scholarly journals Clinical and prognostic significance of CD34 expression in bone marrow biopsies in myelodysplastic syndrome

2010 ◽  
Vol 63 (7-8) ◽  
pp. 487-491
Author(s):  
Aleksandar Savic ◽  
Nebojsa Rajic ◽  
Nada Vlaisavljevic ◽  
Vesna Cemerikic-Martinovic ◽  
Stevan Popovic
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Statistical Significance ◽  
Prognostic Significance ◽  
Low Risk ◽  
Control Group ◽  
Bone Marrow Biopsies ◽  
Significant Difference ◽  
Risk Patients ◽  
Cd34 Expression

Introduction. The expression of CD34 antigen is increased in a substantial portion of MDS patients, particularly in high risk patients, which was associated with unfavorable survival in some studies. The aim of this study was to determine the CD34 expression in bone marrow biopsies and its prognostic significance in MDS patients and to analyze it in the context of different clinical, laboratory and prognostic parameters. Material and methods. The study was conducted in 53 MDS patients and 20 controls with normal bone marrow. The CD34 expression was determined by CD34 monoclonal antibody and labelled streptovidin biotin peroxidase method. The positivity was determined by counting the 500 cells and it was expressed as percentage. Results. Among the 53 MDS patients there were 37 males and 16 females with average age of 62. The average CD34 expression in the MDS group was 1.37%, the range being 0-8.8%, and in the control group 0.78%, the range being 0-1.60%. The difference was statistically significant (p<0.05). There was a statistically significant difference in the CD34 expression comparing RA and CMML group and high risk and low risk MDS (p<0.02). The median survival in the patients with the CD34 expression with less than 2% was 22 months, while it was 6 months in the patients with the CD34 expression over 2% (p<0.05). In a multivariate analysis the CD34 expression together with the karyotype and transfusion dependence had a statistical significance (p<0.05). Conclusion. The CD34 expression in bone marrow biopsies is higher in the MDS patients comparing with the controls as well as in high risk comparing with low risk patients. The cutoff 2% seems to have a prognostic significance.

scholarly journals Is there a protective effect with remote ischemic preconditioning on contrast-induced acute renal injury after coronary angiography in low-risk patients?

2018 ◽  
Vol 8 (4) ◽  
pp. 38-38
Author(s):  
Sanaz Soleymani ◽  
Hamid Reza Samimagham ◽  
Mohammad Tamaddondar ◽  
Hossein Farshidi ◽  
Mahmood Khayatian ◽  
...  
Keyword(s):  
Coronary Angiography ◽  
Serum Creatinine ◽  
Protective Effect ◽  
Ischemic Preconditioning ◽  
Low Risk ◽  
Remote Ischemic Preconditioning ◽  
Control Group ◽  
Renal Biomarkers ◽  
Significant Difference ◽  
Risk Patients

Introduction: Contrast-induced acute kidney injury (CIN-AKI) is a serious complication of coronary angiography. Given the weaknesses in the common protective methods used to prevent CIN-AKI, a safe and effective strategy is needed. RIPC has been shown to have a nephroprotective effect. Objectives: We aimed to determine the protective effect of RIPC on CIN-AKI after angiography or percutaneous coronary intervention (PCI) in low-risk patients. Patients and Methods: In our study, 140 low-risk patients who needed angiography or PCI, were assigned to either RIPC or control group. In each group, serum creatinine and urinary neutrophil gelatinaseassociated lipocalin (uNGAL) were measured before the procedure. Serum creatinine was measured daily for 2 days and uNGAL was measured 6 and 24 hours after the procedure. Diagnosis of AKI was, according to the Kidney Disease; Improving Global Outcomes (KDIGO) criteria (2012). Results: The mean age in the remote ischemic preconditioning (RIPC) group was 56.8 ± 11.4 years and 56.3 ± 11.8 years in the control group. We observed no significant difference regarding patient’s characteristic and renal biomarkers at baseline. There was no significant difference in the incidence of AKI (P = 0.116). The uNGAL increased by 36.2% 6-hour after the procedure in patients with AKI, while at the same time, this biomarker increased only by 4.3% in patients without AKI. Conclusion: We concluded that RIPC, with 3 cycles of 5-minute ischemia and 5-minute reperfusion, did not decrease CIN-AKI or altering renal biomarkers course in low-risk patients undergoing coronary angiography or PCI. Additionally, uNGAL, seems to be an appropriate biomarker for early diagnosis of CIN-AKI, 6 hours after contrast media exposure.

Intensified Conditioning for Children Undergoing BMT for First Bone Marrow Relapse of Acute Lymphoblastic Leukaemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5169-5169
Author(s):  
John Moppett ◽  
Jerry Hancock ◽  
Christopher J.C. Knechtli ◽  
Anthony Oakhill ◽  
Nicholas J. Goulden
Keyword(s):  
High Risk ◽  
Treatment Failure ◽  
Risk Group ◽  
Control Group ◽  
Childhood All ◽  
High Risk Patients ◽  
Significant Difference ◽  
Risk Patients ◽  
High Level ◽  
Risk Of Treatment

Abstract BMT remains the treatment of choice for early BM relapse of childhood ALL. We reasoned that further intensification of cytoreductive therapy pre-BMT may further improve survival amongst those with the highest risk of treatment failure, early BM relapse (BFM groups S3/4) and high level MRD pre-BMT. A cohort of 32 patients transplanted at a single institution (1996–1999) provided an historical control. 8 high risk patients transplanted 1999–2000 received additional fludarabine cytoreduction therapy at the time of transplant (FLA group). MRD analysis and time to relapse were used in a subsequent cohort of 22 patients (BMT 2000–2002) to allocate those at highest risk of treatment failure to receive a further cytoreductive block, FLX, pre-BMT. Method. All patients were conditioned with cyclophosphamide (60mg/m2 x2) and TBI (14.4 Gy). UD and haplo-BMT were T-cell depleted with Campth-1M in vitro and Campath-1G day -9 to -5 (Control and FLA group), and by Miltenyi CD34+ cell depletion (FLX group). GvHD prophylaxis - CSA + MTX for matched related, CSA for Campath treated grafts and none for Miltenyi grafts. The FLA group received fludarabine 25mg/m2 from d −12 to d −10. Patients with on treatment relapse (S4) or high level MRD pre-BMT (MRD++) in the FLX group received DaunoXome 100mg/m2, fludarabine 30mg/m2 x 5d and cytosine 2g/m2 x 5d 3 weeks prior to BMT. Patients and donors. Control group: 28 precursor-B ALL 4 T-ALL; donors - 7 matched related, 13 matched unrelated (MUD) and 12 mismatched unrelated (MMUD); 14 S2, 18 S3/4. FLA group: 5 presursor-B ALL and 3 T-ALL; donors - 2 SIB, 4 MUD, 1 MMUD and 2 haplo; all S4. FLX group: 21 precursor-B and 1 T-ALL; donors - 6 SIB, 7 MUD, 5 MMUD and 4 haplo;13 S2, 9 S4. 7 patients received FLX intensified conditioning (6 S4, 5 high level MRD ++). 3 high risk patients violated protocol and did not receive FLX (1 age &lt;1yr on treatment relapse, 2 S2 MRD ++). Results. Considering those in the high-risk S3/4 group, there was no significant difference in OS between the 3 groups. Survival by study and risk group Study S2 S3/4 Overall Control 10/14 (71%) 3/18 (17%) 13/32 (41%) FLA 2/8 (25%) 2/8 (25%) FLX 11/13 (85%) 3/9 (33%) 14/22 (64%) No excess cardiac events were seen. The TRM is higher in the FLX group than in the control. Outcome data Study TRM Relapse Alive Total Control 3 16 13 32 S2 2 2 10 14 S3/4 1 14 3 18 FLA 3 3 6 12 S2 - - - - S3/4 3 3 3 9 FLX 6 2 14 22 S2 2 0 11 13 S3/4 4 2 3 9 Total 12 21 33 66 2 of 7 patients treated with FLX are in CCR, 2 relapsed and 3 died of TRM. The 3 high risk patients in the FLX study, but who did not receive FLX, are also in CCR. Survival in those in the S2 group (late BM relapse) has been good throughout the study period. Conclusion. In this study the addition of intensive pre-BMT conditioning has not improved survival amongst high risk (S3/4 or MRD ++ pre-BMT) relapses. The number of post-BMT relapses has fallen but this is not clearly related to the use of FLX. The use of more haploidentical donors, more immunosupressive BMT regimes and additional cytoreductive chemotherapy may have contributed to the increased TRM seen. Time and site of relapse remain the clearest predictor of outcome. Further novel strategies are required to improve survival for the S4 risk group. The good OS for children receiving BMT in the S2 group should be noted.

Platelet Functions and Risk Prognosis in Myelodysplastic Syndromes,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3806-3806
Author(s):  
Nora V. Butta ◽  
Mónica Martín Salces ◽  
Raquel de Paz ◽  
Elena G. Arias Salgado ◽  
Ihosvany Fernández Bello ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
High Risk ◽  
Myelodysplastic Syndromes ◽  
Surface Expression ◽  
Low Risk ◽  
Control Group ◽  
Platelet Surface ◽  
High Risk Patients ◽  
Fibrinogen Receptor ◽  
Risk Patients

Abstract Abstract 3806 The myelodysplastic syndromes (MDS) are a heterogenous group of clonal stem cell disorders with peripheral cytopenias and increased incidence of leukemic transformation. The prognosis of MDS is determined by several factors, including the presence of specific cytogenetic abnormalities, the percentage of blastoid cells in bone marrow and peripheral blood, the number of affected cell lineages, and transfusion dependency. The most commonly used risk stratification system is the International Prognostic Scoring System (IPSS). This score divides patients into a lower risk subset (low and intermediate-1) and a higher risk subset (intermediate-2 and high). Patients with MDS may have hemorrhagic complications with serious outcomes that are among the major causes of death in this population. These bleeding episodes that are often related to thrombocytopenia also occur in MDS patients with normal platelet count. The aim of this work was to study functional characteristics of platelets in MDS patients and their relationship to risk evaluated as indicated by IPSS. Eighty diagnosed MDS patients risk-stratified according to IPSS were included: 40 with low-risk, 29 with intermediate-1-risk (I-1), 8 with intermediate-2-risk (I-2) and 3 with high-risk. Eighty healthy donors were included as control group. Platelet-related primary haemostasis was evaluated with an automated platelet function analyzer (PFA-100®, Siemens Healthcare Diagnostics). Samples of citrated blood were aspirated under a shear rate of 4,000–5,000/s through a 150-μm aperture cut into a collagen-ADP (COL-ADP) or collagen-epinephrine (COL-EPI) coated membrane. The platelet haemostatic capacity is indicated by the time required for the platelet plug to occlude the aperture (closure time, CT), which is expressed in seconds. Platelet activation was determined through FITC-PAC-1 (a mAb that recognizes activated conformation of fibrinogen receptor) and FITC-P-selectin mAb binding to quiescent and 100 μM TRAP activated platelets by flow cytometry. Surface expression of fibrinogen receptor (αIIb and β3 subunits) was determined by flow cytometry with specific mAbs. Apoptosis was determined by flow cytometry analysis through FITC-annexin V binding to platelet membrane phosphatidylserine (PS) exposed in basal conditions. I-2 and high-risk patients were gathered together in a high-risk group in order to analyze experimental results. Statistical analysis was performed with one-way ANOVA and Tukey test. CTs obtained with COL-EPI and COL-ADP cartridges in controls and low risk patients were similar and significantly shorter than CTs observed in I-1-risk and high-risk MDS patients (p<0.05). Platelets from all MDS patients showed a reduced capability for being activated by 100 μM TRAP. This impairment was more evident in I-1-risk and high-risk patients: PAC-1 binding, in arbitrary units (AU), was 11368±1017 in controls; 7849±789 in low-risk MDS (p<0.05); 4161±591 in I-1-risk MDS (p<0.01 versus control and p<0.05 versus low-risk) and 492±184 in high-risk MDS (p<0.01 versus control and p<0.05 versus low-risk). The platelet surface expression of P-selectin induced by 100 μM TRAP was also reduced: 5102±340 AU in controls, 3318±400 AU in low-risk MDS (p<0.05); 1880 ±197 AU in I-1-risk MDS (p<0.05 versus control and versus low-risk), and 1211±130 AU in high-risk MDS (p<0.05 versus control and versus low-risk). Diminished responses to TRAP were not due to a reduction in surface expression of fibrinogen receptor in platelets from MDS patients. Platelets from MDS patients expressed more PS than controls under basal conditions. Mean fluorescence values for FITC-annexin binding were: 383±16 in controls; 444±21 in low-risk (p<0.05); 575±52 in I-1-risk MDS (p<0.05 versus control and versus low-risk); 611±17 in high-risk MDS (p<0.05 versus control and versus low-risk). Our results indicated that platelets from MDS patients had less ability to be activated and were more apoptotic than control ones. These dysfunctions were more pronounced when the risk of the disease was higher according to IPSS. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Rituximab Maintenance Benefits Less for Follicular Lymphoma Patients with Low Risk of the Follicular Lymphoma International Index

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3544-3544
Author(s):  
Tingyu Wang ◽  
Ru Li ◽  
Rui Lv ◽  
Ying Yu ◽  
Jiawen Chen ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Low Risk ◽  
Control Group ◽  
Intermediate Risk ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
Risk Patients

Abstract Background Follicular lymphoma (FL) is an incurable indolent disease with a heterogeneous course. The Follicular Lymphoma International Prognostic Index (FLIPI) is the most commonly used prognostic system to predict survival. Rituximab-based immunochemotherapy is now the standard choice for the first-line therapy of FL, followed by rituximab maintenance (RM) in patients with response, which prolongs the progression-free survival (PFS). However, the role of RM in different FLIPI risk groups has never been studied as we know. In this study, we aimed to illustrate the effect of RM in FLIPI risk groups. Methods Newly diagnosed FL patients at our center were enrolled in this analysis. All the patients received the rituximab-based chemoimmunotherapy induction regimens. Response assessments were determined according to Lugano's 2014 criteria. Patients who didn't respond to induction were excluded. Categorical variables were compared using Fisher's exact test. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared with the log-rank test. Results From May 2003 to September 2020, 203 newly diagnosed FL were included. 192 patients (95.0%) achieved remission (complete response, CR/partial response, PR) after immunochemotherapy induction, of whom 96 patients continued rituximab maintenance therapies every 3 months for 1-2 years (RM group) (median 7 times，range 4 to 12). 96 patients received no maintenance or fewer than 4 times (control group) (median 0 times, range 0-3). There were no significant differences in baseline characteristics other than the Ann Arbor stage and pathological grade. The RM group patients were more likely to be at low grade (71.8% vs 54.9%, P = 0.042) and advanced stage (90.6% vs 78.7% , P = 0.027) (Table 1). After a median follow-up of 36.4 months (95% confidence interval [CI], 32.2 to 40.6), median OS and PFS were not reached. The 5-year OS rates and PFS rates were 95.1% (95%CI, 90.2%-100%) and 83.0% (95%CI, 75%-91%)(Fig 1). And RM significantly prolonged the PFS, with 5-year PFS rates 92.2% (95%CI, 85.1%-99.3%) and 70.3%(95%CI, 55%-85.6%) (P = 0.0003) (Fig 2). According to FLIPI risk stratification, patients were classified into low-risk, intermediate-risk, and high-risk groups. The 5-year PFS rates were 97.7% (95%CI, 93.2%-100%), 84.7% (95%CI, 70.4%-99%), and 67.8% (95%CI, 49%-86.6%), respectively (Fig 3). For low-risk patients, there was no significant difference in PFS for the RM group vs the control group. However, for both intermediate risk and high-risk patients, PFS was significantly longer in the RM group compared to the control group (P &lt; 0.0001). The PFS rates at 5 years in intermediate-risk patients were 100% and 77.8% (95%CI, 40.8%-92.6%), for the RM group vs control group, high risk 76.4% (95%CI, 54.3%-98.5%), and 54.9% (95%CI, 21.6%-88.2%), respectively (Fig 4). Conclusion Standard rituximab maintenance significantly prolongs progression-free survival in FLIPI intermediate risk and high-risk patients with FL, but not in the FLIPI low risk group. Figure 1 Figure 1. Disclosures Wang: AbbVie: Consultancy; Astellas Pharma, Inc.: Research Funding.

scholarly journals MR-proADM and MR-proANP levels in patients with acute pulmonary embolism

2019 ◽  
Vol 0 (0) ◽  
Author(s):  
Önsel Öner ◽  
Figen Deveci ◽  
Selda Telo ◽  
Mutlu Kuluöztürk ◽  
Mehmet Balin
Keyword(s):  
Pulmonary Embolism ◽  
High Risk ◽  
Mortality Rate ◽  
Hospital Mortality ◽  
Acute Pulmonary Embolism ◽  
Low Risk ◽  
Control Group ◽  
High Risk Patients ◽  
Risk Patients ◽  
The Relationship

Summary Background The aim of this study was to determine levels of Mid-regional Pro-adrenomedullin (MR-proADM) and Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) in patients with acute pulmonary embolism (PE), the relationship between these parameters and the risk classification in addition to determining the relationship between 1- and 3-month mortality. Methods 82 PE patients and 50 healthy control subjects were included in the study. Blood samples for MR-proANP and MR-proADM were obtained from the subjects prior to the treatment. Risk stratification was determined according to sPESI (Simplified Pulmonary Embolism Severity Index). Following these initial measurements, cases with PE were assessed in terms of all causative and PE related mortalities. Results The mean serum MR-proANP and MR-proADM levels in acute PE patients were found to be statistically higher compared to the control group (p < 0.001, p < 0.01; respectively) and statistically significantly higher in high-risk patients than low-risk patients (p < 0.01, p < 0.05; respectively). No statistical difference was determined in high-risk patients in case of sPESI compared to low-risk patients while hospital mortality rates were higher. It was determined that the hospital mortality rate in cases with MR-proANP ≥ 123.30 pmol/L and the total 3-month mortality rate in cases with MR-proADM ≥ 152.2 pg/mL showed a statistically significant increase. Conclusions This study showed that MR-proANP and MR-proADM may be an important biochemical marker for determining high-risk cases and predicting the mortality in PE patients and we believe that these results should be supported by further and extensive studies.

Phase I clinical and laboratory evaluation of topotecan and cytarabine in patients with acute leukemia.

1997 ◽  
Vol 15 (1) ◽  
pp. 44-51 ◽  
Author(s):  
K Seiter ◽  
E J Feldman ◽  
H D Halicka ◽  
F Traganos ◽  
Z Darzynkiewicz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Acute Leukemia ◽  
S Phase ◽  
Low Risk ◽  
Myelogenous Leukemia ◽  
Laboratory Evaluation ◽  
Apoptotic Cells ◽  
High Risk Patients ◽  
Risk Patients

PURPOSE To determine the maximal-tolerated dose (MTD) of topotecan with cytarabine in acute leukemia patients, and to evaluate leukemia cell apoptosis in these patients. PATIENTS AND METHODS Fifty-three patients with acute leukemia not responsive to standard therapy were treated at eight dose levels of topotecan (2.5 mg/m2/d to 7.75 mg/m2/d). Topotecan was given as a 30-minute infusion daily with cytarabine 1 g/m2/d, both for 5 days. Using a flow-cytometric technique, the percent apoptotic cells in blood and bone marrow samples was determined, and the cell cycle distribution of the leukemic cells studied. RESULTS Oropharyngeal mucositis was dose-limiting. The MTD of topotecan was 4.75 mg/m2/d for 5 days in high-risk patients and 7.0 mg/m2/d for 5 days in low-risk patients. The mean percent apoptotic cells in the peripheral blood reached a peak of 18.8%, a median of 48 hours following the first dose of topotecan. Patients with higher S-phase fractions, either before treatment or following cytarabine, were more likely to achieve bone marrow aplasia than those with lower S-phase fractions (P = .01 and P < .05, respectively). Clinical responses were seen in four of 39 patients with acute myelogenous leukemia (AML; of whom 32 had received prior high-dose cytarabine), three of six with acute lymphoblastic leukemia (ALL), and one of eight with chronic myelogenous leukemia in blast phase (CML-BP). CONCLUSION The recommended phase II dose of topotecan with intermediate-dose cytarabine is 4.75 mg/m2/d for high-risk patients and 7.0 mg/m2/d for low-risk patients. The percentage of cells in S phase was important in determining response to treatment.

Should adult medulloblastoma patients at low risk receive adjuvant chemotherapy? Long-term results of a prospective study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2018-2018
Author(s):  
E. Franceschi ◽  
A. Tosoni ◽  
M. Ermani ◽  
V. Blatt ◽  
P. Amistà ◽  
...  
Keyword(s):  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Survival Rates ◽  
Low Risk ◽  
Long Term Results ◽  
High Risk Patients ◽  
Significant Difference ◽  
Risk Patients

2018 Background: Due to the rarity of medulloblastoma (MB) in adults, the few studies available on this condition are retrospective, and the follow-up tends to be short. Furthermore, the different therapeutic strategies used in these patients makes it difficult to assess survival rates and prognostic factors. Methods: Between January 1989 and February 2001, a prospective phase II trial was performed to evaluate the efficacy of treatment for adults with medulloblastoma. Patients were completely staged with a neuroradiological examination of the brain and neuraxis and by CSF cytology, according to Chang’s staging system. Low risk patients received radiotherapy alone, while high risk patients were given 2 cycles of upfront chemotherapy followed by radiotherapy and adjuvant chemotherapy. The results of the preliminary analysis of this study at a median follow-up of 3.7 years are reported elsewhere. The present papers reports on the long- term results of the same trial. Results: After a median follow up of 7.6 years, among a total of 36 enrolled adults with medulloblastoma, overall progression free survival (PFS) and overall survival (OS) at 5 years were 72% (range 59% to 84%) and 75% (62% to 91%), respectively. No difference was found between low and high risk patients in terms of PFS and OS at 5 years: in low-risk patients the 5-year PFS was 80% (range, 59–100%) and the 5-year OS, 80% (range, 58 - 100%); in high-risk patients the 5-year PFS was 69% (range, 54 -89%) and the 5-year OS, 73% (range, 58 - 92%). Conclusions: A long-term follow-up is essential to evaluate the real impact of treatments in adult patients with MB. Since there is no significant difference between low-risk and high-risk patients for PFS and OS, the use of chemotherapy is also questionable in low-risk patients. No significant financial relationships to disclose.

Comparative calcium levels in high exposed and low exposed group of lead based battery workers

2017 ◽  
Vol 4 (3) ◽  
pp. 315-318
Author(s):  
Vishal Babu GN ◽  
Raviraja A ◽  
Deepak KS ◽  
Thuppil Venkatesh
Keyword(s):  
Blood Pressure ◽  
High Risk ◽  
Statistical Significance ◽  
Self Regulation ◽  
Lead Level ◽  
Low Risk ◽  
Risk Exposure ◽  
Zinc Protoporphyrin ◽  
Significant Difference ◽  
Battery Workers

Introduction: A comparative study of calcium and phosphorus was conducted in high exposed and low exposed groups of lead battery workers to study the effect of lead exposure in these groups as there were very few systematic study reports available in the Indian scenario. Materials and Method: Subjects were selected and classified as Group A àcontrols; Group Bà high risk exposure Group Càlow risk exposure. They were evaluated for their blood lead level (BLL), zinc protoporphyrin (ZPP), Hb, Calcium, Phosphorus, Blood pressure, Total Proteins and albumin. Selections of subjects were in accordance to the protocol developed. Results: This study showed that there is statistical significance between high risk and low risk in BLL (p<0.001), ZPP (p<0.001), Hb (p<0.001) and Calcium (p<0.001). There was no significant difference between the two groups in Phosphorus (p=0.280). Other parameters included Blood pressure, Total protein, albumin and Phosphorus had no significant difference. Conclusions: There was significant difference in BLL, ZPP and calcium between the high risk and low risk group. This difference was mainly due to the absence of precautionary principles, absence of proper disposal methods and lack of knowledge among workers about the ill effects of lead. Thus study reveals the need for self-regulation and a government policy.

Diagnosis and Treatment of Essential Thrombocythemia: Assessment of Current Clinical Practice.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1903-1903
Author(s):  
Vivian H Y Lee ◽  
Erica Peterson ◽  
Leslie Zypchen ◽  
Lynda M Foltz
Keyword(s):  
Bone Marrow ◽  
Clinical Practice ◽  
High Risk ◽  
Diagnostic Criteria ◽  
Bone Marrow Biopsy ◽  
Jak2 V617f ◽  
Low Risk ◽  
Cytoreductive Treatment ◽  
Risk Patients ◽  
History Of

Abstract Abstract 1903 Poster Board I-926 Introduction: The discovery of the JAK2 V617F gene mutation has significantly altered the clinical diagnostic approach to the myeloproliferative neoplasms, reflected in the revised 2008 WHO diagnostic criteria. Both the 2001 and 2008 diagnostic criteria for essential thrombocythemia (ET) require a bone marrow biopsy showing megakaryocytic proliferation to make a diagnosis of ET. Published expert opinion based on clinical studies suggests that ET patients > 60 years old or with history of thrombosis should be characterized as high risk and treated with hydroxyurea. It is unclear whether physicians in clinical practice utilize the WHO diagnostic criteria or follow expert treatment recommendations for ET. Methods: We conducted a retrospective chart review of all patients with a clinical diagnosis of ET made by a hematologist who were seen in clinic from 2006 to 2008 at two university teaching hospitals in Vancouver, Canada. Data collected included demographic information, thrombosis history, diagnostic tests performed and treatment administered. Testing for JAK2 V617F became locally available in 2006, so for assessment of diagnostic tests performed, patients were divided into cohorts of diagnosis pre-2006 and 2006–2008. Patients were characterized as high risk if > 60 y or history of thrombosis at the time of diagnosis. All other patients were considered low risk. Results: Diagnostic information was available for 116 patients diagnosed prior to the availability of testing for JAK2 V617F. 65% (75/116) of patients in this cohort had a bone marrow biopsy performed (table 1). 44 patients received a new diagnosis of ET from 2006–2008. Only 48% (21/44) patients in this cohort had a bone marrow biopsy performed, significantly less than in the historical cohort (p = 0.019). 41/44 had JAK2 V617F testing performed: 41% (17/41) were JAK2 V617F negative, 56% (23/41) positive and 1 equivocal. Bone marrow biopsy was performed in 59% (10/17) of JAK2 V617F negative patients and 39% (9/23) of JAK2 V617F positive patients (p = 0.055) (table 1). Bone marrow biopsy was also performed in 1 patient with equivocal JAK2 V617F testing and 1 patient not tested for JAK2 V617F. 170 patients diagnosed with ET were seen in follow up 2006–2008. 64% (109/170) were high risk due to age > 60 y or history of thrombosis. The remaining 36% (61/170) were considered low risk. Hydroxyurea was used preferentially over anagrelide for treatment of ET (table 2). Only 76% of high risk patients were receiving cytoreductive treatment. 23% of low risk patients received cytoreductive treatment. ASA was prescribed to 89% of high risk and 79% of low risk patients. Conclusion: Despite the requirement for a bone marrow biopsy to meet the WHO criteria for ET, hematologists performed a bone marrow biopsy in less than half of patients they diagnosed with ET since 2006. Hematologists performed bone marrow biopsy less frequently after JAK2 V617F testing became available, particularly in JAK2 V617F positive patients. A substantial portion of high risk patients (24%) were receiving no cytoreductive therapy, contrary to expert recommendation. Further study is required to understand the barriers to implementing treatment recommendations in clinical practice. This study highlights the challenges in translating published diagnostic criteria and treatment guidelines into changes in patient care. Disclosures: No relevant conflicts of interest to declare.

Prevalence and Clinical Implications of N-RAS Mutations in Childhood AML – A Report From the Children's Oncology Group.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3115-3115
Author(s):  
Jason N. Berman ◽  
Robert B. Gerbing ◽  
Lillian Sung ◽  
Kristen Miller ◽  
Jessica A. Pollard ◽  
...  
Keyword(s):  
Signal Transduction ◽  
High Risk ◽  
Prognostic Significance ◽  
Low Risk ◽  
Signal Transduction Pathways ◽  
Free Survival ◽  
Ras Mutations ◽  
Significant Difference ◽  
Pediatric Aml ◽  
The Impact

Abstract Abstract 3115 Poster Board III-52 Mutations in the RAS proto-oncogenes are frequent in acute myeloid leukemia (AML) and serve as prototypic Class I lesions, initiating key downstream hyper-proliferative signal transduction pathways. N-RAS mutations (N-RASmut) are common in AML, occurring in 10-20% of adult and pediatric AML patients; however their prognostic significance in both adults and children remains disputed. Due to a frequent association with a normal karyotype, delineating the impact of these mutations on outcome may enable appropriate risk-adapted therapeutic approaches. Here, we report on the incidence and prognostic significance of N-RASmut in a cohort of 825 pediatric AML patients treated on 2 recent co-operative group studies, CCG-2961 and COG AAML03P1. In total, of the 825 children with de novo AML who underwent N-RAS mutational analysis, 86 (10%) were positive. Gender, age, race, presence of hepatosplenomegaly and FAB subtype were comparable between patients with and without N-RASmut. There was no statistically significant difference between those with and without N-RASmut with respect to specific chromosome class. FLT3/Internal tandem duplications (FLT3/ITD) were less common in those with N-RASmut (2% vs. 9%, p=0.03). In contrast, nucleophosmin (NPM) mutations were more common in those with N-RASmut (13% vs. 5%, p=0.02). Overall, N-RASmut showed a significant correlation with low risk AML (CBF, CEBPαa, or NPM, p=0.04) and an inverse relationship with high risk disease (-5/5q- or -7, FLT3/ITD/high allelic ratio, p=0.007). Patients with N-RASmut had similar complete remission (CR) rates following two courses of induction chemotherapy compared with non-mutated patients (79% vs. 79%, p=0.92). Those in CR had a similar relapse rate regardless of the presence of N-RASmut (RR 39% vs. 36%, p=0.97). Five year event free survival (EFS) and overall survival (OS) from study entry were also comparable, however N-RASmut patients demonstrated a marked increase in overall treatment related mortality (TRM) (21% vs. 14%, p=0.03), which was maintained when high and low risk patients were excluded (22% vs. 11%, p=0.05). Evaluation of TRM in CCG-2961 compared with COG AAML03P1 demonstrated that increased TRM in N-RASmut was only seen in patients treated on CCG-2961 and TRM was primarily due to invasive fungal and gram negative infections. Interestingly, for patients treated on CCG-2961, who received interval compressed intensive induction therapy, this increase in TRM correlated with a decrease in both OS and disease free survival from CR. Remission specimens from patients with N-RASmut were negative for the mutation, demonstrating that an increased infectious risk could not be attributed to a host polymorphism. We found N-RASmut did not contribute to increased disease recurrence in pediatric AML. Our findings indicate that N-RAS mutations do not identify a high risk population, however, as such mutations lead to downstream activation of signal transduction pathways, they may identify a target for directed therapy. Disclosures No relevant conflicts of interest to declare.

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