No abstract available.
Allografts* ; Animals ; Blood Transfusion* ; Cyclosporine* ; Lymphocyte Culture Test, Mixed* ; Rats*

One of the major obstacle for hematopoietic stem cell transplantation (HSCT) to treat patients with beta-thalassemia is graft rejection (GR). The proportion of donor-derived cells continually declined in mixed chimerism (MC), finally leading to graft failure. Monitoring chimerism after transplant consecutively can early find unstable mixed chimerism and rejection, which provide the basis for donor lymphocyte infusion (DLI); for imminent risk of graft rejection, escalating doses of DLI is a feasible method for converting unstable MC towards stable MC or full donor chimerism. This review focuses on advancement of chimerism monitoring and DLI after HSCT for patients with β-thalassemia major.
Graft Rejection ; etiology ; Humans ; Lymphocyte Transfusion ; Thalassemia ; therapy ; Tissue Donors ; Transplantation Chimera

In order to study the value of sequential and quantitative analysis of chimerism in determination of optional time of donor lymphocyte infusion (DLI) and prediction of efficacy of DLI, six patients with leukemias who relapsed or failed of engraftment were treated with DLI. Serial and quantitative analyses of donor chimerism (DC) both prior to and following DLI were performed by multiplex PCR amplification of STR markers (STR-PCR) and capillary electrophoresis with fluorescence detection. The results showed that at the time of relapse or graft rejection, STR-PCR indicated the decreasing donor chimerism in all six patients, at levels ranging from 27.3% to 85.7%. The declining value of DC (<90%) was detected in four patients at 26 days before relapse or graft rejection diagnosed clinically. Therefore the decrease of value of DC can be identified the high risk of relapse or graft failure and can be used to guide DLI implementation at early stage. In this study the clinical response were seen in two patients, the value of DC in these patients increased with convertion to a predominant donor profile (>90%) or converted to stable FDC shortly after DLI, while in the patients without clinical response, the level of DC decreased persistently or declined after transient increase. Three patients without response received second DLI. It is concluded that the monitoring of chimerism is proved to be a valuable to determine the optional time point of DLI and to early evaluate the efficacy of DLI. Furthermore, it can present a rational basis for treatment of intensification in the patients who did not respond to first-line DLI treatment.
Adolescent ; Adult ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphocyte Transfusion ; Recurrence ; Tissue Donors ; Transplantation Chimera

OBJECTIVETo evaluate the protective effect of ligustrazine on T-lymphocyte immunity of patients undergoing autologous blood transfusion (ABT).

METHODSForty American Society of Anesthesiologist (ASA) I - II patients scheduled for receiving selective lumbar surgery, with pre-operational anticipatory blood loss > 400 mL and without any diseases of blood or endocrinal system were enrolled. They were equally randomized into two groups, the trial group and the control group. Ligustrazine was given to patients in the trial group by intravenous dripping at the dose of 2 mg/kg, 30 min before auto-blood collection, also by mixed in the washing saline and heparinized saline solution to make the final concentration of ligustrazine 0.005%. No ligustrazine was given to patients in the control group. The amount of blood loss and autotransfused were measured and recorded; and patients' venous blood samples for T-lymphocyte subsets (CD3, CD4, CD8) determination and CD4/CD8 ratio calculation were collected at different time points, i. e. before surgery (T0) and at 1 h (T1), 1st day (T2) and 5th day (T3) after ABT.

RESULTSCD3 decreased obviously at T1 and T2 in both groups (P < 0.05 or P < 0.01), while at T3, it restored to baseline in the trial group, but remained at the low level in the control group (P < 0.05). Moreover, levels of CD3 at T1-T3 were lower in the control group than those in the trial group respectively (P < 0.05 or P < 0.01). CD4 decreased obviously at T1 (P < 0.01) in both groups, it recovered at T2 in the trial group, but the recovering in the control group was T3, so comparison of CD4 level between groups showed significant difference at T1 and T2 (P < 0.05 or P < 0.01). As for CD4/CD8 ratio, it decreased obviously at T2 and T3 in the control group (P < 0.05), but unchanged in the trial group, showing statistical difference between groups (P < 0.05).

CONCLUSIONLigustrazine had definite protective effect on T-lymphocyte immunity in patients undergoing ABT, which was presented by the milder inhibition and quicker recovery of immunity.

Adult ; Aged ; Blood Transfusion, Autologous ; Female ; Humans ; Male ; Middle Aged ; Pyrazines ; pharmacology ; T-Lymphocyte Subsets ; drug effects ; immunology ; Young Adult

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.
Aged ; Aged, 80 and over ; Cytokine-Induced Killer Cells ; Humans ; Immunotherapy, Adoptive ; Lymphocyte Transfusion ; Male ; Myelodysplastic Syndromes ; therapy

Asthma is a chronic disease of airway inflammation due to excessive T helper cell type 2 (Th2) response. Present treatment based on inhalation of synthetic glucocorticoids can only control Th2-driven chronic eosinophilic inflammation, but cannot change the immune tolerance of the body to external allergens. Regulatory T cells (Tregs) are the main negative regulatory cells of the immune response. Tregs play a great role in regulating allergic, autoimmune, graft-versus-host responses, and other immune responses. In this review, we will discuss the classification and biological characteristics, the established immunomodulatory mechanisms, and the characteristics of induced differentiation of Tregs. We will also discuss the progress of Tregs in the field of asthma. We believe that further studies on the regulatory mechanisms of Tregs will provide better treatments and control strategies for asthma.
Antigens, CD/analysis* ; Apyrase/analysis* ; Asthma/immunology* ; Cell Differentiation ; Cytokines/metabolism* ; Humans ; Lymphocyte Transfusion ; T-Lymphocytes, Regulatory/immunology*

Objective: To explore clinical features and severity of chronic graft- versus- host disease (cGVHD) after chemotherapy plus donor lymphocyte infusion (Chemo-DLI) in a consecutive cohort of acute leukemia patients who were minimal residual disease (MRD) positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The global scoring system proposed by National Institutes of Health (NIH) Consensus Conference was used to identify the characteristics and severity of cGVHD in patients who MRD positive after Chemo-DLI. Results: 54 (59.3%) patients were diagnosed with cGVHD after Chemo-DLI, with the median time of onset of 70 (13-504) days. There were 6 cases (6.6%) of mild cGVHD, 21 cases (23.1%) of moderate cGVHD and 27 cases (29.7%) of severe cGVHD.The 5-year cumulative incidence of relapse after Chemo-DLI was 61.9% (95%CI 45.3%-78.5%) , 15.1% (95%CI 1.1%-29.1%) , and 26.6% (95%CI 9.2%-44.0%) (χ(2)=18.901, P<0.001) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. The 5-year cumulative incidence of relapse after Chemo-DLI was 61.9% (95%CI 45.3%-78.5%) , 19.9% (95%CI 8.1%-31.7%) , and 28.6% (95%CI 0.0%-65.0%) (χ(2)=18.307, P<0.001) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. cGVHD was not associated with non-relapse morality after Chemo-DLI. Probabilities of 5-year leukemia-free survival (LFS) after Chemo-DLI were 24.0% (95%CI 9.1%-38.9%) , 77.2% (95%CI 60.8%-93.6%) , and 64.9% (95%CI 45.7%-84.1%) (χ(2)=24.447, P<0.001) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. Probabilities of 5-year LFS after Chemo-DLI were 24.0% (95%CI 9.1%-38.9%) , 75.5% (95%CI 62.7%-88.3%) , and 42.9% (95%CI 1.8%-84.0%) (χ(2)=25.665, P<0.001) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. Probabilities of 5-year overall survival (OS) after Chemo-DLI were 50.0% (95%CI 31.1%-68.9%) , 87.9% (95%CI 74.7%-100.0%) , and 71.0% (95%CI 52.0%-90.0%) (χ(2)=9.517, P=0.009) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. Probabilities of 5-year OS after Chemo-DLI were 50.0% (95%CI 31.1%-68.9%) , 83.9% (95%CI 72.8%-95.0%) , and 51.4% (95%CI 6.2%-96.6%) (χ(2)=10.673, P=0.005) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. In multivariate analysis, patients receiving allo-HSCT in first complete remission stage and classical cGVHD after Chemo-DLI were associated with lower relapse risk and better survival. Conclusions: These findings highlight the close relation between cGVHD and the graft-versus-leukemia effect in patients who were MRD positive and received Chemo-DLI after allo-HSCT. However, overlap syndrome could not improve the clinical outcomes of these patients.
Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphocyte Transfusion ; Lymphocytes ; Neoplasm, Residual ; Prognosis ; Transplantation, Homologous

BACKGROUNDNonmyeloablative allogeneic bone marrow transplantation has been used since the 1990s as a new hematological stem cell transplantation strategy for treating hematological diseases. The purpose of this study was to explore the graft-versus-leukemia (GVL) effects of donor lymphocyte infusions (DLIs) after nonmyeloablative allogeneic bone marrow transplantations, while assessing the declines in treatment-associated morbidity, mortality, and graft-versus-host disease (GVHD).

METHODSA total of 615 (H-2k) mice were injected with L615 tumor cells and received 500 cGy (60Co gamma-ray) irradiation three days later, followed by an allogeneic bone marrow transplantation (allo-BMT). The allo-grafts consisted of 3 x 10(7) bone marrow cells and 1 x 10(7) spleen cells from BALB/C (H-2d) donor mice. Two days after the allo-BMT, the recipient mice were given 200 mg/kg of cyclophosphamide. Subsequently, recipient mice were infused with either donor spleen cells (2 x 10(7)) on day 14 or 21, or donor spleen cells (5 x 10(7)) pretreated with hydrocortisone and cyclosporin A (CsA) in vitro on day 14 post-BMT.

RESULTSThe median survival time of mice that received DLI on day 21 and pretreated DLI on day 14 post-BMT was longer than that of controls and the day 14 DLI group (P < 0.01). No evidence of severe GVHD was observed in the day 21 DLI group nor in the day 14 treated DLI group. Mixed chimerism was confirmed in the day 14 DLI group, the day 14 treated DLI group, and the day 21 DLI group on the thirteenth day post-transplantation; full donor chimerism was observed two weeks after DLI.

CONCLUSIONDonor lymphocyte infusion after nonmyeloablative bone marrow transplantation may reduce transplantation-associated morbidity and mortality while strengthening graft-versus-leukemia effects.

Animals ; Bone Marrow Transplantation ; immunology ; Cyclosporine ; pharmacology ; Female ; Graft vs Host Disease ; etiology ; Graft vs Leukemia Effect ; immunology ; Hydrocortisone ; pharmacology ; Lymphocyte Activation ; Lymphocyte Transfusion ; Male ; Mice ; Mice, Inbred BALB C ; Transplantation Chimera ; Transplantation, Homologous

PURPOSE: Severe thrombocytopenia is a rare but life threatening side effect of anticancer chemotherapy. This study is for delineating risk factors for anticancer chemotherapy induced thrombocytopenia requiring platelet transfusion in cancer patients. MATERIALS AND METHODS: Ninety seven cases of cancers (stomach cancer 37, lung cancer 31 and breast cancer 29) were included in this study design. Complete blood cell counts were done at day 1 and then twice a week to find lowerest thrombocyte count in each cycle. Discriminant analysis of risk factors for chemotherapy induced thrombocytopenia requiring platelet transfusion were performed. RESULTS: Anticancer chemotherapy induced thrombocytopenia less than 150,000/ microliter developed in 18 cases (20.0%) at day 20.6 8.0 and mean platelet count was 111,060 35,360/ microliter. Thrombocytopenia less than 100,000/ microliter developed in 10 cases (10.3%) at day 20.2 6.9 and mean platelet count was 56,200 30,460/ microliter. Among them platelet transfusions were needed in 6 cases (6.2%). Using discrininant analysis, day 1 platelet count less than 150,000/ microliter with total lymphocyte count less than 900/ microliter were identified as risk factors for anticancer chemotherapy induced thrombocytopenia requiring platelet transfusion. CONCLUSION: Thrombocytopenia less than 150,000 microliter with total lymphocyte count less than 900/ microliter before administrating anticancer drugs are high risk factors for platelet transfusion, and needed proper managements.
Blood Cell Count ; Blood Platelets* ; Breast Neoplasms ; Drug Therapy* ; Humans ; Lung Neoplasms ; Lymphocyte Count ; Platelet Count ; Platelet Transfusion* ; Risk Factors* ; Thrombocytopenia*

OBJECTIVETo investigate the effect of transfusion of apoptotic and necrotic thymocytes prior to sepsis on the survival rate of mice.

METHODSBALB/c mice are divided into 3 groups and received intravenous injection of PBS (control), apoptotic thymocytes, or necrotic thymocytes. Three days later, cecal ligation and puncture (CLP) were performed to induce sepsis in these mice, and their survival and organ damage were observed.

RESULTSThe survival rates of mice in PBS group was 44.6% at the end of first week after CLP, and obvious lung and kidney damages were observed. A significant increase in the survival rate was found in apoptotic cell transfusion group (69.6%, P=0.012), with also lessened lung and kidney damages. The survival rate of mice in necrotic cell transfusion group was only 31.6% at 2 weeks, significantly lower than that in PBS group (P=0.035), and the lung and kidney damage was even more obvious.

CONCLUSIONTransfusion of apoptotic thymocytes 3 days before induction of sepsis can reduce organ damage and improve the survival rate of mice, while necrotic cell transfusion produces the opposite effect.

Animals ; Apoptosis ; Disease Models, Animal ; Lymphocyte Transfusion ; Mice ; Mice, Inbred BALB C ; Necrosis ; Sepsis ; mortality ; therapy ; Survival Rate ; Thymus Gland ; cytology