on disease
outcome.
The current study included forty MM patients who were presented to the hematology
outpatient clinic or admitted to the hematology department of MRI. The IMWG diagnostic
criteria for symptomatic MM were used to establish the diagnosis. ISS staging was used to
categorize MM patients. Ten healthy volunteers of similar age and gender were included as
controls.
Summary, Conclusions& Recommendations
(143)
Peripheral blood samples were taken from the patients. Serum BCMA protein level
was analyzed by ELISA technique for all patients, initially prior treatment and during the
follow up after therapy. The status of CD 56 expression in BM aspirate plasma cells was
determined using flow cytometry. Before treatment, a CBC was performed, and the NLR
was calculated using data from the CBC differential count. Patients were followed till the
end of the study. The treatment response was evaluated, and the PFS was calculated using
Kaplan-Meier survival analysis.
BCMA had a significant positive correlation with the BM plasma cells percentage. A
significant correlation was also found between BCMA and M protein when measured
before induction therapy with VCD and during the follow-up period after treatment. This
implies that estimating BCMA levels might be utilized to assess the efficacy of a
particular treatment much faster than measuring M protein levels. Because serum BCMA
levels correlate with conventional MM markers like M-protein elevation and
BM plasmacytosis, they can be used to recognize alterations in clinical status in MM
patients.
The relationship between CD 56 expression and various clinicopathological
parameters revealed that the majority of patients with stage III lack CD 56 expression;
additionally, osteolytic lesions were absent in all patients who did not have CD 56
expression. Also, patients with CD 56-negative expression had higher levels of serum M
protein. However, no relation was found between CD 56 expression and Hb, creatinine,
calcium, LDH, β2M, or the percentage of BMA plasma cells.
Previously published studies have not used uniform NLR cut-off value for cancer
prognosis. As a result, this study optimized the cut-off for NLR. The ROC curve was used
for stratifying patients into low- and high-risk groups and revealed a cut-off point of 2.31.
There was no significant difference between the NLR < 2.31 patient group and the NLR ≥
2.31 group in terms of bone lesions and other laboratory parameters. However, high NLR
was significantly associated with high CRP and LDH levels.
This study showed that patients with CR could have significantly lower serum
BCMA levels, positive CD 56 expression, and low NLR, confirming the importance of
BCMA, CD 56 expression, as well as NLR in the assessment of therapeutic response.
Consequently, high BCMA levels, CD56 negativity, in addition to, high NLR recognized a
subset of high-risk MM patients, and each one could be a promising surrogate marker for
predicting treatment response in MM.
In addition to providing prognostic information, BCMA, CD 56 expression, and
NLR showed an impact on MM patient survival, as the current study found that high levels
of BCMA or CD 56 negative expression are associated with significantly shorter PFS.
Furthermore, survival seems to be higher in MM patients with lower NLR, although this
was not significant statistically. BCMA was the only independent prognostic factor for
survival of MM patients in multivariate analysis, which was confirmed using the Kaplan-
Meier survival curves.
Taking that into consideration, it’s no surprise that determining the studied parameters
in MM will aid in improved risk stratification and tailored clinical management of patients