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Objective:To explore the clinical features and prognostic related factors of B-cell chronic lymphoproliferative disorders unclassified (B-CLPD-U).Methods:The clinical data of 39 patients diagnosed with B-CLPD-U in the First Affiliated Hospital of Harbin Medical University from January 2012 to January 2019 were retrospectively analyzed. Patients were regularly treated with COP regimen (30 cases) or fludarabine regimen (9 cases). The χ 2 test was used to analyze the relationship between the clinical characteristics and the efficacy of the patients. The Kaplan-Meier method was used for survival analysis and the log-rank test was used for single factor analysis. The Cox proportional hazard regression model was used for multivariate analysis, and the receiver operating characteristic (ROC) curve was used to analyze the value of platelet-to-lymphocyte ratio (PLR) in prognostic evaluation. Results:Among 39 patients, there were 24 males and 15 females, and the median age was 60 years old (37-78 years old). The international prognostic index (IPI) score was 0 to 2 in 19 cases (48.7%), and 3 to 5 in 20 cases (51.3%). The overall response rate (complete remission plus partial remission) rate (ORR) of the patients was 82.1% (32/39). The ORR of patients with normal lactate dehydrogenase (LDH) (≤ 245 U/L) was higher than that of patients with elevated LDH (> 245 U/L). The ORR of patients with Ann Arbor stage Ⅰ-Ⅱ was higher than that of patients with stage Ⅲ-Ⅳ, and the differences were statistically significant [95.5% (21/22) vs. 64.7% (11/17), 100.0% (15/15) vs. 70.8% (17/24), all P < 0.05]. At the end of the follow-up in October 2019, 31 cases (79.5%) survived and 8 cases (20.5%) died of 39 patients; the median overall survival(OS) time was 40.0 months (95% CI 36.0-55.2 months). Univariate analysis showed that patients with elevated LDH and age over 60 years had poor OS, and the difference was statistically significant (all P <0.05), while there were no statistically significant differences in OS between patients with gender, Ann Arbor staging, IPI score, Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) score, anemia, B symptoms, COP-based chemotherapy or fludarabine-based chemotherapy, and different absolute lymphocyte (ALC) stratification (all P > 0.05). Multivariate analysis showed that LDH level ( HR = 0.411, 95% CI 0.172-0.981, P = 0.045) and age ( HR = 2.242, 95% CI 1.045-4.808, P = 0.038) were independent influencing factors of OS (both P < 0.05). The median PLR was 59.07 (1.18-276.26). ROC curve analysis showed that the area under the curve for PLR to predict OS was 0.565. Conclusion:B-CLPD-U is more common in middle-aged and elderly patients, and it is more commonly found in men than women. Elevated LDH and age over 60 years are independent risk factors for survival of patients with B-CLPD-U. The evaluation of sensitivity and specificity of the prognosis in B-CLPD-U patients by using PLR will be not that ideal.
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Objective To study dose-response relationship and screen the optimized fractionated irradiation schedules in subclinical tumors of malignant glioma.Methods Balb/c-nude mice bearing human malignant glioma xenograft were assigned randomly into control group,fractionated irradiation schedules group and nimotuzumab-conventional fraction group.The fractionated schedules were 200 cGy x 5f/w,300 cGy ×5f/w,160 cGy ×2f/d x5 d and 400 cGy ×3f/w with total dose of 40 Gy and 60 Gy,respectively.Measurement indexes were tumor-forming rate,average recurrence time and maximum diameter of the tumor bottom.The observation lasted 24 weeks.Results With the total dose of 40 Gy,none of the significant long-term tumor regression were detected in any fractionated irradiation schedules; 400 cGy x 3f/w with complete tumor response at the end of treatment showed a better short-term curative effect.With the total dose of 60 Gy,long-term control rate of each fractionated irradiation schedule group was improved with prolonged average recurrence time of varable degrees,except 200 cGy x 5f/w fractionated schedule (tumor formation rate was 100％ at the end of treatment and average recurrence time was the poorest of 108 d).160 cGy × 2f/d × 5 d fractionated schedule showed the best curative effect with no tumor formation in 2 of 8 mice and longest recurrence time of 143 d.300 cGy x 5f/w fractionated schedule ranked second with no tumor formation in 1 of 8 mice and average recurrence time was 137 d.400 cGy x 3f/w fractionated schedule produced the poorest outcome with no case cured.There were no significant changes in the tumor-forming rate or average recurrence time when nimotuzumab was concurrently used for subclinical tumors of malignant glioma with total dose of 60 Gy.Conclusions Conventional fractionated irradiation is not the best option to control the sustained growth.160 cGy ×2f/d ×5 d and 300 cGy × 5f/w might be the optimized fractionated irradiation schedules for subclinical tumors of malignant glioma.
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Objective To evaluate the radiobiological effect of different irradiation fractionated regimens in human glioma cells ( BT 325 cell line). Methods The xenografts in Balb/c-nude mice were irradiated with different single and fractionated regimens. The single fraction dose was 10, 20, 30, 40 and 60 Gy, respectively. The fractionated regimens were 2 Gy × 5 fractions ( irradiated every day), and 3 Gy ×3 fractions (irradiated every other day), 3 Gy × 5 fractions (irradiated every day) and 4 Gy × 3 fractions (irradiated every other day), with total doses of 125 Gy, 114 Gy, 126 Gy and 112 Gy, respectively. The growth curve was used to evaluate the tumor doubling time. clonogenic assays was performed to draw the cell survival curve and analyze the radiobiological parameters with doses of 1, 2, 4, 6, 8 and 10 Gy. T1/2 was measured by comet assay. Results Tumor regression were not observed by single fraction irradiation, 2 Gy × 5 fractons and 3 Gy × 3 fractions irradiation regimens. The tumor regress was more significant with the increas of fraction dose. The 4 Gy × 3 fractionrs inhibited tumor more though not curing tumor. The cell doubling time of the BT 325 cell was 30. 16 h and the tumor doubling time of the xenograft was 43 days.When fitted with L-Q model ,α was 0. 36 Gy -1 and β was 0. 057 Gy -2. When fitted with the single-hit multitarget model, D0 was 1. 394 Gy, Dq was 2. 127 Gy and SF2 was 0. 714, respectively. The T1/2 was 9. 999min. Conclusions Glioma is a radioresistant tumor. Increase of the fraction dose improves recent effect.Further study is needed to control the tumor stem cells.