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 Disparities in Mantle Cell Lymphoma Outcomes in Hispanics: A Population Based Analysis in Texas and Florida

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4081-4081
Author(s):  
Brian Warnecke ◽  
Daniel Rosas ◽  
Alexandra Wehbe ◽  
Qianqian Liu ◽  
Joel E Michalek ◽  
...  
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Survival Probability ◽  
Median Survival Time ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Poverty Index ◽  
Significant Difference ◽  
Mantle Cell ◽  
Age Of Diagnosis

Abstract Introduction: Mantle cell lymphoma (MCL) is a rare, aggressive type of B-cell non-Hodgkin lymphoma (NHL) that accounts for approximately 7% of adult NHL's in the United States. (JCO PMID: 9704731)Although recent advancements in treatment have improved survival, prognosis remains poor. (Blood PMID: 30154113) There have been several recent studies demonstrating ethnic disparities in MCL, however, there is a paucity of survival outcome data in Hispanic (H) patients with MCL. (CLMLPMID: 31029647) The purpose of this study was to compare the demographics, treatment patterns, and survival outcomes of H and Non-Hispanic (NH) patients diagnosed with MCL, and to contrast Hispanic cohorts between Texas (TX) and Florida (FL). Methods: This is a retrospective cohort study of patients diagnosed with lymphoma (Hodgkin and Non-Hodgkin) from the Texas Cancer Registry (TCR) and the Florida Cancer Data System (FCDS) from 2006-2017. This particular analysis focuses on patients with diagnosis of MCL. Key variables included gender, race, ethnicity, birthplace, dates of diagnosis and death, primary payer at diagnosis, poverty index, stage at diagnosis, and type of treatment. The significance of variation in distribution of categorical outcomes with ethnicity [H, NH] was assessed with Fisher's Exact tests or Pearson's Chi-square as appropriate; age was assessed with T-test or Wilcoxon. Survival time was measured in years from date of primary diagnosis to date of death. Survival distributions were described with Kaplan-Meier curves and significance of variation in median survival with ethnicity was assessed with log rank testing. All statistical testing was two-sided with a significance level of 0.05. Results: We identified a total 4619 (2078 TX, 2541 FL) patients with MCL. 669 (15%) were H and 3950 (85%) were NH. In TX, the median age of diagnosis was 65.6 years (y) in H and 68.3 y in NH (p &lt; 0.001). In FL, the median age of diagnosis was 67.56 in H and 70.06 in NH (p &lt; 0.001). There was a statistically significant difference in poverty index between the cohorts in both TX and FL. The majority of H (50%) in TX were in the 20-100% bracket while the majority of NH (36%) in TX were in the 10-19.9% bracket (p &lt; 0.001). The majority of H (39%) in FL were in the 10-19.9% bracket, and the majority of NH (35%) were also in the 10-19.9% bracket (p &lt; 0.001). Interestingly, there were only 30% of H in FL in the 20-100% bracket. There was a statistically significant difference in insurance status with the most frequent insurance being government-sponsored insurance for H in TX (48%), NH in TX (58%), H in FL (48%), and NH in FL (62%). Patients were without insurance at time of diagnosis in 14% of H in TX and 9% of H in FL, in contrast to 4% of NH in TX and 2% NH in FL. The most common stage at diagnosis in both cohorts in TX and FL was Stage III/IV with 68% H in TX vs 65% NH in TX (p = 0.746) and 69% H in FL vs 67% NH in FL (p = 0.316). The most frequent chemotherapy regimen included multiple agents for all cohorts, 43% H in TX vs 37% NH in TX (p = 0.063), and 48% H in FL vs 42% NH in FL (p = 0.695). Median survival time was 3.4 y H in TX, 3.5 y NH in TX, 4.1 y H in FL, and 4.3 y NH in FL. The survival probability at 2 years was 0.636, 0.640, 0.707, 0.675 for H in TX, NH in TX, H in FL, and NH in FL, respectively. The survival probability at 5 years was 0.371, 0.379, 0.445, 0.459 for H in TX, NH in TX, H in FL, and NH in FL, respectively. The survival probability at 10 years was 0.147, 0.118, 0.276, 0.245 for H in TX, NH in TX, H in FL, and NH in FL, respectively. There was no statistically significant difference in survival probability at 2, 5, or 10 years between H and NH in TX (p = 0.68) and FL (p = 0.72). Conclusions: Our study of patients diagnosed with MCL demonstrated statistically significant differences between H and NH patients in median age of diagnosis, poverty index, and insurance status at diagnosis. These disparities were observed in patients between the cancer registries in both states. Although there were no statistically significant differences in median survival time or survival probability at 2, 5, and 10 years among the H cohorts within each state, we observed intriguing data when the two states were compared. Strikingly, H in TX had much lower survival probability at 2, 5, and 10 years compared to H in FL. In addition, H in TX were noted to have a shorter median survival time compared to H in FL. These disparities may be a direct reflection of the significantly higher rates of poverty and lack of insurance among H in TX compared to H in FL. Figure 1 Figure 1. Disclosures Diaz Duque: ADCT Therapeutics: Research Funding; Astra Zeneca: Research Funding; Hutchinson Pharmaceuticals: Research Funding; Epizyme: Research Funding.

Improvement in the prognosis of breast cancer from 1965 to 1984.

1998 ◽  
Vol 16 (3) ◽  
pp. 1030-1035 ◽  
Author(s):  
M J Edwards ◽  
J W Gamel ◽  
E J Feuer
Keyword(s):  
Breast Cancer ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Parametric Analysis ◽  
Parametric Models ◽  
Node Negative ◽  
Node Positive ◽  
Significant Difference ◽  
Node Positive Disease

PURPOSE The prognosis of breast cancer has improved over the past three decades. It is uncertain, however, whether this improvement results from an increase in the cure rate, extension of the life span of uncured patients, or some combination. METHODS From the Connecticut Tumor Registry, we obtained data on 25,091 patients with localized (node-negative) and regionally metastatic (node-positive) breast cancer who were diagnosed over the two decades between 1965 and 1984, with follow-up through 1993. The data for these patients were analyzed using a variety of parametric models to quantitate likelihood of cure and median survival time among uncured patients. These models incorporate the assumption that time to death from breast cancer follows a specific distribution. RESULTS For patients with node-negative disease, parametric analysis revealed no significant difference in cured-fraction or median survival time over the two decades studied. For patients with node-positive disease, however, a significant increase in median survival time (P < .001) was found during the second decade (1970 to 1979). There was also a trend toward a higher cured-fraction over time, but this was not statistically significant. CONCLUSION This study confirms that patients with node-positive disease had an improved prognosis over the two decades studied. Parametric analysis suggests that this improvement reflects primarily an increase in the median survival time for uncured patients, although there is a trend toward an increase in the likelihood of cure.

scholarly journals Evaluation of chemotherapy response between Paclitaxel-Cisplatin, Paclitaxel -Gemcitabine and Gemcitabine - Cisplatin among non - resectable lung cancer patients, A retrospective study in tertiary care hospital.

2020 ◽  
Vol 38 (4) ◽  
pp. 172-175
Author(s):  
Md Harun Or Rashid ◽  
Quadrat E Elahi ◽  
Md Ashraful Alam ◽  
Fatima Sarker
Keyword(s):  
Lung Cancer ◽  
Survival Rate ◽  
Survival Time ◽  
Cancer Patients ◽  
Median Survival ◽  
Median Survival Time ◽  
Chemotherapy Response ◽  
Care Hospital ◽  
Lung Cancer Patients ◽  
Significant Difference

Background: To compare the survival rate of paclitaxel plus cisplatin (PC arm), paclitaxel plus gemcitabine (PG arm) and gemcitabine plus cisplatin (GC arm) in chemotherapy patients with non resectable lung cancer. Methods: This was a retrospective observational study to evaluate chemotherapy response among non resectable lung cancer patients with their survival at cancer center CMH, Dhaka since 01 July 2013 to 31 March 2015. One hundred fifty-four (154) non resectable lung cancer patients were randomly divided into three groups, 50 patients in PC arm, 51 patients in PG arm and 53 patients in GC arm. In PC arm paclitaxel 175 mg/m2 (day 1) with cisplatin 75mg/m2 (day 1), in PG arm Paclitaxel 175 mg/m2 (day 1) with gemcitabine 1000 mg/m2 (days 1 and 8) and in GC arm gemcitabine 1000 mg/m2 (days 1 and 8) with cisplatin 100mg/m2 (day 1). Results: Patients characteristics were similar between the three groups. The overall response rate was 40% in the PC arm,43.1% in the PG arm, 43.4% in the GC arm. The median survival time in PC arm was 8.5 months, in PG arm was 8.8 months, in GC arm was 9.2 months. The major side effect was myelosuppression which accounts 71% patients. The average treatment costs were 57% and 30% lower in PC arm as compared with GC and PG arm respectively. Conclusion: The median survival time, disease free survival time and 1-year survival rate in PC, PG, GC arms without significant difference. Treatment were well tolerable; quality of life parameter was mostly similar but paclitaxel with cisplatin was most cost effective than others chemotherapy regimen. J Bangladesh Coll Phys Surg 2020; 38(4): 172-175

Deletion of Any of BCR or ABL Gene on Derivative Chromosome 9 Is a Poor Prognostic Marker That Indicates Rapid Disease Progression in Chronic Myelogenous Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4471-4471
Author(s):  
Young Kyung Lee ◽  
Young Ree Kim ◽  
Cha Ja She ◽  
Sung-Soo Yoon ◽  
Young Soo Kim ◽  
...  
Keyword(s):  
Survival Time ◽  
Disease Progression ◽  
Prognostic Marker ◽  
Bone Marrow Cells ◽  
Prognostic Significance ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Derivative Chromosome ◽  
Rapid Disease Progression ◽  
Short Overall Survival

Abstract To evaluate the prognostic significance of the submicroscopic deletions of ABL or BCR gene associated with t(9;22) in CML, we investigated the incidence of ABL or BCR deletion on derivative chromosome 9 using fluorescent in situ hybridization (FISH), and analyzed the survival. FISH was performed using LSI BCR/ABL, dual fusion translocation probe on bone marrow cells of 86 patients with CML. Of 86 patients, ABL deletion was detected in 13 (15.1%) patients and BCR deletion in 8 patients (9.3%). Patients with ABL deletion showed shorter event-free survival time (EFS) than those without ABL deletion (P=0.020). Patients with BCR deletion showed significantly short overall survival time (OS) (P=0.039). Patients with ABL and/or BCR deletion (14/86 patients, 16.3%) showed significantly short OS and EFS (median OS: 43.0 months, median EFS: 40.0 months), compared to the patients without any deletions of BCR or ABL gene (median OS: 94.0 months, median EFS: 90.0 months)(P=0.041 for OS, P=0.008 for EFS). Patients with BCR deletion, all except one had a concomitant ABL deletion, suggesting that BCR deletion occurs in conjunction with ABL deletion. In patients with ABL deletion only, BCR/ABL rearrangement with b2a2 mRNA type tended to be more frequent than in patients without any deletion of the two genes (P=0.073). Deletion of any of BCR or ABL gene on derivative chromosome 9 was associated with both short OS and EFS. We conclude that deletion of not only ABL gene, but also BCR gene is a poor prognostic marker that indicates rapid disease progression in CML.

The effect of smoking history on survival outcome: An exploratory analysis of a phase III study of gemcitabine and cisplatin in patients with advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7141-7141 ◽  
Author(s):  
B. Nguyen ◽  
S. Paul ◽  
K. Posther ◽  
A. Sandler
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Advanced Nsclc ◽  
Survival Outcome ◽  
Phase Iii ◽  
Smoking History ◽  
P Value ◽  
Significant Difference ◽  
Never Smokers

7141 Background: Exploratory analyses of data from phase II and phase III NSCLC studies of epidermal growth factor receptor (EGFR) inhibitors have shown that smoking history (specifically never smokers) is associated with positive clinical outcomes, indicating increased sensitivity to these agents. A phase III trial in chemonaïve patients (pts) with advanced NSCLC demonstrated that the regimen of gemcitabine-cisplatin is superior to cisplatin alone in terms of response rate, time to disease progression, and overall survival [JCO 2000;18:122–30]. We analyzed data from this trial to examine the effect of smoking history on survival outcome. Methods: All pts entered in the study were combined (524 pts) in a subgroup analysis conducted to evaluate the effect of smoking history (smokers vs non-smokers at baseline; number of never smokers unknown) on survival. In addition, 220 pts with a history of smoking were grouped by the total number of pack-years (pk-yrs) smoked (≤37.5 vs >37.5 pk-yrs), and each group was analyzed with regard to survival relative to the group’s median number of pk-yrs. Results: There was no significant difference in median survival time between smokers (n = 220) and non-smokers (n = 304) (8.5 vs 8.1 months, respectively; hazard ratio [HR]: 0.97 [95% CI: 0.81–1.17]; p-value = 0.739). Although the 112 pts who smoked ≤37.5 pk-yrs had a median of 22.5 pk-yrs and the 108 pts who smoked >37.5 pk-yrs had a median of 55.5 pk-yrs, there was no significant difference in median survival time between the groups (9.2 vs 8.5 months, respectively; HR: 1.00 [95% CI: 0.75–1.34]; p-value = 0.9897). Conclusions: In pts with advanced NSCLC, analyses of survival outcomes for chemotherapy with the combination of gemcitabine-cisplatin or cisplatin indicate that survival is independent of smoking history (smokers vs non-smokers at baseline), unlike targeted therapies, such as EGFR inhibitors for which smoking history (specifically never smokers) is a clinical predictor of the sensitivity of these agents and of survival. [Table: see text]

scholarly journals Clinicopathological Characteristics, Treatment, and Prognosis of 21 Patients with Primary Gastric Squamous Cell Carcinoma

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Yang Chen ◽  
Hong Zhu ◽  
Feng Xu ◽  
Yidan Cao ◽  
Xingting Gu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Survival Time ◽  
Median Survival ◽  
Squamous Cell ◽  
Median Survival Time ◽  
Clinical Manifestations ◽  
R0 Resection ◽  
Male Predominance ◽  
Significant Difference

We performed a retrospective analysis of 21 patients with primary gastric squamous cell carcinoma (PGSCC) who were admitted to our hospital from October 2008 to October 2014. The median age was 67 years and male predominance was observed, the most common tumor locations were the upper third of the stomach, most of the clinical manifestations were identical to those of other types of gastric tumors, and the tumor cells had positive immunoreactivity for p63 and CK5/6. In terms of treatments, surgery (R0 resection) is the main treatment; the effect of other treatments is unclear. The median survival time for the surgery group and nonsurgery group was 46 and 4.5 months, respectively. Probably due to limited number of cases, no significant difference in median survival time was observed between the surgery alone group and the surgery plus adjuvant therapy group (46 versus 51 months,P=0.310). A standard chemotherapy regimen for this disease has not yet been established; the choice of its chemotherapy regimens tends to follow the principle of the treatment of gastric adenocarcinoma or esophageal cancer. PGSCC generally had a poor prognosis, and early detection, early diagnosis, and early surgical treatment are beneficial to patients.

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.

Cystic glioblastoma multiforme: survival outcomes in 22 cases

2004 ◽  
Vol 100 (1) ◽  
pp. 61-67 ◽  
Author(s):  
Marcos V. C. Maldaun ◽  
Dima Suki ◽  
Frederick F. Lang ◽  
Sujit Prabhu ◽  
Weiming Shi ◽  
...  
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Tumor Recurrence ◽  
Tumor Volume ◽  
Matched Cohort ◽  
Content Type ◽  
Imaging Characteristics ◽  
Significant Difference ◽  
Fine Print

Object. The goal of this study was to determine whether the presence of a large tumor cyst was associated with improved outcome in patients undergoing surgery for newly diagnosed glioblastomas multiforme (GBMs) by comparing these patients with a matched cohort of patients with noncystic GBMs in clinical features, tumor imaging characteristics, survival, and time to tumor recurrence after surgery. Methods. A retrospective analysis was conducted in 22 patients by using imaging information and chart reviews of operative reports of GBMs with large cysts (≥ 50% of tumor volume) at The University of Texas M. D. Anderson Cancer Center between 1993 and 2002. Clinical and neurosurgical outcomes and recurrence rates were studied. A statistical comparison was made with a matching cohort of 22 patients with noncystic GBMs. No significant differences in clinical variables were found between the cohort with cystic GBMs and the matched cohort with noncystic GBMs. To avoid bias in preoperative assessment of tumor volume, the tumor burden was compared in patients whose tumors had cysts (excluding the cystic mass) and in patients whose tumors did not contain cysts. There was no statistically significant difference between the two groups (p = 0.8). In patients with cystic GBMs the median survival time after surgery was 18.2 months (95% confidence interval [CI] 11.9–24.5 months) and at 2 years 43% of the patients were still alive. In comparison, in patients with noncystic GBMs, the median survival time was 14.3 months (95% CI 12.1–16.4 months) and only 16% of patients were alive at 2 years. The median time to tumor recurrence was 7.6 months (95% CI 0.01–18 months) in patients harboring cystic GBMs and 4.2 months (95% CI 1.8–6.6 months) in the matched cohort (log-rank test, p = 0.04). In the cystic GBM group, no recurrence was observed in 53% of patients at 6 months, 45% at 1 year, and 38% at 2 years after surgery, whereas the corresponding numbers for the noncystic group were 36, 14, and 9%, respectively. Conclusions. The results indicate that patients harboring a GBM that contains a large cyst survive longer and have a longer time to recurrence than those who lack such a cyst. This is the first such observation in the literature.

Heterogeneous Prognostic Impact of 9q+ Deletions in Patients with Chronic Myelogenous Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2111-2111
Author(s):  
Sebastian Kreil ◽  
Katherine Waghorn ◽  
Markus Pfirrmann ◽  
Andreas Reiter ◽  
Rudiger Hehlmann ◽  
...  
Keyword(s):  
Blood Platelets ◽  
Univariate Analysis ◽  
Chronic Phase ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Prognostic Impact ◽  
Derivative Chromosome ◽  
German Studies ◽  
Reliable Technique ◽  
Significant Difference

Abstract Deletions at the ABL-BCR reciprocal breakpoint on the derivative chromosome 9 are seen in 10–15% of patients with CML and have been associated with a poor prognosis, at least for cases treated with hydroxyurea or interferon alpha (IFN). Studies to date have used different fluorescent-in-situ-hybridization (FISH) probe sets to determine deletion status and thus the results are not always directly comparable. Furthermore, information concerning the extent of deletions is limited and no studies have been performed in the context of a prospective randomised controlled clinical trial. To provide more accurate information about deletion status, we developed a rapid DNA-based screen based on multiplex ligation-dependent probe amplification (MLPA). Der(9) deletions were detected at dilutions of 60% or more MC3 cell DNA in non-deleted DNA, indicating that the method was suitable for analysis of samples with up to 40% normal cells. We then investigated 348 chronic phase (CP) patients that were treated with IFN based therapies in three consecutive prospective controlled German studies. The median duration of IFN-based treatment was 17 months (range, 1–115) with a median observation time of seven years (range, 0.3–16); 160 patients (46%) were alive at the date of analysis. Therapy subsequent to IFN included allogeneic stem cell transplantation (SCT; n=130) or imatinib mesylate (IM; n=62). DNA extracted at diagnosis was tested by MLPA and 9q+ deletions, defined as the loss of at least two consecutive markers, were found in 59/348 (17%) patients. Of these 59 deletions, 21 spanned the ABL-BCR breakpoint and 38 were either upstream only (n=20) or downstream only (n=18) of the breakpoint. Analysis of the baseline parameters age, spleen size, leukocyte count, % eosinophils, basophils and blasts in peripheral blood, platelets, hemoglobin, and prognostic scores according to Hasford and Sokal did not reveal any significant difference between patients with and without deletions. There was no significant difference in overall survival between patients with or without deletions and also no difference in survival when patients were censored at SCT in CP or IM treatment. Patients with large ABL-BCR deletions had a poorer survival compared to all other cases (5.7 vs 8.8 years; p=0.0025) but this fell below the level of significance using censored survival (p=0.08). Patients with low risk Sokal or Hasford scores with breakpoint spanning deletions had a significantly worse prognosis than other cases (p=0.01 and p=0.04, respectively). Patients with ABL-BCR deletions also showed a trend towards a less favourable survival after allogeneic SCT in CP-CML (p=0.06). Surprisingly, patients with deletions that did not span the breakpoint showed a superior outcome (p=0.02). Univariate analysis of baseline data revealed that patients with either ABL or BCR deletions only were younger, presented with more circulating blasts and a larger spleen at diagnosis. Patients with large deletions spanning the breakpoint had fewer additional chromosomal abnormalities. In conclusion, MLPA is a reliable technique for detection of der(9) deletions in CML. Our analysis indicates that only those deletions that span the reciprocal ABL-BCR breakpoint are associated with adverse prognosis but the effect is relatively weak.

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.

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