Association of the GATA3 rs3824662A allele with clinical outcomes in adult patients with adult B-ALL.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7023-7023
Author(s):  
Paul B. Koller ◽  
Hagop M. Kantarjian ◽  
Elias Jabbour ◽  
Sherry A. Pierce ◽  
Kathryn Roberts ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Lymphoblastic Leukemia ◽  
White Blood Count ◽  
Cancer Center ◽  
P Value ◽  
Free Survival ◽  
Genotype Group ◽  
Adults And Children ◽  
Md Anderson

7023 Background: Inherited GATA3 variants (rs3824662) have been described in higher frequency in both adults and children with Ph-like acute lymphoblastic leukemia (Ph-like ALL) (Perez-Andreu, Nat Genetics 2013; Jain, ASH 2017). The clinical outcomes of Ph-like ALL are well known, and as we have previously described, it as a high-risk subtype of ALL in both children and adults (Roberts, NEJM 2014; Roberts, JCO 2017; Jain, Blood 2017). However, the clinical outcomes of ALL patients with different germline variants of GATA3 that are commonly seen in Ph-like ALL is unknown. Methods: Of the newly diagnosed patients treated at MD Anderson Cancer Center (MDACC) with B-ALL, we performed analyses for the GATA3 rs3824662 variant in 85 patients (42 Ph-like ALL, 43 non-Ph-like ALL). Testing for Ph-like ALL, CRLF2 rearrangement, and GATA3 genotypes was performed as previously described (Jain, ASH 2017). Results: Of the 85 patients, the rs3824662 AA genotype was identified in 22 patients, the AC genotype in 33 patients, and the CC genotype in 29 patients. There was a trend towards increased frequency of Hispanic heritage in the AA genotype (86%) vs AC genotype (61%), vs the CC genotype (31%). Additionally, amongst patients with the AA genotype, 91% had the Ph-like ALL vs 45% of the AC genotype vs 10% of the CC genotype. The median white blood count at diagnosis was 52.1 x 109/L in the AA genotype group, 20 x 109/L in the AC genotype group, and 5.9 x 109/L in the CC genotype group. The 5 year event-free-survival (EFS) of the CC group was 55% vs 36% of the AC group vs 14% of the AA group. The EFS between the 3 genotypic groups was statistically significant with a p value of 0.018. The 5 year overall survival (OS) of the CC group was 64% vs 42% of the AC group vs 14% of the AA group. Conclusions: We observed significant differences in the EFS between patients with 0, 1, 2 copies of this genetic polymorphism in the GATA3 gene. The role of genomic AA GATA3 variant on the biology of ALL and understanding of the downstream mechanisms needs to be determined. [Table: see text]

Progression-free survival in metastatic, BRAF-mutated colorectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 458-458
Author(s):  
Van Karlyle Morris ◽  
Michael J. Overman ◽  
Dipen M Maru ◽  
Scott Kopetz
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Disease ◽  
Progression Free Survival ◽  
Chemotherapeutic Agents ◽  
Cancer Center ◽  
P Value ◽  
Braf Mutations ◽  
Free Survival ◽  
Md Anderson ◽  
Line Setting

458 Background: BRAF mutations occur in 5-8% of metastatic colorectal cancers and are associated with a significantly worse overall prognosis relative to patients with BRAF wild-type tumors. However, the outcomes with standard chemotherapy of a large cohort of patients with BRAF mutant tumors have not been described. Methods: We searched the MD Anderson Cancer Center databases for colorectal cancer patients with identified BRAF mutations between December 2003 and May 2012. Patients were analyzed for clinical characteristics, progression-free survival, and chemotherapeutic agents used. Survival was estimated according to the Kaplan-Meier method. Results: Among the 1567 patients tested for BRAF mutations at our institution, 127 (8.1%) had tumors with BRAF mutations. The average age was 59.6 years at the time of diagnosis, and 65/127 patients (51.2%) were male. The 71 patients who presented with metastatic disease received a median of 2 lines of chemotherapy. For the first three lines of chemotherapy, median progression-free survival was 5.6 months (n=69 patients), 3.9 months (n=58), and 3.4 months (n=31), respectively. Median PFS was not affected by the backbone chemotherapeutic agent in the first-line setting, whether oxaliplatin-based or irinotecan-based (6.1 months vs. 5.1 months, respectively, p-value = 0.78). Conclusions: Progression-free survival is expectedly poor for patients with BRAF-mutated metastatic colorectal cancer. Despite the ascertainment bias present in this cohort (with testing preferentially performed in patients suitable for clinical trials in refractory disease), fewer than half of patients with metastatic disease received more than 2 lines of therapy. This data not only provides historic controls suitable for future study design in this population but also supports the idea that novel therapeutic options are essential for this group of patients.

scholarly journals Chemotherapy Delays Are Associated with Inferior Outcome in Acute Lymphoblastic Leukemia: A Retrospective Study from a Tertiary Cancer Center in South India

2021 ◽  
Vol 42 (01) ◽  
pp. 051-060
Author(s):  
Vineet Agrawal ◽  
Smita Kayal ◽  
Prasanth Ganesan ◽  
Biswajit Dubashi
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Cancer Center ◽  
Survival Outcomes ◽  
Separate Analysis ◽  
Term Survival ◽  
Free Survival ◽  
Intensive Phase ◽  
The Impact

Abstract Background Treatment protocols for acute lymphoblastic leukemia (ALL) have evolved over time to give excellent cure rates in children and moderate outcomes in adults; however, little is known how delays in chemotherapy affect long-term survival. Objectives To find the association of delays during different treatment phases on the survival outcomes. Materials and Methods Data from 149 ALL cases treated between 2009 and 2015 were retrospectively analyzed. Treatment course in commonly used protocols was divided into three phases—induction, consolidation (postremission), maintenance, and also a combined intensive phase (induction plus consolidation) for the purpose of analysis, and delay in each phase was defined based on clinically acceptable breaks. Analysis was done to find the impact of treatment delay in each phase on the survival outcomes. Results The median age was 12 years (range, 1–57). Multi-center Protocol-841 (MCP-841) was used for 72%, German Multicenter Study Group for Adult ALL (GMALL) for 19%, and Berlin, Frankfurt, Muenster, 95 protocol (BFM-95) for 9% of patients. Delay in induction was seen in 52%, consolidation in 66%, and during maintenance in 42% of patients. The median follow-up was 41 months, and 3-year survival outcomes for the entire cohort were event-free survival (EFS)—60%, relapse-free survival (RFS)—72%, and overall survival (OS)—68%. On univariate analysis, delay in induction adversely affected EFS (hazard ratio [HR] = 1.78, p = 0.04), while delay in intensive phase had significantly worse EFS and RFS (HR = 2.41 [p = 0.03] and HR = 2.57 [p = 0.03], respectively). On separate analysis of MCP-841 cohort, delay in intensive phase affected both EFS (HR = 3.85, p = 0.02) and RFS (HR = 3.42, p = 0.04), whereas delay in consolidation significantly affected OS with (HR = 4.74, p = 0.04) independently. Conclusion Treatment delays mostly in intensive phase are associated with worse survival in ALL; attempts should be made to maintain protocol-defined treatment intensity while adequately managing toxicities.

scholarly journals Intensified Therapy of Acute Lymphoblastic Leukemia in Adults: Report of the Randomized GRAALL-2005 Clinical Trial

2018 ◽  
Vol 36 (24) ◽  
pp. 2514-2523 ◽  
Author(s):  
Françoise Huguet ◽  
Sylvie Chevret ◽  
Thibaut Leguay ◽  
Xavier Thomas ◽  
Nicolas Boissel ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Standard Dose ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Treatment Phase ◽  
Free Survival ◽  
Treatment Tolerance ◽  
To Receive

Purpose To evaluate randomly the role of hyperfractionated cyclophosphamide (hyper-C) dose intensification in adults with newly diagnosed Philadelphia chromosome–negative acute lymphoblastic leukemia treated with a pediatric-inspired protocol and to determine the upper age limit for treatment tolerability in this context. Patients and Methods A total of 787 evaluable patients (B/T lineage, 525 and 262, respectively; median age, 36.1 years) were randomly assigned to receive a standard dose of cyclophosphamide or hyper-C during first induction and late intensification. Compliance with chemotherapy was assessed by median doses actually received during each treatment phase by patients potentially exposed to the full planned doses. Results Overall complete remission (CR) rate was 91.9%. With a median follow-up of 5.2 years, the 5-year rate of event-free survival (EFS) and overall survival (OS) was 52.2% (95% CI, 48.5% to 55.7%) and 58.5% (95% CI, 54.8% to 61.9%), respectively. Randomization to the hyper-C arm did not increase the CR rate or prolong EFS or OS. As a result of worse treatment tolerance, advanced age continuously affected CR rate, EFS, and OS, with 55 years as the best age cutoff. At 5 years, EFS was 55.7% (95% CI, 51.8% to 59.4%) for patients younger than 55 years of age versus 25.8% (95% CI, 19.9% to 35.6%) in older patients (hazard ratio, 2.16; P < .001). Patients ≥ 55 years of age, in whom a lower compliance to the whole planned chemotherapy was observed, benefited significantly from hyper-C, whereas younger patients did not. Conclusion No significant benefit was associated with the introduction of a hyper-C sequence into a frontline pediatric-like adult acute lymphoblastic leukemia therapy. Overall, tolerability of an intensive pediatric-derived treatment was poor in patients ≥ 55 years of age.

Oligometastasiertes nicht kleinzelliges Lungenkarzinom: Vorteile einer lokalen Konsolidierungstherapie nutzen

2019 ◽  
Vol 7 (6) ◽  
pp. 312-313
Author(s):  
Wolfgang Schütte ◽  
Miriam Möller
Keyword(s):  
Adverse Events ◽  
Maintenance Therapy ◽  
Systemic Therapy ◽  
Maintenance Treatment ◽  
Therapy Group ◽  
Progression Free Survival ◽  
Cancer Center ◽  
First Line ◽  
Free Survival ◽  
Md Anderson

Background: Evidence from retrospective studies suggests that disease progression after first-line chemotherapy for metastatic non-small-cell lung cancer (NSCLC) occurs most often at sites of disease known to exist at baseline. However, the potential effect of aggressive local consolidative therapy for patients with oligometastatic NSCLC is unknown. We aimed to assess the effect of local consolidative therapy on progression-free survival. Methods: In this multicentre, randomised, controlled, phase 2 study, eligible patients from three hospitals had histological confirmation of stage IV NSCLC, three or fewer metastatic disease lesions after first-line systemic therapy, an Eastern Cooperative Oncology Group performance status score of 2 or less, had received standard first-line systemic therapy, and had no disease progression before randomisation. First-line therapy was four or more cycles of platinum doublet therapy or 3 or more months of EGFR or ALK inhibitors for patients with EGFR mutations or ALK rearrangements, respectively. Patients were randomly assigned (1:1) to either local consolidative therapy ([chemo]radiotherapy or resection of all lesions) with or without subsequent maintenance treatment or to maintenance treatment alone, which could be observation only. Maintenance treatment was recommended based on a list of approved regimens, and observation was defined as close surveillance without cytotoxic treatment. Randomisation was not masked and was balanced dynamically on five factors: number of metastases, response to initial therapy, CNS metastases, intrathoracic nodal status, and EGFR and ALK status. The primary endpoint was progression-free survival analysed in all patients who were treated and had at least one post-baseline imaging assessment. The study is ongoing but not recruiting participants. This study is registered with ClinicalTrials.gov, number NCT01725165. Findings: Between Nov 28, 2012, and Jan 19, 2016, 74 patients were enrolled either during or at the completion of first-line systemic therapy. The study was terminated early after randomisation of 49 patients (25 in the local consolidative therapy group and 24 in the maintenance treatment group) as part of the annual analyses done by the Data Safety Monitoring Committee of all randomised trials at MD Anderson Cancer Center, and before a planned interim analysis of 44 events. At a median follow-up time for all randomised patients of 12·39 months (IQR 5·52-20·30), the median progression-free survival in the local consolidative therapy group was 11·9 months (90% CI 5·7-20·9) versus 3·9 months (2·3-6·6) in the maintenance treatment group (hazard ratio 0·35 [90% CI 0·18-0·66], log-rank p=0·0054). Adverse events were similar between groups, with no grade 4 adverse events or deaths due to treatment. Grade 3 adverse events in the maintenance therapy group were fatigue (n=1) and anaemia (n=1) and in the local consolidative therapy group were oesophagitis (n=2), anaemia (n=1), pneumothorax (n=1), and abdominal pain (n=1, unlikely related). Interpretation: Local consolidative therapy with or without maintenance therapy for patients with three or fewer metastases from NSCLC that did not progress after initial systemic therapy improved progression-free survival compared with maintenance therapy alone. These findings suggest that aggressive local therapy should be further explored in phase 3 trials as a standard treatment option in this clinical scenario. Funding: MD Anderson Lung Cancer Priority Fund, MD Anderson Cancer Center Moon Shot Initiative, and Cancer Center Support (Core), National Cancer Institute, National Institutes of Health.

Alemtuzumab Reduces Chronic Graft Versus Host Disease (cGVHD) and Treatment Related Mortality (TRM) after Reduced Intensity Conditioning for AML and MDS.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1076-1076 ◽  
Author(s):  
Koen van Besien ◽  
Marcos de Lima ◽  
Andrew Artz ◽  
Betul Oran ◽  
Wendy Stock ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Cancer Center ◽  
P Value ◽  
Unrelated Donor ◽  
Post Transplant ◽  
Md Anderson

Abstract In vivo T-cell depletion with alemtuzumab has been used to reduce acute and chronic GVHD. In order to evaluate its overall effect on transplant outcomes in AML and MDS we compared 90 pts who received fludarabine/melphalan/alemtuzumab (FMA) conditioning and post-transplant tacrolimus at the University of Chicago, with 112 who received fludarabine/melphalan (FM) and post-transplant tacrolimus/methotrexate at MD Anderson Cancer Center. Pt and transplant characteristics were well balanced except for a higher proportion of MDS in the FM group. Median age, proportion unrelated donor tx and proportion high/intermediate and low risk by ASBMT criteria were balanced between the groups. With median follow up of 28 months in both groups, one year progression free survival and overall survival are identical. TRM is significantly higher after FM, but relapse is higher in FMA. 19/103 d 28 survivors after FM vs 7/84 after FMA developed gr III–IV acute GVHD (p=0.04). 46/77 d100 survivors after FM developed ext cGVHD vs 7/63 after FMA (p=0.0000). 43 patients remain alive after FM and 27 have ext cGVHD. 41 remain alive after FMA and 1 has ext cGVHD. Alemtuzumab results in a considerable reduction in acute and particularly chronic GVHD. TRM is reduced compared with standard GVHD prophylaxis. Low incidence of chronic GVHD and reduced TRM may be the major benefit of this strategy. Relapse rates are increased, because of reduced GVL effects or because of improved early survival of high risk patients. Other approaches are necessary for improving long term outcomes. Patient Characteristics and Outcome FMA FM P-value N 90 102 Age (range) 54 (22–74) 51 (17–77) 0.6 AML/MDS 13/77 29/83 0.04 MUD/related 42/48 59/63 0.5 High./Intermediate/LowRisk 48/13/28 76/10/26 0.12 Median Follow up mths (range) 28 (3–89) 28 (1–66) 0.07 TRM@ 100 days 13% + 7% 24% + 8% 0.04 TRM@ 1 year 30% + 12% 42% + 10% 0.04 Relapse @ 1 year 40% + 12% 26% + 10% 0.01 PFS @ 2 years 33% + 11% 37% + 9% 0.9 OS @ 2 year 42% + 11% 44% + 9% 0.5 AGVD gr III–IV 7/84 19/103 0.04 Ext cGVHD 7/63 46/77 0.0000 Ext cGVHD in survivors 1/41 27/43 0.0000

Homozygous Deletion of p16, p14 and p15 Is a Poor Prognostic Factor in Adult B-Lineage Acute Lymphoblastic Leukemia, Not in Childhood B-ALL: A Comparison through Deletion and Hypermethylation Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4477-4477
Author(s):  
Miyoung Kim ◽  
Seon-Hee Yim ◽  
Hai Rim Shin ◽  
Nam Sun Cho ◽  
Seong_Ho Kang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Promoter Methylation ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Homozygous Deletion ◽  
P Value ◽  
Free Survival ◽  
Kaplan Meier ◽  
P15 Gene

Abstract Backgrounds: The biologic characteristics of childhood acute lymphoblastic leukemia (ALL) is different from those of adult ALL. Tumor suppressor genes, p16, p14, and p15 gene are inactivated either by promoter methylation, deletion or mutation, however, in leukemia, promoter methylation and deletion are the main mechanisms of inactivation. Aims: To compare the alteration status of p16, p14, and p15 gene in childhood and adult ALL, we analyzed the incidences and the prognostic significances of deletion and hypermethylation of p16, p14, and p15 in childhood and adult B-ALL. The association between alterations of those genes and known cytogenetic prognostic factors (BCR-ABL, TEL-AML, MLL rearrangement, and numerical changes) were also assessed. Methods: A total of 91 newly diagnosed B-ALL patients (61 children, 30 adults) were studied. Interphase fluorescent in situ hybridization study (p16, BCR-ABL, TEL-AML, MLL) and methylation specific PCR were performed using bone marrow mononuclear cells. Numerical changes were assessed by FISH and chromosome analysis. Chi-square test, Fisher’s exact test, Kaplan and Meier method and Cox proportional hazards regression were applied for statistical analysis. Results: The frequencies of homozygous deletion of p16, p14, and p15 were 11.5% in children and 30.0% in adult, showing higher incidence in adults (p=0.029). In overall survival study, homozygous deletion was associated with the worse prognosis in adults (Fig 1, p=0.019), but not in childhood. The incidences of promoter methylation of p16, p14, and p15 were as follows: 34.4%, 14.8%, and 34.4% in children; 26.7%, 10.0%, and 40.0% 26.7% in adults, respectively, with no statistical difference between two groups. No significant association was observed between deletion and hypermethylation. Childhood ALL showed inactivation of p16 (39.3%), p14 (24.6%), and p15 (42.6%), while adult ALL showed inactivation of p16 (46.7%), p14 (33.3%), and p15 (56.7%), with the same order of frequencies, but with higher tendency of methylation in adult ALL. In p14 unmethylated adults, the homozygous deletion had adverse effect on overall survival (OS) (p=0.036). There were no significant association between chromosomal aberrations and promoter methylation in childhood and adult ALL. The children with sole MLL rearrangement showed poorer disease free survival (DFS) than those with sole homozygous deletion with low statistical significance (p=0.059). Homozygous deletion was translated into poor prognosis in OS in adults without MLL rearrangement (p=0.011). Adult with normal karyotype showed shorter OS when accompanied by homozygous deletion, although p value was 0.051. Conclusions: We performed a comprehensive analysis of deletion and hypermethylation of p16, p14, and p15 genes in both childhood and adult B-ALL. Homozygous deletion was more frequent in adults, showing association with shorter OS in adults, but not in children. This difference of distribution and prognostic value between childhood and adult ALL could be one of the explanations for the disparity of clinical outcome. Our results suggest that homozygous deletion is an independent prognostic factor in adult ALL. Table 1. Deletion and methylation profiles of p16, p14, and p15, and their prognostic siginificances P16, P14, and P15 Deletion P16 Methylation P14 Methylation P15 Methylation *P: p value by multivariate analysis †OS: Overall survival ‡DPS: Disease free survival Childhood Frequency 11.5% 34.4% 14.8% 34.4% *P (†OS) 0.853 0.979 0.651 0.591 P (‡DPS) 0.716 0.956 0.809 0.977 Adults Frequency 30.0% 26.7% 10.0% 40.0% P (OS) 0.019 0.151 0 892 0.330 P (DPS) 0.218 0.382 0.079 0.760 Figure 1. Kaplan-Meier curve for childhood and adult B-ALL patients.&#x2028; P value was obtained by multivariate analysis using Cox hazard regression model. (A) Childhood B-ALL (B) B. Adult B-ALL Figure 1. Kaplan-Meier curve for childhood and adult B-ALL patients.&#x2028; P value was obtained by multivariate analysis using Cox hazard regression model. (A) Childhood B-ALL (B) B. Adult B-ALL

Adults with Acute Lymphoblastic Leukemia and T(1;19) Abnormality Have a Favorable Outcome with Hyper-CVAD Chemotherapy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3955-3955
Author(s):  
Ravin Jain Garg ◽  
Hagop M Kantarjian ◽  
D. A Thomas ◽  
Stefan Faderl ◽  
Farhad Ravandi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Response Duration ◽  
Complete Response ◽  
Cancer Center ◽  
P Value ◽  
Small Subset ◽  
High Dose ◽  
Cytogenetic Abnormalities

Abstract Among the well-described cytogenetic abnormalities in adults with acute lymphoblastic leukemia (ALL), a translocation involving chromosomes 1 and 19 [t(1;19) (q23;p13)] occurs in a small subset but has varyingly been associated with a good or bad prognosis in different studies. Adults with ALL and t(1;19) treated at M.D. Anderson Cancer Center were reviewed. Their clinical features and outcome were compared to those with other cytogenetic abnormalities. Endpoints included complete remission rate (CR), complete response duration (CRD) and overall survival (OS). Of 411 adults with pre-BALL, 12 patients had t(1;19). Ten of the 12 patients with t(1;19) received Hyper-CVAD (Cyclophosphamide, Vincristine, Adriamycin, Dexamethasone alternating with Methotrexate and high-dose Cytarabine); the other 2 were treated with VAD (Vincristine, Adriamycin, Dexamethasone). All 12 patients achieved CR; the 3-year survival rate was 73%. Patients with t(1;19) had significantly better CRD and OS when compared to all other patients combined as well as individually to patients with Ph+, t(4;11), and lymphoma-like abnormalities [6q(−), 14q+, t(11;14), t(14;18)]. Adults with ALL and t(1;19) have an excellent prognosis when treated with the Hyper-CVAD regimen. Outcome of patients by cytogenetic group: t(1;19) vs. individual cytogenetic groups OVERALL SURVIVAL N Fail 3-Year % Median (weeks) P-value T(1,19) 12 3 73 Not recorded Diploid 138 72 52 179 0.09 Lymphoma-like 20 17 35 54 0.008 Ph+ 117 88 23 68 0.0002 Miscellaneous 112 56 56 236 0.17 T(4,11) 12 10 0 58 0.002 COMPLETE RESPONSE DURATION (CRD) N Fail 3-Year % Median (weeks) P-value T(1,19) 12 2 80 Not recorded Diploid 133 59 54 177 0.06 Lymphoma-like 16 13 34 89 0.009 Ph+ 102 52 42 63 0.006 Miscellaneous 100 41 59 401 0.16 T(4,11) 11 7 NR 45 0.018

Evaluation of the Gene Xpert DX System for Molecular Monitoring in CML

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4794-4794
Author(s):  
Ghayathri Jeyakumar ◽  
Hagop M. Kantarjian ◽  
Alfonso Quintas-Cardama ◽  
Elias J. Jabbour ◽  
Farhad Ravandi ◽  
...  
Keyword(s):  
Real Time ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Great Variability ◽  
Molecular Diagnostic ◽  
Cancer Center ◽  
Molecular Monitoring ◽  
Simple Method ◽  
Two Samples ◽  
Md Anderson

Abstract Abstract 4794 Background: The diagnosis of chronic myeloid leukemia (CML) and the monitoring during therapy requires identification and quantification of the BCR-ABL1 transcripts. Molecular monitoring has become a requirement as therapy has become more efficient in inducing cytogenetic and molecular remissions. Unfortunately, there is great variability in the methodologies used for molecular monitoring, with various levels of expertise, great variability of the results between different laboratories, and frequently limited access. A simple method for rapid detection and quantification of BCR-ABL1 transcripts would benefit patients and improve outcomes. The GeneXpert DX System rapidly detects and quantifies BCR-ABL1 mRNA transcripts (type e13a2/b2a2 or e14a2/b3a2) in patients diagnosed with CML via an automated, quantitative real-time reverse transcription polymerase chain reaction. Results are available within 2 hours and adjusted to the international scale. We assessed the correlation between the GeneXpert system with the results from the Molecular Diagnostic Laboratory (MDL) at MD Anderson Cancer Center. Methods: Peripheral blood specimens were collected from 55 patients with CML, acute lymphoblastic leukemia and acute myeloid leukemia and used for assay development, analytical validation and precision studies that compared the GeneXpert BCR-ABL1 Monitor Assay versus the standard MD Anderson MDL real-time PCR protocol. CML Ph positive was assessed as belonging to categories based on the BCR-ABL1 mRNA transcript level (Category I, >1%; Category 2, >0.1–1%; Category 3, >0.01%–0.1%; Category 4, ≤0.01%). Patients who had tyrosine kinase therapy resulting in stable disease were in categories 3 or 4, whereas newly diagnosed patients or those with acute disease were in categories 1 and 2. Ph-negative patients with ALL (n=2) and AML (n=4) were the negative controls. Results: Of the 55 patients whose blood was tested by the GeneXpert monitoring assay, 49 patients with CML fell into categories 1–4 (3, 7,4,35 respectively). The remaining 6 patients had a diagnosis of ALL or AML and acted as negative control. These patients had undetectable transcript levels by the GeneXpert system. The median time to obtaining results with the GeneXpert system was 1 hour and 30 min (range 1:29:51 to 1:31:16). There was a strong correlation between the results achieved with the GeneXpert system and those obtained at the MDACC MDL (R=0.7597; P=< 0.0001). Only two samples showed clearly discordant values and these likely represent swapping of the samples which were run at the same time. Excluding these samples the correlation is even tighter (R=0.8937; P= < 0.0001). Conclusion: Results from GeneXpert system BCR-ABL1 are rapid and reliable and can be obtained with little training required. These results suggest that this methodology can be used to expand access and reproducibility to molecular monitoring in CML. Disclosures: Cortes: Cepheid: Research Funding.

Plasma GH as a diagnostic and prognostic biomarker in HCC without cirrhosis.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 227-227
Author(s):  
Roberto Carmagnani Pestana ◽  
Manal Hassan ◽  
Reham Abdel-Wahab ◽  
Yehia I. Abugabal ◽  
Lauren Girard ◽  
...  
Keyword(s):  
Cox Regression ◽  
Early Stage ◽  
Tnm Staging ◽  
Cancer Center ◽  
Limited Information ◽  
Cox Regression Analysis ◽  
Diagnostic Role ◽  
Md Anderson ◽  
Plasma Gh

227 Background: The association between the GH/IGF-1 axis and HCC was reported in patients (pt) with underlying cirrhosis. However, there is limited information among HCC pt without (w/o) cirrhosis. We herein investigated the role of GH as a circulating biomarker for HCC diagnosis and prognosis in pt w/o cirrhosis. Methods: Under IRB approval, we prospectively enrolled 1267 newly-diagnosed HCC pt in a case control study at the MD Anderson Cancer Center (2000-2015). Controls were healthy individuals (n = 1104). Plasma GH and AFP were measured 274 HCC pt w/o cirrhosis 200 healthy controls. IGF-1 was measured in 133 and 82 pt, respectively. We classified HCC pt into higher and lower GH values (cutoff for women, 3.7 µg/L; men, > 0.9 µg/L). Results: Most pt (74%) were male, with advanced BCLC staging (C-D, 74%) and 61% were older than 60y. Baseline GH was higher in HCC w/o cirrhosis (mean 3.3 µg/L) than controls (mean 0.4 µg/) (p < .001). ROC curve was plotted to assess diagnostic role. The AUC for AFP was 82.9 (p < .001); for GH 78.2 (p < .001). When only non-cirrhotic HCC pt with early stage (CLIP 0-2) and AFP < 20 ng/m were compared to controls, the GH/IGF-1 ratio had high prediction of early stage HCC - AUC 83 (95% CI 78-89%) (p < .0001). At a specificity of 90%, sensitivity of GH/IGF ratio was 67%. In addition, among HCC w/o cirrhosis, higher GH levels correlated with presence of vascular invasion (p < .001) and thrombosis (p = .004), tumor involvement of > 50% liver (p = .003), and more advanced BCLC (p < .001) and TNM staging (p < .001). Median overall survival (months) of HCC pt w/o cirrhosis with high GH levels was 13.1 (10.8-15.4) compared to 37.4 (19.8-55.1) of pt with lower plasma GH (p < .001). Multivariate cox-regression analysis identified high GH as an independent risk factor for mortality (HR = 1.8; 95% CI, 1.3-2.4; p < .001). Conclusions: Our study demonstrates the diagnostic and prognostic role of plasma GH in non-cirrhotic HCC and identifies the GH/IGF-1 ratio as a promising diagnostic marker for early stage HCC w/o cirrhosis and low AFP; this analysis excludes the confounding effect hepatocyte impaired function by presence of cirrhosis. Further studies are warranted to assess the causes of the observed differences.

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