scholarly journals del 11(q23) as a prognostic factor of iron overload in refractory anemia with ringed sideroblasts

1997 ◽  
Vol 115 (4) ◽  
pp. 1513-1515 ◽  
Author(s):  
Maria de Lourdes Lopes Ferrari Chauffaille ◽  
José Tadeu Stéfano ◽  
Rosana Maria Valério ◽  
Maura Romeo ◽  
Maria Madalena Rodrigues ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Iron Overload ◽  
Poor Prognosis ◽  
Cytogenetic Abnormality ◽  
Refractory Anemia ◽  
Chromosome 11 ◽  
Ringed Sideroblasts

We present the case of a patient with MDS RARS subtype with loss of part of the long arm of chromosome 11 del 11(q23). This a cytogenetic abnormality that occurs in 7% to 20% of RARS cases not related to poor prognosis. It seems that this deletion is a marker of iron overload in MDS.

Neither Serum Ferritin Nor Number of Red Blood Cell Transfusions Affect Overall Survival in Refractory Anemia with Ringed Sideroblasts.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2454-2454 ◽  
Author(s):  
Cheng E. Chee ◽  
David P. Steensma ◽  
Curtis A. Hanson ◽  
Ayalew Tefferi
Keyword(s):  
Overall Survival ◽  
Blood Cell ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Red Blood Cell ◽  
Iron Chelation ◽  
Refractory Anemia ◽  
International Prognostic Scoring System ◽  
Ringed Sideroblasts

Abstract Background: Most experts agree that iron chelation therapy is unlikely to benefit myelodysplastic syndrome (MDS) patients with a bone marrow (BM) blast percentage of ≥ 5% because of the associated short life expectancy. In contrast, using a serum ferritin of 1,000 ng/mL as a surrogate for iron overload, a recent study suggested a negative impact of iron overload on overall survival in MDS patients with < 5% BM blasts including those with refractory anemia with ringed sideroblasts (RARS) (Malcovati et al. JCO2005:23:7594). In the current retrospective study, we examined the validity of this observation in a large group of RARS patients seen at a single institution. Methods: The diagnosis of RARS was based on the French-American-British cooperative group criteria. Serum ferritin levels obtained both at diagnosis and during follow-up as well as total number of packed red blood cells transfused were recorded. Standard statistical methods were used for survival and other analyses. Results: A total of 126 RARS patients (median age 73 years, range 44-90; 67% males) were seen at our institution over the last several years. At diagnosis, median (range) values were 9.4 g/dL (5.7-13.4) for hemoglobin (Hgb), 2.8 × 109/L (0.3-13.7) for absolute neutrophil count (ANC) and 214× 109/L (22-819) for platelet count; 38% of the patients had received red blood cell (RBC) transfusions at the time of initial diagnosis. International Prognostic Scoring System (IPSS) risk distributions in evaluable patients were 66% for low, 28% for intermediate-1 and 6% for intermediate-2 risk. Median follow-up was 36 months and during this time 83 patients (66%) had died and leukemic transformation was documented antemortem in 8 patients (6%). As expected, IPSS was highly predictive of survival outcome (p<0.0001). In addition, history of RBC transfusions at diagnosis (p=0.001) but not the total number of RBC transfusions received during the entire disease course (p=0.17) carried an independent prognostic value for inferior survival. There were no significant correlations between overall survival and serum ferritin level at either diagnosis (median 567 ng/mL, range 16-3,475; p=0.24) or the maximum value during follow-up (median 1,108 ng/mL; range 238-43,500; p=0.72). Similarly, Kaplan-Meier plots of 77 evaluable patients stratified by serum ferritin levels of < or ≥1000 ng/mL at diagnosis or 107 evaluable patients stratified by maximal serum ferritin levels of < 1000, 1000-5000, or > 5000 ng/mL during follow-up revealed similar curves (Figure). Conclusions: The current study suggests no significant association between transfusional hemosiderosis and survival even in good risk patients with MDS. The study also undermines the utility of serum ferritin as a surrogate for assessing the value of therapeutic iron chelation. Figure Figure Figure Figure

scholarly journals Myeloid neoplasms with isolated isochromosome 17q: a yet to be defined entity

2017 ◽  
Vol 9 (1) ◽  
pp. e2017066 ◽  
Author(s):  
Eleftheria Lamprianidou ◽  
Chryssoula Kordella ◽  
Menelaos Papoutselis ◽  
Zoi Bezyrgiannidou ◽  
Evangelia Nakou ◽  
...  
Keyword(s):  
Disease Progression ◽  
Poor Prognosis ◽  
Refractory Anemia ◽  
Molecular Heterogeneity ◽  
Distinct Entity ◽  
Leukemic Transformation ◽  
Ringed Sideroblasts ◽  
Aggressive Form ◽  
Myeloid Neoplasms ◽  
Molecular Complexity

It has been suggested that myeloid neoplasms with isolated isochromosome 17q[MN i(17q)] comprise a distinct entity with poor prognosis. However, literature reports show a considerable clinical and molecular heterogeneity. We describe a 58-year-old male patient who was diagnosed as refractory anemia with multilineage dysplasia and ringed sideroblasts with isolated i(17q). Though he initially responded well to erythropoietin, he gradually progressed to an aggressive form of MDS/MPN refractory to azacytidine and died 29 months after first diagnosis. Notably, in contrast to disease advancement, his karyotype reverted to normal, whereas his mutational profile remained unchanged. To our knowledge this is the first report of karyotype normalization during disease progression in patients with MN i(17q), suggesting that the i(17q) anomaly is dispensable for the leukemic transformation and highlighting the underlying clinical and molecular complexity which both have to be resolved before the establishment of MN with isolated i(17q) as a distinct entity.

KRASandBRAFMutations in Advanced Colorectal Cancer Are Associated With Poor Prognosis but Do Not Preclude Benefit From Oxaliplatin or Irinotecan: Results From the MRC FOCUS Trial

2009 ◽  
Vol 27 (35) ◽  
pp. 5931-5937 ◽  
Author(s):  
Susan D. Richman ◽  
Matthew T. Seymour ◽  
Philip Chambers ◽  
Faye Elliott ◽  
Catherine L. Daly ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Braf Mutation ◽  
Poor Prognosis ◽  
Advanced Colorectal Cancer ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Poor Prognostic Factor ◽  
Minimal Impact ◽  
The Impact

PurposeActivating mutation of the KRAS oncogene is an established predictive biomarker for resistance to anti–epidermal growth factor receptor (anti-EGFR) therapies in advanced colorectal cancer (aCRC). We wanted to determine whether KRAS and/or BRAF mutation is also a predictive biomarker for other aCRC therapies.Patients and MethodsThe Medical Research Council Fluorouracil, Oxaliplatin and Irinotecan: Use and Sequencing (MRC FOCUS) trial compared treatment sequences including first-line fluorouracil (FU), FU/irinotecan or FU/oxaliplatin in aCRC. Tumor blocks were obtained from 711 consenting patients. DNA was extracted and KRAS codons 12, 13, and 61 and BRAF codon 600 were assessed by pyrosequencing. Mutation (mut) status was assessed first as a prognostic factor and then as a predictive biomarker for the benefit of adding irinotecan or oxaliplatin to FU. The association of BRAF-mut with loss of MLH1 was assessed by immunohistochemistry.ResultsThree hundred eight (43.3%) of 711 patients had KRAS-mut and 56 (7.9%) of 711 had BRAF-mut. Mutation of KRAS, BRAF, or both was present in 360 (50.6%) of 711 patients. Mutation in either KRAS or BRAF was a poor prognostic factor for overall survival (OS; hazard ratio [HR], 1.40; 95% CI, 1.20 to 1.65; P < .0001) but had minimal impact on progression-free survival (PFS; HR, 1.16; 95% CI, 1.00 to 1.36; P = .05). Mutation status did not affect the impact of irinotecan or oxaliplatin on PFS or OS. BRAF-mut was weakly associated with loss of MLH1 staining (P = .012).ConclusionKRAS/BRAF mutation is associated with poor prognosis but is not a predictive biomarker for irinotecan or oxaliplatin. There is no evidence that patients with KRAS/BRAF mutated tumors are less likely to benefit from these standard chemotherapy agents.

scholarly journals Preoperative Plasma Fibrinogen and Serum Albumin Score Is an Independent Prognostic Factor for Resectable Stage II-III Gastric Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Menghui Wu ◽  
Yuchen Pan ◽  
Zhifang Jia ◽  
Yueqi Wang ◽  
Na Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factor ◽  
Serum Albumin ◽  
Poor Prognosis ◽  
Response Rate ◽  
Prognostic Significance ◽  
Independent Prognostic Factor ◽  
The Other ◽  
Plasma Fibrinogen ◽  
Radical Gastrectomy

Background. Radical gastrectomy with D2 lymphadenectomy is recognized as the standard treatment for resectable advanced gastric cancer. Preoperative fibrinogen and albumin measurements may bring clinical benefits in terms of providing advanced notice of a poor prognosis or recurrence in patients undergoing radical resection. The aim of this study was to identify markers that are predictive of a poor prognosis prior to surgery. Methods. Eight hundred forty-two consecutive patients who underwent curative radical gastrectomy at our hospital between 2008 and 2012 were retrospectively reviewed. Based on plasma fibrinogen and serum albumin levels, preoperative fibrinogen and albumin scores (Fib-Alb scores) were investigated, and the prognostic significance was determined. Results. The patients were classified according to a Fib-Alb score of 0 (n=376), 1 (n=327), or 2 (n=139). When the correlation between the response rate and the change in the Fib-Alb score was investigated, the response rate was significantly lower in patients with an increased Fib-Alb score than in the other patients. In the survival analysis, patients in the Fib-Alb high-score group exhibited significantly worse recurrence-free survival (RFS) (P=0.030) than patients in the other groups. A multivariate analysis using clinical stage and the change in the Fib-Alb score as covariates revealed that a change in the Fib-Alb score (Fib-Alb score 1, HR: 1.31, 95% CI: 1.03-1.66, P=0.028; Fib-Alb score 2, HR: 1.61, 95% CI: 1.20-2.17, P=0.001) was a significant independent predictive factor for RFS. Conclusions. The prognosis of patients with high fibrinogen and low albumin levels is poor. The Fib-Alb score was shown to be an independent prognostic factor for postoperative recurrence in gastric cancer patients who underwent radical gastrectomy.

scholarly journals Refractory anemia with ringed sideroblasts associated with marked thrombocytosis harbors JAK2 mutation and shows overlapping myeloproliferative and myelodysplastic features

Leukemia ◽  
2006 ◽  
Vol 20 (9) ◽  
pp. 1641-1644 ◽  
Author(s):  
S A Wang ◽  
R P Hasserjian ◽  
J M Loew ◽  
E V Sechman ◽  
D Jones ◽  
...  
Keyword(s):  
Refractory Anemia ◽  
Jak2 Mutation ◽  
Ringed Sideroblasts

scholarly journals Effect of Diagnosis (Refractory Anemia With Excess Blasts, Refractory Anemia With Excess Blasts in Transformation, or Acute Myeloid Leukemia [AML]) on Outcome of AML-Type Chemotherapy

Blood ◽  
1997 ◽  
Vol 90 (8) ◽  
pp. 2969-2977 ◽  
Author(s):  
Elihu Estey ◽  
Peter Thall ◽  
Miloslav Beran ◽  
Hagop Kantarjian ◽  
Sherry Pierce ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Multivariate Analyses ◽  
Patient Characteristics ◽  
Refractory Anemia ◽  
Event Free Survival ◽  
Free Survival ◽  
Current Medical Practice ◽  
Acute Myeloid

Abstract In current medical practice, patients with refractory anemia with excess blasts in transformation (RAEB-t), and especially patients with RAEB, receive chemotherapy regimens (AML Rx) administered to patients with acute myeloid leukemia (AML) less often than do patients with AML. These entities are distinguished primarily by marrow blast percentage (5% to 19% RAEB, 20% to 29% RAEB-t, and ≥30% AML). The poor prognosis of many RAEB or RAEB-t patients, if untreated, led us to give them AML Rx using the same plan as for AML. The purpose of this analysis was to see if diagnosis (RAEB, RAEB-t, or AML) affected outcome. We treated 372 patients with AML (acute promyelocytic leukemia [APL] excluded), 106 with RAEB-t, and 52 with RAEB. AML Rx produced a 62% complete remission (CR) rate in RAEB, essentially identical to the rates in RAEB-t and AML, but event-free survival (EFS) from CR and from start of treatment (start of Rx), as well as overall survival, were poorer in RAEB than in AML or RAEB-t, with AML and RAEB-t being identical. However, patients with RAEB or RAEB-t were more likely to have poor prognostic characteristics, in particular complex abnormalities involving chromosomes 5 and/or 7. Multivariate analyses indicated that, when considered together with cytogenetics and other patient characteristics, a diagnosis of RAEB rather than AML or RAEB-t had no effect on EFS from start of Rx, EFS from CR, survival, or achievement of CR. These analyses suggested a trend for patients with RAEB-t to have better EFS from start of Rx than patients with AML or RAEB (P = .08; relative risk, 0.80; 95% confidence interval, 0.62 to 1.03), but there were no differences with respect to the other outcomes. Our data suggest that the propriety of administering AML Rx to patients with RAEB or RAEB-t who have poor prognosis without treatment is identical to the propriety of treating AML in this fashion. Deterrents to standard AML Rx in these patients could justifiably include cytogenetics, age, etc, but not a diagnosis of RAEB or RAEB-t per se.

P063 Detection of methylation status changes in refractory anemia with ringed sideroblasts (RARS) by MS-MLPA

2007 ◽  
Vol 31 ◽  
pp. S74
Author(s):  
A. Valencia ◽  
J. Cervera ◽  
E. Such ◽  
S. Oltra ◽  
I. Luna ◽  
...  
Keyword(s):  
Methylation Status ◽  
Refractory Anemia ◽  
Ringed Sideroblasts

Hypermethylation of DAP-K Is an Adverse Prognostic Factor in Patients with Multiple Myeloma (MM).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2220-2220
Author(s):  
Esteban Braggio ◽  
Maria E. Gouveia ◽  
Roberto Magalhaes ◽  
Joao T. Souto ◽  
Marcia Garnica ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
Prognostic Factor ◽  
Serum Calcium ◽  
Poor Prognosis ◽  
Methylation Status ◽  
Aberrant Methylation ◽  
Platelet Counts ◽  
E Cadherin

Abstract Aberrant methylation in promoter-associated CpG islands has been recognized as a major mechanism for silencing tumor suppressor genes in many malignant diseases. In multiple myeloma (MM), a limited number of studies of gene methylation have been reported, with conflicting results. We determined the methylation status of 9 suppressor tumor genes in 68 newly diagnosed MM patients by methylation specific PCR (MSP). Ten DNA of normal healthy donors were used as controls. The target genes chosen are involved in many cellular pathways as DNA repair (MGMT), cell cycle regulation (p15INK4b and p16INK4a), cell-cell adherence (E-cadherin), apoptosis (DAP-k and BNIP3), hormonal response (RARb and ER) and Jak/STAT3 signaling pathway (SHP1). An association between hypermethylation and loss of expression of these genes has been demonstrated. The correlation between methylation status and risk factors was assessed by Fisher exact test or Chi-square test (categorical variables) or Student’s t-test (continuous variables). Overall survival (OS) was estimated using the Kaplan-Meier method. Differences between survival curves were estimated by the log-rank test. Multivariate analysis of factors associated with OS was performed by Cox regression. With a median follow-up of 15.5 months, 16 patients died (23%). Healthy donor samples were negative for methylation in all 9 genes tested. Hypermethylation was detected in 50% of patients for E-cadherin, 43% for p16, 16% for p15, 15% for SHP1, 13% for ER and BNIP3, 12% for RARb, 6% for DAP-k, and 0% for MGMT. Overall, 54 patients (79%) presented at least one hypermethylated gene (1 in 19 patients, 2 in 17 patients, 3 in 12 patients, 4 in 5 patients, and 5 in 1 patient). By univariate analysis, hypermethylation of DAP-k (p<0.001) and RARb (p=0.01) genes, platelet counts <100,000/mm3 (p<0.001) and serum calcium >9.5 mg/dL (p=0.03) were identified as adverse prognostic features. The median OS of patients with hypermethylation in DAP-k (4 months) and RARb (34 months) were considerably lower compared to patients without aberrant methylation (median survival not reached, p<0.001 and p=0.01, respectively). Patients with hypermethylation of DAP-k were more likely to have a serum creatinine >2.0 mg/dL (p=0.006), serum calcium >9.5 mg/dL (p=0.05), and Durie-Salmon stage III (p=0.04). No correlation was observed between methylation status of any gene and the presence of chromosome 13 abnormalities, t(4;14)(p16;q32), or t(11;14)(q23;q32). By multivariate analysis, hypermethylation of DAP-k (odds ratio [OR] 5.56, 95% confidence interval [95% CI] 1.4 – 22, p=0.01) and platelet counts <100,000/mm3 (OR 4.13, 95% CI 1.32 – 12.8, p=0.01) were associated with poor prognosis. Our data suggest that hypermethylation of DAP-k is an independent prognostic factor in MM. The impact of these features in identifying a group of poor prognosis beyond the classical prognostic factors warrants a higher sample size and longer follow-up.

Hemochromatois-Associated Gene Mutations in Patients with Myelodysplastic Syndromes with Refractory Anemia and Ringed Sideroblasts.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1541-1541
Author(s):  
Zachary P. Nearman ◽  
Bianca Serio ◽  
Hadrian Szpurka ◽  
Ilka Warshawsky ◽  
Alan Lichtin ◽  
...  
Keyword(s):  
Clinical Features ◽  
Myelodysplastic Syndromes ◽  
Phenotypic Variability ◽  
Gene Mutations ◽  
Differential Susceptibility ◽  
Control Population ◽  
Refractory Anemia ◽  
Hfe Gene ◽  
Jak2 Mutation ◽  
Ringed Sideroblasts

Abstract Complex interaction between a multitude of genetic variants may be responsible for differential susceptibility to specific diseases, and be responsible for phenotypic variability and heterogeneity of clinical presentations. Such a variability in clinical features confounded for many years investigations into the pathogenesis of myelodysplastic syndromes (MDS). We made a curious observation of increased ferritin levels in some newly diagnosed patients with MDS RARS (refractory anemia with ringed sideroblasts) in whom transfusional iron-overload was unlikely due to very low transfusion burden. Hence, we hypothesized that RARS patients may harbor hemochromatosis-related mutations, which could contribute to the pathophysiology of this particular subset of MDS. We studied a cohort of 109 MDS patients; 42 with RARS, and 67 with other forms of MDS (18 RA, 12 RAEB, 7 RAEB-T, 1 CMML, and 29 MDS/MPD overlap). All patients were genotyped using restriction fragment length polymorphism (RFLP) method, designed to detect presence of C282Y and H63D mutations of the HFE gene. We found significantly higher frequency of heterozygozity for the C282Y mutation in 21% of RARS patients (vs 9% in control population, n=2016, p= 0.017) while H63D genotype was not increased. The possible pathogenic role of this finding in RARS was supported by the normal distribution of mutant HFE alleles in patients with other forms of MDS (5% vs. 9%, p =0.35). Interestingly, 3/7 patients with RA not fulfilling the RARS criteria, but having increased numbers of ringed sideroblasts (<15%) also showed heterozygozity for either C282Y or H63D allele. To correlate the presence of C282Y allele with clinical features of RARS patients, we have performed a subset analysis. Within this group we have included patients with a rather nebulous and rare form of MDS, provisionally subclassified by WHO as RARS with thrombocytosis (RARSt); 7 of these patients (n=10) were found to have either C282Y or H63D allele resulting in a frequency of 30% and 40% of C282Y or H63D allele, respectively. The combined prevalence of either of these alleles in the control population is 33% (vs. 70% in RARSt, p=.01). Previously, we have demonstrated that RARSt patients are characterized by a high prevalence of the V617F JAK2 mutation (Szpurka et al, Blood 2006) suggestive of the pathophysiologic derivation of this syndrome from MPD rather than MDS. Consequently, we have tested the frequency of HFE gene variants associated with hemochromatosis in patients with MPD and Jak2 mutations. Of note is that patients with RARS harbored more C282Y alleles than those with other forms of MDS or MPD with Jak2 mutation (except for those with RARSt; (21% vs 5% and 3%, p =0.036 and .012, respectively). We conclude that hemochromatosis associated mutations may contribute to the pathogenesis of RARS. In patients with MPD and Jak2 mutation, concomitant presence of hemachromatosis-predisposing HFE variants may result in the unusual presentation associated with ringed sideroblasts.

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