Significance of cytogenetic clonal evolution in chronic myelogenous leukemia.

1996 ◽  
Vol 14 (1) ◽  
pp. 196-203 ◽  
Author(s):  
A Majlis ◽  
T L Smith ◽  
M Talpaz ◽  
S O'Brien ◽  
M B Rios ◽  
...  
Keyword(s):  
Survival Time ◽  
Chronic Myelogenous Leukemia ◽  
Median Survival ◽  
Median Survival Time ◽  
Interferon Therapy ◽  
Clonal Evolution ◽  
Prognostic Significance ◽  
Risk Groups ◽  
Myelogenous Leukemia ◽  
Chromosome 17

PURPOSE To describe the incidence and significance of clonal evolution patterns. PATIENTS AND METHODS We analyzed 264 patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who developed clonal evolution between 1967 and 1993. RESULTS The median survival time following clonal evolution was 19 months. Factors associated with worse survival (P < .01) were as follows: chromosome 17 abnormality or chromosomal translocations other than Ph, high percentage of abnormal metaphases, longer time to clonal evolution, and presence of other accelerated-phase features. A recursive partitioning technique (CART) identified different risk groups. The best group (37 patients; no chromosome 17 abnormality, abnormal metaphases < 16%, and interval to clonal evolution < or = 24 months) had an estimated median survival time of 54 months. The worst two groups included 27 patients with chromosome 17 abnormalities and > or = 36% abnormal metaphases (estimated median survival time, 6 months), and 22 patients with other accelerated features and > or = 16% abnormal metaphases (estimated median survival time, 7 months). The intermediate group had an estimated median survival time that ranged from 13 to 24 months. Prior interferon therapy evaluated within risk groups showed a significant survival advantage only in the intermediate-risk group. A multivariate analysis showed similar results, and identified the following independent poor prognostic variables: chromosome 17 abnormality, percentage of abnormal metaphases (cutoff, 24%), longer time to clonal evolution (cutoff, 24 months), other accelerated-phase features, and no prior interferon therapy. Patients with none, one, two, three, or more of the first four features had median survivals times of 51, 24, 14, and 7 months, respectively. CONCLUSION The prognostic significance of clonal evolution in CML is not uniform and is related to the specific abnormality, time to its development, its predominance in metaphases, and the presence of other accelerated features, and it may be modified by specific therapies.

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.

scholarly journals Gene-Gene Interaction Analysis for the Survival Phenotype Based on the Kaplan-Meier Median Estimate

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Mira Park ◽  
Jung Wun Lee ◽  
Taesung Park ◽  
SeungYeoun Lee
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Interaction Analysis ◽  
Computing Time ◽  
Gene Interaction ◽  
Risk Groups ◽  
The Cancer Genome Atlas ◽  
Rank Test ◽  
Kaplan Meier

In this study, we propose a simple and computationally efficient method based on the multifactor dimensional reduction algorithm to identify gene-gene interactions associated with the survival phenotype. The proposed method, referred to as KM-MDR, uses the Kaplan-Meier median survival time as a classifier. The KM-MDR method classifies multilocus genotypes into a binary attribute for high- or low-risk groups using median survival time and replaces balanced accuracy with log-rank test statistics as a score to determine the best model. Through intensive simulation studies, we compared the power of KM-MDR with that of Surv-MDR, Cox-MDR, and AFT-MDR. It was found that KM-MDR has a similar power to that of Surv-MDR, with less computing time, and has comparable power to that of Cox-MDR and AFT-MDR, even when there is a covariate effect. Furthermore, we apply KM-MDR to a real dataset of ovarian cancer patients from The Cancer Genome Atlas (TCGA).

scholarly journals Randomized comparison of busulfan and hydroxyurea in chronic myelogenous leukemia: prolongation of survival by hydroxyurea. The German CML Study Group

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 398-407 ◽  
Author(s):  
R Hehlmann ◽  
H Heimpel ◽  
J Hasford ◽  
HJ Kolb ◽  
H Pralle ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Median Survival ◽  
Adverse Reactions ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Risk Groups ◽  
Therapy Resistance ◽  
Myelogenous Leukemia ◽  
Cross Resistance ◽  
Cell Counts

In a randomized multicenter study the influence of hydroxyurea versus busulfan on the duration of the chronic phase and on survival of chronic myelogenous leukemia (CML) was determined. In addition cross resistance and adverse reactions of the drugs were analyzed. From July 1983 to January 1991, 441 CML patients were randomized to receive hydroxyurea or busulfan. Of these, 90.7% were Philadelphia positive; 25.7% were low, 38.2% intermediate, and 36.2% high risk patients according to Sokal's score. The median survival of the busulfan treated Philadelphia-positive patients is 45.4 months and of the hydroxyurea group 58.2 months (P = .008). The survival advantage for the hydroxyurea treated patients is recognized in all risk groups. Sixty four patients reached therapy resistance before blast crisis and were crossed over to the alternative drug. The 23 patients with primary hydroxyurea had a median survival of 5.6 years, the 41 patients with primary busulfan therapy a median survival of 2.7 years (P = .02). Adverse reactions were less frequent with hydroxyurea with no severe adverse effects (lung fibrosis, long lasting bone marrow aplasia). The analysis of white blood cell counts in the course of treatment showed lower counts in the hydroxyurea patients. We conclude that hydroxyurea is superior to busulfan in therapy of CML in chronic phase and should be used as first line therapy. Busulfan may have a role as secondary therapy after hydroxyurea resistance or intolerance.

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&lt;0.005, &lt;0.0001 and &lt;0.0001, respectively). On the contrary, VEGF-C and ANG-1 levels were decreased in patients with AML (p&lt;0.0001 and &lt;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&lt;0.005, &lt;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&lt;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 Randomized comparison of busulfan and hydroxyurea in chronic myelogenous leukemia: prolongation of survival by hydroxyurea. The German CML Study Group

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 398-407 ◽  
Author(s):  
R Hehlmann ◽  
H Heimpel ◽  
J Hasford ◽  
HJ Kolb ◽  
H Pralle ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Median Survival ◽  
Adverse Reactions ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Risk Groups ◽  
Therapy Resistance ◽  
Myelogenous Leukemia ◽  
Cross Resistance ◽  
Cell Counts

Abstract In a randomized multicenter study the influence of hydroxyurea versus busulfan on the duration of the chronic phase and on survival of chronic myelogenous leukemia (CML) was determined. In addition cross resistance and adverse reactions of the drugs were analyzed. From July 1983 to January 1991, 441 CML patients were randomized to receive hydroxyurea or busulfan. Of these, 90.7% were Philadelphia positive; 25.7% were low, 38.2% intermediate, and 36.2% high risk patients according to Sokal's score. The median survival of the busulfan treated Philadelphia-positive patients is 45.4 months and of the hydroxyurea group 58.2 months (P = .008). The survival advantage for the hydroxyurea treated patients is recognized in all risk groups. Sixty four patients reached therapy resistance before blast crisis and were crossed over to the alternative drug. The 23 patients with primary hydroxyurea had a median survival of 5.6 years, the 41 patients with primary busulfan therapy a median survival of 2.7 years (P = .02). Adverse reactions were less frequent with hydroxyurea with no severe adverse effects (lung fibrosis, long lasting bone marrow aplasia). The analysis of white blood cell counts in the course of treatment showed lower counts in the hydroxyurea patients. We conclude that hydroxyurea is superior to busulfan in therapy of CML in chronic phase and should be used as first line therapy. Busulfan may have a role as secondary therapy after hydroxyurea resistance or intolerance.

Suppression of cytogenetic clonal evolution with interferon alfa therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia.

1998 ◽  
Vol 16 (10) ◽  
pp. 3279-3285 ◽  
Author(s):  
J Cortes ◽  
M Talpaz ◽  
S O'Brien ◽  
M B Rios ◽  
A Majlis ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Median Survival ◽  
Clonal Evolution ◽  
Philadelphia Chromosome ◽  
Interferon Alfa ◽  
Myelogenous Leukemia ◽  
Lower Percentage ◽  
Complete Suppression ◽  
Ifn Alpha ◽  
Alpha Therapy

PURPOSE To investigate whether cytogenetic clonal evolution can be suppressed with interferon alfa (IFN-alpha) therapy in patients with chronic myelogenous leukemia (CML). PATIENTS AND METHODS Ninety patients with CML and cytogenetic clonal evolution who received IFN-alpha-based regimens were analyzed. Clonal evolution was defined as the presence of karyotypic abnormalities in addition to the Philadelphia (Ph) chromosome. Patients were evaluated for the suppression of cytogenetic clonal evolution after therapy, the cytogenetic response, and survival. RESULTS The median age of the population was 39 years (range, 15 to 70 years), median time from diagnosis to clonal evolution 14 months (range, 0 to 145 months), and median percentage of abnormal metaphases 18% (range, 4% to 100%). Fifty six patients (62%) achieved some suppression of cytogenetic clonal evolution; in 41 patients (46%), the suppression was complete. The overall median survival was 51 months, with 43% alive at 5 years. Patients who achieved a complete suppression of cytogenetic clonal evolution had a median survival of 66 months, with 51% alive at 5 years. Characteristics associated with a better response include a lower percentage of abnormal metaphases, time to cytogenetic clonal evolution of 24 months or less, and absence of other features of accelerated disease. A prognostic classification for cytogenetic clonal evolution defined three groups with complete response (CR) rates of 85%, 34%, and 0% (P < .0001) and median survival times of 58, 31, and 30 months, respectively (P=.02). CONCLUSION Patients with cytogenetic clonal evolution can respond to IFN-alpha therapy, and this response is associated with longer survival. A previously described prognostic model separates patients into subsets with different probabilities of response to IFN-alpha and survival.

Association of the activation of the mTOR pathway with prognosis in Chinese melanoma patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8561-8561
Author(s):  
Yan Kong ◽  
Lu Si ◽  
Xiao wei Xu ◽  
Keith T. Flaherty ◽  
Zhi Hong Chi ◽  
...  
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Somatic Mutations ◽  
Prognostic Significance ◽  
Pcr Amplification ◽  
Therapeutic Benefit ◽  
Mtor Pathway ◽  
Positive Staining ◽  
Melanoma Patients

8561 Background: mTOR is a ubiquitously expressed protein kinase and a validated target in the treatment of cancer. However, the characterization of mTOR pathway in Asian melanoma populations has not been reported. Methods: This study involved primary tumor samples from 173 melanoma patients (79 acral melanomas, 57 mucosal melanomas, 17 melanomas on skin with chronic sun-induced damage, 20 melanomas on skin without chronic sun-induced damage) in Peking University Cancer Hospital & Institute. Clinical data were collected. Immunohistochemistry assays using antibodies against pmTOR, pS6RP, p4E-BP1 and pAKT were performed on formalin-fixed, paraffin-embedded specimens. Somatic mutations within the hotspot regions of frequently mutated genes in mTOR pathway (AKT1, TSC1, PI3K genes, etc) were analyzed by PCR amplification and Sanger sequencing. Results: Among the 173 samples, 26% of the cases (45/173) demonstrated positive staining with pmTOR. Expression of pS6RP was observed in 37% (64/173) of cases. Expression of p4E-BP1 was observed in 27% (46/173) of cases. pAKT was expressed by 22% (38/173) of cases. Somatic mutations in examined genes were detected. The median survival time for patients with expression of pmTOR was significantly shorter than patients with absence of pmTOR expression (25.3 vs 62.9 months, P =0.048). In addition, statistical differences were found for ulceration rates between melanomas with or without pS6RP (64.1%vs 35.9%, P= 0.049). Moreover, the median survival time for mucosal melanoma patients with pAKT expression was significantly shorter than for patients with absence of pAKT expression (20.4 vs 52.1 months, P =0.022). Conclusions: These data demonstrate that activation of the mTOR signaling pathway carries prognostic significance in Asia patients with melanoma. Targeted therapies to mTOR pathway may offer a therapeutic benefit for these melanoma patients.

Feline diabetes mellitus: a retrospective mortality study of 55 cats (1982-1994)

1997 ◽  
Vol 33 (2) ◽  
pp. 107-111 ◽  
Author(s):  
MS Kraus ◽  
CA Calvert ◽  
GJ Jacobs ◽  
J Brown
Keyword(s):  
Diabetes Mellitus ◽  
Renal Failure ◽  
Prognostic Factors ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Prognostic Significance ◽  
Comorbid Disease ◽  
Common Causes ◽  
One Year

Signalment, concomitant diseases, prognostic factors, and mortality were evaluated, retrospectively, in 55 diabetic cats (mean age, 11 years; range, five to 18 years). Sixty-seven percent of the cats were between 7.5 and 15 years of age. One-year mortality (n = 23) was high; most early deaths were due to comorbid disease, and the rate of death diminished in cats surviving beyond one year. The median survival time for all cats was 29 months; among cats that died, the median survival time was 11 months. Of the cats surviving more than one year, 16 were alive at a mean of 41 months. Only 13 of 37 cats died due to diabetes mellitus; the majority died due to concomitant diseases, with renal failure (n = 8) and hepatopathies (n = 6) being the most common causes. No clinical data was identified as being of prognostic significance.

scholarly journals Bioelectrical impedance phase angle as a prognostic indicator in advanced pancreatic cancer

2004 ◽  
Vol 92 (6) ◽  
pp. 957-962 ◽  
Author(s):  
Digant Gupta ◽  
Christopher G. Lis ◽  
Sadie L. Dahlk ◽  
Pankaj G. Vashi ◽  
James F. Grutsch ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Survival Time ◽  
Median Survival ◽  
Phase Angle ◽  
Median Survival Time ◽  
Prognostic Significance ◽  
Advanced Pancreatic Cancer ◽  
Case Series ◽  
Bioelectrical Impedance ◽  
Prognostic Indicator

Bioelectrical impedance analysis (BIA) is an easy-to-use, non-invasive and reproducible technique to evaluate changes in body composition and nutritional status. Phase angle, determined by BIA, has been found to be a prognostic indicator in several chronic conditions, such as HIV, liver cirrhosis, chronic obstructive pulmonary disease and lung cancer, and in patients undergoing dialysis. The present study investigated the prognostic role of phase angle in advanced pancreatic cancer. We evaluated a case series of fifty-eight stage IV pancreatic cancer patients treated at Cancer Treatment Centers of America® at Midwestern Regional Medical Center (Zion, IL, USA) between January 2000 and July 2003. BIA was conducted on all patients using a bioelectrical impedance analyser that operated at 50kHz. The phase angle was calculated as capacitance (Xc)/resistance (R) and expressed in degrees. The Kaplan–Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of phase angle independent of other clinical and nutritional variables. The correlations between phase angle and traditional nutritional measures were evaluated using Pearson and Spearman coefficients. Patients with phase angle <5·0° had a median survival time of 6·3 (95% CI 3·5, 9·2) months (n 29), while those with phase angle >5·0° had a median survival time of 10·2 (95% CI 9·6, 10·8) months (n 29); this difference was statistically significant (P=0·02). The present study demonstrates that phase angle is a strong prognostic indicator in advanced pancreatic cancer. Similar studies in other cancer settings with larger sample sizes are needed to further validate the prognostic significance of the phase angle.

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