The value of platelet to lymphocytes and neutrophil to lymphocyte Ratios as Prognostic Markers of multiple myeloma in Iraqi patients

Abstract

Keywords: Multiple myeloma, the ratio of neutrophil-to-lymphocyte, the ratio of platelet-to-lymphocyte, new marker of prognosis ABSTRACT Background: Multiple myeloma considered being the most common bone related malignancy. It occurs, especially in older persons, in an increasing frequency trend. In various malignancies, recent researches showed the ration of neutrophils to lymphocyte and platelet to lymphocyte works as an indicator of progression free survival [PFS] and overall survival [OS].

Full text

https://alqalam.utripoli.edu.ly/science/ eISSN 2707-7179
Research Article
The value of platelet to lymphocytes and neutrophil to lymphocyte
Ratios as Prognostic Markers of multiple myeloma in Iraqi patients
Alea farhan salman1, Eham Amer Ali2 ,Inas hazim hameed 3 ,Muthana oweed Hussei 4Assel Abdulsattar1,
Wassan Nor5
1 The National center of Hematology/University of AL-Mustansiriyha / Baghdad-Iraq
2 Department of Chemistry and Biochemistry/College of Medicine/University of AL-Mustansiriyha / Baghdad –Iraq.
3- Department of nursing /Almarref College university
5- College of Medicine/ Department of Obstetrics and Gynecology Mustansiriyha University, Baghdad, Iraq
ARTICLE INFO
Corresponding Email: aliyah_farhan@uomustansiriyah.edu.iq
Keywords: Multiple myeloma, the ratio of neutrophil‐to‐lymphocyte, the ratio of platelet‐to‐lymphocyte, new
marker of prognosis
ABSTRACT
Background: Multiple myeloma considered being the most common bone related malignancy. It occurs, especially in older
persons, in an increasing frequency trend. In various malignancies, recent researches showed the ration of neutrophils to
lymphocyte and platelet to lymphocyte works as an indicator of progression free survival [PFS] and overall survival [OS].
Patients & Methods: This case-control study has been conducted in the clinical biochemistry department at the National
center of Hematology in Baghdad for a period from January 2021 till July 2021, enrolling sixty subjects, thirty patients
diagnosed as multiple myeloma and thirty persons as a control group. In this study, for MM patients, the PLR and NLR the
relevance has been investigated. Whole blood counts have been used to calculate NLR and PLR.
Results: 30 patients were assessed, compared with 30 apparently healthy subjects. The Mean NLR level was 2.06 for
patients and 1.79 for control, Mean PDW levels were 16.34 for patients and 15.77for control, PLR levels were 135.60 for
patients and 265.5 for control, PLT levels was 257.39 ul for patients and 344.4 ul for control. Based on ROC analysis, the
NLR cut-off level of ≤ 1.1 in multiple myeloma patients, and the PLR cut-off level of ≤ 120. Results revealed that reduced
PLR affects the result negatively.
Conclusion: From the results drawn from the experimental work, we came up with the conclusion that in a newly diagnosed
MM patient the significant prognostic factor was PLR.
INTRODUCTION
Researches showed that, multiple myeloma (MM), which contributes to nearly 10% of the total
hematologic cancers [1], is a cause of plasma cell malignancy. Basically, it gets developed from the stage of an
asymptomatic premalignant of clonal plasma cell proliferation, which is “monoclonal gammopathy of
undetermined significance (MGUS)”. It is noted that, (MGUS) occurs about more than 3% in above 50 years
population and, then, progresses, at a rate of 1% every year, to myeloma or related malignancy [2]. Further,
intermediate asymptomatic was noticed in few patients, but it has been clinically recognized that, in case of
more advanced premalignant stage considered to be (SMM) [3].There are two main staging systems used for
multiple myeloma (MM) are the "international staging system" (ISS). This is depend on the blood plasma levels
and beta-2 microglobulin, and the Durie Salmon system (DSS). This depends on the M protein level , level of
red blood cells calcium, along with the degree of necrosis in bones. These conditions divided by the system into
three stages .However, the most severe stage was found to be third stage . There are three stages for ISS cases .
Stage I is for people with a B2M less than 3.5 mg/L and albumin > 3.5 g/dL. Stage III for those with a B2M
higher than 5.5 mg/L and Stage II is between stage I and Stage II [4].

https://alqalam.utripoli.edu.ly/science/ eISSN 2707-7179
Regarding Multiple myeloma risks factor ,it increases with age. Sex is about 1.5× more common among men
than women. Higher rates of obesity and consumption among men, though none of these risk factors have been
confirmed in multiple myeloma [5]. In black persons, it occurs high than ,as twice , in the white population in
rate. Most importantly, the factors of the surrounding environment could get interacted with underlying genetic
factors resulting in an increasing the risk of (MM) [6]. Ionizing radiation, chemicals like benzene, pesticides,
chemotherapy, smoking cigarettes, viral infection and genetic disorders are recognized as multiple myeloma
risk factors [7,8]. However, these risk factors can only explain minority cases and the etiology of multiple
myeloma remains largely unknown [9].
Patients recognized with multiple myeloma that is firstly appears when patient's complaint of difficult to explain
backache or may be with bone pain. In addition, it commonly appears in long bones, skull, pelvis and ribs.
Besides, many patients have a diagnostic of multiple lytic skeletal lesions [2]. It has been noticed that, the most
occurring symptoms of multiple myeloma are anemia that appears in nearly 75% of patients and contributes to
fatigue. Approximately 80% of patients have Osteolytic skeletal lesions [10]. Neutrophils are view as the final
influential cells for the inflammatory response acute stage which has a main role in the extracellular pathogens'
clearance. the functions of these cells have been extended in latest proof. This resent discovery reserve the
effector molecules in the neutrophils including extracellular traps in a broad array, cytokines and effector
molecules of the humoral arm of the innate immune system. The Neutrophils role was devoted to activate the
regulation and the function of effector functions for both adaptive and innate immune cells. Consequently, the
neutrophils role was critical in the pathogenesis of a vast range of diseases. For instance, the case of infections
triggered by intracellular pathogens, autoimmune diseases, and chronic inflammation cases [11].Platelets are
defined as small cells without nucleus, it way of traveling described as fragments of resting discoid inside the
circulation system. The life of theses platelets about 8–9 days in average. Their elegant formation in addition to
its cellular processes, described with finely orchestrated series, called thrombopoiesis and
megakaryocytopoiesis. The process includes the committing of hematopoietic stem cells, terminal
differentiation of megakaryocytic progenitors, proliferation and maturation of megakaryocytes to produce
functional platelets. This very complicated mechanism happens in specialized in the bone marrow endosteal and
vascular niches where megakaryocytes form proplatelet projections and releasing platelets into the circulation
[12].Different in its function, but similar in its appearance, Lymphocytes defined as the white blood cells that
which includes (T, B, and natural killer cells).They are involved in the process of antibody production. In
another words, these cells get involved in tumor cells, and regulation of the immune response and virus infected
direct cell-mediated killing [13]. The aim of the study is : To use the (NLR) and(PLR) values as a prognostic
marker in( MM) patients in routine practice.
PATIENTS AND METHOD:
A case control study had been conducted in the department of clinical biochemistry at the National center of
Hematology in Baghdad for a period from November 2020 till June 2021, involving a total of sixty person,
thirty patients diagnosed as multiple myeloma and thirty persons as a control group with regard to their age and
gender they were matched with (MM) group. An informed consent was taken from all participants to be
enrolled in the study that was approved by the ethical committee of Mustansiriyha University/ College of
medicine (MOG/146 on the 23rd NOV 2020). Multiple myeloma patients, the guidelines of International
Myeloma Working Group (IMWG) have been used to diagnosed and assessed [14,15]. All cases were collected
from the National center of Hematology / Mustansiriyha University and fulfill the diagnostic criteria of MM.
For all patients under investigation, a complete blood count (CBC)was taken at the diagnosis, the control group
was selected randomly from those who attend the National center for routine visits. Beckman Coulter LH 780
has been utilized to perform a whole blood between systems in use, whereas data from of the (CBC) count
during the diagnosis time have been used to calculate both (PLR) and (NLR). The (NLR) has been obtained as
the absolute value count of neutrophil divided by the lymphocyte absolute count. The (PLR) was obtained as the
blood of platelet count divided by the blood of lymphocyte count of the treatment patients.

https://alqalam.utripoli.edu.ly/science/ eISSN 2707-7179
Statistical analysis: Data were expressed as means ± standard deviation with standard error of the mean, A
student-t test was used to analyze the significance of difference between the two groups. (ROC) Curve was
applied to determine the cut off value for (NLR) and (PLR) with the maximum sensitivity and specificity, p
value was significant when less than 0.05.
RESULT
The total number of all enrolled persons was 60 samples divided into 30 newly diagnosed with multiple
myeloma were included in this study and 30 healthy subjects for control. The mean age for patients and control
were 64±2.1 and 62 ±3.2 respectively. The male formed 68% and 32% female in patient group while 55% in
control group as shown in table 1.Mean (NLR) were 2.06 for patients and 1.79 for control, Mean (PDW) level
was 16.34 in patient group while 15.77 in control. Mean (PLR) levels were 135.60 for patients and 265.50 for
control. Mean (PLT) level was 257.39 for patients group and 344 for control as shown in table 2. Table 3 refer
to the cut-off level of ( PLR), (NLR), Sensitivity, and specificity in multiple myeloma Patients in which
based on (ROC) analysis were (PLR) ≤120, (NLR) 1.10 respectively as shown in fig 2 and fig3.
(ROC) Curve was applied for( PLR) analysis and clarified in figure 2 which showed at the cut-off value of
≤120. the sensitivity was 100% and specificity 100% with 95% CI (0.920 to 1.000), area under curve 1.00 with
a significant p- value 0.0001. While (ROC) Curve was applied for (NLR) analysis and clarified in figure 3
which showed at the cut-off value of ≤1.1 the sensitivity was 95.5% and specificity 36.4% with 0.634, area
under curve and a significant p value 0.093.
Table 1: the primary criteria of patients and controls
Characteristics Patients (No. =30) Control (No.=30) p-value
Age (years) 64±2. 1 62 ±3. 2 0.061
SEX
Male 18 (68%) 17 (55%) 0.082
Female 12 (32%) 13 (45%)
BMI mean and percentage %
>25 Kg/m222.1 (12%) No.=15 22.9 (12 %)
0.07
25-29.9 Kg/m227.91 (23%) No.=8 26.53 (22 %)
More than 30 32.03 (65%) No.= 7 33.02 ( 66 %)
Table 2: the hematological parameters and ratios of Healthy subject versus control group.
Parameters
Normal case
(Control groups)
Patients
(Multiple Myeloma) p-value
Mean ±SD Mean± SD
NLR 1.79±0.52 2.06±1.61 0.701
PDW(fL) 15.77±1.72 16.34±3.55 0.1912
PLR(fL) 265.50±69.49 135.60±41.94 P<0.001*
PLT 103/µL 344.40±75.75 257.39±73.90 0.0912

https://alqalam.utripoli.edu.ly/science/ eISSN 2707-7179
Figure 1: Relation NLR, PDW, PLR and PLT parameter with multiple myeloma and control groups
Table 3 : The cut-of level of Around Study for NLR and PLR Sensitivity and specificity in multiple myeloma
Patients
Parameters Cutt-off Area under the
ROC curve Sensitivity Specificity p-value
PLR ≤120 1.0 100 100 <0.0001
NLR ≤ 1.1 0.634 95.5 36.4 0.093
Figure 2:( ROC) Curve analysis of (PLR) Figure 3: (ROC) Curve analysis of (NLR)
In (MM) versus control in( MM) versus control
0
20
40
60
80
100
PLR
0 20 40 60 80 100
100-Specificity
Sen sitivity
AUC = 1.000
P < 0.001
0
20
40
60
80
100
NLR
0 20 40 60 80 100
100-Specificity
Sensitivity
AUC = 0.643
P = 0.093
Sensitivity: 36.4
Specificity: 95.5
Criterion: ≤1.1

https://alqalam.utripoli.edu.ly/science/ eISSN 2707-7179
(ROC) Curve was applied for (PLR) analysis and clarified in figure 2 which showed at cut off value of
(≤120) the sensitivity was (100% )and specificity (100%) with area under curve (1.000) with a significant p
value (0.0001).(ROC) Curve was applied for (NLR) analysis and clarified in figure 3 which showed at the cut-
off value of (≤ 1.1)the sensitivity was (36.4%) and specificity( 95.5%) with area under curve (0.643) with a p-
value (0.093).
DISCUSSION
Prognosis prediction has been crucial in treatment planning for patients with multiple myeloma. Tumor
growth is intimately linked to inflammation [16], and neutrophils and lymphocytes are the primary cells
involved in inflammation and immunological responses [17]. Patients with a high platelet count are at a greater
risk of developing cancers, as well as particular types of cancer that have a stronger association with
thrombocytosis [18]. Multiple past studies established the predictive value of platelet count in the range of solid
tumors including the cases of hepatocellular, renal-cell, lung, colorectal, gastric, and gynecological [19,20]. As
a result, we analyzed data from patients treated at our facility in order to deeply investigate, in case of multiple
myeloma, the type of the relation between (NLR), (PLR), and prognosis prediction.
Neutrophil to Lymphocyte Ratio; lymphopenia and Neutrophil[relative] were predicted based on the natural
response of the immune system of the body during inflammatory process [21]. Numerous researches have been
conducted recently on the immunological profile of individuals with MM, and the specific characteristic of
immunology was proven to be linked with overall survival [22]. The neutrophil-lymphopenia ratio (NLR) is a
direct indication of balance between neutrophilia and lymphopenia. NLR has been a prognostic factor in a
variety of severe illness states and malignancies. There are considerable inconsistencies in the research about
(NLR) influence on overall survival (OS) and progression-free survival (PFS) in patients with hematologic
malignancies [23-25]. Our findings indicated that the (NLR) value raised in patients (2.06 1.61) but was not
statistically significant [p=0.701] when compared to controls (1.79 0.52). The cut-off value was determined to
be [1.1]. Solmaz [26] achieved similar results to ours, indicating that NLR =1.9, or less than 2. In another study,
Kelkitli et al., the authors, divided the participants in their study into two main groups depending on the (NLR)
cutoff criterion of 2.0.The authors discovered that (MM) patients with an (NLR) less than( 2.0) lived longer than
those with an( NLR) greater than (2.0). [27]. This research was the first one to demonstrate a relation between
(NLR) and(OS) in (MM). Numerous scientists have recently focused their attention on the prognostic
significance of (NLR) in malignancies [28]. A meta-analysis of 15 studies on the predictive value of (NLR) in
breast cancer found that elevated (NLR) was linked with poor overall survival and progression-free survival
[29]. Wei performed a meta-analysis on the prognostic significance of (NLR) in urinary malignancies and came
to the same conclusion [30]. Although some research have been conducted on solid tumors, scientists have
begun concentrating their efforts on hematological malignancies. Keam demonstrated that pre-NLR 3 was a
significant predictor of poor outcome in cases with diffuse large B-cell lymphoma [31]. Another research
reached the identical conclusion [32]. The precise mechanism through which elevated (NLR) correlates with a
worse prognosis for cancer is unknown. This outcome can be interpreted in a variety of ways. To begin,
lymphocytes contribute significantly to the antitumor immune response by blocking malignant cell growth and
metastasis [33]. Systemic inflammation induced by malignant cells can result in immunological suppression,
allowing tumor cells to evade the host immune response [34]. Second, neutrophils invade a variety of tumor
tissues. Tumor-associated neutrophils are connected with cancer progression because they are the principal
source of circulating vascular endothelial growth factor (VEGF), which has been shown to increase tumor-
associated angiogenesis [35,36]. By stimulating growth, neutrophils directly assist tumor cells in surviving [37].
Thus, elevated (NLR). Consequently, the increased neutrophils and decreased lymphocytes, shows that the
balance between pro- and anti-tumor status has been broken and tilted toward a pro-tumor inflammatory state,
resulting in tumor progression and poor prognosis.The Ratio of Platelet to Lymphocyte (PLR); in respect of
(PLR), our findings indicated a highly significant reduction in (MM) patients (135.6041.94)as compared to the

https://alqalam.utripoli.edu.ly/science/ eISSN 2707-7179
control group (265.5069.49) (p 0.001) with a a cut off value of [ 120] . In keeping with our findings, a low
platelet count or low PLR (cut-off = 100) has been considered as a poor prognostic factor in patients with
multiple myeloma [38,26]. In contrast to these findings, a high (PLR) level has been attributed to a poor
prognosis in both hematological and non-hematological cancers [39,40] .This discrepancy in (MM) may be
attributable to the disease's pathophysiology. In (MM), the increase of malignant plasma cells in the bone
marrow impairs normal thrombopoiesis. Another study revealed that individuals with multiple myeloma have a
considerably shorter platelet half-life [41]. Shi et al. demonstrated that higher (NLR) and (MLR) levels, as well
as a reduction in (PLR), has been related to worse outcomes in a newly (MM) diagnosed patients [42].
According to the results of multivariate Cox analysis, PLR is not a meaningful independent prognostic factor
and cannot be utilized to predict the( OS) and (PFS) of patients with multiple myeloma [43]. All of these results
may be because (PLR) considers both pro-tumor and anti-tumor immune status, which causes this index to be
imprecise because platelets and lymphocytes must be considered concurrently. The cut-off values for (NLR)
and (PLR) were inconsistent in prior cancer studies. As a result, we used (ROC) analysis to determine the
appropriate cut-off positions for the (PLR) and (NLR)[44].
As a consequence, we found that (PLR) is a significant predictor of overall and progression-free survival
for (MM) newly diagnosed patients. While NLR2 at diagnosis was related with a poor prognosis for individuals
with multiple myeloma who were treated, it could be a significant predictor for the outcome of therapy in
patients diagnosed with (MM). The predictive value of( PLR) and (NLR) in patients with multiple myeloma is
yet unknown. Additional potential studies are required to determine its benefit as a prognostic marker in (MM)
patients treated in normal practice.
CONCLUSION
From our data, we concluded that, platelets are essential for the progression of the disease regulation in the
bone marrow microenvironment of multiple myeloma. Further, and suggest a new prospective therapeutic
strategy that could target the platelet-cancer interaction and (IL-1) as a promising target for probable early
interventions of therapeutic or chemoprevention in( MM).
Acknowledgment
To our beloved University; Al Mustansiriyha for continuous support.
Disclaimer
The article has not been previously presented or published, and is not part of a thesis project.
Conflict of Interest
There are no financial, personal, or professional conflicts of interest to declare.
REFERENCES
1. Abramson, H.N. Monoclonal Antibodies for the Treatment of Multiple Myeloma: An Update. Int. J. Mol. Sci. 2018,19, 3924.
2. Kyle RA, Therneau TM, Rajkumar SV, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J
Med, 2006 , vol. 354 [pg. 1362- 1369].
3. Rajkumar, S.V.; Dimopoulos, M.A.; Palumbo, A, et al. International MyelomaWorking Group updated criteria for the
diagnosis of multiple myeloma. Lancet Oncol.2014, 15,[ e538–e548].
4. Cowan, A.J.; Allen, C.; Barac, A.et al. Global Burden of Multiple Myeloma: A Systematic Analysis for the Global Burden of
Disease Study2016. JAMA Oncol.2018, 4,[ pg1221–1227].
5. Sirohi B, Powles R. Epidemiology and outcomes research for MGUS,myeloma and amyloidosis. Eur J Cancer. 2006;42[11]:
[pg1671-1683].
6. Leuraud Klervi, Richardson David B, Cardis Elisabeth, et al. Ionising radiation and risk of death from leukaemia and
lymphoma in radiation-monitored workers [INWORKS]: an international cohort study. The Lancet Haematology. 2015; 2[7].

https://alqalam.utripoli.edu.ly/science/ eISSN 2707-7179
7. Ezoe Sachiko. Secondary Leukemia Associated with the Anti-Cancer Agent, Etoposide, a Topoisomerase II Inhibitor.
International Journal of Environmental Research and Public Health. 2012; 9[7].
8. Deschler Barbara, Lübbert Michael. Acute myeloid leukemia: Epidemiology and etiology. Cancer. 2006; 107[9].
9. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc.
2003;78[1]:21-33.
10. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc.
2003;78[1]:21-33.
11. Borregaard, N. Neutrophils, from marrow to microbes. Immunity 33, 657–670 [2010].
12. Thon JN, Peters CG, Machlus KR, Aslam R, Rowley J, Macleod H, et al. T granules in human platelets function in TLR9
organization and signaling. The Journal of Cell Biology. 2012;198[4]:561-57.
13. Intlekofer AM, Takemoto N, Wherry EJ, Longworth SA, Northrup JT, Palanivel VR, et al. Effector and memory CD81 T
cell fate coupled by T-bet and eomesodermin. Nat Immunol 2005;6:[pg1236-44].
14. Dimopoulos, M.A.; Sonneveld, P.; Leung, N.; Merlini, G.; Ludwig, H.; Kastritis, E.; Goldschmidt, H.;Joshua, D.; Orlowski,
R.Z.; Powles, R.; et al. International Myeloma Working Group Recommendations for the Diagnosis and Management of
Myeloma-Related Renal Impairment. J. Clin. Oncol. 2016, 34,[pg 1544–1557].
15. Kumar, S.; Paiva, B.; Anderson, K.C.; Durie, B.; Landgren, O.; Moreau, P.; Munshi, N.; Lonial, S.; Blade, J.; Mateos, M.V.;
et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in
multiple myeloma. Lancet Oncol. 2016, 17, [pge328–e346]
16. Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation. Nature 2008;454:[pg436-44].
17. Xue TC, Zhang L, Xie XY, et al. Prognostic significance of the neutrophil-to-lymphocyte ratio in primary liver cancer: a
meta-analysis. PLoS One 2014;9:[pge96072].
18. Bailey, S.E.R.; Ukoumunne, O.C.; Shephard, E.; Hamilton, W. How useful is thrombocytosis in predicting an underlying
cancer in primary care? a systematic review. Fam. Pract. 2017, 34,[pg 4–10]. [CrossRef] [PubMed]
19. Carr, B.I.; Guerra, V. Thrombocytosis and hepatocellular carcinoma. Dig. Dis. Sci. 2013, 58,[pg 1790–1796].
20. Hwang, S.G.; Kim, K.M.; Cheong, J.H.; Kim, H.I.; An, J.Y.; Hyung, W.J.; Noh, S.H. Impact of pretreatment thrombocytosis
on blood-borne metastasis and prognosis of gastric cancer. Eur. J. Surg. Oncol. 2012, 38,[pg 562–567].
21. Takizawa H, Boettcher S, Manz MG. Demand adapted regulation of early hematopoiesis in infection and inflammation.
Blood 2012;119:[pg2991- 3002].
22. Bryant C, Suen H, Brown R, Yang S, Favaloro J, Aklilu E, et al. Long term survival in multiple myeloma is associated with a
distinct immunological profile, which includes proliferative cytotoxic T cell clones and a favourable treg/Th17 balance.
Blood Cancer J 2013;3:[pge148].
23. Wongrakpanich S, George G, Chaiwatcharayut W, Biso S, Candelario N, Mittal V, et al. The prognostic significance of
neutrophil to lymphocyte and platelet to lymphocyte ratios in patients with multiple myeloma. J Clin Lab Anal 2016;30:
[pg1208- 13].
24. Romano A, Parrinello NL, Consoli ML, Marchionni L, Forte S, Conticello C, et al. Neutrophil to lymphocyte ratio [NLR]
improves the risk assessment of ISS staging in newly diagnosed MM patients treated upfront with novel agents. Ann Hematol
2015;94:[pg1875- 83].
25. Atallah JP, Mohammad F, Bhat A, Patel NJ, Azab B, Vivekanandrajah A, et al. Elevated neuthrophil: Lymphocyte ratio does
not predict survival in multipl myeloma patients. Blood 2013;122:[pg5336].
26. Solmaz, Serife Solmaz, Ozcan Uzun1 , Celal Acar, Omur Gokmen Sevindik2 , Ozden Piskin3 , Hayri Guner Ozsan3 , Fatih
Demirkan3 , Bulent Undar3 , Ahmet Alacacioglu4 , Mehmet Ali Ozcan3 , Inci Alacacioglu3, [Is the platelet to lymphocyte
ratio a new prognostic marker in multiple myeloma?], Journal of Laboratory Physicians - Volume 10, Issue 4, October-
December 2018
27. Kelkitli E, Atay H, Cilingir F, Güler N, Terzi Y, Ozatlı D, et al. Predicting survival for multiple myeloma patients using
baseline neutrophil/lymphocyte ratio. Ann Hematol 2014;93:841 6.
28. Ock CY, Nam AR, Lee J, et al. Prognostic implication of antitumor immunity measured by the neutrophillymphocyte ratio
and serum cytokines and angiogenic factors in gastric cancer. Gastric Cancer 2017;20:254-62.
29. Ethier JL, Desautels D, Templeton A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in breast cancer: a systematic
review and meta-analysis. Breast Cancer Res 2017;19:2-14.
30. Wei Y, Jiang YZ, Qian WH. Prognostic role of NLR in urinary cancers: a meta-analysis. PLoS One 2014;9:e92079.
31. Keam B, Ha H, Kim TM, et al. Neutrophil to lymphocyte ratio improves prognostic prediction of International Prognostic
Index for patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine
and prednisone. Leuk Lymphoma 2015;56:2032-8
32. Wang J, Zhou M, Xu JY, et al. Prognostic role of pretreatment neutrophil-lymphocyte ratio in patients with diffuse large B-
cell lymphoma treated with RCHOP. Medicine [Baltimore] 2016;95:e4893.

https://alqalam.utripoli.edu.ly/science/ eISSN 2707-7179
33. Zheng RR, Huang M, Jin C, et al. Cervical cancer systemic inflammation score: a novel predictor of prognosis. Oncotarget
2016;7:15230-42.
34. Martinet L, Garrido I, Filleron T, et al. Human solid tumors contain high endothelial venules: association with T- and B-
lymphocyte infiltration and favorable prognosis in breast cancer. Cancer Res 2011;71:5678-87.
35. Lu LC, Hsu CH. Tumor-associated neutrophils: an emerging player in the immune microenvironment of hepatocellular
carcinoma. Transl Cancer Res 2016;5:S296-9.
36. Moses K, Brandau S. Human neutrophils: their role in cancer and relation to myeloid-derived suppressor cells. Semin
Immunol 2016;28:187-96.
37. Wu J, Chen M, Liang C, et al. Prognostic value of the pretreatment neutrophil- to-lymphocyte ratio in cervical cancer: a
meta-analysis and systematic review. Oncotarget 2017;8:13400-12.
38. Shi L, Qin X, Wang H, Xia Y, Li Y, Chen X, et al. Elevated neutrophil to lymphocyte ratio and monocyte to lymphocyte
ratio and decreased platelet to lymphocyte ratio are associated with poor prognosis in multiple myeloma. Oncotarget
2017;8:18792 801.
39. Wongrakpanich S, George G, Chaiwatcharayut W, Biso S, Candelario N, Mittal V, et al. The prognostic significance of
neutrophil to lymphocyte and platelet to lymphocyte ratios in patients with multiple myeloma. J Clin Lab Anal 2016;30:1208
13.
40. Jung SH, Kim JS, Lee WS, Oh SJ, Ahn JS, Yang DH, et al. Prognostic value of the inverse platelet to lymphocyte ratio
[iPLR] in patients with multiple myeloma who were treated up front with a novel agent containing regimen. Ann Hematol
2016;95:55 61
41. TakagiS, TsukamotoS, ParkJ, JohnsonKE, KawanoY, MoschettaM, et al. Platelets enhance multiple myeloma progression
via IL 1β upregulation. Clin Cancer Res 2018;24:2430 9.
42. Shi L, Qin X, Wang H, Xia Y, Li Y, Chen X, et al. Elevated neutrophil to lymphocyte ratio and monocyte to lymphocyte
ratio and decreased platelet to lymphocyte ratio are associated with poor prognosis in multiple myeloma. Oncotarget
2017;8:18792 801
43. Li Y, Li H, Li W, Wang L, Yan Z, Yao Y, et al. Pretreatment Neutrophil/ Lymphocyte Ratio But Not Platelet/Lymphocyte
Ratio Has a Prognostic Impact in Multiple Myeloma. J Clin Lab Anal [2017] 31[5]:e22107. doi: 10.1002/jcla.22107
44. Ali AI, Nori W. Evaluation of Clinical Characteristics and Laboratory Results of COVID-19 Iraqi Pregnant Women.
AlQalam Journal of Medical and Applied Sciences. 2021 May 28;4(2):51-7.