Low peripheral blood B lymphocyte count predict poor outcome in patients with multiple myeloma

Low peripheral blood B lymphocyte count predict poor outcome in patients with multiple myeloma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Low peripheral blood B lymphocyte count predict poor outcome in patients with multiple myeloma Yuqi Wang, Zhongxin Zheng, Qiaoxi Kang, Linjing Cai, Shanshan Zhang, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5358538/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Previous evidence suggested that B lymphocyte may involve in the progression and prognosis of multiple myeloma (MM). However, the prognostic value of peripheral B lymphocyte counts on MM before and after treatment in the novel agent era was rare reported. Herein, we conducted a retrospective study in our center to detect peripheral B lymphocyte counts by flow cytometry in 110 patients with MM at our center and explore the relation with survival. The B lymphocyte count was significantly lower in MM patients than healthy controls (p < 0.005). The cutoff value of B lymphocyte count at diagnosis was 49/µl in MM and 94 patients divided into in high B lymphocyte group. Patients with low B lymphocyte count had a significant shorter progression-free survival (PFS) (p = 0.025) and a trend of unfavorable overall survival (OS) (p = 0.053) at diagnosis and after 4 cycles’ induction treatments. Furthermore, Multivariate analysis showed that low B lymphocyte count at diagnosis independent of ISS stage was a significantly inferior marker for predicting PFS (p = 0.027, hazard ratio(HR) 2.281, 95% confidence interval (CI) 1.098–4.741) and a trend for OS (p = 0.083, HR 2.394, 95% CI 0.896–6.160). In summary, these results suggested the low B lymphocyte count was associated with poor outcome in MM patients at diagnosis and after treatment in the novel agent era. Multiple myeloma B lymphocyte Outcome Dynamic change Immune profiles Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1 Introduction Multiple myeloma (MM) is the second most common hematological malignant disorder, characterized by the infiltration of monoclonal plasma cells in bone marrow and related organs or tissues impairment. The revised international staging system (R-ISS) is now widely used in clinical practice, which focusing on clinical markers and cytogenetic abnormalities at diagnosis( 1 – 3 ). Immune profiles have been proved to play a crucial role in the pathogenesis and progression of MM( 4 , 5 ).The addition of immune profiles may improve the prediction ability in patients with MM( 6 – 8 ). B lymphocyte is a kind of lymphocytes component. Activated by tumor antigen, B lymphocytes secrete antibodies, which can activate complement system to lyses tumor cells or mediate macrophages, NK cells to exert antibody-dependent cell-mediated cytotoxicity (ADCC) effect( 9 , 10 ).Previous studies indicated that higher circulating blood B cells at diagnosis were a favorable prognostic marker without apparent relationship to circulating plasma cells in patients with multiple myeloma( 11 – 13 ).The depleted B cells in patients with monoclonal gammopathy of undetermined significance and MM were finally recovered after long-term disease control in both the bone marrow and peripheral blood( 9 , 14 ). These data implied B lymphocyte may involve in the progression and prognosis of multiple myeloma. However, the prognostic value of peripheral blood B lymphocyte on multiple myeloma in the novel agent era was rare reported. Therefore, we detected the B lymphocyte count in peripheral blood at diagnosis and after treatment by multiparameter flow cytometry (MFC) to explore the prognostic value and dynamic change of B lymphocyte count in patients with MM. 2 Methods 2.1 Patients Newly diagnosed multiple myeloma (NDMM) patients in Nanfang Hospital, Southern Medical University from January 2020 to January 2023 were enrolled in this study. All patients were diagnosed according to the International Myeloma Working Group (IMWG) criteria( 15 ) and treated with proteasome inhibitor (PI) and/or immunomodulatory (IMiDs) based regimen as first-line treatment after diagnosis. Patients with other malignant tumors, immune deficiency diseases, autoimmune diseases, rheumatism diseases and missing B lymphocyte count were excluded. Patients with good response after four cycles of induction treatment would undergo autologous peripheral blood stem cell transplantation (ASCT) or continue the same regimen as consolidation therapy. Besides, 63 individuals for health physical examination were also recruited in our center as normal control. This study was approved by the Ethics Committee of Southern Medical University affiliated Nanfang Hospital. 2.2 B lymphocytes detection by multiparameter flow cytometry Peripheral blood B lymphocyte was analyzed using fresh peripheral blood samples according to the standard procedure. The following conjugates of monoclonal antibodies were used: anti-CD3-PerCP-Cy5.5 and anti-CD19-PE-Cy7 (BD Biosciences, San Jose, CA, USA). The frequencies of lymphocytes were determined using a FACS Calibur flow cytometer (Becton Dickinson, Franklin Lakes, NJ, USA) and CellQuest software (BD Biosciences) was used for data analysis. At least 5×10 4 events were measured with each sample. B lymphocytes were defined as CD3-CD19 + lymphocytes and recorded as absolute number of cells/µl(normal range: 98.71–364.86 cells/µl) and was detected at diagnosis and the beginning of each cycle of induction therapy: T0, at diagnosis; T1, at the beginning of the second cycle of induction therapy; T2, at the beginning of the third cycle; T3, at the beginning of the fourth cycle; T4, at the beginning of the fifth cycle. 2.3 Statistical analysis Differences between nominal variables were evaluated using the Chi-Square test, and continuous variables were assessed using the Mann-Whitney U test. Optimal cutoff value was detected as a biomarker of survival by surv_cutpoint function. Overall survival (OS) and progression-free survival (PFS) distribution were analyzed by Kaplan-Meier (K-M) curves and log-rank test was applied to estimate differences between different groups. The univariable and multivariable analysis of survival were carried out by Cox regression model. All reported p-values were two-sided and confidence intervals refer to 95% boundaries, and statistical difference was considered as p-value less than 0.05. Statistical analyses were performed using the R4.4.1. 3 Results 3.1 Patients’ characteristics A total of 110 NDMM patient were included in our study. 56 (50.9%) patients were older than 60 years and the male-to-female ratio was 1.75:1. 66 (59.1%) patients were classified as IgG type, and 23 (20.9%) patients belonged to Light Chain type. According to DurieSalmon System (DS), 9 (8.2%) patients were at stage I, 14(12.7%) at stage II, and 87 (79.1%) at stage III. Based on International Staging System (ISS), 18(16.4%) patients were classified as stage I, 36(32.7%) as stage II, and 56 (50.9%) as stage III. Among the 65 (59.1%) patients who received the FISH test, 11 patients (16.9%) were classified as high risk who had 17p-, t (4;14) or t (14;16), while others were classified as standard risk. The most common induction regimen was bortezomib-based regimen in 101 (91.4%) patients, among which 54.5% (60) received a combination with lenalidomide and dexamethasone (VRD) and 37.3% (41) combination with cyclophosphamide and dexamethasone (VCD). Fifty-nine patients (53.6%) underwent ASCT after induction treatment. The baseline characteristics of all patients were summarized in Table 1 . Table 1 Patients’ baseline characteristics and clinical feature Patients' characters n(%) Patients' characters n(%) Sex ISS Stage Male 70 (63.6) I 18 (16.4) female 40 (36.4) II 36 (32.7) III 56 (50.9) Age CA by FISH ≥ 60 56 (50.9) High risk 11 (10.0) < 60 54 (49.1) Standard risk 54 (49.1) Unknown 45 (40.9) Type Regimen IgG 66 (59.1) VCD 41 (37.3) IgA 17 (15.5) VRD 60 (54.5) IgD 2 (1.8) Others 9 (8.2) Light Chain 23 (20.9) ASCT Others 2 (1.8) Yes 60 (54.5) No 50 (45.5) DS Stage Clinical Features median [IQR] I 9 (8.2) HBG (g/L) 88.50 [70.00, 121.75] II 14 (12.7) CR(µmol/L) 92.50 [71.00, 192.75] III 87 (79.1) Ca(mmol/L) 2.27 [2.14, 2.46] M-protein(g/L) 31.52 [4.53, 52.77] Renal Function Stage β2-MG(mg/L) 5.52 [3.42, 13.40] ALB(g/L) 32.95 [27.85, 38.05] A 83 (75.5) LDH(U/L) 169.50 [123.75, 225.75] B 27 (24.5) PCs(%) 25.50 [13.00, 44.00] Abbreviations: DS Durie Salmon, ISS International Stage System, CA Chromosomal Abnormalities [defined by the presence of del(17p): translocation t( 4 , 14 ): or translocation t( 14 , 16 )], FISH Fluorescent in situ hybridization, VCD bortezomib + cyclophosphamide + dexamethasone, VRD bortezomib + lenalidomide + dexamethasone, ASCT Autologous Stem Cell Transplantation, HBG: Hemoglobin, Cr Creatinine, β2-MG β2-Microglobulin, ALB Albumin, LDH Lactate Dehydrogenase. 3.2 The clinical and prognostic value of B lymphocyte in NDMM The mean B lymphocyte count was 131/µl(range, 6–676/µl) in our NDMM patients at diagnosis and 218.05/µl(range, 66.7–650.95/µl) in 63 healthy controls (HCs). The B lymphocyte count of MM patients was significantly lower than that of the health donors (p < 0.001, Fig. 1 ). The optimal B lymphocyte count cutoff value was determined as 49/µl(p < 0.05, Supplement Fig. 1 ) by using the surv_cutpoint function. All patients were divided into two groups: 94 patients in high B lymphocyte group and the left 16 patients in low B lymphocyte group. No significant differences were found in common clinical parameters including age, gender, hemoglobin, serum creatinine, serum calcium, serum lactate dehydrogenase, serum β2-microglobulin, subtypes and ISS stage between these two groups (p > 0.05), as shown in Table 2 . Table 2 Patients’ characteristics based on B lymphocyte level at diagnosis Parameters, n (%) Total B lymphocyte counts P-value > 49/ul(n = 94) ≤ 49/ul(n = 16) Gender Male 70 (63.64) 57 (60.64) 13 (81.25) 0.193 Female 40 (36.36) 37 (39.36) 3 (18.75) Age ≥ 60 years 56 (50.91) 45 (47.87) 11 (68.75) 0.203 < 60 years 54 (49.09) 49 (52.13) 5 (31.25) HBG ≥ 85g/L 38 (46.34) 32 (46.38) 6 (46.15) 1.000 < 85g/L 44 (53.66) 37 (53.62) 7 (53.85) Cr ≥ 177umol/L 82 (74.55) 72 (76.60) 10 (62.50) 0.376 < 177umol/L 28 (25.45) 22 (23.40) 6 (37.50) Ca ≥ 2.65mmol/L 17 (15.45) 12 (12.77) 5 (31.25) 0.129 < 2.65mmol/L 93 (84.55) 82 (87.23) 11 (68.75) β2-MG ≥ 5.5mg/L 54 (49.09) 48 (51.06) 6 (37.50) 0.464 < 5.5mg/L 56 (50.91) 46 (48.94) 10 (62.50) ALB ≥ 35g/L 66 (60.00) 59 (62.77) 7 (43.75) 0.246 < 35g/L 44 (40.00) 35 (37.23) 9 (56.25) LDH ≥ 250U/L 17 (15.45) 16 (17.02) 1 (6.25) 0.467 < 250U/L 93 (84.55) 78 (82.98) 15 (93.75) HR-CA by FISH HR 11 (10.00) 11 (11.70) 0 (0.00) 0.324 SR 54 (49.09) 46 (48.94) 8 (50.00) Unknown 45 (40.91) 37 (39.36) 8 (50.00) DS Stage I-II 23 (20.91) 20 (20.20) 3(18.75) 0.354 III 87 (79.09) 74 (78.72) 13 (81.25) ISS Stage I-II 54 (49.09) 48 (51.06) 6(37.5) 0.424 III 56 (50.91) 46 (48.94) 10 (62.50) Regimen VCD 41 (37.27) 34 (36.17) 7 (43.75) 0.595 VRD 60 (54.55) 53 (56.38) 7 (43.75) Others 9 (8.18) 7 (7.45) 2 (12.50) ASCT YES 60 (54.55) 54 (57.45) 6 (37.50) 0.226 NO 50 (45.45) 40 (42.55) 10 (62.50) Abbreviations: DS Durie Salmon, ISS International Stage System, HR-CA High-Risk Chromosomal Abnormalities [defined by the presence of del(17p): translocation t( 4 , 14 ): or translocation t( 14 , 16 )], FISH Fluorescent in situ hybridization,ASCT autologous stem cell transplantation, HBG: Hemoglobin, Cr creatinine, β2-MG β2-microglobulin, ALB albumin, LDH lactate dehydrogenase. We also explored the dynamic change of B lymphocyte in MM patients during induction treatment. A total of 74 patients finished 4 cycles’ induction treatment: 42 (56.8%) patients received VRD and 27(36.5%) of them received VCD regimens. The B lymphocyte count was dramatically decreased after the first cycle of induction (P 0.05, Fig. 3 ). No significant difference was found between VCD and VRD regimen at each cycle (P > 0.05, Fig. 2 ). With a median follow-up of 27.77 months (range,0.17–51.83 months), 38 patients (34.5%) suffered relapse or progression and 21 patients (19.1%) died. Among them, 10 patients died of MM, 8 patients died of infection and 3 patients died of unknown cause. Patients with low B lymphocyte count had a significant shorter PFS (median PFS 25.8 months vs. not reached, p = 0.025, Fig. 3 A) and a trend of unfavorable OS (both median OS were not reached, p = 0.053, Fig. 3 B) than those with high B lymphocyte level. And then subgroup analysis was conducted based on lymphocyte levels and ISS staging to examine the impact of lymphocyte levels on prognosis in patients at different stages. Consequently, patients in ISS stage III with low B lymphocyte count had a significant shorter PFS (median PFS 19.2 months vs. 42.5 months, p = 0.004, Fig. 4 B), while the difference of outcomes in patients in ISS stage I or II with different B lymphocyte level were non-significant(Fig. 4 A).Furthermore, we explored the prognostic value of B lymphocyte change during induction treatment and found low B lymphocyte count after 4 cycles’ treatment could be a stable unfavorable marker for both PFS (p = 0.001, Fig. 5 A) and OS (p<0.0001, Fig. 5 B). Multivariate analysis showed that low B lymphocyte count at diagnosis independent of ISS stage was a significantly inferior marker for predicting PFS (p = 0.027, hazard ratio(HR) 2.281, 95% confidence interval (CI) 1.098–4.741) and a trend for OS (p = 0.083, HR 2.394, 95% CI 0.896–6.160). The multivariate survival analysis was shown in Table 3 . Table 3 Univariate analysis and multivariate analysis for overall survival and progression-free survival in patients with newly diagnosed multiple myeloma Risk factor Univariate analysis Multivariate analysis HR 95% CI P-value HR 95% CI P-value OS ISS Stage III 2.303 0.920–5.767 0.075 2.209 0.877–5.562 0.093 B lymphocyte counts ≤ 49/ul 2.490 0.956–6.488 0.062 2.349 0.896–6.160 0.083 PFS ISS Stage III 2.492 1.256–4.944 0.009* 2.519 1.267–5.008 0.008* B lymphocyte counts ≤ 49/ul 2.238 1.084–4.622 0.030* 2.281 1.098–4.741 0.027* Abbreviations: OS overall survival, PFS progression-free survival, HR Hazard ratio, CI Confidence interval, *p < 0 .05. 4 Discussion Previous studies showed the high initial of B lymphocytes count in NDMM predicted for favorable survival before the novel agent era( 11 – 13 , 16 ) and the data in the new era is lacked. In this study, we explored the prognostic value and dynamic changing of B lymphocytes in NDMM and found the low B lymphocyte count remained an adverse immune marker for outcome in NDMM patients in the novel drugs era. B lymphocytes are essential for humoral immunity and play multiple roles in the occurrence and progression of human cancers( 17 , 18 ). In our study, B lymphocyte count was markedly decreased in NDMM compared with healthy controls, which may imply that B lymphocyte involves in the onset and development of MM. However, no significant associations were found in NDMM patients with high and low B lymphocyte on clinical parameters including age, sex, paraprotein isotype, hemoglobin, serum creatinine, serum calcium, serum lactate dehydrogenase, serum β2-microglobulin, and ISS stage. Furthermore, we conducted a longitudinal analysis to explore the changing of B lymphocyte count during induction treatment over time and in relation to outcome. The data showed B lymphocyte count was sharply decreased after the 1–2 cycles induction therapy, which may reflect the impact of therapy on blood immune cells of patients with MM. With the ongoing of induction therapy, the B lymphocyte count kept a slight increase trend. This finding suggests the lymphopoiesis was gradually reconstituted along with the control of MM after initial therapy. Together these data suggest that not only the B lymphocyte involves the causes of MM, but tumor cells also impair the host's immune system in turn. We also observed that patients with low B lymphocyte count at diagnosis had poor survival, especially in patients in ISS stage III. But the impact of B lymphocyte on PFS was more obvious than OS, which may imply the death of our MM patients was probably due to disease progress or relapse. Actually, 21 deaths occurred in our study and 10 of them died of MM, 8 died of infection and 3 died of unknown causes. To some extent, this also reflects infection due to B cell deficiency and humoral immunodeficiency may also contribute to the death in MM, especial at the early stage of induction treatment. It should be noted that this study was a retrospective study in a single center and the treatment regimens were inconsistent in our cohort . The B lymphocyte subsets were not explored in our study. Therefore, these findings need to be confirmed by future prospective study and further explore the clinical and prognostic value of different B cell subsets in MM. In conclusion, our study explored the prognostic value of B lymphocyte count in peripheral blood at diagnosis and found low B lymphocyte count was associated with poor outcome in MM patients in the novel agent era. The positive relation of B lymphocyte counts and survival was also kept after 4 cycles’ induction treatment. More attention needs to be paid on B lymphocyte count at diagnosis and during treatment Declarations Acknowledgments This work was supported by the Guangdong Basic and Applied Basic Research Foundation (Grant No. 2024A1515030272). Authors’ contribution WXL and WYQ designed the study. ZZX, KQX, CLJ, ZSS, CH, YYH and ZHZ collected and analyzed the data. WXL and WYQ drafted the manuscript. All authors read and approved the final manuscript. Conflict of interest The authors declare no conflict of interest. Data availability The data that support the findings of this study are available on request from the corresponding author, WYQ，upon reasonable request. The data are not publicly available due to privacy or ethical restrictions. References Bonello F, Cani L, D'Agostino M. Risk Stratification Before and During Treatment in Newly Diagnosed Multiple Myeloma: From Clinical Trials to the Real-World Setting. Front Oncol 2022;12:830922 doi 10.3389/fonc.2022.830922. Hagen P, Zhang J, Barton K. 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Deciphering mechanisms of immune escape to inform immunotherapeutic strategies in multiple myeloma. J Hematol Oncol 2022;15(1):17 doi 10.1186/s13045-022-01234-2. Additional Declarations No competing interests reported. Supplementary Files Supplement.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5358538","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":372537562,"identity":"abbe9b17-b334-436d-a6fd-6d8d984827f6","order_by":0,"name":"Yuqi Wang","email":"","orcid":"","institution":"Nanfang Hospital, Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yuqi","middleName":"","lastName":"Wang","suffix":""},{"id":372537563,"identity":"8f21188c-186c-4301-8dc0-5716fdadc5e3","order_by":1,"name":"Zhongxin Zheng","email":"","orcid":"","institution":"Nanfang Hospital, Southern Medical 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University","correspondingAuthor":false,"prefix":"","firstName":"Hanzhen","middleName":"","lastName":"Zhang","suffix":""},{"id":372537570,"identity":"85b0d6a4-3143-48cb-8416-18f5c1720253","order_by":8,"name":"Xiaolei Wei","email":"","orcid":"","institution":"Nanfang Hospital, Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiaolei","middleName":"","lastName":"Wei","suffix":""},{"id":372537571,"identity":"fb914986-e6d3-41b7-9cf3-2c191ebfd64e","order_by":9,"name":"Ru Feng","email":"","orcid":"","institution":"Nanfang Hospital, Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ru","middleName":"","lastName":"Feng","suffix":""},{"id":372537572,"identity":"e5dec0f7-752a-4f7a-a67e-d1b92880f631","order_by":10,"name":"Yongqiang Wei","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAu0lEQVRIiWNgGAWjYJCCAx//1cixsbcfIFoH48EZbMeM+XjOJBCthfkwDxtz4jwJBwPi1BvcSN5wmIeHLb1NgiGB4UfFNmK0pBUcnCMhk9sm3XiAsefMbcJazG7kGBx4Y8CW2yZzIIGZsY1YLTwJzOlsEgkGxGs5yHOAOYF4LfZnnhUcnNlwzLANGMgHifKLZHvy5g8fG2rk5dvbDz74UUGEFgaBBER0HCBCPRDwHyAyBkfBKBgFo2DkAgAvyUFGyq/ZYQAAAABJRU5ErkJggg==","orcid":"","institution":"Nanfang Hospital, Southern Medical University","correspondingAuthor":true,"prefix":"","firstName":"Yongqiang","middleName":"","lastName":"Wei","suffix":""}],"badges":[],"createdAt":"2024-10-30 05:53:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5358538/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5358538/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":69950495,"identity":"6a3510e1-edb6-41d3-bce2-b46c35368752","added_by":"auto","created_at":"2024-11-27 02:12:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":147279,"visible":true,"origin":"","legend":"\u003cp\u003eThe B lymphocyte count in our NDMM patients and healthy control. ***:P\u0026lt;0.001\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5358538/v1/ea94778fde2642932802b354.png"},{"id":69949344,"identity":"999b6c1f-6559-4c8a-a7c1-7114314e031d","added_by":"auto","created_at":"2024-11-27 02:04:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":136970,"visible":true,"origin":"","legend":"\u003cp\u003eDynamic changes of B lymphocyte during induction treatment grouped in regimen. The B lymphocyte counts were detected at T0, T1, T2, T3 and T4, respectively. All p-values were the results of comparison with T0. *:P\u0026lt;0.0001.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5358538/v1/cf3c9b30405057cf4dc7e007.png"},{"id":69949341,"identity":"5b68f247-8e56-4d1d-8dfa-15bfd9c26703","added_by":"auto","created_at":"2024-11-27 02:04:22","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":147054,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier analysis of survival in groups of patients with different level of B lymphocyte at diagnosis:(A) progression-free survival, (B) overall survival.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-5358538/v1/95d676bd7ec3de05edc1171a.png"},{"id":69950796,"identity":"c9ff0efa-1b55-40d3-bf5c-b1485ecc18c1","added_by":"auto","created_at":"2024-11-27 02:20:22","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":142426,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier analysis of progression-free survival in groups of patients in different ISS stage with different level of B lymphocyte at diagnosis:(A) patients in ISS stage I or II, (B) patients in ISS stage III.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-5358538/v1/69ce05395e85eef2237f6dc6.png"},{"id":69949346,"identity":"10913cf8-421c-4a1d-93b0-22918da378f4","added_by":"auto","created_at":"2024-11-27 02:04:22","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":148516,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier analysis of survival in groups of patients with different level of B lymphocyte after 4 cycles’ induction treatments: (A) progression-free survival, (B) overall survival.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-5358538/v1/d96c3090b7e4cebcfe1ee927.png"},{"id":73886208,"identity":"3f4fe0a4-1dbb-4680-a8b6-68344ffcfaf8","added_by":"auto","created_at":"2025-01-15 14:39:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1577344,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5358538/v1/dc2e4a70-cf75-4133-a388-623c73aff8af.pdf"},{"id":69950497,"identity":"808ec2e6-4a24-4890-b367-0ab17662e175","added_by":"auto","created_at":"2024-11-27 02:12:22","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":73903,"visible":true,"origin":"","legend":"","description":"","filename":"Supplement.docx","url":"https://assets-eu.researchsquare.com/files/rs-5358538/v1/dc5118ba29a754573826cf73.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Low peripheral blood B lymphocyte count predict poor outcome in patients with multiple myeloma","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eMultiple myeloma (MM) is the second most common hematological malignant disorder, characterized by the infiltration of monoclonal plasma cells in bone marrow and related organs or tissues impairment. The revised international staging system (R-ISS) is now widely used in clinical practice, which focusing on clinical markers and cytogenetic abnormalities at diagnosis(\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Immune profiles have been proved to play a crucial role in the pathogenesis and progression of MM(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).The addition of immune profiles may improve the prediction ability in patients with MM(\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eB lymphocyte is a kind of lymphocytes component. Activated by tumor antigen, B lymphocytes secrete antibodies, which can activate complement system to lyses tumor cells or mediate macrophages, NK cells to exert antibody-dependent cell-mediated cytotoxicity (ADCC) effect(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).Previous studies indicated that higher circulating blood B cells at diagnosis were a favorable prognostic marker without apparent relationship to circulating plasma cells in patients with multiple myeloma(\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).The depleted B cells in patients with monoclonal gammopathy of undetermined significance and MM were finally recovered after long-term disease control in both the bone marrow and peripheral blood(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). These data implied B lymphocyte may involve in the progression and prognosis of multiple myeloma. However, the prognostic value of peripheral blood B lymphocyte on multiple myeloma in the novel agent era was rare reported.\u003c/p\u003e \u003cp\u003eTherefore, we detected the B lymphocyte count in peripheral blood at diagnosis and after treatment by multiparameter flow cytometry (MFC) to explore the prognostic value and dynamic change of B lymphocyte count in patients with MM.\u003c/p\u003e"},{"header":"2 Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Patients\u003c/h2\u003e \u003cp\u003eNewly diagnosed multiple myeloma (NDMM) patients in Nanfang Hospital, Southern Medical University from January 2020 to January 2023 were enrolled in this study. All patients were diagnosed according to the International Myeloma Working Group (IMWG) criteria(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) and treated with proteasome inhibitor (PI) and/or immunomodulatory (IMiDs) based regimen as first-line treatment after diagnosis. Patients with other malignant tumors, immune deficiency diseases, autoimmune diseases, rheumatism diseases and missing B lymphocyte count were excluded. Patients with good response after four cycles of induction treatment would undergo autologous peripheral blood stem cell transplantation (ASCT) or continue the same regimen as consolidation therapy. Besides, 63 individuals for health physical examination were also recruited in our center as normal control. This study was approved by the Ethics Committee of Southern Medical University affiliated Nanfang Hospital.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 B lymphocytes detection by multiparameter flow cytometry\u003c/h2\u003e \u003cp\u003ePeripheral blood B lymphocyte was analyzed using fresh peripheral blood samples according to the standard procedure. The following conjugates of monoclonal antibodies were used: anti-CD3-PerCP-Cy5.5 and anti-CD19-PE-Cy7 (BD Biosciences, San Jose, CA, USA). The frequencies of lymphocytes were determined using a FACS Calibur flow cytometer (Becton Dickinson, Franklin Lakes, NJ, USA) and CellQuest software (BD Biosciences) was used for data analysis. At least 5\u0026times;10\u003csup\u003e4\u003c/sup\u003e events were measured with each sample. B lymphocytes were defined as CD3-CD19\u0026thinsp;+\u0026thinsp;lymphocytes and recorded as absolute number of cells/\u0026micro;l(normal range: 98.71\u0026ndash;364.86 cells/\u0026micro;l) and was detected at diagnosis and the beginning of each cycle of induction therapy: T0, at diagnosis; T1, at the beginning of the second cycle of induction therapy; T2, at the beginning of the third cycle; T3, at the beginning of the fourth cycle; T4, at the beginning of the fifth cycle.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Statistical analysis\u003c/h2\u003e \u003cp\u003eDifferences between nominal variables were evaluated using the Chi-Square test, and continuous variables were assessed using the Mann-Whitney U test. Optimal cutoff value was detected as a biomarker of survival by surv_cutpoint function. Overall survival (OS) and progression-free survival (PFS) distribution were analyzed by Kaplan-Meier (K-M) curves and log-rank test was applied to estimate differences between different groups. The univariable and multivariable analysis of survival were carried out by Cox regression model. All reported p-values were two-sided and confidence intervals refer to 95% boundaries, and statistical difference was considered as p-value less than 0.05. Statistical analyses were performed using the R4.4.1.\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Patients\u0026rsquo; characteristics\u003c/h2\u003e \u003cp\u003eA total of 110 NDMM patient were included in our study. 56 (50.9%) patients were older than 60 years and the male-to-female ratio was 1.75:1. 66 (59.1%) patients were classified as IgG type, and 23 (20.9%) patients belonged to Light Chain type. According to DurieSalmon System (DS), 9 (8.2%) patients were at stage I, 14(12.7%) at stage II, and 87 (79.1%) at stage III. Based on International Staging System (ISS), 18(16.4%) patients were classified as stage I, 36(32.7%) as stage II, and 56 (50.9%) as stage III. Among the 65 (59.1%) patients who received the FISH test, 11 patients (16.9%) were classified as high risk who had 17p-, t (4;14) or t (14;16), while others were classified as standard risk.\u003c/p\u003e \u003cp\u003eThe most common induction regimen was bortezomib-based regimen in 101 (91.4%) patients, among which 54.5% (60) received a combination with lenalidomide and dexamethasone (VRD) and 37.3% (41) combination with cyclophosphamide and dexamethasone (VCD). Fifty-nine patients (53.6%) underwent ASCT after induction treatment. The baseline characteristics of all patients were summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatients\u0026rsquo; baseline characteristics and clinical feature\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"13\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003ePatients' characters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003en(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c10\" namest=\"c6\"\u003e \u003cp\u003ePatients' characters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e \u003cp\u003en(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c13\" namest=\"c13\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c8\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003eISS Stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c13\" namest=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e70 (63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c11\" namest=\"c7\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c13\" namest=\"c12\"\u003e \u003cp\u003e18 (16.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003efemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e40 (36.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c11\" namest=\"c7\"\u003e \u003cp\u003eII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c13\" namest=\"c12\"\u003e \u003cp\u003e36 (32.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c11\" namest=\"c7\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c13\" namest=\"c12\"\u003e \u003cp\u003e56 (50.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c7\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e \u003cp\u003eCA by FISH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c13\" namest=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e56 (50.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c11\" namest=\"c7\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c13\" namest=\"c12\"\u003e \u003cp\u003e11 (10.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e54 (49.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c11\" namest=\"c7\"\u003e \u003cp\u003eStandard risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c13\" namest=\"c12\"\u003e \u003cp\u003e54 (49.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c11\" namest=\"c7\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c13\" namest=\"c12\"\u003e \u003cp\u003e45 (40.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eType\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c7\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e \u003cp\u003eRegimen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c13\" namest=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIgG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e66 (59.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c11\" namest=\"c7\"\u003e \u003cp\u003eVCD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c13\" namest=\"c12\"\u003e \u003cp\u003e41 (37.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIgA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e17 (15.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c11\" namest=\"c7\"\u003e \u003cp\u003eVRD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c13\" namest=\"c12\"\u003e \u003cp\u003e60 (54.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIgD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e2 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c11\" namest=\"c7\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c13\" namest=\"c12\"\u003e \u003cp\u003e9 (8.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLight Chain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c7\" namest=\"c3\"\u003e \u003cp\u003e23 (20.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e \u003cp\u003eASCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c13\" namest=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e2 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c11\" namest=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c13\" namest=\"c12\"\u003e \u003cp\u003e60 (54.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c11\" namest=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c13\" namest=\"c12\"\u003e \u003cp\u003e50 (45.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDS Stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c10\" namest=\"c5\"\u003e \u003cp\u003eClinical Features\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e \u003cp\u003emedian [IQR]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c13\" namest=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e9 (8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c10\" namest=\"c5\"\u003e \u003cp\u003eHBG (g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e \u003cp\u003e88.50 [70.00, 121.75]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c13\" namest=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e14 (12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c10\" namest=\"c5\"\u003e \u003cp\u003eCR(\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e \u003cp\u003e92.50 [71.00, 192.75]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c13\" namest=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e87 (79.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c10\" namest=\"c5\"\u003e \u003cp\u003eCa(mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e \u003cp\u003e2.27 [2.14, 2.46]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c13\" namest=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c10\" namest=\"c5\"\u003e \u003cp\u003eM-protein(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e \u003cp\u003e31.52 [4.53, 52.77]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c13\" namest=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eRenal Function Stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c10\" namest=\"c5\"\u003e \u003cp\u003eβ2-MG(mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e \u003cp\u003e5.52 [3.42, 13.40]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c13\" namest=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c10\" namest=\"c5\"\u003e \u003cp\u003eALB(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e \u003cp\u003e32.95 [27.85, 38.05]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c13\" namest=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e83 (75.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c9\" namest=\"c5\"\u003e \u003cp\u003eLDH(U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c12\" namest=\"c10\"\u003e \u003cp\u003e169.50 [123.75, 225.75]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c13\" namest=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e27 (24.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c10\" namest=\"c5\"\u003e \u003cp\u003ePCs(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e \u003cp\u003e25.50 [13.00, 44.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c13\" namest=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"13\"\u003eAbbreviations: DS Durie Salmon, ISS International Stage System, CA Chromosomal Abnormalities [defined by the presence of del(17p): translocation t(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e): or translocation t(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)], FISH Fluorescent in situ hybridization, VCD bortezomib\u0026thinsp;+\u0026thinsp;cyclophosphamide\u0026thinsp;+\u0026thinsp;dexamethasone, VRD bortezomib\u0026thinsp;+\u0026thinsp;lenalidomide\u0026thinsp;+\u0026thinsp;dexamethasone, ASCT Autologous Stem Cell Transplantation, HBG: Hemoglobin, Cr Creatinine, β2-MG β2-Microglobulin, ALB Albumin, LDH Lactate Dehydrogenase.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.2 The clinical and prognostic value of B lymphocyte in NDMM\u003c/h2\u003e \u003cp\u003eThe mean B lymphocyte count was 131/\u0026micro;l(range, 6\u0026ndash;676/\u0026micro;l) in our NDMM patients at diagnosis and 218.05/\u0026micro;l(range, 66.7\u0026ndash;650.95/\u0026micro;l) in 63 healthy controls (HCs). The B lymphocyte count of MM patients was significantly lower than that of the health donors (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The optimal B lymphocyte count cutoff value was determined as 49/\u0026micro;l(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, \u003cb\u003eSupplement\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) by using the surv_cutpoint function. All patients were divided into two groups: 94 patients in high B lymphocyte group and the left 16 patients in low B lymphocyte group. No significant differences were found in common clinical parameters including age, gender, hemoglobin, serum creatinine, serum calcium, serum lactate dehydrogenase, serum β2-microglobulin, subtypes and ISS stage between these two groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), as shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatients\u0026rsquo; characteristics based on B lymphocyte level at diagnosis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eParameters, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eB lymphocyte counts\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;49/ul(n\u0026thinsp;=\u0026thinsp;94)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;49/ul(n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70 (63.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57 (60.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (81.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.193\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (36.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 (39.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (18.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (50.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45 (47.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11 (68.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.203\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54 (49.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49 (52.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (31.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHBG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;85g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (46.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32 (46.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (46.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;85g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 (53.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 (53.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (53.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;177umol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82 (74.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72 (76.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (62.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.376\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;177umol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (25.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (23.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (37.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2.65mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (15.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (12.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (31.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.129\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;2.65mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93 (84.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e82 (87.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11 (68.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ2-MG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;5.5mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54 (49.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48 (51.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (37.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.464\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;5.5mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (50.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46 (48.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (62.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;35g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 (60.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e59 (62.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (43.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.246\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;35g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 (40.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35 (37.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (56.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;250U/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (15.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (17.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (6.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.467\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;250U/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93 (84.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78 (82.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15 (93.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eHR-CA by FISH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (10.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (11.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.324\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54 (49.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46 (48.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (50.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (40.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 (39.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (50.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDS Stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eI-II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (20.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (20.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3(18.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.354\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87 (79.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74 (78.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (81.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eISS Stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eI-II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54 (49.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48 (51.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6(37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.424\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (50.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46 (48.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (62.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegimen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVCD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (37.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34 (36.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (43.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.595\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVRD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 (54.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e53 (56.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (43.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (8.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (7.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (12.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 (54.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54 (57.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (37.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.226\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (45.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (42.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (62.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations: DS Durie Salmon, ISS International Stage System, HR-CA High-Risk Chromosomal Abnormalities [defined by the presence of del(17p): translocation t(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e): or translocation t(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)], FISH Fluorescent in situ hybridization,ASCT autologous stem cell transplantation, HBG: Hemoglobin, Cr creatinine, β2-MG β2-microglobulin, ALB albumin, LDH lactate dehydrogenase.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWe also explored the dynamic change of B lymphocyte in MM patients during induction treatment. A total of 74 patients finished 4 cycles\u0026rsquo; induction treatment: 42 (56.8%) patients received VRD and 27(36.5%) of them received VCD regimens. The B lymphocyte count was dramatically decreased after the first cycle of induction (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) and then kept stable during 2 to 4 cycles(P\u0026thinsp;\u0026gt;\u0026thinsp;0.05, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). No significant difference was found between VCD and VRD regimen at each cycle (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eWith a median follow-up of 27.77 months (range,0.17\u0026ndash;51.83 months), 38 patients (34.5%) suffered relapse or progression and 21 patients (19.1%) died. Among them, 10 patients died of MM, 8 patients died of infection and 3 patients died of unknown cause. Patients with low B lymphocyte count had a significant shorter PFS (median PFS 25.8 months vs. not reached, p\u0026thinsp;=\u0026thinsp;0.025, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA) and a trend of unfavorable OS (both median OS were not reached, p\u0026thinsp;=\u0026thinsp;0.053, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB) than those with high B lymphocyte level. And then subgroup analysis was conducted based on lymphocyte levels and ISS staging to examine the impact of lymphocyte levels on prognosis in patients at different stages. Consequently, patients in ISS stage III with low B lymphocyte count had a significant shorter PFS (median PFS 19.2 months vs. 42.5 months, p\u0026thinsp;=\u0026thinsp;0.004, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB), while the difference of outcomes in patients in ISS stage I or II with different B lymphocyte level were non-significant(Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA).Furthermore, we explored the prognostic value of B lymphocyte change during induction treatment and found low B lymphocyte count after 4 cycles\u0026rsquo; treatment could be a stable unfavorable marker for both PFS (p\u0026thinsp;=\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA) and OS (p\u0026lt;0.0001, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB). Multivariate analysis showed that low B lymphocyte count at diagnosis independent of ISS stage was a significantly inferior marker for predicting PFS (p\u0026thinsp;=\u0026thinsp;0.027, hazard ratio(HR) 2.281, 95% confidence interval (CI) 1.098\u0026ndash;4.741) and a trend for OS (p\u0026thinsp;=\u0026thinsp;0.083, HR 2.394, 95% CI 0.896\u0026ndash;6.160). The multivariate survival analysis was shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate analysis and multivariate analysis for overall survival and progression-free survival in patients with newly diagnosed multiple myeloma\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eRisk factor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eISS Stage III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.303\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.920\u0026ndash;5.767\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.075\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.209\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.877\u0026ndash;5.562\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.093\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB lymphocyte counts\u003c/p\u003e \u003cp\u003e\u0026thinsp;\u0026le;\u0026thinsp;49/ul\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.490\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.956\u0026ndash;6.488\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.062\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.349\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.896\u0026ndash;6.160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.083\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eISS Stage III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.492\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.256\u0026ndash;4.944\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.009*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.519\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.267\u0026ndash;5.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.008*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB lymphocyte counts\u003c/p\u003e \u003cp\u003e\u0026thinsp;\u0026le;\u0026thinsp;49/ul\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.238\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.084\u0026ndash;4.622\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.030*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.281\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.098\u0026ndash;4.741\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.027*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eAbbreviations: OS overall survival, PFS progression-free survival, HR Hazard ratio, CI Confidence interval, *p\u0026thinsp;\u0026lt;\u0026thinsp;0 .05.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003ePrevious studies showed the high initial of B lymphocytes count in NDMM predicted for favorable survival before the novel agent era(\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) and the data in the new era is lacked. In this study, we explored the prognostic value and dynamic changing of B lymphocytes in NDMM and found the low B lymphocyte count remained an adverse immune marker for outcome in NDMM patients in the novel drugs era.\u003c/p\u003e \u003cp\u003eB lymphocytes are essential for humoral immunity and play multiple roles in the occurrence and progression of human cancers(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). In our study, B lymphocyte count was markedly decreased in NDMM compared with healthy controls, which may imply that B lymphocyte involves in the onset and development of MM. However, no significant associations were found in NDMM patients with high and low B lymphocyte on clinical parameters including age, sex, paraprotein isotype, hemoglobin, serum creatinine, serum calcium, serum lactate dehydrogenase, serum β2-microglobulin, and ISS stage. Furthermore, we conducted a longitudinal analysis to explore the changing of B lymphocyte count during induction treatment over time and in relation to outcome. The data showed B lymphocyte count was sharply decreased after the 1\u0026ndash;2 cycles induction therapy, which may reflect the impact of therapy on blood immune cells of patients with MM. With the ongoing of induction therapy, the B lymphocyte count kept a slight increase trend. This finding suggests the lymphopoiesis was gradually reconstituted along with the control of MM after initial therapy. Together these data suggest that not only the B lymphocyte involves the causes of MM, but tumor cells also impair the host's immune system in turn.\u003c/p\u003e \u003cp\u003eWe also observed that patients with low B lymphocyte count at diagnosis had poor survival, especially in patients in ISS stage III. But the impact of B lymphocyte on PFS was more obvious than OS, which may imply the death of our MM patients was probably due to disease progress or relapse. Actually, 21 deaths occurred in our study and 10 of them died of MM, 8 died of infection and 3 died of unknown causes. To some extent, this also reflects infection due to B cell deficiency and humoral immunodeficiency may also contribute to the death in MM, especial at the early stage of induction treatment.\u003c/p\u003e \u003cp\u003eIt should be noted that this study was a retrospective study in a single center and the treatment regimens were inconsistent in our cohort\u003c/p\u003e \u003cp\u003e. The B lymphocyte subsets were not explored in our study. Therefore, these findings need to be confirmed by future prospective study and further explore the clinical and prognostic value of different B cell subsets in MM.\u003c/p\u003e \u003cp\u003eIn conclusion, our study explored the prognostic value of B lymphocyte count in peripheral blood at diagnosis and found low B lymphocyte count was associated with poor outcome in MM patients in the novel agent era. The positive relation of B lymphocyte counts and survival was also kept after 4 cycles\u0026rsquo; induction treatment. More attention needs to be paid on B lymphocyte count at diagnosis and during treatment\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Acknowledgments \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Guangdong Basic and Applied Basic Research Foundation (Grant No. 2024A1515030272).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Authors\u0026rsquo; contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWXL and WYQ designed the study. ZZX, KQX, CLJ, ZSS, CH, YYH and ZHZ collected and analyzed the data. WXL and WYQ drafted the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available on request from the corresponding author, WYQ，upon reasonable request. The data are not publicly available due to privacy or ethical restrictions.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBonello F, Cani L, D\u0026apos;Agostino M. Risk Stratification Before and During Treatment in Newly Diagnosed Multiple Myeloma: From Clinical Trials to the Real-World Setting. Front Oncol 2022;12:830922 doi 10.3389/fonc.2022.830922.\u003c/li\u003e\n\u003cli\u003eHagen P, Zhang J, Barton K. High-risk disease in newly diagnosed multiple myeloma: beyond the R-ISS and IMWG definitions. Blood Cancer J 2022;12(5):83 doi 10.1038/s41408-022-00679-5.\u003c/li\u003e\n\u003cli\u003eJimenez-Zepeda VH, Duggan P, Neri P, Rashid-Kolvear F, Tay J, Bahlis NJ. Revised International Staging System Applied to Real World Multiple Myeloma Patients. Clin Lymphoma Myeloma Leuk 2016;16(9):511-18 doi 10.1016/j.clml.2016.06.001.\u003c/li\u003e\n\u003cli\u003eOmed\u0026eacute; P, Boccadoro M, Gallone G, Frieri R, Battaglio S, Redoglia V, et al. Multiple myeloma: increased circulating lymphocytes carrying plasma cell-associated antigens as an indicator of poor survival. Blood 1990;76(7):1375-79.\u003c/li\u003e\n\u003cli\u003eGarcia-Ortiz A, Rodriguez-Garcia Y, Encinas J, Maroto-Martin E, Castellano E, Teixido J, et al. The Role of Tumor Microenvironment in Multiple Myeloma Development and Progression. Cancers (Basel) 2021;13(2172)doi 10.3390/cancers13020217.\u003c/li\u003e\n\u003cli\u003eZhaoyun L, Rong F. Predictive Role of Immune Profiling for Survival of Multiple Myeloma Patients. Front Immunol 2021;12:663748 doi 10.3389/fimmu.2021.663748.\u003c/li\u003e\n\u003cli\u003eOmed\u0026eacute; P, Boccadoro M, Gallone G, Frieri R, Battaglio S, Redoglia V, et al. Multiple myeloma: increased circulating lymphocytes carrying plasma cell-associated antigens as an indicator of poor survival. Blood 1990;76(7):1375-79.\u003c/li\u003e\n\u003cli\u003eShin SJ, Roh J, Kim M, Jung MJ, Koh YW, Park CS, et al. Prognostic significance of absolute lymphocyte count/absolute monocyte count ratio at diagnosis in patients with multiple myeloma. Korean J Pathol 2013;47(6):526-33 doi 10.4132/KoreanJPathol.2013.47.6.526.\u003c/li\u003e\n\u003cli\u003eAllegra A, Innao V, Allegra AG, Pugliese M, Di Salvo E, Ventura-Spagnolo E, et al. Lymphocyte Subsets and Inflammatory Cytokines of Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma. Int J Mol Sci 2019;20(11)doi 10.3390/ijms20112822.\u003c/li\u003e\n\u003cli\u003eFranssen LE, Mutis T, Lokhorst HM, van de Donk NWCJ. Immunotherapy in myeloma: how far have we come? Ther Adv Hematol 2019;10(2040620718822660)doi 10.1177/2040620718822660.\u003c/li\u003e\n\u003cli\u003ePessoa DMR, Vidriales MB, Paiva B, Fernandez-Gimenez C, Garc\u0026iacute;a-Sanz R, Mateos MV, et al. Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry. Haematologica 2013;98(1):79-86 doi 10.3324/haematol.2012.067272.\u003c/li\u003e\n\u003cli\u003eKay NE, Leong T, Kyle RA, Greipp P, Billadeau D, Van Ness B, et al. Circulating blood B cells in multiple myeloma: analysis and relationship to circulating clonal cells and clinical parameters in a cohort of patients entered on the Eastern Cooperative Oncology Group phase III E9486 clinical trial. Blood 1997;90(1):340-45.\u003c/li\u003e\n\u003cli\u003eHo CM, McCarthy PL, Wallace PK, Zhang Y, Fora A, Mellors P, et al. Immune signatures associated with improved progression-free and overall survival for myeloma patients treated with AHSCT. Blood Adv 2017;1(15):1056-66 doi 10.1182/bloodadvances.2017005447.\u003c/li\u003e\n\u003cli\u003eCheng H, Ji S, Wang J, Hua T, Chen Z, Liu J, et al. Long-term analysis of cellular immunity in patients with RRMM treated with CAR-T cell therapy. Clin Exp Med 2023doi 10.1007/s10238-023-01232-9.\u003c/li\u003e\n\u003cli\u003eRajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15(12):e538-48 doi 10.1016/S1470-2045(14)70442-5.\u003c/li\u003e\n\u003cli\u003eKay NE, Leong TL, Bone N, Vesole DH, Greipp PR, Van Ness B, et al. Blood levels of immune cells predict survival in myeloma patients: results of an Eastern Cooperative Oncology Group phase 3 trial for newly diagnosed multiple myeloma patients. Blood 2001;98(1):23-28 doi 10.1182/blood.v98.1.23.\u003c/li\u003e\n\u003cli\u003eFeyler S, Selby PJ, Cook G. Regulating the regulators in cancer-immunosuppression in multiple myeloma (MM). Blood Rev 2013;27(3):155-64 doi 10.1016/j.blre.2013.04.004.\u003c/li\u003e\n\u003cli\u003eSwamydas M, Murphy EV, Ignatz-Hoover JJ, Malek E, Driscoll JJ. Deciphering mechanisms of immune escape to inform immunotherapeutic strategies in multiple myeloma. J Hematol Oncol 2022;15(1):17 doi 10.1186/s13045-022-01234-2.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Multiple myeloma, B lymphocyte, Outcome, Dynamic change, Immune profiles","lastPublishedDoi":"10.21203/rs.3.rs-5358538/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5358538/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePrevious evidence suggested that B lymphocyte may involve in the progression and prognosis of multiple myeloma (MM). However, the prognostic value of peripheral B lymphocyte counts on MM before and after treatment in the novel agent era was rare reported. Herein, we conducted a retrospective study in our center to detect peripheral B lymphocyte counts by flow cytometry in 110 patients with MM at our center and explore the relation with survival. The B lymphocyte count was significantly lower in MM patients than healthy controls (p\u0026thinsp;\u0026lt;\u0026thinsp;0.005). The cutoff value of B lymphocyte count at diagnosis was 49/\u0026micro;l in MM and 94 patients divided into in high B lymphocyte group. Patients with low B lymphocyte count had a significant shorter progression-free survival (PFS) (p\u0026thinsp;=\u0026thinsp;0.025) and a trend of unfavorable overall survival (OS) (p\u0026thinsp;=\u0026thinsp;0.053) at diagnosis and after 4 cycles\u0026rsquo; induction treatments. Furthermore, Multivariate analysis showed that low B lymphocyte count at diagnosis independent of ISS stage was a significantly inferior marker for predicting PFS (p\u0026thinsp;=\u0026thinsp;0.027, hazard ratio(HR) 2.281, 95% confidence interval (CI) 1.098\u0026ndash;4.741) and a trend for OS (p\u0026thinsp;=\u0026thinsp;0.083, HR 2.394, 95% CI 0.896\u0026ndash;6.160). In summary, these results suggested the low B lymphocyte count was associated with poor outcome in MM patients at diagnosis and after treatment in the novel agent era.\u003c/p\u003e","manuscriptTitle":"Low peripheral blood B lymphocyte count predict poor outcome in patients with multiple myeloma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-27 02:04:17","doi":"10.21203/rs.3.rs-5358538/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5f440c8b-52c8-4018-9e74-9b4ad22dbb48","owner":[],"postedDate":"November 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-15T14:38:22+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-27 02:04:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5358538","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5358538","identity":"rs-5358538","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}