Lili Cai

Repeated transfusions of autologous cytokine-induced killer cells for treatment of haematological malignancies in elderly patients: a pilot clinical trial

The elderly population is susceptible to haematological malignancies, and these elderly patients are intolerant to cytotoxic drugs. Therefore, the exploration of a safe and reliable strategy exclusive of chemotherapy is critical in improving the prognosis of elderly patients with haematological malignancies. We evaluated the safety and the efficacy of autologous cytokine‐induced killer (CIK) cells combined with recombinant human interleukin 2 (rhIL‐2) in the treatment of haematological malignancies in elderly patients. Peripheral blood mononuclear cells were isolated from 20 elderly patients with haematological malignancies, then augmented by priming with interferon gamma, rhIL‐2 and CD3 monoclonal antibody. The autologous CIK cells (2–3 × 109) were transfused back to patients, followed by a subcutaneous injection of IL‐2 (1 mU/day) for 10 consecutive days. The regimen was repeated every 4 weeks. The host cellular immune function, tumour‐related biological parameters, imaging characteristics, disease condition, quality of life and survival time were assessed. Fourteen patients received 8 cycles of transfusion and 6 received 4 cycles. No adverse effects were observed. The percentages of CD3+, CD3+CD8+ and CD3+CD56+ cells were significantly increased (p < 0.05), and the levels of serum β2 microglobulin and lactate dehydrogenase (LDH) were markedly decreased (p < 0.05) after autologous CIK cell transfusion. Cancer‐related symptoms were profoundly alleviated, as demonstrated by the improved quality of life (p < 0.01). Complete remission was observed in 11 patients, persistent partial remission in 7 patients and stable disease in 2 patients. At the end of follow‐up, the mean survival time was 20 months. Transfusion with autologous CIK cells plus rhIL‐2 treatment is safe and effective for treating haematological malignancies in elderly patients. Copyright

Efficacy of cytokine-induced killer cell infusion as an adjuvant immunotherapy for hepatocellular carcinoma: a systematic review and meta-analysis

This study was designed to evaluate the efficacy and safety of cytokine-induced killer (CIK) cell-based immunotherapy as an adjuvant therapy for hepatocellular carcinoma (HCC). Published studies were identified by searching Medline, Cochrane, EMBASE, and Google Scholar databases with the keywords: cytokine-induced killer cell, hepatocellular carcinoma, and immunotherapy. The outcomes of interest were overall survival, progression-free survival, and disease-free survival. Eight randomized controlled trials (RCTs), six prospective studies, and three retrospective studies were included. The overall analysis revealed that patients in the CIK cell-treatment group had a higher survival rate (pooled hazard ratio (HR) =0.594, 95% confidence interval [CI] =0.501–0.703, P<0.001). Patients treated with CIK cells in non-RCTs had a higher progression-free survival rate (pooled HR =0.613, 95% CI =0.510–0.738, P<0.001). However, CIK cell-treated patients in RCTs had progression-free survival rates similar to those of the control group (pooled HR =0.700, 95% CI =0.452–1.084, P=0.110). The comparison between pooled results of RCTs and non-RCTs regarding the progression-free survival rate did not reach statistical significance. Patients in the CIK cell-treatment group had lower rates of relapse in RCTs (pooled HR =0.635, 95% CI =0.514–0.784, P<0.001). Similar results were found when non-RCT and RCTs were pooled (pooled HR =0.623, 95% CI =0.516–0.752, P<0.001). Adjuvant CIK cell-based immunotherapy is a promising therapeutic approach that can improve overall survival and reduce recurrence in patients with HCC.

Treatment of multiple solitary plasmacytomas with cytokine-induced killer cells

BACKGROUND AIMS Currently available treatment methods for advanced plasmacytoma include surgery, chemotherapy, radiotherapy, immunomodulatory agents, hematopoietic stem cell transplantation and donor lymphocyte infusion. We report a case of advanced refractory multiple solitary plasmacytomas in a 68-year-old Asian man with multiple bone lesions, in whom autologous cytokine-induced killer (CIK) cells were administered in an effort to eliminate residual tumor lesions. METHODS CIK cells were infused monthly for 21 courses. RESULTS The patient has survived 63 months since the first hospital visit without disease progression for 40 months. CONCLUSIONS This case represents the first report of autologous CIK cell immunotherapy used successfully to suppress multiple solitary plasmacytomas and resolve bone lesions.

Ultra-Low-Dose Decitabine Combined With Autologous Cytokine-Induced Killer Cells for Elderly Patients With Acute Myeloid Leukemia Transformed From Myelodysplastic Syndrome

PURPOSE Elderly acute myelocytic leukemia (AML) patients have limited treatment options because they poorly tolerate standard-dose chemotherapy. The present article describes our experience with ultra-low-dose decitabine combined with infusion of autologous cytokine-induced killer (CIK) cells for 2 elderly patients with myelodysplastic syndrome-transformed AML. METHODS Decitabine (10 mg) was given on days 1 to 5, and CIK cells on day 14 with 2 to 8 × 10(9) cells per infusion. FINDINGS The therapeutic regimen resulted in marked hematologic recovery and was associated with better than expected survival in both cases. IMPLICATIONS Our experience suggests that the combination therapy is safe and effective for elderly patients with myelodysplastic syndrome-transformed AML.

Antisense oligonucleotide against hTERT (Cantide) inhibits tumor growth in an orthotopic primary hepatic lymphoma mouse model.

Background Human xenograft models, resulting from orthotopic transplantation (implantation into the anatomically correct site) of histologically intact tissue into animals, are important for investigating local tumor growth, vascular and lymphatic invasion at the primary tumor site and metastasis. Methodology/Principal Findings We used surgical orthotopic transplantation to establish a nude mouse model of primary hepatic lymphoma (PHL), HLBL-0102. We performed orthotopic transfer of the HLBL-0102 tumor for 42 generations and characterized the tumor cells. The maintenance of PHL characteristics were supported by immunohistochemical and cytogenetic analysis. We also report the antitumor effect of Cantide, an antisense phosphorothioate oligonucleotide against hTERT, on the growth of HLBL-0102 tumors. We showed a significant, dose-dependent inhibition of tumor weight and serum LDH activity in the orthotopically transplanted animals by Cantide. Importantly, survival was prolonged in Cantide-treated HLBL-0102 tumor-bearing mice when compared to mock-treated mice. Conclusions/Significance Our study provided the basis for the development of a clinical trial protocol to treat PHL.

Effects of Serum Lipid Smoothness on the Progression and Vulnerability of Atherosclerotic Plaques in Rabbits

Objective We aimed to explore the effects of lipid smoothness on the progression and vulnerability of atherosclerotic plaques. Approach 24 rabbits were divided into three groups randomly. Group 1 was given standard chow diet; group 2 was fed with cholesterol-rich diet; for group 3, subjects were planned to take cholesterol-rich diet at the first phase for 12 weeks and during the second phase, low-fat and cholesterol-rich diet was then applied alternately every three weeks till the end of the experiment. Lipid profiles, inflammatory factors, endothelium functions, pathological and histological changes were examined. Expressions of matrix metalloproteinase-9 and lectin-like oxidized LDL receptor-1 were measured by immunohistochemical staining. Results According to data collected during the whole experiment, lipid smoothness index of group 3 was the lowest. Compared with group 2, statistics of the group 3 indicated that: the development of plaques progressed faster; the plaque area and plaque thickness (53.53[22.6]% vs 33.90[24.91]% , 800.38[98.25]µm vs 675.00[109.67]µm) were higher while the fibrous cap thickness (103.50[45.66]µm vs 295.83[97.90]µm) was lower; hs-CRP (0.53[0.07]mg/dL vs 0.45[0.06]mg/dL), interleukin-18 (186.01[8.41]ng/L vs 158.08[2.37]ng/L), OX-LDL (177.15[5.93]µg/L vs 139.57[2.35] µg/L) and endothelin-1 (164.66[9.54]ng/L vs 131.52[4.39]ng/L) were higher while nitric-oxide (22.41[1.69]µmol/L vs 27.23[1.36]µmol/L) was lower; expressions of matrix metalloproteinase-9 (IOD: 37375.87[5634.52] vs 20956.57[4616.93]) and lectin-like oxidized LDL receptor-1 (IOD: 45213.04[16653.81] vs 21921.68[6142.32]) were higher. Conclusions Lipids fluctuation could accelerate the progression and vulnerability of atherosclerotic plaques through worsening arterial endothelium dysfunction and inflammatory reactions.

Haploidentical versus matched donor stem cell transplantation for patients with hematological malignancies: a systemic review and meta-analysis

We compared the safety and efficacy of haploidentical stem cell transplantation (haplo-SCT) to matched donor SCT (matched-SCT) in treating hematological malignancies. The Medline, Cochrane, EMBASE, and Google Scholar databases were searched through 21 June 2017 using the search term “(hematological disease) AND matched AND (haploidentical OR haplo-identical OR haplo identical OR haplo transplantation OR haplo transplant OR haplo-SCT OR haplo-HSCT OR haplo-HCT).” Twenty-five studies enrolling 11,359 patients (haplo-SCT: 2677; matched-SCT: 8682) were included. The primary outcomes were acute and chronic graft-versus-host disease (GVHD), non-relapse mortality, and 1-year cumulative incidence of relapse. Haplo-SCT was associated with similar risks as matched-SCT for all primary endpoints. Subgroup analysis of patients who received a matched-SCT from a related donor revealed that patients who received haplo-SCT had a lower risk of acute GVHD. Among patients who received reduced-intensity conditioning (RIC), those who received haplo-SCT had a higher risk of acute grade II–IV GVHD and non-relapse mortality than did patients who received a matched-SCT from a related or unrelated donor. Haplo-SCT should continue to be considered as a safe and effective transplant option when a matched donor is unavailable, but it may not be suitable for patients who receive RIC.

Excess Free Fructose Beverages and Allergy in Children and Adolescents: Results From NHANES 2005-2006

PURPOSE Our purpose was to investigate the relationship between intake of excess free fructose beverages and allergy among children and adolescents. METHODS We analyzed data of 860 children (aged 6 to 12 years) and 1,142 adolescents (aged 13 to 19 years) from the National Health and Nutrition Examination Survey 2005-2006. Logistic regression analyses were performed to determine the associations between consumption of excess free fructose beverages and allergic symptoms or allergic sensitization. RESULTS The pattern of findings was not entirely consistent, but some analyses supported the hypothesis of an association between intake of excess free fructose beverages and allergy. After controlling for the potential confounders, children who consumed nondiet fruit drinks at least 5 times per week had a nearly 2.5-fold greater odds of allergic sensitization than did those who consumed such drinks only 1 to 3 times per month (OR = 2.446; 95% CI, 1.583-3.780). Adolescents who consumed excess free fructose beverages at least 5 times per week or 1 to 4 times per week had about fivefold greater odds of presence of allergic symptoms than did those who seldom consumed these beverages (OR = 5.164; 95% CI, 1.866-14.297 and OR = 4.112; 95% CI, 1.857-9.107, respectively). Adolescents who consumed apple juice at least 5 times per week had a twofold greater odds of presence of allergic sensitization than did the seldom consumers (OR = 2.215; 95% CI, 1.178-4.164). CONCLUSIONS These findings provide some support for the hypothesis of a link between intake of excess free fructose beverages and allergic symptoms or allergic sensitization in children and adolescents.

Successful management of acute myeloid leukemia transformed from myelodysplastic syndromes in an elderly patient aged over 80 years old by ultralow dose decitabine combined with amifostine and autologous CIK cells.

Dear Editor, The myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell diseases that are characterized by cytopenia, dysplasia in one or more of the major myeloid cell lines, and a tendency to transform into acute myeloid leukemia (AML). Approximately, one third of MDS patients will undergo transformation into AML, which is resistant to treatment and ultimately fatal. We describe here a case of MDS in an 85-year-old male patient with transformation AML from MDS who was successfully treated with ultralow dose decitabine, amifostine, and infusion of autologous cytokineinduced killer (CIK) cells (dubbed the DAC regimen). The patient was admitted on March 11, 2010 due to pancytopenia. Past history was unremarkable except hypertension and COPD. His routine blood chemistries were as follows: white blood cell count, 2.9×10/L (neutrophils, 40 %; lymphocytes, 50 %; monocytes, 4.5 %); platelets, 67×10/L; and hemoglobin, 98 g/L. Bone marrow (BM) aspirate revealed 5.2 % blasts and trilineage dysplasia (Fig. 1a). Cytogenetic analysis demonstrated 46, XY[13]/t(7;11)(q35;q14)[10]/ del(4)(p10),t(7;11)(q35;q14)[2]/subdiploid(44)[2]. He was diagnosed with MDS-RAEB-I, IPSS intermediate-2 risk. The patient was given amifostine and erythropoietin, but hemoglobin progressively declined and he became transfusion dependent. BM aspirate on December 17, 2011 revealed 20.2 % blasts and flow cytometry demonstrated transformation AML-M4 (FAB classification) (Fig. 1b). One week later, the patient was started on the DAC regimen. Decitabine (10 mg; Chia-Tai Tianqing Pharmacy Co., Jiangsu, China) was given on d1, 3, 5, 7, and 9. Autologous CIK cells were prepared as previously described [1]. Briefly, on d0, 54 mL venous blood was collected from the median cubital vein of the patient, and peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll-Hypaque density–gradient centrifugation. PBMCs were then washed and cultured in the presence of anti-human CD3 monoclonal antibody, recombinant human interferon-γ, and recombinant human interleukin-2 for 14 days. On d14, 2–6×10 cells were infused. Amifostine (0.4 g) was given on d14–18 and d21–25. The patient received a total of three courses of the regimen. The main side effects included Bo Yang, Hai-tao Wang, Li-li Cai, Yu Zhao, Xiao-hua Chi, Hong-li Zhu, Hai-hong Ran, Yang Yang, Rui-li Yu, Song-wei Li and Xue-chun Lu contributed equally to this work.