• Clinical and Experimental Pediatrics
• /
• 제55권4호
• /
• pp.115-120
• /
• 2012

Although high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) have improved the prognosis for patients with high-risk neuroblastoma (NB), event-free survival rates remain in the range of 30 to 40%, which is unsatisfactory. To further improve outcomes, several clinical trials, including tandem HDCT/autoSCT, high-dose $^{131}I$-metaiodobenzylguanidine treatment, and immunotherapy with NB specific antibody, have been undertaken and pilot studies have reported encouraging results. Nonetheless, about half of high-risk NB patients still experience treatment failure and have no realistic chance for cure with conventional treatment options alone after relapse. Therefore, a new modality of treatment is warranted for these patients. In recent years, several groups of investigators have examined the feasibility and effectiveness of reduced-intensity allogeneic stem cell transplantation (RI alloSCT) for the treatment of relapsed/progressed NB. Although a graft-versus-tumor effect has not yet been convincingly demonstrated in the setting of relapsed NB, the strategy of employing RI alloSCT has provided hope that treatment-related mortality will be reduced and a therapeutic benefit will emerge. However, alloSCT for NB is still investigational and there remain many issues to be elucidated in many areas. At present, alloSCT is reserved for specific clinical trials testing the immunomodulatory effect against NB.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제31권1호
• /
• pp.46-52
• /
• 2009

The maxillary posterior edentulous region presents unique and challenging conditions in implant dentistry. The height of the posterior maxilla is reduced greatly as a result of dual resorption from the crest of the ridge and pneumatization of the maxillary sinus after the loss of teeth. Materials previously used for sinus floor grafting include autogenous bone, allogeneic bone, xenogenic bone and alloplastic materials. Autogenous bone is the material of choice, but its use is limited by donor-site morbidity, complications, sparse availability, uncontrolled resorption and marked volume loss. One way to overcome this problem would be to use bone substitutes alone as a osteoconductive scaffold for bone regeneration from the residual bone or in combination with allogeneic bone, which also has osteoinductive properties. The purpose of this article is to describe a double layers technique of demineralized and mineralized bone graft materials instead of autogenous bone in sinus floor augmentation of deficient posterior maxillary alveolar process and to report our experience with this technique. Our results show that maxillary sinus augmentation using mineralized and demineralized bone materials, when installed simultaneously with the implant or not, is good results for bone healing.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권1호
• /
• pp.467-474
• /
• 2014

Objective: To observe the effects of allogeneic and autologous transfusion on cellular immunity, humoral immunity and secretion of serum inflammatory factors and perforin during the perioperative period in patients with malignant tumors. Methods: A total of 80 patients (age: 38-69 years; body weight: 40-78 kg; ASA I - II) receiving radical operation for gastro-intestinal cancer under general anesthesia were selected. All the patients were divided into four groups based on the methods of infusion and blood transfusion: blank control group (Group C), allogeneic transfusion group (group A), hemodiluted autotransfusion Group (Group H) and hemodiluted autotransfusion + allogenic transfusion Group (A+H group). Venous blood was collected when entering into the surgery room ($T_0$), immediately after surgery ($T_1$) and 24h ($T_2$), 3d ($T_3$) and 7d ($T_4$) after surgery, respectively. Moreover, flow cytometry was applied to assess changes of peripheral blood T cell subpopulations and NK cells. Enzyme linked immunosorbent assays were performed to determine levels of IL-2, IL-10, TNF-${\alpha}$ and perforin. Immune turbidimetry was employed to determine the changes in serum immunoglobulin. Results: Both CD3+ and NK cells showed a decrease at $T_1$ and $T_2$ in each group, among which, in group A, CD3+ decreased significantly at $T_2$ (P<0.05) compared with other groups, and CD3+ and NK cell reduced obviously only in group A at $T_3$ and $T_4$ (P<0.05). CD4+ cells and the ratio of D4+/CD8+ were decreased in groups A, C and A+H at $T_1$ and $T_2$ (P<0.05). No significant intra- and inter-group differences were observed in CD8+ of the four groups (P<0.05). IL-2 declined in group C at $T_1$ and $T_2$ (P<0.05) and showed a decrease in group A at each time point (P<0.05). Moreover, IL-2 decreased in group A + H only at $T_1$. No significant difference was found in each group at $T_1$ (P<0.05). More significant decrease in group ?? at $T_2$, $T_3$ and $T_4$ compared with group A (P<0.05), and there were no significant differences among other groups (P>0.05). IL-10 increased at $T_1$ and $T_2$ in each group (P<0.05), in which it had an obvious increase in group A, and increase of IL-10 occurred only in group A at $T_3$ and $T_4$ (P<0.05). TNF-${\alpha}$ level rose at $T_1$ (P<0.05), no inter- and intra-group difference was found in perforin in all groups (P<0.05). Compared with the preoperation, both IgG and IgA level decreased at $T_1$ in each group (P<0.05), and they declined only in Group A at $T_2$ and $T_3$ (P<0.05), and these parameters were back to the preoperative levels in other groups. No significant differences were observed between preoperative and postoperative IgG and IgA levels in each group at $T_4$ (P>0.05). No obvious inter- and intra-group changes were found in IgM in the four groups (P>0.05). Conclusions: Allogeneic transfusion during the perioperative period could obviously decrease the number of T cell subpopulations and NK cells and the secretion of stimulating cytokines and increase the secretion of inhibiting cytokines in patients with malignant tumors, thus causing a Th1/Th2 imbalance and transient decreasing in the content of plasma immune globulin. Autologous transfusion has little impact and may even bring about some improvement oo postoperative immune function in patients with tumors. Therefore, cancer patients should receive active autologous transfusion during the perioperative period in place of allogeneic transfusion.

• IMMUNE NETWORK
• /
• 제3권2호
• /
• pp.150-155
• /
• 2003

Background: We investigated the effect of donor marrow T cell depletion, administration of FK506, cyclosporin A (CSA), and 3-deazaadenosine (DZA) on graft versus host disease (GVHD) after allogeneic murine hematopoietic stem cell transplantation (HSCT). Methods: We used 4 to 6 week old Balb/c ($H-2^d$, recipient), and C3H/He ($H-2^k$, donor) mice. Total body irradiated recipients received $1{\times}10^7$ bone marrow cells (BM) and $0.5{\times}10^7$ splenocytes of donor under FK506 (36 mg/kg/day), CSA (5 mg/kg/day, 20 mg/kg/day), and DZA (45 mg/kg/day), which were injected intraperitoneally from day 1 to day 14 daily and then three times a week for another 2 weeks. To prevent the GVHD, irradiated Balb/c mice were transplanted with $1{\times}10^7$ rotor-off (R/O) cells of donor BM. The severity of GVHD was assessed daily by clinical scoring method. Results: All experimental groups were well grafted after HSCT. Mice in experimental group showed higher GVHD score and more rapid progression of GVHD than the mice with R/O cells (R/O group) (p<0.01). There were relatively low GVHD scores and slow progressions in FK506 and low dose CSAgroups than high dose CSA group (p<0.01). The survival was better in FK506 group than low dose CSA group. All mice treated with CSA died within 12 days after HSCT. The GVHD score in DZA group was low and slow in comparison with control group (p<0.05), but severity and progression were similar with low dose CSA group (p=0.11). All mice without immunosuppressive treatment died within 8 days, but all survived in R/O group (p<0.01). Survival in low dose CSA group was longer than in control group (p<0.05), but in high dose CSA group, survival was similar to control group. The survival benefit in DZA group was similar with low dose CSA group. FK506 group has the best survival benefit than other groups (p<0.01), comparable with R/O group (p=0.18), although probability of survival was 60%. Conclusion: We developed lethal GVHD model after allogeneic murine HSCT. In this model, immunosuppressive agents showed survival benefits in prevention of GVHD. DZA showed similar survival benefits to low dose CSA. We propose that DZA can be used as a new immunosuppressive agent to prevent GVHD after allogeneic HSCT.

• IMMUNE NETWORK
• /
• 제15권2호
• /
• pp.66-72
• /
• 2015

Currently, detecting biochemical differences before and after allogeneic stem cell transplantation (SCT) for improved prediction of acute graft-versus-host disease (aGVHD) is a major clinical challenge. In this pilot study, we analyzed the kinetics of circulating adipokine levels in patients with or without aGVHD before and after allogeneic SCT. Serum samples were obtained and stored at $-80^{\circ}C$ within 3 hours after collection, prior to conditioning and at engraftment after transplantation. A protein array system was used to measure the levels of 7 adipokines of patients with aGVHD (n=20) and without aGVHD (n=20). The resistin level at engraftment was significantly increased (p<0.001) after transplantation, regardless of aGVHD occurrence. In the non-aGVHD group, the concentrations of the hepatocyte growth factor (HGF) (mean values${\pm}$SD; $206.6{\pm}34.3$ vs. $432.3{\pm}108.9pg/ml$, p=0.040) and angiopoietin-2 (ANG-2) (mean values${\pm}$SD; $3,197.2{\pm}328.3$ vs. $4,471.8{\pm}568.4pg/ml$, p=0.037) at engraftment were significantly higher than those of the pre-transplant period, whereas in the aGVHD group, the levels of adipokines did not change after transplantation. Our study suggests that changes in serum HGF and ANG-2 levels could be considered helpful markers for the subsequent occurrence of aGVHD.

• Clinical and Experimental Pediatrics
• /
• 제55권3호
• /
• pp.100-106
• /
• 2012

Purpose: The survival rate for childhood acute lymphoblastic leukemia (ALL) has improved significantly. However, overall prognosis for the 20 to 25% of patients who relapse is poor, and allogeneic hematopoietic stem cell transplantation (HSCT) offers the best chance for cure. In this study, we identified significant prognostic variables by analyzing the outcomes of allogeneic HSCT in ALL patients in second complete remission (CR). Methods: Fifty-three ALL patients (42 men, 79%) who received HSCT in second CR from August 1991 to February 2009 were included (26 sibling donor HSCTs, 49%; 42 bone marrow transplantations, 79%). Study endpoints included cumulative incidence of acute and chronic graft-versus-host disease (GVHD), relapse, 1-year transplant-related mortality (TRM), disease-free survival (DFS), and overall survival (OS). Results: Cumulative incidences of acute GVHD (grade 2 or above) and chronic GVHD were 45.3% and 28.5%, respectively. The estimated 5-year DFS and OS for the cohort was $45.2{\pm}6.8%$ and $48.3{\pm}7%$, respectively. Only donor type, i.e., sibling versus unrelated, showed significant correlation with DFS in multivariate analysis ($p$=0.010). The rates of relapse and 1 year TRM were $28.9{\pm}6.4%$ and $26.4{\pm}6.1%$, respectively, and unrelated donor HSCT ($p$=0.002) and HLA mismatch ($p$=0.022) were significantly correlated with increased TRM in univariate analysis. Conclusion: In this single institution study spanning more than 17 years, sibling donor HSCT was the only factor predicting a favorable result in multivariate analysis, possibly due to increased TRM resulting from unrelated donor HSCT.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권10호
• /
• pp.5705-5711
• /
• 2013

Background: Embryonic stem cells (ESCs) have the potential to form teratomas when implanted into immunodeficient mice, but data in immunocompetent mice are limited. We therefore investigated teratoma formation after implantation of three different mouse ESC (mESC) lines into immunocompetent mice. Materials and Methods: BALB/c mice were injected with three highly germline competent mESCs (129Sv, BALB/c and C57BL/6) subcutaneously or under the kidney capsule. After 4 weeks, mice were euthanized and examined histologically for teratoma development. The incidence, size and composition of teratomas were compared using Pearson Chi-square, t-test for dependent variables, one-way analysis of variance and the nonparametric Kruskal-Wallis analysis of variance and median test. Results: Teratomas developed from all three cell lines. The incidence of formation was significantly higher under the kidney capsule compared to subcutaneous site and occurred in both allogeneic and syngeneic mice. Overall, the size of teratoma was largest with the 129Sv cell line and under the kidney capsule. Diverse embryonic stem cell-derived tissues, belonging to the three embryonic germ layers, were encountered, reflecting the pluripotency of embryonic stem cells. Most commonly represented tissues were nervous tissue, keratinizing stratified squamous epithelium (ectoderm), smooth muscle, striated muscle, cartilage, bone (mesoderm), and glandular tissue in the form of gut- and respiratory-like epithelia (endoderm). Conclusions: ESCs can form teratomas in immunocompetent mice and, therefore, removal of undifferentiated ESC is a pre-requisite for a safe use of ESC in cell-based therapies. In addition the genetic relationship of the origin of the cell lines to the ability to transplant plays a major role.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권8호
• /
• pp.4529-4532
• /
• 2013

Background: Acute normovolemic hemodilution (ANH) has been widely used to prevent the massive blood loss during hepatic carcinoma. The influences of ANH on coagulation function are still controversy, especially in elderly patients. The study observed ANH effects on coagulation function and fibrinolysis in elderly patients undergoing the disease. Materials and Methods: Thirty elderly patients (aged 60-70 yr) with liver cancer (ASA I or II) taken hepatic carcinectomy from February 2007 to February 2008 were randomly divided into ANH group (n=15) and control group (n=15). After tracheal intubation, patients in ANH group and control group were infused with 6% hydroxyethyl starch (130/0.4) and Ringer's solution, respectively. Blood samples were drawn from patients in both groups at five different time points: before anesthesia induction (T1), 30 min after ANH (T2), 1 h after start of operation (T3), immediately after operation (T4), and 24 h after operation (T5). Then coagulation function, soluble fibrin monomer complex (SFMC), prothrombin fragment (F1+2), and platelet membrane glycoprotein (CD62P and activated GP IIb/GP IIIa) were measured. Results: The perioperative blood loss and allogeneic blood transfusion were recorded during the surgery. The perioperative blood loss was not significantly different between two groups (p>0.05), but the volume of allogeneic blood transfusion in ANH group was significantly less than in control group ($350.0{\pm}70.7$) mL vs. ($457.0{\pm}181.3$) mL (p<0.01). Compared with the data of T1, the prothrombin time (PT) and activated partial thromboplastin time (APTT) measured after T3 were significantly longer (p<0.05) in both groups, but within normal range. There were no significant changes of thrombin time (TT) and D-dimer between two groups at different time points (p>0.05). SFMC and F1+2 increased in both groups, but were not statistically significant. PAC-1-positive cells and CD62P expressions in patients of ANH group were significantly lower than those at T1 (p<0.05) and T2-T5 (p>0.05). Conclusions: ANH has no obvious impact on fibrinolysis and coagulation function in elderly patients undergoing resection of liver cancer. The study suggested that ANH is safe to use in elderly patients and it could reduce allogeneic blood transfusion.

• Clinical and Experimental Pediatrics
• /
• 제56권11호
• /
• pp.490-495
• /
• 2013

Purpose: The use of cyclosporine and mini-dose methotrexate (MTX) is a common strategy for graftversus- host disease (GVHD) prophylaxis in allogeneic transplants. We investigated whether patients who receive fewer than the planned MTX doses are at increased risk for GVHD. Methods: The study cohort included 103 patients who received allogeneic transplants at the Department of Pediatrics of The Catholic University of Korea College of Medicine, from January 2010 to December 2011. MTX was administered on days 1, 3, 6, and 11 after transplant at a dose of 5 $mg/m^2$ each. Within the cohort, 76 patients (74%) received all 4 doses of MTX [MTX(4) group], while 27 patients (26%) received 0-3 doses [MTX(0-3) group]. Results: Although there was no difference in neutrophil engraftment between the 2 groups, platelet engraftment was significantly faster in the MTX(4) group (median, 15 days), compared to the MTX(0- 3) group (median, 25 days; P =0.034). The incidence of grades II-IV acute GVHD was not different between the MTX(4) and MTX(0-3) groups (P =0.417). In the multivariate study, human leukocyte antigen mismatch was the most significant factor causing grades II-IV acute GVHD (P =0.002), followed by female donor to male recipient transplant (P =0.034). No difference was found between the MTX(4) and MTX (0-3) groups regarding grades III-IV acute GVHD, chronic GVHD, and disease-free survival. Conclusion: Our results indicate that deviations from the full dose schedule of MTX for GVHD prophylaxis do not lead to increased incidence of either acute or chronic GVHD.

• Molecules and Cells
• /
• 제38권11호
• /
• pp.966-974
• /
• 2015

Despite the presence of toll like receptor (TLR) expression in conventional $TCR{\alpha}{\beta}$ T cells, the direct role of TLR signaling via myeloid differentiation factor 88 (MyD88) within T lymphocytes on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation (allo-SCT) remains unknown. In the allo-SCT model of C57BL/6 ($H-2^b$) ${\rightarrow}$ B6D2F1 ($H-2^{b/d}$), recipients received transplants of wild type (WT) T-cell-depleted (TCD) bone marrow (BM) and splenic T cells from either WT or MyD88 deficient (MyD88KO) donors. Host-type ($H-2^d$) P815 mastocytoma or L1210 leukemia cells were injected either subcutaneously or intravenously to generate a GVHD/GVL model. Allogeneic recipients of MyD88KO T cells demonstrated a greater tumor growth without attenuation of GVHD severity. Moreover, GVHD-induced GVL effect, caused by increasing the conditioning intensity was also not observed in the recipients of MyD88KO T cells. In vitro, the absence of MyD88 in T cells resulted in defective cytolytic activity to tumor targets with reduced ability to produce IFN-${\gamma}$ or granzyme B, which are known to critical for the GVL effect. However, donor T cell expansion with effector and memory T-cell differentiation were more enhanced in GVHD hosts of MyD88KO T cells. Recipients of MyD88KO T cells experienced greater expansion of Foxp3- and IL4-expressing T cells with reduced INF-${\gamma}$ producing T cells in the spleen and tumor-draining lymph nodes early after transplantation. Taken together, these results highlight a differential role for MyD88 deficiency on donor T-cells, with decreased GVL effect without attenuation of the GVHD severity after experimental allo-SCT.