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Biomedical subjects

W S Min

Publications and source records attributed to W S Min.

At least 19 recordsLinked to original sources
PubMed2006

Vascular endothelial growth factor (VEGF) is associated with reduced severity of acute graft-versus-host disease and nonrelapse mortality after allogeneic stem cell transplantation.

This study investigated whether or not there is a correlation between the changes in the serum levels of vascular endothelial growth factor (VEGF) and the outcome of allogeneic stem cell transplantation (allo-SCT). Eighty-five patients undergoing allo-SCT were prospectively studied. The serum VEGF levels were measured on days 0, +7 and +14 after transplantation. The VEGF levels decreased significantly on day +7 and recovered on day +14. The highest levels from day +7 through day +14 were categorized by cluster analysis, which were then correlated with the nonrelapse mortality (NRM). There was a significant correlation between a low VEGF level and the occurrence of severe acute graft-versus-host disease (GVHD) including grade III-IV (P=0.029). The 1-year probability of NRM in patients with a low VEGF level was 22.5% compared with 3.5% for those with a high VEGF level (P=0.024). Multivariate analysis revealed clinically defined infections (P=0.011), advanced disease (P=0.014) and a low VEGF cluster (P=0.05) to be significantly associated with the occurrence of NRM in the cohort. In conclusion, low VEGF levels after allo-SCT are associated with NRM with an exacerbated severity of acute GVHD. VEGF monitoring after a transplant might identify those patients at risk of severe transplant-related mortality.

Acute Disease↗
PubMed2006

The JAK2 V617F mutation in de novo acute myelogenous leukemias.

A missense somatic mutation in JAK2 gene (JAK2 V617F) has recently been reported in chronic myeloproliferative disorders, including polycythemia vera, essential thrombocythemia and myelofibrosis with myeloid metaplasia, strongly suggesting its role in the pathogenesis of myeloid disorders. As activation of JAK2 signaling is occurred in other malignancies as well, we have analysed 558 tissues from common human cancers, including colon, breast and lung carcinomas, and 143 acute adulthood leukemias by polymerase chain reaction -- single strand conformation polymorphism analysis. We found three JAK2 mutations in the 113 acute myelogenous leukemias (AMLs) (2.7%), but none in other cancers. The mutations consisted of two V617F mutations and one K607N mutation. None of the AML patients with the JAK2 V617F mutation had a history of previous hematologic disorders. This is the first report on the JAK2 gene mutation in AML, and the data indicated that the JAK2 gene mutation may not only contribute to the development of chronic myeloid disorders, but also to some AMLs.

Adult↗
PubMed2006

Patterns of C-reactive protein release following allogeneic stem cell transplantation are correlated with leukemic relapse.

The C-reactive protein (CRP) is an acute-phase protein produced by hepatocytes, and is a reliable marker of systemic inflammation, which is relevant to the release of the proinflammatory cytokines. The value of monitoring the CRP levels after stem cell transplantation (SCT) can identify patients at risk of treatment-related complications and mortality. Inflammatory cytokines facilitate donor T-cell activation via antigen presenting cells immediately after SCT. This study examined the relationship between the post-SCT CRP levels and a leukemic relapse. Fifty-four consecutively transplanted patients who relapsed after the allogeneic SCT were compared with nonrelapsing patients. The serum CRP levels were measured on day 0 and every 7 days thereafter until 4 weeks after the SCT. The mean CRP levels throughout the early post-SCT episode were significantly lower in the relapsing patients than in those who did not experience relapse (mean+/-s.e.: 26.8 +/- 6.3 vs 65.3 +/- 9.4 for first week, P = 0.001; 23.9 +/- 3.8 vs 44.6 +/- 6.6 for second week, P = 0.008). Univariate analysis showed that the CRP level on the first and second week, and graft-versus-host disease were significantly associated with a relapse. Multivariate analysis showed that the CRP level on the first week was the strongest independent variable predicting the risk of a relapse after SCT (P = 0.04). These results indicate that the serum CRP levels early after allogeneic SCT might display the graft-versus-leukemia (GvL) effect. CRP is a surrogate of the proinflammatory cytokine release that was not measured in this study. The GvL effect appears to be efficiently strengthened by the high CRP levels that may be reflecting T-cell activation.

Adolescent↗
PubMed2005

Impact of ABO incompatibility on outcome after allogeneic peripheral blood stem cell transplantation.

Few studies have addressed the incidence of graft-versus-host disease (GVHD) or survival after ABO-incompatible allogeneic peripheral blood stem cell transplantation (PBSCT). We analyzed the clinical outcome of ABO incompatibility after allogeneic PBSCT. A total of 89 consecutive adult patients with hematological diseases including 49 ABO-identical, 20 major, 15 minor, and five bidirectional ABO-incompatible transplants were enrolled from four medical centers in Korea. No significant difference in engraftment times, graft failure, or transfusion requirements between groups was noted. A clinical diagnosis of severe immune hemolysis or pure red cell aplasia was not made for any patient after transplantation. The incidence of acute or chronic GVHD did not statistically differ between groups. With a median follow-up duration of 13 months (range, 0.5-61 months), the 3-year overall survival estimates for the ABO-identical, major/bidirectional, and minor group were 44.6.0+/-9.0, 43.1+/-11.6, and 43.8+/-13.5%, respectively (P=0.8652), while the 3-year disease-free survival estimates were 33.8+/-7.6, 39.9+/-11.4, and 45.7+/-13.1%, respectively (P=0.8546). We observed that time to neutrophil, platelet, and red blood cell engraftment, transfusion requirements, incidence of acute or chronic GVHD, relapse, and survival were not influenced by ABO incompatibility after allogeneic PBSCT from HLA-matched sibling donors.

ABO Blood-Group System↗
PubMed2004

Relationship between circulating cytokine levels and thyroid function following bone marrow transplantation.

The relation between thyroid hormone changes and cytokines in bone marrow transplantation (BMT) patients has not been studied. This prospective study was designed to determine the relation between thyroid hormones and cytokine levels after BMT and their effects on the mortality. We studied 80 patients undergoing allogeneic BMT. Serum thyroid hormone parameters and cytokine levels were measured before and serially during 6 months after BMT. Serum T(3) decreased to a nadir 3 weeks post-BMT and serum T(4) was lowest at 3 months post-BMT. Serum thyroid stimulating hormone (TSH) sharply decreased to a nadir at 1 week and recovered. Serum interleukin-6 increased for 2 weeks after BMT and declined thereafter. Serum tumor necrosis factor-alpha increased for 3 weeks after BMT and declined thereafter. After 3 weeks post-BMT, both cytokine levels were negatively correlated with serum T(3) and T(4) levels. A total of 29 patients died before 1 year post-BMT and 51 patients survived longer than 1 year. Those patients who died before 1 year post-BMT had significantly lower levels of T(4) at 3 weeks, 3 and 6 months than surviving patients. In conclusion, increased levels of serum IL-6 and TNF-alpha were negatively correlated with thyroid hormone concentrations in BMT recipients suggesting the role of these cytokines in euthyroid sick syndrome.

Adult↗
PubMed2003

Successful allogeneic hematopoietic stem cell transplantation using triple agent immunosuppression in severe aplastic anemia patients.

Graft rejection in patients with severe aplastic anemia (SAA) following allogeneic hematopoietic stem cell transplantation (HSCT) is strongly associated with a large number of prior transfusions and with prolonged disease duration before transplant. We retrospectively analyzed the outcomes and the factor affecting these multitransfused SAA patients, who had received triple agent immunosuppression and high doses of stem cells to overcome rejection. In total, 113 patients with SAA who had a median 16 months (range 1-216) of disease duration were transplanted using HLA-matched sibling donors after conditioning with cyclophosphamide (CY), procarbazine (PCB), and ATG. Graft failure occurred in 16 of the eligible 113 patients, and with a median follow-up of 30 months (range, 1-80), probability of overall rejection was 15%. Specifically, the multitransfused patients who received high doses of stem cells with T-cell depletion showed the lowest rejection rate, 5.6%, compared with 30.3% in multitransfused patients with bone marrow stem cells alone (P=0.0310). Disease duration (P=0.0338) and the number of infused CD34+cells (P=0.0101) were associated with a high risk of graft rejection on multivariate analysis. ABO mismatch and the number of CD34+ cells were significant factors in the incidence of acute graft-versus-host-disease (GVHD). The incidence of chronic GVHD among patients with sustained engraftment was 13/109 (11.9%). With the same follow-up period, probability of disease-free survival for the entire group of patients at 6 years was 89% and the only factor associated with long-term survival was rejection (P=0.0241). These results suggest that allogeneic HSCT conditioned with triple agent immunosuppression, and specifically with high-dose stem cell return is probably an effective treatment for successful engraftment in SAA patients with a high risk of rejection.

ABO Blood-Group System↗
PubMed2001

Allogeneic bone marrow transplantation for chronic myeloid leukemia: a retrospective study of busulfan-cytoxan versus total body irradiation-cytoxan as preparative regimen in Koreans.

From January 1990 to December 1997, 53 Korean patients with chronic myeloid leukemia (CML) receiving bone marrow transplantation (BMT) from human leucocyte antigen (HLA)-identical sibling donors conditioned with either busulfan and cyclophosphamide (BU/CY regimen) or total body irradiation and cyclophosphamide (TBI/CY regimen) were compared retrospectively. Transplantation-related mortality was 19% in BU/CY and 12% in TBI/CY, and early death (<100 d) occurred in 3 patients conditioned with BU/CY. Grade II-IV acute graft-versus-host disease (GVHD) was 9% of BU/CY and 52% of TBI/CY patients. Overall incidence of chronic GVHD was 50% of BU/CY and 52% of TBI/CY patients. In patients with chronic phase, 5-yr overall survival was 73% in the BU/CY group compared with 87% in the TBI/CY group (p=NS), and overall disease-free survival was 75% in the BU/CY group and 59% in the TBI/CY group (p=NS). So far, with a median follow-up of 45 months, 11 patients have relapsed; three relapses occurred after BU/CY and 8 after TBI/CY. The actuarial 5-yr relapse rate was 15% after BU/CY, 34% after TBI/CY (p=0.46). For patients transplanted in chronic phase within 1 yr after diagnosis, there was a clear trend for a lower relapse rate in the BU/CY group (5-yr relapse rate 0%) compared with the TBI/CY group (5-yr relapse rate 30%). The BU/CY group had similar BMT-related toxicity and similar overall survival and showed a clear trend of low relapse compared with the TBI/CY group. Therefore, BU/CY is an acceptable alternative for patients with CML during HLA-identical sibling allogeneic BMT.

Adult↗
PubMed2001

Effect of induced GVHD in leukemia patients relapsing after allogeneic bone marrow transplantation: single-center experience of 33 adult patients.

In a retrospective single center study, we examined the outcome of induced GVHD in leukemia patients relapsing after allogeneic BMT. Thirty-three adult patients with leukemia (15 AML, 3 ALL, and 15 CML) persisting or relapsing 1-36 months (median, 6) after allogeneic BMT underwent various immune manipulations and consequently developed acute and/or chronic GVHD at our center. Immunotherapies to elicit GVHD comprised chemotherapy followed by PBSC (n = 18), non-myeloablative transplant (n = 2), PBL followed by IFN-alpha (n = 5), PBL alone (n = 3), abrupt cessation of CsA (n = 3), and CsA withdrawal combined with IFN-alpha (n = 2). Twenty-four (72.7%) patients obtained a remission including complete hematological or cytogenetic remission, respectively, for acute leukemias or CML. Overall survival of patients, estimated at 3 years using the Kaplan-Meier method, was 33.9% (95% CI, 20-52%). Twelve patients including two patients with ALL remain in complete hematological (n = 5) or cytogenetic remission (n = 7) 3-93 months (median 12) after achieving remission. Twelve (63.2%) of 19 dead patients died due to treatment-related toxicities; five patients from acute GVHD, three from GVHD followed by infections and four from infections. By multivariate Cox analysis, only chronic GVHD resulted in a higher probability of disease-free survival (P = 0.026). Eight patients who had both acute GVHD < or = grade I and chronic GVHD are all alive without leukemia. We conclude that acute GVHD is associated with considerable toxicity while chronic GVHD plays a role in retaining remission in leukemia relapsing after allogeneic BMT.

Adolescent↗
PubMed2001

Changes in autoimmune thyroid disease following allogeneic bone marrow transplantation.

Autoimmune diseases can be transmitted and eliminated by bone marrow transplantation (BMT). There have been several cases of autoimmune thyroid disease (AITD) occurring after BMT, but AITD remission has been rarely reported. We present four cases in which the remission or transfer of AITD occurred after an allogeneic BMT. Two patients with severe aplastic anemia (SAA) showed evidence of remission of Hashimoto's thyroiditis which they had before allogeneic BMT. One patient with SAA, which developed during treatment with propylthiouracil for Graves' disease, underwent allogeneic BMT and showed evidence of Graves' disease remission following BMT. In one patient, new AITD occurred after an allogeneic BMT from an HLA-matched sibling who already had AITD. These cases support the evidence that the immune system is newly reconstituted after BMT, and severe autoimmune disease can be an indication for BMT. To fully understand the real changes in autoimmune status after BMT, long-term prospective studies are necessary.

Adolescent↗
PubMed2001

The kinetics of circulating cytokines including IL-6, TNF-alpha, IL-8 and IL-10 following allogeneic hematopoietic stem cell transplantation.

Pro-inflammatory (IL-6, TNFalpha and IL-8) and anti-inflammatory (IL-10) cytokines were determined in weekly samples from 52 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). IL-6 increased immediately after transplant peaking at week +3, but IL-8 concentrations were elevated only during week +1. After a slight decrease in week +1, TNF-alpha significantly increased from week +2 and peaked at week +3, whereas, IL-10 values started to rise in week +2 and peaked during week +4. IL-6 and TNF-alpha were positively correlated from week +2 to week +4, and IL-6 levels at week +1 were related with fever and severe stomatitis. Serum levels of IL-6 at week +1 and IL-10 at week +4 were significantly higher in patients with early transplant-related complications, such as fever, severe stomatitis or acute GVHD > or = overall grade II than in those without the complications. We conclude that a high serum IL-6 level at week +1 may be an early predictor of transplant-related complications and that it seems to trigger pro- and anti-inflammatory cytokine release. Kinetic patterns of IL-6 and IL-10 were more exaggerated in those with complications after HSCT.

Acute Disease↗
PubMed2001

Hematopoietic stem cell transplantation for high-risk adult patients with severe aplastic anemia; reduction of graft failure by enhancing stem cell dose.

BACKGROUND AND OBJECTIVES: The main causes of failure after allogeneic hematopoietic stem cell transplantation (HSCT) in patients with severe aplastic anemia (SAA) are graft-versus-host disease (GVHD), infection and graft failure, often exacerbated by large numbers of transfusions and prolonged disease duration before transplant. This study retrospectively analyzes the outcome and factors related to survival or graft failure in high-risk patients with SAA receiving HSCT in our institution. DESIGN AND METHODS: Between January 1995 and December 1999, 40 consecutive adult patients who were multi-transfused (more than 40 units of red blood cells +/- platelets) and/or had a 3 years or longer period prior to transplant were enrolled. Their median age was 27.5 years (range, 16 to 43) and 21 (52.5%) were women. All donors were human leukocyte antigen (HLA)-matched siblings. Before transplant, 29 patients (72.5%) received a course of antithymocyte globulin (ATG) and cyclosporin A (CsA). The median interval from diagnosis to transplant was 59 months (range, 2 to 216). The median number of transfusions was 115 units (range, 10 to 480). All patients received a conditioning regimen of cyclophosphamide, ATG, and procarbazine. Our patients received either bone marrow (BM) alone (n=20) or BM+peripheral blood stem cells (PBSC) (n=20) as a stem cell source. T-cells of PBSC were depleted using the CD34 enrichment method. GVHD prophylaxis consisted of CsA and short-term methotrexate. RESULTS: In the BM+PBSC group, neutrophil recovery to 0.5 x 10(9)/L and platelet recovery to 20 x 10(9)/L were achieved more rapidly than in the BM group (p=0.005 and 0.039, respectively). The incidences of graft failure, grade II to IV acute GVHD, and chronic GVHD were 22.5%, 12.8% and 23.1%, respectively. Graft failure occurred in 2 of 20 patients (10%) receiving BM+PBSC and in 7 of 20 (35%) receiving BM alone (p=0.069). Seven of 9 patients who had graft failure received a booster treatment and recovered normal marrow function. GVHD incidence was comparable between the BM+PBSC and BM groups. Six patients (15%) died from graft failure (n=2), interstitial pneumonia (n=2), cyclophosphamide-induced heart failure (n=1), and chronic GVHD followed by pneumonia (n=1). The Kaplan-Meier estimate of survival was 83.7% with a median follow-up duration of 40.5 months (range 8-67). In multivariate analysis only chronic GVHD adversely influenced survival (p=0.042). INTERPRETATION AND CONCLUSIONS: These results suggest that HSCT is an effective treatment for multi-transfused SAA patients with prolonged disease duration. It is highly possible that the infusion of a large number of stem cells leads to a reduction of graft failure and a faster speed of engraftment. Booster treatment is successful in achieving engraftment in patients with graft failure.

Adolescent↗
PubMed2000

Rapid intravenous administration of amino acids prevents biliary sludge induced by total parenteral nutrition in humans.

The aim of this study was to evaluate whether daily rapid intravenous administration of amino acids (IVAA) prevented the formation of biliary sludge in humans receiving long-term total parenteral nutrition (TPN). Thirty adult patients receiving TPN for more than 28 consecutive days were studied. They were randomized to receive either saline solution (placebo) intravenously (15 patients) or 6.9% branched chain amino acid (BCAA)-enriched amino acid (15 synthetic amino acids; Freamine HBC) solution given by administration rapid intravenous (15 patients). The groups were similar with respect to age, sex, diagnosis, liver function test results, amylase levels, TPN time, and time of study. All patients underwent weekly ultrasound studies. Volume and emptying studies of the gallbladder in response to the study drug were performed after 1 week. As a result, none of the patients receiving rapid IVAA had sludge, whereas 11 of the 15 patients receiving placebo had sludge (P < 0.01). Results of emptying studies showed significant contraction of the gallbladder in those in the rapid IVAA group, but not in the placebo group. Consequently, the data suggest that rapid IVAA given daily prevents TPN-induced stasis and sludge in the gallbladder. We conclude that rapid IVAA should be used as routine prophylaxis against biliary sludge and formation of gallstones in patients receiving long-term TPN.

Adult↗
PubMed2000

Liver disease during the first post-transplant year in bone marrow transplantation recipients: retrospective study.

Liver dysfunction is a common problem in BMT recipients and it is important to determine the etiology in order to institute appropriate therapy. The purpose of this study was to evaluate the possible causes of liver dysfunction during the first post-transplant year in BMT recipients and to identify a possible relationship between pre-existing liver dysfunction and viral hepatitis with prognosis after BMT. We reviewed liver status before and after BMT in 130 consecutive patients at the Catholic Hematopoietic Stem Cell Transplantation Center. Liver dysfunction during the first post-transplant year occurred in 85 out of 101 (84. 2%) allogeneic BMT recipients and 13 out of 29 (44.8%) autologous BMT recipients. In allogeneic BMT, GVHD and drug hepatotoxicity were major causes. In autologous BMT, drug hepatotoxicity was the most common cause. Eighteen out of 130 patients (13.8%) had abnormal liver function tests before BMT. These patients did not have an increased risk of post-transplant liver dysfunction, GVHD, and death compared to patients who had normal liver function tests prior to BMT. Nine patients were hepatitis B antigen positive and three patients were anti-HCV positive prior to BMT. There was no significant increase in the incidence of post-transplant liver dysfunction, GVHD, and death in these patients.

Adult↗
PubMed2000

Expression of functional markers in acute nonlymphoblastic leukemia.

Multidrug resistance parameters, tissue infiltration parameters, receptors for colony-stimulating factors (CSFr) and cell cycle parameters were analyzed using flow cytometry in 145, 109 initial and 36 relapsed or refractory, acute nonlymphoblastic leukemia (ANLL) patients to find out clinically more reliable functional parameters. Lung resistance-associated protein (LRP) was most frequently expressed in ANLL (44.1%) followed by P-glycoprotein (PGP) (35.9%) and multidrug resistance-associated protein (MRP) (8.3%). LRP and PGP were expressed more frequently in relapsed or refractory ANLL than initial ANLL cases. Complete remission rate after standard chemotherapy falls in PGP-positive cases (p = 0.001). CD44-positive ANLL cases relapsed more frequently. The organ tropism is different depending on the infiltration parameters, vascular cell adhesion molecule to splenomegaly, matrix metalloprotease-2 to hepatomegaly and to extramedullary infiltration other than spleen, liver or lymph node. The percentage of the granulocyte-macrophage-CSFr expression was high in M4 and M5, and granulocyte-CSFr-positive ANLL showed less extramedullary infiltration (p = 0.007) and more PGP expression. Ki-67 was expressed significantly less in refractory ANLL than initial ANLL and DNA topisomerase IIalpha was expressed significantly more in the surviving patients group. In conclusion, analysis of these new functional parameters could help to predict and overcome the clinical behavior of each ANLL at the time of diagnosis.

Adolescent↗