Prognostic Implications of the IDH1 synonymous SNP rs11554137 In Pediatric and Adult AML: a Children's Oncology Group and Southwest Oncology Group Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2737-2737
Author(s):  
Phoenix A. Ho ◽  
Todd A. Alonzo ◽  
Kenneth J. Kopecky ◽  
Kristen L. Miller ◽  
Julia Kuhn ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Expression Profiling ◽  
Prognostic Significance ◽  
Normal Karyotype ◽  
Prognostic Impact ◽  
Wild Type ◽  
Bone Marrow Blast ◽  
Free Survival ◽  
Cytogenetic Abnormalities ◽  
Pediatric Aml

Abstract Abstract 2737 Synonymous SNPs may directly impact gene function through various translational or post-translational mechanisms. Further, such “silent” SNPs in the mutational hotspots of AML-associated genes have recently been reported to carry prognostic impact. We aimed to determine the prevalence, clinical associations, and prognostic significance of a known SNP in exon 4 of IDH1, near the location of the frequently-mutated R132 codon. Diagnostic marrow specimens from 253 pediatric AML patients (treated on the COG trial AAML03P1) and 274 adult AML patients (treated on SWOG trials S9031, S9333, or S9500) were analyzed for the presence of SNP rs11554137 via direct sequencing. In the pediatric cohort (median age 9.8 years), SNP rs11554137 was present in 27 of 253 (10.7%) patients. SNP+ pediatric patients did not differ significantly from wild-type patients in terms of sex, racial distribution (African American patients accounted for 23% of SNP+ patients vs. 14% of wild-type patients, P=0.24), bone marrow blast percentage, or age distribution, except in patients aged 0–2 years, who accounted for 44% of SNP+ patients vs. 23% of wild- type patients (P=0.013). Recurrent cytogenetic abnormalities occurred with similar frequencies in both the SNP+ and wild-type pediatric populations, as did FLT3/ITD, NPMc, and CEBPA mutations. Miscellaneous cytogenetic abnormalities accounted for 33% of SNP+ patients vs. 14% of wild-type patients, P=0.033. IDH1 SNP status had no prognostic impact on survival in the pediatric cohort, as SNP+ and wild-type patients had similar rates of five-year overall survival (OS, 76% vs. 63%, P=0.50), disease-free survival (DFS, 48% vs. 53%, P=0.97), and relapse rate (RR, 39% vs. 39%, P=0.94). In the adult cohort (median age 63 years), the IDH1 SNP was present in 30 of 274 (10.9%) patients. A slight female predominance for the SNP (63% vs. 37%, P=0.052) occurred among adult patients. The SNP was more prevalent in African American patients, who accounted for 30% of the SNP+ patients vs. 7% of wild-type patients, P=0.0046. SNP+ patients also had somewhat higher diagnostic bone marrow blast percentages (medians 80% vs. 70%, P=0.025). The normal karyotype subset accounted for similar proportions of SNP+ vs. wild-type patients (42% vs. 46%, P=0.83). Notably, SNP rs11554137 was not present in adult core-binding factor AML. Miscellaneous cytogenetic abnormalities were significantly more common in SNP+ patients (46% vs. 22%, P=0.022). SNP status was not significantly associated with FLT3/ITD status when all adult patients were considered (P=0.14). However, within the normal karyotype subset, FLT3/ITD was present in 90% of SNP+ patients vs. 59% of wild-type patients (P=0.0053). SNP+ patients had somewhat poorer 5 year OS (10% vs. 18%, hazard ratio [HR]=1.17) though this difference was not statistically significant (P=0.44). Among the 142 patients who achieved complete remission (CR), however, 5-year relapse-free survival (RFS) was significantly worse for SNP+ patients (0% vs. 25%, HR = 2.89, P=0.0014). Of the 14 SNP+ patients who achieved CR, 13 relapsed and the 14th patient died of sepsis in remission after 61 days. In multivariate analysis, after adjusting for the effects of age and cytogenetic group, SNP rs11554137 retained an independent prognostic effect (P=0.0062) regarding RFS. Notably, when FLT3/ITD status is included in multivariate analysis, SNP positivity loses independent prognostic significance (HR=1.72, P=0.18). Genome-wide expression profiling was performed on 134 pediatric AML specimens in whom IDH1 SNP status was known. By comparing SNP+ patients with wild-type patients, we derived a distinct gene-expression signature for patients with SNP rs11554137. Among the most upregulated probe sets in the SNP+ cohort were those representing PEX6 and NFYA, both of which interact with the TGF-beta/SMAD signaling network; the retinoid × receptor beta gene RXRB; and the FER gene, a tyrosine kinase critical to FLT3 signaling. The IDH1 SNP rs11554137 is present in approximately 11% of pediatric and adult AML patients, and gene expression profiling data suggests that leukemia in SNP+ patients may have unique biologic features. The SNP was an independent predictor of decreased RFS in adult AML in univariate analysis, but not in multivariate analysis when adjusting for FLT3/ITD status. Disclosures: No relevant conflicts of interest to declare.

Multivariate Analysis Suggests That the Prognostic Impact of Poor Cytogenetics Is Potentially Underestimated in the IPSS.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 248-248 ◽  
Author(s):  
Julie Schanz ◽  
Elihu H. Estey ◽  
Christian Steidl ◽  
Ulrich Germing ◽  
Barbara Hildebrandt ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multivariate Analysis ◽  
Cox Regression ◽  
Normal Karyotype ◽  
Prognostic Impact ◽  
Bone Marrow Blast ◽  
P Values ◽  
Large Patient ◽  
Increased Risk ◽  
Bone Marrow Blasts

Abstract Introduction: The IPSS-Score, published by Greenberg et al., defines the gold standard in risk stratification of patients suffering from MDS. Nevertheless, the assessment of cytogenetic findings within the IPSS was discussed intensively since its implementation in 1997. Within the IPSS, patients with a high number of bone marrow blasts are rated with a higher risk as compared to those with unfavourable cytogenetics. In a further univariate anylysis, we were able to demonstrate that poor cytogenetics are associated with the same prognostic risk as blast counts >20%. The aim of our present study was to investigate the prognostic impact of poor cytogenetics and bone marrow blast count in a multivariate analysis of a large patient cohort. Patients and Methods: 3169 patients were extracted from our large database, including 3860 patients with MDS and secondary AML following MDS. This data pool was collected in the framework of a cooperative project merging data from the German-Austrian Cooperative MDS Study Group (GACMSG; 55% of pts.) and the MD Anderson Cancer Centre, Houston, USA (45% of pts.). Median age of all study patients was 65.9 years, the female-male ratio 1:1.53. Complex abnormalities occurred in 21.2% of all patients. Multivariate analysis was done using a Cox-regression hazard model with overall survival as primary endpoint. The following groups were established for analysis: Blasts <5%, 5–10%, 11–20% and >20%, normal karyotype, complex abnormalities including chromosomes 5 or 7, complex abnormalities not including abnormalities of chromosomes 5 or 7 and −7/7q- (as single abnormality). Results: Former Kaplan-Meier analysis (data presented last year) showed that median survival (ms) in patients with unfavourable cytogenetics (n=516, ms=7.9 months) is similar to those showing >20% bone marrow blasts (n=197; ms=8.9 months). In multivariate analysis, relative Hazard ratio (HR) was 1.50 in pts. with 5–10% blasts, 1.64 in 11–20% blasts and 1.81 in >20% blasts (baseline for relative HR: <5% blasts, all p-values <0.0001). On the other hand, pts. with unfavourable cytogenetics show an considerable increased risk (normal karyotype was defined as baseline, all p-values <0.001): HR was 3.88 in pts. showing complex abnormalities including chromosomes 5/7 and 2.09 when −7/7q- occurred. Complex abnormalities not including chromosomes 5/7 were associated with a HR of 1.76. Conclusions: Our data suggests that complex abnormalities constitute a prognostic risk factor that is as unfavourable as high bone marrow blast counts. As demonstrated by calculated HR, the occurrence of unfavourable cytogenetics raises the prognostically risk disproportionately. Nevertheless, the IPSS assesses poor cytogenetics (rated with 1.0 points) with a lower risk as compared to increased bone marrow blast counts (rated with 1.5 points for 11–20% blasts; 2.0 points for 21–30% blasts). We conclude that the prognosic impact of unfavourable, especially complex abnormalities, is potentially underestimated in the IPSS. Further data will be shown and presented in detail.

Analysis of Kohne's prognostic index in KRAS wild-type patients with metastatic colorectal cancer (mCRC) treated with salvage-line cetuximab-based regimen: HGCSG0901.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 634-634
Author(s):  
Ayako Doi ◽  
Satoshi Yuki ◽  
Yasushi Tsuji ◽  
Takahide Sasaki ◽  
Hiraku Fukushima ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Prognostic Impact ◽  
Wild Type ◽  
Free Survival ◽  
Significant Difference

634 Background: In the treatment for mCRC, it is essential for understanding the prognosis of each individual patient. Köhne’s index (KI) based on performance status, white blood cell count, alkaline phosphatase and number of metastatic sites has been previously proposed. However, in the salvage setting, the validity of KI has not been reported in patients treated by cetuximab-based chemotherapy. Methods: 269 patients with mCRC treated by cetuximab contained chemotherapy were retrospectively registered from 27 centers in Japan. This analysis was included in the KRAS wild-type patients who were refractory to or intolerant for 5-FU/irinotecan/oxaliplatin and were never administered anti-EGFR-antibody. Univariate and multivariate analysis for overall survival were performed using patient characteristics. Survival analyses were performed with Kaplan-Meier method, log-rank test and Cox proportional hazards model. The analysis was also designed to determine whether the Köhne’s classification could be extended to other endpoints such as progression-free survival. Results: All data were available for prognostic categorization in 127 patients. Median overall and progression-free survival was 9.8 and 4.2 months. The distribution and median survival / progression-free survival for KI were as follows: low risk (L) (n = 40; 13.1/5.1 months), intermediate risk (I) (n = 17; 9.6/3.5 months), and high risk (H) (n = 70; 7.6/4.1 months). For overall survival, there was significant difference between L and H (p = 0.004), but not between L and I (p = 0.213), and between I and H (p = 0.321). For progression-free survival, there was tended to difference between L and H (p = 0.083), but not between L and I (p = 0.392), and between I and H (p = 0.630). In Cox multivariate analysis, KI showed an independent prognostic impact (HR 1.370, p = 0.010), but not predictive impact (HR 1.147, p = 0.212). Conclusions: In this analysis, KI might be a prognostic factor in salvage treatment with cetuximab-based regimen, but no effect predicted impact. Moreover, the prospective evaluation is needed for the further validation.

Nucleophosmin Gene Mutations Identify a Favorable Risk Group in Childhood Acute Myeloid Leukemia with a Normal Karyotype.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 366-366
Author(s):  
Iris H. Hollink ◽  
Christian M. Zwaan ◽  
Marry M. van den Heuvel-Eibrink ◽  
Martin Zimmerman ◽  
Susan Arentsen-Peters ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
Normal Karyotype ◽  
Type A ◽  
Prognostic Impact ◽  
Wild Type ◽  
Molecular Abnormalities ◽  
Pediatric Aml ◽  
Acute Myeloid

Abstract Exon 12 gene mutations in nucleophosmin (NPM1) were recently discovered in approximately 30% of adult acute myeloid leukemia (AML) samples, and cluster in the normal karyotype subgroup (NK-AML). NPM1-mutated adult NK-AML has a favorable outcome (pOS in the 40-50% range), but in case a FLT3 internal tandem duplication (FLT3/ITD) is also present outcome is worse with 25–30% pOS. In pediatric AML, NPM1 mutations are less frequent (6–8%; Cazzaniga, Blood 2005 & Brown, Blood 2007). No studies have specifically addressed pediatric NK-AML, a subgroup lacking favorable prognostic cytogenetic aberrations and therefore mostly stratified in the intermediate risk arm of pediatric AML treatment protocols. We screened 292 newly diagnosed AML samples, and detected NPM1 mutations in 25 cases (8.6%). We also screened 46 initial diagnosis-relapse pairs, and no clonal instability was observed, which suggests that NPM1 mutations may be used for minimal residual disease detection. In contrast to adults, where type A mutations (TCTG-insertion) are most frequent (80%), in our cohort type B (CATG-insertion) mutations were found in 39% and type A in 23%. In the NK-AML cohort (n=98), 20% was NPM1-mutated, which was age dependent: <3 years, 0%; 3–10 years, 19%; >10 years, 29% (p=0.04). None of the 10 FAB M5 cases was NPM1 mutated (p=0.09). NPM1 mutations had an independent favorable prognostic impact on outcome in patients with NK-AML (5-year pEFS 77% vs. 41% for wild type patients; p=0.003), irrespective of FLT3 mutational status. In fact, NPM1-mutated patients with a FLT3/ITD did better than patients without an ITD, although this was not statistically significant (5-year pEFS 90% vs. 63%, respectively; p=0.48). In NK-AML without NPM1 mutations, patients with FLT3/ITD positive AML did significantly worse than wild type FLT3 AML patients (5-year pEFS 18% vs. 52%, p=0.002). The differential prognostic impact of FLT3/ITD between the NPM1-mutated vs. the wild type patients was not caused by differences in the FLT3/ITD allelic ratio or ITD length, nor was there a relationship with the type of NPM1 mutations. Multivariate analysis, including age, white blood cell count, NPM1 and FLT3 status and stem cell transplantation as time-dependent co-variable, showed that only NPM1 mutations had independent prognostic significance for pEFS (RR 0.34, p=0.02). We conclude that the incidence of NPM1 mutations increases with age, and that NPM1 mutations define a subgroup with favorable prognosis in pediatric NK-AML. Our data suggest that these molecular abnormalities allow stratification of children with NK-AML. However, different from adult NK-AML, we observed that all children with NPM1 mutations did well, irrespective of FLT3 status. Therefore, treatment in the ‘good risk’ arm should be considered for children with NPM1-mutated NK-AML.

scholarly journals The prognostic significance of pretreatment serum γ-glutamyltranspeptidase in primary liver cancer: a meta-analysis and systematic review

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Yang Ou ◽  
Junwei Huang ◽  
Liping Yang
Keyword(s):  
Liver Cancer ◽  
Primary Liver Cancer ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Prognostic Impact ◽  
Free Survival ◽  
Effect Measure ◽  
Pretreatment Serum ◽  
Disease Free

Aim: To assess the prognostic value of the pretreatment serum γ-glutamyltranspeptidase (GGT) level in patients with primary liver cancer (PLC). Methods: Relevant studies were systematically searched online on Web of Science, PubMed, and Embase databases published until 9 October 2018. The end points were overall survival (OS), recurrence-free survival (RFS), and disease-free survival (DFS). Meta-analysis was conducted using hazard ratio (HR), and its 95% confidence interval (CI) as effect measure. Results: A total of 33 eligible studies with 9238 patients with PLC were included in this meta-analysis. The synthesized analysis showed that that higher serum GGT level was significantly related to poorer OS (HR: 1.79, 95% CI: 1.66–1.93, P<0.01), RFS (HR: 1.60, 95% CI: 1.46–1.77, P<0.01), and DFS (HR: 1.52, 95% CI: 1.33–1.73, P<0.01) of patients with PLC. Subgroup analyses demonstrated that the negative prognostic impact of higher serum GGT level on OS and RFS was still of significance regardless of ethnicity, pathological type, sample size, cut-off value, first-line treatment, and analysis type. Conclusion: The pretreatment serum GGT might be a predictive factor of poor prognosis for PLC patients.

Prognostic significance of surgery after chemotherapy in patients with type 4 gastric cancer

2020 ◽  
Author(s):  
Takaaki Arigami ◽  
Daisuke Matsushita ◽  
Keishi Okubo ◽  
Takako Tanaka ◽  
Ken Sasaki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multivariate Analysis ◽  
Tumor Response ◽  
Prognostic Significance ◽  
Distant Metastases ◽  
Clinical Indication ◽  
R0 Resection ◽  
Prognostic Impact ◽  
Chemotherapeutic Regimen ◽  
Response To Chemotherapy

Abstract Background The majority of patients with type 4 gastric cancer have distant metastases with extremely poor prognosis. Consequently, considering a therapeutic strategy that improves the prognosis of these patients is clinically important. The present study aimed to assess the clinical indication and prognostic impact of surgery in patients with type 4 gastric cancer who underwent chemotherapy. Methods A total of 67 patients with type 4 gastric cancer who underwent chemotherapy were retrospectively enrolled. All patients were grouped into progressive disease (PD) and non-PD groups by tumor response to chemotherapy. Results Distant metastases occurred in 58 patients. With regard to tumor response, 16 and 51 patients had PD and non-PD, respectively. The prognosis was significantly poorer in patients with PD than in those with non-PD (p < 0.0001). Among 23 patients who underwent surgery after chemotherapy, 21 had a R0 resection. The presence or absence of surgery was significantly correlated with age, first-line chemotherapeutic regimen, lymph node metastasis, clinical stage, number of distant metastatic sites, peritoneal dissemination, and tumor response (p = 0.0412, p = 0.0096, p = 0.0024, p = 0.0059, p = 0.0128, and p = 0.0020, and p = 0.0066, respectively). Multivariate analysis selected tumor response and surgery as an independent prognostic factor (p = 0.0001 and p = 0.0009, respectively). Moreover, multivariate analysis for the surgery group demonstrated that metastatic nodal status (N0-1 vs N2-3) and residual tumor status (R0 vs R1-2) were significant independent prognostic factors (p = 0.0258 and p = 0.0458, respectively). Conclusion Our retrospective study suggests that surgery after chemotherapy for type 4 gastric cancer may improve the prognosis of responders with N0-1 status and a curative R0 resection.

scholarly journals Prognostic significance of CD20 expression in childhood B-cell precursor acute lymphoblastic leukemia

Blood ◽  
2006 ◽  
Vol 108 (10) ◽  
pp. 3302-3304 ◽  
Author(s):  
Sima Jeha ◽  
Frederick Behm ◽  
Deqing Pei ◽  
John T. Sandlund ◽  
Raul C. Ribeiro ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Prognostic Impact ◽  
Event Free Survival ◽  
Cell Precursor ◽  
Free Survival ◽  
Cd20 Expression ◽  
Therapy Studies

Abstract CD20 expression is associated with inferior survival in adults with acute lymphoblastic leukemia (ALL). We analyzed the prognostic impact of CD20 expression in 353 children with B-cell precursor ALL treated in 3 consecutive St Jude Total Therapy studies. CD20 expression (> 20%) was found in 169 patients (48%) and was more frequent in patients between 1 and 10 years of age than in those younger than 1 or older than 10 years (P = .001). None of 14 patients with MLL-AF4 expressed CD20. There was no association between CD20 expression and E2A-PBX, TEL-AML1, ploidy, white blood cell count at diagnosis, or sex. In contrast to the experience in adult ALL, our patients with CD20 expression tended to have a better treatment outcome than those without the expression: 5-year event-free survival 84% ± 2.9% versus 78% ± 3.1% (P = .08). These data suggest that CD20 expression is not associated with inferior outcome in pediatric patients treated with contemporary regimens.

scholarly journals Lymphopenia associated with adjuvant chemotherapy after potentially curative surgery for colorectal cancer correlates with recurrence

2016 ◽  
Author(s):  
Masatsune Shibutani ◽  
Kiyoshi Maeda ◽  
Hisashi Nagahara ◽  
Hiroshi Ohtani ◽  
Tetsuro Ikeya ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Multivariate Analysis ◽  
Adjuvant Chemotherapy ◽  
Lymphocyte Count ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Curative Surgery ◽  
Free Survival ◽  
Background Data ◽  
Disease Free

Abstract Objective: The aim of this retrospective study was to evaluate the prognostic significance of lymphopenia associated with chemotherapy in patients with colorectal cancer who received adjuvant chemotherapy after undergoing potentially curative surgery. Summary of background data: Lymphocyte plays an important role in anti-tumor immunity. Lymphopenia is sometimes induced during the period of adjuvant chemotherapy after potentially curative surgery for colorectal cancer. However, the prognostic significance of lymphopenia associated with chemotherapy is unknown. Methods: One hundred and fifteen patients who received adjuvant chemotherapy after potentially curative surgery for stage II/III colorectal cancer were enrolled in this study. All patients were classified into two groups, the lymphopenia group and the normal group, according to minimum lymphocyte count during the period of adjuvant chemotherapy. Lymphopenia was defined as a lymphocyte count of less than 1,000/Ã&#x8e;¼l. Lymphopenia associated with chemotherapy was found in 17 of the 115 patients (14.8%). Results: Lymphopenia was associated with a worse disease-free survival (p=0.018). Moreover, in a multivariate analysis, lymphopenia associated with chemotherapy was identified to be an independent prognostic factor.

Immunophenotypic and Genetic Characteristics of Diffuse Large B-Cell Lymphoma (DLBCL), and Prognostic Significance of Cell of Origin (COO) in a Southeast Asian Cohort

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4222-4222 ◽  
Author(s):  
Vanessa CL Chong ◽  
Eng Soo Yap ◽  
Liu Xin ◽  
Suk Teng Chin ◽  
Anand Jeyasekharan ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
B Cell ◽  
Prognostic Markers ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Southeast Asian ◽  
Disease Stage ◽  
Prognostic Impact ◽  
Cell Of Origin ◽  
Asian Patients

Abstract BACKGROUND/OBJECTIVE: DLBCL is a heterogeneous disease which on gene expression profiling studies (GEP) can be divided into 2 distinct subtypes, germinal center (GCB) as well as activated B cell subtype (non GCB) based on the cell-of-origin. Immunochemistry (IHC) based algorithms have been shown to have good concordance with GEP for COO classification. While Western data suggests that GCB-subtypes are associated with improved outcomes, there has been limited and conflicting data on the prognostic significance of COO amongst Asian patients. The prevalence and prognostic significance of other prognostic markers such as MYC overexpression or translocation amongst DLBCL Asian patients also remains unclear. Our study aimed to evaluate i) the prevalence of MYC translocation and overexpression, as well as COO subgroups of DLBCL in a cohort of Singaporean patients, and ii) the prognostic impact of these factors in comparison with International Prognostic Index (IPI) score and other standard prognostic markers. METHODS: A single-center retrospective analysis of 384 consecutive DLBCL patients diagnosed 2013 - 2018 was performed. Hans criteria was used to assign COO. (Prior validation studies from the hospital's pathology laboratory had confirmed concordance between Hans algorithm and GEP of 75 %.) Majority of the patients received R-CHOP (N =228) or R-EPOCH (N =47) chemotherapy RESULTS: The median age of the cases was 61 years (range 18-88), 223 were female and the majority had stage 3-4 disease (62%). Of the 297 cases with IHC data for COO, 120 (40%) were GCB subtype and 177 cases (60%) were non-GCB. MYC was overexpressed in 75% of cases (165/220) tested, while MYC FISH was positive in 23% of cases (28/122) tested. 10 of the 28 patients with MYC FISH positive were treated with R-EPOCH chemotherapy. With a median follow up of 1.2 years (0.1-5.3 years), the projected 5-year OS and PFS for the entire cohort was 69.5% and 65.6% respectively. Amongst baseline clincopathologic characteristics, only age, IPI and disease stage was associated with improved OS on both univariate and multivariate analysis. Age, IPI and disease stage was associated with PFS in univariate analysis but only IPI remained significant (p<0.001) after multivariate analysis. Neither MYC overexpression, MYC translocation nor COO was found to be prognostic for OS or PFS on multivariate analysis. The 5-year PFS and OS for the GCB vs the non-GCB subgroups was 72% vs 66%, (p=0.10), and 71% vs 70%, (p=0.06) respectively. (See Figure 1A and 1B). CONCLUSION: In this Southeast Asian DLBCL cohort, we confirmed the prognostic significance of the IPI score for both PFS and OS. GCB subtype of DLBCL comprised 40% of all DLBCL cases. COO based on Hans criteria had no prognostic significance on PFS or OS. This is in contrast to Western series where GCB subtypes identified by IHC-algorithms are associated with better prognosis. Disclosures Jeyasekharan: PerkinElmer: Other: Collaboration; Merck Sharp & Dohme: Honoraria; Janssen: Research Funding; AstraZeneca: Other: Collaboration.

Secondary Cytogenetic Abnormalities and Outcome in Children with TEL-AML1-Positive Acute Lymphoblastic Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1450-1450
Author(s):  
Oussama A. Abla ◽  
Johann Hitzler ◽  
Charles Ye ◽  
Mohamed Abdelhaleem ◽  
Ronald Grant ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Prognostic Indicator ◽  
Similar Rate ◽  
Chromosome 21 ◽  
Prognostic Impact ◽  
Extra Copy ◽  
Cytogenetic Abnormalities

Abstract The t(12;21) translocation, which results in the fusion of the TEL (ETV6) and AML1 (RUNX1) genes, is present in ~25% of pediatric B-precusor acute lymphoblastic leukemia (ALL) patients. Although initially thought to be a favorable prognostic indicator, the t(12;21) was associated with a similar rate of relapse as t(12;21)-negative pre-B ALL in subsequent studies. While secondary cytogenetic abnormalities are often present, their prognostic significance is unknown. The objective of this study is therefore to examine the type, frequency and prognostic impact of secondary cytogenetic abnormalites in t(12;21)-positive blasts of children with ALL. We studied retrospectively 56 patients diagnosed with t(12;21)-positive ALL at the Hospital for Sick Children between 2000–2005. The mean age at diagnosis was 4.9 years (range &lt;1 to 12 years). Nine patients (16%) presented with a white blood cell count of greater than 50 × 109/L. Cytogenetic studies consisted of a combination of FISH, G-banding and spectral karyotyping. The most frequent secondary cytogenetic changes in patients with t(12;21)-positive ALL were: the deletion of the non-translocated TEL allele (38%), an extra copy of the TEL-AML1 fusion gene (14%). Additional numerical abnormalities were seen in approximately one-third of the cases, with the most common being a gain of chromosome 21(13%). Recurrent deletions of chromosomal regions 6q and 11q were observed (14%). A surprising degree of karyotypic complexity was noted. Three or more additional chromosome abnormalities, two abnormal clonal lines, and complex structural rearrangements involving TEL-AML1 were detected in 28%, 21%, and 9% of patients, respectively. Five children (9%) in this cohort have developed a relapse of ALL. The 5-year event-free survival (EFS) was 83±7%. The 5-year EFS for patients with a deleted second TEL allele or an extra TEL-AML1 fusion was not statistically different. Of note, 4 of the children who relapsed had high-risk features at presentation (NCI criteria). All were treated with chemotherapy protocols developed for lower risk ALL. The realization that TEL-AML1 does not always predict excellent prognosis indicates that an on-going study of patients and their survival, with detailed analysis of complex genetic changes, is necessary for a reliable assessment of the prognostic value of the t(12;21) in pediatric ALL.

Metaphase Cytogenetics Adds to Gene Expression Profiling in the Identification of High Risk Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 114-114
Author(s):  
Guido Tricot ◽  
Fenghuang Zhan ◽  
Bart Barlogie ◽  
Yongsheng Huang ◽  
Jeffrey Sawyer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Prognostic Significance ◽  
Staging System ◽  
Treatment Modalities ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Prognostic Information

Abstract The International Staging System (ISS), based on B2-microglobulin and albumin levels at the time of diagnosis, has now generally been adopted as a new prognostic classification system for multiple myeloma (MM). While readily and widely applicable, ISS does not account for genetic disease features, such as metaphase (CA) and interphase fluorescence in situ hybridization (FISH) cytogenetic abnormalities, which when examined in the context of standard prognostic variables, confer higher hazards of relapse and disease-related death. Recently, gene expression profiling (GEP) uncovered the major prognostic significance for outcome of high expression of CKS1B, a gene mapping to an amplicon at chromosome 1q21. We have performed a comprehensive study of CA, FISH, GEP and ISS staging in 351 newly diagnosed MM patients, treated uniformly on Total Therapy 2. We have analyzed outcome based on a combination of high CKS1B by GEP and CA. GEP-based t(11;14) was prognostically favorable, irrespective of expression of CKS1B and, therefore, was removed from the group of patients with high CKS1B expression. After this adjustment, with the combination of both CA and high CKS1B (approximately 10% of all patients) conferred a very poor outcome with only 24% and 40% of such patients being event-free and/surviving at 3 years, compared with 72% and 84% for the others (p values : &lt;.0001). Such patients fared poorly, irrespective of their ISS stage. Similar prognostic information could be gained by combining CA with FISH-defined amplification of 1q21 and t(11;14). Because of their major prognostic impact, all newly diagnosed patients should be tested for these genetic markers. Novel treatment modalities are justified in the small subgroup of such poor prognosis patients, since they derive only a minor benefit from advances in MM therapy. CKS1B Q4 + CA (with no CCND1) vs. Others CKS1B Q4 + CA (with no CCND1) vs. Others

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