Clinical study of autologous cytokine induced killer cells combined with chemotherapy for elderly patients with acute myeloid leukemia / 中国实验血液学杂志

This study was purposed to evaluate the effectiveness and safety of autologous cytokine induced killer (CIK) cells combined with chemotherapy in treatment of elderly patients with acute myeloid leukemia. Peripheral blood mononuclear cells (PBMNC) were isolated from 5 elderly patients with acute myeloid leukemia, and then augmented by priming with interferon gamma (IFN-γ) followed by IL-2 and monoclonal antibody (mAb) against CD3. The autologous CIK cells thus obtained were infused back to individual patients, 28 days as one cycle. The changes in cellular immune function, incidence of infection, independence of hematoglobin or blood transfusion, and progression of disease were observed and assessed before and after therapy. The results showed that the 46 cycles of CIK cell infusion were performed for 5 patients, no adverse reaction was observed in these patients. The percentages of CD3(+), CD3(+)CD8(+) and CD3(+)CD56(+) increased significantly (P < 0.05), The therapy of CIK could significantly reduce the incidence of infection (P < 0.05) and shorten the time of high fever in AML patients (P < 0.05). CIK also could reduce the volume of erythrocyte infusion to maintenance hematoglobin level (P < 0.05). We found that although CIK could not change the outcome of AML, the combination of CIK and chemotherapy could control patients' condition and prolong their survival during the development and end stage of AML. It is concluded that autologous CIK cells combined with chemotherapy is safe and efficacious for the elderly patients with acute myeloid leukemia.

Analysis for clinicopathological features, therapy and prognosis of 30 elderly patients with non-Hodgkin's lymphoma / 中国实验血液学杂志

The purpose of this study was to explore the clinicopathological features, therapy and prognostic factors of elderly patients with non-Hodgkin's lymphoma (NHL). The clinical data including general clinical characteristics, pathological features, chemotherapy selection and treatment response of 30 patients with NHL in our hospital from January 2003 to December 2012 were analyzed retrospectively. The survival was analyzed by using Kaplan-Meier methods, and the prognosis was evaluated by COX regression multivariate analysis model. The clinical parameters selected include age, Ann Arbor stage, international prognostic index (IPI), B symptom and lactate dehydrogenase (LDH) levels. The results showed that all the patients suffered from underlying disease, and the cardiovascular disease (hypertension, coronary heart disease, arrhythmia) is the most common, and minority (8/30) combined with secondary tumor, the 63% (19/30) cases had B symptoms at diagnosis. only 2 cases were diagnosed as T-cell lymphoma; the 93% (28/30) cases combined with B-cell lymphoma, 57% (17/28) of them combined with diffuse large B-cell lymphoma. Ann-Arbor stage ≤ IIwas 37% (11/30);10(37%) patient's IPI score was ≤ 2, and 67% (20/30) was scored 3-5; 13(43%) patient's serum LDH level was abnormal. Modified R-CHOP chemotherapy was given individually on the basis of clinical features. The patients achieved complete remission, partial remission, stable disease, or progressive disease accounted for 14 (46.7%), 13 (43.3%), 1 (3.3%), and 2 (6.7%), respectively; the total reaction rate was 90% after 4 cycles of chemotherapy; the overall survival (OS) rate at 1 and 2 years was 73.3% and 43.3%, and progression-free survival (PFS)rate at 0.5 and 1 years was 62.2% and 54.9%; multivariate analysis by COX regression showed that B symptoms and Ann-Arbor stage were independent factors (P = 0.014, 0.039; RR = 6.678, 4.939, respectively) affecting the OS of elderly NHL, and IPI score affected PFS independently. It is concluded that elderly patients with NHL usually are of late stage at newly diagnosis and have suffered from underlaying diseases. Besides strengthening supportive treatment, modified R-CHOP chemotherapy should be given individually according to different prognosis. B symptoms and Ann-Arbor stage >II are indicators for poor prognosis of elderly NHL.

Short-term curative efficacy of autologous cytokine induced killer cells combined with low-dose IL-2 regimen containing immune enhancement by thymic peptide in elderly patients with B-cell chronic lymphocytic leukemia / 中国实验血液学杂志

This study was purposed to evaluate the safety and curative effect of autologous cytokine induced killer cells (CIK) combined with low-dose IL-2 regimen containing immune enhancement of thymic peptide on elderly patients with B-cell chronic lymphocytic leukemia (B-CLL). Thymic peptide α1 was subcutaneously given as the immunoenhancement agent at a dose of 1.6 mg/d, 14 days as one cycle. Peripheral blood mononuclear cells (PBMNC) from 5 patients with B-CLL were isolated once a week to induce ex vivo CIK cells through culture in the context of interferon (IFN)-γ, interleukin (IL)-2 and anti-CD3 monoclonal antibody. The PBMNC were separated from patients before and after 14 days as one cycle of thymic peptide α1 administration. Parameters of amplification ability, effector cells quantity, lymphocyte subgroups percentage and antitumor cytotoxicity were compared before and after thymic peptide administration. The 5 patients were treated with CIK cells combined with low-dose IL-2 regimen immediately after injection of thymic peptide α1. The CIK cells plus low-dose IL-2 regimen containing thymic peptide enhancement was defined as: thymic peptide α1 1.6 mg/d was subcutaneously administered once every other day; (4 - 6) ×10(9) of CIK cells were transfused followed by IL-2 subcutaneous administration of 1 mU/d on days 1-10, 28 days as one cycle. Clinical evaluation parameters including cellular immunity function, CLL related biomarkers, disease state and infectious frequency and degree were investigated before and after CIK cells infusion puls IL-2. The results showed that the amount of amplified CIK cells, the percentage and amplification times of effector cells and antitumor cytotoxicity more significantly increased after thymic peptide α1 treatment than before its use (P < 0.05). The total 46 cycles of CIK cells infusion plus IL-2 were completed in the 5 CLL patients. No adverse reaction was observed. After treatment of CIK cells plus IL-2, the general conditions of 5 CLL patients were to different extent improved. Simultaneously, percentages of CD3(+), CD3(+)CD8(+), and CD3(+)CD56(+) cells in peripheral blood remarked by raised (P < 0.05), the serum level of β2 microglobulin was significantly declined (P < 0.05), and the frequency and degree of infection was also decreased (P < 0.05). Following CIK cells plus IL-2 therapy, the transformation of disease state from partial remission (PR) to complete remission was seen in 3 patients, from stable disease (SD) to PR in 1 patient, and from progress of disease to SD in 1 patient. It is concluded that the regimen of autologous CIK cells combined with low-dose IL-2 containing immune enhancement of thymic peptide is safety and effective for the treatment of elderly patients with B-CLL.

Research progress on immunocyte senescence - review / 中国实验血液学杂志

The function of immune system degenerates in an aging-dependent manner and this results in immunosenescence. Human immune system includes two parts: genetic/innate immunity and adaptive immunity. The former is involved in monocytes, nature killer cells, and dendritic cells, the later is involved in acquired B and T lymphocytes. During the aging of immunity system, the both parts of immunity are damaged to some degree. Generally, innate immunity seems well-retained and the acquired immunity is degenerative seriously with aging. Immunocyte senescence is closely related to the elderly decreased ability to control infectious disease, cancer and to their generally poor response to vaccination. This review summarized the research progress on immunosenescence characteristics in aged phase.

Curative efficiency of rituximab combined with autologous cytokine induced killer cells on aged patient with orbital diffuse large B cell lymphoma / 中国实验血液学杂志

The aim of this study was to observe the curative effects and safety of autologous cytokine induced killer (CIK) cells in treatment of aged patients with orbital diffuse large B cell lymphoma after rituximab therapy. The patient was given rituximab three times with low dose COP chemotherapy one time when he was diagnosed with orbital diffuse large B cell lymphoma. Two months later, the patient began to receive five cycles CIK cells infusion. One course of therapy was defined as follows: about (2-3)×10(9) of CIK cells (survival rate > 95%) was transfused twice and then rhIL-2 (1 MU daily) was subcutaneously administered for 10 consecutive days. Efficacy and adverse effect was observed during or after CIK cells infusion. The results showed that the peripheral blood mononuclear cells of the patient could be cultured and expanded into CIK cells. The majority of CIK cells was positive for CD3 and CD8 after culture. The CD3(+)CD56(+) cells markedly increased after culture. After two cycles of CIK cell infusion, the orbital lymphoma and possible involvement of the kidney disappeared. The patient obtained complete remission after five cycles of CIK cells infusion. The side effects of CIK cell treatment were minor. It is concluded that CIK cell infusion may prevent recurrence, prolong progression-free survival and improve quality of life after rituximab (alone or with chemotherapy) for aged patients with orbital diffuse large B-cell lymphoma.

Clinical study of autologous cytokine induced killer cell infusion treating for elderly patients with myelodysplastic syndrome / 中国实验血液学杂志

Objective of this study was to evaluate the effectiveness and safety of autologous cytokine induced killer (CIK) cells combined with IL-2 in treatment of elderly patients with myelodysplastic syndromes (MDS). Peripheral blood mononuclear cells were isolated from 6 elderly MDS patients and were stimulated by cytokines in vitro to form CIK cells. The autologous CIK cells were then infused back into the corresponding patients. The regimen was repeated every 4 weeks. Effector cell proportion changes, adverse effects, effects on inflammation, hemoglobin level and blood transfusion were assessed after treatment. The results showed that after autologous CIK cell infusion, the percentages of CD3(+), CD3(+)CD8(+) and CD3(+)CD56(+) increased significantly (p < 0.05). No severe adverse effects were observed in all patients. It also significantly reduced inflammation frequency and shortened high fever duration. During stable stage of disease, the CIK cell infusion could reduce the red blood cell infusion amount and stabilize hemoglobin level. However, the natural course of transformation from myelodysplastic syndromes to high-risk subtypes could not be changed by CIK cell treatment. It is concluded that the autologous CIK cell infusion is a safe and effective therapy for geriatric myelodysplastic syndrome.

Clinical study of autologous cytokine induced killer cells combined with IL-2 for therapy of elderly patients with B-cell malignant lymphoma / 中国实验血液学杂志

Objective of this study was to evaluate the effectiveness and safety of autologous cytokine induced killer (CIK) cells combined with IL-2 in treatment of elderly patients with B-cell malignant lymphoma. Peripheral blood mononuclear cells (PBMNC) were isolated from 9 elderly patients with B-cell malignant lymphoma, and then induced into CIK cells by IFN-γ, IL-2 and monoclonal antibody (mAb) against CD3. The autologous CIK cells [(2-3)×10(9)] thus obtained were infused back to individual patients, then followed by subcutaneous injection of IL-2 at single daily dose of 1×10(4) U/day for 10 consecutive days. The regimen was repeated every 4 weeks and total 64 cycles of CIK cell transfusion were completed. The changes in cellular immune function, tumor-related biological parameters, imaging characteristics, the condition of remission, quality of life and survival time were assessed. 7 patients received 8 cycles of CIK cell infusion, and 4 cycles were completed in 2 patients. The results showed that no adverse reaction was observed in all above mentioned patients. The percentages of CD3+, CD3+CD8+ and CD3+CD56+ increased significantly (p<0.05), and serum levels of β2-microglobulin and LDH were markedly decreased (p<0.05) after autologous CIK cell transfusion. The lymphoma symptoms were relieved with quality of life obviously elevated (p<0.01) in all patients. Complete remission was seen in 8 patients. Though one patient received 8 cycles of CIK cell transfusion therapy and achieved transient very good partial remission, but he died of acute large-area myocardial infarction and persistent progression of lymphoma. In conclusion, regimen of autologous CIK cells combined with IL-2 is safe and effective for the therapy of elderly patients with B-cell malignant lymphoma.

Application of immune function test to evaluate effect of cytokine-induced autologous killer cell infusion for elderly patients with hematological malignancies / 中国实验血液学杂志

The aim of study was to explore the efficacy of cytokine induced autologous killer (CIK) cell infusion as an immune therapy for elderly patients with hematological malignancies. Peripheral blood mononuclear cells (PBMNC) were isolated from 20 elderly patients with hematological malignancies, and then augmented by priming with human recombinant interferon gamma (rhIFN-γ) followed by human recombinant interleukin 2 (rhIL-2) and monoclonal antibody (mAb) against CD3. The obtained autologous CIK cells [(2-3)×10(9)] were infused back to individual patients, then followed by subcutaneous injection of IL-2 at single daily dose of 1×10(6) U for 10 consecutive days. The regimen was repeated every 4 weeks and total 136 cycles of CIK cells transfusion were completed. The changes in cellular immune function, tumor-related biological parameters, imaging characteristics, the condition of remission, quality of life (QOL) and survival were assessed. The results indicated that 14 patients received 8 cycles of CIK cells infusion, and 4 cycles were completed in 6 patients. No adverse reaction was observed in all patients. The percentages of CD3+, CD3+CD8+ and CD3+CD56+ cells increased significantly (p<0.05), and serum levels of β2-microglobulin and LDH markedly decreased (p<0.05) after autologous CIK cells transfusion. The tumor-related symptoms were relieved, QOL obviously improved (p<0.01) in all patients. Complete remission was seen in 11 patients, and partial remission was observed in 7 patients. It is concluded that the autologous CIK cell infusion can improve immunity in elderly patients of hematological malignancies and displays its effectiveness and safety for elderly patients.

Therapy of 17 cases of idiopathic thrombocytopenia purpura by amifostine / 中国实验血液学杂志

The objective of this study was to explore the effect of amifostine (AMF) in treating patients with idiopathic thrombocytopenic purpura (ITP) and its adverse effects. 17 ITP patients (aged from 13 to 92, mean 65 years) were treated with AMF and their therapeutic regimen was following: 0.4 g AMF was dissolved in 100 ml physiological saline, the intravenous drop was performed at day and lasted 5 days per week, with interval 2 days, 4 weeks were considered as a course of treatment. The results showed that the normal counts of platelets were observed in 17 ITP patients after 1 course of treatment, and remained unchanged for 2 months following stop of therapy. In that time, no any drugs such as hormonal preparation, gamma-globulin, blood transfusion and so on were given in all treated patients, the main adverse effect of AMF was discomfort in digestive system that all patients could endure. Therefore, the patient's life quality was obviously improved. It is concluded that the AMF has been initially and successfully used to treat ITP patients with positive response, and may be considered as a safe-effective drug for treating old patients with ITP, but the long-term effect and pharmacological mechanism of this drug needs further evaluation.

Recent progress of study on mechanism of immune thrombocytopenic purpura and its clinical treatment - review / 中国实验血液学杂志

Immune thrombocytopenia purpura (ITP) is a disorder mediated by antiplatelet antibodies and characterized by accelerated destruction of platelets and impaired platelet production. The mainstay therapies for ITP have included corticosteroids, the immune globulin intravenous immunoglobulin and IV anti-D (monoclonal antibodies against the D antigen of the Rh system), vinblastine or a monoclonal anti-CD20 antibody that transiently depletes CD20(+) B cells, danazol, cyclophosphamide and even splenectomy to refractory one. Most of ITP patients responded to those treatment, while more than 30% of whom may relapse sooner or later. The recombinant forms of human TPO were discontinued from human use in clinic because recipients of these agents developed significant thrombocytopenia secondary to production of neutralizing antibodies that cross-reacted with endogenous TPO. All above mentioned treatments have side effects and severe infection may arise post splenectomy. The more powerful treatment with less side effects are needed. There are two TPO receptor agonist, AMG531 and Eltrompobag, have approved in Europe for the treatment of ITP. Both of them can improve the differentiation of megakaryocyte and platelets production. Combination treatment including pancytoprotector shows good effect in the treatment of refractory and relapsed ITP in China. Altogether, individual treatment of ITP is the contemporary trend in both clinical and preclinical practice. In this review the pathogenesis of ITP and its clinical therapies were reviewed, the individual regiments for treating ITP patients were discussed.

Amifostine used in the treatment of patients with myelodysplastic syndrome / 中国实验血液学杂志

The study was aimed to investigate the curative effects and adverse effects of amifostine in the treatment of patients with myelodysplastic syndrome (MDS). Amifostine (AMF) was used alone (4/12) or combined with recombinant human erythropoietin (rh-EPO) (8/12) in 12 MDS patients. The therapeutic regimen was adopted with AMF 0.4 g/day for 5 days, then took a break of 2 days and then went on for 3 weeks consecutively, that was reputed as one treatment cycle. rh-EPO 6 000 U was used for 3 days per week. The results showed that 12 patients all attained hematological improvement in peripheral blood. 11 cases showed major effective response rate (91.7%), while 1 case showed minor response rate (8.3%). The effective response rate of hemoglobin, leukocytes and platelets was 100%, 75% and 58.3% respectively. The intervals of red cell transfusions (RCT) in 2 cases living on red cell transfusion before AMF treatment were prolonged after AMF treatments, and the amount of each RCT was decreased obviously. The side effect was usually discomfort of digestive system, but all patients can endure. In conclusion, Amifostine is a potential drug in the treatment of MDS patients with safety especially to those elder patients who often suffered from other multiple organ disfunctions, and the curative effect will be improved by more treatment cycles.

Early effect of amifostine in treating aged patients with idiopathic thrombocytopenia purpura / 中国实验血液学杂志

The purpose of this study was to explore the effect of amifostine in treating aged patients with idiopathic thrombocytopenic purpura (ITP). Three aged ITP patients (one aged 88, one aged 75, another aged 65) were treated with amifostine over a period of 4 weeks for each. The results showed that the early positive responses were observed in all 3 aged patients after treatment with amifostine 5 x 400 mg per week for 4 weeks, the recovery of platelet counts to normal level were found in 2 cases after 1 week and in 1 case after 2 weeks. Following 4 months after stop of treatment with amifostine, the normal platelet counts still remains in all patients, no more blood transfusions, hormonal preparation and gamma-globulin were given. Amifostine has never been reported elewhere as to treat of aged ITP. In conclusion, amifostine has a good early therapeutic effect on aged ITP patients, but its clinical outcome of long-term still needs further evaluation.

Damage effect of hepatocytic growth-promoting substance from neonatal calf on DNA of HL-60 cells / 中国实验血液学杂志

The present study was aimed to investigate the damage effect of hepatocyte growrh promoting substance (HGS) on the HL-60 cell DNA in vitro and to explore the possible mechanism underlying the effect. Experiment was divided into 3 groups: one was control group, in which 0.9% NaCl solution was added, and other two were experimental group 1 and group 2, where 22.5 microg/ml and 40 microg/ml HGS were added, respectively. HL-60 cell growths were compared between groups with and without HGS. Single cell gel electrophoresis (SCGE) was used to detect DNA damage of HL-60 cell. DNA electrophoresis was used to detect the apoptosis of HL-60 cells caused by HGS. The results showed that the inhibitory effects of HGS on growth of HL-60 cells were observed in group with 22.5 microg/ml and group with 40 microg/ml after culture for 2 days, the DNA ladder and the apoptosis of HL-60 cells occurred in these 2 groups on day 2 after addition of HGS, the counts of HL-60 cells with comet tail in these experimental groups were found to be more increased in comparison with control group. In conclusion, the HGS can inhibit the growth of HL-60 cell and the apoptosis of HL-60 cells should be induced through pathway of DNA damage caused by HGS.

Short-term curative effect of amifostine combined with rhEPO on aged patients wilh myelodysplastic syndrome / 中国实验血液学杂志

The aim of this study was to investigate the curative effect of amifostine (AMF) combined with recombinant human erythropoietin (rhEPO) on the aged patients with myelodysplastic syndrome. Two aged MDS patients (one aged 91; another 86) were treated with amifostine and rhEPO over a period of 4 weeks. The results showed that a short-term curative effect was observed and transfusion interval was prolonged in both patients after 4 week treatment with 5 x 0.4 g AMF plus 3 x 6,000 U rhEPO per week. The reticulocyte count in MDS-RA patient returned to normal at first week of treatment and still remained in normal level for 4 weeks; leukocyte, hemoglobin and platelet values in peripheral blood of MDS-RCMD patient obviousby increased, the abnormally increased reticulocyte value displayed a decrease trend after amifostine plus rh-EPO treatment. In conclusion, amifostine plus rhEPO may have a good therapeutic effect for aged MDS patients, and its clinical long-term curative effect still needs further evaluation.

Comparison of curative effect of autologous peripheral blood stem cell transplantation versus bone marrow transplantation for acute leukemia / 中国实验血液学杂志

To compare the clinical outcome of autologous peripheral blood stem cell transplantation (APBSCT) and autologous bone marrow transplantation (ABMT) in treatment of patients with acute leukemia in first remission, 41 patients received APBSCT, 17 patients received unpurged ABMT and 30 patients received purged ABMT. The results showed that hematopoietic recovery was significantly earlier after APBSCT than that after purged or unpurged ABMT. The 3-year disease-free survival (DFS), relapse rate (RR) and transplant-related mortality (TRM) for all patients of 3 groups were 51.7%, 41.7% and 6.8%, respectively. DFS and RR were significantly influenced by disease types (ALL or AML) and intervals between diagnosis and CR(1) or CR(1) and transplant. The main causes of transplant-related death were infection and hemorrhage. After APBSCT, DFS, RR and TRM were 48.4%, 43.9% and 4.9%, respectively, and did not differ significantly from those found in unpurged ABMT (47.1%, 45.6% and 11.8%) or purged ABMT (66.5%, 29.6% and 6.7%). It is concluded that the clinical outcome of APBSCT is similar to unpurged or purged ABMT but APBSCT allows faster recovery of hematopoiesis and needs less transfusion support.

Hairy cell leukemia: report on one case with survival for 10 years / 中国实验血液学杂志

One case of hairy cell leukemia with survival for 10 years was reported. The patient received Interferon-alpha(2b) treatment continuously for more than 9 years and intravenous administration of fludarabine for 2 courses of treatment in the later period, and died due to complication of severer infection in thd end. The manifestation, diagnosis and treatment of hairy cell leukemia were discussed.

The expression of Fas, FasL and Bcl-2 on RMA cells during the process of apoptosis induced by chemotherapeutic drugs / 中国实验血液学杂志

The objective of the study is to explore the effect of Fas, FasL and Bcl-2 on the process of apoptosis induced by chemotherapeutic drugs through detecting the expression of Fas, FasL and Bcl-2 on murine lymphoma cell line RMA. Dexamethasone(DEX), etoposide (VP-16), arsenic trioxide As(2)O(3) and all trans-retinoic-acid (ATRA) were added to the RMA cells as well as to the cells preincubated with interleukin-2 (IL-2), interleukin-6 (IL-6) or granulocyte-macrophage colony-stimulating factor (GM-CSF), respectively. The effect on apoptosis was observed and the expression of Fas and FasL mRNA as well as the expression of Fas and Bcl-2 antigen were measured. DEX and VP-16 could promote apoptosis of RMA cells while upregulating the expression of Fas and FasL without affecting the expression of Bcl-2. ATRA downregulated the expression of Bcl-2 without any change of Fas and FasL, and no apoptosis of RMA cells induced by ATRA was observed. Although As(2)O(3) induced apoptosis of RMA cells, it did not affect the expression of Fas, FasL and Bcl-2, which suggested that different drugs induce apoptosis of the same kind of cells by different signal transduction system and apoptosis induced by Fas system needed the coexistence of Fas and FasL. Although IL-2, IL-6 and GM-CSF upregulated the expression of Fas protein when adding to RMA cells separately, none of them induced apoptosis. Apoptosis could be induced by combination of IL-2 and IL-6 along with the upregulation of Fas and FasL. The cytokines facilitated the apoptotic action of chemotherapeutic drugs, the drug concentration for inducing apoptosis decreased and the time period of starting apoptosis shortened. Apoptosis could be observed without the expression of FasL when anti-Fas-antibody was added to RMA cells. The results demonstrated that there was synergistic effect of chemotherapeutic drugs and some cytokines for induction of apoptosis. Fas-FasL system participated in the apoptosis induced by DEX and VP-16; different drugs induce apoptosis by different pathway of signal transduction.