Hongfeng Guo

Increased frequency and clinical significance of myeloid- derived suppressor cells in human colorectal carcinoma

AIM To investigate the frequency and clinical significance of the myeloid-derived suppressor cells (MDSC) in human colorectal carcinoma (CRC). METHODS Samples of peripheral blood and tumor tissue from 49 CRC patients were analyzed. Mononuclear cells were isolated by Ficoll-Hypaque density gradient centrifugation and were subjected to a flow cytometry-based immunophenotypic analysis. RESULTS A considerable increase in the percentage of CD33⁺HLA-DR⁻ MDSCs was observed in the peripheral blood (1.89% ± 0.75%) and tumor tissues (2.99% ± 1.29%) of CRC patients as compared with that in the peripheral blood of healthy controls (0.54% ± 0.35%). This expanded CD33⁺HLA-DR⁻ subset exhibited immature myeloid cell markers, but not lineage markers, and showed up-regulation of CD18/CD11b expression as compared with the MDSCs from healthy donors. Further studies showed that the MDSC proportion in CRC peripheral blood was correlated with nodal metastasis(P = 0.023), whereas that in tumor tissues was correlated with nodal/distant metastasis (P = 0.016/P = 0.047) and tumor stage (P = 0.028), suggesting the involvement of MDSCs in CRC tumor development. CONCLUSION Characterization of MDSCs in CRC suggests the clinical significance of circulating and tumor-infiltrating MDSCs and may provide new insights into the CRC immunotherapy targeting MDSCs.

Coagulation profiles and thromboembolic events of bortezomib plus thalidomide and dexamethasone therapy in newly diagnosed multiple myeloma.

Patients with multiple myeloma (MM) are at relatively high risk of developing thromboembolic event (TEE), especially during treatment with immunomodulatory agents. We characterized coagulation profiles and evaluate the incidence of TEE associated with the combination therapy of bortezomib-thalidomide-dexamethasone (VTD) in Chinese patients with newly diagnosed MM. The results indicated that the platelet count and platelet aggregation induced by the agonists were decreased after a short exposure to bortezomib in vivo. The incidence of TEE was low in VTD therapy for an overall rate of 3%. We do not recommend routine thromboprophylaxis for VTD therapy in Chinese patients with MM.

Family haploidentical donor-derived cytokine-induced killer cell biotherapy combined with bortezomib in two patients with relapsed multiple myeloma in a non-allogeneic transplant setting

Multiple myeloma (MM) is a malignant plasma-cell proliferative disorder that remains an aggressive and incurable disease. Despite advances in the treatment of MM using conventional and novel therapeutics in combination with transplant, patients still experience disease progression, and long-term survival is rare [1]. Adoptive cellular immunotherapy aims at eliminating cancer cells through the transfer of ex vivo expanded active immune cells. Cytokine-induced killer (CIK) cells are a heterogeneous subset of T cells with a natural killer (NK) phenotype whose biological features make them appealing for adoptive immunotherapy. Th e combination of CIK cells and chemotherapy has shown synergistic eff ects in clinical practice, and has potential benefi ts in patients with recurrent carcinomas [2,3]. We report here the potential eff ect of family haploidentical donor-derived CIK cells combined with bortezomib treatment on response evaluation and tolerability in two patients with relapsed multiple myeloma in a non-allogeneic transplant setting. Patient 1 is a 76-year-old man diagnosed with with immunoglobulin G (IgG)/lambda MM stage IIIB in January 2008. Cytogenetic analysis of the bone marrow was normal at diagnosis. He obtained a complete response (CR) after four cycles of COMP (cyclophosphamide 650 mg/m 2 , vincristine 1.4 mg/m 2 on day 1, melphalan 2 mg/m 2 on days 1 – 4 and prednisone 60 mg/day on days 1 – 5). Th ree months later the MM relapsed, with increasing IgG. Th e patient received four cycles of VAD (vincristine 0.5 mg/m 2 , adriamycin 9 mg/m 2 and dexamethasone 20 mg daily on days 1 – 4) and three cycles

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.

Rapid Fatal Pulmonary Complications in a Chinese Patient After Bortezomib Treatment for ALK-Negative Anaplastic Large-Cell Lymphoma

Bortezomib, a reversible proteasome inhibitor, is used for the treatment of hematologic malignancies. Common adverse events with bortezomib include gastrointestinal symptoms, thrombocytopenia, and neuropathy, whereas severe pulmonary complications have been rarely described. Herein, we present a case of rapid fatal pulmonary complications in a patient with ALK-negative anaplastic large-cell lymphoma after receiving a treatment with bortezomib.

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.

Short‑course bortezomib‑based retreatment for patients with multiple myeloma who had received bortezomib‑thalidomide‑dexamethasone (VTD) as an initial therapy: A single‑center case series

Studies have shown that the bortezomib-based retreatment of patients with multiple myeloma (MM) may prolong control of the disease. The optimal duration of bortezomib-based retreatment in relapsed or refractory MM is unknown. The present retrospective study evaluated the efficacy and safety of short-course bortezomib-based retreatment in patients who had received bortezomib-thalidomide-dexamethasone (VTD) treatment for the initial therapy of newly diagnosed MM. The clinical records of 20 patients who had received short-course bortezomib-based retreatment in a single center were reviewed. Patients received a median of two cycles of bortezomib as the retreatment and the overall response rate was 90%. Six (30%), eight (40%) and four (20%) patients achieved a complete response (CR), a very good partial response and a partial response, respectively. Of the 10 patients who had achieved a CR during the initial VTD treatment, six experienced a repeat CR during the retreatment. The median duration of the response was nine months and the median time to progression was 10.5 months. The most common grade I and II adverse events were thrombocytopenia and neutropenia. The short-course bortezomib-based retreatment was well tolerated and the favorable response rates observed suggest that it may be an effective and convenient treatment option for certain patients, particularly elderly patients.

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 (

Clinical Manifestation of Calreticulin Gene Mutations in Essential Thrombocythemia without Janus Kinase 2 and MPL Mutations: A Chinese Cohort Clinical Study

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