Can negative ureteroscopy be predicted in ureteral stone treatment?

Introduction: We aimed to evaluate factors predictive of negative ureteroscopy (URS) in ureteral stones. Methods: Patients who underwent URS between January 2007 and June 2018 were included in the study. Patients were divided into two groups; group 1: positive URS (841 patients) and group 2: negative URS (75 patients). These two groups were compared in terms of demographic data, stone characteristics, and postoperative outcomes. Results: The mean age of the study patients was 44.5±15.1 years. The absence of collecting system dilatation due to the present stone was found to be a significant predictive factor for negative URS in univariate analysis, but there was no significant difference in multivariate analysis. In the multivariate analysis, low body mass index (BMI), no history of stone surgery, stone located in the distal ureter, small stone area, longer time between the last imaging procedure and URS, and medical expulsive therapy (MET) application were statistically significant in predicting negative URS. Conclusions: In this study, the parameters that significantly predicted negative URS were found to be low BMI, no history of stone surgery, distal localization of the stone, small stone area, longer time between the last imaging procedure and URS, and MET applied for the current stone. These parameters should be considered to avoid negative URS and patients should be informed of the possibility of negative URS prior to operation.

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Percutaneous ultrasound guided radiofrequency and microwave ablation in the treatment of hepatic metastases. A monocentric initial experience.

Medical Ultrasonography ◽

10.11152/mu-1957 ◽

2019 ◽

Vol 21 (3) ◽

pp. 217 ◽

Cited By ~ 3

Author(s):

Zeno Sparchez ◽

Tudor Mocan ◽

Nadim All Hajjar ◽

Adrian Bartos ◽

Claudia Hagiu ◽

...

Keyword(s):

Multivariate Analysis ◽

Microwave Ablation ◽

Univariate Analysis ◽

Hepatic Metastases ◽

Tumor Ablation ◽

Tumor Control ◽

Local Tumor ◽

Long Term Outcome ◽

Significant Difference ◽

Multiple Metastases

Aim: Percutaneous radiofrequency (RFA) and microwave ablation (MWA) are currently the best treatment options forpatients with liver metastases (LM) who cannot undergo a liver resection procedure. Presently, few studies have evaluated theefficacy of tumor ablation in beginner’s hands but none at all in hepatic metastasis. Our aim was to report the initial experiencewith ultrasound as a tool to guide tumor ablation in a low volume center with no experience in tumor ablation.Material and methods: We conducted a retrospective cohort study, on a series of 61 patients who had undergone percutaneous US-guided ablations for 82 LM between 2010 and 2015. Long term outcome predictors were assessed using univariate and multivariate analysis.Results: Complete ablation was achieved in 86.9% of cases (53/61). All MWA sessions (20/20) attained ablation margins >5mm, compared to 79% (49/62) for RFA sessions (p=0.031). Ablation time was significantly shorter for MWA, with a median duration of 10 minutes (range: 6-12) vs. 14 minutes (range: 10-19.5, p=0.003). There was no statistically significant difference in local tumor progression (LTP)-free survival rates between MWA and RFA (p=0.154). On univariate analysis, significant predictors for local recurrence were multiple metastases (p=0.013) and ablation margins <5 mm (p<.001), both retaining significance on multivariate analysis. Significant predictors for distant recurrence on both univariate and multivariate analysis were multiple metastases (p<0.001) and non-colorectal cancer metastases (p<0.05).Conclusion: A larger than 5 mm ablation size is critical for local tumor control. We favor the use of MWA due to its ability to achieve ablation in significantlyshorter times with less incomplete ablations.

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Demographic and Clinical Characteristics Associated With Adherence to Guideline-Based Polysomnography in Children With Down Syndrome

Otolaryngology ◽

10.1177/0194599820954837 ◽

2020 ◽

pp. 019459982095483

Author(s):

Philip D. Knollman ◽

Christine H. Heubi ◽

Susan Wiley ◽

David F. Smith ◽

Sally R. Shott ◽

...

Keyword(s):

Socioeconomic Status ◽

Down Syndrome ◽

Clinical Characteristics ◽

Medical Center ◽

Demographic Data ◽

Children With Down Syndrome ◽

Medical Need ◽

Obstructive Sleep ◽

Significant Difference ◽

History Of

Objectives To compare the demographic and clinical characteristics of children with Down syndrome who did and did not receive polysomnography to evaluate for obstructive sleep apnea after publication of the American Academy of Pediatrics’ guidelines recommending universal screening by age 4 years. Study Design Retrospective cohort study. Setting Single tertiary pediatric hospital. Methods Review was conducted of children with Down syndrome born between 2007 and 2012. Children who obtained polysomnography were compared with children who did not, regarding demographic data, socioeconomic status, and comorbidities. Results We included 460 children with Down syndrome; 273 (59.3%) received at least 1 polysomnogram, with a median age of 3.6 years (range, 0.1-8.9 years). There was no difference in the distribution of sex, insurance status, or socioeconomic status between children who received polysomnography and those who did not. There was a significant difference in race distribution ( P = .0004) and distance from home to the medical center ( P < .0001) between groups. Among multiple medical comorbidities, only children with a history of hypothyroidism ( P = .003) or pulmonary aspiration ( P = .01) were significantly more likely to have obtained polysomnography. Conclusions Overall, 60% of children with Down syndrome obtained a polysomnogram. There was no difference between groups by payer status or socioeconomic status. A significant difference in race distribution was noted. Proximity to the medical center and increased medical need appear to be associated with increased likelihood of obtaining a polysomnogram. This study illustrates the need for improvement initiatives to increase the proportion of patients receiving guideline-based screening.

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Prevalence of cesarean section on demand in Assiut Governorate, Egypt

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20191175 ◽

2019 ◽

Vol 8 (4) ◽

pp. 1223

Author(s):

Mahmoud S. Zakherah ◽

Tarek A. Farghaly ◽

Elham S. Ahmed ◽

Ahmed M. Abbas

Keyword(s):

Cesarean Section ◽

Demographic Data ◽

Previous Experience ◽

Central Hospital ◽

Fear Of Pain ◽

Cross Sectional ◽

On Demand ◽

Significant Difference ◽

History Of ◽

Health Hospital

Background: The current study aims to evaluate the prevalence of CS on demand in Women's health hospital, Assiut University and Abnob Central Hospital in Assiut Governorate, Egypt.Methods: A cross sectional study conducted in Assiut Women Health Hospital and Abnob central hospital from January 2017 to December 2017. The total number of cesarean section done was 180 cases and the number of CS on demand was 64 (35.6%). The demographic data were collected by one of the study investigators. Women were asked about the causes of requesting CS before surgery.Results: The study group was 64 women with age ranging from 18-40 years old, 40 primipara and 24 multipara. Of those 24 women, 21 of them previously delivered vaginally and only 3 women delivered by emergency CS. Twenty- six women had a history of previous abortion. Fear of pain was the main cause for CS on demand in the whole study participants (57.8%). In primipara, the main cause for requesting CS is fear of pain in 62.5% of participants followed by fear on the baby in 45 % of women. On the other hand, in multipara, the main cause for CS on demand was bad history of previous experience (60%) followed by fear of pain in 50% of cases. There was statistical significant difference between both groups in only two causes; fear of pelvic floor injuries (50% in multipara vs. 20% in primipara, p=0.02) and bad history of previous experience (60% in multipara vs. 0% in primipara, p=0.001). Other causes were not statistically different.Conclusions: The incidence of cesarean sections performed on request without medical indications is rising. The reasons for this are not only for perceived medical benefit, but also due to social, cultural, and psychological factors.

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Clinical Factors Associated with the Diagnosis of Granulomatosis with Polyangiitis

Otolaryngology ◽

10.1177/0194599816685696 ◽

2017 ◽

Vol 156 (3) ◽

pp. 484-488 ◽

Cited By ~ 4

Author(s):

Erdem Eren ◽

Toygar Kalkan ◽

Seçil Arslanoğlu ◽

Mustafa Özmen ◽

Kazım Önal ◽

...

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Nasal Mucosa ◽

Odds Ratio ◽

Granulomatosis With Polyangiitis ◽

Univariate Analysis ◽

Binary Logistic Regression ◽

Binary Logistic Regression Analysis ◽

Significant Difference ◽

History Of

Objective To determine the predictive value of nasal endoscopic findings and symptoms in the diagnosis of granulomatosis with polyangiitis (GPA). Study Design A cross-sectional study. Setting A tertiary university hospital. Subjects and Methods A total of 116 adults were enrolled in the study: 19 patients with GPA, 29 patients with other rheumatic diseases, and 68 healthy volunteers. All patients were examined with a flexible endoscope, and nasal endoscopic images were recorded and evaluated blindly. The medical history of each patient was taken by a physician blinded to the patient’s diagnosis. Results Univariate analysis indicated a statistically significant difference in rhinorrhea ( P = .002), postnasal drip ( P = .015), epistaxis ( P < .001), and saddle nose ( P = .017). However, binary logistic regression analysis demonstrated that only history of epistaxis ( P = .012; odds ratio, 5.6) was statistically significant in predicting GPA. Univariate analysis showed a statistically significant difference in nasal secretion ( P = .028), nasal septal perforation ( P < .017), nasal crusting ( P < .001), nasal adhesion ( P < .001), nasal granuloma ( P = .017), and hemorrhagic fragile nasal mucosa ( P < .001). A binary logistic regression analysis demonstrated that only hemorrhagic fragile nasal mucosa ( P < .001; odds ratio, 52.9) was a statistically significant predictor of GPA. Conclusions Given the results of this study, we believe that hemorrhagic fragile nasal mucosa and history of recurrent epistaxis may put patients at risk for GPA and should be investigated accordingly.

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Lymphatic Vessel Invasion As a Prognostic Factor in Patients With Primary Resected Adenocarcinomas of the Esophagogastric Junction

Journal of Clinical Oncology ◽

10.1200/jco.2005.12.151 ◽

2005 ◽

Vol 23 (4) ◽

pp. 874-879 ◽

Cited By ~ 67

Author(s):

Burkhard H.A. von Rahden ◽

Hubert J. Stein ◽

Marcus Feith ◽

Karen Becker ◽

J. Rüdiger Siewert

Keyword(s):

Multivariate Analysis ◽

Prognostic Factor ◽

Esophagogastric Junction ◽

Lymphatic Vessel ◽

Univariate Analysis ◽

Prognostic Significance ◽

Residual Tumor ◽

Lymphatic Vessel Invasion ◽

Vessel Invasion ◽

Significant Difference

Purpose To evaluate the value of lymphatic vessel invasion (LVI) as a predictor of survival in patients with primary resected adenocarcinomas of the esophagogastric junction (AEG). Patients and Methods We prospectively evaluated 459 patients undergoing primary surgical resection for tumors of the esophagogastric junction at our institution between 1992 and 2000 (180 adenocarcinomas of the distal esophagus, AEG I; 140 carcinomas of the cardia, AEG II; and 139 subcardial gastric cancers, AEG III). Median follow-up was 36.8 months. The prevalence of LVI was evaluated by two independent pathologists. Univariate and multivariate analysis of prognostic factors was performed. Results The total rate of LVI was 49.9%, with a significant difference between AEG I (38.9%) and AEGII/III (57.0%, P = .0002). Univariate analysis showed a significant correlation between LVI and T category (P < .0001), N category (P < .0001), and resection status (R [residual tumor] category; P < .0001). This was shown for the group of all AEG tumors, as well as for the subgroups AEG I and AEG II/III. On multivariate analysis, LVI was identified as a significant and independent prognostic factor (P = .050) in the population of all patients and in patients with AEG II/III, but not in the subgroup with AEG I. Conclusion These data demonstrate the prognostic significance of LVI in patients with AEG tumors, with marked differences between the subgroups AEG I versus AEG II/III. The lower prevalence and lack of prognostic significance of LVI in AEG I might be explained by inflammation involved in the pathogenesis of this entity.

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Factors contributing to intentional injuries in Iranian university students

International Journal of Adolescent Medicine and Health ◽

10.1515/ijamh-2017-0002 ◽

2017 ◽

Vol 31 (3) ◽

Cited By ~ 2

Author(s):

Kobra Abedian Kasgary ◽

Zeinab Hamzehgardeshi ◽

Zohreh Shahhosseini

Keyword(s):

University Students ◽

Demographic Data ◽

Human Action ◽

Cross Sectional Study ◽

Cross Sectional ◽

Intentional Injuries ◽

Significant Difference ◽

History Of ◽

And Gender ◽

The University

Abstract Background Intentional injuries refer to injuries resulting from purposeful human action, whether directed at oneself or others. This study was performed to assess intentional injuries in Iranian university students. Methods This cross-sectional study was carried out with 430 female and male university in three higher education institutions located in the northern part of Iran in the year 2015. Samples were chosen through the stratified cluster random sampling method. They were requested to fill out the demographic data form and the Persian version of the Youth Risk Behavior Survey Questionnaire. Descriptive and inferential statistics were used for data analysis via the SPSS v.13 software. Findings Intentional injuries were more frequent in the male university students than female (p < 0.05). Also, 9.1% and 6.7% of the university students were physically injured or sexually assaulted by a boy/girl friend. No statistically significant difference was reported in dating violence between the male and female university students. The logistic regression test showed that the history of stealing money from parents without their permission, son’s preferences in the family and gender are the most important predisposing factors for the university students’ intentional injury. Conclusion It is suggested that health policy makers consider the role of family in programs that have been designed for improving the health of young people.

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A New Cytokine-Based Stratification Is Highly Predictive of Survivals in AML Patients

Blood ◽

10.1182/blood-2019-125774 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1412-1412

Author(s):

Pierre Peterlin ◽

Joelle Gaschet ◽

Thierry Guillaume ◽

Alice Garnier ◽

Marion Eveillard ◽

...

Keyword(s):

Multivariate Analysis ◽

Risk Stratification ◽

Univariate Analysis ◽

Standard Of Care ◽

Healthy Controls ◽

First Line ◽

Serum Samples ◽

Gm Csf ◽

Significant Difference ◽

The Impact

Introduction: Recently, a significant impact of the kinetics of Fms-like tyrosine kinase 3 ligand concentration (FLc) during induction (day[D]1 to D22) has been reported on survivals in first-line acute myeloid leukemia (AML) patients (pts) (Peterlin et al, 2019). Three different FLc profiles were disclosed i) sustained increase of FLc (FLI group, good-risk), ii) increase from D1 to D15, then decrease at D22 (FLD group, intermediate-risk) and iii) stagnation of low levels (<1000 pg/mL, FLL group, high-risk). An update of this prospective monocentric study (www.ClinicalTrials.gov NCT02693899) is presented here evaluating also retrospectively the impact on outcomes of 6 other cytokine level profiles during induction. Methods: Between 05/2016 and 01/2018, 62 AML pts at diagnosis (median age 59 yo [29-71], <60 yo n=33) eligible for first intensive induction were included and provided informed consent. They received standard of care first-line chemotherapy. Serum samples collected on D1, 8, 15 & 22 of induction were frozen-stored until performing ELISA for FL, TNFa, SCF, IL-1b, IL-6, IL-10, GM-CSF. Normal values were assessed in 5 healthy controls. Pts outcomes considered were relapse/leukemia-free (LFS) and overall (OS) survivals. Results: FLI, FLD and FLL profiles were observed for 26, 22 and 14 pts respectively. A total of 372 samples were assayed for the 6 other cytokines. Median concentrations at D1, D8, D15, D22 for these 6 cytokines were as follows, considering the whole cohort (and healthy donors): TNFa: 0.53, 0, 0, 0 (0); SCF: 5.91, 0, 0, 0 (3); IL-1b : 0, 0, 0, 0 (0); IL-6: 4.85, 16.28, 10.11, 7.1 (0), IL-10: 0, 0, 0, 0 (0) and GM-CSF:1.63, 1.8, 0.67, 1.34 (9.98). Median IL-6 and GM-CSF levels, compared to healthy controls, were respectively higher and lower during induction. No significant difference was observed in terms of median cytokine concentrations at any time when comparing the three FL sub-groups or FLI vs FLD pts. With a median follow-up of 28 months (range: 17-37), FLI and FLD pts show now similar 2-y LFS (62.9% vs 59%, p=0.63) and OS (69.2% vs 63.6%, p=0.70). FLL pts have a significantly higher rate of relapse (85,7% vs FLI 19,2% vs FLD 32%, p=0,0001). Comparing FLL vs FLI+FLD pts disclosed significantly different LFS (7.1% vs 61.1%, p<0.001) but not OS (36.7% vs 66.6%, p=0.11). In univariate analysis, 2y LFS and OS were not affected by the concentration (< or > median) of the 7 cytokines studied except for LFS and GM-CSFc at D8 (p=0,04) and D15 (p=0,08), for LFS and FLc at D1 (p=0.06), D8 (p=0,03), D15 (p=0,04) and D22 (p=0,03) and for OS and GM-CSF at D15 (p=0.08). A significant association between LFS was observed with ELN 2017 risk stratification (2-y LFS: favorable: 68,1% vs intermediate: 48,1% vs unfavorable: 30,7%, p=0.03) but not OS (2 y: 77% vs 55,5% vs 46,1%, p=0.09). Multivariate analysis showed that no factor was independently associated with OS while LFS remained significantly associated with the FLc profile (FLL vs others, HR: 5.79. 95%CI: 2.48-13.53, p<0.0001) and GM-CSF at D15 (HR: 0.45; 95%CI: 0.20-0.98, p=0.04) but not with ELN 2017 risk stratification (p=0.06). Cytokine levels were then assessed to try to better discriminate FLI and FLD pts. A significant higher IL-6 level at D22 was found in relapsed or deceased FLI/FLD pts (median:15,34 vs 5,42 pg/mL, p=0,04). FLI/FLD pts with low IL-6 at D22 (< median, 15.5 pg/mL, n=35 vs n=14 with high level) had significant better 2y LFS and OS (74,2% vs 38,4%, p=0,005 and 77,1% vs 38,4%, p=0,009, respectively). A new prognostic risk-stratification could thus be proposed, i.e. FLI/FLD with IL-6 <15.5 pg/mL (favorable), FLI/FLD with IL-6 >15.5 pg/mL (intermediate) and FLL (unfavorable). This new classification was considered for a second multivariate analysis, showing that it is the strongest factor associated with OS (p=0.006, ELN p=0.03, FL profile p=0.04) and LFS (p<0.0001, ELN p=0.005, GM-CSFc D15 p=0.03) (figure 1). Conclusion: This study confirms stagnation of low FLc during AML induction as a strong poor prognosis factor. Moreover, IL-6 levels at D22 further discriminate FLI/FLD pts. Thus, a new cytokine-based risk-stratification integrating FL kinetics and IL-6 levels during induction may help to better predict outcomes in first-line AML patients. These results need to be validated on a larger cohort of AML patients while anti-IL-6 therapy should be tested in combination with standard 3+7 chemotherapy. Figure 1 Disclosures Peterlin: AbbVie Inc: Consultancy; Jazz Pharma: Consultancy; Daiichi-Sankyo: Consultancy; Astellas: Consultancy. Moreau:Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Chevallier:Jazz Pharmaceuticals: Honoraria; Incyte: Consultancy, Honoraria; Daiichi Sankyo: Honoraria.

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Evaluation of Exercise Capacity In Children with SCD by Six Minute Walk Test

Blood ◽

10.1182/blood.v116.21.2664.2664 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2664-2664

Author(s):

Caterina Minniti ◽

Shoaib Alam ◽

Gregory J. Kato ◽

Mehdi Nouraie ◽

Craig Sable ◽

...

Keyword(s):

Multivariate Analysis ◽

Exercise Capacity ◽

Conflicts Of Interest ◽

Strong Predictor ◽

Univariate Analysis ◽

History Of ◽

Rate Of Decline ◽

Changes Over Time ◽

Minute Walk

Abstract Abstract 2664 Background: The six-minute walk (6MW) test is used in pediatrics in clinical practice and research to determine cardiopulmonary functional status. A change in 6MW may be affected by factors not strictly related to cardiopulmonary function, which may be different in different patient populations. In children and adolescents, age and height has been found to be a strong predictor of 6MW distance. We set out to study the effects of hematological and echocardiographic variables on 6MW distance in children with sickle cell disease (SCD) and its changes over time. Methods: We reviewed prospectively collected hematological, 6MW distance, and echocardiographic data from four hundred children with SCD (including 311 Hb SS or β0) and 69 controls (including 21 Hb AS) enrolled in PUSH (Pulmonary Hypertension and the Hypoxic Response in SCD). Subjects were evaluated at baseline and after 18–24 months, as per protocol. An un-encouraged 6MW was performed in children 5 years or older by trained personnel as per the guidelines of the American Thoracic Society. Subjects were studied at steady state, at least three weeks after any acute exacerbation of SCD. We used ANOVA for univariate analysis and stepwise linear regression for multivariate analysis. Results: Median (interquartile range) 6MW in severe SCD genotype (SS and S-β0) was 444 (399-508) and in controls was 495 meters (435-539) (P = 0.0002), while it was 461 meters (408-518) in milder SCD genotypes (P=0.2 for comparison with severe genotypes) (Table 1). In multivariate analysis, Hb, WBC and history of frequent pain episodes were significantly associated to distance of 6MW. Follow up 6MW obtained in 174 SCD subjects revealed a decline of 10% or more in distance in 22% of subjects with severe genotypes and 33% of other genotypes. The decline was more frequent in the subset of SS subjects with TRV>2.59 (40% vs 19%). CONCLUSION: Six minute walk distance is significantly shorter in children with SCD, even as young as 5 years of age, when compared to age and race appropriate controls, indicating early compromise of exercise capacity. SS and S-β-0 genotype subjects have more impairment of exercise capacity compared to milder genotypes. Predictors of 6MW distance are similar in SCD and non SCD subjects, which validates the use of this test in this patient population. Longitudinal changes in subjects with SCD are similar, with declines in about a quarter of the subjects. Patients with SS who have an elevated TRV have the highest rate of decline in 6MW. These results validate the use of 6MW as a tool for assessing exercise capacity in children with SCD. Disclosures: No relevant conflicts of interest to declare.

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Improved Outcome with Busulfan, Melphalan, and Thiotepa Conditioning (BuMelTt) in Autologous Hematopoietic Stem Cell Transplantation for Relapsed/Refractory Hodgkin Lymphoma

Blood ◽

10.1182/blood.v118.21.3110.3110 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3110-3110

Author(s):

Tarunpreet Bains ◽

Andy I Chen ◽

Andrew Lemieux ◽

Brandon Hayes-Lattin ◽

Jose F. Leis ◽

...

Keyword(s):

Multivariate Analysis ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Hodgkin Lymphoma ◽

Cell Transplantation ◽

Univariate Analysis ◽

Disease Status ◽

Significant Difference ◽

Conditioning Regimens ◽

Refractory Hodgkin Lymphoma

Abstract Abstract 3110 High-dose therapy followed by autologous stem cell transplantation (ASCT) is standard therapy for patients with relapsed or refractory Hodgkin Lymphoma (HL), although the optimal conditioning regimen remains uncertain. The three drug alkylating agent regimen, BuMelTt, has been established as our institutional regimen. We performed a retrospective review of outcomes obtained with BuMelTt compared to those achieved with other standard conditioning regimens. 133 patients with relapsed/refractory HL who underwent ASCT between January 1990 and December 2009 were analyzed. 62 patients received BuMelTt and 71 patients received other standard preparative regimens (Standard) consisting of CBV (44), CyVp16TBI (20), BEAM (4), CyTBI (2), and Mel (1). The median follow-up (range) was 4.3 years (0.01–14.24) in BuMelTt and 3.9 years (0.07–20.21) in Standard. The two groups (BuMelTt vs Standard) were balanced for gender (65% male vs 65% male), median age (29 vs 33), median number of prior regimens (2 vs 2), and pre-transplant disease status. Disease status was categorized as PR2/CR2 (48% vs 42%), primary induction failure sensitive (16% vs 17%), and Other which included PIF-refractory, 1st relapse refractory, and greater than 1st relapse (35% vs 41%). The 5 year overall survival (OS) was superior for patient who received BuMelTt conditioning (74% vs 54%, p = 0.03). There was also a trend for improved 5 year event free survival (EFS) for BuMelTt at 56% vs 39% for Standard (p=0.07). Other risk factors for outcome after ASCT were also analyzed and included disease status, more than 2 chemotherapy regimens before ASCT, Karnofsky score < 90% at ASCT, time from diagnosis to ASCT < 12 months, prior extranodal involvement, and age > 40 years. By univariate analysis, >2 chemotherapy regimens before ASCT (HR 1.7, p=0.05) and disease status of Other (HR 2.8, p<0.01) were predictive for lower OS. There was a trend for influence on OS for BuMelTt (HR 0.6, p=0.07) and PIF-sensitive (HR 1.9, p=0.09). By multivariate analysis, disease status of PIF-sensitive or Other predicted worse outcomes for OS (HR 2.4 & 2.9, p 0.03 & <0.01, respectively), and there was still a trend for benefit with BuMelTt (HR 0.6, p=0.09), although >2 chemotherapy regimens lost significance (p=0.22). For EFS, disease status of PIF-sensitive or Other were prognostic in univariate analysis (HR 2.1 or 2.3, p=0.02 or <0.01, respectively), and there was a trend for improved EFS with BuMelTt (HR 0.66, p=0.08). In multivariate analysis, disease status of PIF-sensitive or Other remained prognostic (p=0.03 & 0.004, respectively), while BuMelTt was not significant (p=0.27). There was no significant difference in 100 day non-relapse related mortality for BuMelTt vs Standard conditioning (5% vs 3%, p=0.88). More patients developed NCI CTCAE grade 3/4 mucositis with BuMelTt than Standard (89% vs 61%, p<0.01), but fewer patients had bacteremia with BuMelTt than Standard (7% vs 23%, p=0.02). There was no difference in duration of hospitalization, episodes of febrile neutropenia, incidence of veno-occlusive disease, time to neutrophil engraftment, or time to platelet engraftment. Our results suggest that BuMelTt may improve OS and EFS compared to standard conditioning regimens with increased but manageable toxicity. A case matched control study is planned. Disclosures: No relevant conflicts of interest to declare.

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ABCA3 Expression Predicts Response to Gemtuzumab Ozogamicin in AML

Blood ◽

10.1182/blood.v128.22.3946.3946 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3946-3946 ◽

Cited By ~ 1

Author(s):

Antony Ceraulo ◽

Aminetou Mint-Mohamed ◽

Delphine Maucort-Boulch ◽

Etienne Paubelle ◽

Xavier Thomas ◽

...

Keyword(s):

Multivariate Analysis ◽

Prognostic Factors ◽

Relapse Rate ◽

Small Sample Size ◽

Univariate Analysis ◽

Gemtuzumab Ozogamicin ◽

Small Sample ◽

Control Group ◽

Prognostic Impact ◽

Significant Difference

Abstract Background. The ATP binding cassette transporter 3 (ABCA3) has been recently found to induce a significant reduction in cytotoxicity following exposure to anthracyclines, mitoxantrone, etoposide, Ara-C, vincristine, and rituximab. ABCA3 acts through the modulation of multivesicular bodies (MVB) and contributes to drug sequestration in late endosomal organelles, i.e. MVB and lysosomes. Studies having investigated the prognostic impact of ABCA3 expression in AML have yielded conflicting results as ABCA3 expression has both been reported to exert unfavorable or neutral effects on patient outcomes. In addition, the small sample size of these studies precluded the use of multivariate analyses. Methods. Our goal was to investigate the prognostic impact of ABCA3 expression in adult patients with AML treated with IC with or without gemtuzumab ozogamicin (GO). To this end we investigated the relationship between ABCA3 expression and EFS in a representative series of 221 AML homogeneously treated in the ALFA-0701 trial. qRTPCR amplification of conserved ABCA3 mRNA sequences, as identified with FasterDB database, was performed with GUS and ABL as reference genes. Primer sets were complementary to conserved ABCA3 exons 6-7 and exon 19-20 junctions. Patients were given a 3+7 induction course without (control group, n=110) or with fractionated intravenous GO (n=111) (Castaigne S, Lancet 2012; 379:1508-1516). Results. Among the 278 randomized patients, 221 had available bone-marrow diagnostic samples with high-quality RNA. The same benefits associated with GO were observed in the 221 patients from the present study as in the entire trial population. Overall, median age, CR rate, relapse rate, median follow-up, 3-years EFS were 62.1 years, 76.5%, 66%, 47.45 months, 28±3%, respectively. There was no significant difference in the level of ABCA3 expression between responders and non-responders. In the 169 responders, ABCA3 expression at diagnosis was more than 3-fold higher in the 111 remitters who subsequently relapsed than in the 58 patients who remained in persistent CR (p=0.033). The level of ABCA3 expression was significantly lower in ELN favorable group than in intermediate and adverse risk AML (p= 0.004) and negatively correlated with CD33 expression (R=-0.272, p<10-4). Through univariate analysis, higher ABCA3 expression was associated with shorter EFS (3-years: 22±3 vs 45±7 % p=0.002). Multivariate analysis identified age, treatment arm, and ELN risk group as independent prognostic factors for EFS. In the control group, there was no significant association between ABCA3 expression and CR rate, relapse rate, and EFS. In the 111 patients within the GO arm, there was no significant difference in the level of ABCA3 expression between responders and non-responder whereas in the 89 responders, ABCA3 expression at diagnosis was more than 7-fold higher in the 53 remitters who subsequently relapsed than in the 36 patients who remained in persistent CR (p=0.006). Through univariate analysis, higher ABCA3 expression was associated with shorter EFS (3-years: 22±5 vs 64±9 % p=0.0002). Multivariate analysis identified ABCA3 expression, cytogenetics, CD33 expression, and ECOG as independent prognostic factors for EFS (Figure 1). Conclusion. WhileABCB1 has been previously found to attenuate GO-induced cytotoxicity in AML cells (Walter RB, Blood 2003; 102:1466-1473), present results indicate that higher ABCA3 expression independently predicts poor outcome in AML patients treated with fractionated GO and intensive chemotherapy (IC). GO is an anti-CD33 antibody carrying a toxic calicheamicin derivative that, after hydrolytic release within lysosomal vesicles, induces DNA strand breaks, apoptosis, and cell death. Whether the clinical effect of ABCA3 expression relies on the modulation of CD33 internalization, calicheamicin release or combination thereof is under investigation. Finally our results encourage inhibiting ABCA3, such as with indomethacin, in order to overcome drug resistance in AML treated with GO-IC. Figure 1 Figure 1. Disclosures Thomas: Pfizer: Consultancy.

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