Biomedical subjects

Dong Il Won

Publications and source records attributed to Dong Il Won.

8 recordsLinked to original sources

PubMed2007

Flow cytometry PRA using lymphocyte pools from random donors.

BACKGROUND: Pools of lymphocytes from carefully chosen donors have been used for flow cytometry (FC) panel reactive antibody (PRA) assays. We intended to devise an FC PRA assay using mixed lymphocyte pools from a large number of randomly selected donors (RD FC PRA) to accurately predict the likelihood of a positive HLA crossmatch. METHODS: Lymphocyte pools were prepared from randomly selected donors (N = 120). %PRA was calculated based on the anti-IgG FITC histogram of the T cells. The proposed RD FC PRA assay was assessed in comparison with the bead FC PRA, antiglobulin-augmented CDC (AHG-CDC) PRA assay, and the expected %PRA calculated by summing up the antigen frequencies of the known specificities. RESULTS: In 29 FC crossmatch positive sera, the positivity rate for the bead FC, RD FC, and AHG-CDC PRA was 100, 100, and 79%, and the mean %PRA was 77% +/- 0.205). In 19 sensitized patients with a negative FC crossmatch, the positivity rate was 21% using the RD FC PRA and 16% using the bead FC PRA, which suggested that both assays had similar abilities to detect low levels of HLA antibodies. CONCLUSIONS: The RD FC PRA assay allows easy panel preparation, reduces cost, and naturally reflects the probabilities of a positive crossmatch in the population to which the cadaveric donor belongs. Therefore, this new assay is expected to be useful as another approach to determine the % PRA.

Antigens, Surface↗

PubMed2006

Survival benefit of asymptomatic cytomegalovirus reactivation after HLA-identical allogeneic peripheral blood stem cell transplantation.

BACKGROUND: Cytomegalovirus (CMV) reactivation (CMV-R) is associated with increased morbidity after allogeneic stem cell transplantation (SCT). However, after the introduction of ganciclovir preemptive therapy, CMV-R can be successfully controlled if the recipient's immunity recovers. Although many investigations have already focused on CMV-R as a risk factor, data related to the impact of asymptomatic CMV-R on transplant outcomes is scarce. Accordingly, the present study analyzed the differences in the transplant outcomes the immune reconstitution according to the CMV-R after allogeneic PBSCT. METHODS: A total of 76 patients undergoing allogeneic peripheral blood stem cell transplantation (PBSCT) were included in the current study. The transplant outcomes and immune reconstitution after 3, 6, and 12 months were analyzed according to the occurrence of CMV-R in 33 patients. RESULTS: The analysis revealed a favorable prognosis for the group with CMV-R compared to those without CMV-R: P = 0.0037 for OS, P = 0.0204 for NRM, and P = 0.05 for the risk of relapse. CMV-R was also found to correlate to the lymphoid reconstitution (P = 0.024). In multivariate analyses, CMV-R was found to be a favorable prognostic factor in terms of OS (P = 0.010, hazard ratio [HR] 2.948) and NRM (P = 0.05, HR 2.665), along with a higher transplant CD34 cell dose (P = 0.003 for OS, P = 0.002 for NRM), standard risk (P = 0.023 for OS), and acute GVHD grades 0-2 (P = 0.007 for NRM). CONCLUSION: In a PBSCT setting, CMV-R did not seem to be a poor prognostic factor in terms of OS and NRM, possibly due to the accelerated lymphoid immune reconstitution associated with CMV-R.

Adolescent↗

PubMed2006

Simultaneous detection of antibody binding and cytotoxicity in flow cytometry crossmatch for renal transplantation.

BACKGROUND: The anti-HLA antibody can be detected using either a complement-dependent lymphocytotoxicity (CDC) assay or a flow cytometry crossmatch (FCXM) in renal transplantation. Discordant results are often obtained because the two methods detect different reaction phases between the donor lymphocytes and the recipient sera. This study was intended to confirm that antibody binding and cytotoxicity to the lymphocytes can be detected simultaneously in a single FCXM assay, cytotoxic FCXM. METHODS: In the cytotoxic FCXM, the antibody binding to the lymphocytes was measured using anti-IgG-FITC, and the cytotoxicity using 7-aminoactinomycin D (7-AAD) after adding complement. For an evaluation of two test parameters, the cytotoxicity test moiety (dead-cell percentage) was compared with the anti-human globulin (AHG)-CDC, and the antibody-binding test moiety (sample/control fluorescence ratio) with the conventional FCXM in 77 positive and 30 negative crossmatches. RESULTS: In the cytotoxic FCXM, both antibody binding and cytotoxicity could be assessed in a single anti-IgG-FITC/7-AAD plot. Regarding the correlation between the presence of HLA antibodies and the test result, the cytotoxicity parameter (r = 0.55) appeared to be more suitable than that of the AHG-CDC (r = 0.50) but the antibody-binding parameter (r = 0.83) was worse than that of the conventional FCXM (r = 0.93). The sensitivity of both parameters of the cytotoxic FCXM was not significantly different from each conventional counterpart (P = 0.33 and P = 0.22, respectively). CONCLUSIONS: The simultaneous detection of Ab binding and cytotoxicity was possible by the cytotoxic FCXM with the test efficiencies similar to the conventional counterparts. If this new assay is improved through the further studies to optimize the critical assay variables, this may be used as an alternative to the conventional assays to acquire more information on the characteristics of the recipient's HLA alloantibodies.

Antibodies, Anti-Idiotypic↗

PubMed2006

Non-CD34+ cells, especially CD8+ cytotoxic T cells and CD56+ natural killer cells, rather than CD34 cells, predict early engraftment and better transplantation outcomes in patients with hematologic malignancies after allogeneic peripheral stem cell transplantation.

The effect of the transplant dose of each cell subset on engraftment kinetics and transplantation outcomes was evaluated in HLA-identical allogeneic peripheral blood stem cell transplantation (PBSCT). Sixty-nine patients were included in this retrospective study. Engraftment kinetics, transplantation outcomes, and immune reconstitution up to 1 year after transplantation were analyzed according to the transplant dose of CD34+ and non-CD34+ cells, including natural killer (NK) cells and CD8+ cytotoxic T (Tc) cells. An accelerated neutrophil engraftment was strongly associated with a higher transplant dose of NK cells (12 versus 16 days, P < .001) and Tc cells (13 versus 16 days, P < .001) but not CD34+ cells (P = .442). Survival analyses revealed a favorable prognosis for patients who received a higher dose of non-CD34+ cell subsets, rather than CD34+ cells, in terms of overall survival (OS; P = .024 for NK cells and .050 for Tc cells) and nonrelapse mortality (NRM; P = .005 for NK cells, .060 for Tc cells). In addition, a higher transplant dose of NK and Tc cells was correlated with a faster lymphoid reconstitution. In multivariate analyses, rapid neutrophil engraftment was correlated with a higher transplant dose of NK cells (P = .001) and Tc cells (P = .004). Moreover, an increased OS was associated with the NK cell dose (P = .007) and chronic graft-versus-host disease (P = .009), whereas a decreased NRM was associated with the NK dose (P = .024). In conclusion, in a PBSCT setting, a higher transplant dose of NK and Tc cells accelerated neutrophil engraftment, improved the immune reconstitution, and decreased NRM, thereby increasing OS after allogeneic PBSCT.

Adolescent↗

PubMed2006

Clinical significance of platelet count at day +60 after allogeneic peripheral blood stem cell transplantation.

Thrombocytopenia (TP) is a frequent complication after allogeneic stem cell transplantation (SCT) and regarded as a poor prognostic factor, especially in patients with chronic graft-versus-host disease (GVHD), although various factors were related to the development of TP after allogeneic SCT. Sixty-three patients receiving allogeneic peripheral blood stem cell transplantation (PBSCT) were stratified according to platelet count (PC) at day +60 and analyzed in terms of overall survival (OS) and the incidence of non-relapse mortality (NRM). Ten patients (15.9%) were stratified in group 1 (PC </= 29 x 10(9)/L), 23 patients (36.5%) in group 2 (PC 30-79 x 10(9)/L), and 30 patients in group 3 (PC >/= 80 x 10(9)/L). Group 3 was associated with lower incidence of extensive chronic GVHD (p=0.013), better 3-yr OS (p=0.0030), and lower NRM rate (p<0.0001). In multivariate analyses, the PC at day +60 was identified as an independent prognostic factor (p=0.003) together with CD34+ cell dose (p<0.001), disease risk (p=0.004), and acute GVHD (p=0.033) in terms of NRM, and the PC (p=0.047) and CD34+ cell dose (p=0.026) in terms of incidence of infectious events. Measuring the platelet count at day +60 is a simple method for predicting the risk of chronic GVHD development and prognosis after allogeneic PBSCT.

Adolescent↗

PubMed2005

Daunorubicin efflux assay in determining multidrug resistance of patients with acute myeloid leukemia.

We evaluated the predictive value of mdr1 mRNA RT-PCR, P-glycoprotein (Pgp), and Daunorubicin efflux assays as regards achieving complete remission (CR), overall survival (OS), and leukemia-free survival (LFS) in 72 patients with AML. mdr1 mRNA, Pgp, and Efflux were expressed in 55.6%, 36.1%, and 33.3%. Efflux+ was associated with a lower CR rate (P = 0.006). A multivariate analysis of OS identified 3 prognostic factors: WBC (P = 0.028), age (P = 0.002), and Efflux (P = 0.005), while those of LFS identified 2 prognostic factors: age (P = 0.021) and Efflux (P < 0.001). Efflux was the most reliable method in predicting an achievement of CR and stratifying the patients according to the prognosis in terms of OS and LFS in AML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Transplantation with higher dose of natural killer cells associated with better outcomes in terms of non-relapse mortality and infectious events after allogeneic peripheral blood stem cell transplantation from HLA-matched sibling donors.

BACKGROUND: Little is known about the role of the CD56+ natural killer (NK) cell dose on the outcome of allogeneic peripheral blood stem cell transplantation (PBSCT). Recently, higher dose of NK cells has been associated with a lower incidence of severe graft-versus-host disease (GVHD). The current study attempted to evaluate the effect of the NK cell dose on transplant outcomes in allogeneic PBSCT setting. METHODS AND MATERIALS: Sixty-one cytokine mobilized PBSC recipients were analyzed according to the infused dose of CD34+ cells and NK cells in relation to overall survival (OS), non-relapse mortality (NRM), GVHD, and infectious events. RESULTS: The group received a higher dose of NK cells (> or =5 x 10(7)/kg) showed a lower incidence of NRM (P = 0.0186) and infectious events (P = 0.0107). In a multivariate analysis, a higher dose of NK cells was correlated to better transplant outcomes for NRM (P = 0.042) with CD34+ cell dose (P = 0.018), and for infectious events (P = 0.013) with CD34+ cell dose (P = 0.016). Higher NK cell infusion group also showed a faster immune recovery in serial measurements at days +90, +180, and +365. CONCLUSIONS: High dose of NK cells may play an important role in improving transplant outcomes, in terms of reducing NRM and infectious events together with CD34+ cells.

Adolescent↗

PubMed2004

Outcome of allogeneic peripheral blood stem cell transplantation using matched sibling donors in patients with high-risk hematological diseases.

Although the use of peripheral blood stem cells instead of bone marrow is still a matter of debate in transplantation from HLA-identical sibling donors, allogeneic peripheral blood stem cell transplantation (PBSCT), with a stronger graft-versus-leukemia (GVL) effect, may be preferable as a source of stem cells, especially in the case of advanced hematologic diseases. As such, the current paper reports on the outcomes of 27 consecutive patients with high-risk hematologic diseases treated with allogeneic PBSCT. The median dose of CD34+, CD3+ cells, and MNC infused was 8.18 x 10(6)/kg (range: 2.78-14.93), 1.50 x 10(8)/kg (range: 0.06-4.25), and 7.17 x 10(8)/kg (range: 0.95-15.85), respectively. The median time taken for the ANC and platelets to reach 500 and 20,000 x 10(6)/microL was 15 (range: 9-25) and 16 d (range: 10-56), respectively. Three patients (11.1%) experienced transplant-related mortality within 90 d of transplantation, and 15 (62.5%) of 24 evaluated patients developed chronic graft-versus-host disease (GVHD; six limited, nine extensive). There was a significant difference in overall survival (OS) between the group with chronic GVHD and the group without chronic GVHD (P = 0.0253). The causes of death included relapse (six cases) and non-relapse mortality (infection: four cases, chronic GVHD-related death: three cases). The 4-yr OS rate and disease-free survival rate was 43.3 +/- 10.9% and 35.8 +/- 10.2%, respectively. Accordingly, chronic GVHD was found to have a positive role in patients with high-risk hematologic diseases that received allogeneic PBSCT.

Adolescent↗