Effect of Young Age on Outcomes in Pediatric Acute Promyelocytic Leukemia (APL): North American Intergroup Study CALGB 9710 (Alliance)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2301-2301 ◽  
Author(s):  
Matthew A. Kutny ◽  
Susan Geyer ◽  
Kristina M Laumann ◽  
John Gregory ◽  
Cheryl L. Willman ◽  
...  
Keyword(s):  
Young Children ◽  
Arsenic Trioxide ◽  
North American ◽  
De Novo ◽  
Group Analysis ◽  
Older Age ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Pediatric All ◽  
Intergroup Trial

Abstract Purpose: Clinical trials in APL have generally reported similar outcomes for children and adults. However, sub-group analysis of pediatric patients treated on 2 consecutive trials of the European APL group demonstrated that children <5 years (yr) had an increased risk of relapse (Bally et al., JCO, 2012). Here we report the effect of age < 5 yr on outcome for the North American Intergroup Study C9710. Methods: Outcomes were compared among young children (age <5 yr, n=16) to those of older age (5-12 yr, n=25 and 13-18 yr, n=45) enrolled on C9710. Treatment on C9710 included induction with daunorubicin, cytarabine and ATRA followed by two consolidation cycles with daunorubicin and ATRA and maintenance for one year with ATRA +/- mercaptopurine and methotrexate. Patients of age ≥15 yr were randomized to receive or not receive two 5-week cycles of arsenic trioxide (ATO) before the chemotherapy consolidation. However, analysis in this study of young children compared to those of older age was restricted to patients who did not receive ATO. Results: Clinical remission (CR) rates were similar between the 3 age groups (age <5 yr= 88%, age 5-12 yr= 80%, age 13-18 yr= 82%; P=0.93). Overall survival (OS) Kaplan-Meier estimates were not significantly different (log rank P=0.84), and 5 yr OS rates were 77% (age <5 yr), 80% (age 5-12 yr), and 84% (age 13-18 yr). Similarly, event-free survival (EFS) Kaplan-Meier estimates were not significantly different (log rank P=0.48), and 5 yr EFS rates were 56% (age <5 yr), 47% (age 5-12 yr), and 59% (age 13-18 yr). Young children did not have a higher relapse rate (5-yr cumulative incidence of relapse by age: <5 yr=29%, 5-12 yr=49%, 13-18 yr=29%). Conclusions: Results of this intergroup trial demonstrate that ATRA administration during induction, consolidation and maintenance leads to CR rates >80% and 5 yr OS rates >75%. These results are superior to recently published results of pediatric non-APL acute myeloid leukemia and confirm results from the prior APL intergroup trial (INT0129) that demonstrated that ATRA in induction and/or maintenance significantly improved outcomes for pediatric APL (Gregory et al., Ped Blood and Cancer, 2009). Our sub-group analysis showed no association of age with outcomes in children treated with this regimen. Disclosures Off Label Use: Daunorubicin- labeled for use in AML for adults and for pediatric ALL (not pediatric AML) Arsenic Trioxide- labeled for use in relapsed/refractory APL (not de novo APL) Mercaptopurine and Methotrexate- labeled for use in pediatric ALL (not APL).

scholarly journals A Comparison of Outcomes Between Adolescents and Young Adults (AYA) and Children with Acute Promyelocytic Leukemia (APL): North American Intergroup Study CALGB 9710 (Alliance)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2306-2306
Author(s):  
Matthew A. Kutny ◽  
Susan Geyer ◽  
Kristina M Laumann ◽  
John Gregory ◽  
Cheryl L. Willman ◽  
...  
Keyword(s):  
Young Adults ◽  
Arsenic Trioxide ◽  
North American ◽  
Group Analysis ◽  
Disease Free Survival ◽  
Adolescents And Young Adults ◽  
Free Survival ◽  
Differential Outcomes ◽  
Significant Difference ◽  
Pediatric All

Abstract Purpose: Recent studies have demonstrated differential outcomes for adolescents and young adults (AYAs) vs. children treated for acute myeloid leukemia. Here we analyze outcomes by age group for APL patients treated on the North American Intergroup Study C9710. Methods: Patient characteristics and outcomes were compared between children (<15 yr, n=55) vs. AYAs (15-31 yr, n=42). To control for differences in treatment center, only young adults registered at Children’s Oncology Group (COG) treatment sites were included. Treatment included induction with daunorubicin, cytarabine and ATRA. All patients (pts) received two consolidation cycles with daunorubicin and ATRA and maintenance for one year with ATRA +/- mercaptopurine and methotrexate. Pts ≥15 yr were randomized to an additional two cycles of arsenic trioxide (ATO). Sub-group analysis was also performed to exclude pts ≥15 yr who received ATO and thus compare only patients <15 yr vs. ≥15 yr who had not received ATO. Results: Children and AYAs had similar characteristics of gender, race/ethnicity, Sanz risk grouping and M3v histology. Among all pts enrolled at COG sites on the study, complete response (CR) rates were similar (<15yr =85% vs. ≥15yr =81%, P=0.59). AYAs had improved 5 yr disease-free survival (DFS) from time of CR compared to younger pts (<15 yr =47% vs. ≥15 yr =70%, log rank P=0.05), and there was a trend toward difference in 5 yr event-free survival (EFS) (<15 yr =46% vs. ≥15 yr =63%, log rank P=0.13). Overall survival (OS) at 5 years was not significantly different (<15 yr =82% vs. ≥15 yr =75%, log rank P=0.47). Twenty-three of 42 pts ≥15 yr received ATO consolidation cycles, which may have contributed to their improved DFS and EFS. Thus, we analyzed outcomes by removing from the analysis patients ≥15 yr who received ATO consolidation cycles, and compared pts <15 yr who did not receive ATO (n=55) to pts ≥15 yr who were randomized to no ATO (n=19). CR rates were again similar (<15 yr =85% vs. ≥15 yr no ATO =84%, P=1.0). There was no significant difference in other outcomes including 5-yr DFS from time of CR (<15 yr =47% vs. ≥15 yr no ATO =63%, log rank P=0.31), 5-yr EFS (<15 yr =46% vs. ≥15 yr no ATO=53%, log rank P=0.89), or 5-yr OS (<15 yr =82% vs. ≥15 yr no ATO=79%, log rank P=0.78). Conclusions: The C9710 study demonstrated improved EFS, DFS and OS among adult patients receiving ATO consolidation compared to those who did not receive ATO (Powell et al., Blood, 2010). The current analysis of results for AYAs versus younger pediatric pts showed improved DFS among the whole AYA cohort (of which 55% received ATO consolidation) compared to pts <15 yr (of which 0% received ATO). When the analysis was restricted to AYA pts not receiving ATO, however, the results of this intergroup APL trial showed similar CR, DFS, EFS and OS for AYAs and younger pts. Thus, unlike other subtypes of AML, APL appears to have a consistent response across the pediatric and AYA age groups. The most recent COG clinical trial in APL is now evaluating whether pediatric patients can also benefit from ATO consolidation. Disclosures Off Label Use: Daunorubicin- labeled for use in AML for adults and for pediatric ALL (not pediatric AML) Arsenic Trioxide- labeled for use in relapsed/refractory APL (not de novo APL) Mercaptopurine and Methotrexate- labeled for use in pediatric ALL (not APL).

Toxicity in patients (pts) age 65 or older with dose-adjusted REPOCH (DA-REPOCH) for untreated diffuse large B-cell lymphoma (DLBCL).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18508-e18508
Author(s):  
Deborah Marie Stephens ◽  
Amy S. Ruppert ◽  
Beth Christian ◽  
Jeffrey Alan Jones ◽  
Joseph M. Flynn ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
De Novo ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Median Number ◽  
Front Line ◽  
Bulky Disease ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Number Of Cycles

e18508 Background: ORR of 97-99% and 5-yr PFS of 75-79% are reported with front-line DA-REPOCH in pts age 19-85. In these prospective series, 72% of pts escalated ≥ 1 dose level (DL), febrile neutropenia (FN) occurred in 36-51% pts, and 3-4% died of toxicity. Methods: We performed retrospective analysis of pts ≥ 65 treated with DA-REPOCH front-line for DLBCL at Ohio State University from 2002-2011. PFS estimates were calculated by the Kaplan-Meier method. Logistic regression and proportional hazards models were fit to identify variables associated with ORR and PFS, respectively. Results: 69 pts ≥ 65 yrs (range, 65-92) received DA-REPOCH for de novo (n=42) or transformed (prior CLL=16, FL=9, HL=2) DLBCL, including 28 pts ≥ 75. Performance status (PS) was ≥ 2 in 43%, 86% were stage III-IV, 77% had an aaIPI ≥ 2, 19% had bulky disease ≥ 10 cm, 83% had extranodal disease, and median creatinine clearance (CrCl) was 64 ml/min. Median number of cycles was 5 (range 1-7). Max DL was 1, 2, and 3 in 72, 13, and 6% of pts, respectively, and 9% received all cycles below DL 1. Max DL and number of cycles were similar between pts 65-74 and > 75. Dose reductions (DR), delays, FN, and hospitalization occurred in 48, 39, 38, and 42% of pts, respectively. DR were associated with age ≥ 75 (p=0.001) or reduced CrCl (p=0.02) and delays strongly associated with PS ≥ 2 (p=0.001). FN was associated with bulky disease (p=0.03); 31% of pts without bulky disease developed FN compared to 67% with bulk. Nine pts (13%, 3 pts ≥ 75) died of toxicity (7 pts at DL 1 and 2 at DL < 1). ORR was 67% (95% CI 52-75%). Median PFS was 17 mos (95% CI 6-43). Increased LDH (p=0.008 and p<0.001) and number of prior chemotherapies (p=0.04 and p<0.001) were independently predictive for ORR and PFS, respectively. DR and age were not associated with ORR or PFS, controlling for LDH and number of prior regimens. In 42 pts with de novo DLBCL, ORR was 71% (95% CI 54-85%) and median PFS was 36 mos (95% CI 7-94). Conclusions: In this retrospective study, toxicity is increased with DA-REPOCH in pts ≥ 65 with DLBCL, compared to published results in a younger population. Age ≥ 75, impaired CrCl, and poor PS are associated with increased risk of DR and delays, although age and DR do not appear to impact ORR and PFS.

scholarly journals Cross-sectional observational study of epidemiology of COVID-19 and clinical outcomes of hospitalised patients in North West London during March and April 2020

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e044384
Author(s):  
Guduru Gopal Rao ◽  
Alexander Allen ◽  
Padmasayee Papineni ◽  
Liyang Wang ◽  
Charlotte Anderson ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Clinical Outcomes ◽  
Severe Infection ◽  
Older Age ◽  
Cross Sectional ◽  
North West ◽  
Icu Admission ◽  
Risk Of Death ◽  
Hospitalised Patients ◽  
Increased Risk

ObjectiveThe aim of this paper is to describe evolution, epidemiology and clinical outcomes of COVID-19 in subjects tested at or admitted to hospitals in North West London.DesignObservational cohort study.SettingLondon North West Healthcare NHS Trust (LNWH).ParticipantsPatients tested and/or admitted for COVID-19 at LNWH during March and April 2020Main outcome measuresDescriptive and analytical epidemiology of demographic and clinical outcomes (intensive care unit (ICU) admission, mechanical ventilation and mortality) of those who tested positive for COVID-19.ResultsThe outbreak began in the first week of March 2020 and reached a peak by the end of March and first week of April. In the study period, 6183 tests were performed in on 4981 people. Of the 2086 laboratory confirmed COVID-19 cases, 1901 were admitted to hospital. Older age group, men and those of black or Asian minority ethnic (BAME) group were predominantly affected (p<0.05). These groups also had more severe infection resulting in ICU admission and need for mechanical ventilation (p<0.05). However, in a multivariate analysis, only increasing age was independently associated with increased risk of death (p<0.05). Mortality rate was 26.9% in hospitalised patients.ConclusionThe findings confirm that men, BAME and older population were most commonly and severely affected groups. Only older age was independently associated with mortality.

scholarly journals OP0051 STRUCTURAL ENTHESEAL LESIONS IN PSORIASIS PATIENTS ARE ASSOCIATED WITH AN INCREASED RISK OF PROGRESSION TO PSORIATIC ARTHRITIS - A PROSPECTIVE COHORT STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 33.1-34 ◽  
Author(s):  
D. Simon ◽  
K. Tascilar ◽  
A. Kleyer ◽  
S. Bayat ◽  
E. Kampylafka ◽  
...  
Keyword(s):  
Cohort Study ◽  
Psoriatic Arthritis ◽  
Musculoskeletal Pain ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Progression Rate ◽  
Research Support ◽  
Advisory Boards ◽  
Kaplan Meier ◽  
Increased Risk

Background:We have previously reported that the presence of musculoskeletal pain in psoriasis patients is associated with a higher risk of developing psoriatic arthritis (PsA) (1). Furthermore, a subset of psoriasis patients shows evidence for structural entheseal lesions (SEL) in their hand joints (2), sometimes also referred as “Deep Koebner Phenomenon”, which are highly specific for psoriatic disease and virtually absent in healthy controls, rheumatoid arthritis and hand osteoarthritis patients (2-4). However, it remains unclear whether SEL alone or in combination with musculoskeletal pain are associated with the development of PsA.Objectives:To test whether the presence of SEL in psoriasis patients increases the risk for progression to PsA and how this is related to the presence of musculoskeletal pain.Methods:Psoriasis patients without evidence of PsA were enrolled in a prospective cohort study between 2011 and 2018. All patients underwent baseline assessment of SEL in their 2ndand 3rdMCP joints by high-resolution peripheral quantitative computed tomography (HR-pQCT). The risk of PsA development associated with SEL and arthralgia was explored using survival analyses and multivariable Cox regression models.Results:114 psoriasis patients (72 men/42 women) with a mean (SD) follow-up duration of 28.2 (17.7) months were included, 24 of whom developed PsA (9.7 /100 patient-years, 95%CI 6.2 to 14.5) during the observation period. Patients with SEL (N=41) were at higher risk of developing PsA compared to patients without such lesions (21.4/100 patient-years, 95%CI 12.5 to 34.3, HR 5.10, 95%CI 1.53 to 16.99, p=0.008) (Kaplan Meier plot A). Furthermore, while patients without arthralgia and without SEL had a very low progression rate to PsA (1/29; 3.4%), patients with arthralgia but no SEL showed higher progression (5/33; 15.2%), which was in line with previous observations (1) (Kaplan Meier plot B). Presence of SEL further enhanced the risk for progression to PsA both in the absence (6/16; 37.5%) and presence (6/14; 42.8%) of arthralgia with the highest progression rate in those subjects with both arthralgia and SEL (p<0.001 by log rank test for trend) (Kaplan Meier plot B).Conclusion:Presence of SEL is associated with an increased risk of developing PsA in patients with psoriasis. If used together with pain, SEL allow defining subsets of psoriasis patients with very low and very high risk to develop PsA.References:[1]Faustini F et al. Ann Rheum Dis. 2016;75:2068-2074[2]Simon D et al. Ann Rheum Dis. 2016;75:660-6[3]Finzel S et al. Ann Rheum Dis. 2011;70:122-7[4]Finzel S et al. Arthritis Rheum. 2011;63:1231-6Disclosure of Interests:David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Koray Tascilar: None declared, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, Sara Bayat Speakers bureau: Novartis, Eleni Kampylafka Speakers bureau: Novartis, BMS, Janssen, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, Jürgen Rech Consultant of: BMS, Celgene, Novartis, Roche, Chugai, Speakers bureau: AbbVie, Biogen, BMS, Celgene, MSD, Novartis, Roche, Chugai, Pfizer, Lilly, Louis Schuster: None declared, Klaus Engel: None declared, Michael Sticherling Grant/research support from: Novartis, Consultant of: Advisory boards Abbvie, Celgene, Janssen Cilag, Lilly, Pfizer, MSD, Novartis, Amgen, Leo, Sanofi, UCB, Speakers bureau: Abbvie, Celgene, Janssen Cilag, Leo, MSD, Novartis, Pfizer, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB

Constipation is Associated with Development of Cognitive Impairment in de novo Parkinson’s Disease: A Longitudinal Analysis of Two International Cohorts

2021 ◽  
pp. 1-11
Author(s):  
Valentina Leta ◽  
Daniele Urso ◽  
Lucia Batzu ◽  
Daniel Weintraub ◽  
Nataliya Titova ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
De Novo ◽  
Motor Dysfunction ◽  
Group Differences ◽  
Motor Symptoms ◽  
Kaplan Meier ◽  
Patients At Risk ◽  
Non Motor Symptoms

Background: Constipation is regarded as one of the prodromal features of Parkinson’s disease (PD) and there is emerging evidence linking gastrointestinal dysfunction and cognitive impairment (CI) in PD. Objective: We explored whether constipation is associated with development of CI in two independent cohorts of de novo PD patients (n = 196 from the Non-motor International Longitudinal Study [NILS] and n = 423 from the Parkinson’s Progression Markers Initiative [PPMI] study). Methods: Constipation was clinically defined using the Non-Motor Symptoms Scale (NMSS) item-21 [NILS] and Scales for Outcomes in PD-Autonomic (SCOPA-AUT) item-5 [PPMI]. We assessed baseline group differences (PD with or without constipation) in CI, global non-motor symptoms burden, motor dysfunction, and striatal dopaminergic denervation. Kaplan-Meier method estimated group differences in cumulative proportion of patients with incident CI over three years. In PPMI, we subsequently performed univariate and multivariate Cox survival analyses to evaluate whether constipation predicts incident mild cognitive impairment or dementia over a 6-year period, including constipation and other known predictors of CI as covariates. Results: Patients with constipation had greater motor and global non-motor burden in both cohorts at baseline (p <  0.05). Kaplan-Meier plots showed faster conversion to CI in patients with constipation in both cohorts (p <  0.05). In PPMI, 37 subjects developed dementia during a mean follow-up of 4.9 years, and constipation was an independent predictor of dementia onset (hazard ratio = 2.311; p = 0.02). Conclusion: Constipation in de novo PD patients is associated with development of cognitive decline and may serve as a clinical biomarker for identification of patients at risk for cognitive impairment.

scholarly journals Impact of Inadequate Calorie Intake on Mortality and Hospitalization in Stable Patients with Chronic Heart Failure

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 874
Author(s):  
Yoshikuni Obata ◽  
Naoya Kakutani ◽  
Shintaro Kinugawa ◽  
Arata Fukushima ◽  
Takashi Yokota ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Outcomes ◽  
Energy Requirement ◽  
Multivariate Logistic Regression Analysis ◽  
Calorie Intake ◽  
Energy Deficiency ◽  
Intrinsic Nature ◽  
Clinical Events ◽  
Kaplan Meier ◽  
Increased Risk

Malnutrition is highly prevalent in patients with heart failure (HF), but the precise impact of dietary energy deficiency on HF patients’ clinical outcomes is not known. We investigated the associations between inadequate calorie intake and adverse clinical events in 145 stable outpatients with chronic HF who had a history of hospitalization due to worsening HF. To assess the patients’ dietary pattern, we used a brief self-administered diet-history questionnaire (BDHQ). Inadequate calorie intake was defined as <60% of the estimated energy requirement. In the total chronic HF cohort, the median calorie intake was 1628 kcal/day. Forty-four patients (30%) were identified as having an inadequate calorie intake. A Kaplan–Meier analysis revealed that the patients with inadequate calorie intake had significantly worse clinical outcomes including all-cause death and HF-related hospitalization during the 1-year follow-up period versus those with adequate calorie intake (20% vs. 5%, p < 0.01). A multivariate logistic regression analysis showed that inadequate calorie intake was an independent predictor of adverse clinical events after adjustment for various factors that may influence patients’ calorie intake. Among patients with chronic HF, inadequate calorie intake was associated with an increased risk of all-cause mortality and rehospitalization due to worsening HF. However, our results are preliminary and larger studies with direct measurements of dietary calorie intake and total energy expenditure are needed to clarify the intrinsic nature of this relationship.

scholarly journals Fast-Track Programs in Total Hip and Knee Replacement at Swedish Hospitals—Influence on 2-Year Risk of Revision and Mortality

2021 ◽  
Vol 10 (8) ◽  
pp. 1680
Author(s):  
Urban Berg ◽  
Annette W-Dahl ◽  
Anna Nilsdotter ◽  
Emma Nauclér ◽  
Martin Sundberg ◽  
...  
Keyword(s):  
Fast Track ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Total Hip ◽  
Total Knee Replacements ◽  
Risk Of Death ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Hip And Knee Arthroplasty ◽  
Total Knee

Purpose: We aimed to study the influence of fast-track care programs in total hip and total knee replacements (THR and TKR) at Swedish hospitals on the risk of revision and mortality within 2 years after the operation. Methods: Data were collected from the Swedish Hip and Knee Arthroplasty Registers (SHAR and SKAR), including 67,913 THR and 59,268 TKR operations from 2011 to 2015 on patients with osteoarthritis. Operations from 2011 to 2015 Revision and mortality in the fast-track group were compared with non-fast-track using Kaplan–Meier survival analysis and Cox regression analysis with adjustments. Results: The hazard ratio (HR) for revision within 2 years after THR with fast-track was 1.19 (CI: 1.03–1.39), indicating increased risk, whereas no increased risk was found in TKR (HR 0.91; CI: 0.79–1.06). The risk of death within 2 years was estimated with a HR of 0.85 (CI: 0.74–0.97) for TKR and 0.96 (CI: 0.85–1.09) for THR in fast-track hospitals compared to non-fast-track. Conclusions: Fast-track programs at Swedish hospitals were associated with an increased risk of revision in THR but not in TKR, while we found the mortality to be lower (TKR) or similar (THR) as compared to non-fast track.

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