Serum free light chains benefit diagnosis of multiple myeloma in orthopaedic patients with normal serum total proteins, creatinine, calcium and hemoglobin

doi:10.21203/rs.3.rs-2475294/v1

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Serum free light chains benefit diagnosis of multiple myeloma in orthopaedic patients with normal serum total proteins, creatinine, calcium and hemoglobin

https://doi.org/10.21203/rs.3.rs-2475294/v1

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Background:

A substantial number of MM patients with bone destruction are initially admitted into Orthopedics due to bone pain. However, routine laboratory tests usually fail to identify these patients and delay optimal therapy. Therefore, there is a clear medical need in early diagnose MM on these patient population.

Methods

Ninety-four orthopaedic patients were enrolled from July 2019 to December 2021. Of them, 42 patients were diagnosed as MM during postoperative pathology, but exhibited normal serum total proteins, creatinine, calcium and hemoglobin before operation. The rest 52 orthopaedic patients were pathologically excluded from MM and recruited into control group. The immunofixation electrophoresis (IFE) assays were performed to detect sFLC levels of all the subjects for comprehensively analyzed.

Results

The sFLC κ/λ ratios in 37 out of 42 MM patients were outside the reference range (0.31 ~ 1.56). All 42 MM patients were divided into two groups based on sFLC, κ/λ ratio > 1 or κ/λ < 1 respectively. And there were no significant differences in levels of serum total proteins, creatinine, calcium and hemoglobin between these two groups and control group.

Conclusions

This study highlighted the clinical significance of sFLC detection in early diagnosis of MM in orthopedics patients with unexplained bone destruction, supporting appropriate treatment choices preoperatively.

Biological sciences/Biochemistry

Biological sciences/Cancer

Orthopedics

serum free light chains

sFLC κ/λ ratio

multiple myeloma

immunofixation electrophoresis

Multiple myeloma (MM) is characterized by the clonal proliferation of malignant plasma cells in bone marrow and the presence of paraprotein in serum and urine, associated with organ dysfunction (1, 2). Elevated serum total proteins, creatinine, calcium, and low hemoglobin are the typical features of MM patients in laboratory examination. However, a population of MM patients from orthopaedic clinics barely show these typical laboratory features. Serum free light chains (SFLC) evaluation has been long recommended as a part of the International Myeloma Working Group (IMWG) guidelines for MM diagnosis and response assessment (3). This recommendation was based on the first commercialized sFLC detection assay kit- Freelite™ assay (The Binding Site Group Ltd, UK) developed in 2001 (4). To date, other kits are also available in market including the N Latex™ sFLC κ and λ (Siemens Healthcare Diagnostics GmbH, Germany), which utilize deviated sFLC κ/λ ratios (reference range 0.31 ~ 1.56) as the indicator of certain type of abnormal proliferation of monoclonal plasma cells (5). Although the value of this ratio solely can’t be directly used for making definitive diagnosis of MM, it is strongly associated with a high risk of MM. Additional tests such as immunofixation electrophoresis (IFE) assays and bone marrow biopsy examinations are applied to further confirm MM. In orthopaedic clinic, MM patients are sporadically admitted as bone injury initially. The typical changes with MM such as elevated serum total proteins, creatinine, calcium, and decreased hemoglobin are not observed on these patients before surgical operation, and they are usually identified post operation and confirmed by pathological examinations or bone marrow biopsy tests.

In this study, we recruited and analyzed postoperative pathology or tissue biopsy or bone marrow biopsy confirmed MM patients with normal levels of serum total proteins, creatinine, calcium and hemoglobin prior to operation. The subsequent analyses revealed that the serum level of immunoglobulin monoclonal protein (M-protein) was significantly decreased in these patients. Our results prove that sFLC κ/λ ratio through SFLC measurement and IFE assays has a great potential in improving the diagnosis of MM in orthopaedic patients.

1.1 Patient selection

This study was approved by Human Research Ethics Committee of XX Hospital and conducted according to the guidelines of Declaration of Helsinki. All the subjects investigated in this research had bone injury as clinical symptoms and admitted into the departments of spine or thoracic surgery from July 2019 to December 2021. The preoperative examinations including serum total proteins, creatinine, calcium and hemoglobin were shown normal on these patients. MM diagnoses were later made on the partial of these patients through pathological examination or bone marrow biopsy. Preoperative sFLC test was applied to determine MM diagnosis for these patients. Meanwhile patients with thoracolumbar fracture or spinal tumor were selected as control group, and patients with plasma cell tumor were excluded by postoperative pathology.

1.2 Laboratory analysis

Serum κ and λ FLC concentrations were measured by nephelometry, on a Dade-Behring BN™ II Analyzer (Siemens Healthcare Diagnostics GmbH, Germany) following the manufacturers’ instructions. Serum dilutions were using recommendation by the manufacturers. The sFLC κ/λ ratios were compared to the published reference range (κ/λ: 0.31 ~ 1.56). IFE assays were preformed using a Sebia Hydragel Protein kit and a Hydragel Immunofixation PE kit on a Hydrasys system to test the values of γ, α, µ, κ and λ immunoglobulin chains (Sebia, Lisses, France).

Serum total proteins, creatinine and calcium were detected on a Roche automatic biochemical analyzer cobas 8000, using commercial reagents (Roche Diagnostics, Mannheim, Germany). Hemoglobin was determined by a Sysmex XN-1000 automatic blood cell analyzer, and reagents were commercially provided by Sysmex (Sysmex Co., Japan).

1.3 Statistical analysis

Continuous variable data were tested to validate normal distribution. The results were shown as mean ± standard deviation (SD), and comparison between two groups of sample data was adopted independent sample t-test. The quartile method was used to represent data of skew distribution, and comparisons between two groups of sample data were adopted the Mann Whitney U nonparametric test. SPSS software version 26.0, Graphpad prism 8.0 and MedCalc version 20.0.14 were used for statistical analysis and mapping, P < 0.05 was considered as statistical significance.

2.1 Patient characteristics

In this study, a total of 42 MM patients were enrolled as research subjects. These patients were divided into two groups by sFLC κ/λ ratio: group A (n = 25, κ/λ > 1, indicating kappa FLC proliferation) and group B (n = 17, κ/λ < 1, indicating lambda proliferation). Among all patients, 34 patients had bone lesions, 6 patients had low back pain possibly due to bone destruction, 1 patient found mediastinal space occupation during physical examination, and 1 patient had chest tightness. The serum total proteins, creatinine, calcium and hemoglobin were within reference ranges before operation on all these subjects. 32 out of 42 patients underwent surgery or bone puncture in the Department of Orthopedics, while others were directly transferred to the Department of Hematology for further treatment because of abnormal values of sFLC detected before operation. After all, all the patients had confirmed definitively diagnosed of MM by postoperative pathology or tissue biopsy or bone marrow biopsy. The details of clinical characteristics were shown in (Table 1). Concurrently, another 52 patients who were hospitalized for spinal surgery were selected into control group in the same period. These patients were also tested for sFLC and had postoperative pathology examinations to exclude from MM. All the results of sFLC and IFE assays were obtained prior to any chemotherapy and within one month after surgery.

Table 1

Clinical Characteristics of Study Participants with multiple myeloma
Case	Gender	Age	Serum IFE	Urine IFE	Admission diagnosis or main clinical manifestations	Treatment plan
Group A(n = 25)
1	female	54	negative	Only κ light chain	C7 vertebral bone destruction	Surgical resection of lesions
2	female	62	negative	Only κ light chain	T4 degenerative thoracic spine	Surgical resection of lesions
3	female	66	negative	Only κ light chain	Sacrum Intraspinal space occupying	Microsurgical resection of lesions
4	male	49	Only κ light chain	Only κ light chain	The mass of right clavicle is gradually enlarged	Biopsy of clavicle
5	female	65	negative	negative	Undetermined tumor of spine	Puncture biopsy of lumbar lesions
6	male	52	negative	Only κ light chain	Pathological fracture of T9 thoracic vertebra	Closed reduction and internal fixation of thoracic fracture
7	male	56	negative	negative	Left femur mass with pain	Surgical removal of lesion mass
8	male	53	negative	Only κ light chain	Right clavicle pain and bone destruction	Clavicle biopsy
9	male	56	negative	negative	Lesion of the 7th cervical vertebra,, undetermined tumor of spine	Surgical resection of lesions
10	male	72	IgGκ	Only κ light chain	Abnormal signal of T2 vertebral body, considering metastatic cancer	Bone graft fusion and screw rod internal fixation
11	female	46	negative	Only κ light chain	Pathological fracture of thoracic vertebra (T7-11)	Transferred to hematology department without surgical
12	female	68	IgAλ	Only κ light chain	Tumor pathological fracture of left humerus and right femur	Excision of lesion of femur
13	male	53	Only κ light chain	negative	Sacral tumor with pain	Spinal joint biopsy
14	female	69	negative	negative	Bone destruction of the 7th cervical vertebra	Surgical resection and implantation of fusion
15	male	75	Not done	Not done	Compression fracture of the 12th thoracic vertebra	Biopsy of thoracic vertebrae
16	male	67	negative	negative	Low back pain, possible bone destruction	Transferred to hematology department without surgical
17	female	42	Only κ light chain	Only κ light chain	Low back pain, possible bone destruction	Transferred to hematology department without surgical
18	male	71	negative	Only κ light chain	Subpleural space occupying involving ribs	Biopsy of rib lesion
19	male	66	IgAκ	negative	Pathological fracture of humerus (left)	Excision of lesion of humerus
20	male	51	negative	negative	Clavicular mass (left) with pain	Puncture biopsy of sternoclavicular joint
21	female	73	IgAκ	Only κ light chain	Skull bone space occupying with defect	Skull lesion excision and skull titanium plate implantation
22	male	60	Only κ light chain	Only κ light chain	Low back pain for 2 months, possible bone destruction	Bone cement surgery was performed in the local county-level hospital a month ago
23	male	60	negative	Only κ light chain	Low back pain, possible bone destruction	Transferred to hematology department without surgical
24	female	56	IgGκ	negative	Pathological fracture of cervical spine	Excision of cervical vertebra lesion
25	male	72	IgGκ	Not done	Compression fracture of the 8th thoracic vertebra	Excision of thoracic vertebra lesion
Group B(n = 17)
26	male	58	Only λ light chain	Only λ light chain	Left 7th rib bone destruction with soft tissue mass	Surgical resection of rib lesions
27	female	54	IgAλ	negative	CT showed a goose egg size tumor in the 11th rib	Excision of right 11th rib lesion
28	male	50	Only λ light chain	Only λ light chain	Destruction of sternal stalk and second bone of right rib	Sternal puncture biopsy
29	male	53	Only λ light chain	negative	sacral tumor with pain	Sacral biopsy
30	female	66	Only λ light chain	Only λ light chain	Fourth lumbar compression fracture	Transferred to hematology department without surgical
31	male	54	IgGλ	negative	Bone destruction of left iliac bone and left sacrum	Biopsy of left iliac bone and left sacral bone lesions
32	male	51	negative	negative	Destruction of left iliac bone	Excision of lesion of left iliac bone
33	male	48	Only λ light chain	Only λ light chain	Sternal mass, no obvious tenderness, bone destruction on PET-CT.	Puncture biopsy of sternal angle lesions
34	female	55	Only λ light chain	Not done	Low back pain, possible bone destruction	Transferred to hematology department without surgical
35	male	62	negative	negative	Tenderness in the left chest, pathological fracture of the 4th flank	Transferred to hematology department without surgical
36	female	56	IgGλ	Only λ light chain	Mediastinal space occupying was found during physical examination	Surgical resection of lesions
37	male	49	Only λ light chain	negative	Costal pain for more than 1 year, CT showed rib bone destruction.	Transferred to hematology department without surgical
38	male	68	negative	negative	Low back pain, PETCT showed multiple bone destruction	Transferred to hematology department without surgical
39	female	58	Not done	Only λ light chain	Chest tightness	Transferred to hematology department without surgical
40	male	59	IgGλ	negative	Fracture of the second lumbar spine	Excision of lumbar vertebra lesion and Lumbar fusion
41	male	77	negative	negative	Pathological fracture of the first thoracic vertebra	Biopsy of thoracic vertebra
42	female	51	IgAλ	Only λ light chain	Limb joint and lumbar pain	Transferred to hematology department without surgical

2.2 Comparison of routine biochemical and sFLC analyses

The values of serum total proteins, albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, glutamyltransferase, urea, creatinine, calcium, hemoglobin, and platelet count haven’t shown any significant differences among A, B and control group (Table 2 and Fig. 1A). However, immunoglobulin light chain κ/λ ratios and sFLC κ/λ ratios in both group A and group B were statistically different from those in control group. sFLC κ/λ ratios have more obvious alterations than immunoglobulin light chain κ/λ ratios do (Figs. 2A and 2B). In MM group, abnormal immunoglobulin light chain κ/λ ratios were found in 31 cases (73.8%), while sFLC κ/λ ratios in 37 cases (88.1%) were out of reference range. Five patients (11.9%) presented sFLC κ/λ ratios within the reference range, and were all from group B. Three of the five patients have abnormal immunoglobulin light chain κ/λ ratios and positive serum IFE results. Two patients (Patient No. 32 and 41) were negative in both serum and urine IFE assays (Table 1).

Table 2

Clinical characteristics and analytical data of study participants with multiple myeloma and contrast group
Characteristic	Reference Range	Group A (Multiple myeloma with increased FK/FL ratio) (n = 25)	Group B (Multiple myeloma with reduced FK/FL ratio) (n = 17)	Control Group (n = 52)	P Value^a	P Value^b
Age,mean years(SD)		60.6(9.2)	57.0(7.6)	67.5(7.9)
Age range		42–75	48–77	48–78
Male, n(%)		15(60.0%)	10(58.8%)	32(61.5%)
Kappa (g/L)	1.70–3.70	2.49(1.82, 4.19)	1.53(1.02, 1.82)	2.72(2.30, 3.18)	0.732	0.000
Lambda (g/L)	0.90–2.10	0.96(0.57, 1.30)	1.68(1.10, 2.79)	1.64(1.30, 1.87)	0.000	0.770
Kappa/Lambda	1.35–2.65	3.11(2.03, 4.24)	1.07(0.50, 1.36)	1.77(1.48, 1.93)	0.000	0.000
Free Kappa (mg/L)	6.70–22.40	501.00(218.50, 1475.00)	15.50(9.48, 20.40)	21.10(17.70, 27.87)	0.000	0.011
Free Lambda (mg/L)	8.30–27.00	19.7(12.450, 34.70)	276.00(66.50, 636.50)	26.90(21.70, 32.07)	0.197	0.000
Free Kappa/Free Lambda	0.31–1.56	35.00(9.41, 79.04)	0.05(0.01, 0.42)	0.80(0.68, 0.99)	0.000	0.000
Total Protein (g/L)	65.0–85.0	65.628 ± 5.7947	66.847 ± 5.9253	67.213 ± 4.5451	0.195	0.790
Albumin (g/L)	40.0–55.0	41.104 ± 4.5000	42.406 ± 4.2983	40.075 ± 3.9960	0.313	0.044
Globulin (g/L)	20.0–40.0	24.524 ± 4.4098	24.441 ± 6.3797	27.150 ± 4.2342	0.014	0.049
Albumin / Globulin		1.7384 ± 0.40278	1.870 ± 0.60458	1.5208 ± 0.32180	0.013	0.003
Total Bilirubin (µmol/L)	0.0–23.0	12.60(10.80, 15.90)	13.20(10.70, 18.70)	14.20(11.20, 16.65)	0.765	0.933
Direct Bilirubin (µmol/L)	0.0–8.0	5.00(3.90, 5.45)	3.90(3.25, 6.75)	5.25(3.20, 6.20)	0.571	0.754
Alanine aminotransferase (U/L)	9.0–50.0	23.00(15.00, 49.50)	21.00(14.00, 37.00)	22.00(13.25, 30.75)	0.257	0.707
Aspartate aminotransferase (U/L)	15.0–40.0	20.00(17.00, 27.00)	17.00(12.50, 26.00)	19.00(15.25, 24.00)	0.283	0.383
Alkaline phosphatase (U/L)	45.0-125.0	88.00(67.00, 121.00)	84.00(69.50, 98.50)	103.50(85.50, 129.00)	0.118	0.018
Gammaglutamyltransferase (U/L)	10.0–60.0	22.00(15.50, 50.00)	20.00(13.00, 33.50)	29.00(17.00, 43.75)	0.648	0.172
Urea (mmol/L)	3.60–9.50	5.5236 ± 2.09115	5.8353 ± 1.33197	5.6702 ± 1.74480	0.747	0.722
Creatinine (µmol/L)	57.0-111.0	64.08 ± 14.106	66.12 ± 14.313	62.29 ± 14.098	0.604	0.336
Calcium (mmol/L)	2.11–2.52	2.3644 ± 0.14672	2.3606 ± 0.12382	2.3077 ± 0.10730	0.059	0.094
IgG (g/L)	7.60–16.60	7.68(5.89, 10.82)	7.37(4.58, 8.77)
IgA (g/L)	0.71–3.35	1.12(0.41, 2.42)	0.85(0.45, 2.05)
IgM (g/L)	0.48–2.12	0.44(0.24, 0.72)	0.26(0.16, 0.84)
Haemoglobin (g/L)	130–175	125.56 ± 11.962	135.18 ± 18.709	130.08 ± 16.617	0.228	0.291
Platelet counts (×10⁹/L)	125–350	223.80 ± 70.958	227.18 ± 88.796	238.13 ± 95.862	0.509	0.679
Note–Continuous variables are described by their quartiles[median(25thpercentile,75thpercentile)for nonormal distribution or means ± standard for normal distribution].
^a P Values between participants(all participants with Kapp Group and Contrast Group)calculated with unpaired Student t test(for normal distribution) or Mann-Whitney U test (for nonnormal distribution) with continuous variables or χ² test with categorical variables.
^bP Values between participants(all participants with Lamb Group and Contrast Group)calculated with unpaired Student t test(for normal distribution) or Mann-Whitney U test (for nonnormal distribution) with continuous variables or χ² test with categorical variables.

2.3 SFLC response evaluation for MM diagnosis

In order to evaluate the diagnostic values of immunoglobulin light chain κ/λ ratio and sFLC κ/λ ratio for this specific MM population, a ROC curve was made with sensitivity as ordinate and (1-specificity) as abscissa according to the postoperative pathology and/or bone marrow biopsy as gold standard. SFLC κ/λ ratio (AUC = 1.000) vs. immunoglobulin light chain κ/λ ratio (AUC = 0.833) were compared and presented with P = 0.0108. The diagnostic performance of sFLC κ/λ ratio for MM with bone injury in group A was significantly higher than that of immunoglobulin light chain κ/λ ratio (Fig. 2C). The specific comparative analyses were as follows: SFLC κ/λ ratio (AUC = 0.947) vs. immunoglobulin light chain κ/λ ratio (AUC = 0.935), P = 0.7688; combining sFLC κ/λ ratio and immunoglobulin light chain κ/λ ratio (AUC = 0.967) vs. immunoglobulin light chain κ/λ ratio (AUC = 0.935), P = 0.2369; combining sFLC κ/λ ratio and immunoglobulin light chain κ/λ ratio (AUC = 0.967) vs. immunoglobulin light chain κ/λ ratio (AUC = 0.947), P = 0.2569. Although the diagnostic performance of sFLC κ/λ ratio for MM with bone injury in group B was higher than that of immunoglobulin light chain κ/λ ratio, it did not show statistical significance even if sFLC κ/λ ratio and immunoglobulin light chain κ/λ ratio were combined together (Fig. 2D).

2.4 Negative IFE assay in certain patients with MM

A total of 40 out of total 42 MM patients completed identification of serum IFE (the rest two cases were not tested owing to insufficient specimens). Negative results were demonstrated in 14 cases (58.3%) in group A and 4 cases (25.0%) in group B (Fig. 1C). Among these patients, immunoglobulin light chain κ/λ ratios were found within reference ranges in 9 cases (50%) and slightly abnormal in the rest 9 cases (50%).

2.5 Normal levels of serum IgG, IgA and IgM in most patients with MM

Among the 42 MM patients with bone injury as clinical manifestation, a total of 38 patients had tests on serum IgG, IgA and IgM (the rest four cases due to insufficient specimens), including 2 cases with elevated IgG, 4 with elevated IgA, but no cases showing elevated IgM (Fig. 1B). 7 patients (Patient No. 3, 16, 17, 22, 23, 26 and 35; Table 1) have low levels of serum IgG, IgA and IgM out of the reference range.

MM is the second most common hematological malignancy in the world (6, 7). SFLC has long become a valuable marker for diagnosing and monitoring light-chain MM, amyloid light-chain amyloidosis, and monoclonal gammopathies of undetermined significance (MGUS) (8–12). According to the IMWG diagnostic criteria, sFLC assay is recommended for disease surveillance in oligo-secretory and micromolecular MM (13).

The typical manifestations of MM are often accompanied with elevated levels of serum total proteins and creatinine, hypercalcemia and anemia. We found some orthopaedic patients have normal results in these preoperative laboratory tests but confirmed to be MM by postoperative pathology. The purpose of this study was to explore the diagnostic values of sFLC in atypical MM patient population with bone injury as clinical manifestation. Our findings revealed that the immunoglobulin light chain κ/λ ratios and sFLC κ/λ ratios from 42 bone injured atypical MM patients were significantly different from control group (MM pathological excluded after orthopedic surgery). The change of sFLC κ/λ ratios is more significant than that of immunoglobulin light chain κ/λ ratios, indicating that a test on sFLC κ/λ ratio could support a more precise diagnosis for those MM patients shown in orthopedic clinics, especially for patients with unexplained bone destruction.

In this study, sFLC κ/λ ratios were abnormal in 88.1% in MM patients from orthopaedic (37 cases), and the rest (5 cases) were inside the reference range. Three of the 5 cases had abnormal immunoglobulin light chain κ/λ ratios and positive results in serum IFE assays. In clinical practice, usually for immunoglobulin light chain κ/λ For patients with abnormal ratio, the serum M protein level is usually high through serum protein electrophoresis, so the serum IFE test is positive. Although sFLC κ/λ ratios may be within reference ranges in these patients, abnormal immunoglobulin light chain κ/λ ratios and positive IFE assay results can be a clear indicator for making a diagnosis of MM. The two patients (Patient No. 32 and 41 in Table 1) in the study had normal sFLC κ/λ ratios and immunoglobulin light chains κ/λ ratio, and negative results in their serum and urine IFE assays. These are non secretory M protein myeloma patients or their M-protein levels were below the detection limit of IFE assay, so this type of patients might have to rely on tissue biopsy to get diagnosed.

The serum IFE assay is recognized as a “gold standard” to confirm the presence of M-protein (14). However, patients with oligo-secretory and non-secretory MM usually have a negative or weakly positive result in IFE test, so sFLC identification can improve the detection rate of MM in these population. The M-protein of orthopedic patients in this study is at a low level as well. Serum IFE assays contributed to negative results in 14 cases (58.3%) of group A and 4 cases (25.0%) of group B. Among these 18 patients, 9 (50%) had normal immunoglobulin light chain κ/λ ratios and the other 9 (50%) had slightly abnormal. It is speculated that the level of M-protein was associated with immunoglobulin light chain κ/λ ratios. The low level of M-protein (under the detection limit of IFE assay) directly resulted in negative readouts in these 18 patients. Thus detection in sFLC κ/λ ratio can be a good and beneficial supplement to IFE assay. Combining these two assays would be more helpful to improve the detection rate and accuracy of MM. It is worth noting that sFLC κ/λ ratio is not a final proof of monoclonal gammopathy. Any abnormal sFLC κ/λ ratios need be further confirmed by IFE assays and/or bone marrow biopsy (15, 16). The present study pointed out that MM should be highly suspected in patients with unexplained bone damage and abnormal sFLC κ/λ ratios. Further tissue or bone marrow biopsy is required in these patients, even IFE assay results are negative. Through detection of serum IgG, IgA and IgM, it turned out that immunoglobulin was within reference ranges in most patients. There were several cases with elevated IgG and IgA, but no patients with elevated IgM were found. Probably patients with elevated IgM may have other symptoms before bone damage.

Previous studies reported that prognosis of solitary plasmacytoma of bone (SPB) varied remarkably. Some patients recovered after surgical removal or local fractional radiation therapy, and others progressed to MM years later (17–23). In some patients having no any progression risk factors, their SPB of lumbar vertebra may develop into MM in less than two months later despite appropriate treatments (24). Patient No. 22 in this study have persistent bone pain which was not relieved after spinal surgery in a local hospital (Table 1). He had a very high value of sFLC κ/λ ratio at the one-month visit and was diagnosed with MM then. It can be speculated that surgery procedure could accelerate the dissemination of MM cells and may lead to be a considerable risk factor for MM patients potentially. More importantly tremendous progress has been made in MM treatments, thereby early and accurate diagnosis of MM is increasingly meaningful in improving the prognosis (25–27).

In summary, orthopaedic MM patients with unexplained bone destruction frequently fail to get right diagnosis by routine laboratory examinations. sFLC identification should be considered as a supplement tool to support an early diagnosis, and lead to more reasonable treatment choices preoperatively in clinic.

Ethical Approval

This study was approved by Human Research Ethics Committee of the First Affiliated Hospital of Anhui Medical University, and conducted according to the guidelines of Declaration of Helsinki.

statement confirming

Informed consent was obtained from all subjects and/or their legal guardian(s).

Competing interests

The authors declare no Competing interest relevant to this study.

Funding

No funding received.

Authors' contributions

All authors wrote the main manuscript text . All authors prepared figures 1-2. All authors reviewed the manuscript.

Availability of data and materials

The datasets used or analysed during the current study are available from the corresponding author on reasonable request.

Declaration of Interest

No conflicts of interest to declare.

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No competing interests reported.

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Serum free light chains benefit diagnosis of multiple myeloma in orthopaedic patients with normal serum total proteins, creatinine, calcium and hemoglobin

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Abstract

Background:

Methods

Results

Conclusions

Figures

Introduction

Materials And Methods

1.1 Patient selection

1.2 Laboratory analysis

1.3 Statistical analysis

Results

2.1 Patient characteristics

2.2 Comparison of routine biochemical and sFLC analyses

2.3 SFLC response evaluation for MM diagnosis

2.4 Negative IFE assay in certain patients with MM

2.5 Normal levels of serum IgG, IgA and IgM in most patients with MM

Discussion

Conclusions

Declarations

References

Additional Declarations

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