Xifeng Qian

Variant genotypes of MDR1 C3435T increase the risk of leukemia: evidence from 10 case–control studies

Abstract The C3435T (Ile1142Ile) polymorphism of the multidrug resistance gene (MDR1) has been implicated in leukemia risk, but the reported results are inconsistent. Here we performed a meta-analysis to evaluate the association between C3435T polymorphism and the risk of leukemia using all case–control studies published before June 2011 according to PubMed. A total of 10 case–control studies were included in this analysis. We found that variant genotypes of C3435T (CT/TT) were significantly associated with an increased risk of leukemia (CT/TT vs. CC: odds ratio [OR] = 1.29; 95% confidence interval [CI] = 1.11–1.50, p = 0.284 for heterogeneity test). Additionally, the association was more significant in chronic leukemia (specifically B-cell chronic lymphocytic leukemia [B-CLL]) (OR = 1.94; 95% CI = 1.32–2.85, p = 0.648 for heterogeneity test) than in acute leukemia (OR = 1.19; 95% CI = 1.01–1.40, p = 0.616 for heterogeneity test), p = 0.021 for heterogeneity test between groups. These findings provide further evidence that the MDR1 C3435T variant may modify the susceptibility to leukemia.

Ganoderma lucidum polysaccharide exerts anti-tumor activity via MAPK pathways in HL-60 acute leukemia cells

Abstract In this study, we investigated the anti-tumor activity both in vitro and in vivo of a polysaccharide obtained from Ganoderma lucidum on HL-60 acute myeloid leukemia cells, and focused on its targeting effect on mitogen-activated protein kinase (MAPK) pathways. It was found by the methods such as western blot and flow cytometry (FCM), that G. lucidum polysaccharide (GLP) blocked the extracellular signal-regulated kinase/MAPK signaling pathway, simultaneously activated p38 and JNK MAPK pathways, and therefore regulated their downstream genes and proteins, including p53, c-myc, c-fos, c-jun, Bcl-2, Bax, cleaved caspase-3 and cyclin D1. As a result, cycle arrest and apoptosis of HL-60 cells were induced. Therefore, GLP exerted anti-tumor activity via MAPK pathways in HL-60 acute leukemia cells.

Potentially functional polymorphism in IL-23 receptor and risk of acute myeloid leukemia in a Chinese population.

The interleukin-23 (IL-23) and its receptor (IL-23R) mediate the direct antitumor activities in human hematologic malignancies including pediatric acute leukemia. Two potentially functional genetic variants (IL-23R rs1884444 T>G and rs6682925 T>C) have been found to contribute to solid cancer susceptibility. In this study, we conducted a case-control study including 545 acute myeloid leukemia (AML) patients and 1,146 cancer-free controls in a Chinese population to assess the association between these two SNPs and the risk of AML. We found that IL-23R rs1884444 TG/GG and rs6682925 TC/CC variant genotypes were associated with significantly increased risk of AML [rs1884444: adjusted odds ratio (OR) = 1.28, 95% confidence interval (CI) = 1.01–1.62; rs6682925: adjusted OR = 1.30, 95%CI = 1.01–1.67], compared to their corresponding wild-type homozygotes, respectively. These findings indicated that genetic variants in IL-23R may contribute to AML risk in our Chinese population.

Bortezomib plus intermediate-dose dexamethasone and thalidomide in elderly untreated patients with multiple myeloma: A Chinese experience†

Bortezomib has proven to be active in patients with multiple myeloma (MM), including elderly patients. The aim of this study was to evaluate the efficacy and toxicity of bortezomib in combination with intermediate‐dose dexamethasone (Dex) and thalidomide in untreated MM patients aged ≥65 years in a Chinese single center. In this study, 18 patients were treated with bortezomib at 1.3 mg/m2 IV on Days 1, 4, 8, and 11 and Dex at 20 mg/day IV on Days 1–4 and 8–11 simultaneously. Thalidomide at dose of 100 mg/day was given everyday. The mean number of cycles of bortezomib treatment was 2.06. Three patients (17%) achieved a complete response (CR), four (22%) a very good partial response (VGPR), and nine (50%) a PR, resulting in an overall response rate of 89%. The median time to response was 22 days (range 14–50 days). The duration of response was significantly longer in patients achieving a CR/VGPR with respect to those achieving only a PR (8.5 vs. 4.2 months, P = 0.03). Grade 3–4 toxicities occurring in patients comprised weakness, thrombocytopenia, diarrhea, infection, and neuropathy. Only one patient suffered from deep vein thrombosis. This preliminary experience in Chinese patients indicated that bortezomib‐Dex‐thalidomide is highly effective in elderly untreated patients with MM, even in patients with poor prognostic features. Am. J. Hematol. 2010.

Contributions of T lymphocyte abnormalities to therapeutic outcomes in newly diagnosed patients with immune thrombocytopenia.

T cell abnormalities have been reported to play an important role in pathogenesis of immune thrombocytopenia (ITP) besides specific autoantibodies towards platelet. The aim of this study was to explore the clinical importance of T lymphocyte subsets in adult patients with newly diagnosed ITP before and after first-line treatment. Elderly ITP patients were also studied and we tried to analyze the relationships between these items and therapeutic outcomes. The patients were treated with intravenous immunoglobulin (IVIG) plus corticosteroids and therapeutic responses were evaluated. As a result, compared with the controls, absolute lymphocyte counts in ITP patients decreased significantly before treatment. After treatment, lymphocyte counts restored to control level regardless of their treatment outcomes. In addition, we observed increased IgG and CD19+ cell expression and decreased CD4+/CD8+ cell ratio in both whole ITP group and elderly group before treatment. After treatment, the increased IgG and CD19+ cell expression could be reduced in both respond and non-respond group regardless of patient age, while CD4+/CD8+ cell ratio could not be corrected in non-respond ITP patients. In non-respond ITP patients, increased CD8+ cell expression was noticed and could not be corrected by first-line treatment. Furthermore, even lower NK cell expression was found in non-respond elderly patients after treatment when compared with that in controls. Our findings suggest that ITP patients usually had less numbers of peripheral lymphocytes and patients with higher levels of CD8+ cells or lower levels of CD4+/CD8+ cell ratio were less likely to respond to first-line treatment. Lower levels of NK cells made therapies in elderly ITP patients even more difficult.

Varicella-Zoster Virus Prophylaxis with the Traditional Chinese Medicine Radix Isatidis (Banlangen) in Patients with Multiple Myeloma Treated with Bortezomib

Dear Editor: Bortezomib has contributed to the remarkable advancement of the treatment of patients with multiple myeloma (MM). The common side-effects of bortezomib are peripheral neuropathy, thrombocytopenia, weakness, and gastrointestinal toxicity. Recently, an increased incidence of varicella zoster virus (VZV) reactivation (herpes zoster) was reported in patients with MM undergoing treatment with bortezomib. Based on these observations, VZV prophylaxis was recommended in subsequent clinical trials, and the incidence decreased markedly after acyclovir prophylaxis was administered. Dasanu et al. state that the use of long-term acyclovir prophylaxis could cause significant renal and neurological toxicity. Traditional herbal medicines have been used for a long time in the treatment of human infectious diseases in many countries, and some of them are reported to exhibit antiviral activity in the literature. Traditional Chinese Medicine (TCM) commands a unique position among all traditional medicines because of its 5000 years of history. The Chinese medicinal herb Radix Isatidis has been suggested to possess antiviral activity, and it has fewer side-effects. From January 2009 to October 2010, the authors evaluated the efficacy of VZV prophylaxis with Radix Isatidis in 30 patients with MM treated with a bortezomib-based regimen. The median age of the patients was 63 years (range, 42–76 years). The median number of administered cycles of bortezomib per patient was 2 (range, 2–4 cycles). Baseline characteristics of the patient cohort are shown in Table 1. Bortezomib was used alone or combined with other drugs such as dexamethasone and thalidomide. Bortezomib 1.3 mg/m was administered at days 1, 4, 8, and 11 of each 21-day cycle. Dose reductions or treatment delays were allowed if adverse effects occurred. Patients discontinued treatment if they had progressive disease, developed unacceptable toxicity, withdrew consent, or maintained a confirmed complete response for 2 cycles. The first 12 patients did not receive any VZV prophylaxis. Because of the high incidence of herpes zoster, it was decided to use Radix Isatidis 10 g orally 3 times daily in the subsequent 18 patients. All statistical analyses were performed using a statistical software package (SPSS; Version 13.0). Of the 12 patients who did not receive any antiviral prophylaxis during bortezomib treatment, 3 patients (25%) developed herpes zoster. The median time to onset of herpes zoster was 24 days. One (1) patient had previous VZV infection. One (1) patient developed a typical rash with blisters on part of his face; the 2 other patients had a rash on their neck or trunk, respectively. All 3 patients applied acyclovir ointment in the affected area and Radix Isatidis 10 g orally 3 times daily. The skin lesions were resolved without any complications in the patients. The subsequent 18 patients treated with bortezomib received VZV prophylaxis with Radix Isatidis. During the period of observation, no cases of VZV reactivation occurred. The incidence of VZV reactivations in patients without VZV prophylaxis was significantly higher than that in patients treated with Radix Isatidis ( p = 0.003). A multivariate analysis did not show an association between risk of herpes zoster and Karnofsky Performance Scale, prior history of VZV, baseline levels of b2 microglobulin, hemoglobin, or albumin. No adverse effects were noted that could be definitely attributed to Radix Isatidis. As bortezomib has been shown highly effective in the treatment of MM through changing the response rates and the general prognosis of patients, herpes zoster has been more frequently observed. To the authors’ knowledge, the reason for this is not fully understood. Herpes zoster is the result of reactivation of latent VZV from the dorsal root ganglion. Cell-mediated immunity plays a major role in the prevention of development of herpes zoster. With these recent developments, antiviral prophylaxis seems to be increasingly important in ameliorating the risk of VZV reactivation in patients receiving bortezomib-based therapies. Traditional medicines contain various metabolites derived from nucleic acid, protein, and lipid metabolism. Some of these specific metabolites may recognize the differences between viral and host metabolism resulting in antiviral activity; hence traditional medicines may be useful sources for new antiviral agents. TCM is considered a complementary or alternative medical system in most Western countries while remaining as a form of primary care throughout most Asian countries. In China, Chinese medicine accounts for 30%–50% of total medicine consumption, with low costs and low toxicity. Many TCMs and related active compounds have been reported that have promising and potent antivirus activities.

Evaluation of pretreatment red cell distribution width in patients with multiple myeloma.

BACKGROUND Red blood cell distribution width (RDW) has been reported as an inflammatory biomarker and a predictor of prognosis in different types of cancer. However, the role of RDW at diagnosis in patients with multiple myeloma (MM) has been less explored. OBJECTIVE We aimed to investigate the association between RDW and the response to treatment and overall survival (OS) in patients with MM. METHODS We retrospectively analyzed the data for 196 MM patients between January 1, 2007 and December 31, 2015. Kaplan-Meier analysis and Cox regression model were used. RESULTS High RDW values were associated with lower platelet count, lower hemoglobin levels, lower albumin levels, and higher lactate dehydrogenase (LDH) level. Among the entire cohort, the overall response rates (ORR) and complete response (CR) rate of initial therapy were markedly higher in the low-RDW group compared to the high-RDW group. RDW was significant lower in CR in comparison to Non-CR groups in patients treated with bortezomib-based regimens as induction therapy. The patients with low-RDW at diagnosis had better OS when compared to those with high-RDW. CONCLUSIONS Elevated RDW was associated with worse survival in patients with MM and could predict treatment responses. Further larger and prospective studies are required.

Real-world outcome and healthcare costs of relapsed or refractory multiple myeloma: A retrospective analysis from the Chinese experience

Objectives: Our aim was to retrospectively investigate the real-world outcome and healthcare costs associated with the treatment of patients with relapsed or refractory multiple myeloma (RRMM) in a Chinese single center. Methods: A retrospective study was conducted for 93 patients between January 2008 and December 2013 in a Chinese hematology department. Total monthly costs attributable to each cost component were described across all regimens and for bortezomib-based treatment regimens. Results: Mean total cost per patient-month (

The functional polymorphisms of ARID5B and IKZF1 are associated with acute myeloid leukemia risk in a Han Chinese population

1139.85) varied depending on the sequence of therapy (range: mean

The functional polymorphisms of LIS1 are associated with acute myeloid leukemia risk in a Han Chinese population

51.63–