scholarly journals Obesity Does Not Affect the Recurrence Free Survival Rates in Children Less Than 20 Years of Age in Acute Promyelocytic Leukemia (APL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 957-957 ◽  
Author(s):  
Ji Heon (Paul) Lee ◽  
Alfred W. Rademaker ◽  
Bayard L. Powell ◽  
Susan Geyer ◽  
Richard A. Larson ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Clinical Outcomes ◽  
Pediatric Patients ◽  
Normal Weight ◽  
Prognostic Impact ◽  
Recurrence Free Survival ◽  
Obese Patients ◽  
Age Group ◽  
Free Survival ◽  
Weight Groups

Abstract Introduction Emerging data are demonstrating that obesity continues to be an epidemic among the pediatric population. A number of studies in children and adults reported that obesity at diagnosis affects survival in some cancers. Some reports show that obesity is an independent prognostic factor in patients in APL.1,2 The impact of obesity and outcome has never been studied in pediatric patients with APL. Methods Patient data were collected and analyzed from APL patients treated on the North American Leukemia Intergroup C9710 study led by the Cancer and Leukemia Group B (Alliance), with participation by the Children’s Oncology Group (COG). Only patients with BMI data were included in these analyses (n=529) across all age groups. Children and adolescents (<20 years old) were divided into weight categories as follows: underweight, less than the 5th percentile; normal weight, from the 5th percentile to less than the 85th percentile; overweight, from the 85th percentile to less than 95th percentile; and obese, equal or greater than the 95th percentile (Center for Disease Control and Prevention; http://apps.nccd.cdc.gov/dnpabmi/). BMI for patients ≥20 years old were divided into weight categories: underweight, normal weight, overweight, obese, using the following cutpoints: underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5-25 kg/m2), overweight (BMI 25-29.9 kg/m2), and obese (BMI ≥ 30 kg/m2). Body weight categories were defined according to age- and sex-specific BMI percentiles. Both univariate and multivariate analysis were calculated using other factors such as age, gender, ethnicity and WBC at diagnosis (high risk if WBC ≥10,000). Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan and Meier methods, and Log-rank tests used to assess prognostic impact of factors on survival distributions; p-values <0.05 were considered statistically significant. Results In this group of 529 patients, 428 were ≥20 years old (y.o.) vs. 101 who were < 20 y.o. Within the < 20 y.o. group, the majority had normal weight (44.6%) based on BMI while the majority of the ≥20 y.o. group were obese (50.2%). A high percentage of those < 20 y.o. were also obese (33.7%). Median follow-up times for the <20 y.o. vs. >20 y.o. groups were 62.0 months (range, 1-149.8 months) vs. 96.7 months (range, 0.03 – 156.3 months), respectively. When compared to all other weight groups, OS and RFS did not significantly differ between obesity and other weight groups in patients < 20 y.o. (5-year OS rates: 64% vs 57%, p=0.94; and 5-year RFS rates: 83% vs 79%; p=0.60). However, in patients ≥20 years of age, RFS was worse in obese patients versus other weight groups (67% vs 77%, p = 0.026) as was OS (76% vs 85%, p = 0.023). Furthermore, we investigated therapy-related toxicities in the same weight groups. None of the toxicities (hematologic, infection, metabolic, pain, pulmonary) were significantly related to weight group (obese vs non-obese) for either age group (<20 years or >20 years). Discussion This is the first study to report obesity in relation to clinical outcomes or toxicity in children and adolescents with APL <20 years of age. Here, obesity did not confer poorer RFS or OS in this younger age group. In contrast, this study confirms a previous Alliance study showing that increased BMI in adult patients (>18 years) with APL is associated with worse RFS and OS.2 It is not clear why BMI and obesity do not have prognostic influence on clinical outcomes in patients less than 20 years of age. Possible theories include confounding factors in adults such as poor compliance by race or socioeconomic status in obese patients, whereas close monitoring by parents may play a role for pediatric patients in this setting. Future studies would need to be dedicated to address these theories. 1. Breccia M, Mazzarella L, Bagnardi V, et al. Blood. 2012;119(1):49-54. 2. Castillo JJ, Mulkey F, Geyer S, et al. Blood. 2013;122(21):832. Disclosures Rademaker: NIH Grant Review: Honoraria; AACR Faculty: Honoraria; Georgetown Univeristy Advisor: Honoraria. Hijiya:Sanofi: Consultancy; Jazz Pharma: Consultancy; Pfizer: Consultancy; Sigma Tau: Consultancy.

Role of obesity and race in predicting recurrence rates and survival in renal cell carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16052-e16052
Author(s):  
C. Ritch ◽  
D. J. Lee ◽  
M. Desai ◽  
J. M. McKiernan
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Normal Weight ◽  
Overweight And Obesity ◽  
The Other ◽  
Recurrence Free Survival ◽  
Obese Patients ◽  
Free Survival ◽  
The Relationship

e16052 Background: Two in three Americans are obese or overweight, and African-Americans are 1.4 times as likely to be obese than whites. However, the relationship between obesity, race, and renal cell carcinoma (RCC) is highly debated. We sought to explore the relationship between BMI and race, and determine the predictors for survival and recurrence after nephrectomy (Nx) for RCC. Methods: A retrospective analysis of the Columbia Urologic Oncology Database found that 1118 consecutive patients underwent partial or radical Nx for RCC between 1988 and 2008. Of these, 499 patients had BMI and race data available. 379 (76%) were white, 51 (10.2%) were black, 37 (7.4%) were Hispanic, and 32 (6.4%) were Asian. 341 (68.3%) were male compared to 158 (31.7%) females; 215 (50.3%) had partial Nx while 284 (56.9%) had a radical Nx. Overweight and obesity were defined as having a BMI > 25 kg/m2 and a BMI > 30 kg/m2, respectively. Cox proportional hazards models were used to assess the relationship between BMI, race, and recurrence- free survival (RFS). Results: The 499 patients had a median age of 63 years were followed for a mean of 25 months. Asians had significantly lower BMI than the other races (p=0.02), but the other ethnicities had similar BMI distributions. The two year cancer-specific survival was 89.6%, 92.7%, and 96.1% for normal weight, overweight, and obese patients, respectively (p=0.036). Race did not have a significant impact on predicting RFS. A multivariate Cox regression found that male sex, BMI, size of tumor removed, tumor stage, and margin were independent predictors of RFS. Overweight and obese patients were more likely to survive from RCC without recurrence than normal weight patients (p=0.04). An analysis assessing the effect of an interaction between race and BMI demonstrated that hazard ratios for increased BMI did not differ significantly by race. Conclusions: BMI is an independent predictor of RFS in patients undergoing partial or radical Nx for RCC. Recurrence free-survival did not differ significantly among the different ethnicities, and the impact of race on recurrence-free survival did not vary among different BMI classes. The importance of these findings needs to be addressed in large multi- institutional analyses. No significant financial relationships to disclose.

Prognostic impact of K-RAS mutational status and primary tumor location in patients undergoing resection for colorectal cancer liver metastases: an update

2019 ◽  
Vol 15 (27) ◽  
pp. 3149-3157
Author(s):  
Juan M O´Connor ◽  
Fernando Sanchez Loria ◽  
Victoria Ardiles ◽  
Jorge Grondona ◽  
Pablo Sanchez ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Primary Tumor ◽  
Kras Mutation ◽  
Tumor Location ◽  
Prognostic Impact ◽  
Recurrence Free Survival ◽  
Mutation Status ◽  
Free Survival ◽  
Primary Tumor Location ◽  
Kras Mutation Status

Aim: To determine the impact of KRAS mutation status on survival in patients undergoing surgery for colorectal liver metastases (CLM). Patients & methods: Patients with resected CLM and KRAS mutations. Survival was compared between mt-KRAS and wt-KRAS. Results: Of 662 patients, 174 (26.3%) were mt-KRAS and 488 (73.7%) wt-KRAS. mt-KRAS patients had significantly lower recurrence-free survival (HR: 1.42; 95% CI: 1.10–1.84). There were no differences between the groups for sidedness. Poorer survival was associated with mt-KRAS with positive lymph nodes, >1 metastases, tumors >5 cm, synchronous tumors and R1–R2. Conclusion: KRAS mutation status can help predict recurrence-free survival. Primary tumor location was not a prognostic factor after resection. KRAS mutation status can help design a multidisciplinary approach after curative resection of CLM.

scholarly journals Long-term outcomes of upfront surgery in patients with resectable pathological N2 non-small-cell lung cancer

2020 ◽  
Vol 58 (1) ◽  
pp. 59-69 ◽  
Author(s):  
Jae Kwang Yun ◽  
Jin San Bok ◽  
Geun Dong Lee ◽  
Hyeong Ryul Kim ◽  
Yong-Hee Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Small Cell ◽  
Recurrence Free Survival ◽  
Small Cell Lung ◽  
Free Survival ◽  
N2 Disease

Abstract OBJECTIVES Although the standard treatment for pathological N2 (pN2) non-small-cell lung cancer (NSCLC) patients is definitive chemoradiation, surgery can be beneficial for resectable pN2 disease. Herein, we report the long-term clinical outcomes of upfront surgery followed by adjuvant treatment for selected patients with resectable pN2 disease. METHODS We performed a retrospective analysis of clinical outcomes for patients with pN2 disease who underwent surgery as the first-line therapy. Multivariable Cox regression analysis was used to identify the significant factors for overall survival (OS) and recurrence-free survival. RESULTS From 2004 to 2015, a total of 706 patients with pN2 NSCLC underwent complete anatomical resection at our institution. The patients’ clinical N stages were cN0, 308 (43.6%); cN1, 123 (17.4%) and cN2, 275 (39.0%). Adjuvant chemotherapy, radiotherapy and chemoradiotherapy were administered to 169 (23.9%), 115 (17.4%) and 299 patients (42.4%), respectively. With a median follow-up of 40 months, the respective median time and 5-year rate of OS were 52 months and 44.7%. According to subdivided pN2 descriptors, the median OS time was 80, 53 and 37 months for patients with pN2a1, pN2a2 and pN2b, respectively. Adjuvant chemotherapy was a significant prognostic factor for both OS [hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.28–0.52; P &lt; 0.001] and recurrence-free survival (HR 0.42, 95% CI 0.30–0.58; P &lt; 0.001). CONCLUSIONS Upfront surgery followed by adjuvant therapy for resectable N2 disease showed favourable outcomes compared to those reported in previous studies. Adjuvant chemotherapy is essential to improve the prognosis for patients undergoing upfront surgery for N2 disease.

Prognostic impact of body mass index upon cancer recurrence and survival in stage III colon cancer patients from adjuvant chemotherapy trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11088-11088
Author(s):  
F. Sinicrope ◽  
N. R. Foster ◽  
D. J. Sargent ◽  
S. R. Alberts ◽  
M. J. O'Connell
Keyword(s):  
Colon Cancer ◽  
Cancer Recurrence ◽  
Disease Free Survival ◽  
Normal Weight ◽  
Stage Iii ◽  
Obese Patients ◽  
Tumor Site ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Disease Free

11088 Background: Obesity is associated with an increased risk of colon cancer. However, the influence of body mass index (BMI) upon the prognosis of patients with established colon cancer remains unknown. Methods: We conducted a retrospective study of 1,803 patients with surgically resected stage III colon cancer who were enrolled in five randomized trials of 5-fluorouracil-based adjuvant chemotherapy conducted by the North Central Cancer Treatment Group. Patient height and weight were recorded at study entry and BMI (kg/m2) was calculated and categorized. Cancer recurrence or death were monitored during 5 years of follow-up. The score and likelihood ratio p-values were determined from univariate and multivariate Cox regression models respectively, after stratifying by study. Results: Among stage III colon cancer patients, 19% were obese (BMI 30 kg/m2), 37% were overweight (BMI, 25 to 29.9 kg/m2), 38% were of normal-weight (BMI, 20 to 24.9 kg/m2), and 6% were underweight (BMI < 20 kg/m2). Obese versus normal-weight patients showed higher rates of lymph node (LN) metastasis (>3 LNs; 38% vs. 29%, p <0.01) and tumor site was more likely to be distal versus proximal (52% vs. 45%, p= 0.03). No differences in age, gender, or histologic grade were found. In a univariate analysis, obese patients had significantly worse disease-free survival (DFS) compared with normal-weight patients (hazard ratio 1.25 (95% CI: 1.04 -1.51; p= 0.02). The 5 year DFS rates were 49% in obese patients versus 57% in normal weight subjects. Furthermore, poorer DFS was observed for obese patients after adjusting for age, sex, histologic grade, and tumor site (p= 0.03). Neither overweight nor underweight patients (vs. normal-weight) had significantly different DFS. Analysis of the predictive impact of BMI for 5-FU-based adjuvant therapy is in progress. Conclusions: Obesity (BMI 30 kg/m2) was associated with a greater number of metastatic lymph nodes and poorer disease-free survival in patients with stage III colon cancer, suggesting that obesity influences tumor progression. No significant financial relationships to disclose.

scholarly journals Moyamoya disease in pediatric patients: outcomes of neurosurgical interventions

2008 ◽  
Vol 24 (2) ◽  
pp. E16 ◽  
Author(s):  
Anand Veeravagu ◽  
Raphael Guzman ◽  
Chirag G. Patil ◽  
Lewis C. Hou ◽  
Marco Lee ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Moyamoya Disease ◽  
Pediatric Patients ◽  
Pediatric Population ◽  
Small Populations ◽  
Age Group ◽  
Radiological Findings ◽  
Advantages And Disadvantages ◽  
Pediatric Age Group ◽  
Revascularization Procedures

✓Neurosurgical interventions for moyamoya disease (MMD) in pediatric patients include direct, indirect, and combined revascularization procedures. Each technique has shown efficacy in the treatment of pediatric MMD; however, no single study has demonstrated the superiority of one technique over another. In this review, the authors explore the various studies focused on the use of these techniques for MMD in the pediatric population. They summarize the results of each study to clearly depict the clinical outcomes achieved at each institution that had utilized direct, indirect, or combined techniques. In certain studies, multiple techniques were used, and the clinical or radiological outcomes were compared accordingly. Direct techniques have been shown to aid a reduction in perioperative strokes and provide immediate revascularization to ischemic areas; however, these procedures are technically challenging, and not all pediatric patients are appropriate candidates. Indirect techniques have also shown efficacy in the pediatric population but may require a longer period for revascularization to occur and perfusion deficits to be reversed. The authors concluded that the clinical efficacy of one technique over another is still unclear, as most studies have had small populations and the same outcome measures have not been applied. Authors who compared direct and indirect techniques noted approximately equal clinical outcomes with differences in radiological findings. Additional, larger studies are needed to determine the advantages and disadvantages of the different techniques for the pediatric age group.

scholarly journals Results of the nerve-sparing radical prostatectomy in obese patients

2020 ◽  
Vol 8 (2) ◽  
pp. 43-49
Author(s):  
E. A. Sokolov ◽  
E. I. Veliev
Keyword(s):  
Radical Prostatectomy ◽  
Functional Outcomes ◽  
Surgical Intervention ◽  
Prostate Volume ◽  
Control Group ◽  
Nerve Sparing ◽  
Recurrence Free Survival ◽  
Obese Patients ◽  
Free Survival ◽  
Oncological Results

Introduction. According to several studies, an increased body mass index (BMI) may be one of the unfavorable prognostic factors of prostate cancer (PC) associated with lower oncological and functional outcomes of radical prostatectomy (RP).Purpose of the study. To evaluate pathomorphological characteristics, recurrence-free survival, and restoration of erectile function (EF) after RP with nerve-sparing technique (NST) in obese patients.Materials and methods. The study group consisted of 91 patients with BMI ≥ 30 kg/m2 , the control group consisted of 356 patients with BMI < 30 kg/m2 who underwent RP with unilateral or bilateral NST from January 2012 to December 2019. A comparative analysis of pathomorphological results, the rate of complications, recurrence-free survival, and the dynamics of EF restoration in both groups was performed.Results. Obese patients had a larger prostate volume, a higher score for the International Prostate Symptom Score (IPSS) questionnaire. Unilateral and bilateral NST was used in both groups in equal proportions: 50.5% and 49.5% in the group with BMI ≥ 30 and 51.4% and 48.6% in the group with BMI < 30 (p = 0.88 ) There were no significant differences between the groups in the rate of adverse pathomorphological characteristics, serious postoperative complications and the volume of intraoperative blood loss. The five-year recurrence-free survival after RP was 93.1% in the BMI group ≥ 30 and 95.1% in the BMI group < 30 (p = 0.55). The total rate of EF recovery after RP with NST after 24 months was 75% and 78.5% (p = 0.24). The restoration of EF in obese patients was slower: sufficient for sexual intercourse EF after 6 and 12 months was observed in 17.9% and 32.1% versus 35.4% and 53.8% in the group with BMI < 30, and the meantime to recovery was 10.9 (± 1) and 8.6 (± 0.6) months, respectively (p = 0.04).Conclusions. Obesity does not affect the pathomorphological and oncological results of RP with NST. EF recovery in patients with a BMI of ≥ 30 is slowed down, however, 24 months after surgery, the results are comparable with the potency level in patients with a BMI < 30. The data obtained may be of value in counselling and planning surgical intervention in obese patients with PC.

scholarly journals Low ETV1 mRNA expression is associated with recurrence in gastrointestinal stromal tumors

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Keiichi Sakamaki ◽  
Kohei Funasaka ◽  
Ryoji Miyahara ◽  
Kazuhiro Furukawa ◽  
Takeshi Yamamura ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Clinical Outcomes ◽  
Gastrointestinal Stromal Tumors ◽  
Recurrence Free Survival ◽  
Independent Factor ◽  
Clinical Role ◽  
Free Survival ◽  
Stromal Tumors ◽  
Malignant Gists

Abstract Although the majority of gastrointestinal stromal tumors (GISTs) possess KIT mutations that induce constitutive signal transduction, the clinical outcomes are variable. The ETS translocation variant 1 (ETV1) gene encodes a transcription factor that is reported to cooperate with KIT in GISTs. However, the clinical role of ETV1 is largely unknown. The aim of this study was to examine ETV1 expression and its associations with clinical features in GISTs. We conducted a cohort study involving 64 patients with GISTs who underwent surgical resection between October 2008 and February 2015. ETV1 mRNA expression was compared with that in non-GISTs and was analyzed among risk classifications or clinical outcomes. The GIST samples exhibited significantly higher ETV1 mRNA expression than the non-GIST samples (P < 0.0001). Sixty-four GISTs were stratified into high or low ETV1 mRNA expression groups based on the median relative abundance of ETV1 mRNA. The multivariate analysis showed that low ETV1 expression, as well as tumor size and mitotic index, was an independent factor of recurrence (hazard ratio: 8.1). Patients with high ETV1 expression achieved significantly longer recurrence-free survival (RFS) times than those with low ETV1 expression (P = 0.025). Our study revealed that low ETV1 expression is an independent factor of recurrence after surgery in patients with GISTs, and thus, low ETV1 expression might be a marker of more aggressive malignant GISTs.

Tumor-associated CD66b+ neutrophil and CD8+ lymphocyte densities as independent prognostic factors for recurrence in localized cervical cancer: Automated digital image analysis and observer-assisted stereological assessments.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5532-5532
Author(s):  
Andreas Carus ◽  
Morten Ladekarl ◽  
Patricia Switten Nielsen ◽  
Henrik Hager ◽  
Bettina S Nedergaard ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Image Analysis ◽  
Prognostic Factors ◽  
Digital Image ◽  
Digital Image Analysis ◽  
Figo Stage ◽  
Prognostic Impact ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Macrophage Density

5532 Background: The prognostic impact of tumor-associated immune cells in cervical cancer is unclear. Methods: Automated digital image analysis (DIA) software and observer-assisted stereological (OAS) assessments were used to obtain densities of immunostains for CD66b+ neutrophils, CD163+ macrophages, and CD8+lymphocytes in scanned whole slide images of tumor sections from 101 patients with FIGO stage IB and IIA cervical cancer. Primary end-point was recurrence-free survival (RFS). Results: The highest densities of CD66b+ neutrophils and CD163+ macrophages were observed by OAS in the peritumoral compartment (median 53.1 cells/mm2 and 1.3% area fraction, respectively). DIA required far less human resources than OAS assessments. We observed high correlations between DIA and OAS variables of corresponding parameters; spearman ρ was 0.79 for CD8+ lymphocytes , 0.85 for CD66b+ neutrophils, and 0.92 for CD163+ macrophages (all p <0.0001). Hazard rates for DIA assessments in the global tumor area were comparable with the prognostically strongest OAS assessments in the peritumoral compartment. In multivariate analysis, high density of CD66b+ neutrophils (HR 2.6; 95% CI 1.2–5.7; p = 0.02), low density of CD8+ lymphocytes (HR 2.3; 95% CI 1.1–4.9; p = 0.03), and presence of lymph node metastases (HR 2.6; 95% CI 1.2–5.5; p = 0.02) were independent predictors of poor RFS, whereas FIGO stage and CD163+macrophage density were not. The CD66b/CD8 immunostain index obtained by DIA had excellent discriminatory power for each quartile with 5-year RFS of 92%, 80%, 65%, and 48% for quartile I (<0.019), II (0.02-0.05), III (0.06-0.24), and IV (>0.25), respectively (p = 0.001). Conclusions: High tumor-associated CD66b+ neutrophil and low CD8+ lymphocyte densities are independent prognostic factors for short recurrence-free survival in cervical cancer assessed by DIA and OAS. Combined CD66b+ neutrophil/CD8+ lymphocyte immunostain index obtained by DIA is a strong and cost-efficient prognostic variable with potential for routine application.

Prognostic impact of LDH and HCG levels in marker-positive seminomas.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 392-392 ◽  
Author(s):  
Christoph Alexander Seidel ◽  
Gedske Daugaard ◽  
Tim Nestler ◽  
Alexey Tryakin ◽  
Christian Daniel Fankhauser ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Serum Levels ◽  
Rank Test ◽  
Prognostic Impact ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Oncological Outcomes ◽  
Log Rank Test

392 Background: The prognostic impact of LDH and HCG serum levels in marker positive metastatic seminoma patients is uncertain. This analysis evaluated the association between LDH and HCG levels with oncological outcomes in this patient population. Methods: Seminoma patients with elevated HCG levels were retrospectively analyzed. After stratification according to tumor marker levels pre- and post-orchiectomy, outcomes of subgroups were compared using log-rank test and cox-regression analysis. Study endpoints were cancer specific- (CSS) and recurrence-free survival (RFS). Results: In total, 429 HCG-positive metastatic seminoma patients (stage II n=291; stage III n=138) diagnosed between 1981 and 2018 were included. LDH + HCG levels ranged from 124 U/l to 8833 U/l (median: 619; IQR: 955) + 2 IU/l to 283,782 IU/l (median: 20; IQR: 63) pre- and from 107 U/l to 8650 U/l (median: 324; IQR: 481) + 0 IU/l to 36700 IU/l post-orchiectomy (median: 30; IQR: 121), respectively. Five-year CSS and RFS rates were 90% and 79%, respectively. Patients with LDH levels pre-orchiectomy <1.5 UNL (n=142) had a 5-year CSS (RFS) rate of 97% (88%), compared to 86% (81%) for ≥1.5 to 3 UNL (n=40), 83% (77%) for >3 to 5 UNL (n=44) and 83% (72%) for >5 UNL (n=44) (CSS p <0.001; RFS p=0.142). Concerning LDH levels post-orchiectomy this stratification was not significant but patients with LDH levels ≥3 UNL (n=77) displayed an impaired prognosis associated with a 5-year CSS (RFS) rate of 85% (79%) compared to 94% (82%) for levels <3 UNL (n=186) (CSS p=0.025; RFS p=0.447). Patients with HCG levels ≥2000 IU/l (n=17) pre- but not post-orchiectomy had a 5-year CSS (RFS) rate of 73% (60%) compared to 94% (79%) for patients with HCG levels <2000 IU/l (n=855) (CSS p=0.09; RFS p=0.04). In cox-regression analysis LDH ≥1.5 UNL (p=0.037; HR 3.32, CI95%1.08-10.26) and HCG levels ≥2000 IU/l (p=0.044; HR 3.69, 95%CI1.04-13.13) pre-orchiectomy were confirmed as prognostic factors for CSS. Conclusions: LDH levels inversely correlate with survival outcomes, suggesting ≥1.5 UNL pre- and ≥3 UNL post-orchiectomy as potential cut-off values for further risk assessment. Patients with extensive HCG elevations may represent an unfavorable subgroup concerning RFS and CSS, but only few patients were affected.

Cumulative Efficacy and Safety of 5-Year Deferasirox (Exjade®) Treatment in Pediatric Patients with Thalassemia Major: A Phase II Multicenter Prospective Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5413-5413 ◽  
Author(s):  
Antonio Piga ◽  
Kamila Kebaili ◽  
Renzo Galanello ◽  
Valentine Jehl ◽  
Corinne Rebischung ◽  
...  
Keyword(s):  
Iron Overload ◽  
Children And Adolescents ◽  
Sexual Development ◽  
Pediatric Patients ◽  
Prospective Trial ◽  
Thalassemia Major ◽  
Age Group ◽  
Iron Intake ◽  
Relative Change

Abstract Background: Pediatric thalassemia major (TM) patients may begin lifelong iron chelation therapy (ICT) as early as 2 years to avoid potential complications of iron overload, such as impaired growth and the later development of cardiac dysfunction. Deferasirox (Exjade®), administered orally once daily, was developed to improve compliance to long-term ICT in patients with transfusion-dependent anemias. We report cumulative efficacy, safety and development data in pediatric patients with transfusion-dependent TM treated with deferasirox for 5 years (study 106). Methods: Pediatric TM patients stratified into two age groups (children 2-≤12 years; adolescents 12–17 years) were enrolled in study 106 and received deferasirox 10 mg/kg/day for 1 year. Patients completing the 1 year study were able to continue deferasirox treatment for an additional 4 years at adjusted doses, to evaluate long term safety and effect on liver iron concentration (LIC). Safety was assessed by the incidence and type of adverse events (AEs), laboratory parameters and growth/sexual development. Efficacy was evaluated by changes in LIC by SQUID. Results: 20 children (mean age 6.7±2.8 years) and 20 adolescents (mean age 14.1±1.6 years) were enrolled. Children had a greater mean iron intake (0.46–0.49 mg/kg/day) than adolescents (0.39–0.41 mg/kg/day). Median exposure to deferasirox was 5.0 years for children, 5.5 years for adolescents; mean dose in children and adolescents was 18.9±5.7 and 20.9±4.5 mg/kg/day, respectively. On average, 30% of children and 10% of adolescents received &lt;15 mg/kg/day. Mean final dose was 26.3 mg/kg/day for children and 27.8 mg/kg/day for adolescents. Relative change in LIC over the treatment period is shown in Figure 1. Figure 1. Boxplot of relative change in LIC during deferasirox treatment, by age group Figure 1. Boxplot of relative change in LIC during deferasirox treatment, by age group Overall, 24 patients (60.0%; 11 children and 13 adolescents) completed the 5-year study. Reasons for discontinuation were AEs (n=8), consent withdrawal (n=7), unsatisfactory therapeutic effect (n=1). Most common AEs were cough, pyrexia (n=34, 85%) and rhinitis (n=30, 75%); the annual frequency of reported AEs did not increase from year to year and generally occurred in similar proportions for children and adolescents. One child had a serious AE (increased transaminases) assessed as drug-related. Two other patients had an ALT increase &gt;10 × ULN on at least one visit; baseline levels were &gt;8 × ULN in one patient, and normal in the other. Both patients were restarted on deferasirox after 2 week interruptions without further incident. No patient had an increase in serum creatinine &gt;33% above baseline and ULN at two consecutive visits. Neutropenia (neutrophil count &lt;1.5×109/L at two consecutive visits), assessed unrelated to treatment, occurred in one child and two adolescents. There were no clinically significant visual defects and one child had a drug-related audiometric abnormality (hypoacusis). Physical development was normal in both groups; growth velocity was higher in children. Sexual development progressed normally in adolescents. Conclusions: Deferasirox dose-dependently reduced iron overload over 5 years of treatment in these heavily transfused pediatric patients with TM. Dose increases over time, with a stable iron intake, were associated with a decrease in LIC for both groups, but the reduction in LIC was greater in adolescents. Despite having a higher transfusional iron intake, more children than adolescents were on a dose &lt;15 mg/kg/day, highlighting that transfusional iron intake should be considered when selecting deferasirox dose. Deferasirox was generally well tolerated. There was no evidence of progressive renal, hepatic or bone marrow dysfunction. Deferasirox treatment had no negative impact on growth and sexual development.

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