scholarly journals Arsenic Combined With All-Trans Retinoic Acid for Pediatric Acute Promyelocytic Leukemia: Report From the CCLG-APL2016 Protocol Study

2021 ◽  
pp. JCO.20.03096
Author(s):  
Huyong Zheng ◽  
Hui Jiang ◽  
Shaoyan Hu ◽  
Ning Liao ◽  
Diying Shen ◽  
...  
Keyword(s):  
High Risk ◽  
Pediatric Patients ◽  
Risk Group ◽  
High Risk Group ◽  
Event Free Survival ◽  
Free Survival ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Standard Risk

PURPOSE Arsenic combined with all-trans retinoic acid (ATRA) is the standard of care for adult acute promyelocytic leukemia (APL). However, the safety and effectiveness of this treatment in pediatric patients with APL have not been reported on the basis of larger sample sizes. METHODS We conducted a multicenter trial at 38 hospitals in China. Patients with newly diagnosed APL were stratified into two risk groups according to baseline WBC count and FLT3-ITD mutation. ATRA plus arsenic trioxide or oral arsenic without chemotherapy were administered to the standard-risk group, whereas ATRA, arsenic trioxide, or oral arsenic plus reduced-dose anthracycline were administered to the high-risk group. Primary end points were event-free survival and overall survival at 2 years. RESULTS We enrolled 193 patients with APL. After a median follow-up of 28.9 months, the 2-year overall survival rate was 99% (95% CI, 97 to 100) in the standard-risk group and 95% (95% CI, 90 to 100) in the high-risk group ( P = .088). The 2-year event-free survival was 97% (95% CI, 93 to 100) in the standard-risk group and 90% (95% CI, 83 to 96) in the high-risk group ( P = .252). The plasma levels of arsenic were significantly elevated after treatment, with a stable effective level ranging from 42.9 to 63.2 ng/mL during treatment. In addition, plasma, urine, hair, and nail arsenic levels rapidly decreased to normal 6 months after the end of treatment. CONCLUSION Arsenic combined with ATRA is effective and safe in pediatric patients with APL, although long-term follow-up is still needed.

Minimal Residual Disease by Flow Cytometry in Children with Acute Lymphoblastic Leukemia. Single-Center Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4238-4238
Author(s):  
Marcela Eugenia Soria ◽  
Marcela Ema Gutierrez ◽  
Maria Isabel Gaillard ◽  
Maria Cores ◽  
Gimena Gil ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
High Risk ◽  
Residual Disease ◽  
Risk Group ◽  
High Risk Group ◽  
Event Free Survival ◽  
Free Survival ◽  
Wbc Count ◽  
Minimal Residual

Abstract Abstract 4238 Introduction: Minimal residual disease (MRD) allows detection of blasts in patients in morphologically complete remission. Detection of MRD in patients with ALL is an independent risk factor associated with lower event-free survival (EFS). Objectives: 1) Evaluate MRD in bone marrowaspirateby flow cytometry at days 15 and 33 of induction in children with ALL. 2) Determine MRD association with hematologic features. 3) To correlate MRD association with overall survival (OS) and event-free survival (EFS). Design and Statistical Analysis: Descriptive, retrospective study. Univariate analysis was performed by T- test for continuous varibles and byχ2or Fisher tests for categorical variables. Survival was estimated with Kaplan Meier method. Regression multiple was used for multivariate analysis. p values < 0.05 were deemed as statistically significant. SPSS 15.0 program was used for the analyses. Patients: From January 2006 to December 2009, 84 patients with newly diagnosed ALL, aged 1 –18 years, were admitted at our institution. They were treated according to ALLIC / BFM / GATLA 2002 protocol. Immunophenotypic studies were performed by standard Four-color flow cytometry (FC) using FACSCalibur BD cytometer, MDR follow up panels were tailored depending on aberrant finding at diagnosis. 300.000–500.000 events were acquired using the CellQuest Pro and Paint -a-gate software for data analysis. MDR status has been defined as positive if at least 30–50 clustered events displaying leukemia –associated immunophenotypic characteristics (0,01%). Results: The mean age at diagnosis was 7.7 years (r: 2.1–18). Mean follow-up 33.9 months (r: 1–66). 38% were female. Immunophenotype: Pro B 5%, common B 87%, Pre B 2%, and T 6%. Good response to prednisone was achieved by 92% of patients. With regard to risk groups, the distribution was: 28% standard, 55% intermediate and 17% high. MRD at day 15 was evaluable in 66 patients (78%), being positive in 35 of them (45%). MRD at day 33 was evaluable in 75 patients (89%), being positive in 10 (12%). Conclusion: Positive MRD at day 15 was associated with: increased WBC count at diagnosis, high-risk group, higher relapse rate, lower EFS and OS. Otherwise, positive MRD at day 33 was associated: increased WBC count at diagnosis, T immunophenotype, poor response to prednisone, high risk group, lower EFS and OS. Our data indicate that positive MRD at days 15 and 33 result an independent variable of poor prognosis in children with ALL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Pre-Enucleation Chemotherapy in Advanced Intraocular Retinoblastoma. Central America Follow Up: AHOPCA II

2016 ◽  
Vol 2 (3_suppl) ◽  
pp. 75s-75s
Author(s):  
Sandra Luna-Fineman ◽  
Soad L. Alabi ◽  
Mauricio E. Castellanos ◽  
Yessika Gamboa ◽  
Ligia Fu ◽  
...  
Keyword(s):  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Central America ◽  
Conflicts Of Interest ◽  
Risk Group ◽  
High Risk Group ◽  
Globe Rupture ◽  
Neo Adjuvant Chemotherapy ◽  
Standard Risk

Abstract 57a Purpose: A significant percentage of patients in Central America present with buphthalmos, carrying a high risk of globe rupture and orbital contamination. In 2007, AHOPCA introduced chemotherapy before enucleation in children with buphthalmos. Methods: Patients with advanced intraocular disease were considered standard-risk and underwent enucleation. Those with diffuse invasion of choroid, postlaminar optic nerve, or anterior chamber invasion received 4-6 cycles of adjuvant chemotherapy (vincristine, carboplatin, etoposide). Patients with buphthalmos or perceived to be at risk for abandonment were considered high-risk, given 2-3 cycles of chemotherapy before enucleation to compete 6 cycles regardless of pathology. All cases were discussed via online meetings. Results: From 2007 to 2014, 396 patients were enrolled; 240 had IRSS stage I (174 unilateral). 143 had upfront enucleation, 95 had pre-enucleation chemotherapy, 1 is pending enucleation and 1 abandoned before enucleation. The standard-risk group 69 had risk pathology and 76 had no risk factors; 125 had no events, 5 abandoned 11 relapsed/progressed and 2 died of toxicity. Of 95 high-risk group, 8 abandoned, 20 relapse/progressive, 6 had toxic deaths and 61 are alive at last follow-up (median time of 4 years). Of high risk group, 55 were unilateral, 82% are alive. At 7 years OS (abandonment-censored) was 95±0.02 and 79±0.04 for standard-risk and high-risk (p=0.008). Conclusion: AHOPCA addressed advanced intraocular disease with an innovative approach. In eyes with buphthalmos and patients with risk of abandonment, neo-adjuvant chemotherapy is effective, when followed by post-enucleation chemotherapy. This approach avoids ocular rupture and intensified therapy, and reduces refusal/abandonment rate. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: No COIs from the authors.

High Prevalence of Relapse in Australian Children with Ph-like Acute Lymphoblastic Leukemia Despite Risk Adapted Treatment

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1419-1419 ◽  
Author(s):  
Susan L Heatley ◽  
Teresa Sadras ◽  
Eva Nievergall ◽  
Chung Hoow Kok ◽  
Phuong Dang ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Risk Groups ◽  
High Risk Group ◽  
Event Free Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
Medium Risk

Abstract Introduction: While remission rates for childhood acute lymphoblastic leukemia (ALL) now exceed 80%, relapsed ALL remains the leading cause of non-traumatic death in children. Recently, a high-risk group of B-progenitor ALL patients has been identified. Such cases exhibit a gene expression profile similar to that of BCR-ABL1 positive (Ph+) ALL but are BCR-ABL1 negative, and also experience poor treatment outcomes. This subset, termed Ph-like ALL, is characterised by a range of genetic alterations that activate cytokine receptor and kinase signalling, allowing potential targeting by available tyrosine kinase inhibitors (TKI). The frequency of Ph-like ALL in the Australian community and the prognosis in the setting of the first MRD (minimal residual disease) intervention trial by the Australian and New Zealand Children's Haematology/Oncology Group (ANZCHOG ALL8) is unknown. Method: We retrospectively screened 250 unselected samples that were available from children diagnosed with B-ALL, for Ph-like ALL. The children, aged between 1 and 18 years, were enrolled on the ANZCHOG ALL8 trial and recruited from 2002-2011. The criteria for stratification to the high-risk group, based upon Berlin-Frankfurt-Munster (BFM) protocols, were BCR-ABL1 or MLL t(4;11) translocation; poor prednisolone response at day 8; failure to achieve remission by day 33 or high MRD (>5 x10-4) at day 79. MRD was measured by RQ-PCR for patient-specific immunoglobulin and T-cell receptor rearrangements. All patients received a standard BFM four drug induction chemotherapy regimen including a prednisolone pre-phase and intrathecal methotrexate. High-risk patients received a further three novel intensive blocks of chemotherapy followed by transplant in most cases. Patients were screened for Ph-like ALL using a custom Taqman Low Density Array (TLDA) based upon previous reports. Fusions were then confirmed by RT-PCR for 30 known fusions, Sanger sequencing, mRNA sequencing and/or FISH. Results: Ten percent (25/250) of children in this cohort were identified as having Ph-like ALL, with most fusions converging on kinase activating pathways (Table 1). Three Ph-like ALL patients were considered high-risk, the remaining 22 (88%) were medium risk. Five children with Ph-like ALL, that did not have a fusion identified by RT-PCR, are currently under further investigation. Furthermore, 15 of the 20 (75%) of rearrangements involved CRLF2 with 10 (66%) of these children relapsing. Strikingly, 56% (14/25) of children in the ALL8 cohort who were identified as Ph-like subsequently relapsed compared to 16% (36/225) who were not, with significantly worse event free survival (p<0.0001) (Figure 1). Conclusion: Here we demonstrate a significantly higher frequency of relapse amongst Australian children with Ph-like ALL compared to non Ph-like disease despite a MRD-adjusted intensification regimen. In this cohort, these children should be classified as high-risk due to high treatment failure rates with standard/medium risk regimens. Importantly, rapid identification of these patients may guide future intervention with targeted therapies, such as TKI, matched to the causative genetic lesion in this high-risk group. Figure 1. Fusions identified in Ph-like ALL from ANZCHOG ALL8 cohort. Figure 1. Fusions identified in Ph-like ALL from ANZCHOG ALL8 cohort. Figure 2. Kaplan-Meier estimates of event free survival for patients with Ph-like ALL and non Ph-like ALL (all risk groups). Figure 2. Kaplan-Meier estimates of event free survival for patients with Ph-like ALL and non Ph-like ALL (all risk groups). Disclosures Hughes: ARIAD: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Mullighan:Incyte: Consultancy, Honoraria; Cancer Science Institute: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Speakers Bureau; Loxo Oncology: Research Funding. White:Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding.

scholarly journals Clinical Investigation of Stratified Therapy in Childhood Acute Promyelocytic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5286-5286 ◽  
Author(s):  
Yuming Zhang ◽  
Xiaoqing Feng ◽  
Cuiling Wu ◽  
Wenling Guo ◽  
Huiping Li ◽  
...  
Keyword(s):  
High Risk ◽  
Acute Promyelocytic Leukemia ◽  
Risk Group ◽  
Disease Free Survival ◽  
High Risk Group ◽  
Promyelocytic Leukemia ◽  
Free Survival ◽  
Standard Risk ◽  
Disease Free

Abstract OBJECTIVE: The aim of this study was to investigate the clinical biological features, treatment strategy, prognosis and long-term survival in children with acute promyelocytic leukemia（APL）. Focus on the effect of stratified therapy in childhood APL. METHODS: The clinical data of 42 cases of APL with t (15;17) from April 2004 to December 2012 were analyzed retrospectively. Patients were stratified into three risk-group based on white blood cell count and platelet count at diagnosis: standard, intermediate and high-risk group. Induction treatment consisted of all-trans retinoic acid（ATRA）and Idarubicin（IDA）), followed by multi-drug chemotherapy consolidation and a long term maintenance therapy including ATRA,6-Mercaptopurine（6-MP), Methotrexate（MTX）. The complete remission (CR) rate, overall survival (OS) rate, disease free survival (DFS) rate, hematologic and cytogenetic cumulative incidence of relapse (CIR) were compared among the three groups, the stratified therapy in childhood APL and its correlation with clinical prognosis was analyzed. The statistical analyses were performed by SPSS. RESULTS: 42 patients were enrolled (median age 5.8 years, range 1.5-14, 64% males and 36% females), 11 in standard-risk group, 18 in intermediate-risk group, 13 in high-risk group. Immunophenotyping analysis indicated that MPO, CD33, CD13 and CD117 were commonly expressed antigens while HLA-DR and CD34 were mostly the negative markers on APL cells. Of the 42 patients receiving treatment, 38 children (90.5%) achieve complete remission. 1 patient from the high risk group died of intracranial hemorrhage, 1 patient from the Standard Risk group died of anthracycline cardiotoxicity, 1 patient from the intermediate group died of severe infection. The estimated overall survival (OS) rates at 3 and 5 years were （74.2±6.7%）and（70±7.4%）respectively, the disease free survival (DFS) rates were（71±3.8%）and（57±8.1%）respectively. The 3 and 5-year cumulative incidence of relapse (CIR) were 18% and 27%. OS for three groups were (86±7.4%),（71±4、8%）and（57±4.7%）respectively, the 5-year DFS were (82±6.3%), (61±5.3%)and(50±7.2%) and 5-year CIR were 6.7%、18%、35%.There were significant differences in 5-year OS, DFS and CIR rates of three groups (P< 0.05). CONCLUSION: The results indicated that ATRA combined with Anthracycline is effective and safe for treatment of newly diagnosed childhood APL. Prognosis of childhood APL was associated with clinical types. It indicates that stratified therapy according to different risk group can improve the OS and EFS rate and decrease the CIR rate while minimizing chemotherapy-related toxicity. Now, real-time quantitative polymerase chain reaction (RQ-PCR), which can performed to detect PML-RARα fusion transcripts, has become an important means for minimal residual disease (MRD) assays, but it is rarely used in children. Compared with RQ-PCR, clinical risk-adapted classification is a simple, validated and highly predictive index for the determination of stratified therapy in childhood acute promyelocytic leukemia. Disclosures No relevant conflicts of interest to declare.

Abstract 15870: External Validation of a Risk Score for Heart Failure in Acute Myeloid Leukemia

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Gregory Cascino ◽  
Peter Doukas ◽  
Borko Jovanovic ◽  
Jessica Altman ◽  
Yu Kang ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Risk Group ◽  
External Validation ◽  
High Risk Group ◽  
Risk Category ◽  
Average Risk ◽  
Event Free Survival ◽  
Free Survival ◽  
Clinical Criteria

Introduction: HF is a major cause of morbidity and mortality in AML patients. This study was designed as an external evaluation of a risk score to determine the risk of HF in patients treated with anthracyclines for AML. Methods: A validation cohort was composed of 204 consecutive patients with AML treated with anthracyclines. 2DSTE was performed using TomTec software to obtain baseline GLS values. LVEF was calculated using modified Simpson’s biplane method. HF hospitalizations were defined using standard clinical criteria. The HF risk score included a baseline GLS > - 15% (6 points), baseline LVEF<50% (4 points), pre-existing cardiovascular disease (4 points), anthracycline dose >/= 250 mg/m 2 (2 points), and age > 60 years (1 point). Patients were stratified into low (0 to 2 points), medium (3 to 9 points), and high risk (10 to 17 points). Statistical analysis was performed to evaluate event-free survival of the risk categories. Results: The average age of the cohort was 54 with an average risk score of 7 points. 55% of the patients were male. In total, 44 patients (21%) experienced a hospitalization for HF (median time to hospitalization 1 month) within the follow-up period (median 18 months). The observed incidence of HF by risk category was 14% (18 of 130) in the low, 31% (19 of 61) in medium, and 54% (7 of 13) in high risk group. The association between HF and the risk group category was highly significant (p = 0.001). Event-free survival by risk category (Figure 1) was also statistically significant (p = 0.05), with individuals in the high risk category having a reduced event-free survival. Conclusions: This is the first external validation study of a risk score for HF in AML patients. The risk score that we evaluated was successful at identifying patient who were at higher risk of hospitalization for HF. This may be a useful tool in clinical practice to counsel patients regarding the risk of HF after induction chemotherapy with anthracyclines.

Factors associated with effectiveness of trifluridine/tipiracil versus regorafenib in patients with pretreated metastatic colorectal cancer (mCRC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 137-137 ◽  
Author(s):  
Peter Grell ◽  
Simona Borilova ◽  
Renata Schwanzerova ◽  
Sabina Kukolikova ◽  
Josef Dvorak ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Progression Free Survival ◽  
High Risk Group ◽  
Median Line ◽  
Free Survival ◽  
Treatment Groups ◽  
Factors Associated ◽  
Patient Will

137 Background: Trifluridine/tipiracil (T) and regorafenib (R) are indicated for patients with refractory mCRC. Currently, no biomarkers are used to select which patient will benefit from which treatment. Methods: We retrospectively evaluated 212 patients who received T and/or R. Different factors associated with progression-free survival (PFS) and overall survival (OS) were analyzed. Results: T received 132, R 52, both drugs 28 patients. Median age was 64 (range 28-83), male 64%, PS 0 37%, median line of treatment 3, characteristic was similar between treatment groups. Median follow-up was 16.5 months. Median OS for T was 10.2, for R 6.9 months, P = 0.03. Factors significantly associated with OS were: ≥ 24 months from diagnosis of mCRC (0.49, P < 0.001), PS 0 (HR 1.54, P = 0.007), baseline WBC < 8 × 109/L (HR 0.47, P < 0.001), normal baseline CRP (HR 0.47, P < 0.001), ≥ 3 months from last therapy (fluoropyrimidine for T, anti-VEGF for R) (HR 0.66, P = 0.006). We developed a scoring system TASREG from these factors, 1 point for each factor, the overall score was the sum of these points and patients were divided into 3 groups: high risk group with 0 to 1 point, intermediate with 2 to 3, favorable with 4 or more points. OS for all patients according to risk group was 4.6 for high risk, 7.9 intermediate, 11.8 months favorable risk (P < 0.001). Score was also significant for T and R group evaluated separately. Score was also significant for PFS. Factors associated with OS specific for T were neutropenia G≥2 (HR 0.34, P < 0.001); for R normal baseline LDH (HR 0,40. P < 0.001), no liver metastases (HR 0.45, P = 0.002), non-synchronous disease (HR 0,40, P < 0.001). Conclusions: We could find factors associated with better outcomes for both treatment groups and factors specific for T or R. TASREG is simple prognostic tool for patients with refractory mCRC.

scholarly journals Real World Data of Concurrent Arsenic Trioxide and All-Trans Retinoic Acid with Minimal Use of Anthracycline in the Treatment of Acute Promyelocytic Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2338-2338
Author(s):  
Uday Prakash Kulkarni ◽  
Sushil Selvarajan ◽  
Sharon Lionel ◽  
Mithun Abraham Prakash ◽  
Hamenth Kumar Palani ◽  
...  
Keyword(s):  
High Risk ◽  
Induction Therapy ◽  
Real World ◽  
Risk Group ◽  
High Risk Group ◽  
Newly Diagnosed ◽  
Real World Data ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Life Threatening

Abstract In the setting of clinical trials, high cure rates have been reported for acute promyelocytic leukemia (APL) with the chemotherapy-free combination of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) for low-intermediate risk disease, and with the addition of gemtuzumab ozogamicin or minimal anthracycline for high-risk disease. Despite clear in-vitro synergy between ATO and ATRA, most clinical trial protocols in APL have not used these drugs concurrently beyond induction. There is limited real world data on the use of chemotherapy-free combination of ATO and ATRA with minimal anthracycline use in the treatment of APL, especially in the high risk group. We did a retrospective analysis of the clinical outcomes of patients with newly diagnosed APL treated at our center from January 2015 to May 2020 using concurrent ATO, ATRA and minimal anthracycline in a risk stratified manner. The data was frozen and analyzed as on 1st June 2021. During the study period, 167 patients were diagnosed to have APL at our hospital. Of these, we excluded 5 patients who had presented with relapsed disease and 28 patients who were treated with single agent ATO. The remaining 134 patients were treated with a uniform protocol as summarized in Figure 1a. Figure 1b shows the KM plot for EFS (2 year: 90.8±2.5%) for these 134 patients. For analysis of regimen safety and efficacy, we excluded patients who wished to pursue treatment elsewhere within the first 1 week of treatment (n=7), and patients who had severe infections or life-threatening bleeding at presentation or before therapy initiation and subsequently died (n=4). Thus, a total of 123 patients with newly diagnosed APL were included for further analysis. The median age was 35 years (IQR: 24 to 45 years). Forty-six (37.4%) were females. The median duration of symptoms prior to admission was 14 days (IQR: 7 to 28 days). Sixty-one (49.6%) had high risk APL while the remaining 62 (50.4%) had low-intermediate risk APL. During induction, 28 (22.7%) patients had major bleeding while 5 (4%) patients developed major thrombosis. Sixty-seven (55%) patients had at least one documented infection during induction therapy. The median number of packed red cell concentrates, fresh frozen plasma, platelet rich concentrates and cryoprecipitates transfused during induction therapy was 5 (IQR: 3 to 6.5), 10 (IQR: 3 to 30), 40 (IQR: 23 to 55) and 6 (IQR: 0 to 18) respectively. Nineteen (15.4%) patients developed differentiation syndrome; all were treated with steroids, 8 required transient cessation of treatment and 6 required intensive care. Eight (6.5%) patients died during induction. During induction, grade 3 hepatotoxicity was noted in 8 (6.5%) patients, 10 (8.1%) patients had ATRA related headache or benign intracranial hypertension of which 5 required transient cessation of ATRA, while 11 (8.9%) patients had transient QTc prolongation of which 6 required transient cessation of ATO. Seventeen (13.8%) patients developed symptomatic sensory neuropathy requiring treatment. None required permanent discontinuation of therapy. At a median follow up of 854 days, there were 2 (1.6%) hematologic relapses and no deaths beyond induction therapy. The 2-year OS and EFS for the cohort (n=123) are 93.4% ± 2.3% and 91.6% ± 2.6% respectively (Figure 1c). Two (1.6%) patients have developed second malignancies. In a real world setting, concurrently administered ATO and ATRA with minimal anthracycline use results in excellent long term survival, even in the high risk group. Early deaths due to delayed presentation with infections and life threatening bleeding remain an unmet need for future research along with the need for strategies to reduce treatment-related toxicities. Figure 1 Figure 1. Disclosures Mathews: Christian Medical College: Patents & Royalties: US 2020/0345770 A1 - Pub.Date Nov.5, 2020; AML: Other: Co-Inventor.

Genome-Wide Genotype-Based Risk Model for Survival in Core Binding Factor Acute Myeloid Leukemia Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1623-1623
Author(s):  
Silvia Park ◽  
Choi Hangseok ◽  
Hee-Je Kim ◽  
Jae-Sook Ahn ◽  
Hyeoung Joon Kim ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Risk Model ◽  
Risk Group ◽  
Snp Array ◽  
High Risk Group ◽  
Event Free Survival ◽  
Free Survival ◽  
Genome Wide ◽  
Binding Factor

Abstract Introduction: The present study attempted to build a single nucleotide polymorphism (SNP)-based risk model for predicting overall survival (OS) and event free survival (EFS) in patients with core binding factor acute myeloid leukemia (CBF-AML). Methods: Adopting genome-wide SNP array using Affymetrix SNP array 6.0, we analyzed 868,157 SNPs with respect to OS and EFS in 104 patients with CBF-AML. Significant SNPs were identified from single SNP analysis. The risk model was constructed with incorporation of six SNPs and three clinical factors (age, c-kit exon 17 mutation, and LDH) for OS, and six SNPs and three clinical factors (age, WBC, and LDH) for EFS. The model was further defined into low and high risk groups based on risk scores. Results: The median age was 39 years, and the subgroup of t(8;21) and inv(16) or t(16;16) was assessed in 68 (65.4%) and 36 patients (34.6%). Finally 6 SNPs per each OS (rs4353685, rs4908185, rs7709207, rs12034, rs1554844, and rs17241868) and EFS (rs13385610, rs11210617, rs11169282, rs7709207, rs4438401 and rs16894846) were incorporated into the risk model. OS was significantly different in favor of the low risk group (80.4%) compared to the high risk group (22.0% at 3 years; p= 8.75 x 10-13; HR 8.67). For EFS, there was also a significant difference between the low (75.0%) versus high risk group (17.1% at 3 years; p=5.95 x 10-13; HR 7.67). Conclusion: A genome-wide SNP based risk model can stratify CBF-AML patients according to their OS and EFS in 104 patients. Figure 1 Overall survival and event free survival by risk model composed of SNPs and clinical risk factors Figure 1. Overall survival and event free survival by risk model composed of SNPs and clinical risk factors Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Survival and prognostic factors in a series of adults with medulloblastomas

2009 ◽  
Vol 111 (3) ◽  
pp. 478-487 ◽  
Author(s):  
Laurent Riffaud ◽  
Stephan Saikali ◽  
Emmanuelle Leray ◽  
Abderrahmane Hamlat ◽  
Claire Haegelen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
High Risk ◽  
Survival Time ◽  
Risk Group ◽  
Survival Rates ◽  
Event Free Survival ◽  
Term Survival ◽  
Free Survival ◽  
Standard Risk

Object In this article, the authors report their experience in the management of adult patients with medulloblastoma at their institution to identify prognostic factors important for survival and disease control. Methods Between 1977 and 2005, 27 patients who were ≥ 16 years old and had medulloblastoma were treated consecutively. There were 16 women and 11 men with a median age of 21 years (range 16–54 years). Gross-total resection was performed in 21 patients, subtotal (≥ 90%) in 2, incomplete in 1, and biopsy in 3 patients. Six patients had the desmoplastic variant, and 21 patients presented with classic medulloblastoma. Staging according to the Chang classification showed 4 patients with tumors invading the brainstem (2 with Stage T3b and 2 with Stage T4), 3 patients with metastases (2 with Stage M2 and 1 with Stage M3), and 1 patient in whom the stage was unknown (Stage MX) who died 10 days postoperatively. Twenty patients were assigned to the standard-risk group and 7 to the high-risk group. All patients except the one whose status was classified as Stage MX underwent craniospinal radiotherapy at our institution. Seven patients received chemotherapy before radiotherapy. Results The 5- and 10-year overall survival rates for the present study were 81 and 62%, respectively. The median overall survival time was 17.7 years. The 5- and 10-year event-free survival rates were 72 and 57%, respectively. The median event-free survival time was 17.9 years. Univariate analysis showed that survival was significantly correlated with sex (women had a better prognosis than men) and M stage (patients without metastases had a better outcome). Patient age, duration of symptoms, Karnofsky Performance Scale score at presentation, hydrocephalus, tumor location, brainstem invasion, extent of resection, histological subtype, preradiotherapy chemotherapy, risk group, and period of presentation were not significant variables. Multivariate analysis identified sex and M stage as well as the period of presentation as independent prognostic factors for overall and event-free survival times. Eleven patients suffered tumor recurrence within a median time of 4.2 years. The posterior fossa was not the most common site of recurrence, and delayed recurrence was not rare. All patients in whom the tumor recurred have died despite aggressive treatments. The median survival time after diagnosis of recurrence was 2.5 years. Questionnaires on quality of life and cognition showed high scores in favor of limited negative effects in the perception of mental and physical health after treatment. The authors observed 1 supposed second malignancy (thyroid carcinoma) and no evidence of pituitary dysfunction. Conclusions Long-term survival is possible in adults treated for medulloblastoma. Although rare, metastasis seeding at presentation is a poor prognostic factor. The possibility of delayed recurrence necessitates close follow-up of all patients. Tumor recurrences should be treated with aggressive therapies as some patients may have sustained response. Adjuvant chemotherapy should be given to high-risk patients, but its role in reducing recurrences, particularly distant ones, remains unclear in the standard-risk group.

scholarly journals Multidrug resistance gene 1 polymorphisms in pediatric patients with leukemia at a national referral hospital in Indonesia

2017 ◽  
Vol 9 (5) ◽  
pp. 625-630 ◽  
Author(s):  
Rina Mutiara ◽  
Bernadius Agustinus ◽  
Christian Badia Sitompul ◽  
Amarila Malik ◽  
Djajadiman Gatot ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
High Risk ◽  
Resistance Gene ◽  
Pediatric Patients ◽  
Risk Group ◽  
Pediatric Population ◽  
Lymphoblastic Leukemia ◽  
High Risk Group ◽  
Multidrug Resistance Gene ◽  
Standard Risk

Abstract Background Acute lymphoblastic leukemia (ALL) is the most prevalent cancer in the pediatric population. From 25% to 30% of patients with ALL will have a relapse that leads to death when they are teenagers. At Cipto Mangunkusumo Hospital, 40% of 126 pediatric patients with ALL relapsed from 2005 to 2011. A multiple variant of multidrug resistance gene 1 (MDR1) is C3435T, which can be used to understand the genetic basis of susceptibility to relapse. Objectives To identify the profile of MDR1 polymorphism in pediatric Indonesian patients with ALL. Methods We collected data from 44 patients with ALL who attended Cipto Mangunkusumo Hospital between January and June 2014. We investigated a silent C3435T polymorphism in MDR1 exon 26 with polymerase chain reaction- restriction fragment length polymorphism using MboI. Results There were 32 male and 12 female patient participants in this study. Eighteen patients were 1–3 years old and 26 were over 3 years. The mean age at 1–3 years was 2.4 ± 0.86, and over 3 years it was 6.3 ± 2.67 years. There were 27 patients with ALL in the standard risk group and 17 in the high risk group. We determined that the 25 samples from patients with ALL in the standard risk group were not digestible (allele T) and the 6 samples from patients with ALL in the high risk group were digestible (allele C). Conclusions The prevalence of the T allele was higher than that of the C allele in pediatric Indonesian patients with ALL.

Sign in / Sign up

Export Citation Format

Share Document