Prognostic value of Ki67LI in HER2-negative luminal (HNL) early breast cancer (EBC): A 14-year single institution experience with long follow-up.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11569-e11569
Author(s):  
Antonella Ferro ◽  
Lucianna Russo ◽  
Claudio Eccher ◽  
Alessia Caldara ◽  
Renza Triolo ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Prognostic Significance ◽  
Routine Practice ◽  
Prognostic Information ◽  
Ki 67 ◽  
Younger Age ◽  
Independent Prognostic Significance ◽  
Her 2 ◽  
Biological Entities

e11569 Background: Several studies have emphasized the biologic and prognostic value of Ki67LI and its role in routine practice, particularly to define prognostic subgroups of luminal tumors. Methods: Ki67LI was identified by immunohistochemical staining in 3760 consecutive EBC pts followed from 1995 to 2008. Median age was 61 y. The relationship with clinic-pathological parameters and the prognostic significance of KI67LI were investigated in all EBCs and in 2380 HER2 negative luminal (HNL) cases, stratified on homogeneous grading (594 G1, 1282 G2, 504 G3). Results: Median Ki67LI values were 22% in all cases, 20% in HNL and 10%, 20% and 35% in HNL- G1,G2,G3 respectively. Ki67LI > 22% (1873 pts) was significantly (p<0.001) associated with younger age, ductal type, greater size, positive N, poor G, absent or low ER /PR, positive HER-2, triple negative subtypes. Local and Distant Relapses were 138 (7.3%) and 355 (18.9%) in < or > 22% Ki67LI respectively. Median time to first event was 31.7 ms in > 22% vs 50.1 ms in < 22% Ki67. At a median f-up of 77 months EFS and OS were 91.9 and 92.1% in < 22% vs 78.9% and 81% in > 22% Ki67 respectively (p <0.001). The prognosis was consistently worse for > 22% Ki 67 in all clinical-pathological subsets, except in negative ER group. In multivariate analysis, KI67 maintained an independent prognostic significance for DFS and OS. In HNL, EFS and OS were 93.7 and 92% in < 20% vs 81.7 and 83.3% in >20% Ki67(p <0.001). Using median ki67LI value for different homogenous HNL-GG as cutoffs, we stratified these populations in low and high risk. Results are summarized in the Table. Conclusions: Our study confirms the prognostic value of Ki67LI in EBC,as well as other clinical pathological characteristics such as age, tumor size, histological type, nodal and hormonal receptors status. Cutoffs are different into HNL.They could identify different biological entities in each grading group providing additional prognostic information in outcome prediction. [Table: see text]

scholarly journals GATA3 as an Adjunct Prognostic Factor in Breast Cancer Patients with Less Aggressive Disease: A Study with a Review of the Literature

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 604
Author(s):  
Patrizia Querzoli ◽  
Massimo Pedriali ◽  
Rosa Rinaldi ◽  
Paola Secchiero ◽  
Paolo Giorgi Rossi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Value ◽  
Tissue Microarrays ◽  
Routine Practice ◽  
Lower Grade ◽  
Breast Cancer Patients ◽  
Wild Type ◽  
Ki 67 ◽  
Luminal B

Background: GATA binding protein 3 (GATA3) expression is positively correlated with estrogen receptor (ER) expression, but its prognostic value as an independent factor remains unclear. Thus, we undertook the current study to evaluate the expression of GATA3 and its prognostic value in a large series of breast carcinomas (BCs) with long-term follow-up. Methods: A total of 702 consecutive primary invasive BCs resected between 1989 and 1993 in our institution were arranged in tissue microarrays, immunostained for ER, progesterone receptor (PR), ki-67, HER2, p53, and GATA3, and scored. Clinico-pathological data were retrospectively collected. Results: GATA3 was evaluable in 608 (87%) of the 702 cases; it was positive in 413 (68%) cases and negative in 195 (32%) cases. GATA3 positivity was significantly associated with lower grade (p < 0.0001), size (p = 0.0463), stage (p = 0.0049), ER+ (p < 0.0001), PR+ (p < 0.0001), HER2− (p = 0.0175), and p53 wild-type pattern (p < 0.0001). The median follow-up was 183 months, GATA3 positivity was associated with better overall survival (HR 0.70, p = 0.001), and its prognostic value was retained in a multivariate analysis. The association with better overall survival was stronger in patients with grade 1–2, pT1–2, pN0, stage I–II, ER+, PR+, ki-67 < 20%, HER2−, a wild-type p53 immunohistochemical pattern, and in luminal B BC. Conclusions: Our findings indicate that GATA3 is a positive prognostic marker in BC patients, especially in patients with biologically less aggressive BC. Incorporating GATA3 immunohistochemistry into routine practice could help further stratify BC patients for their risk.

scholarly journals The Prognostic Value of Baseline Lymphocyte, Neutrophil, and Monocyte Counts in Locally Advanced Cervical Carcinoma Treated with Radiation

2017 ◽  
Vol 2017 ◽  
pp. 1-9
Author(s):  
Sareena Singh ◽  
Justin Himler ◽  
Christa I. Nagel ◽  
Kimberly Resnick
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Cervical Carcinoma ◽  
Prognostic Value ◽  
Locally Advanced ◽  
Prognostic Significance ◽  
Prognostic Information ◽  
Advanced Cervical Carcinoma ◽  
Leukocyte Counts

Background. To determine the prognostic significance of pretreatment levels of circulating lymphocyte (CLC), neutrophil (CNC), and monocyte (CMC) counts in patients with locally advanced cervical carcinoma (CC) treated with definitive radiation.Methods. A retrospective, dual-institution review of patients with Stage IB2-IVA CC from 2005 to 2015. Progression-free (PFS) and Overall Survival (OS) were determined for high and low CLC, CNC, and CMC groups. Multivariate analysis was used to confirm prognostic value of baseline leukocyte counts.Results. 181 patients were included. Median follow-up time was 26 (3–89) months. CNC had no effect on PFS or OS. PFS was similar between CMC groups; however, OS was significantly improved for patients with low CMC (62.5 versus 45.3 months,p=0.016). High CLC was associated with improved PFS (48.5 versus 27.8 months,p=0.048) and OS (58.4 versus 34.9 months,p=0.048). On multivariate analysis, high CNC was associated with increased relapse risk (HR 1.12,p=0.006) and low CLC was associated with increased mortality risk (HR 0.67,p=0.027).Conclusion. This study demonstrates that leukocyte values can provide prognostic information in CC. These hypothesis-generating findings warrant further prospective investigations.

Oncogenes and Male Breast Carcinoma: c-erbB-2 and p53 Coexpression Predicts a Poor Survival

2000 ◽  
Vol 18 (16) ◽  
pp. 2948-2956 ◽  
Author(s):  
Achille Pich ◽  
Elena Margaria ◽  
Luigi Chiusa
Keyword(s):  
Breast Carcinoma ◽  
Prognostic Value ◽  
Ductal Carcinoma ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Male Breast ◽  
Male Breast Carcinoma ◽  
P53 Immunoreactivity ◽  
Mib 1

PURPOSE: To investigate the prognostic value of biomarkers in male breast carcinoma (MBC). PATIENTS AND METHODS: Fifty patients (mean age, 62.2 years) with invasive ductal carcinoma were retrospectively studied. All patients received surgery; 35 had adjuvant postoperative therapy. The median follow-up was 59 months (range, 1 to 230 months). c-myc, c-erbB-2, p53, and bcl-2 proteins were immunohistochemically detected on sections from formalin-fixed, paraffin-embedded tissues using 9E11, CB11, DO7, and bcl-2 124 monoclonal antibodies (mAbs). Estrogen, progesterone, and androgen receptors were detected using specific mAbs. Cell proliferation was assessed by MIB-1 mAb. RESULTS: In univariate analysis, c-myc, c-erbB-2, and p53 protein overexpression was significantly correlated with prognosis. The median survival was 107 months for c-myc–negative and 52 months for c-myc–positive patients (P = .01), 96 months for c-erbB-2–negative and 39 months for c-erbB-2–positive patients (P = .02), and 100 months for p53-negative and 33 months for p53-positive patients (P = .0008). Tumor histologic grade (P = .01), tumor size (P = .02), patient age at diagnosis (P = .03), and MIB-1 scores (P = .0004) also had prognostic value. In multivariate analysis, only c-erbB-2 and p53 immunoreactivity retained independent prognostic significance. All nine patients who did not express c-erbB-2 and p53 proteins were alive after 58 months, whereas none of the 14 patients expressing both proteins survived at 61 months follow-up (P = .0002). CONCLUSION: Overexpression of c-myc, c-erbB-2, and p53 proteins may be regarded as an additional prognostic factor in MBC. The combination of c-erbB-2 and p53 immunoreactivity can stratify patients into different risk groups.

scholarly journals The Prognostic Value of NANO Scale Assessment in IDH-Wild-Type Glioblastoma Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Johannes Kasper ◽  
Tim Wende ◽  
Michael Karl Fehrenbach ◽  
Florian Wilhelmy ◽  
Katja Jähne ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Univariate Analysis ◽  
Extent Of Resection ◽  
Survival Prediction ◽  
Wild Type ◽  
Prognostic Information ◽  
Nano Scale ◽  
Scale Assessment ◽  
General Physical

BackgroundIDH-wild-type glioblastoma (GBM) is the most frequent brain-derived malignancy. Despite intense research efforts, it is still associated with a very poor prognosis. Several parameters were identified as prognostic, including general physical performance. In neuro-oncology (NO), special emphasis is put on focal deficits and cognitive (dys-)function. The Neurologic Assessment in Neuro-Oncology (NANO) scale was proposed in order to standardize the assessment of neurological performance in NO. This study evaluated whether NANO scale assessment provides prognostic information in a standardized collective of GBM patients.MethodsThe records of all GBM patients treated between 2014 and 2019 at our facility were retrospectively screened. Inclusion criteria were age over 18 years, at least 3 months postoperative follow-up, and preoperative and postoperative cranial magnetic resonance imaging. The NANO scale was assessed pre- and postoperatively as well as at 3 months follow-up. Univariate and multivariate survival analyses were carried to investigate the prognostic value.ResultsOne hundred and thirty-one patients were included. In univariate analysis, poor postoperative neurological performance (HR 1.13, p = 0.004), poor neurological performance at 3 months postsurgery (HR 1.37, p &lt; 0.001), and neurological deterioration during follow-up (HR 1.38, p &lt; 0.001), all assessed via the NANO scale, were associated with shorter survival. In multivariate analysis including other prognostic factors such as the extent of resection, adjuvant treatment regimen, or age, NANO scale assessment at 3 months postoperative follow-up was independently associated with survival prediction (HR 1.36, p &lt; 0.001). The optimal NANO scale cutoff for patient stratification was 3.5 points.ConclusionNeurological performance assessment employing the NANO scale might provide prognostic information in patients suffering from GBM.

scholarly journals Stratification by interferon-γ release assay level predicts risk of incident TB

Thorax ◽  
2018 ◽  
Vol 73 (7) ◽  
pp. 652-661 ◽  
Author(s):  
Brita Askeland Winje ◽  
Richard White ◽  
Heidi Syre ◽  
Dag Harald Skutlaberg ◽  
Fredrik Oftung ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Risk Model ◽  
Large Population ◽  
Interferon Γ ◽  
National Registry ◽  
Routine Practice ◽  
Prescription Database ◽  
Prognostic Information ◽  
Increased Risk ◽  
Ifn Γ

IntroductionTargeted testing and treatment of latent TB infection (LTBI) are priorities on the global health agenda, but LTBI management remains challenging. We aimed to evaluate the prognostic value of the QuantiFERON TB-Gold (QFT) test for incident TB, focusing on the interferon (IFN)-γ level, when applied in routine practice in a low TB incidence setting.MethodsIn this large population-based prospective cohort, we linked QFT results in Norway (1 January 2009–30 June 2014) with national registry data (Norwegian Surveillance System for Infectious Diseases, Norwegian Prescription Database, Norwegian Patient Registry and Statistics Norway) to assess the prognostic value of QFT for incident TB. Participants were followed until 30 June 2016. We used restricted cubic splines to model non-linear relationships between IFN-γ levels and TB, and applied these findings to a competing risk model.ResultsThe prospective analyses included 50 389 QFT results from 44 875 individuals, of whom 257 developed TB. Overall, 22% (n=9878) of QFT results were positive. TB risk increased with the IFN-γ level until a plateau level, above which further increase was not associated with additional prognostic information. The HRs for TB were 8.8 (95% CI 4.7 to 16.5), 19.2 (95% CI 11.6 to 31.6) and 31.3 (95% CI 19.8 to 49.5) times higher with IFN-γ levels of 0.35 to <1.00, 1.00 to <4.00 and >4.00 IU/mL, respectively, compared with negative tests (<0.35 IU/mL).ConclusionsConsistently, QFT demonstrates increased risk of incident TB with rising IFN-γ concentrations, indicating that IFN-γ levels may be used to guide targeted treatment of LTBI.

Prognostic Value of Thymidylate Synthase, Ki-67, and p53 in Patients With Dukes’ B and C Colon Cancer: A National Cancer Institute–National Surgical Adjuvant Breast and Bowel Project Collaborative Study

2003 ◽  
Vol 21 (2) ◽  
pp. 241-250 ◽  
Author(s):  
Carmen J. Allegra ◽  
Soon Paik ◽  
Linda H. Colangelo ◽  
Allyson L. Parr ◽  
Ilan Kirsch ◽  
...  
Keyword(s):  
Colon Carcinoma ◽  
Thymidylate Synthase ◽  
Prognostic Value ◽  
Collaborative Study ◽  
Ki 67 ◽  
Free Survival ◽  
National Surgical Adjuvant Breast ◽  
Bowel Project ◽  
Immunohistochemical Techniques

Purpose: To define the value of thymidylate synthase (TS), Ki-67, and p53 as prognostic markers in patients with stage II and III colon carcinoma. Patients and Methods: We retrospectively analyzed the prognostic value of TS, Ki-67, and p53 in 706 patients with Dukes’ B (291 patients) or Dukes’ C (415 patients) colon carcinoma who were treated with either surgery alone (275 patients) or surgery plus fluorouracil (FU)-leucovorin chemotherapy (431 patients) in National Surgical Adjuvant Breast and Bowel Project (NSABP) protocols C01-C04. All three markers were assayed using immunohistochemical techniques. Results: Using 5 years of follow-up data, our retrospective analysis demonstrated an association between TS intensity (relapse-free survival [RFS]: risk ratio [RR] = 1.46, P = .01; overall survival [OS]: RR = 1.54, P = .002), Ki-67 (RFS: RR = 0.76, P = .05; OS: RR = 0.62, P = .001), and p53 (RFS: RR = 1.49, P = .01; OS: RR = 1.21, P = .18) for RFS and OS. High TS intensity levels and positive p53 staining were associated with a worse outcome. Tumors containing a high percentage of Ki-67-positive cells enjoyed an improved outcome compared with those patients whose tumors contained relatively few positive cells. An interaction with treatment was not identified for any of the markers. Conclusion: This retrospective investigation demonstrated that TS, Ki-67, and p53 staining each had significant prognostic value for patients with Dukes’ B and C colon carcinoma. However, none of the markers could be used to clearly discern groups of individuals who would be predicted to derive greater or lesser benefit from the use of adjuvant chemotherapy.

Topoisomerase IIα (TopoIIα) Expression in Hodgkin’s Lymphoma (HL): Correlations with Conventional and Biological Markers and Prognostic Significance under Treatment with ABVD or Equivalent Regimens with or without Radiotherapy (RT).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 967-967
Author(s):  
Theodoros P. Vassilakopoulos ◽  
Ipatia A. Doussis-Anagnostopoulou ◽  
Despina Karandrea ◽  
Penelope Korkolopoulou ◽  
Maria K. Angelopoulou ◽  
...  
Keyword(s):  
Lymph Node ◽  
Biological Markers ◽  
Prognostic Score ◽  
Prognostic Significance ◽  
Cytotoxic Agents ◽  
Proliferation Marker ◽  
Prognostic Information ◽  
Ki 67 ◽  
Soluble Cd30 ◽  
And Biological Markers

Abstract TopoIIα is a proliferation marker, as well as a target for cytotoxic agents used in HL, such as doxorubicine, epirubicine, etoposide, and mitoxantrone. High topoIIα expression has been associated with adverse prognosis in some neoplasms, but in the single study of 42 patients with HL, it was a favorable feature. We aimed to evaluate the immunohistochemical expression of topoIIα in patients with HL and investigate its potential association with clinical and biologic features and prognosis in lymph node biopsy sections of 235 patients with HL treated with ABVD or equivalents ± RT. Immunohistochemistry was performed with the streptavidin-biotin-peroxidase method, using the monoclonal antibody KiS1 (DAKO, Denmark,) and DAB as substrate. The proliferation marker Ki-67 was evaluated in 74 patients [MIB1 (YLEM)]. The median age of the patients was 30 years (15–82), 49% were males, 23%, 49%, 17% and 12% had stage I,II,III and IV (47% advanced stages, i.e.IB/IIB/III/IV), 36% B-symptoms, 15% ≥5 involved sites, 38% anemia, 16% leukocytes ≥15x109/l, 7% severe lymphocytopenia, 37% albumin &lt;4 g/dl, and 32% elevated LDH. TopoIIα expression was also evaluated with repect to biological markers, including serum levels of interleukin-10 (sIL-10) and soluble CD30 (sCD30) (n=87), and morphometric parameters reflecting angiogenesis in lymph node sections, such as microvascular density (MVD), total vascular area (TVA), and shape factor (SF) (n=224). The mean±SD percentage of topoIIα+ Hodgkin-Reed-Sternberg (HRS) cells was 63±19% (5%–98%), being 80±17% (17%–99%) for Ki-67+. TopoIIα and Ki-67 were loosely correlated (Spearman’s rho 0.265, p=0.02). Among conventional factors, topoIIα expression correlated with gender only (higher in males, p=0.04), while there was no correlation with sIL-10, sCD30, MVD, TVA or SF. The percentage of topoIIα+ HRS cells was &lt;30% in 15 patients (6%), 30–74% in 149 (63%) and ≥75% in 71 (30%) patients respectively. The 10-year failure free survival (FFS) for these 3 groups was 100%, 85±3% και 67±7% (p=0.002). In multivariate analysis independent adverse prognostic factors for FFS were high topoIIa expression (either as a continuous covariate or at a cutoff of 75%, p=0.002), followed by advanced stage and involvement of ≥5 sites. TopoIIα expression remained an independent prognostic factor when adjusted for the value of the International Prognostic Score (IPS). TopoIIα expression appears to be a ’’primary’’ prognostic variable in HL, because it did not correlate with established conventional and biological markers. Under standard anthracycline-based treatment, high topoIIα expression provided independent prognostic information, which may reflect its role in cell proliferation. Patients with high topoIIα expression might benefit from first-line chemotherapy regimens including another topoIIα inhibitor in addition to doxorubicine, such as etoposide in BEACOPP-escalated.

Prognostic Significance of Serial Determinations of LDH Levels in Primary (De Novo) Myelodysplastic Syndromes.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4828-4828
Author(s):  
Friedrich Wimazal ◽  
Wolfgang R. Sperr ◽  
Anja Vales ◽  
Michael Kundi ◽  
Alexandra Boehm ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lactate Dehydrogenase ◽  
Disease Progression ◽  
Myelodysplastic Syndromes ◽  
Prognostic Value ◽  
De Novo ◽  
Prognostic Significance ◽  
Bone Marrow Examination ◽  
Probability Of Survival

Abstract An increased lactate dehydrogenase (LDH) level at diagnosis is associated with a reduced probability of survival and an enhanced risk of AML development in primary (de novo) myelodysplastic syndromes (MDS). However, so far, little is known about the prognostic value of an increase in LDH levels during the follow up in these patients. We have serially determined LDH levels in 221 patients (102 males, 119 females) with de novo MDS (median age 70 years; FAB-types: RA, n=62; RARS, n=46; RAEB, n=48; RAEBT, n=36; CMML, n=29), and examined the prognostic value of LDH as a follow-up parameter. Confirming previous data, an elevated LDH level at diagnosis was found to be associated with a significantly increased probability of AML evolution and a significantly decreased probability of survival (p&lt;0.05). In the follow up, an increase in LDH (from normal to elevated) was found to be associated with progression of MDS and AML evolution in most cases. Moreover, in those patients who progressed to AML, LDH levels were found to be significantly higher in the two three-months-periods preceding progression compared to the two initial three-months-periods examined (p&lt;0.005). In most patients, the increase in LDH was accompanied or followed by other signs of disease progression, such as the occurrence of thrombocytopenia or an increase in blasts. Together, our data show that LDH can be employed as a prognostic follow-up variable in patients with MDS. In those patients in whom an increase in LDH is noted, a thorough re-evaluation of the progression-status of the disease including a bone marrow examination should be considered.

Growth Differentiation Factor-15 in Patients with Light Chain (AL) Amyloidosis Has Independent Prognostic Significance and Adds Prognostic Information Related to Risk of Early Death and Renal Outcomes

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 306-306 ◽  
Author(s):  
Efstathios Kastritis ◽  
Ioannis Papassotiriou ◽  
Evangelos Terpos ◽  
Athanassios Akalestos ◽  
Erasmia Psimenou ◽  
...  
Keyword(s):  
High Risk ◽  
Prognostic Significance ◽  
Early Death ◽  
Cardiac Biomarkers ◽  
Al Amyloidosis ◽  
Prognostic Information ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Hematological Response ◽  
Independent Prognostic Significance

Abstract Growth differentiation factor-15 (GDF-15) is a member of the TGF-beta family, which is involved in several pathological conditions, including inflammation, cancer, cardiovascular, pulmonary and renal diseases. GDF-15 has prognostic value in patients with cardiovascular disorders and adds prognostic information to conventional prognostic factors, such as NT-proBNP and high-sensitivity troponin (hs-TnT). Cardiac involvement is the most important determinant of prognosis in patients with AL amyloidosis and cardiac biomarkers have major prognostic importance in AL. The aim of the study was to explore the value of GDF-15 in patients with AL amyloidosis. We measured the circulating levels of GDF-15, NT-proBNP and hs-TnT in 77 patients with newly diagnosed AL amyloidosis, before and 3 months post frontline treatment. GDF-15 was measured by a novel pre-commercial immunoassay (Roche Diagnostics). Patients' median age was 68 years; most patients had cardiac (61%) or renal involvement (74%); 61% had NT-proBNP >1284 pg/ml and 46% had hsTnT>54 ng/ml. Median eGFR was 57 ml/min/1.73m2, 52% had eGFR <60 ml/min/1.73m2, while 12% required dialysis at the time of treatment initiation. All patients received primary therapy with bortezomib- (49%) or lenalidomide-based regimens (51%). Median levels of GDF-15 were 3594 pg/ml (range 626-71,475pg/ml); 95% of patients with AL had GDF-15 levels >1200 pg/ml (the upper limit of normal for individuals without cardiovascular disease). GDF-15 correlated with NT-proBNP (r=0.538, p<0.001), hs-TnT (r=0.447, p=0.02) and eGFR (r=-0.570, p<0.001). Patients with GDF-15 levels within the upper quartile (>7575 pg/ml) had a very poor outcome (median overall survival (OS) 3 months) compared to patients with GDF-15 levels below the upper quartile (p=0.01; see the Figure). Among other cardiac markers, hs-TnT >54 ng/ml (12 vs >48 months, p=0.001) and NT-proBNP >1284 pg/ml (11 vs >48 months, p<0.001) were also associated with shorter OS. Higher cut-off levels for NT-proBNP and hs-TnT did not discriminate patients at high risk for early death more accurately. In a multiple logistic regression model which included GDF-15, NT-proBNP and hs-TnT, only GDF-15 in the upper quartile (HR: 8.427, 95% CI 1.73-41.1, p=0.008) was independently predictive of early death at 3 months. Similar results were obtained when these biomarkers were treated as continuous variables. Regarding OS, GDF-15 had independent prognostic significance in a multivariate model that included both NT-proBNP and hs-TnT. We also evaluated changes in the levels of GDF-15, NT-proBNP and hs-TnT in patients who received lenalidomide after 3 months of treatment. In these patients NT-proBNP often increases without obvious deterioration of cardiac function, thus complicating the assessment of cardiac response early, during the course of therapy. GDF-15 levels did not change significantly either in patients with hematological response (p=0.998) or those without hematological response (p=0.774). However, NT-proBNP levels increased substantially both in those with hematological response (p=0.05) and in those without hematological responses (p=0.013). Similarly, hs-TnT levels increased in non-responders (p=0.006) and did not change in patients with hematological response (p=0.251). As GDF-15 reflects heart and renal defects, we further evaluated whether GDF-15 could be associated with the risk of progression to ESRD and need for dialysis. Using ROC analysis, GDF-15 >median was identified to better discriminate patients which had a shorter time to dialysis (29 months vs not reached, p=0.001, see the Figure; with 38% vs. 8% progressing to ESRD, respectively). eGFR< 60 ml/min/m2 was also a strong predictor of ESRD (p=0.004). However, in multivariate analysis which included GDF-15 >median, eGFR <60 ml/min/m2 and proteinuria >5 g/day, only GDF-15 was independently associated with a higher risk of ESRD requiring dialysis (HR: 4.25, 95% CI 1.01-18, p=0.045). In conclusion, GDF-15 is a novel biomarker with prognostic implications for different outcomes in patients with AL; it is associated with a high risk of early death, with OS and also with renal outcome. More importantly GDF-15 adds prognostic information independent of the traditional cardiac biomarkers and thus, its measurement in larger series of patients is recommended. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Genetic Markers Add Significant Prognostic Information to Age and WBC Count in High-Risk, Ph-Negative, B-Precursor Adult Acute Lymphoblastic Leukemia (ALL): Study of 96 Patients Treated According to Risk-Adapted Protocols from the Pethema Group

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3798-3798
Author(s):  
Jordi Ribera ◽  
Lurdes Zamora ◽  
Eulàlia Genescà ◽  
Mireia Morgades ◽  
Pau Montesinos ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Homozygous Deletion ◽  
Advanced Age ◽  
Prognostic Information ◽  
Independent Prognostic Significance ◽  
Multivariable Analyses ◽  
Wbc Count

Abstract Introduction Recurrent Copy Number Alterations (CNA) in genes potentially involved in the pathogenesis of ALL have been identified in genes involved in B-cell development, cell cycle regulation, proliferation, apoptosis and drug resistance. Their independent prognostic significance in adult ALL patients is controversial. The aim of this study was to analyze the prognostic significance of CNA in a series of 96 high-risk, Ph-negative, B-precursor adult ALL patients treated according to risk-adapted protocols from the Spanish PETHEMA Group. Methods MLPA assays (MRC-Holland) were performed for the following genes: IKZF1, IKZF2, IKZF3, EBF1, CDKN2A/B, PAX5, ETV6, BTG1, RB1, hsa-miR-31, X/Y PAR1 region genes (CRLF2, CSF2RA, IL3RA) and 14q32.33 region genes (IGH D, MTA1, KIAA0284). Fragment analysis was made by Genescan in an ABI-3130 sequencer (Applied Biosystems). Data normalization provided a value indicative of the presence or absence of CNA: 0-0.20 homozygous deletion, 0.21-0.70 heterozygous deletion, 0.71-1.30 normal, 1.31-1.70 heterozygous duplication and 1.71-2.20 homozygous duplication. Univariable and multivariable analyses including the most relevant clinical parameters (age, WBC count, phenotype, cytogenetics, CNS involvement) were performed for CR attainment, CR duration and OS. Results The median age [range] of the 96 patients was 39 [15-72] years, 50 (52%) patients were males, with a median WBC count 14.3 x109/L [0.4-388]. Phenotype: early pre-B 19 (20%), common 51 (54%), pre-B 22 (24%), unknown 2 (2%). Cytogenetics: normal 18 (19%), hyperdiploid 5 (5%), hypodiploid 2 (2%), near haploid 6 (6%), t(1;19) 7 (8%), 11q23/MLL 11 (12%), complex 1 (1%), other 27 (29%), no growth 17 (18%). The most frequent CNA deletions involved CDKN2A/B (43/96, 45%), PAX5 (34/94, 36%), IKZF1 (32/95, 34%), hsa-miR-31 (25/96, 26%), 14q32.33 region (18/96, 19%), RB1 (17/96, 18%), EBF1(12/91, 13%) and X/Y PAR (10/96, 10%). The most frequent duplications involved X/Y PAR (11/96, 12%) and 14q32.33 region (7/96, 7%). The CR rate was 83% (80/96), the median (95%CI) of CR duration was 2.7 years (0-5.9) and the median (95%CI) of OS was 2.1 (1.0-3.2), being the median (range) follow-up of the series of 3.8 (0.6-8.0) years. Table 1 shows the results of univariable and multivariable analyses. By multivariable analyses advanced age and EBF1 deletions were significantly associated with less CR rate, WBC count and X/Y PAR duplication were associated with shorter CR duration, and advanced age and CDKN2A/Bdeletion were associated with shorter OS. Conclusions The CNA of EBF1, X/Y PAR1 genes and CDKN2A/Bhave independent prognostic significance in adult patients with high-risk, Ph-negative, B-precursor ALL. This study suggests that these genetic studies should be added to the initial work-up of these patients for more accurate prognostic assessment Supported by grants PI10/01417, RD12-0036-0029 from Instituto Carlos III, 2014 SGR225 (GRE) from Generalitat de Catalunya and a grant from the Spanish Society of Hematology and Hemotherapy (2012). Abstract 3798. Table 1. Results of the univariable and multivariable studies. Variable CR rate CR duration OS P (univ) OR (95%CI) P (univ) HR (95%CI) P (univ) HR (95%CI) Age 0.011 0.93 (0.89 - 0.98) NS - 0.005 1.03 (1.01 - 1.05) WBC NS - <0.001 1.01 (1.00 - 1.01) NS - IKZF1 * NS - 0.048 - NS - EBF1 * 0.025 0.11 (0.02 - 0.54) NS - NS - CDKN2A/B * NS - NS - 0.014 2.32 (1.35 - 4.00) X/Y PAR** NS - 0.013 4.26 (1.64 - 11.09) NS - *Normal versus deleted; ** Normal versus duplicated; NS: not significant Disclosures No relevant conflicts of interest to declare.

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