scholarly journals Febrile Neutropenia in Children with Acute Lymphoblastic Leukemia Treated with BFM Protocols

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5245-5245
Author(s):  
Gul Nihal Ozdemir ◽  
Gulen Tuysuz ◽  
Hilmi Apak ◽  
Alp Ozkan ◽  
Inci Yildiz ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Febrile Neutropenia ◽  
Cause Of Death ◽  
Risk Group ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Newly Diagnosed ◽  
Risk Patients

Abstract Aim: Overall survival from leukemia is less in low and middle-income countries than in high-income countries. The aim of this study is to review febrile neutropenia (FN) episodes in children with acute lymphoblastic leukemia (ALL) treated with BFM (Berlin-Franfurt-Münich) protocols at a single center in Turkey. Methods: Retrospective data were extracted from medical records of children (1-18 years old) with newly diagnosed and relapsed ALL and who were treated between 1995-2010 at Istanbul University, Cerrahpasa Medical Faculty, Pediatric Hematology Oncology Dept. Results: Two hundred -forty-five FN episodes were detected in 96 evaluable children (mean age: 5.9±3.7 years; M/F: 50/46). According to BFM risk groups; 32 were SRG (standard risk group), 56 were MRG (medium risk group) and 8 were HRG (high risk group) patients. Fifteen patients had relapsed on follow-up and 2 of them had a second relapse. The mean number of FN episodes was 2.5 (±1.58; 0-8) per newly diagnosed patient and 3.6 (±1.88; 1-8) per relapsed patient. Febrile neutropenia episodes were more frequent at high risk patients compared to standart risk patients (p≤0.05). Patients diagnosed before year 2000 had less FN episodes compared to patients diagnosed after 2000 (p≤0.05). Fifty-seven of the FN episodes were fever of unknown origin, 16% were clinically documented infection and 27% were microbiologically documented infection. Of the microbiologically documented infections, 44% of them were caused by gram positive bacteria and 43% were by gram negative bacteria. Eight of 96 patients developed invasive fungal infection during initial treatment and 4 out of 15 patients who relapsed. Of 9 patients who expired on follow-up, the cause of death was fungal infections in 4 and FN in 1. Conclusion: The high rate of infectious deaths in leukemia compared to that reported in high-income countries, suggests that improvements in infection care and prevention are necessary to improve survival in patients with leukemia. We showed that over the years FN episodes increased at our center in contrast to better quality of patient care. This increase in infections may be atrributed to more intensive treatment regimens. We also showed that high risk and relapsed patients who are treated more aggresively have increased infection rate. The most common cause of death was fungal infections. Disclosures No relevant conflicts of interest to declare.

scholarly journals Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3122-3133 ◽  
Author(s):  
A Reiter ◽  
M Schrappe ◽  
WD Ludwig ◽  
W Hiddemann ◽  
S Sauter ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Multicenter Trial ◽  
Low Risk ◽  
Event Free Survival ◽  
Free Survival ◽  
Risk Patients ◽  
To Receive

Abstract In trial ALL-BFM 86, the largest multicenter trial of the Berlin- Frankfurt-Munster (BFM) study group for childhood acute lymphoblastic leukemia (ALL), treatment response was used as an overriding stratification factor for the first time. In the previous trial ALL-BFM 83, the in vivo response to initial prednisone treatment was evaluated prospectively. A blast cell count of > or = 1,000/microL peripheral blood after a 7-day exposure to prednisone and one intrathecal dose of methotrexate (MTX) identified 10% of the patients as having a significantly worse prognosis. In trial ALL-BFM 86 patients with > or = 1,000/microL blood blasts on day 8 were included in an experimental branch EG. Patients with < 1,000/microL blood blasts on day 8 were stratified by their leukemic cell burden into two branches, Standard Risk Group (SRG) and Risk Group (RG). SRG patients received an eight- drug induction followed by consolidation protocol M (6-mercaptopurine, high-dose [HD] MTX 4 x 5 g/m2) and maintenance. RG patients were treated with an additional eight-drug reinduction element. For EG patients protocol M was replaced by protocol E (prednisone, HD-MTX, HD- cytarabine, ifosfamide, mitoxantrone). All patients received intrathecal MTX therapy; only those of branches RG and EG received cranial irradiation. In branch RG, patients were randomized to receive or not to receive late intensification (prednisone, vindesine, teniposide, ifosfamide, HD-cytarabine) in the 13th month. During the trial reinduction therapy was introduced in branch SRG, because in the follow-up of trial ALL-BFM 83 the randomized low-risk patients receiving reinduction did significantly better. Nine hundred ninety- eight evaluable patients were enrolled, 28.6% in SRG, 61.1% in RG, 10.3% in EG. At a median follow-up of 5.0 (range 3.4 to 6.9) years, the estimated 6-year event-free survival was 72% +/- 2% for the study population, 58% +/- 5% in branch SRG for the first 110 patients without reinduction therapy, 87% +/- 3% for the next 175 patients with reinduction therapy, 75% +/- 2% in branch RG, and 48% +/- 5% in branch EG. Late intensification did not significantly affect treatment outcome of RG patients; however, only 23% of the eligible patients were randomized. Prednisone poor response remained a negative prognostic parameter despite intensified therapy. The results confirmed the benefit of intensive reinduction therapy even for low-risk patients. The strategy of induction, consolidation, and intensive reinduction may offer roughly 75% of unselected childhood ALL patients the chance for an event-free survival.

scholarly journals Impact of IKZF1 Deletions and IKZF1 Plus in Pediatric Acute Lymphoblastic Leukemia Outcome

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4091-4091
Author(s):  
Maria Sara Felice ◽  
Patricia Laura Rubio ◽  
Myriam Ruth Guitter ◽  
Jorge Gabriel Rossi ◽  
Jorge Alberto Digiorge ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Relapse Rate ◽  
Copy Number ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Rank Test ◽  
Copy Number Alterations ◽  
Risk Patients ◽  
Pediatric All

Abstract Introduction: Survival of children with acute lymphoblastic leukemia (ALL) has improved in the last decades, achieving approximately 80% in Argentina. However, relapses remain the most frequent adverse event and the identification of patients with higher risk need to be refined. Deletions in IKZF1(IKZF1del) in addition with deletion of CDKN2A, CDKN2B,PAX5 or PAR1 region define a new subgroup of patients (IKZF1plus) with higher relapse rate and poor survival. Objectives: To analyze the characteristics of patients with IKZF1del and IKZF1plus, assessing the impact of the copy number alterations in several genes on survival of pediatric ALL treated with ALLIC strategy. Methods: This is a retrospective analysis performed in the population of patients admitted from October 2009 to May 2018. Samples of 432 patients with diagnosis of ALL were collected and analyzed by MLPA P-335 (MRC-Holland) for copy number alterations of IKZF1, EBF1, JAK2, CDKN2A, CDKN2B, PAX5, ETV6, BTG1, RB1 genes and PAR1 region. IKZF1plus cases were defined as those with IKZF1del with at least one additional deletion in: PAX5, CDKN2A, CDKN2B, PAR1 region. Patients were treated with 2 consecutive ALLIC protocols, according to studies stratification. Patient characteristics were compared with chi-square and Wilcoxon-sum-rank-test. Survival probability was analyzed with Kaplan-Meier calculation and survival results compared with Log-rank-test. Results: IKZF1 was not deleted in 345 cases, IKZF1del was detected in 87 cases and 47 of them were defined as IKZF1plus. Statistically significant higher WBC, MRD+ positivity on day 15, day 33 and week 12, more BCR-ABL+ and high-risk group cases, null response and higher relapse rate were observed in the IKZF1del group (total) when comparing with IKZF1 not del, and also when comparing IKZF1plus vs IKZF1 not del + IKZF1del only. EFS (SE) and DFS (SE) probabilities were: 73 (4)% and 75 (3)% for IKZF1 not del, 66 (9)% and 70 (9)% for IKZF1del, and 20 (10)% and 21 (10)% for IKZF1plus, respectively (p<0.00001).DFS of the standard-risk group was not influenced by the presence of only 1 case of IKZF1del detected in this risk-group of patients. However, DFS of intermediate-risk patients was 41 (11)% for IKZF1plus while 70 (7)% and 73 (4)% were achieved for IKZF1del and IKZF1 not del respectively (p=0,0083). Therefore, high-risk patients with IKZF1plus achieved DFS of 12 (19)% vs 65 (7)% and 50 (21)% for IKZF not del and IKZF1del respectively (p=0.0085). DFS of patients with IKZF1del + CDKN2Adel was 30 (10)% and CDKN2A not deleted 67 (9)% (p=0.0433). DFS of patients with IKZF1del + CDKN2Bdel was 42 (12)% and 66 (9)% for CDKN2B not del. DFS of cases with IKZF1del in addition to deletion of ETV6, BTG1, EBF1 orJAK2 did not show statistically significant differences when comparing with IKZF1del + normal copy number of these genes. In addition, DFS of cases with RB1del was 36 (13)% while cases without RB1del showed 70 (3)% (p=0.0071). Conclusions: 1- Patients with IKZF1del and IKZF1plus disclosed biological features related to poor outcome. 2- IKZF1plus was associated with a poor outcome in intermediate and high-risk groups according to ALLIC stratification. 3- The addition of CDKN2Adel to IKZF1del influence the outcome. However, CDKN2Bdel did not show the same effect. 4- Copy number alterations of ETV6, BTG1, EBF1 or JAK2 did not demonstrate prognostic impact. 5- RB1 showed negative influence in survival. 6- Identification of patients with IKZF1plus at diagnosis could be very useful for improving risk-group stratification of pediatric ALL patients. Disclosures No relevant conflicts of interest to declare.

Outcome and Toxicities of Modified Augmented Berlin-Frankfurt-Muenster (ABFM) Therapy Used in the Treatment of Acute Lymphoblastic Leukemia in Adolescent and Young Adult Patients, Single Center Experience From Saudi Arabia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3569-3569
Author(s):  
Suhaib Radi ◽  
Anas Merdad ◽  
Mona Al-Dabbagh ◽  
Ahmed Almohanad Absi ◽  
Ahmad Alsaeed ◽  
...  
Keyword(s):  
Overall Survival ◽  
Saudi Arabia ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Risk ◽  
Complete Remission ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Inclusion Criteria

Abstract Abstract 3569 Introduction: Acute lymphoblastic leukemia (ALL) is a neoplasm of precursor lymphoid cells known as lymphoblasts. ALL is the most common cancer in children. The prognosis among Adolescents and young adults (AYA) is intermediate between children, who have a very good prognosis with a 5-year survival rate of 80%, and adults, who have a worse prognosis with an overall survival of about 30–50%. We found no studies in Saudi Arabia which assessed the use of a Berlin-Frankfurt-Muenster (BFM) to treat patients in the AYA group. The purpose of this study is to measure the outcome and toxicities of the BFM protocol used in treatment of ALL patients in the AYA population seeking treatment at Princess Noorah Oncology Center (PNOC), at the National Guard Hospital, Jeddah, Saudi Arabia. PNOC is a tertiary referral center for the Western region of the Kingdom of Saudi Arabia. Patients referred between the ages of 14 to 25 were treated according to an augmented modified version of the Berlin-Frankfurt-Muenster (BFM) protocol. Patients' treatments were based on risk factor stratification. High risk category was identified based on the presence of one of following factors: phenotype of the leukemia (i.e. T-cell ALL is considered high risk), lack of response to therapy on day 29 of induction, cytogenetics, presence of extramedullary disease e.g. testicular or CNS disease and whether they have received steroid treatment prior to the first diagnostic marrow. High risk group was treated with doubled blocks of interim maintenance, delayed intensification the first of delayed intensification blocks included a high dose methotrexate at the dose of 5g/m2 which was first started at our center in 2008. Methodology: This study is a retrospective chart review. Patients who met the inclusion criteria within the last five years were included. The inclusion criteria were those with confirmed ALL (excluding mature B cell phenotype) aged between 14 to 25 years, and were treated with the Modified Augmented Berlin-Frankfurt-Muenster (ABFM) therapy protocol. 45 patients were indentified who fulfilled the above criteria 4 were excluded due to the lack of data and loss to follow up. Data were analyzed using SPSS version 19. Results: The mean age of 41 patients treated was 16.4 years (range; 14 – 25 years). Of 41 patients treated, 23 (56%) were males. Only one patient (2%) had CNS involvement at presentation. B cell ALL compromised 61% of the patients while 39% were T cell ALL. All 41 (100%) patients achieved complete remission after induction therapy however two patients (5%) required extended induction to achieve a complete remission status. Five (12.2%) patients relapsed at a median follow up of 30 months. Two (4.9%) patients died while in complete remission from treatment related causes. The probability of Overall Survival (OS) is 95.1% and 87.8% at 2 and 3 years, respectively. The probability of Event-free Survival (EFS) of our 41 patients is 90.2% and 82.9% at 2 and 3 years respectively. Thirty three (81%) patients developed febrile neutropenia with a total of 50 documented episodes. Thirty two (64%) of the febrile neutropenia episodes occurred during induction and re-intensification phases those two blocks were associated with a statistically significant increased risk of neutropenia (P < 0.001)compared to other blocks. Five (12%) of patients developed fungal infections there is one patient who developed two separate episodes of fungal infection. Four fungal infection episodes occurred during induction and re-intensification phases which constituted the highest risk phases for the development of fungal infections. In 38% of febrile neutropenic episodes an infectious agent was identified in 8% of episodes the isolate was a fungus. Eight patients (20%) developed Venous Thromboembolism (VTE) with a total of 9 episodes. Discussion & Conclusion: In our study population the OS & EFS were comparable to other reported groups despite the relatively increased numbers of T cell ALL (39%) patients compared to the reported average of 15–25%. The reported incidence of VTE is similar to the incidence reported by other groups while the incidence of fungal infections is relatively more than we would have expected. Complete remissions, survival, relapse and death rates are comparable to international studies. However new measures are required to lower the increased rates of fungal infections & VTE for future patients. Disclosures: No relevant conflicts of interest to declare.

Risk Factors in Childhood Acute Lymphoblastic Leukemia: A Single Center Experience in a Developing Country.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4475-4475
Author(s):  
Sema S. Anak ◽  
Leyla Agaoglu ◽  
Arzu Akcay ◽  
Ebru T. Saribeyoglu ◽  
Didem Y. Atay ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Event Free Survival ◽  
Free Survival ◽  
Risk Patients ◽  
Pediatric All

Abstract Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, with the survival rates up to 80–90%, but in high-risk patients the survival rate is still unsatisfactory. The aim of this study is to analyze the pediatric ALL data of a single pediatric university center between 1987–2005 retrospectively to identify risk factors effecting the event free survival (EFS). In order to determine the risk factors possibly effecting the survival, we analyzed gender, age, physical examination findings, blood cell count, FAB morphology, immunophenotyping results, translocations and extramedullary involvement. During the same period, chemotherapy regimens used and response to these protocols were also analyzed. A total of 372 cases [220 male (60%) and 151 female (41%)] were diagnosed and treated in our center between 1987–2005. The age distribution was as follows: 7% patients under 2 years, 68% between 2–10 years, 25% above 10 years of age. At diagnosis, 76% patients had a hemoglobin level <10gr/dl, 56% WBC >10.000/mm3, 74% platelet <100.000/mm3. Primary CNS involvement was positive in 2.5%, mediastinal mass in 8% of all patients. The morphological subtypes were as follows: L1 64%, L2 32%, L3 4%. Immunophenotypic results revealed T ALL in 22%, mature B ALL in 8% and B ALL (common, pre B, proB) in 70%. All patients received CCG modified BFM protocol (80% of all patients) until 1999. Since then high-risk patients were treated with the augmented BFM protocol and L3 patients BFM NHL 95 Protocol, while standard risk patients continued to get the CCG modified BFM protocol. The remission rate at day 33 was 97.8%. Eighty-one patients relapsed (68% patients isolated bone marrow, 16% bone marrow + extramedullary, 9% CNS, 7% testes). According to the univariate analysis of our patient population, the factors negatively effecting the EFS were age <1 year, hepatomegaly >2cm., white blood cell >50.000/mm3 and platelet count <20.000/mm3, L3 FAB morphology, ≥M2 bone marrow status at day 14; CD3, HLADR, CD45 and Tdt negativity. According to the multivariate analysis the most important negative risk factors effecting the EFS were age <1 year, hepatomegaly >2cm. and ≥M2 bone marrow status at day 14 and CD 45 negativity. After a follow up of 72±59 months (1–300 months) 58% of patients are alive & well, 28% were lost to follow up and 14% patients succumbed to death. Overall survival (OS) for 60&120 months follow up were 83%, 83% and event free survival (EFS) 72%, 70% respectively. In conclusion, in ALL patients risk assessment is very important to conduct appropriate therapy. Identifying such factors and implementing risk adapted therapy will improve our treatment results decreasing the toxicity rates in pediatric ALL. Therefore treatment of all ALL patients still remains a challenge.

Outcome of Patients with Acute Lymphoblastic Leukemia in an Egyptian Institution with Limited Resources. January 2000 - August 2011

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4882-4882
Author(s):  
Emad Ebeid ◽  
Amr Abdallah ◽  
Mahmoud Hammad ◽  
Amira Mansour ◽  
Mai Khairy ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Developing Country ◽  
Rural Area ◽  
Conflicts Of Interest ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Disease Recurrence ◽  
Newly Diagnosed

Abstract Introduction: Acute lymphoblastic Leukemia (ALL) is associated with distinctive biologic and clinical features. The diagnoses and treatments have encountered several challenges in rural area of developing countries populations. Objectives: To evaluate the response and outcome of children with newly diagnosed ALL to a protocol that was modeled after the St Jude total XIII and to assess its effectiveness and treatment obstacles in the population of a developing country. Methodology: A retrospective analysis of patients under the age of 20 treated in Pediatric Oncology department, Menia Oncology Center was conducted. The outcome is reported using descriptive measures. Estimates of Overall survival (OS) and Disease free survival (DFS) will be analyzed. Results: One hundred patients (median age 9 years, range 1 to 19 years) with newly diagnosed ALL were considered eligible between January 2000 and August 2011. Fifty-three (53%) patients were male. Initial risk stratification comprised of 28 % low risk and 71% high-risk patients. One patient was not evaluable due to early induction death. Median total leukocytic count (TLC) at presentation was 30.000/cc (range; 1.500 - 628.000/cc). Twenty-one patients had anterior mediastinal mass detected by chest x-ray. Diagnosis was confirmed by blood and bone marrow examination with Leishman stain, PAS, and Sudan Black. According to the French-American-British (FAB) classification, 96% of patients had L2 morphology. Immunophenotyping and cytogenetic analysis were not available. Central nervous system (CNS) disease at diagnosis was found in 2% of cases. Eighty-three cases achieved complete remission (CR) post induction therapy. At a median follow up of 29.7 months (range 0.1 to 130 months), 73/100 (73%) patients maintained complete remission (CR). Five patients relapsed, including hematological relapse in 4 patients and CNS relapse in 1 patient. Twenty-seven patients died during the period of follow up. Causes of death were as follows; Septicemia and multi-organ failure (n=17), Disease recurrence (n= 5), Methotrexate toxicity (n=3), and invasive fungal infections (n=2). The 5-year OS and DFS for the whole group were 69.3% and 69.9% respectively. On multivariate analysis, TLC >50.000/ cc was an independent factor of disease recurrence (P=0.02) and non-relapse mortality (P=0.01). Age >10 years at diagnosis was associated with borderline significant inferior OS (P=0.09) and DFS (P=0.08). Conclusions: This is one of the largest reports of newly diagnosed ALL in a rural area of a developing country. Major cause of death was attributed to uncontrolled infections. Insufficient resources (e.g. lack of immunophenotyping, unavailable cytogenetics, limited supportive care, and absence of methotrexate level data) adversely affect the outcome. Further studies must be done to adequately report experiences of cancer centers in the developing world after adopting United States inspired protocols. Disclosures No relevant conflicts of interest to declare.

scholarly journals Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3122-3133 ◽  
Author(s):  
A Reiter ◽  
M Schrappe ◽  
WD Ludwig ◽  
W Hiddemann ◽  
S Sauter ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Multicenter Trial ◽  
Low Risk ◽  
Event Free Survival ◽  
Free Survival ◽  
Risk Patients ◽  
To Receive

In trial ALL-BFM 86, the largest multicenter trial of the Berlin- Frankfurt-Munster (BFM) study group for childhood acute lymphoblastic leukemia (ALL), treatment response was used as an overriding stratification factor for the first time. In the previous trial ALL-BFM 83, the in vivo response to initial prednisone treatment was evaluated prospectively. A blast cell count of > or = 1,000/microL peripheral blood after a 7-day exposure to prednisone and one intrathecal dose of methotrexate (MTX) identified 10% of the patients as having a significantly worse prognosis. In trial ALL-BFM 86 patients with > or = 1,000/microL blood blasts on day 8 were included in an experimental branch EG. Patients with < 1,000/microL blood blasts on day 8 were stratified by their leukemic cell burden into two branches, Standard Risk Group (SRG) and Risk Group (RG). SRG patients received an eight- drug induction followed by consolidation protocol M (6-mercaptopurine, high-dose [HD] MTX 4 x 5 g/m2) and maintenance. RG patients were treated with an additional eight-drug reinduction element. For EG patients protocol M was replaced by protocol E (prednisone, HD-MTX, HD- cytarabine, ifosfamide, mitoxantrone). All patients received intrathecal MTX therapy; only those of branches RG and EG received cranial irradiation. In branch RG, patients were randomized to receive or not to receive late intensification (prednisone, vindesine, teniposide, ifosfamide, HD-cytarabine) in the 13th month. During the trial reinduction therapy was introduced in branch SRG, because in the follow-up of trial ALL-BFM 83 the randomized low-risk patients receiving reinduction did significantly better. Nine hundred ninety- eight evaluable patients were enrolled, 28.6% in SRG, 61.1% in RG, 10.3% in EG. At a median follow-up of 5.0 (range 3.4 to 6.9) years, the estimated 6-year event-free survival was 72% +/- 2% for the study population, 58% +/- 5% in branch SRG for the first 110 patients without reinduction therapy, 87% +/- 3% for the next 175 patients with reinduction therapy, 75% +/- 2% in branch RG, and 48% +/- 5% in branch EG. Late intensification did not significantly affect treatment outcome of RG patients; however, only 23% of the eligible patients were randomized. Prednisone poor response remained a negative prognostic parameter despite intensified therapy. The results confirmed the benefit of intensive reinduction therapy even for low-risk patients. The strategy of induction, consolidation, and intensive reinduction may offer roughly 75% of unselected childhood ALL patients the chance for an event-free survival.

scholarly journals Uptake and detection rate of a stepwise cardiometabolic disease detection program in primary care—a cohort study

2019 ◽  
Vol 30 (3) ◽  
pp. 402-407
Author(s):  
Daphne M Stol ◽  
Monika Hollander ◽  
Ilse F Badenbroek ◽  
Mark M J Nielen ◽  
François G Schellevis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Primary Care ◽  
Cohort Study ◽  
High Risk ◽  
Newly Diagnosed ◽  
Additional Risk ◽  
High Risk Patients ◽  
Detection Program ◽  
Risk Patients

Abstract Background Early detection and treatment of cardiometabolic diseases (CMD) in high-risk patients is a promising preventive strategy to anticipate the increasing burden of CMD. The Dutch guideline ‘the prevention consultation’ provides a framework for stepwise CMD risk assessment and detection in primary care. The aim of this study was to assess the outcome of this program in terms of newly diagnosed CMD. Methods A cohort study among 30 934 patients, aged 45–70 years without known CMD or CMD risk factors, who were invited for the CMD detection program within 37 general practices. Patients filled out a CMD risk score (step 1), were referred for additional risk profiling in case of high risk (step 2) and received lifestyle advice and (pharmacological) treatment if indicated (step 3). During 1-year follow-up newly diagnosed CMD, prescriptions and abnormal diagnostic tests were assessed. Results Twelve thousand seven hundred and thirty-eight patients filled out the risk score of which 865, 6665 and 5208 had a low, intermediate and high CMD risk, respectively. One thousand seven hundred and fifty-five high-risk patients consulted the general practitioner, in 346 of whom a new CMD was diagnosed. In an additional 422 patients a new prescription and/or abnormal diagnostic test were found. Conclusions Implementation of the CMD detection program resulted in a new CMD diagnosis in one-fifth of high-risk patients who attended the practice for completion of their risk profile. However, the potential yield of the program could be higher given the considerable number of additional risk factors—such as elevated glucose, blood pressure and cholesterol levels—found, requiring active follow-up and presumably treatment in the future.

P9 Novel use of CHA2DS2VASC score to select patients to undergo repeat atrial fibrillation screening

2020 ◽  
Vol 41 (Supplement_1) ◽  
Author(s):  
W Sun ◽  
B P Y Yan
Keyword(s):  
Atrial Fibrillation ◽  
High Risk ◽  
Clinical Outcomes ◽  
Cross Validation ◽  
Risk Group ◽  
Curve Analysis ◽  
Low Risk ◽  
Decision Curve Analysis ◽  
Risk Patients

Abstract Background We have previously demonstrated unselected screening for atrial fibrillation (AF) in patients ≥65 years old in an out-patient setting yielded 1-2% new AF each time screen-negative patients underwent repeated screening at 12 to 18 month interval. Selection criteria to identify high-risk patients for repeated AF screening may be more efficient than repeat screening on all patients. Aims This study aimed to validate CHA2DS2VASC score as a predictive model to select target population for repeat AF screening. Methods 17,745 consecutive patients underwent 24,363 index AF screening (26.9% patients underwent repeated screening) using a handheld single-lead ECG (AliveCor) from Dec 2014 to Dec 2017 (NCT02409654). Adverse clinical outcomes to be predicted included (i) new AF detection by repeated screening; (ii) new AF clinically diagnosed during follow-up and (ii) ischemic stroke/transient ischemic attack (TIA) during follow-up. Performance evaluation and validation of CHA2DS2VASC score as a prediction model was based on 15,732 subjects, 35,643 person-years of follow-up and 765 outcomes. Internal validation was conducted by method of k-fold cross-validation (k = n = 15,732, i.e., Leave-One-Out cross-validation). Performance measures included c-index for discriminatory ability and decision curve analysis for clinical utility. Risk groups were defined as ≤1, 2-3, or ≥4 for CHA2DS2VASC scores. Calibration was assessed by comparing proportions of actual observed events. Results CHA2DS2VASC scores achieved acceptable discrimination with c-index of 0.762 (95%CI: 0.746-0.777) for derivation and 0.703 for cross-validation. Decision curve analysis showed the use of CHA2DS2VASC to select patients for rescreening was superior to rescreening all or no patients in terms of net benefit across all reasonable threshold probability (Figure 1, left). Predicted and observed probabilities of adverse clinical outcomes progressively increased with increasing CHA2DS2VASC score (Figure 1, right): 0.7% outcome events in low-risk group (CHA2DS2VASC ≤1, predicted prob. ≤0.86%), 3.5% intermediate-risk group (CHA2DS2VASC 2-3, predicted prob. 2.62%-4.43%) and 11.3% in high-risk group (CHA2DS2VASC ≥4, predicted prob. ≥8.50%). The odds ratio for outcome events were 4.88 (95%CI: 3.43-6.96) for intermediate-versus-low risk group, and 17.37 (95%CI: 12.36-24.42) for high-versus-low risk group.  Conclusion Repeat AF screening on high-risk population may be more efficient than rescreening all screen-negative individuals. CHA2DS2VASC scores may be used as a selection tool to identify high-risk patients to undergo repeat AF screening. Abstract P9 Figure 1

scholarly journals Leukemic cell growth in SCID mice as a predictor of relapse in high- risk B-lineage acute lymphoblastic leukemia

Blood ◽  
1995 ◽  
Vol 85 (4) ◽  
pp. 873-878 ◽  
Author(s):  
FM Uckun ◽  
H Sather ◽  
G Reaman ◽  
J Shuster ◽  
V Land ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cell ◽  
Scid Mice ◽  
Leukemic Cells ◽  
Newly Diagnosed ◽  
B Lineage ◽  
Human Leukemic Cells ◽  
Overt Leukemia

Mice with severe combined immunodeficiency (SCID) provide a model system to examine the in vivo homing, engraftment, and growth patterns of normal and malignant human hematopoietic cells. The relation between leukemic cell growth in this model and the treatment outcome in patients from whom cells were derived has not been established. Leukemic cells from 42 children with newly diagnosed high-risk B- lineage acute lymphoblastic leukemia were inoculated intravenously into CB.17 SCID mice. Mice were killed at 12 weeks or when they became moribund as a result of disseminated leukemia. All mice were necropsied and subjected to a series of laboratory studies to assess their burden of human leukemic cells. Twenty-three patients whose leukemic cells caused histopathologically detectable leukemia in SCID mice had a significantly higher relapse rate than the 19 patients whose leukemic cells did not (estimated 5-year event-free survival: 29.5% v 94.7%; 95% confidence intervals, 11.2% to 50.7% v 68.1% to 99.2%; P < .0001 by log- rank test). The occurrence of overt leukemia in SCID mice was was a highly significant predictor of patient relapse. The estimated instantaneous risk of relapse for patients whose leukemic cells caused overt leukemia in SCID mice was 21.5-fold greater than that for the remaining patients. Thus, growth of human leukemic cells in SCID mice is a strong and independent predictor of relapse in patients with newly diagnosed high-risk B-lineage acute lymphoblastic leukemia.

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