Prognostic value of low platelets in MDS patients with del(5q)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7078-7078
Author(s):  
N. Galili ◽  
A. Ahmed ◽  
F. Quddus ◽  
S. Jandani ◽  
Z. Gul ◽  
...  
Keyword(s):  
Platelet Count ◽  
Median Survival ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Chromosomal Abnormalities ◽  
Prognostic Significance ◽  
Interstitial Deletion ◽  
Survival Times ◽  
Platelet Counts ◽  
Additional Chromosomal Abnormalities

7078 The most common (10–15%) chromosomal abnormality found in myelodysplastic syndromes (MDS) is an interstitial deletion of the long arm of chromosome 5 (del(5q)). The recent finding that lenalidomide is efficacious for MDS patients with del(5q) as either the sole abnormality or as part of a complex karyotype has focused renewed interest in the prognostic characteristics of these patients. We analyzed 189 patients with del(5q), 70 having isolated and 119 having additional chromosomal abnormalities. The median survival for the isolated del(5q) patient was 2.45 years and for those with complex abnormalities was 0.63 years (p=0.001). Each of these groups was then divided by IPSS category; median survival for Low/Int1 (n=56) was 2.46 years and 0.49 years for Int2/High (n=10, p=0.019).Thus our median survival times match previously published results and we have a representative dataset. Since 5q- syndrome patients with normal to high platelets have the best survival, platelet count may be of prognostic significance. We determined the median platelet count for our dataset to be 115,000 and analyzed median survival for patients with greater (n=89) or less (n=88) than the median value. Survival for those with higher platelet counts was 2.6 years, but dropped to 0.54 years with lower counts (p=0.0001). We then analyzed each of these two groups independently for survival based on IPSS, blast % and karyotype. Median survival for patients with >115,000 platelets and either Low/Int1-risk (n=62), <5% blasts (n=46) or an isolated del(5q) (n=46) was 2.95–3.0 years. The survival of these patients dramatically decreased (0.63 years) if they had Int2/High IPSS (n=19) or >10% blasts (=11). The presence of additional chromosomal abnormalities decreased survival to 1.85 years (n=28). A different range of survival times occurred with patients that had <115,000 platelets. Their median survival based on Low/Int1 IPSS (n=20), <5% blasts (n=18) or isolated del(5q)(n=20) was only 0.68–0.84 years. Int2/High IPSS (n=64), >5% blasts (n=50) or additional chromosomal abnormalities (n=68) lowered survival to 0.44–0.49 years. Thus lower platelet counts in del(5q) MDS patients with favorable IPSS (median survival 0.84 years), <5% blasts (median survival 0.68 years) or isolated del(5q) (median survival 0.74 years) appear to have poor prognosis. No significant financial relationships to disclose.

scholarly journals Clinical and prognostic significance of 3q26.2 and other chromosome 3 abnormalities in CML in the era of tyrosine kinase inhibitors

Blood ◽  
2015 ◽  
Vol 126 (14) ◽  
pp. 1699-1706 ◽  
Author(s):  
Wei Wang ◽  
Jorge E. Cortes ◽  
Pei Lin ◽  
Michael W. Beaty ◽  
Di Ai ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Poor Prognosis ◽  
Kinase Inhibitors ◽  
Chromosomal Abnormalities ◽  
Prognostic Significance ◽  
Chromosome 3 ◽  
Predominant Role ◽  
Key Points ◽  
Tki Treatment ◽  
Additional Chromosomal Abnormalities

Key Points The emergence of 3q26.2 rearrangements in CML is associated with resistance to TKI treatment and poor prognosis. 3q26.2 rearrangements play a predominant role in determining prognosis, irrelevant to the presence or absence of other additional chromosomal abnormalities in CML.

scholarly journals p53 mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4302-4310 ◽  
Author(s):  
TC Greiner ◽  
MJ Moynihan ◽  
WC Chan ◽  
DM Lytle ◽  
A Pedersen ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Median Survival ◽  
Poor Prognosis ◽  
Denaturing Gradient Gel Electrophoresis ◽  
Cell Lymphoma ◽  
P53 Protein ◽  
Prognostic Significance ◽  
Missense Mutations ◽  
P53 Mutations ◽  
Mantle Cell

Mutations of the p53 tumor suppressor gene have been described in several subtypes of non-Hodgkin's lymphoma, but the incidence of p53 mutations in mantle cell lymphoma (MCL) is unknown. We hypothesized that cases of MCL with a variant or high-grade cytology would have a higher likelihood of p53 mutations than typical MCL. We were also interested in the prognostic significance of p53 mutations in MCL. Therefore, a series of 53 well-characterized cases of MCL with DNA from 62 tissue samples were analyzed by the polymerase chain reaction with denaturing gradient gel electrophoresis for exons 5–8 of p53. Immunoperoxidase studies with the antibody DO-7 to p53 protein were also performed on frozen sections. We found mutations of the p53 gene in 8 of the 53 cases (15%) of MCL. Missense mutations predominated, and 50% of the mutations occurred at known p53 hotspot codons. Of 21 cases with variant cytology (ie, anaplastic or blastic), 6 (28.6%) had p53 mutations as compared with only 2 of 32 cases (6.3%) with typical MCL cytology (P = .05), and p53 mutations preceded the development of variant cytology in 2 patients. Overexpression of p53 protein was observed in 6 of the 8 cases (75%) with p53 mutations and in none of the 45 wild-type cases. The median survival of the cases with mutant p53 was only 1.3 years (all died), whereas the median survival of cases with germline p53 was 5.1 years (P = .023). These results suggest that mutations of p53 may be one mechanism involved in the development of variant forms of MCL and indicate that p53 mutations in MCL predict a poor prognosis.

scholarly journals Prognostic implications of morphology and karyotype in primary myelodysplastic syndromes

Blood ◽  
1986 ◽  
Vol 67 (6) ◽  
pp. 1765-1772 ◽  
Author(s):  
RH Jacobs ◽  
MA Cornbleet ◽  
JW Vardiman ◽  
RA Larson ◽  
MM Le Beau ◽  
...  
Keyword(s):  
Median Survival ◽  
Myelodysplastic Syndromes ◽  
Chromosomal Abnormalities ◽  
Bone Marrow Cells ◽  
Normal Karyotype ◽  
Refractory Anemia ◽  
Survival Times ◽  
Trisomy 8 ◽  
Leukemic Transformation ◽  
Abnormal Karyotype

Abstract Forty-nine patients with primary myelodysplastic syndromes (MDS) were subclassified according to French-American-British (FAB) Cooperative Group criteria. Eight patients had acquired idiopathic sideroblastic anemia (AISA), ten had chronic myelomonocytic leukemia (CMMoL), 14 had refractory anemia (RA), nine had refractory anemia with excess blasts (RAEB), and five had refractory anemia with excess blasts in transformation (RAEB-T); three patients could not be subclassified. The actuarial median survival for patients with AISA or with RA had not been reached at 60 months of follow-up. The median survival times for patients with CMMoL, RAEB, and RAEB-T were 25, 21, and 16 months, respectively. The percentages of patients with each subtype who developed ANLL were none in AISA, 20% in CMMoL, 7% in RA, 56% in RAEB, and 40% in RAEB-T. Patients with CMMoL had a poor prognosis independent of transformation to acute nonlymphocytic leukemia (ANLL), whereas patients with RAEB and RAEB-T had a high incidence of transformation and short survival times. Clonal chromosomal abnormalities were present in bone marrow cells from 19 patients at the time of diagnosis, and two others developed an abnormal karyotype at the time of leukemic transformation. The most frequent abnormalities, including initial and evolutionary changes, were trisomy 8 (9 patients), deletion of 5q (4 patients), and deletion of 20q (4 patients). The median survival times were 32 months for patients with an abnormal karyotype, and 48 months for those with a normal karyotype (P = 0.2). Specific chromosomal abnormalities were not associated with particular histologic subtypes; however, a high percentage of patients with RAEB and RAEB-T had an abnormal clone (89% and 80%, respectively). The percentages of patients with clonal abnormalities were 13% for AISA, 20% for CMMoL, and 29% for RA. The MDS transformed to ANLL in 42% of patients with an abnormal karyotype, compared to 10% of those with an initially normal karyotype (P less than .01). Among patients with RA, RAEB, and RAEB-T, the risk of leukemic transformation was confined to those with an abnormal karyotype (P less than .01). Thus, in the present study, morphology and karyotype combined were the best indicators of outcome in patients with MDS.

scholarly journals Clinical staging of chronic lymphocytic leukemia

Blood ◽  
1975 ◽  
Vol 46 (2) ◽  
pp. 219-234 ◽  
Author(s):  
KR Rai ◽  
A Sawitsky ◽  
EP Cronkite ◽  
AD Chanana ◽  
RN Levy ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Median Survival ◽  
Prognostic Significance ◽  
Stage Iv ◽  
Staging System ◽  
Lymphocytic Leukemia ◽  
Stage Ii ◽  
Stage Iii ◽  
Clinical Staging ◽  
Survival Times

A method of clinical staging of chronic lymphocytic leukemia (CLL) has been proposed which is based on the concept that CLL is a disease of progressive accumulation of nonfunctioning lymphocytes: stage O, bone marrow and blood lymphocytosis only; stage 1, lymphocytosis with enlarged nodes; stage II, lymphocytosis with enlarged spleen or liver or both; stage III, lymphocytosis with anemia; and stage IV:lymphocytosis with thrombocytopenia. Analysis of 125 patients. in the present series showed the following median survival times (in months) from diagnosis: stage 0, is greater than 150; stage I 101; stage II, 71; stage III, 19; stage IV, 19, The median survival for the entire series was 71 mo. The prognostic significance of the stage remained even after adjustment was made for age and sex. However, both sex and age were shown to be poor predictors of survival after adjustment for stage. The method of staging proved to be a reliable predictor of survival whether used at diagnosis or during the course of the disease. The proposed staging system was an equally accurate indicator for survival when applied to two other previously published studies of large series of patients.

scholarly journals Upregulated expression of pyruvate kinase M2 mRNA predicts poor prognosis in lung adenocarcinoma

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8625
Author(s):  
Guiping Wang ◽  
Yingying Zhong ◽  
Jiecong Liang ◽  
Zhibin Li ◽  
Yun Ye
Keyword(s):  
Lung Adenocarcinoma ◽  
Pyruvate Kinase ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Prognostic Significance ◽  
Tumor Stage ◽  
Pooled Analysis ◽  
Copy Number Variations ◽  
Pyruvate Kinase M2 ◽  
Kaplan Meier

Background Pyruvate kinase M2 (PKM2) is critical regulator contributing to Warburg effect. However, the expression pattern and prognostic value of PKM2 remain unknown in lung adenocarcinoma (LUAD). The aim of this study is to clarify the prognostic value of PKM2 via intergrated bioinformatics analysis. Methods Firstly, mRNA expression levels of PKM2 in LUAD were systematically analyzed using the ONCOMINE and TCGA databases. Then, the association between PKM2 expression and clinical parameters was investigated by UALCAN. The Kaplan–Meier Plotter was used to assess the prognostic significance of PKM2. Finally, the relationship between PKM2 expression and its genetic and epigenetic changes was evaluated with MEXPRESS and MethHC database. Results Pooled analysis showed that PKM2 is frequently upregulated expression in LUAD. Subsequently, PKM2 expression was identified to be positively associated with tumor stage and lymph node metastasis and also strongly correlated with worse OS (P = 2.80e−14), PPS (P = 0.022), FP (P = 1.30e−6) and RFS (P = 3.41e−8). Importantly, our results demonstrated that over-expressed PKM2 is associated with PKM2 hypomethylation and copy number variations (CNVs). Conclusion This study confirms that over-expressed PKM2 in LUAD is associated with poor prognosis, suggesting that PKM2 might act as a promising prognostic biomarker and novel therapeutic target for LUAD.

scholarly journals Prognostic discrimination in "good-risk" chronic granulocytic leukemia

Blood ◽  
1984 ◽  
Vol 63 (4) ◽  
pp. 789-799 ◽  
Author(s):  
JE Sokal ◽  
EB Cox ◽  
M Baccarani ◽  
S Tura ◽  
GA Gomez ◽  
...  
Keyword(s):  
Platelet Count ◽  
Median Survival ◽  
Risk Group ◽  
Cox Model ◽  
Prognostic Significance ◽  
Philadelphia Chromosome ◽  
Spleen Size ◽  
Chronic Granulocytic Leukemia ◽  
Granulocytic Leukemia ◽  
Good Risk

Abstract The prognostic significance of disease features recorded at the time of diagnosis was examined among 813 patients with Philadelphia chromosome- positive, nonblastic chronic granulocytic leukemia (CGL) collected from six European and American series. The survival pattern for this population was typical of “good-risk” patients, and median survival was 47 mo. There were multiple interrelationships among different disease features, which led to highly significant correlations with survival for some that had no primary prognostic significance, such as hematocrit. Multivariable regression analysis indicated that spleen size and the percentage of circulating blasts were the most important prognostic indicators. These features, and age, behaved as continuous variables with progressively unfavorable import at higher values. The platelet count did not influence survival significantly at values below 700 X 10(9)/liter but was increasingly unfavorable above this level. Basophils plus eosinophils over 15%, more than 5% marrow blasts, and karyotypic abnormalities in addition to the Ph1 were also significant unfavorable signs. The Cox model, generated with four variables representing percent blasts, spleen size, platelet count, and age, provided a useful representation of risk status in this population, with good fit between predicted and observed survival over more than a twofold survival range. A hazard function derived from half of the patient population successfully segregated the remainder into three groups with significantly different survival patterns. We conclude that it should be possible to identify a lower risk group of patients with a 2-yr survival of 90%, subsequent risk averaging somewhat less than 20%/yr and median survival of 5 yr, an intermediate group, and a high- risk group with a 2-yr survival of 65%, followed by a death rate of about 35%/yr and median survival of 2.5 yr.

Associations Between Platelet Count and Survival and Disease Progression In Thrombocytopenic Patients with Myelodysplastic Syndromes

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2905-2905
Author(s):  
Mellissa Yong ◽  
Carrie Kuehn ◽  
Michael Kelsh ◽  
Meghan Wagner ◽  
Allen Yang ◽  
...  
Keyword(s):  
Platelet Count ◽  
Survival Time ◽  
Disease Progression ◽  
Median Survival ◽  
Myelodysplastic Syndromes ◽  
Research Funding ◽  
Employment Equity ◽  
Classification Schemes ◽  
Platelet Counts ◽  
Equity Ownership

Abstract Abstract 2905 Introduction: Myelodysplastic syndromes (MDS) are a group of malignant bone marrow stem cell disorders characterized by a predisposition for transformation to acute myelogeneous leukemia (AML). MDS disorders are heterogeneous in their morphology, cytogenetics, survival time, and ability to transform to AML. Although numerous classification schemes have been developed to provide a reproducible method for estimating patient survival and risk of leukemic evolution, research continues to identify factors that affect prognosis and survival time (e.g., treatment type, WHO FAB subgroups, karyotype, and transfusion status) and refine existing classification schemes. The goal of this analysis was to evaluate the effect of platelet counts on survival and disease progression to AML among thrombocytopenic (platelet count <100 × 109/L) MDS patients (n = 303) using the International MDS Risk Analysis Workshop (IMRAW) database. Methods: The IMRAW dataset includes demographic, clinical and prognostic information for patients treated in the United States, Europe, and Japan who were diagnosed with MDS between 1972 and 1994. Platelet count (× 109/L) was categorized as follows: 0 to <20, 20 to <30, 30 to <50, 50 to <70, 70 to <80, 80 to <90, 90 to <100, and ≥100. Survival was modeled using the Kaplan-Meier (K-M) estimator. One-, two-, and three-year survival rates and median, quartile, and restricted mean survival time were estimated using K-M methods. Time to evolution to AML was modeled using the Nelson-Aalen (N-A) cumulative hazard estimator with death prior to onset of AML as a competing risk event. One-, two-, and three-year cumulative rates of AML evolution were generated using N-A methods. Mean, median, and quartile values for time to AML evolution were also summarized. Cox proportional hazards modeling was used to estimate the hazard ratio (HR) for survival and evolution of MDS to AML. Results: Among thrombocytopenic MDS patients (n = 303), one-, two- and three-year survival were 58%, 44%, and 33%, respectively. Median survival was 19.6 months, with the lowest among those with a platelet count 0 to <20 × 109/L (10.9 months) and the highest among those with a platelet count 90 to <100 × 109/L (33.2 months). Patients with platelet counts (x 109/L) <70, 70 to <90, and ≥90 formed three distinct survival groups for approximately three years after MDS diagnosis (Figure 1). Across platelet categories, one-, two- and three-year survival ranged from 48.2% to 83.4%, 37.3% to 68.0%, and 30.5% to 39.9%, respectively (Table 1). Among non-thrombocytopenic MDS patients (platelet count ≥100 × 109/L), the one-, two- and three-year survival were 83.1%, 68.6%, and 59.1%, respectively, and the median survival was 47.3 months. Results of Cox models for thrombocytopenic MDS patients suggested an increased risk of death with platelet counts <90 × 109/L compared to platelet counts 90 to <100 × 109/L and no relationship was shown between strength of the HR and decreasing platelet count when adjusted for gender, age, year of diagnosis and institution (Table 1). Among thrombocytopenic MDS patients who developed AML (n = 73), median time to AML diagnosis from MDS diagnosis was 9.2 months. One-, two- and three-year evolution to AML rates were 21%, 30%, and 38%, respectively. Conclusions: Platelet count in thrombocytopenic MDS patients may be clinically relevant to survival and should be evaluated further. Platelet count does not appear to be associated with risk of evolution to AML. Evaluation of these relationships in a larger sample is warranted. Disclosures: Yong: Amgen Inc: Employment, Equity Ownership. Kuehn:Amgen Inc: Research Funding. Kelsh:Amgen Inc: Research Funding. Wagner:Amgen Inc: Research Funding. Yang:Amgen Inc: Employment, Equity Ownership. Franklin:Amgen Inc: Employment, Equity Ownership.

Inversion of Chromosome 12 and Translocations of 12q13-q15 In Primary Myelofibrosis (PMF) Are Associated with Disease Progression and a Poor Prognosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4110-4110 ◽  
Author(s):  
Vesna Najfeld ◽  
Joseph Tripodi ◽  
Nathaniel Wisch ◽  
Amory Novoselac ◽  
Heike L. Pahl ◽  
...  
Keyword(s):  
Stem Cell ◽  
Disease Progression ◽  
Poor Prognosis ◽  
Chromosomal Abnormalities ◽  
Prognostic Significance ◽  
Primary Myelofibrosis ◽  
Myelogenous Leukemia ◽  
Jak2v617f Mutation ◽  
Chromosome 12 ◽  
Band Region

Abstract Abstract 4110 Recurrent chromosomal abnormalities are occurring at the frequency of 45–50% among patients (pts) with primary myelofibrosis (PMF). The prognostic significance of these abnormalities is largely unknown. Among 377 pts (242 from the Mount Sinai Medical Center and 135 from the MPD-RC data base) with primary myelofibrosis (PMF) 187 pts (50%) were cytogenetically abnormal. Of these, 17 pts (9%) had abnormalities of chromosome 12. We postulated that chromosome 12 abnormalities have prognostic significance and investigated whether they are associated with progression of disease. The cohort included 13 males and 4 females with an average age of 55 years (range 26 to 74). The JAK2V617F mutation was present in 4 pts, was absent in 7 pts and in the remaining 6 pts the status was unknown. Four of 17 pts (23.5%) had a terminal deletion of band p12 on the short arms while the remaining 13 pts (76.5%) had structural aberrations of the long arms. Five pts (29%) had an inversion of chromosome 12: 3 pts had had a pericentric inversion involving the p12 band region on the short arms and q13 band region on the long arms; while 2 pts had a paracentric inversion involving q13 and q24 segments on the long arm. In 3 of 5 pts with inv(12)) two cytogenetic events occurred: first, the formation of an inversion followed by the translocation of 12q to another chromosome, indicating that this region(s) is under selective pressure for multiple genetic events. The most frequent partner chromosome in 12q translocations were chromosome 2 (3 pts), and chromosome 10 (3 pts). Since the q13 band region was involved in 77% (10 of 13) pts with 12q abnormalities including all 5 pts with inv(12) we postulated that the NF-E2 transcription factor, at the 12q13.13 chromosomal site, may be structurally rearranged. The NF-E2 expression is increased in PMF pts (Wang et al, Blood, 2010). RP11-968A15 BAC FISH probe, which containes the entire NF-E2 was hybridized to metaphase and interphase cells from 3 pts with inv (12) and 2 pts with 12q13 translocations. FISH analysis of over 1,000 cells showed a structurally intact NF-E2 in all 5pts without evidence of rearrangements or deletions. Disease progression, transformation to acute myelogenous leukemia (AML) and death was observed in 70% (7 of 10) of pts with 12q13 abnormalities and 2 additional pts with 12q15 chromosome aberrations. Therefore, region q13 to q15 on chromosome 12 is associated with a poor prognosis in 92% of patients with PMF. Specifically, 3 of 5 pts with inv(12) expired, one transformed to AML and the 5th pt underwent stem cell transplant. Both pts with 12q15 abnormalities transformed to AML, one of them expired. An additional 4 pts with advanced disease underwent SCT and are doing well after 5 to 18 months. Our observations demonstrated that 12q13-q15 chromosomal abnormalities are more frequent in males (3:1 ratio) and occurring in 40% of JAK2V617F mutation negative pts. The presence of inv(12) and/or translocations of 12q13-q15 at diagnosis is associated with disease progression in 92% of pts with PMF and therefore stem cell transplantation should be considered as a treatment option early in the disease course. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Prognostic significance of thrombocytosis in idiopathic sideroblastic anemia

Blood ◽  
1977 ◽  
Vol 50 (3) ◽  
pp. 427-432 ◽  
Author(s):  
RR Streeter ◽  
CA Presant ◽  
E Reinhard
Keyword(s):  
Platelet Count ◽  
Acute Leukemia ◽  
Case Reports ◽  
Prognostic Significance ◽  
Additional Case ◽  
Literature Analysis ◽  
Sideroblastic Anemia ◽  
Leukemic Transformation ◽  
Platelet Counts ◽  
Normal Platelet

Abstract In order to determine the prognostic significance of thrombocytosis in idiopathic sideroblastic anemia, the clinical courses of 17 patients were reviewed. Six patients (36%) had thrombocytosis, and none developed acute leukemia. Nine patients (53%) had normal platelet counts, and one developed acute leukemia. Two patients (12%) were thrombocytopenic, and one died of acute leukemia. There was little correlation between survival and platelet count. Sixty-three additional case reports of idiopathic sideroblastic anemia were collected from the literature. Analysis of those patients and the patients in the present study documented transformation to acute leukemia in 5 of 9 (56%) thrombocytopenic patients, 4 of 54 (7.4%) patients with normal platelet counts, and 0 of 17 patients with thrombocytosis (p less than 0.05). Therefore patients with idiopathic sideroblastic anemia and thrombocytosis appear to have a decreased likelihood of leukemic transformation.

Sign in / Sign up

Export Citation Format

Share Document