Chronic idiopathic myelofibrosis: prognostic impact of myelofibrosis and clinical parameters on event-free survival in 122 patients who presented in prefibrotic and fibrotic stages

2003 ◽  
Vol 82 (10) ◽  
pp. 605-611 ◽  
Author(s):  
A. Kreft ◽  
M. Wei� ◽  
B. Wiese ◽  
H. Choritz ◽  
T. Buhr ◽  
...  
Blood ◽  
2006 ◽  
Vol 108 (10) ◽  
pp. 3302-3304 ◽  
Author(s):  
Sima Jeha ◽  
Frederick Behm ◽  
Deqing Pei ◽  
John T. Sandlund ◽  
Raul C. Ribeiro ◽  
...  

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


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3482-3482
Author(s):  
Friederike Schneider ◽  
Eva Hoster ◽  
Marietta Rottenkolber ◽  
Stephanie Schneider ◽  
Annika Dufour ◽  
...  

Abstract Background: Prognosis of AML is influenced by different clinical and molecular alterations. We performed a multivariate analysis including five molecular markers NPM1, FLT-ITD, CEBPA, FLT-TKD and MLL-PTD combined with clinical parameters at initial diagnosis to refine risk stratification. Patients and methods: Prognostic impact of clinical and molecular parameters in respect to OS, EFS, RFS and CR was assessed in 803 patients with normal karyotype included in the AMLCG (German AML Cooperative Group) 2000 trial until 01/2006. Patients were randomly assigned to treatment with TAD (thioguanine, conventional-dose AraC, daunorubicin) followed by HAM (high-dose AraC, mitoxantrone) or with the double-induction regimen consisting of two courses of HAM (quotation Buechner JCO 2006). Patient age ranged from 17 to 85 years (median: 60 yrs). 51% of patients were male, 49% female. 81% of patients had de novo AML. Performance status was normal or slightly impaired in the majority of patients (71% ECOG 0/1). Median blood counts at diagnosis were: Hb: 9.2 g/dl (4.2–16.4 g/dl); WBC: 16.0 G/l (0.1–798.2 G/l); platelets: 58 G/l (0.02–643 G/l), LDH: 410 U/l (8–14332 U/l) and bone marrow (BM) blasts: 80% (6–100%). Molecular markers’ mutation status and all mentioned clinical parameters were included in univariate analyses. In multivariate analyses only univariate significant parameters were used. Results: In 560 patients with all five molecular markers analyzed by routine molecular techniques at diagnosis the frequency of mutations were the following: 52.7% NPM1+, 29.3% FLT3-ITD+, 6.1% FLT3-TKD+, 7.5% MLL-PTD+ and 7.5% CEBPA+. The majority of analyzed patients (44.1%) showed one single mutation only. About one quarter of patients displayed either none (27.5%) or two (26.2%) mutations. A minority of 2.1% had 3 mutations, whereas the combination of four or all five molecular alterations was not found. The most frequent single mutation was NPM1 (28.4%), followed by FLT3-ITD (5.4%), CEBPA (4.8%), MLL-PTD (4.6%) and FLT3-TKD (0.9%). The combination of FLT3-ITD and NPM1 was detected in 18.8% of patients. Complete remission (CR) rate was 65.1%. Median overall survival (OS), event-free survival (EFS) and relapse-free survival (RFS) were 19.3, 7.7 and 17.2 months. Multivariate analyses identified the following parameters to have significant impact on prognosis. OS: NPM1, FLT3-ITD, WBC, age (p<0.0001 each) and CEBPA (p=0.003); EFS/RFS: NPM1, FLT3-ITD and age (p<0.0001 each / p<0.0001 each) and LDH (p=0.020 / p=0.040); CR: NPM1 and age (p=0.001 each). Conclusions: Our data show in a large cohort of 560 patients that at least one molecular marker can be identified in 72.5% of patients with NK-AML. The NPM1 mutation and age are the only parameters with an independent impact on all outcome parameters (OS, EFS, RFS, CR). These data provide the basis for a prognostic model in NK-AML that can be used for risk stratification and selection of patients that will benefit from allogeneic stem cell transplantation.


2021 ◽  
Author(s):  
Zohair Selmani ◽  
Chloé Molimard ◽  
Alexis Overs ◽  
Fernando Bazan ◽  
Loic Chaigneau ◽  
...  

Abstract Background: Breast cancers expressing high levels of Ki67 are associated with poor outcomes. To provide individualized patient care, reliability of prognostic and predictive information deriving from Ki67 assessment is essential. Oncotype DX® test was designed for ER+/HER2- early-stage breast cancers to help adjuvant chemotherapy decision by providing a Recurrent Score® (RS®). RS® measures the expression of 21 specific genes from tumor tissue, including Ki67, and aim to predict the benefit of chemotherapy and the risk of distant recurrence. The primary aim of this study was to assess the agreement between Ki67RNA obtained with Oncotype DX® RS® and Ki67IHC. Other objectives were to analyze the association between the event free survival (EFS) and the expression level of Ki67RNA; and association between RS® and Ki67RNA.Methods: In a cohort of 98 patients with early ER+/HER2- breast cancers, we obtained: Recurrence score®, RNA level of Ki67 expression measured when assessing RS® and Ki67 tumor labelling by immunohistochemistry (Ki67IHC). The Ki67RNA was compared to the Ki67IHC by Kappa Cohen test. With a mean follow-up of 57 months, the association between the event free survival (EFS) and Ki67 status was measured using R package survival. Results: This population was essentially composed of no special type tumor (91%), N0 or Nmic (71%), grade 1 (62%), and tumor size pT1c (1-2 cm) (58%). The RS® values were <18 in 38% (n=37), 18-30 in 51% (n=50) and >30 in 11% (n=11) of the patients. A low agreement of 0.24 was found by Cohen’s kappa test between Ki67IHC and Ki67RNA. Moreover, Ki67RNAhigh tumors were significantly associated with the occurrence of events (p=0.02). On the other hand, we did not find any association between Ki67IHC and EFS (p=0.25).Conclusion: We observed of low agreement between expression level of Ki67RNA and Ki67 protein labelling by IHC. Unlike Ki67IHC and independently of the RS®, Ki67RNA could have a prognostic value. It would be interesting to better assess the prognosis and predictive value of Ki67RNA measured by qRT-PCR. The Ki67RNA in medical routine could be a good support in countries where Oncotype DX® is not accessible.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2959-2959
Author(s):  
Yesid Alvarado ◽  
Hagop Kantarjian ◽  
Dushyant Verma ◽  
Gloria Mattiuzzi ◽  
Ahmed Aribi ◽  
...  

Abstract Background: ESA have been reported to effectively improve the hemoglobin (Hb) in pts with CML who develop anemia during the course of therapy with imatinib and other tyrosine kinase inhibitors. Recently, it has been suggested that when ESA were administered to target a Hb ≥12 g/dL, they may promote tumor growth and decreased survival among pts with advanced head and neck cancer receiving radiation therapy, pts with non-small cell lung cancer, and pts with metastatic breast cancer receiving chemotherapy. We thus investigated whether pts with CML who had received ESA during the course of therapy with imatinib had an inferior long-term outcome. Methods: We analyzed the outcome of 565 pts with CML in chronic phase treated with imatinib in our institution (306 previously untreated, 259 post imatinib failure). Results: Based on the Common Terminology Criteria for Adverse Events (CTCAE) V. 3.0 of the National Cancer Institute (NCI), grade 1 anemia occurred in 235 (42%) pts, grade 2 in 180 (32%), grade 3 in 47 (8%), and grade 4 in 12 (2%) pts. A total of 245 (43%) pts received ESA at some point during the course of therapy. The median nadir Hb among pts treated with ESA was 9.4 g/dL [45 (18%) with grade 3–4 anemia] vs 11.2 g/dL [14 (4%) with grade 3–4 anemia] in those not treated with ESA. Treated patients received therapy with variable intermittent doses during a median time of 14 months (mo) range (1–96 mo). The observed increase in Hb with ESA therapy was >3 g/dL in 132 (54%) pts, 2–3 g/dL in 64 (26%), 1-<2 g/dL in 35 (14%), and <1 g/dL in 14 (6%) pts. The median Hb level achieved with ESA was 12.6 g/dL. The table summarizes the 5-year overall survival and event free survival (EFS) among pts treated with ESA and those not treated with ESA: As previously reported (Cortes et al. Cancer2004; 100:2396–402), the presence of anemia itself has a significant adverse effect on outcome in this patient population. The 5-year EFS for pts with anemia grade 3–4 was 56% vs. 79% for those with grade 0–2 (p=0.002). Corresponding figures for 5-yr OS were 82% and 88% (p=0.006). Conclusion: There is no evidence that the use of ESA to manage anemia associated with imatinib therapy in pts with CML in chronic phase adversely affects long term overall survival or event-free survival. INF- failure (%) Frontline Imatinib (%) OS: overall survival, EFS: event free survival (event = loss of complete hematologic response, loss of major cytogenetic response, transformation to accelerated or blast phase or death from any cause), INF: interferon, ESA: erythropoiesis-stimulating agents. ESA use OS EFS OS EFS No 84 75 92 84 Yes 82 68 89 85 P Value 0.59 0.12 0.58 0.68


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2860-2860 ◽  
Author(s):  
Caroline Algrin ◽  
Nathalie Bérenger ◽  
Sylvie Chevret ◽  
Laetitia Vercellino ◽  
Cédric de Bazelaire ◽  
...  

Abstract Abstract 2860 Introduction. Histological lymphoma diagnosis of adult patients with bulky mediastinal mass is either HL or PMBL, two distinct diseases with a specific outcome. PET interpretation is often difficult for mediastinal lymphoma because of the volume of the tumor and the presence of blood pool. No specific criteria for interpretation of interim-PET have yet been defined in this clinical entity. The purpose of this study was to investigate the prognostic value of qualitative and semiquantitative evaluations of interim-PET in mediastinal lymphoma. Methods. We retrospectively included 72 patients with either HL (n=48) or PMBL (n=24), previously untreated, aged under 60 at diagnosis and who underwent at least one interim-PET evaluation. Patients with sub-diaphragmatic or medullar localisations of lymphoma were excluded. All PET scans were reviewed. Qualitative evaluation included global visual evaluation (GVE) (positive or negative) and 5 points-scale (5PS). Semiquantitative evaluation consisted in maximum standardized uptake value (SUVmax) and SUVmax reduction between the baseline PET (PET0) and the evaluation performed after two (PET2) or four (PET4) cycles of chemotherapy. Prognostic impact was evaluated on the event-free survival (EFS), defined as disease progression/first relapse (n=18) or death (n=2). ROC (Receiver Operating Characteristic) curve was used to assess the value of SUVmax reduction in discriminating future deaths or relapses, based on area under the curve (AUC). The “best“ cut-off that provides both the lowest false positive and the lowest false negative rates was computed. Results. Median age was 29 (24 - 35), 60% male. Tumoral mass was more than 7.5 cm in 70% of the patients, and M/T ratio>= 0.35 in 79%. Median SUVmax at baseline, PET2 and PET4 were 12.8 (4.1;33.2), 1.9 (1.7;3.1), and 2.4 (1.7;3.1), respectively. With a median follow-up at 24 months, 2-year event-free survival (EFS) was 67%, without significant difference between HL and PMBL (p=0.98). Except for ECOG performance status in PMBL, neither clinical nor biological feature was predictive for EFS. Using GVE, a negative PET2 (n=36/59) and PET4 (n=24/34), were achieved in 61% and 71%, respectively. GVE and 5PS have a significant negative predictive value (NPV) at PET2 (HR=3.2, 95%CI: 1.2–8.2; p=0.012, and HR=1.9, 95%CI: 1.1–3.3, p=0.01) and at PET4 (HR=13.9, 95%CI: 3.5–55; p=0.0001, and 2.6, 95%CI: 1.5–4.7, p=0.001 respectively), with a 2-year estimated EFS of 69% for PET2-negative patients versus 51% for PET2-positive patients (p=0.012), and of 86% for PET4-negative patients versus 20% for PET4-positive patients (p=0.001). An optimal cut-off of 81% SUVmax reduction from PET0 to PET2 or PET4 yielded a 2-year estimated EFS of 70% in patients with reduction of more than 81%, versus 47% in those with reduction of 81% or less (p=0.004). In the HL subgroup, GVE and SUVmax reduction higher than 81% at PET2 (p=0.0001, p=0.015, respectively) and PET4 (p=0.004, p=0.015, respectively) showed significant prognostic values for EFS. In the PMBL subgroup, neither qualitative nor semiquantitative evaluation at PET2 was predictive for EFS. At PET4, GVE and 5PS were strongly predictive for EFS (p=0.005, p=0.0001). Patients with SUVmax reduction higher than 81% between PET0 and PET4 reached a 67% 2-year EFS, while patients with lower SUVmax reduction had only a 33% 2-year EFS (p=0.13). Conclusion. The cut-off value of SUVmax reduction estimated for predicting EFS with best accuracy in mediastinal lymphoma was 81%. Although the SUV semiquantification helps to reduce the number of false positives, visual global analysis had a significant negative predictive value in interim-PET in mediastinal lymphoma, with a possible very early prediction, as early as PET2 in HL, and a better prediction at PET4 than PET2 in PMBL. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 8 (B) ◽  
pp. 623-630
Author(s):  
Yasser H. ElNahass ◽  
Magda M. Assem ◽  
Magdy M. Saber ◽  
Sarah K. Abdalla ◽  
Hossam K. Mahmoud ◽  
...  

BACKGROUND: Emergence of additional chromosomal abnormalities (ACAs) in chronic myeloid leukemia (CML) is associated with disease progression to advanced phases and reflects the genetic instability of CML. AIM: Is to evaluate the frequency of ACAs in chronic phase (CP) and advanced disease (AP) CML patients and study their impact on patient’s outcome, overall survival (OS) and event-free survival (EFS). RESULTS: The studied group (n = 73) included 31 males (43%) and 42 females (57%). Median age of patients at diagnosis was 37 years (17–76). Median TLC was 208×109/L (2.1–784.2), median Hb was 9.4 g/dL (5.7–13), and median platelets count was 290.5×109/L (13–1271). We identified 32 patients (44%) with ACAs. ACAs emergence was significantly associated with advanced phases of CML (13/21, 62%) compared to CP (19/52, 36%) (p = 0.048). ACAs were associated with lower median OS and EFS in CP compared to AP (38 vs. 120 ms) and (58.3 vs. 77 ms) (p = 0.026 and p = 0.065, respectively). Early molecular responders (6/17, 35%) at 3 months, and 6 months (10/26, 38%) developed ACAs less than nonoptimal responders. Disease phase, hepatomegaly and bone marrow eosinophilia were significant predictors of OS (p < 0.001, p = 0.02, p = 0.04, respectively). CONCLUSION: Early identification of ACAs in Ph+ metaphases at diagnosis and during therapy predicts CML outcome. ACAs emergence occurred at a higher frequency and at a younger age in our CML patients and are related to inferior EFS and OS.


2015 ◽  
Vol 33 (12) ◽  
pp. 1371-1378 ◽  
Author(s):  
Tilmann Bochtler ◽  
Ute Hegenbart ◽  
Christina Kunz ◽  
Martin Granzow ◽  
Axel Benner ◽  
...  

Purpose Bortezomib has become a cornerstone in the treatment of AL amyloidosis. In this study, we addressed the prognostic impact of cytogenetic aberrations for bortezomib-treated patients. Patients and Methods We analyzed a consecutive series of 101 patients with AL amyloidosis treated with bortezomib-dexamethasone as first-line treatment by interphase fluorescence in situ hybridization (iFISH). Patients were ineligible for high-dose chemotherapy, which would put them at risk for cardiac or renal failure, and thus represented a poor-risk group. Results Presence of t(11;14), versus its absence, was associated with inferior hematologic event-free survival (median, 3.4 v 8.8 months, respectively; P = .002), overall survival (median, 8.7 v 40.7 months, respectively; P = .05), and remission rate (≥ very good partial remission; 23% v 47%, respectively; P = .02). In multivariable Cox regression models incorporating established hematologic and clinical risk factors, t(11;14) was an independent adverse prognostic marker for hematologic event-free survival (hazard ratio, 2.94; 95% CI, 1.37 to 6.25; P = .006) and overall survival (hazard ratio, 3.13; 95% CI, 1.16 to 8.33; P = .03), but not for remission (≥ very good partial remission). Markedly, the multiple myeloma high-risk iFISH aberrations t(4;14), t(14;16), del(17p), and gain of 1q21 conferred no adverse prognosis in this bortezomib-dexamethasone–treated group. After backward variable selection, the final multivariable model was validated in a consecutive series of 32 patients treated with bortezomib, dexamethasone, and cyclophosphamide. Conclusion iFISH results are important independent prognostic factors in AL amyloidosis. In contrast to our recently published results with melphalan and dexamethasone standard therapy, bortezomib is less beneficial to patients harboring t(11;14), whereas it effectively alleviates the poor prognosis inherent to high-risk aberrations. Given the discrepant response to different treatment modalities, iFISH may help to guide therapeutic choices in these poor-risk patients requiring rapid hematologic response.


2000 ◽  
Vol 18 (7) ◽  
pp. 1525-1532 ◽  
Author(s):  
Michael H. Woo ◽  
Lawrence J. Hak ◽  
Michael C. Storm ◽  
John T. Sandlund ◽  
Raul C. Ribeiro ◽  
...  

PURPOSE: Development of antibodies and hypersensitivity to asparaginase are common and may attenuate asparaginase effect. Our aim was to determine the relationship between antiasparaginase antibodies or hypersensitivity reactions and event-free survival (EFS). PATIENTS AND METHODS: One hundred fifty-four children with acute lymphoblastic leukemia received Escherichia coli asparaginase 10,000 IU/m2 intramuscularly three times weekly for nine doses during multiagent induction and reinduction phases and for seven monthly doses during continuation treatment. Erwinia asparaginase was used in case of clinical hypersensitivity to E coli but not for subclinical development of antibodies. Plasma antiasparaginase antibody concentrations were measured on day 29 of induction in 152 patients. RESULTS: Antibodies were detectable in 54 patients (35.5%), of whom 30 (55.6%) exhibited hypersensitivity to asparaginase. Of the 98 patients who had no detectable antibodies, 18 (18.4%) had allergic reactions. Patients with antibodies were more likely to have a reaction than those without antibodies (P < .001). Among the 50 patients who experienced allergic reactions (including two for whom antibodies were not measured), 36 (72.0%) were subsequently given Erwinia asparaginase; seven (19.4%) reacted to this preparation. EFS did not differ among patients who did and did not have antibodies (P = .54), with 4-year EFS (± 1 SE) of 83% ± 6% and 76% ± 5%, respectively. Similarly, EFS did not differ among patients who did and did not develop allergic reactions (P = .68), with 4-year estimates of 82% ± 6% and 78% ± 5%, respectively. CONCLUSION: In this setting, in which most patients with allergy were switched to another preparation, there was no adverse prognostic impact of clinical or subclinical allergy to asparaginase.


Blood ◽  
2006 ◽  
Vol 107 (10) ◽  
pp. 3847-3853 ◽  
Author(s):  
Ulrike Bacher ◽  
Torsten Haferlach ◽  
Claudia Schoch ◽  
Wolfgang Kern ◽  
Susanne Schnittger

We analyzed 2502 patients with acute myeloid leukemia at diagnosis for NRAS mutations around the hot spots at codons 12, 13, and 61 and correlated the results to cytomorphology, cytogenetics, other molecular markers, and prognostic relevance of these mutations. Two hundred fifty-seven (10.3%) of 2502 patients had NRAS mutations (NRASmut). Most mutations (112 of 257; 43.6%) were found at codon 12, mostly resulting in changes from glycine to asparagine. The history of AML did not differ significantly in association with NRAS mutations. The subgroups with inv(16)/t(16;16) and inv(3)/t(3;3) showed a significantly higher frequency of NRASmut (50 of 133, 37.6% [P < .001], and 11 of 41, 26.8% [P = .004], respectively) than the total cohort. In addition, in these 2 subgroups, mutations of codon 61 were significantly overrepresented (both P < .001). In contrast, NRAS mutations were significantly underrepresented in t(15;17) (2 of 102; 2%; P = .005) in the subgroup with MLL/11q23 rearrangements (3 of 77; 3.9%; P = .061) and in the complex aberrant karyotype (4 of 258; 1.6%; P < .001). Overall, we did not find a significant prognostic impact of NRASmut for overall survival, event-free survival, and disease-free survival. However, there was a trend to better survival in most subgroups, especially when other molecular markers (FLT3-LM, MLL-PTD, and NPM) were taken into account.


2018 ◽  
Vol 46 (9) ◽  
pp. 3675-3683 ◽  
Author(s):  
JunYu Zhang ◽  
WeiE Liu ◽  
Jing Du ◽  
YangJin Jin ◽  
MinLei Zhao ◽  
...  

Objective The prognostic effect of miR-196a/b expression in adult patients with leukaemia remains unclear. This study aimed to determine whether miR-196a/b expression can serve as a prognostic factor for patients with acute myeloid leukaemia. Methods We enrolled 124 patients with acute myeloid leukaemia. We measured miR-196a/b expression by real-time reverse transcription-polymerase chain reaction. We classified patients into high and low expression groups based on the median expression value. Cox regression analyses were carried out to assess the prognostic significance of miR-196a/b expression in the context of well-established predictors. Results Patients with high miR-196a/b expression were older in age, and had higher white blood cell and platelet counts than did patients with low miR-196a/b expression. Patients with high miR-196a/b expression were associated with the French–American–British classification M5 subtype and with the presence of nucleophosmin and FLT3 internal tandem duplication mutations, but were not associated with the favourable karyotype risk subgroup. Moreover, patients with high miR-196a/b expression had a shorter event-free survival rate compared with those with low miR-196a/b expression in univariate and multivariate analyses. Conclusion High miR-196a/b expression is associated with poor event-free survival.


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