Direct comparison of adenosine and adenosine 5'-triphosphate as pharmacologic stress agents in conjunction with Tl-201 SPECT: Hemodynamic response, myocardial tracer uptake, and size of perfusion defects in the same subjects.

BACKGROUND: Adenosine 5'-triphosphate (ATP), a potent and inexpensive coronary vasodilator, was introduced as a pharmacologic stress agent for thallium 201 single photon emission computed tomography (SPECT). However, there has been no direct comparison of ATP and adenosine as myocardial stressors in the same subjects. METHODS AND RESULTS: Thirty-six patients underwent consecutive Tl-201 SPECT imaging with adenosine and ATP in a randomly assigned order. There were no changes in clinical status and no invasive procedures were performed between the two tests. The hemodynamic response and side effects were monitored, and myocardial tracer uptake was assessed by use of a visual grading system and quantitative analysis via a CEqual map. The hemodynamic changes and adverse effects did not differ significantly between the two groups. There were no changes in the detection of any perfusion defect on a per-subject basis, except in one. The exact agreement rate for the visual grading of the myocardial tracer uptake was 84.8%. However, the average extent of the perfusion defect and the severity score were higher with adenosine. CONCLUSION: The hemodynamic changes and the degree of myocardial uptake were similar between the adenosine and ATP infusion. However, quantitative analysis by use of a CEqual map revealed smaller perfusion defects and lower severity scores in subjects undergoing Tl-201 SPECT with ATP.

The association between multidrug resistance-1 gene polymorphisms and outcomes of allogeneic HLA-identical stem cell transplantation.

The impact of single nucleotide polymorphisms of two loci (C3435T and G2677T/A) of the multidrug resistance-1 gene (MDR1) was investigated in 82 patients undergoing allogeneic stem cell transplantation (SCT). The GG genotype on G2677T/A loci was associated with higher non-relapse mortality than was the non-GG genotype (67% vs. 32%, p=0.0073), but not the C3435T (p=0.2026) or MDR1 haplotype (p=0.2238). Accordingly, overall survival was significantly correlated with the G2677T/A genotype (p=0.0048). Multivariate analysis also showed that the GG genotype at G2677T/A had an unfavorable prognosis in terms of overall survival (p=0.003) and non-relapse mortality (p=0.031). In conclusion, the G2677T/A genotype seems to be associated with transplantation outcomes, especially non-relapse mortality.

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.

Unpredicted severe toxicity after 5-fluorouracil treatment due to dihydropyrimidine dehydrogenase deficiency.

Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU). Thus, patients with a DPD deficiency are at risk of developing severe 5-FU-associated toxicity. A 37-year-old female with gastric cancer underwent a curative operation, followed by adjuvant chemotherapy consisting of 5-FU and epirubicin. After the first cycle of chemotherapy, the patient manifested grade 2 mucositis and febrile neutropenia, and when her treatment was subsequently continued with doxifluridine she developed severe mucositis and febrile neutropenia. A PCR study revealed that her DPD mRNA level was lower than that in a control group. Thus, when considering the routine use of 5-FU for the treatment of cancer patients, an analysis of DPD activity or screening for DPD mutations is warranted in confined patients who experience unpredicted severe toxicity after initial 5-FU administration, even though DPD deficiency is a rare metabolic defect.

Clinical role of Bcl-2, Bax, or p53 overexpression in peripheral T-cell lymphomas.

Apoptosis pathways are known to be involved in the pathogenesis of peripheral T-cell lymphomas (PTCLs). As such, the current study attempted to investigate the overexpression of Bcl-2, Bax, or p53 with respect to the progression of PTCL. Paraffin-embedded specimens from 74 patients were analyzed immunohistochemically for Bcl-2, Bax, or p53 overexpression including PTCL-unspecified (n=45), extranodal natural killer cell/T-cell lymphoma (n=10), angioimmunoblastic T-cell lymphoma (n=7), anaplastic large cell lymphoma (n=7), and cutaneous T-cell lymphoma (n=5). The Bcl-2 overexpression was exhibited in 33 (45%), Bax, 17 (23%), and p53, 33 patients (45%). Bcl-2 overexpression was strongly associated with advanced stage (p=0.021) and higher international prognostic indices (IPI) (p=0.038). Bcl-2(+)/p53(+) group was found to be associated with advanced stage (p=0.008) and higher IPI (p=0.001), compared with the other groups. The independent expression of Bcl-2 or p53 was not correlated with survival. Meanwhile, when confined to Bcl-2 overexpressing groups, p53 overexpression was significantly associated with poor survival (p=0.05), as the 3-year OS rate was 82.5% for Bcl-2(+)/p53- cases, yet only 32.9% for Bcl-2(+)/p53(+) cases. Multivariate analyses for OS found the Bcl-2/p53 co-expression (p=0.004) as independent prognostic factor, together with advanced stage (p<0.001) and higher prognostic index for PTCL (p=0.008). Bcl-2 overexpression seemed to correlate with the progression of PTCL interacting with a p53-dependent pathway.

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 /= 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.

Prognostic scoring model based on multi-drug resistance status and cytogenetics in adult patients with acute myeloid leukemia.

Clinical heterogenicity exists within an acute myeloid leukemia (AML) patient group with the same cytogenetic risk. Multi-drug resistance (MDR) is also regarded as one of the potential prognostic factors for AML. Accordingly, the prognostic scoring model can be generated based on both consideration of cytogenetic risk and the MDR status for AML. The CR rate, event-free (EFS) and overall survival (OS) were analysed according to cytogenetic risk, MDR status and clinical factors. Prognostic score was calculated by the sum of MDR status (0 for negative, 1 for positive) and dichotomized scoring for cytogenetic risk (0 for favorable/intermediate and 1 for unfavorable cytogenetics). MDR expression was noted in 36.6% of the patients and associated with a lower CR rate (p = 0.037). MDR, cytogenetics and the use of SCT were identified as independent prognostic factors for EFS and OS. The CR rate of the group scored with 0, 1 and 2 was 81.4, 66.7, and 44.4%, respectively (p = 0.050). The prognostic scoring model depicted a discriminating role in terms of EFS (p < 0.0001) and OS (p = 0.0001). The prognostic scoring model based on cytogenetic risk and MDR provided an improved method for evaluating the prognosis in AML and helped to stratify the risk of patients with the same cytogenetic risk.

Predicting outcomes of HLA-identical allogeneic stem cell transplants from variable number of tandem repeat disparity between donors and recipients.

BACKGROUND AND OBJECTIVES: Detecting differences in the variable number of tandem repeats (VNTR) between a recipient and a donor has already been used to monitor the degree of chimerism after allogeneic stem cell transplantation (SCT). Alongside major histocompatibility complex disparity, the disparity of various polymorphous proteins encoded by several genes may play a critical role in the pathogenesis of graft-versus-host disease (GVHD) in allogenic SCT. However, the biological effect of VNTR disparity has scarcely been studied. BACKGROUND AND OBJECTIVES: Eighty-four patients receiving an SCT from an HLA-identical sibling (n=68) or an unrelated donor (n=16) were analyzed. The patients were transplanted because of acute myeloid leukemia (ns=48), acute lymphoblastic leukemia (n=8), chronic myeloid leukemia (n=15), non-Hodgkin's lymphoma (n=18) and myelodysplastic syndrome (n=3). Polymerase chain reaction analysis was performed to amplify three VNTR regions (D1S80, D1S111, and D17S5). These regions were classified as fully matched, partially matched, or mismatched between donors recipients. RESULTS: A strong correlation was observed between D1S80 matching status and transplant outcomes in terms of overall survival (p=0.0179) and non-relapse mortality (p=0.0305), but not for the D1S111 or D17S5 disparity. The fully matched D1S80 pairs showed a better overall survival (72% vs 38%) and lower non-relapse mortality (17% vs 50%) compared to the partially matched or mismatched pairs. In multivariate analyses, a fully matched D1S80 pair was found to be an independent favorable prognostic factor for overall survival (p=0.03) and non-relapse mortality (p=0.05). In addition, D1S80 disparity was significantly associated with the occurrence of gut chronic GVHD (p=0.05). INTERPRETATION AND CONCLUSIONS: The present data suggest that disparities in D1S80--located in chromosome 1--are associated with an increased incidence of gut chronic GVHD and non-relapse mortality.

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.

CHOP plus etoposide and gemcitabine (CHOP-EG) as front-line chemotherapy for patients with peripheral T cell lymphomas.

OBJECTIVE: The present study evaluated the feasibility of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus etoposide and gemcitabine (CHOP-EG) as front-line chemotherapy in patients with peripheral T cell lymphomas (PTCLs). PATIENTS AND METHODS: Twenty-six patients with newly diagnosed PTCLs were enrolled into the pilot study. Treatment consisted of classical CHOP plus etoposide 100 mg/m(2) intravenously (i.v.) on day 1 and gemcitabine 600 mg/m(2) i.v. on day 1 in a 3 week interval. RESULTS: Fifteen complete responses (CR, 57.7%) or one unconfirmed complete response (uCR, 3.8%) and four partial responses (PR, 15.4%) were confirmed, giving an overall response rate of 76.9% (95% CI, 58.3-96.3%). Median survival has not yet been reached, while median event free survival was 215 days at a median follow-up duration of 383 days. Estimated overall survival at 1 year was 69.6%. The most severe haematological adverse event was neutropaenia, which occurred with a grade 4 intensity in 14 patients (53.8%). Additionally, febrile neutropaenia was observed in four patients (15.4%). However, there was no treatment-related death. CONCLUSION: The CHOP-EG regimen was found to be feasible in patients with PTCLs. For further investigation on the role of gemcitabine in the treatment of PTCLs, a more large scale phase II or phase III study is warranted.

c-kit Expression and mutations in peripheral T cell lymphomas, except for extra-nodal NK/T cell lymphomas.

The present study evaluated the expression and mutations of c-kit in peripheral T-cell lymphomas (PTCLs), except for extra-nodal NK/T cell lymphomas, as a potential target for treatment with imatinib mesylate. Fifty-two patients diagnosed with PTCLs (peripheral T-cell lymhoma, unspecified, 38 cases; angioimmunoblastic T-cell, 7 cases; anaplastic large cell, 7 cases) were enrolled. The immunohistochemistry was performed using standard procedures with anti-c-kit monoclonal IgG, while the c-kit mutations were analysed on paraffin-embedded specimens using PCR-single-stranded conformational polymorphism followed by direct DNA sequencing. The median age of the patients was 52 years (19 to approximately 75 years) with a male-to-female ratio of 69%:31%. Weak expression of c-kit was found in 16 (30.8%) patients, while only 3 (5.8%) patients exhibited mutations in exon 11 or exon 13. The c-kit mutations in exon 11 occurred at codon 558 (AAG --> TAG; Lys --> Stop) and at codon 571 (CTA --> ATA; Leu --> Ile), respectively, while the mutation in exon 13 occurred at codon 634 (CGG --> CGA; Arg --> Arg). The current study only found c-kit mutations in a few patients with PTCLs, except for extra-nodal NK/T cell lymphomas. Therefore, c-kit would not seem to be a good target for a new therapeutic approach to PTCLs.

Multidrug resistance-1 gene polymorphisms associated with treatment outcomes in de novo acute myeloid leukemia.

Multidrug resistance-1 (MDR-1) gene single nucleotide polymorphisms (SNPs) have been identified as associated with the treatment outcomes of acute myeloid leukemia (AML) in Caucasians; yet, similar evidence is lacking for Asian populations. A total of 101 AML patients were enrolled in the current study. Two MDR1 SNPs (C3435T and G2677T/A) were analyzed with PCR/RFLP assay. As regards C3435T polymorphism, C/C genotype was significantly correlated with lower functional P-glycoprotein (P-gp) activity in leukemic blasts (7.5%) compared with C/T (10.7%) or T/T genotype (19.9%, p = 0.029). In genotypic analyses, C/C at -3435 (p = 0.05) and G/G at -2677 (p = 0.04) were strongly associated with a higher probability of complete remission (CR). In addition, the 3-year event-free survival (EFS) was higher in G/G genotype at -2677 (60.6%) than nonG/G (21.9%; p = 0.0241), in C/C at -3435 was higher than nonC/C genotype (p = 0.0139), and was higher in GC haplotype homozygote (58.2%) than nonGC homozygote (22.6%; p = 0.0427). In a multivariate analysis, the group without GC haplotype showed worse EFS (p = 0.030), with unfavorable cytogenetic risk (p = 0.008). However, no differences were noted in overall survival according to the MDR1 SNPs (p = 0.491 for C3435T and p = 0.955 for G2677T/A).

Biweekly irinotecan and cisplatin as second-line chemotherapy in pretreated patients with advanced gastric cancer: a multicenter phase II study.

The current phase II study was conducted to evaluate the response rate and safety of a combination regimen of biweekly irinotecan plus cisplatin in pretreated patients with advanced gastric cancer. Patients with previously treated metastatic or recurrent gastric cancer received intravenous irinotecan 70 mg/m2 and cisplatin 30 mg/m2 on day 1 and 15 every 4-week cycle. Thirty-two patients were enrolled in the current study. Of these, 31 patients were assessable for efficacy and all for toxicity. No complete response and 5 partial responses were confirmed, giving an overall response rate of 15.6% (95% CI; 2.3-28.9%). The median time to progression and median overall survival for all patients was 113 days and 184 days, respectively. Grade 3/4 neutropenia occurred in 6 patients (18.8%), yet no febrile neutropenia was observed. In addition, grade 3 anorexia was observed in 4 patients (12.5%) and grade 3 diarrhea occurred in 2 patients (6.2%). The combination chemotherapy of biweekly irinotecan and cisplatin was found to be moderately effective and well tolerated in pretreated patients with advanced gastric cancer. Accordingly, this regimen can be regarded as an important second-line treatment option for advanced gastric cancer.

Phase II trial of amsacrine plus intermediate-dose Ara-C (IDAC) with or without etoposide as salvage therapy for refractory or relapsed acute leukemia.

OBJECTIVE: The current trial attempted to evaluate the efficacy and toxicity of a salvage therapy consisting of amsacrine plus intermediate-dose Ara-C (IDAC) with or without etoposide for acute leukemia patients in refractory or relapsed states. METHODS: A total of 51 patients with refractory or relapsed acute leukemia were included in the current trial. Twenty-nine patients with acute myeloid leukemia (AML) received a salvage therapy of amsacrine plus IDAC and etoposide, while 22 patients with acute lymphoblastic leukemia (ALL) received amsacrine plus IDAC. RESULTS: The overall complete remission rate was 55% (45% for AML, 68% for ALL) and the median duration of overall survival was 144 days (95% confidence interval = 101-186 days). Grade 3, 4 infectious toxicities were observed in 43 patients (87%), while treatment-related toxicity, excluding infectious causes, included heart failure from myocarditis (n = 1) and central nervous system toxicity (n = 1). CONCLUSION: A salvage therapy consisting of amsacrine plus IDAC with or without etoposide appears to be safe and an effective bridge therapy into a stem cell transplantation programme for patients with refractory or relapsed acute leukemia.

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.

Multidrug resistance as a potential prognostic indicator in acute myeloid leukemia with normal karyotypes.

INTRODUCTION: Approximately 45% of adults with acute myeloid leukemia (AML) have normal karyotypes and therefore lack structural abnormalities that can assist in the localization and characterization of molecular defects. The current study attempted to evaluate the potential prognostic role of multidrug resistance (MDR), regarded as one of the potential prognostic factors for the outcome of overall AML, for AML with normal karyotypes. METHOD AND MATERIALS: A functional MDR assay was performed in pretreatment samples from AML patients with normal karyotypes. The complete remission (CR) rate, event-free survival (EFS), and overall survival (OS) were analyzed according to the MDR status and clinical prognostic factors for 88 patients with AML with normal karyotypes. RESULTS: MDR by efflux was expressed in 14 out of 48 evaluable patients (29%) but failed to identify the association with CR (p = 0.124). However, MDR was identified as an independent prognostic factor for EFS and OS (p = 0.013 and 0.046) together with the use of stem cell transplantation (p = 0.009 for EFS and 0.029 for OS) and the WBC count at presentation (p = 0.023 for EFS and 0.034 for OS). CONCLUSION: The functional MDR assay may provide information on the prognosis of AML patients with normal karyotypes, and it might be a possible guideline for risk-stratified treatment strategies in AML with normal karyotypes.

Prognostic factors identifiable at the time of onset of acute graft-versus-host disease after allogeneic hematopoietic cell transplantation.

BACKGROUND AND OBJECTIVES: Current grading systems of acute graft-versus-host disease (GVHD) cannot effectively identify patients with poor prognosis at the onset of acute GVHD after allogeneic hematopoietic cell transplantation. DESIGN AND METHODS: In a retrospective analysis, we evaluated the prognostic value of various clinical parameters at the initiation of treatment in 83 patients who developed systemic treatment-requiring acute GVHD after allogeneic hematopoietic cell transplantation. RESULTS: Forty-three of 83 patients (52%) experienced initial treatment failure (40 required secondary treatment due to lack of response and 3 died) and 43 (52%) experienced treatment success, defined as completion of treatment (initial and, if given, secondary) within 100 days. The GVHD-specific survival rate was 65.5%, with 27 deaths due to GVHD-related complications without relapse of underlying malignancies within 1 year. HLA-mismatched transplantation, visceral initiation, and peripheral blood lymphocytopenia ( pound100/mL) were independent variables predicting higher initial treatment failure (Odd ratios (OR)=12.225, 12.036, and 7.481, respectively). The above variables and initial acute GVHD grade III-IV vs. II were independent variables predicting shorter GVHD-specific survival (OR=0.322, 0.247, 0.340, and 0.385, respectively). High-risk disease status, visceral initiation, and hypoalbuminemia ( pound2.8 g/dL) were independent variables predicting lower treatment success (OR=0.221, 0.162, and 0.270, respectively). The predictive value of visceral initiation and lymphocytopenia for GVHD-specific survival was verified in an independent cohort of 58 patients. INTERPRETATION AND CONCLUSIONS: Lymphocytopenia and hypoalbuminemia may be useful baseline prognostic factors for acute GVHD after allogeneic hematopoietic cell transplantation.

Clinical implications of angiogenic factors in patients with acute or chronic leukemia: hepatocyte growth factor levels have prognostic impact, especially in patients with acute myeloid leukemia.

The present study evaluated the serum levels of known angiogenic factors and analysed their prognostic significance in patients with acute or chronic leukemia. Enzyme-linked immunosorbent assays (ELISAs) were performed to quantify the basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), tumor necrosis factor-alpha (TNF-alpha), angiogenin, and matrix metalloproteinase-9 (MMP-9) in stored samples obtained before treatment from patients with acute myeloid leukemia (AML; 30 patients), acute lymphoblastic leukemia (ALL; 10 patients), and chronic myelogenous leukemia (CML; 14 patients). The levels of VEGF, HGF, angiogenin, and MMP-9 were all significantly higher in patients with CML than in healthy individuals. The HGF levels were also higher in patients with AML than in healthy individuals, plus there was a significant correlation between the HGF level and the white blood cell count, monocyte count, and serum level of lactate dehydrogenase (LDH) in patients with AML. In a univariate analysis, age and HGF level were both found to be significant parameters predictive for an achievement of complete remission (CR) in patients with AML. Meanwhile, in a multivariate analysis using a logistic regression model, the HGF level was the only parameter strongly predictive for CR (P=0.047). The leukemia-free survival (LFS) rate for AML patients with a lower HGF concentration was better than that for AML patients with a higher HGF concentration (1 year LFS rates=75.0% vs. 37.5%, P=0.065). The HGF concentration was an independent prognostic factor for an achievement of CR, plus higher HGF concentrations were associated with a lower survival in patients with AML.

Phase II study of docetaxel and capecitabine in patients with metastatic or recurrent gastric cancer.

OBJECTIVES: A phase II study was conducted to evaluate the response rate and safety of a combination regimen of docetaxel plus capecitabine in patients with advanced gastric cancer. PATIENTS AND METHODS: Patients with previously untreated metastatic or recurrent measurable gastric cancer received i.v. docetaxel 75 mg/m2 on day 1 and oral capecitabine 1,000 mg/m2 twice daily from day 1 to 14 every 3-week cycle. RESULTS: Thirty-two patients were enrolled in the current study. Of these, 30 patients were assessable for efficacy and 31 assessable for toxicity. One complete response and 13 partial responses were confirmed, giving an overall response rate of 43.8% (95% CI; 25.6-61.9%). The median time to progression and median overall survival for all patients was 5.07 months and 8.4 months, respectively. Grade 3/4 neutropenia occurred in 3 patients (9.7%) and febrile neutropenia was observed in 2 patients (6.3%). Grade 1/2 nausea was observed in 45.2% of patients. Grade 2-3 hand-foot syndrome occurred in 4 patients (12.9%). CONCLUSIONS: The combination of docetaxel and capectabine was found to be well tolerated and effective in patients with advanced gastric cancer. Accordingly, this regimen can be regarded as an important first-line treatment option for advanced gastric cancer.

Retrospective multicenter study of allogeneic peripheral blood stem cell transplantation followed by reduced-intensity conditioning or conventional myeloablative regimen.

This retrospective study compared the results of reduced-intensity conditioning stem cell transplantation (RIST) and a conventional myeloablative regimen (CST) followed by allogeneic peripheral blood stem cell transplantation. In this respect, 63 RISTs and 41 CSTs were performed at 5 transplantation centers in Korea between April 1998 and December 2002. The RIST group had more adverse pretransplant characteristics. More aggressive diseases, like acute myeloid or lymphoblastic leukemia, were included in the CST group, while the RIST group included more indolent diseases, like chronic myeloid leukemia or myeloma (p < 0.001). The incidence of acute graft-versus-host disease (GVHD) grades 2-4 was 29.1 and 57.9% for the RIST and CST groups, respectively (p = 0.010), yet the incidence of chronic GVHD was similar in the two groups (57.4 vs. 71.9%). With a median follow-up of 13 months (0.5-61 months, 17 months in 52 survivors), the 3-year overall (OS) and disease-free survival (DFS) was similar in the RIST and CST groups (p = 0.965 for OS, p = 0.545 for DFS). In a multivariate analysis, RIST (p = 0.010), good performance status (p = 0.006) and a higher CD34+ cell dose (p = 0.008) were all identified as independent favorable prognostic factors for OS. Accordingly, in the current study, RIST produced equivalent or acceptable results compared with CST in terms of OS. Therefore, a prospective randomized trial of RIST and CST is warranted.