Benefit of Targeted Intensification for NCI High Risk Childhood Lymphoblastic Leukaemia: Results of the United Kingdom Medical Research Council Trial ALL97 and ALL97/99.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1869-1869
Author(s):  
Ajay Vora ◽  
Rachel Ward ◽  
Jeanette Payne ◽  
Chris Mitchell ◽  
Tim Eden ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Groups ◽  
Cell Phenotype ◽  
Cranial Radiotherapy ◽  
Childhood All ◽  
Relapse Risk ◽  
Treatment Regimens ◽  
Cns Relapse ◽  
Low Incidence ◽  
The Uk

Abstract In November1999, the UK childhood ALL trial, ALL 97, adopted CCG risk stratification and treatment regimens in favour of the UKALL approach due to concerns over lower event-free survival (EFS) in the UK compared to the US. A key new feature in the amended trial, ALL97/99, was NCI risk group and early marrow response targeted intensification. Of 1935 patients registered in the trial between January 1997 and June 2002, 997 were treated on ALL97 and 938 on ALL97/99. EFS was better in ALL97/99 compared with ALL 97 (5 year EFS: ALL 97 = 74.1%, 95% CI 71.4%–76.8% vs ALL 97/99 = 78.9%, 76.0%–81.8%, p=0.002). To investigate whether particular sub-groups benefited more or less with the CCG approach, we compared outcomes for different risk groups within the two parts of the trial in regard to EFS, overall survival (OS) and CNS relapse risk. All p values quoted are two-sided. EFS and OS were significantly better in ALL97/99 compared with ALL97 for NCI high risk (HR) patients (5 year EFS: ALL 97 = 61.8%, 95% CI: 56.9–66.7%, ALL 97/99 = 71.8% 95% CI: 66.7–76.9%, p = 0.0006. 5 year OS: ALL97 = 71.3%, 95% CI: 66.8–75.8%, ALL97/99 = 80.3% 95% CI: 76.0–84.6%, p = 0.005), but did not differ significantly for NCI standard risk (SR) patients (5 year EFS: ALL 97 = 81.7% 95% CI: 78.6–84.8%, ALL 97/99 = 83.3% 95% CI: 79.8–86.8%, p = 0.3. 5 year OS: ALL97 = 91.2% 95% CI: 89.0–93.4%, ALL97/99 = 92.6% 95% CI: 90.4–94.8%, p = 0.5). The incidence of isolated CNS relapse was also significantly lower in ALL97/99 for NCI HR (ALL97 = 8% vs ALL97/99 = 3.5%, p = 0.01) but not NCI SR patients (ALL97 = 3.5% vs ALL97/99 = 2.7%, p = 0.6). Despite restricting the use of cranial radiotherapy to patients with overt CNS disease (CNS 3, <5% of all patients), the incidence of isolated CNS relapse in ALL97/99 was reassuringly low, even for sub-groups at high risk of CNS relapse such as those with WCC > 100 × 10 9/l (4.8%) or T cell phenotype (3.8%). Isolated CNS relapse risk in ALL97/99 patients randomised to dexamethasone (which was compared with prednisolone in the trial) was 1.8%, similar to that reported with use of cranial radiotherapy for a higher proportion of patients. A targeted intensification approach improves EFS for NCI HR patients and, especially when combined with systemic dexamethasone, results in a low incidence of isolated CNS relapse for high risk sub-groups without use of cranial radiotherapy.

scholarly journals Prophylaxis of venous thromboembolism in general surgery: guidelines differ and we still need local policies

2011 ◽  
Vol 93 (5) ◽  
pp. 370-374
Author(s):  
D Veeramootoo ◽  
L Harrower ◽  
R Saunders ◽  
D Robinson ◽  
WB Campbell
Keyword(s):  
At Risk ◽  
Venous Thromboembolism ◽  
High Risk ◽  
Risk Groups ◽  
Low Risk ◽  
Vte Prophylaxis ◽  
Risk Patients ◽  
Local Policies ◽  
One Year ◽  
The Uk

INTRODUCTION Venous thromboembolism (VTE) prophylaxis has become a major issue for surgeons both in the UK and worldwide. Sev-eral different sources of guidance on VTE prophylaxis are available but these differ in design and detail. METHODS Two similar audits were performed, one year apart, on the VTE prophylaxis prescribed for all general surgical inpatients during a single week (90 patients and 101 patients). Classification of patients into different risk groups and compliance in prescribing prophylaxis were examined using different international, national and local guidelines. RESULTS There were significant differences between the numbers of patients in high, moderate and low-risk groups according to the different guidelines. When groups were combined to indicate simply ‘at risk’ or ‘not at risk’ (in the manner of one of the guidelines), then differences were not significant. Our compliance improved from the first audit to the second. Patients at high risk received VTE prophylaxis according to guidance more consistently than those at low risk. CONCLUSIONS Differences in guidance on VTE prophylaxis can affect compliance significantly when auditing practice, depending on the choice of ‘gold standard’. National guidance does not remove the need for clear and detailed local policies. Making decisions about policies for lower-risk patients can be more difficult than for those at high risk.

High Dose Methotrexate (HD MTX at 2 gr/sqm x 4) Associated to Extended Intrathecal (IT) Chemotherapy Is Effective for Prevention of Central Nervous System (CNS) Relapse in Childhood ALL Treated with BFM Systemic Therapy.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 10-10 ◽  
Author(s):  
Valentino Conter ◽  
Carmelo Rizari ◽  
Maria Grazia Valsecchi ◽  
Daniela Silvestri ◽  
Maurizio Aricò ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Relapse Rate ◽  
Preventive Therapy ◽  
High Dose ◽  
Cranial Radiotherapy ◽  
Eligibility Criteria ◽  
Secondary Neoplasms ◽  
Childhood All ◽  
Continuation Phase ◽  
Cns Relapse

Abstract Introduction: In the last two decades, treatment to prevent CNS relapses in childhood ALL has been characterized by a progressive replacement of cranial radiotherapy (CRT) with HD-MTX and/or protracted IT chemotherapy. AIEOP has already reported that HD-MTX (5 g/sqm x 4), associated with protracted use of IT MTX led to a 6-year isolated CNS relapse rate of 0.8% in a relatively small fraction of intermediate risk (IR) ALL children (30% of the total) treated in the BFM-oriented AIEOP ALL 88 study (J Clin Oncol, 13; 10: 2497–2502, 1995). Aim: To evaluate if adequate CNS relapse prevention is obtained also by using HD-MTX at lower doses (2 gr/sqm x 4 instead of 5 gr/sqm x 4) and in a larger proportion of patients (up to 80% of the overall population) when associated to protracted IT chemotherapy. Patients and methods: Eligibility: children with newly diagnosed non-T ALL with no HR features [i.e. no poor-prednisone response and/or no t(9;22) or t(4;11) clonal translocations and/or no CR after protocol IA] and no CNS or testicular involvement at the onset. Chemotherapy was based on a traditional BFM back-bone (protocols IA+B, M, II, continuation phase). CNS relapse preventive therapy consisted of one IT MTX at diagnosis; TIT x 4 in protocol IA+IB; HD-MTX (2 g/sqm x 4) + TIT x 4 in protocol M; TIT x 2 in protocol II; during the continuation phase, TIT x 6 in the IR group and TIT x 8 in the standard risk (SR) group. Results: From 4/95 to 8/2000 1745 patients were recruited in the study AIEOP ALL 95; of these, 1441 (82.6 % of the overall ALL population) were SR (n=115) or IR (n=1326) and fulfilled the eligibility criteria for the present study. Among these 1441 patients, the following events have been observed: 264 relapses, 8 deaths in induction, 13 deaths in complete remission and 3 secondary neoplasms. Among relapses, 198 were isolated in the bone marrow, 15 isolated in the CNS, 15 isolated in the testes, 12 in the CNS+bone marrow, 10 in the testis+bone marrow, 9 in other sites +bone marrow, 5 in other isolated extramedullary sites. With a median follow-up of 5.5 years, the 6-year event-free survival (EFS) of the 1441 patients was 78.6% (SE 1.2) with an isolated CNS relapse rate of 1% (SE 0.3); when also the combined relapses involving the CNS were counted, the CNS relapse rate was 2%. Conclusions: These data confirm and extend our previous findings, suggesting that, in the context of an intensive chemotherapy program, prevention of CNS relapse may be effectively obtained in non-HR ALL children using HD-MTX at 2 gr/sqm x 4, associated with protracted IT chemotherapy, thus permitting to avoid the use of CRT.

Outcome of Patients with T-Cell Lymphoblastic Leukemia or Lymphoma: The GRAALL Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2818-2818
Author(s):  
Stéphane Leprètre ◽  
Martine Escoffre-Barbe ◽  
Patrice Chevallier ◽  
Thibaut Leguay ◽  
Laurence Legros ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Early Response ◽  
Cell Phenotype ◽  
High Dose ◽  
Cns Involvement ◽  
Childhood All ◽  
High Risk Disease ◽  
Mediastinal Disease

Abstract In 2003, the GRAALL intergroup initiated two twin protocols for adult patients with acute lymphoblastic leukemia (ALL; ≥ 20% marrow blasts) or lymphoblastic lymphoma (LL; < 20% marrow blasts), namely the GRAALL-2003 and LL-2003 trials. Treatment strategy was inspired by childhood ALL trials, including corticosteroid prephase, 5-drug induction, high dose-intensity consolidation, late intensification, CNS prophylaxis with IT injections and cranial irradiation, and 2-year maintenance. An original induction reinforcement with sequential cyclophosphamide (HyperC) was offered to ALL patients with poor early response (cortico- and/or chemo-resistance) and to all LL patients. A total of 108 patients with T-cell phenotype have been treated (76 ALL and 32 LL; median age, 30 years; M/F sex ratio, 86/22; CNS+, 9; median follow-up, 2 years). Baseline characteristics were not different among ALL and LL subgroups, except for marrow blast percentage and mediastinal enlargement (47% vs 78% for ALL vs LL; P=.005), which correlated negatively, as well as for blood counts (WBC, 27 vs 8.7 × 109/L; platelets, 60 vs 328 × 109/L; Hb, 116 vs 134 g/L for ALL vs LL; P<.001). Bulky mediastinal disease was present in 57% LL vs 22% ALL patients (P=.002). Two patients (1 ALL, 1 LL) died early while the 106 remaining (98%) reached CR. With respect to mediastinal involvement, need for a salvage course with idarubicine and high-dose cytarabine to reach CR was more frequent in LL than in ALL patients (10 LL vs 2 ALL, P<.001). Allogeneic stem cell transplantation (SCT) was offered to patients with high-risk disease, defined here as CNS involvement, poor early response, or need for salvage. Among the 55 CR patients with high-risk disease (41 ALL, 14 LL), 26 received allogeneic SCT in first CR (20 ALL, 6 LL). Overall, 23/106 CR patients relapsed (18 ALL, 5 LL) while 8 died in first CR (7 ALL, 1 LL; 4 after SCT). At 2 years, estimated DFS and overall survival were 66% (64% vs 75% for ALL vs LL, P=.59) and 75% (74% vs 78% for ALL vs LL, P=.75), respectively. The only factors which influenced outcome in this risk-adapted strategy were need for salvage (higher relapse incidence) and CNS involvement (shorter survival). As compared to historical experiences, we report here a notable gain in outcome when treating patients with T-cell lymphoblastic disease, including lymphoma, with a pediatric-inspired ALL strategy. The efficacy of this approach leads to comparable outcome for both diseases. The systematic use of HyperC induction in LL patients was well tolerated, but the need for salvage therapy was more frequent in these patients possibly due to difficulty in early mediastinal response evaluation. The presence of CNS disease at diagnosis remains an unfavorable feature. The role of HyperC during induction and the place of allogeneic SCT in first CR deserve further evaluation in this new context.

An evaluation of the performance of OraQuick® ADVANCE Rapid HIV-1/2 Test in a high-risk population attending genitourinary medicine clinics in East London, UK

2008 ◽  
Vol 19 (10) ◽  
pp. 665-667 ◽  
Author(s):  
J Zelin ◽  
N Garrett ◽  
J Saunders ◽  
F Warburton ◽  
J Anderson ◽  
...  
Keyword(s):  
High Risk ◽  
Test Performance ◽  
Predictive Value ◽  
Risk Groups ◽  
Antibody Detection ◽  
High Risk Population ◽  
Antibody Testing ◽  
Observer Error ◽  
The Uk ◽  
Hiv 1

To date, no data have been published on the use of OraQuick® ADVANCE Rapid HIV-1/2 Test (OraQuick) in the UK. We report preliminary findings of an ongoing evaluation of OraQuick in UK genitourinary (GU) medicine clinics. A total of 820 samples from patients in high-risk groups for HIV were tested with OraQuick and results were compared with standard HIV antibody testing. HIV prevalence (enzyme immunoassay [EIA]) was 5.73%, sensitivity of OraQuick was 93.64% (95% CI 82.46–98.66%), specificity 99.87% (99.28–100%), positive predictive value 97.78% (88.27–99.94%) and negative predictive value 99.61% (98.87–99.92%). This includes three false-negatives considered to be due to observer error and now rectified by further training. This has increased test sensitivity to 100%. Our observed test performance of OraQuick compares well with EIA and with other rapid tests. We believe that simple, non-invasive antibody detection tests such as OraQuick can increase HIV testing and diagnosis in UK GU medicine and community settings.

scholarly journals Nonrandom abnormalities of chromosome 9p in childhood acute lymphoblastic leukemia: association with high-risk clinical features

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 409-415 ◽  
Author(s):  
SB Murphy ◽  
SC Raimondi ◽  
GK Rivera ◽  
M Crone ◽  
RK Dodge ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Risk ◽  
Clinical Features ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Cell Phenotype ◽  
Term Survival ◽  
Childhood All ◽  
Chromosome 9P

To assess the frequency and significance of nonrandom abnormalities of chromosome 9p in childhood acute lymphoblastic leukemia (ALL), we analyzed our experience with 398 consecutive cases with completely banded karyotypes. Forty cases (10%) with abnormalities of 9p were identified: 26 with deletions, nine with unbalanced translocations resulting in the loss of 9p material, and five with apparently balanced reciprocal translocations. As compared with children with ALL lacking 9p abnormalities, these 40 cases were significantly older, had higher initial circulating WBC counts, more “lymphomatous” disease characteristics (including presence of a mediastinal mass in 15%. T- cell phenotype in 26%, splenomegaly greater than 8 cm in 25%), an increased failure rate in the first 2 to 3 years after diagnosis, and a higher incidence of extramedullary relapse. Conversely, lymphomatous ALL cases were twice as likely (19% v 8%) to have an abnormality of chromosome 9p than ALL cases lacking lymphomatous features (P = .01). The finding of an abnormal chromosome 9p, however, was not specific for lymphomatous ALL or T-cell lineage, because most cases were neither lymphomatous nor T-cell, and the overall Kaplan-Meier distribution of treatment failures for abnormal 9p cases was not statistically significantly different from control ALL cases receiving the same treatment who lacked abnormalities of 9p (P = .06, by log-rank test). We conclude that nonrandom abnormalities of chromosome 9p, especially a breakpoint in 9p21–22, occur with increased frequency in childhood ALL in association with some high-risk clinical features. Despite this association, the chromosome anomaly is nonspecific in its syndrome delineation and confers no major adverse consequence on long-term survival of childhood ALL treated with modern therapy. However, due to an apparently increased hazard of involvement of the CNS (eight of 17 failures), it may be inadvisable to lessen the intensity of CNS preventive therapy for this group of patients.

scholarly journals Younger ages at risk of Covid-19 mortality in communities of color

2020 ◽  
Vol 4 ◽  
pp. 69 ◽  
Author(s):  
Keith P. Klugman ◽  
Solomon Zewdu ◽  
Barbara E. Mahon ◽  
Scott F. Dowell ◽  
Padmini Srikantiah ◽  
...  
Keyword(s):  
South Africa ◽  
High Risk ◽  
Age Groups ◽  
Risk Groups ◽  
Minority Communities ◽  
Communities Of Color ◽  
Younger Age ◽  
Disaggregated Data ◽  
The Uk ◽  
Selection Of

More than 85% of Covid-19 mortality in high income countries is among people 65 years of age or older. Recent disaggregated data from the UK and US show that minority communities have increased mortality among younger age groups and in South Africa initial data suggest that the majority of deaths from Covid-19 are under 65 years of age. These observations suggest significant potential for increased Covid-19 mortality among younger populations in Africa and South Asia and may impact age-based selection of high-risk groups eligible for a future vaccine.

Difference in Outcome of Adolescents with Acute Lymphoblastic Leukemia (ALL) Enrolled in Pediatric (AIEOP) and Adult (GIMEMA) Protocols.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1954-1954 ◽  
Author(s):  
Anna Maria Testi ◽  
Maria Grazia Valsecchi ◽  
Valentino Conter ◽  
Marco Vignetti ◽  
Francesca Paoloni ◽  
...  
Keyword(s):  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Treatment Modalities ◽  
High Dose ◽  
Cranial Radiotherapy ◽  
Childhood All ◽  
High Risk Patients ◽  
Drug Induction ◽  
Risk Patients

Abstract Progress in the treatment of acute lymphoblastic leukaemia (ALL) has led to better survival rates; however, children have had a greater benefit from improved treatment modalities than adolescent who show an overall lower event-free survival (EFS) compared to younger patients. Some differences in the clinical and biologic characteristics of adolescents compared to childhood ALL may partly account for the different outcome, but adolescents treated on pediatric ALL trials seem to have a significantly better EFS than those treated on adult trials. We retrospectively compared the results obtained in a series of 245 patients ranging in age from 14 to 18 years diagnosed and enrolled in specific Italian children and adult ALL trials, between 4/1996 and 10/2003. One hundred and fifty patients, from 30 pediatric centers, underwent the childhood AIEOP ALL 95 and 2000 protocols; the other 95, from 28 adult centers, were enrolled in the GIMEMA ALL 0496 and 2000 protocols. The AIEOP 95 and 2000 trials are BFM-like protocols with a 7 drug induction followed by risk-modulated post-remission therapy that includes high-dose MTX and reinduction for low and intermediate groups, and intensive blocks (high-dose MTX and cytarabine) for high-risk patients. Standard maintenance therapy is administered up to a total of 2 years. Cranial radiotherapy is limited to high-risk patients. Stem cell transplantation is planned for very high-risk patients. The GIMEMA regimens are instead based on an induction with high-dose anthracyclines (cumulative dose 550 mg/m2), high-dose cytarabine as consolidation and do not include high-dose MTX and the reinduction phase. Standard maintenance with vincristine + daunorubicin/cyclophosphamide pulses is given for 2 years. Cranial radiotherapy is administered to all patients. The main patients characteristics at diagnosis, in the two groups under examination, were comparable except for age: median age was 15 and 16 years, respectively in the AIEOP and GIMEMA trials.Poor risk cytogenetic translocations and T-immunophenotype were equally dinstributed. Adolescents in the AIEOP protocols had a higher CR rate (94% vs 89%) and a lower relapse rate (17% vs 45%) compared to the adolescents enrolled in the GIMEMA trials. The 2-year overall survival rate was 80% in the AIEOP protocols and 71% in the GIMEMA trials. Detailed results according to the different clinical and biologic features of the adolescents analyzed will be presented. The results of our comparative study indicate that adolescents enrolled in pediatric trials have a more favourable clinical outcome.

scholarly journals Cost effectiveness of ramipril treatment for cardiovascular risk reduction

Heart ◽  
2001 ◽  
Vol 85 (5) ◽  
pp. 539-543
Author(s):  
I S Malik ◽  
V K Bhatia ◽  
J S Kooner
Keyword(s):  
Cardiovascular Risk ◽  
Cost Effectiveness ◽  
High Risk ◽  
Risk Reduction ◽  
Risk Groups ◽  
Cardiovascular Risk Reduction ◽  
Medium Risk ◽  
The Uk ◽  
Annual Mortality ◽  
Lifetime Treatment

OBJECTIVETo assess the cost effectiveness of ramipril treatment in patients at low, medium, and high risk of cardiovascular death.DESIGNPopulation based cost effectiveness analysis from the perspective of the health care provider in the UK. Effectiveness was modelled using data from the HOPE (heart outcome prevention evaluation) trial. The life table method was used to predict mortality in a medium risk cohort, as in the HOPE trial (2.44% annual mortality), and in low and high risk groups (1% and 4.5% annual mortality, respectively).SETTINGUK population using 1998 government actuary department data.MAIN OUTCOME MEASURECost per life year gained at five years and lifetime treatment with ramipril.RESULTSCost effectiveness was £36 600, £13 600, and £4000 per life year gained at five years and £5300, £1900, and £100 per life year gained at 20 years (lifetime treatment) in low, medium, and high risk groups, respectively. Cost effectiveness at 20 years remained well below that of haemodialysis (£25 000 per life year gained) over a range of potential drug costs and savings. Treatment of the HOPE population would cost the UK National Health Service (NHS) an additional £360 million but would prevent 12 000 deaths per annum.CONCLUSIONSRamipril is cost effective treatment for cardiovascular risk reduction in patients at medium, high, and low pretreatment risk, with a cost effectiveness comparable with the use of statins. Implementation of ramipril treatment in a medium risk population would result in a major reduction in cardiovascular deaths but would increase annual NHS spending by £360 million.

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