MYC protein expression is associated with poor prognosis in diffuse large B cell lymphoma patients treated with RCHOP chemotherapy.

This study aims to investigate the prognostic significance of the MYC protein expression in diffuse large B cell lymphoma (DLBCL) patients treated with RCHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). A total of 60 patients with DLBCL from 2008 to 2013 were included. Formalin-fixed, paraffin-embedded DLBCL samples were analyzed for MYC protein expression and divided into high or low MYC group. The MYC protein expression and the international prognostic variables were evaluated. The high MYC protein expression predicted a shorter 3-year estimated overall survival (OS) and progression-free survival (PFS) versus the low MYC protein expression (57 % vs. 96 %, P < 0.001 and 50 % vs. 96 %, P = 0.001, respectively). Multivariate analysis confirmed the prognostic significance of the MYC protein expression for both OS (HR, 11.862; 95 % CI, 1.462-96.218; P = 0.021) and PFS (HR, 6.073; 95 % CI, 1.082-34.085; P = 0.040). MYC protein expression with International Prognostic Index (IPI) score distinguished patients into three risk groups with different 3-year OS rates (χ (2) 23.079; P < 0.001) and distinct 3-year PFS rates (χ (2) 15.862; P < 0.001). This study suggests that the MYC protein expression is an important inferior prognostic factor for survival in patients with DLBCL treated with RCHOP. The combinative model with IPI score and MYC protein expression could stratify DLBCL patients into prognostically relevant subgroups more effectively than either the IPI or the MYC alone.

[Profiles of different subsets of CD(4)(+) T cells in chronic idiopathic thrombocytopenic purpura].

OBJECTIVE: To explore the profiles of Th1, Th2, Th17 and Regulatory T (Treg) cells in patients with chronic idiopathic thrombocytopenic purpura (ITP). METHODS: Samples of peripheral blood were collected from 35 chronic ITP patients (21 in an active stage group, 5 in a non-remission stage group, 9 in a remission stage group) and also from 18 healthy subjects. Flow cytometry was used to measure the intracellular cytokines interferon (IFN)gamma, interleukin (IL)-4 and IL-17 so as to identify the Th1, Th2 and IL-17 cells. Treg cells were identified with CD(4)(+) CD(25)(+) Foxp3(+) cells and uncultured peripheral blood was used to measure the CD(4)(+) CD(+)(25) Foxp3(+) cells with flow cytometry. The concentrations of IFNgamma, IL-4, IL-17 and IL-10 in plasma specimens were detected with ELISA method and its correlation with peripheral platelets counts and megakaryocytes number was analyzed, respectively. RESULTS: There were no statistically significant differences between any two of the three groups for the percentage of Th1 cells, Th17 cells and Th1/Th17 ratio. The percentage of Th2 cells was (1.01 +/- 0.88)% in active stage and (1.22 +/- 1.04)% in non-remission stage, being significantly decreased than those in remission stage (1.93 +/- 1.04)% (P < 0.05) and the controls (1.86 +/- 0.59)% (P < 0.05). Th1/Th2 ratio was 15.04 +/- 9.67 in active stage, 11.65 +/- 9.32 in non-remission stage, which were significantly higher than those in remission stage (7.17 +/- 5.38, P < 0.05) and the controls (7.02 +/- 3.01, P < 0.05). The percentage of Treg cells was (0.89 +/- 0.58)% in active stage and (1.46 +/- 1.27)% in non-remission stage, being significantly decreased than those in remission stage (6.41 +/- 1.86)% (P < 0.01) and the control (5.73 +/- 0.71)% (P < 0.01). There was no statistic difference between any two of the three groups for plasma IFNgamma and IL-17 level. The plasma IL-4 level was (2.25 +/- 2.05) ng/L in active stage and (2.33 +/- 2.14) ng/L in non-remission stage, being significantly decreased than those in remission stage (6.00 +/- 4.57) ng/L (P < 0.05) and the controls (5.54 +/- 4.00) ng/L (P < 0.05). The plasma IL-10 level was (5.07 +/- 4.10) ng/L in active stage and (5.66 +/- 4.35) ng/L in non-remission stage, being significantly decreased than those in remission stage (10.92 +/- 6.17) ng/L (P < 0.01) and the controls (14.21 +/- 7.31) ng/L (P < 0.01). The plasma level of IL-10 in patients in active stage was positively related to the platelet counts (r = 0.16, P = 0.03). CONCLUSION: Deficiency of Treg cells might be one of mechanisms that cause immune regulation dysfunction in chronic ITP. Th17 cells might not play a role in the development of chronic ITP.

Prognostic value of expression of nuclear factor kappa-B/p65 in non-GCB DLBCL patients.

PURPOSE: We estimated the expression of nuclear factor kappa B/p65 in non-germinal center B-cell-like subtype diffuse large B-cell lymphoma, to investigate its relationship to clinicopathological features, and to further evaluate its prognostic value and clarify its impact on survival. RESULTS: Among the 49 patients enrolled in this study, 14 (28.6%) had positive p65 expression. The negative p65 group had significantly better survival compared to the positive p65 group in terms of both the 3-year estimated OS (91.2% vs. 39.3%, p = 0.003) and PFS (75.6% vs. 26.5%, p = 0.002). In patients with 4 or more risk factors, p65 was an independent prognostic factor of OS (HR 5.99, 95%CI=1.39-25.75, p=0.016) and PFS (HR 4.01, 95%CI=1.15-14.00, p=0.029). MATERIALS AND METHODS: The expression of the NF-κB/p65 protein was deteremined by immunohistochemistry in 49 non-GCB DLBCL. Survival was assessed by the Kaplan-Meier method and Cox multivariate analysis. The median patient follow-up period was 24 months. CONCLUSIONS: The expression of NF-κB/p65 has prognostic value in high risk non-GCB DLBCL, and it is a suitable target for the development of new therapies.

JAK2, MPL, and CALR mutations in Chinese Han patients with essential thrombocythemia.

BACKGROUND: Mutations in Janus kinase 2 (JAK2), myeloproliferative leukemia (MPL), and CALR are highly relevant to Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms. METHODS: Assessing the prevalence of molecular mutations in Chinese Han patients with essential thrombocythemia (ET), and correlating their mutational profile with disease characteristics/phenotype. RESULTS: Of the 110 subjects studied, 62 carried the JAK2 V617F mutation, 21 had CALR mutations, one carried an MPL (W515) mutation, and 28 had non-mutated JAK2, CALR, and MPL (so-called triple-negative ET). Mutations in JAK2 exon 12 were not detected in any patient. Two ET patients had both CALR and JAK2 V617F mutations. Comparing the hematological parameters of the patients with JAK2 mutations with those of the patients with CALR mutations showed that the ET patients with CALR mutations were younger (p = 0.045) and had higher platelet counts (p = 0.043). CONCLUSION: Genotyping for CALR could be a useful diagnostic tool for JAK2/MPL-negative ET, since the data suggest that CALR is much more prevalent than MPL, therefore testing for CALR should be considered in patients who are JAK2 negative as its frequency is almost 20 times that of MPL mutation.

Prognostic role of pretreatment neutrophil-lymphocyte ratio in patients with diffuse large B-cell lymphoma treated with RCHOP.

This study aims to investigate whether neutrophil to lymphocyte ratio (NLR) is an independent predictor in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients in the rituximab era. Data from newly diagnosed DLBCL patients at Nanjing Drum Tower Hospital from 2006 to 2015 were retrospectively reviewed. We used the receiver operating characteristic (ROC) curve analysis to generate the optimal cutoff value for NLR. Among those 156 patients enrolled, the NLR was < 3.0 in 46.8% (73/156) of the patients, and the remaining 53.2% (83/156) had an NLR ≥ 3.0. Patients with higher pretreatment NLR were found to correlate with poorer OS and PFS than these with lower NLR (hazard ratio [HR] = 2.66, 95% confidence interval [CI] = 1.43-4.97, P = 0.002 and HR = 1.79, 95% CI = 1.05-3.07, P = 0.034, respectively). The multivariate Cox proportional hazard model analysis further showed that high NLR was found independently predictive of poor OS (HR = 0.40; CI = 0.19-0.84, P = 0.015) and PFS (HR = 0.57; CI = 0.33-0.98, P = 0.042). Consequently, pretreatment NLR was an independent prognostic predictor in patients with DLBCL in the rituximab era.

MYC and BCL-2 adjusted-International Prognostic Index (A-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP.

The International Prognostic Index (IPI) has been the basis for determining prognosis in patients with diffuse large B-cell lymphoma (DLBCL) for the past 20 years. The utility of the IPI must be reassessed in the era of immunochemotherapy. Seven risk factors at diagnosis were identified, and a maximum of 7 points were assigned to each patient. Four risk groups were created: low (0-1), low-intermediate (2-3), high-intermediate (4), and high (5-7). Using MYC and BCL-2 clinical data from the Drum Tower Hospital collected during the rituximab era, we performed a retrospective analysis of patients with DLBCL treated with R-CHOP and built an biological markers adjusted IPI with the goal of improving risk stratification.Clinical features from 60 adults with de novo DLBCL diagnosed from 2008-2013 were assessed for their prognostic significance. The IPI remains predictive, but it cannot identify the high-risk subgroup. Compared with the IPI, the MYC and BCL-2 adjusted-IPI (A-IPI) better discriminated patients in the high-risk subgroup (4-year overall survival [OS]: 33.3%) than did the IPI (4 year OS: 48.0%). In the era of R-CHOP treatment, MYC and BCL-2 adjusted-IPI is more powerful than the IPI for helping guide treatment planning and interpretation of clinical trials.

Meta-analysis of randomised clinical trials comparing idarubicin + cytarabine with daunorubicin + cytarabine as the induction chemotherapy in patients with newly diagnosed acute myeloid leukaemia.

BACKGROUND: To determine whether the use of idarubicin+cytarabine (IA) is more effective than the use of daunorubicin+cytarabine (DA) as induction chemotherapy for patients with newly diagnosed acute myeloid leukaemia. METHODS: A computer-based search was performed. Randomised trials comparing IA with DA as induction therapy for newly diagnosed AML were included in this meta-analysis. The primary outcome of interest for our analysis was survival (disease-free survival, event-free survival and overall survival); the secondary endpoint was complete remission. RESULTS: Ten trials with 4,060 patients were eligible for this meta-analysis. Our pooled results suggest that IA is associated with a significant advantage in CR (RR = 1·23; 95% CI = 1·07-1·41, p = 0.004), EFS (HR = 0·64; 95% CI = 0·45-0·91, p = 0.013), and OS (HR = 0·88; 95% CI = 0·81-0·95, p = 0.02) but not in DFS (HR = 0·90; 95% CI = 0·80-1·00, p = 0.06). In the subgroup analysis, age had a significant interaction with OS and CR benefits. CONCLUSION: Our analysis indicated that IA could improve the duration of overall survival compared to DA as induction therapy for young patients with newly diagnosed AML. Further study is needed to determine whether IA can produce clinical benefits in selected genetic or molecular subgroups of young AML patients.