Clinical Features and Prognosis of MDS Patients with Chromosome 5 Abnormalities Other Than ‘5q-Syndrome’: Results of Multi-Center Analysis in Korea.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4618-4618
Author(s):  
June-Won Cheong ◽  
Inho Kim ◽  
Sung-Soo Yoon ◽  
Dong Soon Lee ◽  
Chul Won Jung ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Features ◽  
Chromosomal Abnormalities ◽  
Normal Chromosome ◽  
Retrospective Evaluation ◽  
Chromosome 5 ◽  
Good Responder ◽  
Mosaic Pattern ◽  
Leukemic Transformation ◽  
5Q Deletion

Abstract Introduction: The myelodysplastic syndrome (MDS) is frequently associated with various chromosomal abnormalities. ‘5q− syndrome’ is low-risk MDS known as good responder of lenalidomide recently. However, the patients with other abnormalities in chromosome 5 showed quite different clinical features from those with ‘5q− syndrome’. The aim of this study was a retrospective evaluation for Korean MDS patients with abnormalities in chromosome 5 other than ‘5q− syndrome’. Materials and Methods: Among 456 patients with MDS diagnosed at 16 hospitals in Korea between 1996 and 2006, 370 with available cytogenetic data entered the study. Univariate and multivariate analysis were performed. Results: Ninety three patients (25.1%) showed abnormalities in chromosome 5 and the ‘5q− syndorme’ was only 10 patients (2.7%). Among the rest, 39 patients (10.5%) had various abnormalities other than 5q deletion such as translocation or 5 monosomy, 38 (10.3%) had complex abnormalities with 5q−, and 2 had mosaic pattern with normal chromosome. Four patients had isolated 5q− but blasts in marrow were over 5%. The deletion of 5q was interstitial but with a predominance for 5q13-33 deletions (34.8%). MDS patients with chromosome 5 abnormalities other than ‘5q− syndrome’ didn’t share the clinical features with ‘5q− syndrome’. There was no leukemic transformation in ‘5q− syndrome’ group, but 18 (21.7%) with other abnormalities in chromosome 5 finally transformed to acute leukemia. Five year overall survival was significantly inferior in non-’5q− syndrome’ patients than ‘5q− syndrome’ (14.3% vs. 79.6%, P=0.0115). Conclusions: Patients with isolated 5q− and excess blast (>5%), other abnormalities than isolated 5q−, or mosaic chromosome with isolated 5q− and normal chromosome didn’t share the clinical features such as lower rate of leukemic transformation and long survival.

Clinical Significance Of SF3B1, U2AF1 and SRSF2 Spliceosomal Gene Mutations For The Treatment Of Hypomethylating Agents In Myelodysplastic Syndrome

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2802-2802
Author(s):  
Jae-Sook Ahn ◽  
Hye-Ran Kim ◽  
Hyeoung-Joon Kim ◽  
Yeo-Kyeoung Kim ◽  
Sung-Hoon Jung ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myelodysplastic Syndrome ◽  
Gene Mutation ◽  
Clinical Features ◽  
Somatic Mutations ◽  
Splicing Factor ◽  
Hypomethylating Agents ◽  
Wild Type ◽  
Leukemic Transformation ◽  
Treatment Indications

Abstract Background Many reports state that hematopoietic malignancies mostly result from somatic mutations in HSCs in the bone marrow. Somatic mutations of spliceosomal gene such as SF3B1, U2AF1 and SRSF2 have been widely described in myelodysplastic syndrome (MDS). Some studies presented that MDS patient with splicing factor mutations influence the clinical outcomes. However, the clinical significances for the treatment of hypomethylating agents (HMA) in splicing factor mutation were not reported. Therefore, this study investigated the influences of the SF3B1, U2AF1 and SRSF2 splice gene mutation in MDS patients who received the HMAs. Materials and Methods MDS harboring ring sideroblast and association with somatic spliceosomal gene mutation was well demonstrated but, comparatively rare and showed good prognosis. So, we excluded MDS harboring ring sideroblast in this study. The study cohort of 133 MDS patients without harboring ring sideroblast was examined for somatic mutations in SF3B1, U2AF1 and SRSF2 splicing gene using direct sequencing method and 59 out of 133 patients received the treatment of HMAs (43 of Azacitidine and 16 of decitabine) for the treatment of MDS. Using the international prognostic scoring system(IPSS), the treatment indications for the HMA were as follows, 1) inermediate-1 with anemia and no response for the treatment of erythropoietin, 2) intermediate-1 with anemia accompanying other cytopenia ( neutrophil <1,000/uL or PLT <100,000/uL), 3) intermediate-2 or high risk. The response analysis was followed the modified IWG MDS response criteria. Results In 59 patients, mutations in K700E of SF3B1; S34T, S34P or Q157P of U2AF1; P95H or P95R of SRSF2 were found in 6 (10.2%), 7 (11.8%), and 4 (6.8%) patients, respectively. The 17 patients were observed any mutation (SF3B1, U2AF1 or SRSF2) in 59 patients. We compared the clinical features, treatment responses and survivals according to the somatic mutations of spliceosomal gene vs wild type (WT) in each mutation. The disease composition of 59 patients was like as follows; 1 of MDS with del(5q), 6 of RCUD, 24 of RCMD, 9 of RAEB-1, 19 of RAEB-2. In the clinical features, lower risk (according to IPSS, WPSS and revised-IPSS) patients was included in the group with SF3B1 mutation (P<0.05). The hematologic improvement or more response for the HMA was observed in 33% vs 47% in SF3B1 mutation vs WT, 29% vs 48% in U2AF1 and 75% vs 44% in SRSF2, respectively. There was no difference in the response rates for the HMA therapy according to the mutation or wild type (P>0.05). Overall survival did not show the statistical differences in each mutation (P>0.05). The leukemia free survival in patients with SRSF2 mutation was inferior to the WT (p=0.001). However, anyone showed the leukemic transformation in the patients with SF3B1 mutation without statistical significance (p=0.247) (Fig. 1). Conclusion Our results show that mutation of SF3B1, U2AF1 and SRSF2 spliceosomal gene in MDS patients without harboring ring sideroblast did not influence the treatment response and overall survival for the HMAs. However, alteration of SRSF2 splice gene may be regarded as a risk factor of leukemic transformation. So, the patients with SRSF2 mutation treated with HMA have to consider the aggressive therapy such as allogeneic stem cell transplantation before leukemic transformation. To confirm this result, it will be needed more study for large number of patients. Disclosures: No relevant conflicts of interest to declare.

Incidence and Biologic Features of 5q Deletion and 5q- Syndrome in Myelodysplastic Syndrome in Korea; According to Reclassification of Myelodysplastic Syndrome by WHO 2008.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2778-2778
Author(s):  
Hye Ryun Lee ◽  
Dae Sik Hong ◽  
Dae Young Zang ◽  
Hong Ghi Lee ◽  
Hwi-Joong Yoon ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Who Classification ◽  
Chromosomal Abnormalities ◽  
Refractory Anemia ◽  
Fish Analysis ◽  
Prognostic Impact ◽  
Chromosome 5 ◽  
Prognostic Features ◽  
5Q Deletion

Abstract Abstract 2778 Poster Board II-754 Introduction: Interstitial deletions involving the long arm of chromosome 5, one of the good prognostic factors, are the most common chromosomal abnormality either as a sole or in combination with other abnormalities in myelodysplastic syndromes (MDS). However, the prognostic impact of del(5q) accompanied by additional chromosome abnormalities remains controversial. We investigated the hematologic, cytogenetic and prognostic features of del(5q) in MDS. Also, we mapped the deleted region on 5q by fluorescence in situ hybridization (FISH), whether the difference of deleted region between 5q- syndrome and MDS with del(5q) accompanied by additional abnormalities makes the clinical and prognostic differences. Methods: 137 adult patients, newly diagnosed as de novo MDS in Seoul National University Hospital from April 2000 through March 2009, were enrolled. We reclassified MDS subtypes according to WHO classification 2008. To compare the hematologic, cytogenetic and prognostic features according to presence of del(5q), we categorized the patients with del(5q) into 3 groups: patients with additional chromosomal abnormalities with del(5q) as 'MDS with del(5q)'; patients with other chromosomal abnormalities other than del(5q) as 'MDS with other chromosomal abnormalities (CA)'; and patients with isolated del(5q) as '5q- syndrome'. Also, the mapping with FISH for EGR1, CSF1R, and PDGFRβ on 5q, was performed in conjunction with G-banding to all patients and additional 16 patients with alleged del(5q) by G-banding from Korean MDS working party. Results: According to the new WHO classification of 2008, the 33 refractory anemia patients according to the previous WHO classification of 2001 were reclassified into refractory cytopenias with unilineage dysplasia (13 patients), refractory cytopenia with multilineage dysplasia (six patients) and MDS - unclassified (14 patients) (Fig 1). The median age of Korean MDS was 59 years, and the frequencies of 5q- syndrome and 5q deletion was 2.2% (3/137 patients) and 15.3%, respectively. Among 137 patients, 17 patients were grouped into 'MDS with del(5q)', and 53 patients into 'MDS with other CA'. The 'MDS with del(5q)' were significantly older and showed higher % of blasts in PB and BM than 'MDS with other CA'. And, they were categorized into higher risk group according to the International Prognostic Scoring System (IPSS) (Table 1). As a results of mapping for EGR1, PDGFRβ and CSF1R, deletion of all 3 regions was 93.3% in patients of 'MDS with del(5q)' and 66.7% in patients of '5q- syndrome', showing no difference in deleted genes between the two groups. Half (53%) of patients of 'MDS with del(5q)' accompanied complex abnormalities including chromosome 7 abnormalities. The del(5q) was detected only by FISH, showing discrepant results between G-banding and FISH analysis. Especially, marker chromosomes by G-banding in some patients were proved to be chromosome 5 with del(5q) by FISH. Conclusion: The biologic and prognostic features of MDS in Korea seem to be markedly different from those of Caucasian; younger age and low frequency of 5q- syndrome. The incidence of complex cytogenetic abnormalities including del(5q) was higher than that of Caucasian, while that of isolated del(5q) was quite low in Korea, which can explain that higher proportion of MDS with del(5q) belongs to higher risk IPSS group. And, we suggest FISH for del(5q) at initial diagnosis and during follow-up after treatment of MDS with alleged del(5q), since the presence of del(5q) in MDS is important for choosing the lenalidomide treatment. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Overall Survival Prediction in Renal Cell Carcinoma Patients Using Computed Tomography Radiomic and Clinical Information

2021 ◽  
Author(s):  
Zahra Khodabakhshi ◽  
Mehdi Amini ◽  
Shayan Mostafaei ◽  
Atlas Haddadi Avval ◽  
Mostafa Nazari ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Clinical Features ◽  
Renal Cell ◽  
Radical Nephrectomy ◽  
Clinical Information ◽  
Tumor Grade ◽  
Imaging Biomarkers ◽  
Area Density

AbstractThe aim of this work is to investigate the applicability of radiomic features alone and in combination with clinical information for the prediction of renal cell carcinoma (RCC) patients’ overall survival after partial or radical nephrectomy. Clinical studies of 210 RCC patients from The Cancer Imaging Archive (TCIA) who underwent either partial or radical nephrectomy were included in this study. Regions of interest (ROIs) were manually defined on CT images. A total of 225 radiomic features were extracted and analyzed along with the 59 clinical features. An elastic net penalized Cox regression was used for feature selection. Accelerated failure time (AFT) with the shared frailty model was used to determine the effects of the selected features on the overall survival time. Eleven radiomic and twelve clinical features were selected based on their non-zero coefficients. Tumor grade, tumor malignancy, and pathology t-stage were the most significant predictors of overall survival (OS) among the clinical features (p < 0.002, < 0.02, and < 0.018, respectively). The most significant predictors of OS among the selected radiomic features were flatness, area density, and median (p < 0.02, < 0.02, and < 0.05, respectively). Along with important clinical features, such as tumor heterogeneity and tumor grade, imaging biomarkers such as tumor flatness, area density, and median are significantly correlated with OS of RCC patients.

scholarly journals P-82 Impact of type 2 diabetes mellitus in overall survival and clinical features of Latin patients with colorectal cancer: A 15-year follow-up

2021 ◽  
Vol 32 ◽  
pp. S125-S126
Author(s):  
G. Calderillo-Ruiz ◽  
C. Diaz ◽  
H. Lopez Basave ◽  
E. Ruiz-Garcia ◽  
A. Apodaca ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Colorectal Cancer ◽  
Type 2 Diabetes ◽  
Overall Survival ◽  
Type 2 Diabetes Mellitus ◽  
Clinical Features

scholarly journals Epigenetic Alterations Associated with the Overall Survival and Recurrence Free Survival among Oral Squamous Cell Carcinoma Patients

2020 ◽  
Vol 9 (4) ◽  
pp. 1035 ◽  
Author(s):  
Yasmen Ghantous ◽  
Aysar Nashef ◽  
Imad Abu-Elnaaj
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Features ◽  
Squamous Cell ◽  
Methylation Status ◽  
Recurrence Free Survival ◽  
Epigenetic Alterations ◽  
Free Survival

Oral squamous cell carcinoma (OSCC) is a fatal disease caused by complex interactions between environmental, genomic, and epigenetic alterations. In the current study, we aimed to identify clusters of genes whose promoter methylation status correlated with various tested clinical features. Molecular datasets of genetic and methylation analysis based on whole-genome sequencing of 159 OSCC patients were obtained from the The Cancer Genome Atlas (TCGA) data portal. Genes were clustered based on their methylation status and were tested for their association with demographic, pathological, and clinical features of the patients. Overall, seven clusters of genes were revealed that showed a significant association with the overall survival/recurrence free survival of patients. The top ranked genes within cluster 4, which showed the worst prognosis, primarily acted as paraneoplastic genes, while the genes within cluster 6 primarily acted as anti-tumor genes. A significant difference was found regarding the mean age in the different clusters. No significant correlation was found between the tumor staging and the different clusters. In conclusion, our result provided a proof-of-principle for the existence of phenotypic diversity among the epigenetic clusters of OSCC and demonstrated the utility of the use epigenetics alterations in devolving new prognostic and therapeutics tools for OSCC patients.

scholarly journals P-226 Analysis of Hispanic Latino American patients with colorectal cancer, clinical features and laterality as a prognosis factor of overall survival

2020 ◽  
Vol 31 ◽  
pp. S164
Author(s):  
G. Calderillo-Ruiz ◽  
C. Diaz ◽  
D. Heredia ◽  
B. Carbajal-López ◽  
H. Lopez Basave ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Clinical Features ◽  
Prognosis Factor ◽  
Latino American

P012 Clinical features and prognosis of patient with chromosome 5 abnormalities: results of multi-center analysis in Korea

2007 ◽  
Vol 31 ◽  
pp. S47
Author(s):  
J.-W. Cheong ◽  
I. Kim ◽  
S.-S. Yoon ◽  
D.S. Lee ◽  
C.W. Jung ◽  
...  
Keyword(s):  
Clinical Features ◽  
Chromosome 5

scholarly journals Clinical Features and Outcome of HTLV-1 Carriers Diagnosed with Hodgkin Lymphoma in Peru: A Matched Cohort Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-23
Author(s):  
Gustavo Sandival-Ampuero ◽  
Ursula Aviles-Perez ◽  
Bryan Valcarcel ◽  
Juan C Haro ◽  
Daniela Dueñas ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Hodgkin Lymphoma ◽  
Clinical Features ◽  
National Cancer Institute ◽  
Matched Control ◽  
Response Rates ◽  
Control Group ◽  
Matched Control Group ◽  
Cell Neoplasm

Background: The human T-cell lymphotropic virus type 1 (HTLV-1) is an oncogenic retrovirus that affects CD4+ T-cell lymphocytes and is the cause for adult T-cell leukemia/lymphoma (ATLL), an aggressive peripheral T-cell neoplasm. Hodgkin-like ATLL subtype is a unique entity usually indistinguishable from Hodgkin lymphoma (HL) in the setting of HTLV-1 infection. HTLV-1 proviral integration and TCR Cb1 gene rearrangement testing are often necessary to differentiate both entities. However, less is known on HTLV-1 carriers diagnosed with HL (HTLV-1+ HL). We aim to compare survival outcomes between HTLV-1+ HL and matched controls treated at the National Cancer Institute in Peru. Methods: We reviewed medical records of patients diagnosed and managed for HL at the National Cancer Institute (Instituto Nacional de Enfermedades Neoplasicas, INEN) in Lima-Peru between 2002 and 2019. All patients should have had serologic evaluation for HTLV-1 infection at the time of diagnosis and should have had no suspicion (or confirmation) of a T-cell neoplasm during pathological examination. To investigate the impact of HTLV-1 infection on survival, we matched HTLV-1+ HL cases to HTLV-1-negative HL patients (controls) based on age, sex, cancer staging, and comorbidities. Treatment responses were assessed according to the Lugano criteria. Survival curves (event-free and overall survival) were estimated using the Kaplan-Meier method and compared with the Log-rank test. Multivariate Cox regression analysis was fitted and reported as Hazard Ratios (HR) with a 95% confidence interval (95% CI). Results: A total of 68 HL patients were identified and had sufficient data for analysis. Twenty cases had HTLV-1+ HL and 48 HTLV-1-negative HL. Table 1 summarizes the clinical features and outcomes of HL patients. In all patients the median age at diagnosis was 55 years with a female/male ratio of 1:1. Histological subtypes of HL were not statistically different among both groups with mixed cellularity as the most common subtype (HTLV-1+ HL 50% vs. HTLV-1-negative HL 38%), followed by nodular sclerosis (HTLV-1+ HL 15% vs. 31%), lymphocyte-rich (HTLV-1+ HL 15% vs. 15%), and nodular lymphocyte-predominant (HTLV-1+ HL 5% vs. 4%). ECOG performance status ≤2, advanced-stage disease (III-IV), presence of B symptoms, and presence of extranodal disease at the time of diagnosis were not different in both groups. Co-infections were presented in 5 (7.4%) HL patients (1 strongyloidiasis and 3 tuberculosis in the HTLV-1+ HL group, and 1 tuberculosis in the HTLV-1 negative HL group). All HTLV-1-negative HL patients were treated with first-line ABVD regimen compared to 18 (90%) HTLV-1+ HL patients; the remaining HTLV-1+ HL patients received involved-field radiation (n=1) and best supportive care (n=1). HTLV-1+ HL patients had inferior response rates (complete and partial response) compared to the matched control group (CR: 60% vs. 71%, and PR: 15% vs. 27%, respectively, p=0.015). At a median follow-up of 5-years, the overall survival was 55% in HTLV-1+ HL versus 67% in the matched control group (aHR: 1.39, 95%CI [0.6-3.4], p=0.47) (Figure 1). In the multivariate analysis, HTLV-1 infection was not a significant prognostic factor for worse event-free or overall survival. Relapsed rates were not different between both groups (HTLV-1+ HL 25% vs. 20.8%), however, more deaths were seen in the HTLV-1+ HL group (60% vs. 35%) but this was not statistically significant. Conclusion: To the best of our knowledge, this is the first case series describing the characteristics and outcome of HTLV-1 carriers diagnosed with HL. We found lower response rates to conventional treatment in HTLV-1+ HL patients compared to HTLV-1 negative individuals. However, long-term outcomes and relapsed rates were not different among groups. Further investigation is needed to confirm the potential impact of HTLV-1 infection in HL outcome. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document