Significance of Marrow Angiogenesis Factors in Patients with Acute Myelogenous Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4424-4424
Author(s):  
Liang-In Lin ◽  
Cheng-Yeh Lee ◽  
Chung-Yi Hu ◽  
Jih-Luh Tang ◽  
Hwei-Fang Tien
Keyword(s):  
Growth Factors ◽  
Survival Time ◽  
Median Survival ◽  
Acute Myelogenous Leukemia ◽  
Median Survival Time ◽  
Myelogenous Leukemia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Kaplan Meier ◽  
Acute Myelogenous ◽  
Endothelial Growth Factor

Abstract Bone marrow (BM) neoangiogenesis plays an important role in the pathogenesis of acute myelogenous leukemia (AML). Paracrine exchange of growth factors among AML blasts, endothelial cells, and other marrow compartments is believed to contribute to the pathogenesis of AML. The vascular endothelial growth factor (VEGF) and the angiopoietin (ANG) family are the two major classes of growth factors associated with angiogenesis. In the present study, BM plasma from 52 AML patients and 20 normal donors were investigated. We measured the marrow concentrations of seven molecules associated with angiogenesis, VEGF, VEGF/PlGF, VEGF-C, VEGF-D, ANG-1, ANG-2, and Tie-2, by using enzyme-linked immunosorbent assay (ELISA). Compared to normal donors, the marrow levels of VEGF/PlGF, ANG-2, and Tie-2 were increased in patients with AML (p<0.005, <0.0001 and <0.0001, respectively). On the contrary, VEGF-C and ANG-1 levels were decreased in patients with AML (p<0.0001 and <0.0005, respectively). Although the values were not completely normalized, sequential study revealed that at complete remission (CR) period, VEGF/PlGF, ANG-2, and Tie-2 levels were decreased (p<0.005, <0.005 and =0.02, respectively), while VEGF-C increased (p=0.04). Kaplan-Meier survival curves showed that the subgroup of patients with lower Tie-2 level (29 ng/ml) had a longer median survival time than those with higher Tie-2 level (18.9 months versus 2.5 months, p<0.005). In addition, subgroups of patients with higher VEGF/PlGF level (1 pg/ml) and VEGF-D level (350 pg/ml) also had a longer median survival time than those with lower levels (20.8 months versus 7.2 months, p=0.03 and 18.9 months versus 3.4 months, p=0.03, respectively). Taken together, there were significant differences in VEGF/PlGF, VEGF-C, ANG-1, ANG-2, and Tie-2 expressions between AML patients and normal donors. Expressions of VEGF/PlGF, VEGF-D, and Tie-2 might be prognostic markers in AML patients.

scholarly journals Chemotherapy for acute myelogenous leukemia in children and adults: VAPA update

Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 315-319 ◽  
Author(s):  
HJ Weinstein ◽  
RJ Mayer ◽  
DS Rosenthal ◽  
FS Coral ◽  
BM Camitta ◽  
...  
Keyword(s):  
Complete Remission ◽  
Maintenance Therapy ◽  
Induction Chemotherapy ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Kaplan Meier ◽  
High Incidence ◽  
Acute Myelogenous ◽  
Leukemia In Children

Abstract We designed a protocol (VAPA) that featured 14 mo of intensive postremission induction chemotherapy in an effort to improve remission durations for patients with acute myelogenous leukemia (AML). One hundred and seven patients under 50 yr of age were entered into this study. The rate of complete remission is 70%. A Kaplan-Meier analysis of patients entering remission predicts that 56% +/- 7% (+/-SE) of patients less than 18 yr and 45% +/- 9% of patients aged 18–50 yr will remain in remission at 3 yr (median follow-up is 43 mo). Patients with the monocytic subtype had a statistically significant shorter duration of remission (2-sided p less than 0.05). There was a high incidence of primary CNS relapse in children. Thirty-one of 41 patients who completed the regimen remain in remission without maintenance therapy. We conclude that the VAPA protocol continues to offer a promising approach to treatment of AML.

Clinical and Interphase-FISH Studies of Deletion of Derivative Chromosome 9 in Patients with Chronic Myelogenous Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4482-4482
Author(s):  
Wei Wu ◽  
Yong-quan Xue ◽  
Ya-fang Wu ◽  
Jin-lan Pan ◽  
Juan Shen
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Derivative Chromosome ◽  
Interphase Fish ◽  
Significant Difference ◽  
Cytogenetical Analysis ◽  
Variant Ph Translocation

Abstract Objective: To determine the frequency of the deletion of derivative 9 [der(9)] among chronic myeloid leukemia (CML) patients with classic Ph translocation and variant Ph translocation, and to assess the association between this deletion and clinical prognosis. Methods: Cytogenetical analysis of bone marrow cells was performed by direct method and /or 24h culture method. RHG banding was used for karyotype analysis. Dual-color and dual-fusion DNA probe was used to perform interphase-FISH to investigate the deletion of der(9) in Ph+ CML patients and all patients were followed up. Result: Cytogenetical studies showed typical Ph translocation in 76/105 and variant Ph translocation in 29/105. Interphase-FISH studies showed deletion of der(9) in 12 cases(15.8%) of 76 patients with classic Ph translocation and in 4 cases (13.7%) of 29 patients with variant translocation. The frequency of deletion was similar in classic and variant translocations (P>0.9). This result is contrary to previous reports which suggested that deletions are much more common in variant Ph translocation than in classic Ph translocation. When the deletion was seen in a patient, it was present in all the Ph+ metaphases and nuclei. Three patients with heterogeneous cell populations mixed with cells with single 5′-ABL or 3′-BCR deletion and with both 5′-ABL and 3′-BCR deletion. It may suggest clone evolution in the progression of deletion. Complete clinical information was available in 54 patients. There were no significant difference in peripheral leukocyte count, platelet count, hemoglobin and percentage of peripheral blood blast cells between patients with and without der(9)deletion. However, the results of following up showed that the median survival time of patients with der(9) deletion was significantly shorter than those without der(9) deletion (34 months vs 76 months; P<0.05, log-rank Test). Conclusion: A deletion of der(9) is seen in about 1/6 Ph+ CML patients in china, with which Ph+ CML patients have shorter median survival time than those without it, indicating that it is a poor prognostic index. For evolution the prognosis of CML patients more precisely, it is best to perform cytogenetical analysis and FISH analysis for der(9) deletion simultaneously at diagnosis.

Chromosome 17 Abnormalities Are Associated with Worse Overall and Relapse Free Survival in Patients with Acute Myelogenous Leukemia and Poor-Risk Cytogenetics.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1501-1501
Author(s):  
Gautam Borthakur ◽  
Constantine Tam ◽  
Hagop Kantarjian ◽  
E. Lin ◽  
Jorge Cortes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Chromosome 17 ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Cytogenetic Abnormalities ◽  
Kaplan Meier ◽  
Variate Analysis ◽  
Acute Myelogenous

Abstract Purpose: Chromosome 17 abnormalities define a group of patients with acute myelogenous leukemia (AML) (Nahi, H. et al. Leukemia and Lymphoma2008;49:508) with poor outcomes. We analyzed the additional impact of chromosome 17 abnormalities (−17, −17p, −17q, der17) among patients with AML and cytogenetic abnormalities traditionally considered to be of adverse prognosis. Patients and Methods: 1086 patients with AML [excluding inv 16, t (8;21), t (15;17), Diploid/-y abnormality] were included in this analysis. Based on cytogenetic abnormalities patients were grouped into: −5,−7,−5and −7, complex. The following parameters were included in uni and multi-variate analysis: age, performance status, WBC, hemoglobin, platelets, marrow blast percentage, bilirubin, creatinine, albumin, LDH, chromosome 17 abnormality (yes/no). Results: Four hundred and fourteen (45%) patients achieved complete remission (CR) or CR with incomplete platelet recovery (CRp) and 267 (64.5%) patients relapsed. Two hundred seventy (24.9%) patients had abnormalities of chromosome 17. Abnormalities of chromosome 17 were associated with lower CR or CRp rate (p=0.02) and higher possibility of having cytogenetic abnormality of −5 or −7 (p&lt;0.0001). Multivariate analysis showed that patients with abnormalities of chromosome 17 had worse overall survival (OS) compared to patients without (p= 0.003)(Fig.1). Multi-variate analysis within cytogenetic subgroups showed that chromosome 17 abnormalities were associated with worse OS in patients with chromosome 5 abnormality(p=.02) (data not shown) and in those with complex cytogenetics (p=.04)(Fig.2) and not in patients with chromosome 7 (p=.17)or combined 5 and 7 abnormalities (p=.33). Similar analysis restricted to patients achieving CR/CRp after induction therapy showed that impact of chromosome 17 abnormalities on relapse free survival (RFS) mirrored their impact on OS. Conclusion: chromosome 17 abnormalities are associated with worse OS and RFS in patients with AML and adverse cytogenetics and have additional negative impact on the outcomes in certain well-known adverse cytogenetic subgroups. Figure 1: Kaplan-Meier estimates of overall survival by status of chromosome 17 Figure 1:. Kaplan-Meier estimates of overall survival by status of chromosome 17 Figure 2: Kaplan-Meier estimates of overall survival by status of chromosome 17 in subgroup of patient, complex Figure 2:. Kaplan-Meier estimates of overall survival by status of chromosome 17 in subgroup of patient, complex

scholarly journals Blasts from patients with acute myelogenous leukemia express functional receptors for stem cell factor

Blood ◽  
1992 ◽  
Vol 80 (1) ◽  
pp. 60-67
Author(s):  
VC Broudy ◽  
FO Smith ◽  
N Lin ◽  
KM Zsebo ◽  
J Egrie ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Acute Myelogenous Leukemia ◽  
Stem Cell Factor ◽  
Mononuclear Cells ◽  
Colony Growth ◽  
Receptor Expression ◽  
Myelogenous Leukemia ◽  
Gm Csf ◽  
Acute Myelogenous

Stem cell factor (SCF) acts in concert with lineage-specific growth factors to stimulate the growth of hematopoietic colonies. To determine if neoplastic human hematopoietic cells would also respond to SCF, we cultured marrow mononuclear cells from 20 patients with newly diagnosed acute myelogenous leukemia (AML) and two normal donors with SCF, interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or combinations of growth factors in semisolid medium, and assessed colony growth. SCF receptors (c-kit receptors) were quantitated by equilibrium binding studies with 125I-SCF, and binding parameters were estimated using the ligand program. The cellular distribution of c-kit receptors was determined by autoradiography. Our results show that SCF alone or in combination with IL-3 or GM-CSF increased both the number and size of colonies in 10 of the patients. Receptors for SCF were identified on the blasts from all 20 AML patients. The number of receptors ranged from 600 to 29,000 per cell. In the majority of patients, both high- and low-affinity binding sites were identified. Neither the number of receptors per cell nor the finding of one or two classes of receptors correlated with growth response to SCF. Autoradiographic analysis of 125I-SCF binding to normal marrow mononuclear cells revealed grains associated with blasts and megakaryocytes. Grain counts on blasts from 10 AML patients and on normal marrow blasts suggested that high-affinity c-kit receptor expression on AML blasts is lower than or similar to that of normal blasts. These results identify c-kit receptors on human AML blasts, and indicate that SCF acts synergistically with IL-3 or GM-CSF to stimulate colony growth from the marrow cells of a portion of patients with AML.

scholarly journals Chemotherapy for acute myelogenous leukemia in children and adults: VAPA update

Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 315-319 ◽  
Author(s):  
HJ Weinstein ◽  
RJ Mayer ◽  
DS Rosenthal ◽  
FS Coral ◽  
BM Camitta ◽  
...  
Keyword(s):  
Complete Remission ◽  
Maintenance Therapy ◽  
Induction Chemotherapy ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Kaplan Meier ◽  
High Incidence ◽  
Acute Myelogenous ◽  
Leukemia In Children

We designed a protocol (VAPA) that featured 14 mo of intensive postremission induction chemotherapy in an effort to improve remission durations for patients with acute myelogenous leukemia (AML). One hundred and seven patients under 50 yr of age were entered into this study. The rate of complete remission is 70%. A Kaplan-Meier analysis of patients entering remission predicts that 56% +/- 7% (+/-SE) of patients less than 18 yr and 45% +/- 9% of patients aged 18–50 yr will remain in remission at 3 yr (median follow-up is 43 mo). Patients with the monocytic subtype had a statistically significant shorter duration of remission (2-sided p less than 0.05). There was a high incidence of primary CNS relapse in children. Thirty-one of 41 patients who completed the regimen remain in remission without maintenance therapy. We conclude that the VAPA protocol continues to offer a promising approach to treatment of AML.

Behenoyl cytosine arabinoside, daunorubicin, 6-mercaptopurine, and prednisolone combination therapy for acute myelogenous leukemia in adults and prognostic factors related to remission duration and survival length.

1986 ◽  
Vol 4 (12) ◽  
pp. 1740-1747 ◽  
Author(s):  
R Ohno ◽  
Y Kato ◽  
E Nagura ◽  
T Murase ◽  
M Okumura ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Acute Myelogenous Leukemia ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Myelogenous Leukemia ◽  
Wilcoxon Test ◽  
Kaplan Meier ◽  
Acute Myelogenous ◽  
Initiation Of Therapy ◽  
Wbc Count

Fifty-one consecutive previously untreated adult patients with acute myelogenous leukemia (AML) were treated with BHAC-DMP (N4-behenoyl-I-beta-D-arabinofuranosyl-cytosine, daunorubicin, 6-mercaptopurine, and prednisolone) therapy. Forty-two patients (82.4%) achieved complete remission (CR). The Kaplan-Meier analysis revealed a probability for remaining in remission of 14% and for survival of 23% at 6 years. Pretreatment factors related to the achievement of CR, such as age, French-American-British (FAB) classification and WBC at the start of treatment, were not identified. Factors related to the CR duration and survival time of the patients who had achieved CR were first analyzed by a univariate analysis with the generalized Wilcoxon test. WBC count at the start of treatment, percent of blasts in the marrow at 1 and 2 weeks after the initiation of therapy, days required until CR, number of courses of induction therapy required until CR, and days required for the disappearance of circulating blasts were identified as statistically significant prognostic factors. When these characteristics were further analyzed by the Cox multivariate regression model, the percent of blasts in the bone marrow at 2 weeks was the most important prognostic factor with a statistical significance, and WBC count at the start of treatment and days required until CR (or number of courses required to achieve CR) were also important factors, with borderline significance.

Liver metastases of colorectal carcinoma: Prospective study on the use of transarterial chemoembolization (TACE)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4062-4062
Author(s):  
T. J. Vogl ◽  
T. Gruber ◽  
S. Zangos ◽  
J. O. Balzer
Keyword(s):  
Colorectal Cancer ◽  
Survival Rate ◽  
Liver Metastases ◽  
Survival Time ◽  
Cancer Patients ◽  
Median Survival ◽  
Local Control ◽  
Median Survival Time ◽  
Kaplan Meier ◽  
Colorectal Cancer Patients

4062 Background: To evaluate the efficacy of chemoembolization (TACE) in the treatment of liver metastases in colorectal cancer patients concerning local control and survival. Methods: 207 patients with liver metastases of colorectal cancer were treated with repeated TACE in 4-week intervals. In total, 1,307 chemoembolizations were performed with a mean of 6.3 sessions per patient. At the time of first chemoembolization the average age of the patients was 68.8 years (range, 39.4–83.5 years). 158 patients were treated palliatively, 35 symptomatically and 14 patients neoadjuvantly. The chemotherapy consisted of Mitomycin C with/without Gemcitabin; embolization was performed with Lipiodol and starch microspheres for vessel occlusion. Tumor response was evaluated by magnetic resonance imaging (MRI). The change in size was calculated and the response was evaluated according to the RECIST criteria. Survival rates from the first diagnosis and from the first TACE session were both calculated according to the Kaplan-Meier method to obtain the median survival. Results: While 70% of the patients showed multiple metastases, 6% had 1 metastasis, 5.8% had 2 metastases and 18.2% had 3 to 4 metastases. Lesion size and number before, during and after treatment were assessed to deduce the morphological response. Local control results according to the RECIST criteria were as follows: partial response 12% of patients, stable disease in 51% and progressive disease in 37%. The 1-year survival rate after TACE was 62%, but the 2-year survival rate had been reduced to 38%. The median survival time from the date of diagnosis of metastases was 3.4 years (according to Kaplan-Meier), the median survival time from the start of TACE treatment was 1.34 years. The median survival time of the palliative group was 1.4 years, of the symptomatic group 0.8 years and of the neoadjuvant group 1.5 years. Conclusions: TACE is an effective minimal-invasive therapy for neoadjuvant, symptomatic or palliative treatment of liver metastases in colorectal cancer patients. No significant financial relationships to disclose.

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