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Objective: To investigate the value of serum free light chain (sFLC) and serum calcium ion in the diagnosis and prognosis of multiple myeloma (MM)., Methods: Forty patients with MM treated in Henan Provincial People's Hospital from January 2018 to January 2022 were selected as the observation group, and 40 healthy volunteers were selected as the control group. The differences of sFLC-κ、sFLC-λ、sFLC-κ/λ, serum calcium ions, etc between the two groups were compared. Meanwhile, the differences of sFLC-κ、sFLC-λ、sFLC-κ/λ, serum calcium ions, etc in different international staging systems (ISS), chemotherapy efficacy and prognosis patients were analyzed., Results: The levels of sFLC-κ［(98.39±21.19) vs (12.01±4.45) mg/L］, sFLC-λ［(210.20±45.54) vs (14.10±5.11) mg/L］ and proportions of hypocalcemia （65% vs 0） in the observation group were significantly higher than those in the control group ( P < 0.05), while sFLC-κ/ λ ratio［（0.44±0.10） vs (0.87±0.12)］ and serum calcium ions ［（1.98±0.46） vs （2.42±0.40）mmol/L］ were significantly lower than those in the control group ( P < 0.05). The sFLC-κ, sFLC-λ, the proportion of hypocalcemia and the course of hypocalcemia in ISS stage III patients in the observation group were significantly higher than those in stage I and II patients ( P < 0.05), while sFLC-κ/λ ratio, and serum calcium ions were significantly lower than those in stage I and II patients ( P < 0.05). The levels of sFLC-κ ［（107.76±21.22） vs （94.67±20.11）mg/L］, sFLC- λ［（245.54±41.12） vs （205.54±50.22）mg/L］ of patients with hypocalcemia in the observation group was significantly higher than those without hypocalcemia ( P < 0.05), while the sFLC-κ/λ ratio was significantly lower than those without hypocalcemia ［（0.42±0.04） vs （0.47±0.06）； P < 0.05］. The levels of sFLC-κ ［(107.29±20.14） vs （ 91.11±18.92）mg/L］, sFLC-λ［（247.98±42.26） vs （179.29±39.32）mg/L］ in patients with ineffective chemotherapy were significantly higher than those in patients with effective chemotherapy ( P < 0.05), while the sFLC-κ/λ ratio was significantly lower than those in patients with effective chemotherapy ［(0.43±0.10) vs (0.50±0.09)； P < 0.05）］. The area under the ROC curve for sFLC-κ, sFLC-λ, sFLC-κ/λ predicting ineffective chemotherapy was 0.803, 0.793 and 0.699 respectively, P < 0.05. There was no significant difference in sFLC-κ, sFLC-λ, sFLC-κ/λ ratio, serum calcium ion, hypocalcemia ratio and hypocalcemia course between survival and death patients ( P >0.05)., Conclusion: sFLC and serum calcium are related to ISS stage of MM patients. sFLC level has a certain value to predict the curative effect of chemotherapy in MM patients. However, the prognostic values of sFLC and serum calcium are not yet confirmed for MM patients.

Objective: To investigate the clinical and prognostic characteristics of newly diagnosed multiple myeloma (NDMM) patients with myelofibrosis (MF). Methods: The clinical data of 160 NDMM patients admitted to Henan Provincial People's Hospital from January 2012 to July 2022 were analyzed retrospectively. They were divided into MF group( n =74) and non-MF group( n =86) according to whether combined with MF. Patients in MF group were further splited into MF-1 group ( n =47) and MF-2/3 group ( n =27). All patients were treated with bortezomib and immunomodulatory-based combination therapy. The efficacy was evaluated after 4 courses, and the clinical features and prognosis between the two groups were compared. The deadline for follow-up was December 30, 2022 and the median follow-up period [ M ( Q 1 , Q 3 )] was 23.5 (14.4, 40.5) months. Kaplan-Meier method was used for survival analysis, and Cox regression model was used to analyze the influencing factors of survival. Results: Among 160 patients with NDMM, 91 were males and 69 were females, with a median age [ M ( Q 1 , Q 3 )] of 59 (54, 69) years. In MF group, the bone marrow immature plasma cell percentage, total plasma cell percentage were 9.6% (3.2%, 28.5%) and 36.4% (18.5%, 51.1%), respectively, which were higher than 6.0% (1.2%, 17.2%) and 24.0% (12.0%, 46.0%) of the non-MF group (both P <0.05). Hb level was 84.0(74.5, 100.5)g/L and PLT was (151.99±90.68) ×10 9 /L in the MF group, which were lower than 96.0 (81.0, 112.0)g/L and (180.38±85.32) ×10 9 /L of non-MF group (both P <0.05). But there were no significant differences in ISS stage, karyotypic and fluorescence in situ hybridization (FISH) high-risk genetic abnormalities between the two groups (all P >0.05). Objective response rate (ORR), overall survival (OS) and progression-free survival (PFS) were not significantly different between the two groups (all P >0.05). The rate of 17p- was 25.9% (7/27) in MF-2/3 group, which was higher than 8.1% (7/86) of non-MF group ( P =0.049). The median OS of the MF-2/3 group was 25.0 ( 95%CI : 23.6-26.4) months, which was shorter than that of the non-MF group (54.0 months, P =0.031). Multivariate Cox regression analysis showed that grade MF-2/3 was not a risk factor for OS in NDMM patients ( HR =1.507, 95%CI : 0.624-3.993, P =0.425). Conclusions: The ratio of bone marrow immature plasma cells and total plasma cells in NDMM patients with MF are higher than that in patients without MF, and the Hb and PLT are lower than that in patients without MF. NDMM patients with grade 2/3 MF have shorter survival than those without MF.

Objective: To investigate the influence and clinical significance of proteasome inhibitor on serum bone metabolite markers including tartrate-resistant acid phosphatase 5b isoenzyme (TRACP-5b), type I collagen carboxy terminal peptide β(β-CTX), type I procollagen amino terminal prolongation peptide (PINP) and vitamin D3 in patients with myeloma bone disease (MBD). Methods: From April 2015 to June 2018, 68 patients with newly diagnosed MBD who admitted to our hospital were treated with proteasome inhibitor-based regimen. Serum concentration of TRACP-5b、β-CTX、PINP and vitamin D3 were measured before treatment and after 4 and 8 cycles of chemotherapy, and imaging changes were observed. Results: After 4 and 8 cycles of chemotherapy, serum levels of TRACP-5b, β-CTX and vitamin D3 were decreased significantly ( P< 0.05). The serum concentration of PINP was (78.1±44.9) ng/L before chemotherapy, while after 4 cycles, it turned to (94.5±56.1) ng/L without significant difference ( t= -1.871, P= 0.063). Moreover, it increased to (173.3±80.5) ng/L after 8 cycles of chemotherapy with significant difference ( t= -8.272, P< 0.001). The proportion of imaging classification ≥3 among all patients was 66.2%, and it decreased to 60.3% after 4 cycles of chemotherapy without significant difference (χ(2)=0.569, P= 0.477). The proportion of imaging classification ≥3 after 8 cycles of chemotherapy decreased to 44.5%, which was significantly lower than that before treatment (χ(2)=6.260, P= 0.012). After 8 cycles of chemotherapy, 63 patients were evaluable, of which 50 were effective and 13 were ineffective. Serum concentration of PINP in the effective group was higher than that in the ineffective group ((190.7±78.5) ng/L vs (106.5±47.3) ng/L, t= 5.762, P< 0.001), and the serum concentration of vitamin D3 in the effective group was lower than that in the ineffective group ((11.7±4.8) μg/L vs (15.6±5.5) μg/L, t= -2.478, P= 0.016). The proportion of patients with more than grade 3 bone disease of the effective group was also significantly lower than that of the ineffective group (38.0% vs 69.2%, χ(2)=4.076, P= 0.044). There was no significant difference in the serum concentration of TRACP-5b and β-CTX between two groups. Conclusion: After treatment with the proteasome inhibitor -based regimen, the serum concentrations of TRACP-5b, β-CTX and vitamin D3, which reflect osteoclast activity in MBD patients were decreased, the serum concentration of PINP indicating osteoblast activity was increased, and the grade of imaging of bone disease was decreased.

Objective: To explore the expression of CD45 in newly diagnosed multiple myeloma (MM) and its relationship with clinical efficacy and prognosis. Methods: This study retrospectively analyzed expression and distribution of CD45 in 130 cases of newly diagnosed MM, comparing clinical efficacy and prognosis in CD45(+)/CD45(-) groups. Results: ①The CD45(+) group was 33 cases (25.38%) , and CD45(-) group was 97 cases (74.62%) . ②The objective remission rate (ORR) of CD45(+) and CD45(-)group was 33.33% and 64.95%, respectively. The difference was statistically significant ( P =0.002) . For patients in Bortezomib regimen, the ORR of CD45(+) and CD45(-) group was 35.71% and 66.25%, respectively. The difference was statistically significant ( P =0.005) . ③The median progress free survival (PFS) of CD45(+) group and CD45(-) group was 29.8 (95% CI 10.0-59.0) months vs 34.5 (95% CI 6.0-69.0) months ( χ (2)=14.59, P <0.001) and the median overall survival (OS) was 32.5 (95% CI 10.0-68.0) months vs 37.6 (95% CI 6.0-78.0) months ( χ (2)=11.42, P =0.001) , respectively. Among the patients in bortezomib regimen, The median PFS and median OS of CD45 (+) group and CD45(-) group were 30.3 (95% CI 10.0-59.0) months vs 36.3 (95% CI 6.0-69.0) months ( χ (2)=14.75, P =0.001) and 34.0 (95% CI 10.0-68.0) months vs 39.5 (95% CI 6.0-78.0) months ( χ (2)=10.62, P =0.001) . ④Cox risk regression model analysis showed that serum creatinine≥176.8 μmol/L ( HR =5.078, 95% CI 1.744-14.723, P =0.001) , CD45 positive ( HR =14.504, 95% CI 0.168-0.42, P =0.001) , LDH≥220 IU/L ( HR =1.308, 95% CI 1.16-2.417, P =0.015) were independent risk prognostic factors. Conclusion: CD45 expression is a risk prognostic factor of MM patients. Bortezomib did not improve the poor prognosis of CD45(+) MM patients.

Objective: To explore the clinical significance of serum bone metabolites β C-termianl telopeptide of type Ⅰ collagen(β-CTX), Procollagen type Ⅰ N-terminal peptide(PINP) concentration and ratio of beta -CTX/PINP in multiple myeloma bone disease (MMBD) and bone metastases. Methods: A total of 31 cases of MM, 46 cases of bone metastases and 12 healthy controls were enrolled in the department of hematology, oncology and physical examination center of Henan Provincial People's Hospital respectively from October 2016 to October 2017. According to the imaging findings, MMBD was divided into 0-4 grades, group A included the patitents with grade 0-2 of osteopathy ( n =8), and group B included the grade 3-4 ( n =23). After two courses of chemotherapy, the curative effect was evaluated. MM group were divided into effective group (above partial remission , n =22) and uneffective group (unreached partial remission, n =9). ELISA method was used to detect the concentration of serum beta -CTX and PINP, and the ratio of beta -CTX/PINP was calculated. Results: The serum beta -CTX concentration in newly diagnosed MM, bone metastases and healthy control were (3 563 ± 544)ng/L, (6 690±343)ng/L, (2 726±1 026)ng/L (χ 2 =22.207, P <0.001), PINP concentration were (72 ± 14) ng/L, (112 ± 62) ng/L, (171 ± 62) ng/L (χ 2 =7.418, P =0.024) , and beta -CTX/PINP ratio were 93±19, 141±21, 17±8 (χ 2 =20.192, P <0.001), the differences were statistically significant. The ratio of initial MM beta -CTX/PINP was higher than that of healthy control ( P =0.001). The concentration of beta -CTX ( P =0.003) and the ratio of beta -CTX/PINP( P <0.001) in bone metastases were higher than those in healthy controls. The serum concentration of beta-CTX in newly diagnosed MM was lower than that in bone metastases ( P <0.001). Before chemotherapy, the serum levels of beta -CTX and PINP in A and B groups were not statistically significant, but the ratio of serum beta -CTX/PINP in A group was lower than that in group B, and the difference was statistically significant. After two courses chemotherapy, the concentration of serum beta -CTX ( P =0.023) and the ratio of beta -CTX/PINP ( P <0.001) were decreased in MM group. There were no significant difference of serum beta -CTX, PINP concentration, and beta-CTX/PINP ratio before and after treatment in Group A. Patients in the group B, there was no significant difference in the changes of serum PINP concentration, but both serum beta -CTX concentration and beta-CTX/PINP ratio decreased after two courses[(4 027 ± 648)ng/L vs (2 370± 460) ng/L, P =0.043; 111± 23 vs 30± 6, P =0.002]. The ratio of serum beta-CTX/PINP decreased in the effective group, and the difference was statistically significant. There was no significant difference in serum beta-CTX, PINP concentration and beta-CTX/PINP ratio before and after treatment in the uneffective group. Conclusions: There is a difference between newly diagnosed MMBD and bone metastases in serum beta-CTX, which might be helpful for differential diagnosis, and the ratio of beta-CTX/PINP is positively correlated with the severity of MMBD, which might be used to evaluate the severity of bone disease and have a certain monitoring significance for the treatment of MM.

Objective: To explore the anti-myeloma effect of suberoylanilide hydroxamic acid (SAHA) and on mouse myeloma cell line SP2/0 in vitro and in vivo and its mechanism., Methods: The inhibitory effect of SAHA on SP2/0 cells was measured by CCK-8 assay,and the apoptosis and cell cycle were analyzed by flow cytometry FACS. The protein expression of Caspase-3 and p53 of SP2/0 cells treated with SAHA were examined by Western blot. Annexin V/7-AAD double staining was performed to detect the apoptosis of SP2/0 induced by SAHA in vitro. SP2/0 cells (1×10 6 ) resuspended in 200 µl PBS were inoculated subcutaneously and intravenously into BALB/c mice, so as to establish aggressive or non-aggressive myeloma-bearing mouse models respectively. On day 3 after modeling, mice received SAHA or vehicle control treatment by intraperitoneal injection. The dose of SAHA was 60 mg/kg·d, 5 times a week for 3 weeks., Results: In SAHA-treated SP2/0 cells, the proliferation inhibition rate and apoptotic cells increased in a dose dependent manner. Also, SAHA significantly increased the ratio of cells in G 2 phase and decreased in S phase. Molecular mechanisms of apoptosis and cell cycle arrest of SP2/0 induced by SAHA partly correlated with up-regulating the expression level of Caspase-3 and p53. In the non-aggressive myeloma-bearing mice, SP2/0 cells disappeared in peripheral blood after SAHA treatment. In the aggressive myeloma-bearing mice, inhibition of tumor growth and prolongation of the cell survival were observed after SAHA treatment., Conclusion: SAHA inhibited SP2/0 cell proliferation, this effect associates with inducing apoptosis and cell cycle arrest, the mechanism of SAHA ralates partly with activating Caspase-3 and p53 pathway.