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.

Prediction Of Therapeutic Resistance In Adult Acute Myeloid Leukemia: Analysis Of 4,550 Newly Diagnosed Patients From MRC/NCRI, HOVON/SAKK, SWOG, and MD Anderson Cancer Center

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 64-64
Author(s):  
Roland B Walter ◽  
Megan Othus ◽  
Alan K. Burnett ◽  
Bob Löwenberg ◽  
Hagop M. Kantarjian ◽  
...  
Keyword(s):  
Cancer Research ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Cancer Center ◽  
Therapeutic Resistance ◽  
Refractory Disease ◽  
Newly Diagnosed ◽  
Md Anderson ◽  
Acute Myeloid

Abstract Background Primary failure of induction chemotherapy or disease recurrence after short remission duration (“therapeutic resistance”) remains the principal problem in adult acute myeloid leukemia (AML). Although cytogenetic and molecular abnormalities have proven useful in the identification of subsets of patients with distinct disease risks, it is unclear to what degree therapeutic resistance can be predicted for individual patients. Patients and Methods We used information on patients with newly diagnosed AML other than acute promyelocytic leukemia receiving curative-intent treatment on trials conducted by the U.K. Medical Research Council/National Cancer Research Institute (MRC/NCRI; 1988-2010; n=2,615), the Dutch-Belgian Cooperative Trial Group for Hematology/Oncology and the Swiss Group for Clinical Cancer Research (HOVON/SAKK; 1987-2008; n=1,098), the U.S. cooperative group SWOG (1987-2009; n=428), and MD Anderson Cancer Center (2000-2011; n=409). Achievement of a complete remission (CR) with the initial 1-2 courses of induction chemotherapy was defined as therapeutic success. Patients who failed to achieve CR were defined as primary refractory for the purpose of this analysis; patients who experienced treatment-related mortality (i.e., death within 28 days of treatment initiation) were excluded from this analysis. We used logistic regression analyses to assess the relationship between individual covariates and various measures of therapeutic resistance. The following pre-treatment covariates were used in the regression modeling: age at diagnosis, gender, white blood cell (WBC) count, platelet count, bone marrow blast percentage, disease type (primary vs. secondary), cytogenetic risk, FLT3/NPM1 status, and treatment site. We then used the area under the receiver operator characteristic curve (AUC) to quantify a model’s ability to predict therapeutic resistance; in this approach, an AUC of 1 indicates perfect prediction while an AUC of 0.5 indicates no prediction; AUC values of 0.6-0.7, 0.7-0.8, and 0.8-0.9 are commonly considered as poor, fair, and good, respectively. Results A total of 4,550 patients (median age: 52 years [range: 15-90 years]) were included in this study. A CR to the initial 1-2 courses of induction chemotherapy was achieved in 3,597 (79.1%) of patients, whereas 953 (20.9%) were primary refractory; 1,304/4,497 patients (29.0%) with sufficient follow-up time were either primary refractory or had a relapse-free survival (RFS) of 3 months or less after CR achievement, 1,774/4,445 patients (39.9%) with sufficient follow-up time were either primary refractory or had a RFS of 6 months or less after CR achievement, and 2,523/4,386 patients (57.5%) with sufficient follow-up time were primary refractory or had a RFS of 12 months or less after CR achievement. Increasing age (p<0.001) and WBC (p<0.001), secondary disease (p<0.001), FLT3/NPM1 status (p<0.001), and cytogenetic risk (favorable or intermediate vs. adverse, p<0.001) were independently associated with being primary refractory to induction chemotherapy in a combined analysis of all patients. In the total patient cohort, a bootstrap-corrected multivariate model predicting primary refractoriness yielded an AUC of 0.79; removal of FLT3 and NPM1 from the model minimally, but statistically significantly, decreased the AUC (0.77). Between individual treatment sites, these AUCs varied from 0.82/0.81 to 0.69/0.67. Prediction of therapeutic resistance, as defined as primary refractoriness or relapse after short remission duration, was more difficult. Specifically, when analyzing the entire study cohort, the AUCs for models predicting primary refractory disease or relapse within 3 months were 0.76/0.74 (with/without inclusion of FLT3/NPM1 data) and further decreased to 0.76/0.73 and 0.75/0.71 for models predicting primary refractory disease or relapse within 6 or 12 months, respectively. Conclusion Our ability to predict therapeutic resistance based on routinely available clinical covariates, even with inclusion of commonly used molecular data on FLT3 and NPM1, is relatively limited. This finding would support the continued use of randomization to assign patients between standard and investigational therapies, and argues for the integration of early treatment response measures (e.g. minimal residual disease) to optimize prediction of therapeutic resistance. Disclosures: No relevant conflicts of interest to declare.

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]

scholarly journals Immunotherapy for T-Cell ALL and T-NHL: Highlights From SOHO 2020

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Allyson Price, MPAS, PA-C
Keyword(s):  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Cancer Center ◽  
University Of Texas ◽  
Keynote Presentation ◽  
Non Hodgkin Lymphoma ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Md Anderson ◽  
The University ◽  
Washington University

In his keynote presentation, John DiPersio, MD, PhD, of Washington University, recipient of the SOHO 2020 Distinguished Lecturer Award, discussed immunotherapy for T-cell acute lymphoblastic leukemia and T-cell non-Hodgkin lymphoma. Allyson Price, MPAS, PA-C, of The University of Texas MD Anderson Cancer Center, distills the seminal research by Dr. DiPersio and discusses implications for advanced practitioners.

scholarly journals Molecular, Cytogenetic, and Hematological Analysis of Chronic Myeloid Leukemia Patients and Discovery of Two Novel Translocations

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Muhammad Asif ◽  
Abrar Hussain ◽  
Abdul Wali ◽  
Nazeer Ahmed ◽  
Irfan Ali ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Real Time ◽  
Imatinib Mesylate ◽  
Real Time Pcr ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Hematopoietic Stem ◽  
Two Samples ◽  
Hematological Analysis ◽  
Variant Translocation

Chronic myeloid leukemia (CML) is a disease of hematopoietic stem cells and is caused by the balanced translocations among the long arms of chromosomes 9 and 22, which are called the Philadelphia (Ph) chromosome. In this study, 131 CML patients were enrolled. Complete blood cell count was performed at the time of diagnosis for all the patients. Cytogenetic (karyotyping) examination using bone marrow samples was conducted on 76 CML patients for the confirmation of Ph-positive (9;22)(q34;q11) standard translocation, complex variant translocation, and additional chromosome abnormalities. FISH was performed on 38 patients for diagnostic purposes and on 39 patients for monitoring purposes. Twenty-two samples of CML patients were evaluated by reverse transcriptase PCR and real-time PCR for the patients who failed to respond against imatinib mesylate. In this study, 72 (54.96%) were males and 59 (45.03%) were females with a median age of 38.5 years. CBC values in the diagnosis process showed that 75 patients had high values of WBC being > 100 × 10 3 / μ l , while 71 (58.01) patients exhibited reduced values of hemoglobin, i.e., <10.00 mg/dl, and high values of PLTs > 100 were observed in 40 (30.53%) patients. Cytogenetic results show that standard translocation was developed in 63 (82.89%), development of complex variant translocations in 4 (5.32%), additional chromosomal abnormalities (ACAs) in 3 (3.94%), and ACAs together with complex variant translocations in 1 (1.31%) patient. At the time of diagnosis, 61 (92.95%) patients were in the chronic phase, 4 (5.63%) were in the accelerated phase, and only 1 (1.40%) was in the blast crisis. Out of twenty-two patients, only 6 CML patients who were shifted from imatinib mesylate to nilotinib showed BCR-ABL-positive amplification. However, only 7 out of twenty-one patients exhibit BCR-ABL gene values ≥ 1 after three months of follow-up when analyzed by the quantitative real-time PCR. In conclusion, we found a novel five-way translocation 46XX,t(1;2;2;17;9;22)(p36.3,q21;q11.2,q21,q34,q11.2) and a novel four-way complex variant translocation 48XY,+8(8;17)(9;22),+der(22)(q11.2;q23)(q34;q11.2) in the accelerated phase.

From the archives of MD Anderson Cancer Center: BCR-ABL1-like B acute lymphoblastic leukemia with IGH/EPOR fusion

2020 ◽  
Vol 46 ◽  
pp. 151514
Author(s):  
Wei Liu ◽  
Beenu Thakral ◽  
Guilin Tang ◽  
Wei Wang ◽  
L. Jeffrey Medeiros ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Cancer Center ◽  
Md Anderson

scholarly journals Real-time quantitative PCR: a reliable molecular diagnostic and follow-up tool for ‘minimal residual disease’ assessment in chronic myeloid leukemia

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Niyaz A. Azad ◽  
Zafar A. Shah ◽  
Arshad A. Pandith ◽  
Roohi Rasool ◽  
Samoon Jeelani
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Real Time ◽  
Quantitative Pcr ◽  
Myeloid Leukemia ◽  
Pearson Correlation ◽  
Disease Assessment ◽  
Molecular Diagnostic ◽  
Imatinib Treatment ◽  
Rt Pcr ◽  
Real Time Quantitative Pcr

Molecular monitoring of BCR-ABL transcript levels by real-time quantitative PCR is increasingly being used to diagnose the disease and assess treatment response in patients with chronic myeloid leukemia (CML). This has become particularly relevant when residual levels of leukemia usually fall below the level of detection by cytogenetic analysis. Forty-two CML patients, including 18 males (42.86%) and 24 females (57.14%) aged 7–75 years, were enlisted for the study and followed-up for the response to imatinib treatment. Patients were subjected to Multiplex RT-PCR (reverse-transcriptase PCR) and were all found to harbor either e13a2 or the e14a2, which could be analyzed by a single Taqman probe based quantitation kit (Geno-Sen’s) to quantitate the BCR-ABL transcript load. The Multiplex RT-PCR and peripheral blood cytogenetics providing specific and sensitive detection of BCR-ABL fusion transcripts and metaphase signal load respectively were used as parallel reference tools to authenticate the q-PCR findings. There was 100% concordance between the multiplex RT-PCR and the q-PCR as every positive RT-PCR assay for a transcript reflected as q-PCR load of above 0% for that transcript. q-PCR also demonstrated a strong Pearson correlation with the cytogenetic response.

scholarly journals Predicting Drug Response in Acute Lymphoblastic Leukemia: Highlights From SOHO 2020

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Allyson Price, MPAS, PA-C
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Annual Meeting ◽  
Drug Response ◽  
Lymphoblastic Leukemia ◽  
Cancer Center ◽  
Research Hospital ◽  
University Of Texas ◽  
Md Anderson ◽  
The University

Allyson Price, MPAS, PA-C, of The University of Texas MD Anderson Cancer Center, summarizes the session on the genomics of drug response in acute lymphoblastic leukemia presented by Jun J. Yang, PhD, of St. Jude’s Research Hospital, at the 2020 SOHO Annual Meeting.

Acute Myeloid Leukemia in Adolescents and Young Adults (AYA): The MD Anderson Cancer Center (MDACC) Experience

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3982-3982
Author(s):  
Naveen Pemmaraju ◽  
Hagop M. Kantarjian ◽  
Farhad Ravandi ◽  
Susan O’Brien ◽  
William G. Wierda ◽  
...  
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Treatment Options ◽  
Adolescent And Young Adult ◽  
Cancer Center ◽  
Secondary Malignancy ◽  
Clonal Proliferation ◽  
Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic neoplasms demonstrating clonal proliferation of myeloid precursors and is typically a disease of older adults. In acute lymphoblastic leukemia (ALL) adolescent and young adult (AYA) patients (pts) have a distinct outcome, possibly influenced by type of therapy (i.e., usually better with more intensive regimens). There is little information about outcome of AML in AYA. Aims: To define the characteristics and outcome of AYA pts with AML treated at MDACC. Methods: We retrospectively analyzed the data of all pts with AML treated at MDACC from 1965 to 2008. Those aged 16 to 21 years were defined as AYA. Results: Among 3934 adult pts seen during this period, 163 (4%) were AYA. The median age was 19 yrs. These included 27 (17%) pts with Core Binding Factor (CBF)-AML [inv(16), t (8:21)]and 19 pts (12%) with acute promyelocytic leukemia (APL). Among other evaluable pts, 50% had diploid cytogenetics, 39% miscellaneous changes, and 11% 5-and/or 7- abnormalities. Antecedent hematologic disorders were present in 33 (20%) and AML was a secondary malignancy in 6%. Among 20 evaluable pts, FLT3 ITD was documented in 4 and mutation in 2. CR rates were 89% for CBF AML, 79% for APL, and 75% for all others. The median survival for the total group was 88 weeks (wks) with 36% alive at 3 yrs, and median CR duration of 67 wks (30% CR at 3 yrs). Outcome is better for pts with CBF leukemias (3-yr survival 56%, CR duration 49%) and APL (3-yr survival 51%, CR duration 36%) compared to other AML (3-yr survival 28%, CR duration 24%). CR rates have improved from 71% in 1965–84, to 85% in 1985–94 and 83% after 1994. Similarly, overall survival (OS) has increased during the same time periods (3-yr survival 18%, 44%, and 53%, respectively) together with CR duration (3-yr CR duration 21%, 32% and 39%, respectively) as early mortality has decreased (11%, 8%, and 4%, respectively). To compare outcome with older adults, we focused on those with diploid cytogenetics (Table 1): Percentage by age group Outcome 16–21 22–45 46–60 &gt;60 CR 81 75 68 54 Induction mortality 2 11 13 24 3-year survival 46 36 28 16 3-year remission duration 39 32 30 22 Conclusion: The outcome of AYA pts with AML is significantly better than that of older adults with AML. Despite these improvements over time, there is still significant room for improvement in this area, particularly among those with AML other than CBF and APL. Exploration of new treatment options is needed in this patient population.

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