Qiguo Zhang

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.

Low-temperature glycol methacrylate resin embedding method: A protocol suitable for bone marrow immunohistochemistry, PCR, and fish analysis

Molecular analyses such as fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) are demanded to improve diagnostic accuracy in addition to immunohistopathology of bone marrow (BM) trephine specimens. Conventional BM embedding method needs decalcification, and its procedure may impair tissue morphology and DNA quality. Here, we report an undecalcified method by which glycol methacrylate resin is polymerized at low temperature (4°C). Using this method, BM enzyme activity and antigenic determinants are well preserved, and moreover, DNA extracted from plastic embedding sections is suitable for PCR amplification and sequencing, FISH analysis can be well done because of the DNA integrity of BM sections. If working with BM trephine specimen, our protocol offers the possibility to combine superior morphology with modern molecular analysis. Microsc. Res. Tech. 73:1067–1071, 2010.

High-dose chemotherapy followed by autologous stem cell transplantation as a first-line therapy for high-risk primary breast cancer: a meta-analysis.

Background and Objectives Several trials have generated conflicting results about the results of high-dose chemotherapy followed by autologous stem cell transplantation (HDCT) for primary breast cancer. This meta-analysis summarizes the available evidence from all suitable studies. Design and Methods Prospective, randomized trials with HDCT as a first-line therapy for primary breast cancer were included in this meta-analysis. The primary outcome of interest for our analysis was survival (disease-free survival and overall survival); secondary endpoints included treatment-related mortality (TRM) and second (non-breast) cancers. We used a median age of 47, a PR positive rate of 50% and a premenopausal rate of 70% as cutoff values to complete the subgroup analyses, which were pre-planned according to the prepared protocol. Results Fourteen trials with 5747 patients were eligible for the meta-analysis. Compared with non-HDCT, non-significant second (non-breast) cancers (RR = 1.28; 95% CI = 0.82–1.98) and higher TRM (RR = 3.42; 95% CI = 1.32–8.86) were associated with HDCT for primary breast cancer. A significant DFS benefit of HDCT was documented (HR = 0.89; 95% CI = 0.79–0.99). No difference in OS (overall survival) was found when the studies were pooled (HR = 0.91; 95% CI = 0.82–1.00, p = 0.062). In subgroup analysis, age and hormone receptor status had a significant interaction with prolonged DFS and OS. Conclusions HDCT has a benefit on DFS and OS compared to SDC in some special patients with high-risk primary breast cancer.

Prognostic relevance of protein expression, clinical factors, and MYD88 mutation in primary bone lymphoma

Primary bone lymphomas (PBLs) are composed of malignant lymphoid cells presenting in osseous sites, without supra-regional lymph node or extranodal involvement. We systematically characterized the immunophenotype and the myeloid differentiation factor 88 (MYD88)-L265P gene mutation status in PBL. Clinical data from 19 patients with PBL treated at Nanjing Drum Tower Hospital between 2009 and 2015 were analyzed retrospectively. Protein expression patterns were identified immunohistochemically, and MYD88 mutation was assessed using polymerase chain reaction and direct DNA sequencing. Fifteen patients presented with diffuse large B-cell lymphoma. Clinical factors favoring a good prognosis were an age < 60 years and rituximab treatment. B-cell lymphoma 2 expression was detected in 5/15 diffuse large B-cell lymphoma patients, and was associated with a poor prognosis in a univariate model. Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling factors were upregulated in PBLs. All eighteen evaluable PBL samples harbored wild-type MYD88. These data thus suggest that age and rituximab treatment are independent prognostic factors determining overall survival, and that activation of JAK/STAT3 signaling may promote the pathogenesis of PBL. Moreover, the absence of MYD88-L265P mutation in PBL indicate there are distinct pathogenetic backgrounds among extranodal lymphomas.

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

ABSTRACT 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.

The level of peripheral blood circulating CD34+ cells is higher in acute promyelocytic leukemia patients with adverse prognostic factors.

Introduction: The increased flow cytometry enumeration of peripheral blood circulating CD34+ cells in patients with acute leukemia has been found in our previous work. In this study, we also demonstrated that acute promyelocytic leukemia (APL) patients not only had elevated CD34+ cell count, but also had some clinical features. Methods: Fifty APL patients and 19 healthy volunteers were included in the study. The enumeration of circulating CD34+ cells, cytogenetic subgroup, immunophenotype analysis, and leukemic-related gene mutation detection were performed. Results: Some APL patients with higher count of CD34+ cells (≤10 × 106/l) usually possessed one or more poor prognostic factors (higher WBCs count, PML/RARa gene complex fusion, chemotherapy-related APL, normal karyotype/complex karyotype abnormalities, CD56/CD34 antigen positive expression, FLT3-ITD positive mutation, myelofibrosis, and marrow necrosis). A cut-off value of 10 × 106/l CD34+ cells may have the power to distinguish APL patients with above adverse clinical prognostic factor from other APL subjects. Conclusion: The circulating CD34+ cell count appears to increase in some APL patients and a higher CD34+ cell count may be indicative of inferior survival and serve as an adverse biomarker for APL.