Prognostic Impact of FLT3 Mutation Load in NPM1 Mutated AML.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 826-826 ◽  
Author(s):  
Susanne Schnittger ◽  
Tamara Weiss ◽  
Claudia Haferlach ◽  
Wolfgang Kern ◽  
Torsten Haferlach

Abstract Abstract 826 According to the new WHO classification NPM1 mutated AML is defined as a provisional entity. Those AML without FLT3-ITD (also referred to as FLT3-LM) are regarded as prognostically favorable whereas those with detectable FLT3-ITD in addition are defined as unfavorable. However, some previous studies not taking NPM1 status into account have shown that the prognostic impact of the FLT3 mutation is highly dependent on the load of the mutation. To evaluate a possible impact of FLT3 load in NPM1 mutated AML we have quantified the FLT3 load in 641 NPM1 mutated AML.The cohort was composed of 341 females and 300 males with a median age of 65.2 years (range 17.8-88 years). The NPM1 mutation was detected by melting curve analysis whereas the FLT3-ITD was quantitatively analysed by fragment analysis (Gene Scan, 3130 sequence detection system, ABI). The FLT3-ITD load was quantified as the ratio of the mutation compared to the wildtype allele. All ratios >1 are indicative for allelic loss of the wildtype allele (wt). Overall in 242/641 (37.8%) of the NPM1 mutated AML an FLT3- ITD was detected. The length of the mutation (LM) varied between 9 and 579 bp (median: 51 bp). The ratio of FLT3- ITD was in the range between 0.016 and 44.85 (median: 0.565). Using Cox regression analysis we demonstrated that increasing FLT3-ITD/wt ratio has a significantly unfavorable influence on EFS (p=0.028) . At next, for Kaplan Meier analysis 3 groups were defined according to FLT3-ITD/wt ratio: 1) only FLT3wt (n=398); 2) FLT3-ITD/wt ratio ≤1 (n=189) and 3) FLT3-ITD/wt ratio ≥1 (n=53). It was shown that the FLT3wt group had the best median EFS of 230 days compared to 203 day in group 2 (p=0.032) and only 86 days in group 3 (p<0.001). In a next step the FLT3 ratios were further subdivided into smaller groups 1) only WT (n=398), 2) ratio <0.25 (n=63) 3) ratio > 0.25 but <0.5 (n=44); 4) ratio ≥0.5 but <1 (n=82) 5) ratio ≥1 (n=53). Although the median EFS was continuously decreasing from group 1 to 5 (230 vs 200 vs 198 vs 96 vs 86 days, respectively) a significant difference compared to the FLT3wt group was only detected for group 4 (p=0.014) and group 5 (p<0.001). This analysis demonstrated that only FLT3-ITD/wt ratios ≥0.5 led to inferior outcome in NPM1 mutated AML. The impact of the FLT3/wt ratio on overall survival (OS) could also be detected only for group 5 with a median OS of 142 days compared to 293 days in the FLT3-WT group (p<0.002) and for group 4 (median 147 days) (p=0.033), respectively. In addition other known prognostic factors were analysed for EFS: karyotype (p=0.788; n.s.), gender (p=0.042; better for female) age (p<0.001), WBC (p<0.001), FLT3-status irrespective of ratio (p=0.001) and FLT3-ITD length (p=0.002). In a multivariate analysis only age (p<0.001), WBC (p=0.001) and FLT3-ITD/wt ratio (p=0.042) came out to be independent prognostic factors in NPM1 mutated AML. For OS ratios ≥0.5 came out to be more important than FLT3 status per se (0=0.044 vs. p=0.359). Subsequently ratios '0.5 were multivariately tested against age and WBC. All three parameters came out to be of independent significance for OS (p<0.001, p=0.001, and p=0.008, respectively). In conclusion, this study clearly demonstrates that not FLT3-ITD status per se is predictive for survival in NPM1 mutated AML but ratios of FLT3-ITD load has to be taken into account. Only ratios of ≥0.5 demonstrated to have a significant impact on prognosis in NPM1 mutated AML. This data has enormous implication on clinical decision making in AML including the option of allogeneic transplantation in first CR. Disclosures: Schnittger: MLL Munich Leukemia Lab: Equity Ownership. Weiss:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Lab: Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership.

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3207-3207
Author(s):  
Sabine Jeromin ◽  
Claudia Haferlach ◽  
Frank Dicker ◽  
Manja Meggendorfer ◽  
Torsten Haferlach ◽  
...  

Abstract Background: In chronic lymphocytic leukemia (CLL) one of the strongest prognostic factors is IGHV mutational status. Infrequently, patients present not only with a single IGHV rearrangement but with multiple productive rearrangements. In about 2% of all CLL patients analyzed on cDNA level multiple rearrangements display the same mutational status and are categorized accordingly following ERIC recommendations. In another 1% rearrangements with discordant IGHV mutational status are detected and preclude a definite risk assignment. Only limited data exist on these rare subgroups. Aim: To characterize treatment-naive CLL patients with multiple productive IGHV rearrangements and determine the impact on prognosis. Patients and Methods: Out of 8,016 treatment-naive CLL patients between 2005 and 2015 and with data on IGHV mutational status we identified 204 (3%) with multiple productive rearrangements. IGHV mutational status was analyzed on cDNA and in all cases according to ERIC recommendations. IGHV mutated status (M) was defined by sequence identity <98% and unmutated status (U) by ≥98%. Chromosome banding analysis was available in 102 cases and interphase FISH with probes for 17p13, 13q14, 11q22 and centromeric region of chromosome 12 in 191. Male:female ratio was 3:1 and median age 68 years (range: 38-89). Additionally, data on SF3B1 and TP53 mutations was present in all cases. Follow-up data on time to first treatment (TTT) and overall survival (OS) was available in 105 cases with a median follow-up of 4 years. For statistical comparison we used a cohort of 1,262 untreated CLL patients with single IGHV rearrangement (median age: 67 years; range: 30-91, median follow-up: 6 years). Results: Out of 204 patients with multiple, productive rearrangements 199 (98%) presented with two and 5 patients (2%) with three IGHV rearrangements. Concordant IGHV mutated status (MM) was present in 120 cases (59%), whereas concordant unmutated status (UU) was seen in 34 patients (17%). In 50 cases (25%) a mixed IGHV status (UM) was detected. We analyzed frequencies of complex karyotype by CBA, biclonality according to immunophenotype (concurrent kappa restricted and lambda restricted subpopulations) and/or CBA, TP53 disruption (TP53mut and/or del(17p)), SF3B1mut, del(11q), trisomy 12, and del(13q). Overall, a higher frequency of biclonality was detected in patients with multiple vs. single IGHV rearrangements (16% vs. 1%, p<0.001). However, association to neither MM, UU nor UM existed. MM presented with molecular and cytogenetic characteristics similar to M. Correspondingly, UU showed similar frequencies of mutations and aberrations to U, except for higher frequency of trisomy 12 in UU vs. U (42% vs. 19%, p=0.003). Interestingly, UM presented with characteristics similar to U and UU. UM was associated with TP53 disruption vs. M (16% vs. 5%, p=0.003) and vs. MM (5%, p=0.035) as well as with SF3B1mut vs. M (16% vs. 5%, p=0.008). Furthermore, UM cases showed high frequency of del(11q) vs. M (29% vs. 3%, p<0.001) and vs. MM (1%, p<0.001) and less frequently del(13q) sole vs. M (41% vs. 60%, p=0.011) and MM (41% vs. 69%, p=0.001). No significantly differences in TTT were observed between MM and M (median: 13 vs. 14 years) and between UU and U (6 vs. 4 years), respectively. However, the difference between MM vs. UU (p=0.022) and M vs. U (p<0.001) was significant. The UM subgroup presented with a TTT (median: 4 years) similar to U and UU, whereas it was significantly shorter vs. M (p=0.003) and MM (p=0.006), respectively. A similar picture emerged for survival. 5-year OS of MM was not different vs. M (94% vs. 90%) but vs. U (78%, p=0.001). The statistical analysis of OS in UU was hampered by low case numbers. UM presented again with similar 5-year OS vs. U (81% vs. 78%, n.s.) and significantly worse OS vs. M (90%, p=0.049) and vs. MM (94%, p=0.014). Conclusions: (1) Patients with multiple productive IGHV rearrangements and concordant IGHV status show similar prognosis and characteristics to patients with single rearrangement with the respective IGHV status. (2) Cases with mixed IGHV status show similar prognosis to patients with IGHV unmutated status and accordingly are characterized by high frequencies of adverse prognostic factors like TP53 disruption, SF3B1mut, and del(11q), whereas del(13q) sole is less frequent. Disclosures Jeromin: MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Dicker:Munich Leukemia Laboratory: Employment. Meggendorfer:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.


Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2367
Author(s):  
Lavinia Elena Chiti ◽  
Roberta Ferrari ◽  
Paola Roccabianca ◽  
Patrizia Boracchi ◽  
Francesco Godizzi ◽  
...  

Adjuvant treatments are recommended in dogs with incompletely excised cutaneous soft-tissue sarcoma (STS) to reduce the risk of local recurrence (LR), although guidelines are lacking on how to manage clean but close margins (CbCM). This retrospective study investigates the impact of CbCM on LR of canine STS. Ninety-eight surgically excised canine STS at first presentation were included. Tissue samples were routinely trimmed and analyzed. Cumulative incidence of LR was estimated for each category of margins (tumor-free, infiltrated, CbCM), and included CbCM in the tumor-free and infiltrated category, respectively. The prognostic impact on LR was then adjusted for relevant prognostic factors. Cumulative incidence of LR at three years differed significantly between the three categories (p = 0.016), and was estimated to be 42% with infiltrated margins, 23% with CbCM, 7% with tumor-free margins. Both when CbCM were grouped with infiltrated margins (p = 0.033; HR = 5.05), and when CbCM were grouped with tumor-free margins (p = 0.011; HR = 3.13), a significant difference between groups was found. STS excised with infiltrated margins had the greatest risk of LR. The rate of LR with CbCm was greater than recurrence rate of tumor-free margins. The category CbCM may be considered as a separate prognostic category.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1635-1635
Author(s):  
Fredrik Ellin ◽  
Jenny Landström ◽  
Mats Jerkeman ◽  
Thomas Relander

Abstract Introduction Comorbidity has repeatedly been established to have a negative impact on the survival of patients with cancer, but it has not been investigated in peripheral T-cell lymphomas (PTCLs). The impact of comorbidity depends on the prognosis of the malignancy, and because PTCLs are aggressive diseases that generally respond less well to treatment compared to aggressive B-cell lymphomas, we aimed to investigate how comorbidities affect outcome in a large population-based cohort of PTCL patients. Materials and methods Through the Swedish Lymphoma Registry all patients diagnosed with T-cell lymphomas between 2000 and 2009 were identified. After informed consent, data on comorbidity at the time of diagnosis was collected from the patient records and classified according to the Charlson Comorbidity Index (CCI). All cases of diabetes mellitus were awarded 1 CCI point because complications to diabetes mellitus could not reliably be evaluated from available medical records. Non-melanoma skin tumors were not recorded as malignancies. Results In total 755 patients with non-cutaneous, non-leukemic PTCL were identified. Comorbidity data was available for 676 of the 755 patients (90%). Four-hundred twenty-five (56%) of the patients had no co-morbidity, while 267 (35%) had CCI scores between 1 and 7 points. The 5-year overall survival (OS) rates for patients with CCI 0, 1 and ≥2 were 41%, 23% and 12 % respectively. There was no significant difference in survival of patients with CCI 2 or higher. Individual CCI factors with prognostic impact on OS in univariable analysis were previous malignancy (Hazard ratio [HR] 1.68, p=0.001), active malignancy (HR 2.04, p<0.001), renal failure (HR 5.56, p<0.001), liver disease (HR 2.66, p=0.018), peptic ulcer (HR 1.82, p=0.020), diabetes mellitus (HR 1.85, p<0.001), myocardial infarction (HR 1.62, p=0.001), congestive heart failure (HR 2.17, p<0.001), stroke (HR 1.74, p=0.005) and autoimmune disease (HR 1.50, p=0.034). The cause of death was known in 451 patients and lymphoma related death was more common among patients with CCI 0 (82%) than with CCI 1 (69%) or CCI ≥2 (65%) (p=0.008 and p=0.001 respectively). In multivariable analysis, comorbidity was an independent negative factor for both OS and progression-free survival (PFS). Among patients receiving chemotherapy (N=551) the presence of comorbidity together with age, male gender, stage III-IV, LDH>ULN, extranodal involvement >1, WHO PS >1, gastrointestinal involvement and NK/T-cell, nasal type lymphoma were independent risk factors for OS with HR 1.46 for CCI 1 (p=0.004) and HR 1.76 for CCI ≥2 (p<0.001). The impact of comorbidity was age dependent as patients above the median age of the cohort (>67 years) had inferior OS (HR 1.64, p=0.006) and PFS (HR1.51, p=0.027) only if they presented with CCI ≥2. Up-front autologous stem cell transplantation (auto-SCT) was planned in 154 out of 755 patients. Comorbidity data was available in 149, and auto-SCT as part of first-line therapy was performed in 101 (68%) of these patients. In this group comorbidities were uncommon but diabetes mellitus was most frequent (n=10) with an impact on OS (HR 3.31, p=0.01, n=10) and PFS (HR 2.86, p=0.003) and was an independent risk factor in multivariable analysis (data not shown). Using the CCI, instead of individual comorbidities, independent prognostic factors for OS were age (HR 1.028, p=0.017), skin involvement (HR 2.29, p=0.016) and CCI (CCI 1 HR 1.94, p=0.019 and CCI ≥2 HR 3.67, p=0.004). For PFS, skin involvement (HR 3.70, p<0.001) and CCI (CCI 1 HR 1.80, p=0.039 and CCI ≥2 HR 3.56, p=0.012) but not age, were independent adverse prognostic factors, while ALKneg ALCL histologic subtype was associated with favorable PFS (HR 0.49, p=0.028). There was no difference in the proportion of patients with planned auto-SCT actually performed between the CCI groups, although there were only 5 patients with CCI ≥2 in this group. Conclusions Our data demonstrates that even though PTCLs are aggressive diseases with a substantial proportion of cases responding poorly to chemotherapy, comorbidity has an important impact on outcome, not the least in patients planned for up-front auto-SCT. Despite medical advances in the treatment of several of the conditions included in the score, the CCI still seems to be a useful tool to capture comorbidity. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Liu ◽  
Jing Li ◽  
Wanyu Zhang ◽  
Yihong Guo

AbstractOestradiol, an important hormone in follicular development and endometrial receptivity, is closely related to clinical outcomes of fresh in vitro fertilization-embryo transfer (IVF-ET) cycles. A supraphysiologic E2 level is inevitable during controlled ovarian hyper-stimulation (COH), and its effect on the outcome of IVF-ET is controversial. The aim of this retrospective study is to evaluate the association between elevated serum oestradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and neonatal birthweight after IVF-ET cycles. The data of 3659 infertile patients with fresh IVF-ET cycles were analysed retrospectively between August 2009 and February 2017 in First Hospital of Zhengzhou University. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E2 levels ≤ 1000 pg/mL, n = 230), group 2 (serum E2 levels between 1001 and 2000 pg/mL, n = 524), group 3 (serum E2 levels between 2001 and 3000 pg/mL, n = 783), group 4 (serum E2 levels between 3001 and 4000 pg/mL, n = 721), group 5 (serum E2 levels between 4001 and 5000 pg/mL, n = 548 ), and group 6 (serum E2 levels > 5000 pg/mL, n = 852). Univariate linear regression was used to evaluate the independent correlation between each factor and outcome index. Multiple logistic regression was used to adjust for confounding factors. The LBW rates were as follows: 3.0% (group 1), 2.9% (group 2), 1.9% (group 3), 2.9% (group 4), 2.9% (group 5), and 2.0% (group 6) (P = 0.629), respectively. There were no statistically significant differences in the incidences of neonatal LBW among the six groups. We did not detect an association between peak serum E2 level during ovarian stimulation and neonatal birthweight after IVF-ET. The results of this retrospective cohort study showed that serum E2 peak levels during ovarian stimulation were not associated with birth weight during IVF cycles. In addition, no association was found between higher E2 levels and increased LBW risk. Our observations suggest that the hyper-oestrogenic milieu during COS does not seem to have adverse effects on the birthweight of offspring after IVF. Although this study provides some reference, the obstetric-related factors were not included due to historical reasons. The impact of the high estrogen environment during COS on the birth weight of IVF offspring still needs future research.


2017 ◽  
Vol 21 (03) ◽  
pp. 189-197 ◽  
Author(s):  
Vlad Dionisie ◽  
Simona Clichici ◽  
Rodica M. Ion ◽  
Oana O. Danila ◽  
Remus Moldovan ◽  
...  

Several studies have shown that some anti-oxidant natural compounds in combination with photodynamic therapy (PDT) can enhance the effectiveness of treatment. The aim of this study is to evaluate the effect of silymarin (SIL) in combination with 5,10,15,20-tetra-sulphonato-phenyl-porphyrin (TSPP) based photodynamic therapy, on experimental tumors. 30 Wistar rats with Walker carcinosarcoma, were divided into 6 groups: group 0 (control) — control, untreated group; group 1 (TSPP) — one dose of TSPP; group 2 (SIL) — silymarin; group 3 (PDT) — TSPP and irradiation 24 h after; group 4 (SIL[Formula: see text]PDT) — silymarin, TSPP and irradiation 24 h after; group 5 (SIL[Formula: see text]IR) and group 6 (IR) — irradiation and in addition, group 5 received SIL. Silymarin administered before photodynamic therapy decreased the lipid peroxidation ([Formula: see text] < 0.05) and modulated the antioxidant defense in tumor treated with PDT and silymarin suggesting that silymarin administration along with photodynamic therapy has an anti-oxidant effect. The caspase — 8 level and -3 activity increased in PDT and PDT [Formula: see text] SIL groups compared to the control; between the two groups there was a significant difference in term of apoptosis in favor to PDT. In conclusion, silymarin administration inhibited the reactive oxygen species generation and reduced the tumoral cells’ apoptosis, suggesting that natural compound administered before photodynamic therapy did not improve the therapy’s effect.


Author(s):  
TAOPHEEQ MUSTAPHA ◽  
VARIJA BHOGIREDDY ◽  
HARTMAN MADU ◽  
ADU BOACHIE ◽  
ABDUL OSENI ◽  
...  

BACKGROUND: Heart failure (HF) and Chronic kidney disease (CKD) are major public health problems that often co-exist with a resultant high mortality and morbidity. Most of the studies evaluating their reciprocal prognostic impact have focused on mortality in majority populations. There is limited literature on the impact of CKD on HF morbidities in ethnic minorities. AIMS: Our study seeks to compare HF outcomes in patients with or without CKD in an African-American predominant cohort. METHODS: We obtained data from the NGH at Meharry Heart Failure Cohort; a comprehensive retrospective HF database comprised of patient care data (HF admissions, non-HF admissions, and emergency room visits) were assessed from January 2006 to December 2008. The study group consist of 306 subjects with a mean age of 65±15 years. 81% were African-American (AA), 19% Caucasian and 48.5% are females. Following the NKF KDOQI guidelines, 5 stages of CKD were outlined based on GFR. RESULTS: The overall prevalence of CKD in this population is 54.2%. CKD stage 1 was most prevalent with 45.8%, prevalence for stages 2-5 are 21.6%, 18.3%, 9.5% and 4.9% respectively. The comparison of the mean of ER visits, non HF hospitalizations and HF hospitalizations between normal and CKD patients was done using independent t-test and showed no significant difference in the mean number of ER visits (p=0.564), or HF hospitalizations(p=0.235). However, there is a statistically significant difference in the mean number of non -HF hospitalizations between normal and CKD patients (p=0.031). CONCLUSION: This study shows that the prevalence of CKD in this minority -predominant HF cohort is similar to prior studies in majority populations. However, only the non-HF hospitalizations were significantly increased in the CKD group. Future prospective studies will be needed to define the implications of this in the management of HF patients with CKD.


2020 ◽  
Vol 33 (8) ◽  
pp. 726-733
Author(s):  
Francesca Coccina ◽  
Anna M Pierdomenico ◽  
Chiara Cuccurullo ◽  
Jacopo Pizzicannella ◽  
Rosalinda Madonna ◽  
...  

Abstract BACKGROUND Masked uncontrolled hypertension (MUCH), that is, nonhypertensive clinic but high out-of-office blood pressure (BP) in treated patients is at increased cardiovascular risk than controlled hypertension (CH), that is, nonhypertensive clinic and out-of-office BP. Using ambulatory BP, MUCH can be defined as daytime and/or nighttime and/or 24-hour BP above thresholds. It is unclear whether different definitions of MUCH have similar prognostic information. This study assessed the prognostic value of MUCH defined by different ambulatory BP criteria. METHODS Cardiovascular events were evaluated in 738 treated hypertensive patients with nonhypertensive clinic BP. Among them, participants were classified as having CH or daytime MUCH (BP ≥135/85 mm Hg) regardless of nighttime BP (group 1), nighttime MUCH (BP ≥120/70 mm Hg) regardless of daytime BP (group 2), 24-hour MUCH (BP ≥130/80 mm Hg) regardless of daytime or nighttime BP (group 3), daytime MUCH only (group 4), nighttime MUCH only (group 5), and daytime + nighttime MUCH (group 6). RESULTS We detected 215 (29%), 357 (48.5%), 275 (37%), 42 (5.5%),184 (25%) and 173 (23.5%) patients with MUCH from group 1 to 6, respectively. During the follow-up (10 ± 5 years), 148 events occurred in patients with CH and MUCH. After adjustment for covariates, compared with patients with CH, the adjusted hazard ratio (95% confidence interval) for cardiovascular events was 2.01 (1.45–2.79), 1.53 (1.09–2.15), 1.69 (1.22–2.34), 1.52 (0.80–2.91), 1.15 (0.74–1.80), and 2.29 (1.53–3.42) from group 1 to 6, respectively. CONCLUSIONS The prognostic impact of MUCH defined according to various ambulatory BP definitions may be different.


2018 ◽  
Vol 159 (38) ◽  
pp. 1543-1547
Author(s):  
Krisztina Juhász ◽  
Imre Boncz ◽  
Péter Kanizsai ◽  
Andor Sebestyén

Abstract: Introduction: Although several national studies reported on the risk factors for contralateral hip fracture, there are no data about the prognostic factors of the time until contralateral hip fractures. Aim: The aim of the study was to analyse the impact of different prognostic factors on the time until the development of contralateral fracture and to determine the incidence of contralateral hip fractures after femoral neck fractures. Method: Patients aged 60 years and over with contralateral hip fracture between 01 Jan 2000 and 31 Dec 2008 were identified among those who suffered their femoral neck fracture in Hungary in 2000. Risk factors as age, sex, comorbidities, type of fracture and surgery, place of living and hospitals providing treatment for primary fracture were analysed by one way ANOVA focusing on the time until the development of contralateral hip fracture. Results: 312 patients met the inclusion criteria. The incidence of contralateral hip fracture after femoral neck fracture ranged between 1.5% and 2.1%, the cumulative incidence was 8.24%. The mean time until the development of contralateral hip fracture was 1159.8 days. The incidence of contralateral hip fracture showed no significant deviation. Significantly shorter time (p = 0.010) was detected until the contralateral hip fracture in older patients with femoral neck fracture. Conclusions: The yearly incidence of contralateral hip fracture showed no significant difference by patients with femoral neck fracture over 60 years. The shorter time until the contralateral hip fracture by the older age groups highlights the need of elaboration of prevention strategies. Orv Hetil. 2018; 159(38): 1543–1547.


2009 ◽  
Vol 10 (4) ◽  
pp. 17-25 ◽  
Author(s):  
Andre Figueiredo Reis ◽  
Flávio Henrique Baggio Aguiar ◽  
Marcelo Giannini ◽  
Patricia Nóbrega Rodrigues Pereira

Abstract Aim The aim of this study was to assess the influence of surface texture and etching technique on surface roughness (Ra) and bond strength (BS) to enamel and to determine if a correlation exists between them. Methods and Materials Fifty enamel blocks were either roughened with 600-grit SiC paper or polished with diamond pastes. After establishing ten test groups (n=5), the initial Ra measurements, rough (R) and smooth (S) enamel surfaces were etched according to the following protocols: Group 1(R)/Group 2(S)- 35% phosphoric acid gel (H3PO4) for 15 seconds; Group 3(R)/Group 4(S)- 35% H3PO4 for 60 seconds; Group 5(R)/Group 6(S)- Clearfil SE Bond primer for 20 seconds; Group 7(R)/Group 8(S)- self-etching primer (SEP) for 60 seconds; Group 9(R)/ Group 10(S)- 35% H3PO4 for 15 seconds + SEP for 20 seconds. After treatments, a new Ra measurement was performed and enamel surfaces were bonded with either Single Bond (Group 1 to Group 4) or Clearfil SE Bond (Group 5 to Group 10). Afterwards, specimens were prepared for the microtensile test. Ra values were analyzed using repeated-measures analysis of variance (ANOVA) and the BS values were analyzed using a two-way ANOVA and Tukey test (5%). Correlation between BS and Ra values was assessed using the Pearson's test. Results The application of SEP produced the lowest Ra values. No significant difference was detected between the BS values of polished and rough surfaces. No correlation was observed between Ra and BS values. Even though etching enamel with the SEP resulted in a surface with less roughness, similar BS values were observed for both self-etching and etch-and-rinse techniques. Conclusion Within the limits of this study increasing the etching time or combining both etching techniques failed to improve the BS using SEP or etch-and-rinse systems. Clinical Significance Based on the findings of this study, there is no clinical justification for increasing the etching time or for combining the use of a SEP following the use of a 35% H3PO4 etchant to achieve a greater BS to ground enamel. Citation Reis AF, Aguiar FHB, Pereira PNR, Giannini M. Effects of Surface Texture and Etching Time on Roughness and Bond Strength to Ground Enamel. J Contemp Dent Pract 2009 July; (10)4:017-025.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1949-1949
Author(s):  
Richard F. Schlenk ◽  
Konstanze Dohner ◽  
Martina Kerz ◽  
Francisco del Valle ◽  
Björn Heydrich ◽  
...  

Abstract Background: In primary refractory patients the achievement of a response to salvage therapy is of enormous prognostic impact. Aims: To evaluate the impact of all-trans retinoic acid (ATRA) and gemtuzumab ozogamicin (GO) given as adjunct to high-dose cytarabine based intensive salvage therapy in primary refractory younger patients on clinical outcome. Methods: Between 1993 and 2006 264 consecutive patients (median age: 48 yrs) were evaluated. All patients had primary refractory AML after one cycle of ICE (idarubicine, cytarabine, etoposide). The different salvage therapies were as follows: from 1993–1998: S-HAM for patients <55 years of age [cytarabine 3g/m2 bid. days 1,2,8,9, mitoxantrone 10mg/m2 days 3,4,10,11] and HAM for patients >=55 years of age [cytarabine 3g/m2 bid., days 1–3, mitoxantrone 12mg/m2 days 2,3]; from 1998 to 2004 A-HAM [HAM with ATRA 45mg/m2 days 3–5, 15mg/m2 days 6–28]; from 2004 up to date: GO-A-HAM [A-HAM with gemtuzumab ozogamicin 3g/m2 day 1]. Results: The distribution of the different salvage therapies was HAM n=21, S-HAM n=22, A-HAM n=118, GO-A-HAM n=62, other n=31, or no further therapy n=10. CR-rate according to salvage therapy was GO-A-HAM 49%, A-HAM 34% S-HAM 23%, HAM 14%. Treatment related mortality did not differ between regimens. No CTC-grade 3–5 liver toxicity was seen in patients receiving GO-A-HAM. Logistic regression on the achievement of CR revealed that regimens containing ATRA (odds ratio 2.0, p=0.05) and GO (odds ratio 1.9 p=0.05) were associated with response. 151 of 264 patients have received a stem cell transplantation as consolidation therapy (n=59 MRD, n=79 MUD, n=6 haplo-identical donor, n=7 autologous). The rates of severe veno occlusive disease after transplant was identical (5%) for patients receiving a salvage therapy including GO and those who did not. Survival analysis revealed a significant difference (p= 0.00178) with a median survival of 16.2 months for GO+ATRA, 12.5 months for ATRA versus 7.2 months for the others. Conclusions: Although retrospective in nature our study suggests that ATRA and GO as adjunct to salvage therapy improves CR rates and survival in primary refractory AML patients.


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