Clinical and molecular biological characterization of patients with accelerated chronic lymphocytic leukemia / 中华血液学杂志

Objective: To investigate the clinical and molecular biological characteristics of patients with accelerated chronic lymphocytic leukemia (aCLL) . Methods: From January 2020 to October 2022, the data of 13 patients diagnosed with aCLL at The First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed to explore the clinical and molecular biological characteristics of aCLL. Results: The median age of the patients was 54 (35-72) years. Prior to aCLL, five patients received no treatment for CLL/small lymphocytic lymphoma (SLL), while the other patients received treatment, predominantly with BTK inhibitors. The patients were diagnosed with aCLL through pathological confirmation upon disease progression. Six patients exhibited bulky disease (lesions with a maximum diameter ≥5 cm). Positron emission tomography (PET) -computed tomography (CT) images revealed metabolic heterogeneity, both between and within lesions, and the median maximum standardized uptake value (SUVmax) of the lesion with the most elevated metabolic activity was 6.96 (2.51-11.90). Patients with unmutated IGHV CLL accounted for 76.9% (10/13), and the most frequent genetic and molecular aberrations included +12 [3/7 (42.9% ) ], ATM mutation [6/12 (50% ) ], and NOTCH1 mutation [6/12 (50% ) ]. Twelve patients received subsequent treatment. The overall response rate was 91.7%, and the complete response rate was 58.3%. Five patients experienced disease progression, among which two patients developed Richter transformation. Patients with aCLL with KRAS mutation had worse progression-free survival (7.0 month vs 26.3 months, P=0.015) . Conclusion: Patients with aCLL exhibited a clinically aggressive course, often accompanied by unfavorable prognostic factors, including unmutated IGHV, +12, ATM mutation, and NOTCH1 mutation. Patients with CLL/SLL with clinical suspicion of disease progression, especially those with bulky disease and PET-CT SUVmax ≥5, should undergo biopsy at the site of highest metabolic uptake to establish a definitive pathological diagnosis.

Primary thymic mucosa-associated lymphoid tissue lymphoma: 7 clinical cases report and a review of the literature / 中华血液学杂志

Objective: To reveal clinical features, pathological diagnosis, treatment and prognosis of primary thymic mucosa-associated lymphoid tissue (MALT) lymphoma and review literatures. Methods: The clinical characteristics, pathological diagnosis, laboratory texts, treatment and prognosis of 7 cases of primary thymic MALT lymphoma identified at the First Affiliated Hospital of Nanjing Medical University from November 2017 to January 2019 were collected and analyzed. Results: Of 7 primary thymic MALT lymphoma cases, six were female. Patients were often asymptomatic and were found mediastinal mass by chest CT. After mediastinal mass resection, pathologist reported a primary thymic MALT lymphoma. Laboratory tests showed all patients were positive for anti-nuclear antibody, anti-Ro52 antibodies and anti-Sjogren's syndrome A antibodies, and increased erythrocyte sedimentation rate (ESR) . Four were diagnosed with Sjogren's syndrome (SS) . After surgery, the patients were given the positron emission tomography computed tomography (PET-CT) scans. All cases received "watch and wait" approach. Up to now, all cases showed good prognoses and none of them relapsed. Conclusion: Primary thymic MALT lymphoma was rare, and it was often associated with autoimmune diseases. Such patients who usually had good prognoses should be followed up closely and avoided excessive treatments if there were no indications of intervention.

Roles of PET/CT in Predicting the Prognosis of Diffuse Large B Cell Lymphoma Patients Treated with Chimeric Antigen Receptor T Cell Therapy / 中国实验血液学杂志

OBJECTIVE@#To investigate the prognosis prediction value of PET/CT in DLBCL patients treated with CAR-T therapy.@*METHODS@#The effects of PET/CT were retrospectively explored on 13 R/R DLBCL patients who were treated with CAR-T therapy. Parameters reflecting tumor metabolic burden, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured before and after CAR-T treatment.@*RESULTS@#Patients with larger baseline MTV or longer sum of longest diameters showed shorter overall survival (OS) time than those with low tumor burden. Patients achieved complete remission (CR), partial remission (PR) and minor remission (MR) determined by response evaluation criteria in lymphoma (RECIL) in 12 weeks showed progression-free survival and OS time superior to those of patients with no remission. In addition, it was found that 2 patients with residual masses classified as PR by contrast-enhanced CT of patients were evaluated as complete metabolic response by PET/CT imaging.@*CONCLUSION@#PET/CT shows a great value in the evaluation of prognosis and response in CAR-T-treated R/R DLBCL patients.

The Clinical and Laboratory Characteristics of Adult Langerhans Cell Histiocytosis Patients and the Influencing Factors of Prognosis / 中国实验血液学杂志

OBJECTIVE@#To observe the clinical and laboratory characteristics of adult Langerhans cell histiocytosis(LCH) patients and to analyze the influencing factors of its prognosis.@*METHODS@#The clinical and laboratory charac-teristics of 38 adult LCH patients treated in our hospital from January 2010 to August 2019 were retrospective analyzed, and the clinical prognosis of the patients was analyzed.@*RESULTS@#The median age of 38 patients was 41 (21-65) years old, and the ratio of male and female was about 2∶1. Among 38 patients, 44.7% (17/38) were involved in multiple systems, and 31.6% (12/38) were involved in high-risk organs (including liver, lung, hematopoietic system or spleen). The bone involvement was the most common (21/38, 55.3%), and the most common clinical symptom was pain (19/38, 50.0%). The result of laboratory showed that anemia (4/38，10.5%), thrombocytopenia (1/38，2.6%), neutropenia (2/38，5.3%), lymphopenia (6/38，15.8%), monocytosis (11/38，28.9%), C-reactive protein increasing (6/21，28.6%), erythrocyte sedimentation rate increasing (10/18, 55.3%), and ferritin protein increasing (9/17, 55.3%). The median follow-up time was 53 months, and a total of 5 patients were died. The 10-year overall survival rate of patients with single-system involvement was 100%, which was significantly higher than that of patients with multiple-system involvement (70.1%) (P=0.0078). The prognosis of patients without risk-organ involvement was better than that of patients with risk-organ involvement (10-year overall survival rate: 100% vs 60.6%) (P=0.0007). Further analysis showed that in addition to multiple-system involvement and risk-organ involvement, the increase of peripheral blood monocyte cells and the increase of ferritin protein were also associated with poorer prognosis of the patients.@*CONCLUSION@#The multiple system involve-ment and risk-organ involvement, the increasing of monocyte cells and the increasing of ferritin protein were the independent risk factors of adult LCH patients.

EBV-miR-BHRF1-1 Targets p53 Gene: Potential Role in Epstein-BarrVirus Associated Chronic Lymphocytic Leukemia / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The purpose of this study was to investigate the prognostic impact of Epstein-Barr virus(EBV)–microRNA (miRNA, miR)-BHRF1-1 with chronic lymphocytic leukemia (CLL) as wellas role of EBV-miR-BHRF1-1 in p53 gene. @*Materials and Methods@#Quantitative reverse transcription–polymerase chain reaction and western blotting wereused to quantify EBV-miR-BHRF1-1 and p53 expression in cultured CLL. @*Results@#p53 aberration was associated with the higher expression level of EBV-miR-BHRF1-1 (p <0.001) which was also an independent prognostic marker for overall survival (p=0.028;hazard ratio, 5.335; 95% confidence interval, 1.193 to 23.846) in 97 newly-diagnosed CLLpatients after adjusted with International Prognostic Index for patients with CLL. We identifiedEBV-miR-BHRF1-1 as a viral miRNA regulator of p53. EBV-miR-BHRF1-1 repressedluciferase reporter activity by specific interaction with the seed region within the p53 3-untranslated region. Discordance of p53 messenger RNA and protein expression wasassociated with high EBV-miR-BHRF1-1 levels in CLL patients and cell lines. EBV-miR-BHRF1-1 inhibition upregulated p53 protein expression, induced cell cycle arrest and apoptosisand decreased cell proliferation in cell lines. EBV-miR-BHRF1-1 mimics downregulated p53protein expression, decreased cell cycle arrest and apoptosis, and induced cell proliferationin cell lines. @*Conclusion@#This study supported the role of EBV-miR-BHRF1-1 in p53 regulation in vitro. Our resultssupport the potential of EBV-miR-BHRF1-1 as a therapeutic target in EBV-associated CLLwith p53 gene aberration.

Diabetes Mellitus Is Associated with Inferior Prognosis in Patients with Chronic Lymphocytic Leukemia: A Propensity Score-Matched Analysis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Diabetes mellitus (DM) is associated with elevated cancer risk and poor survival outcome in malignancies. The objective of this study was to evaluate the prognostic value of preexisting DM in chronic lymphocytic leukemia (CLL). @*Materials and Methods@#Six hundred and thirty-three subjects with newly-diagnosed CLL between 2007 and 2016 were recruited. Propensity score-matched method was performed to balance baseline characteristics and eliminate possible bias. Univariate and multivariate Cox regression analyses screened the independent risk indicators for time-to-first-treatment (TTFT) and cancer-specific survival (CSS) of CLL. Receiver operator characteristic curves and the corresponding areas under the curve assessed the predictive accuracy of CLL–International Prognostic Index (IPI) together with DM. @*Results@#The results showed that 111 patients had pre-existing DM. In the propensity-matched cohort, DM was correlated with inferior TTFT and CSS in CLL patients, and it was an independent prognostic factor for both CSS and TTFT. Pre-diabetics also shared undesirable prognostic outcome compared with patients with no diabetic tendency, and a positive association between longer diabetic duration and poorer prognosis of CLL was identified. DM as one additional point to CLL-IPI had larger area under the curve compared with CLL-IPI alone in CSS prediction and could improve the prognostic capacity of CLL-IPI. @*Conclusion@#Pre-existing DM was found to be a valuable prognostic predictor and could help predict life expectancy and build refined prognostication models for CLL.

High-dose methylprednisolone with Rituximab and fresh frozen plasma in the treatment of six patients with B-cell lymphoproliferative disorders harboring TP53 abnormalities / 中华血液学杂志

Objective: To investigate whether high-dose methylprednisolone with Rituximab and fresh frozen plasma (HDMP+RTX+FFP) is an effective therapy for patients with B-cell chronic lymphoproliferative disorders (B-CLPD) with TP53 abnormalities. Methods: Six B-CLPD patients with TP53 abnormalities from May 2008 to May 2012 were prospectively enrolled in the study. The patients were treated with HDMP+RTX+FFP for up to 6 cycles. Results: Of the six B-CLPD patients, there were 4 cases of chronic B-cell lymphoproliferative disorders-unclassified (B-CLPD-U) , 1 B-cell prolymphocytic leukemia (B-PLL) and 1 mantle cell lymphoma (MCL) . After a median 3 courses of treatment, 4 patients achieved complete remission (CR) including 3 with undetectable minimal residual disease (MRD(-)) . One patient was evaluated as stable disease (SD) and another one patient was in disease progression (PD) . After a median follow-up of 30 (4-56) months, 2 non-responders progressed quickly and died. All of CR patients survived and no one succumbed to disease progression at the last follow-up. The hematopoietic function was significantly improved after the treatment whereas there was also significant decrease in serum IgA, IgG and IgM levels. All patients showed well tolerance to this regimen. The incidence of myelosuppression was low and adverse events (AE) were mainly neutropenia which did not exceed grade 3 and infection. All AE were controllable. Conclusion: HDMP+RTX+FFP is an effective and relatively tolerable therapy for patients with B-CLPD accompanying with TP53 abnormalities.

Clinical observation of five pediatric-type follicular lymphoma in adult / 中华血液学杂志

Objective: To investigate the characteristics in pathological diagnosis, clinical features, treatment and prognosis of adult patients with pediatric-type follicular lymphoma (PTFL) . Methods: The clinical and pathological features, laboratory examination, diagnosis and treatment, follow-up results of 5 adult PTFL patients admitted in Jiangsu Province Hospital were retrospectively analyzed, and literature review was conducted in combination with related reports. Results: All 5 patients developed PTFL in their adulthood with a median age of 22 years old (15-33 years) . The initial inanifestation of the disease was local painless lymphadenopathy with no fever, night sweats, emaciation or other systemic B symptoms. Pathological characteristics including typical large follicular structures and high proliferation index were found. Meanwhile, additional clonal rearrangement of immunoglobulin heavy chain gene was observed. However, there was no BCL-2 expression in histochemistry as well as BCL-2 gene abnormality in fluorescence in situ hybridization among these PTFL patients. These adult PTFL patients were all in stage Ⅰ-Ⅱ of the disease. For treatment, they were only treated with local surgical excision after diagnosis while didn't receive subsequent local radiotherapy or systemic immunochemotherapy. During a median follow-up of 27 months, the 5 cases of PTFL kept in a state of sustained complete remission. Conclusion: Adult-onset PTFL is characterized by high pathological proliferation index, while no BCL-2 expression or BCL-2 gene abnormality. Besides, PTFL is clinically manifested as a localized disease that can achieve a quite good prognosis through local surgical intervention. The aforementioned attributes of PTFL are distinctly different from classic adult follicular lymphoma.

The Prognostic Role of Circulating Epstein-Barr Virus DNA Copy Number in Angioimmunoblastic T-Cell Lymphoma Treated with Dose-Adjusted EPOCH / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Determine the frequency and prognostic value of circulating Epstein-Barr virus (EBV) DNA copy number in angioimmunoblastic T-cell lymphoma (AITL) patients who were treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH) regimens. MATERIALS AND METHODS: Sixty newly-diagnosed AITL patients were retrospectively enrolled in the present study. All patients were treated with DA-EPOCH regimen. RESULTS: Twenty-two subjects (36.7%) had a EBV DNA-positive test at diagnosis. EBV DNA‒positive patients were associated with lower lymphocyte-monocyte ratio (p=0.024). Median follow-up was 40 months (range, 14 to 100 months). The overall response rate for all the 60 AITL patents were 71.7% (95% confidence interval [CI], 58.6 to 82.5) with 3-year progressive-free survival (PFS) rate of 30.9%±6.1% and overall survival (OS) rate of 60.1%±6.6%. Not only did PFS estimation differ between the EBV DNA‒positive and EBV DNA‒negative group (hazard ratio [HR], 2.24; 95% CI, 1.15 to 4.35; p=0.006), but also worse OS was observed in the pretreatment EBV DNA‒positive group than in the EBV DNA‒negative group (HR, 2.74; 95% CI, 1.22 to 6.19; p=0.006). EBV DNA test positivity was independent prognostic marker for both PFS (HR, 2.17; 95% CI, 1.17 to 4.00; p=0.014) and OS (HR, 3.24; 95% CI, 1.48 to 7.11; p=0.004) after adjusting International Prognostic Index and prognostic index for AITL score. Reduction in EBV copies was significantly associated with therapy-response. CONCLUSION: Circulating EBV DNA level was an important prognostic and monitoring marker for AITL patients who treated with DA-EPOCH regimens which cannot improve outcomes for AITL patients.

Clinical Analysis of 37 Patients with Primary Tonsil Diffuse Large B Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical manifestation, immunophenotypes and prognostic factors of patients with primary tonsil afftive large B cell lymphoma ( PT-DLBCL ).@*METHODS@#The clinical data including clinical characterstics, typing, staging, treatment efficacy and prognostic factors of PT-DLBCL patients were collected and analyzed restrospectively.@*RESULTS@#Out of 36 cases with the detinite cell origin, 24 cases (66.7%) were detecmined as the type of germinal center B-cell (GCB) and 12 cases (33.3%) was non-germinal center B-cell (non-GCB), 15 (40.5%) out of 37 cases were in Ann Arbor stage Ⅰ, and 22 (59.5%) in stage Ⅱ. With the median follow-up of 44 (10-101) months, 2 cases (5.4%) failed to be followed-up, after treatment for 6 (3-8) cycles 35 patients were evaluated. Among them 26 cases (74.3%) reached to complete remission (CR), 8 cases (22.9%) to partial remission ( PR ), and 1 (2.8%) to stable disease (SD). Both the 3 years and 5 years progression-free survival ( PFS ) were 82.5%, and both 3 and 5 years overall survival (OS) were 95.5%. 5 cases (13.5%) received radiotherapy. The patients aged＞60 ( P＜0.05 ) or aged＞70 (P＜0.05) had shorter PFS than younger patients. The patients with increased lactic dehydrogenase ( LDH ) level (P＜0.01) and without rituximab (R) (P＜0.05) in the treatment regimen had relatively short OS.@*CONCLUSION@#The patients sensitive to chemotherapy and/or radiotherapy have a good prognosis. Most of the patients can obtain long-term survival after treatment. The effect of combined immunotherapy are better than that of the simple chemotherapy.

Circulating Low Absolute CD4⁺ T Cell Counts May Predict Poor Prognosis in Extranodal NK/T-Cell Lymphoma Patients Treating with Pegaspargase-Based Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is a rare subtype of non-Hodgkin lymphoma, and asparaginase-based regimens are the best first-line treatments. Data on the role of specific circulating lymphocyte subsets in the progression of ENKTL are limited. The aim of this study was to investigate the clinical correlation and distribution of circulating absolute CD4+ T-cell counts (ACD4Cs) in ENKTL. MATERIALS AND METHODS: We retrospectively searched medical records for 70 newly diagnosed ENKTL patients treated with pegaspargase-based regimens. Comparison of ACD4Cs as a continuous parameter in different groups was calculated. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS). RESULTS: Stage III/IV, B symptoms, elevated lactate dehydrogenase, monocytopenia, high-intermediate and high risk International Prognostic Index (IPI) and Korean Prognostic Index (KPI), high risk Prognostic Index of Natural Killer Lymphoma (PINK), and lower lymphocytes were significantly associated with low ACD4C at diagnosis. With a median follow-up time of 32 months, patients who had an ACD4C < 0.30×109/L had a worse OS. Median OS was 11 months and median PFS was 5 months in the low ACD4C cohort. There were significant differences in both OS and PFS between the two cohorts. Moreover, multivariate Cox analysis identified ACD4Cs as an independent predictor for OS and PFS. CONCLUSION: Low ACD4Cs were associated with poorer survival and could act as a negative predictor for ENKTL patients treated with asparaginase-based regimens.

Clinical analysis of 100 adult patients with pure red cell aplasia / 中国实用内科杂志

OBJECTIVE: To evaluate clinical characteristics and treatment response of 100 patients with pure red cell aplasia(PRCA).METHODS: We retrospectively analyzed the clinical data of 100 adult patients with acquired PRCA from October2009 to July 2019, and compared the difference in efficacy between idiopathic and secondary patients.RESULTS: 100 patients were evaluated, including 60 idiopathic patients and 40 secondary patients.The most common reasons for secondary PRCA were large granular lymphocytic leukemia(LGLL)(28 cases,70.0%)and thymoma(6 cases, 15.0%). The remission induced regimens included corticosteroids(CS), cyclosporine A(CsA), or other agents, and the response rate were 66.7%,71.4% and 50%, respectively(P=0.336). Secondary PRCA was less effective than idiopathic PRCA(52.5%,78.3%,P=0.007). PRCA related to large granular lymphocytic leukemia was also less effective compared to idiopathic PRCA(46.4%,79.3%,P=0.003). When treated by CsA, idiopathic PRCA was more effective than secondary PRCA and LGLL related PRCA(P=0.001, P=0.000). Logistic regression analysis showed that lower response rate was related to secondary PRCA and LGLL related PRCA.CONCLUSION: The response rate were similar by different induced regimens. Idiopathic PRCA could acquired better response to CsA than secondary, LGLL related PRCA was less effective to treatment.

The prognostic significance of peripheral lymphocyte/monocyte ratio and PET-2 evaluation in adult Hodgkin's lymphoma / 中华血液学杂志

Objective: To evaluate the prognostic value of lymphocyte to monocyte ratio (LMR) and PET scan performed after first two cycles of chemotherapy (PET-2) in Hodgkin's lymphoma (HL) . Methods: The clinical data of 133 patients with HL diagnosed from January 2007 to March 2016 at the First Affiliated Hospital of Nanjing Medical University, were retrospectively analyzed. The X-tile software was used to calculate the optimal cut-off value of LMR. Kaplan-Meier method and Cox regression were used for survival analysis. Results: The median age of 133 HL patients was 33 (18-84) years, and the male to female ratio was 1.9∶1. The optimal cut-off value of LMR was 2.5, and progression free survival (PFS) (P<0.001) and overall survival (OS) (P<0.001) were significantly lower in the LMR<2.5 group than that of LMR≥2.5. Multivariate survival analysis showed that LMR<2.5 was an independent predictor of PFS (P=0.002, HR=2.35, 95%CI 1.36-4.07) and OS (P=0.002, HR=10.36, 95%CI 2.35-45.66) in HL patients. The analysis of PET-2 from 56 HL patients showed that PET-2 positive patients had significantly poorer PFS (P=0.022) . After grouping LMR combined with PET-2, significant differences were found in PFS and OS between the three groups (P values were 0.009 and 0.012) . Conclusion: LMR<2.5 is an independent prognostic factor for patients with HL. PET-2 combined with LMR may have better prognostic value.

Survival analysis of 118 chronic lymphocytic leukemia patients with abnormal TP53 gene in the era of traditional immunochemotherapy / 中华血液学杂志

Objective: To analyze the survival and first-line immune-chemotherapy (CIT) of chronic lymphocytic leukemia (CLL) with abnormal TP53 gene in the era of traditional CIT. Methods: The clinical data of 118 CLL patients diagnosed from January 2003 to August 2017 were collected. Survival was analyzed according to indicators including sex, age, Binet risk stratification, B symptoms, β(2)-microglobulin (β(2)-MG) , immunoglobulin heavy chain variable region gene (IGHV) mutation status, chromosome karyotype and TP53 gene deletion/mutation. The efficacy of first-line CIT of 101 CLL patients was further analyzed. Results: Among 118 patients, median progression-free survival (PFS) was 12 (95%CI 10.148-13.852) months and median overall survival (OS) was 53 (95%CI 41.822-64.178) months, only 30.5% patients survived over 5 years. Low β(2)-MG<3.5 mg/L indicated longer PFS (P=0.027) , female and Binet A patients had longer OS (P=0.011 and 0.013, respectively) . Of 118 patients, 17 (14.4%) didn't receive any therapy until follow-up time or the dead time. Among the 101 patients who received ≥1 CIT, median time to first treatment (TTFT) was 1 (0-62) months, patients in Binet A had longer TTFT (P<0.001) compared to the patients in Binet B/C. According to statistical needs, we divided those first-line CIT into four groups: there were 30 cases (29.7%) in mild chemotherapy group (mainly treated with nitrogen mustard phenylbutyrate or rituximab alone) , 32 cases (31.7%) in the fludarabine-containing group, 23 cases (22.8%) in high-dose methyprednisolone (HDMP) containing group and 16 cases (15.8%) in the other chemotherapy group. The first regimen contained HDMP can bring longer PFS (P<0.001) , however the OS between four groups had no statistical differences. Conclusion: CLL patients with abnormal TP53 gene had poor response to immunotherapy, rapid clinical progressing, first-line immunotherapy containing HDMP can prolong PFS and will create an opportunity for patients to participate in clinical trials of novel drugs.

Presence of serum antinuclear antibodies correlating unfavorable overall survival in patients with chronic lymphocytic leukemia / 中华医学杂志(英文版)

BACKGROUND@#Serum antinuclear antibodies (ANAs) are positive in some patients with chronic lymphocytic leukemia (CLL), but the prognostic value of ANAs remains unknown. The aim of this study was to evaluate the role of ANAs as a prognostic factor in CLL.@*METHODS@#This study retrospectively analyzed clinical data from 216 newly diagnosed CLL subjects with ANAs test from 2007 to 2017. Multivariate Cox regression analyses were used to screen the independent prognostic factors related to time to first treatment (TTFT), progression free survival (PFS) and overall survival (OS). Receiver operator characteristic curves and area under the curve (AUC) were utilized to assess the predictive accuracy of ANAs together with other independent factors for OS.@*RESULTS@#The incidence of ANAs abnormality at diagnosis was 13.9%. ANAs positivity and TP53 disruption were independent prognostic indicators for OS. The AUC of positive ANAs together with TP53 disruption was 0.766 (95% confidence interval [CI]: 0.697-0.826), which was significantly larger than that of either TP53 disruption (AUC: 0.706, 95% CI: 0.634-0.772, P = 0.034) or positive ANAs (AUC: 0.595, 95% CI: 0.520-0.668, P < 0.001) in OS prediction. Besides, serum positive ANAs as one additional parameter to CLL-international prognostic index (IPI) obtained superior AUCs in predicting CLL OS than CLL-IPI alone.@*CONCLUSION@#This study identified ANAs as an independent prognostic factor for CLL, and further investigations are needed to validate this finding.

Prognostic Value of Baseline and Interim Total Metabolic Tumor Volume and Total Lesion Glycolysis Measured on ¹⁸F-FDG PET-CT in Patients with Follicular Lymphoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to investigate the prognostic significance of total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) in patients with follicular lymphoma (FL) at baseline and mid-treatment with ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scans. MATERIALS AND METHODS: The study analyzed data from 48 patients with FL who were treated in Jiangsu Province Hospital and reviewed their baseline PET-CT scans. TMTV and TLG were computed by using the absolute value of 2.0, 2.5, and 3.0 thresholding method, respectively. RESULTS: Median age was 53 years, 75.0% of patients had stage III to IV disease, 43.8% had a Follicular Lymphoma International Prognostic Index 1 (FLIPI1) score of 3 to 5 and 20.8% had a FLIPI2 score of 3 to 5. Receiver operating characteristic (ROC) curve analysis showed the optimal cut-off values for TMTV3.0 and TLG3.0 were 476.4 (sensitivity, 85.7%; specificity, 78.0%; area under the curve [AUC], 0.760; p=0.003) and 2,676.9 (sensitivity, 71.4%; specificity, 78.0%; AUC, 0.760; p=0.003). On multivariable analysis, TMTV3.0 and TLG3.0 were independent predictors of both progression-free survival (PFS) (hazard ratio [HR], 5.406; 95% confidence interval [CI], 1.326 to 22.040; p=0.019 and HR, 6.502; 95% CI, 1.079 to 39.182; p=0.042) and overall survival (OS) (HR, 4.111; 95% CI, 1.125 to 15.027; p=0.033 and HR, 5.885; 95% CI, 1.014 to 34.148; p=0.049). ROC curve analysis showed the optimal cut-off values for ΔTMTV3.0 and ΔTLG3.0 were 66.3% (sensitivity, 85.7%; specificity, 63.4%; AUC, 0.774; p 66.3%) and TLG (ΔTLG > 64.5%) reduction are valuable tools for early treatment response assessment in FL patients.

Albumin-to-Fibrinogen Ratio as an Independent Prognostic Parameter in Untreated Chronic Lymphocytic Leukemia: A Retrospective Study of 191 Cases / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Chronic lymphocytic leukemia (CLL) is one of the most frequent type of B-cell chronic lymphoproliferative disorders and chronic inflammation takes part in the development of CLL. However, there has been no valid immune biomarker to predict the prognosis of untreated CLL patients. MATERIALS AND METHODS: In this retrospective study, we analyzed the clinical correlations and prognostic value of albumin-to-fibrinogen ratio (AFR) detected at diagnosis in 191 CLL patients. RESULTS: The cut-off value of AFR was 9.7 calculated by X-tile. Patients who were more than 65 years old were often accompanied by low level of AFR (p < 0.001). Survival analysis showed that patients with low level of AFR had shorter overall survival (OS) than patients with high level of AFR (p < 0.001). Multivariate analysis illustrated that AFR had a negative impact on OS (p=0.003) and was independent of parameters involved in CLL international prognostic index and other prognostic markers such as CD38 and ZAP-70. CONCLUSION: These data provide a comprehensive view of AFR and shows that AFR at diagnosis is an adverse prognostic factor in untreated CLL patients.

Prognostic value of lymphocyte-to-monocyte ratio in angioimmunoblastic T cell lymphoma / 中华血液学杂志

Objective: To evaluate the prognostic value of lymphocyte-to-monocyte ratio (LMR) in angioimmunoblastic T cell lymphoma (AITL). Methods: Data of 64 patients diagnosed as AITL at the First Affiliated Hospital of Nanjing Medical University between June 2009 and July 2017, were analyzed retrospectively. Receiver Operator Characteristic (ROC) curve was used to calculate the cutoff value of LMR to divide this cohort of patients into high and low LMR groups. Characteristics between groups were compared by Pearson Chi-square or Fisher exact tests. Kaplan-Meier method and Cox regression were performed to probe prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Results: A total of 64 cases [39 cases male and 25 ones female with the median age of 63 (29-89) years old] were enrolled. The cutoff value of LMR was 3.07. Patients with low LMR showed inferior PFS (9 months vs 13 months, P=0.044) and OS (16 months vs not reached, P=0.014), respectively than those without low LMR during a median follow-up of 33 months (5 to 103 months). Multivariate analysis showed that low LMR was an independent prognostic factor associated with poor outcomes (HR=0.48, 95% CI 0.26-0.92 for PFS, P=0.027; HR=0.38, 95% CI 0.18-0.82 for OS, P=0.013, respectively). Subgroup analysis showed that patients with low LMR and under the situation of high score of Prognostic Index for peripheral T-cell lymphoma, Unspecified (PIT) (2-4) had shorter PFS and OS (P=0.013 and P=0.031, respectively). But in low score of PIT (0-1) group, low LMR seemed to play almost no effects on PFS and OS (P=0.949 and P=0.238, respectively). Conclusions: The disease risk status of patients could be initially assessed according to PIT score and LMR level. Low LMR was demonstrated to be able to predict poor outcome in AITL.

Prognostic significance of CLL-IPI for Chinese patients with chronic lymphocytic leukemia / 中华血液学杂志

Objective: To validate the prognostic value of chronic lymphocytic leukemia-international prognostic index (CLL-IPI) for Chinese CLL patients. Methods: Two hundred and fifteen CLL patients who were initially diagnosed and treated in Jiangsu Province Hospital from January 2002 to November 2017 were included in the retrospective analysis. Risk stratification and prognosis were evaluated by CLL-IPI scoring system. Results: ①Of the 215 patients, 143 were males and 72 were females, with a median age of 60 (16-85) years old. The median treatment-free survival (TFS) and overall survival (OS) was 16 months (4-24 months) and 180 months (145-215 months), respectively. ② The median TFS for low (n=60), intermediate (n=50), high (n=45) and very high risk group (n=60) according to the CLL-IPI scoring system was 56, 15, 12 and 5 months, respectively (P<0.001). ③ The median follow-up was 48 months (1-192 months). The median OS for low risk group was not reached and for intermediate, high, and very high risk group was 180, 89 and 74 months, respectively. The estimated 5-year OS rate was 97.6%, 83.7%, 67.8% and 55.2%, respectively (P<0.001). ④ Multivariate analysis indicated that unmutated immunoglobulin heavy chain variable region (IGHV) gene and β(2)-microglobulin>3.5 mg/L(P<0.001) were independent prognostic factors of TFS, while TP53 deletion and/or mutation(P=0.008), unmutated IGHV (P=0.017) and age>65 years(P=0.045) were independent prognostic factors of OS. Conclusion: CLL-IPI is the powerful tool for risk stratification in Chinese CLL patients.

Expression of BAG3 Gene in Acute Myeloid Leukemia and Its Prognostic Value / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression of BAG3 gene in acue myeloid leukemia (AML) and its prognostic value.</p><p><b>METHODS</b>Real-time quantitative RT-PCR was used to detect the expression of BAG3 mRNA in 88 previously untreated AML patients. The corelation of BAG3 expression level with clinical characteristics and known prognostic markers of AML was analyzed.</p><p><b>RESULTS</b>In 88 patients with AML, the expression of BAG3 mRNA in NPMI mutated AML patients was obviously lower than that in NPMI unmutated patients (P = 0.018). The expression level of BAG3 mRNA did not related to clinical parameters, such as age, sex, FAB subtype, WBC count, extra-modullary presentation, and to prognostic factors including cytogenetics, FLT3-ITD, c-kit and CEBPα mutation status (P > 0.05). The expression level of BAG3 had no obvious effect on complete remission (CR) of patients in first treatment. The expression level of BAG3 in non-M3 patients was higher than that in relapsed patients (P = 0.036). The expression level of BAG3 had no effect on overall survival (OS) of patients.</p><p><b>CONCLUSION</b>The expression level of BAG3 does not correlated with known-prognostic markers of AML, only the expression level of BAG3 in NPM1 mutated patients is lower than that in NPM1 unmutated patients. The expression level of BAG3 has no effect on OS of AML patients, the BAG3 can not be difined as a prognostic marker in AML.</p>