Faculty Opinions recommendation of Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy.

2014 ◽  
Author(s):  
Greg Bociek
Keyword(s):  
Response To Therapy ◽  
Molecular Characteristics

Will the “new biology” Affect the Future of Histopathology?

2001 ◽  
Vol 16 (1) ◽  
pp. 1-4 ◽  
Author(s):  
A. Carbone
Keyword(s):  
Molecular Techniques ◽  
Response To Therapy ◽  
Molecular Characteristics ◽  
Cancer Management ◽  
Molecular Tests ◽  
Specific Tumor ◽  
Diagnosis And Classification ◽  
New Biology ◽  
The Impact

The technologies used in histopathology are changing as a consequence of the current revolutionary progress in several areas of biology. It is likely that general cancer management will improve because of the impact of molecular techniques and immunohistochemistry on tumor diagnosis and classification and on the determination of prognosis and response to therapy. Moreover, as therapies are starting to be modelled after the distinctive molecular characteristics of a specific tumor, the availability of molecular tests to all patients will become a matter of great importance.

Molecular characterization of squamous cell carcinoma of the anal canal (SCCA).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 538-538 ◽  
Author(s):  
Benjamin Adam Weinberg ◽  
Heinz-Josef Lenz ◽  
David Arguello ◽  
Wafik S. El-Deiry ◽  
Joanne Xiu ◽  
...  
Keyword(s):  
Low Frequency ◽  
Hpv Infection ◽  
Response To Therapy ◽  
Molecular Characteristics ◽  
Missense Mutations ◽  
Chi Square ◽  
Gene Testing ◽  
Tumor Mutational Burden ◽  
N 93

538 Background: Nivolumab has shown promising results in SCCA patients. The majority of SCCA cases have been linked to prior human papillomavirus (HPV) infection. However, HPV negative tumors are frequently TP53 mutated and often resistant to therapy. Molecular characteristics of SCCA are largely undefined. Here we explored the underlying biology of SCCA and the differences between TP53-wild type ( TP53-WT) and TP53-mutated ( TP53-MT) tumors. Methods: SCCA specimens underwent multiplatform testing with protein expression (IHC), gene amplification (ISH), and sequencing (NGS). Tumor mutational burden (TMB) was calculated using only somatic nonsynonymous missense mutations. Chi-square tests were used for comparative analyses. Results: In total, 253 tumors were studied. The most frequently mutated genes included PIK3CA (24%), BRCA2 (14%), FBXW7 (12.4%), TP53 (9.7%), and PTEN (8.9%). In a subset of 23 tumors subjected to Illumina NextSeq (592 gene) testing, the most common mutations were NOTCH2 (30%), NOTCH1 (27.3%), POLE (21.7%) , TSC2 (17.4%), PTEN (14.3%), BRAF (13.6%), BRCA2 (13.0%), PIK3CA (13.0%), and FBXW7 (9.5%). Tumors frequently expressed MRP1 (97.6%), EGFR (92.7%), TOP2A (88.5%), TOPO1 (69.5%), MGMT (67.8%), and RRM1 (59.9%). Expression of PD-1 was seen in 55.8% (24/43) of tumors, and PD-L1 in 15.4% (9/34). HER2 was amplified in 2% (3/147) of samples, which has not been previously described in SCCA. When compared with TP53-WT (n = 93) tumors, T P53-MT (n = 10) had higher rates of BRAF (22% vs. 1%, p < 0.001) and RB1 mutations (44% vs. 0%, p < 0.001), whereas TP53-WT had higher expression of TOPO1 (76% vs. 40%, p = 0.01) and TUBB3 (19% vs. 50%, p = 0.02). There were no differences between the two groups in the frequency of PD-1 or PD-L1 expression. Mean TMB was 8.6 mutations/megabase and, using a TMB cut-off > 17 mutations/megabase to define high vs. low TMB, 6.7% of tumors were TMB-High. High TMB did not correlate with PD-1 (p = 0.50) or PD-L1 status (p = 0.52). Conclusions: Molecular profiling differences between TP53-MT and TP53-WT SCCA indicate different carcinogenic pathways and biology, which may influence response to therapy. Low frequency mutations in several druggable genes may provide therapeutic opportunities for patients with SCCA.

Clinical and Laboratory Features of Community-Associated Methicillin-ResistantStaphylococcus aureus:Is It Really New?

2006 ◽  
Vol 27 (2) ◽  
pp. 133-138 ◽  
Author(s):  
Leonard B. Johnson ◽  
Sajjad Saeed ◽  
Joan Pawlak ◽  
Odette Manzor ◽  
Louis D. Saravolatz
Keyword(s):  
Medical Center ◽  
Academic Medical Center ◽  
Response To Therapy ◽  
Laboratory Analysis ◽  
Molecular Characteristics ◽  
Molecular Features ◽  
Type Iv ◽  
Single Clone ◽  
Systemic Antibiotics ◽  
Staphylococcal Cassette Chromosome

Objective.To review the epidemiologic and molecular characteristics of community-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) in Detroit, Michigan, to assess the risk factors for infection and the response to therapy.Design.Prospective clinical and laboratory study of 2003-2004 CA-MRSA isolates. Molecular features were compared with CA-MRSA isolates from 1980.Setting.A 600-bed urban academic medical center.Patients.Twenty-three patients with CA-MRSA infections from 2003-2004 were evaluated. In addition, laboratory analysis was performed on 13 CA-MRSA isolates from 1980.Main Outcome Measures.Laboratory analysis of isolates included antimicrobial susceptibility testing, pulsed-field genotyping, testing for Panton-Valentine leukocidin (PVL) genes, and staphylococcal cassette chromosomemectyping.Results.Patients were predominantly young African American males and presented with skin and soft-tissue infections. All isolates were resistant to erythromycin and highly susceptible to other agents. Patients were generally treated successfully with combination incision and drainage and systemic antibiotics. Among the 23 isolates, 20 (87%) were the same strain. This strain carried the staphylococcal cassette chromosomemectype IV and PVL genes and is genetically identical to USA 300. Thirteen isolates of patients from our community who presented with CA-MRSA infections in 1980 represented a single clone that is unique compared with the 2003-2004 isolates. This strain carried staphylococcal cassette chromosomemectype IVA but did not carry the PVL genes.Conclusions.In our community, CA-MRSA is largely due to a single clone with a type IVmecgene and PVL gene. The type IV staphylococcal cassette chromosomemectype can be demonstrated in CA-MRSA isolates from a remote period, suggesting that earlier outbreaks were not related to healthcare exposure.

scholarly journals Evaluation of p53, HoxD10, and E-Cadherin Status in Breast Cancer and Correlation with Histological Grade and Other Prognostic Factors

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Preethi Sekar ◽  
Jyotsna Naresh Bharti ◽  
Jitendra Singh Nigam ◽  
Ankit Sharma ◽  
Priyanka Bhatia Soni
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Gene Mutation ◽  
Histological Grade ◽  
Response To Therapy ◽  
Molecular Characteristics ◽  
Mrna Levels ◽  
Cdh1 Gene ◽  
P53 Expression ◽  
E Cadherin

Background. Study of tumor molecular characteristics is necessary to understand both the risk of breast cancer recurrence and the response to therapy.Aims. To evaluate p53, HoxD10, and E-cadherin status in breast cancer and to correlate with histological grade and other prognostic factors.Material and Methods. The study was conducted in 60 cases of invasive ductal carcinoma NOS with 20 cases belonging to each grade and evaluation of p53 was done by IHC and that of HoxD10 and E Cadherin status by PCR and correlation was done with histological grade and other prognostic factors.Result. p53 expression was seen in 71.67% (43/60) of the tumors. HoxD10 gene was downregulated in 46.67% (28/60) of the tumors. p53 overexpression and lower HoxD10 mRNA levels showed statistically significant association higher histological grade of the tumor (P<0.05). CDH1 gene mutation was seen in 60% (15/25) of the tumors. No significant association was found between p53 expression, HoxD10 gene, CDH1 gene mutation, and other prognostic factors.Conclusion. p53 over expression and lower HoxD10 mRNA levels were found to be significantly associated with higher grade tumours. This suggests that p53 and HoxD10 gene play an important tumor suppressor role and the loss of which results in breast cancer progression.

scholarly journals Biological and therapeutic implications of a unique subtype of NPM1 mutated AML

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Arvind Singh Mer ◽  
Emily M. Heath ◽  
Seyed Ali Madani Tonekaboni ◽  
Nergiz Dogan-Artun ◽  
Sisira Kadambat Nair ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Ex Vivo ◽  
Therapeutic Benefit ◽  
Response To Therapy ◽  
World Health ◽  
Molecular Characteristics ◽  
Molecular Heterogeneity ◽  
Rna Seq ◽  
Therapeutic Implications ◽  
Health Organization

AbstractIn acute myeloid leukemia (AML), molecular heterogeneity across patients constitutes a major challenge for prognosis and therapy. AML with NPM1 mutation is a distinct genetic entity in the revised World Health Organization classification. However, differing patterns of co-mutation and response to therapy within this group necessitate further stratification. Here we report two distinct subtypes within NPM1 mutated AML patients, which we label as primitive and committed based on the respective presence or absence of a stem cell signature. Using gene expression (RNA-seq), epigenomic (ATAC-seq) and immunophenotyping (CyToF) analysis, we associate each subtype with specific molecular characteristics, disease differentiation state and patient survival. Using ex vivo drug sensitivity profiling, we show a differential drug response of the subtypes to specific kinase inhibitors, irrespective of the FLT3-ITD status. Differential drug responses of the primitive and committed subtype are validated in an independent AML cohort. Our results highlight heterogeneity among NPM1 mutated AML patient samples based on stemness and suggest that the addition of kinase inhibitors to the treatment of cases with the primitive signature, lacking FLT3-ITD, could have therapeutic benefit.

scholarly journals Identification of an Immune Gene-Associated Prognostic Signature and its Association with A Poor Prognosis in Gastric Cancer Patients

2020 ◽  
Author(s):  
Xiaoqing Guan ◽  
Zhi-Yuan Xu ◽  
Runzhe Chen ◽  
Jiangjiang Qin ◽  
Xiang-Dong Cheng
Keyword(s):  
Gastric Cancer ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Response To Therapy ◽  
Molecular Characteristics ◽  
Immune Gene ◽  
Cell Type ◽  
Prognostic Signature ◽  
Immune Signature ◽  
Gene Sets

Abstract Background: The immune response plays a critical role in gastric cancer (GC) initiation, progression, metastasis, and response to therapy. A better understanding of the tumor-immune system interactions in GC may provide promising diagnostic, prognostic, and therapeutic biomarkers for patients with this disease. In the present study, we aimed to identify a prognostic signature of GC through a comprehensive bioinformatics analysis on the tumor-immune interactions as well as the molecular characteristics. Methods: We employed the single sample Gene Sets Enrichment Analysis (ssGSEA) to define immune-related subtypes, used Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) to evaluate the content of tumor and stroma, and utilized Cell type Identification By Estimating Relative Subsets of RNA Transcripts (CIBERSORT) to assess the immune cell type infiltration. We also investigated the complicated biological functions and regulatory networks of these subtypes using Gene Sets Enrichment Analysis (GSEA). Next, we developed a risk model using Lasso Cox regression and verified it via the external validation set. Finally, we systematically correlated the immune signature with GC clinicopathologic features and genomic characteristics. Results: We observed two immune subgroups depending on the activity and level of immune cell in GC patients. We also identified a six-immune-gene signature as a promising independent prognostic biomarker for GC. A nomogram was constructed based on the immune signature and clinical characteristics and showed high potential for GC prognosis prediction. The receiver operating characteristic (ROC) curve analysis distinguishing patients with distinct prognosis yielded an area under the curve (AUC) of 0.779 for 5 years.Conclusions: Our work supports the clinical significance of this immune gene-associated signature for predicting the prognosis of GC patients. This study also shed light on the treatment strategies for GC patients from the perspective of immunology.

scholarly journals Large Cell Neuro-Endocrine Carcinoma of the Lung: Current Treatment Options and Potential Future Opportunities

2021 ◽  
Vol 11 ◽  
Author(s):  
Miriam Grazia Ferrara ◽  
Alessio Stefani ◽  
Michele Simbolo ◽  
Sara Pilotto ◽  
Maurizio Martini ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Treatment Options ◽  
Large Cell ◽  
Small Sample ◽  
Response To Therapy ◽  
World Health ◽  
Molecular Characteristics ◽  
Management Options ◽  
Early Stage Disease ◽  
Cell Lung Carcinoma

Large-cell neuroendocrine carcinomas of the lung (LCNECs) are rare tumors representing 1–3% of all primary lung cancers. Patients with LCNEC are predominantly male, older, and heavy smokers. Histologically, these tumors are characterized by large cells with abundant cytoplasm, high mitotic rate, and neuroendocrine immunohistochemistry-detected markers (chromogranin-A, synaptophysin, and CD56). In 2015 the World Health Organization classified LCNEC as a distinct subtype of pulmonary large-cell carcinoma and, therefore, as a subtype of non-small cell lung carcinoma (NSCLC). Because of the small-sized tissue samples and the likeness to other neuroendocrine tumors, the histological diagnosis of LCNEC remains difficult. Clinically, the prognosis of metastatic LCNECs is poor, with high rates of recurrence after surgery alone and overall survival of approximately 35% at 5 years, even for patients with early stage disease that is dramatically shorter compared with other NSCLC subtypes. First-line treatment options have been largely discussed but with limited data based on phase II studies with small sample sizes, and there are no second-line well defined treatments. To date, no standard treatment regimen has been developed, and how to treat LCNEC is still on debate. In the immunotherapy and targeted therapy era, in which NSCLC treatment strategies have been radically reshaped, a few data are available regarding these opportunities in LCNEC. Due to lack of knowledge in this field, many efforts have been done for a deeper understanding of the biological and molecular characteristics of LCNEC. Next generation sequencing analyses have identified subtypes of LCNEC that may be relevant for prognosis and response to therapy, but further studies are needed to better define the clinical impact of these results. Moreover, scarce data exist about PD-L1 expression in LCNEC and its predictive value in this histotype with regard to immunotherapy efficacy. In the literature some cases are reported concerning LCNEC metastatic patients carrying driver mutations, especially EGFR alterations, showing targeted therapy efficacy in this setting of disease. Due to the rarity and the challenging understanding of LCNEC, in this review we aim to summarize the management options currently available for treatment of LCNEC.

Cell-free circulating tumor DNA (cfDNA) analysis of advanced thymic epithelial tumors (TETs).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8577-8577
Author(s):  
Hiba I. Dada ◽  
Leylah Drusbosky ◽  
Giuseppe Giaccone
Keyword(s):  
Statistical Significance ◽  
Circulating Tumor Dna ◽  
Small Sample ◽  
Response To Therapy ◽  
Molecular Characteristics ◽  
Genomic Alterations ◽  
Thymic Epithelial Tumors ◽  
Epithelial Tumors ◽  
Tumor Dna ◽  
Thymic Carcinomas

8577 Background: Thymic epithelial tumors (TETs) are rare tumors originating from the epithelial cells of the thymus. Thymomas tend to be slowly growing, whereas thymic carcinomas are more aggressive and often metastasize wildly. TETs have a very low tumor mutational burden (TMB). cfDNA has been used in several tumor types to describe the molecular characteristics and select treatment options, especially in absence of tissue availability. There is no information on the cfDNA detected in TETs. The purpose of this study was to identify common genomic alterations occurring in circulating tumor DNA (ctDNA) in patients with advanced TETs, detected using a cfDNA assay. Methods: We retrospectively evaluated 157 TET samples from the Guardant Health database between November 2017 – November 2020. The cfDNA analysis interrogated single nucleotide variants (SNV), fusions, indels and copy number variations (CNV) of up to 83 genes using a commercially available liquid biopsy assay (Guardant360; Guardant Health, Redwood City, CA) . We evaluated the frequency of genomic alterations based on diagnosis, age, and sex. Results: In this cohort, 66% of the patients had thymic carcinoma and 34% had thymoma. The median age was 60 years, and 59% of patients were male. 126 patients (80%) of this cohort had ≥1 somatic alteration detected. The most prevalent mutations detected are TP53 (55%), KIT (13%), EGFR (12%), BRCA2 (11%), PIK3CA (10%), ARID1A (10%), ATM (10%), KRAS (9%), APC (9%), and BRAF (9%). Mutations were more commonly observed in thymic carcinomas than thymomas, but statistical significance was not reached due to the small sample size. Frequencies of the observed genomic alterations are shown in the table below. Conclusions: This study confirms that advanced stage TETs shed tumor DNA into the circulation that can be picked up in the majority of patients, using a solid tumor platform, despite the low TMB typically observed in these tumors. This assay can potentially be used to monitor response to therapy. A more targeted gene panel, enriched for genes commonly mutated in TETs (e.g. GTF2I, BAP1, CYLD) might provide further insights in the future in the management of TETs.[Table: see text]

Treatment of Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma (ALL/LL). Results of a Single Center.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4108-4108
Author(s):  
Josep Sarra ◽  
Esmeralda de la Banda ◽  
Encuentra Maite ◽  
Jose Petit ◽  
Eva Gonzalez-Barca ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Response To Therapy ◽  
Molecular Characteristics ◽  
Unrelated Donor ◽  
Induction Phase ◽  
Haematological Malignancies

Abstract Abstract 4108 Introduction ALL/LL is a heterogenous disease with various subtypes that differ markedly in their cellular and molecular characteristics. Chemotherapy regimens, response to therapy and risk of relapse also vary among different disease subtypes. Here we report the experience in our center in the management of this heterogeneous group of haematological malignancies. Objectives The objectives of the study are: - To determine the event free survival (EFS) in patients diagnosed with different subtypes of ALL/LL, including those who received an allogeneic stem cell transplantation. - To determine the overall survival (OS) for the patients diagnosed of ALL/LL and for those who received an allogeneic stem cell transplantation. Patients and Methods: Forty-two patients have been diagnosed of ALL/LL in our hospital from February'02 to April'09. 24 male (57%) and 18 female (43%), median age of 42,5 years (18-74), including sixteen cases of B-ALL (38%); 13 Ph+ ALL (31%); 6 T-ALL (14%) and 7 LL (17%). B and T-ALL were treated with the same chemotherapy regimen (Pethema: Spanish group for the treatment of haematological malignancies). Ph+ ALL were treated with chemotherapy and the addition of Imatinib (Pethema regimen) and Lymphoblastic Lymphomas (LL) were treated with HyperCVAD regimen. Elderly patients or those with significant comorbidities were treated with “adapted risk” chemotherapy regimens. Allogeneic stem cell transplantation, related or unrelated, was indicated in first complete remission (CR) for all cases of Ph+ ALL, and cases of B or T ALL who do not achieved CR with negative Minimal Residual Disease (MRD), or in second CR for cases with LL. Results Thirty-three patients (78%) achieved CR at the end of the first induction phase. Two patients (5%) died in this phase and 5 patients (14% of the evaluable patients) relapsed at any moment of the treatment scheduled for them. Fourteen patients (33%) received an allogeneic transplantation: 7 (50%) from an unrelated donor. Nine of this 14 patients (64%) were transplanted in 1st CR. At the moment of the study, 21 patients (50%) are alive. The EFS for the patients included in the study is 41% with a median follow-up of 10,47 months (1,1-78,1). The EFS for the different subtypes are: 57% for B-ALL; 23% for Ph+ ALL; 44% for T-ALL and 57% for LL. The EFS for the transplanted patients is 34% and for the non transplanted patients group is 49% The OS is 43% with a median follow up of 11,57 months (1,11-78,1). The OS for the transplanted patients is 40% and for the rest of the patients is 48% Conclusions Pethema chemotherapy regimens for B, T and Ph + ALL, achieve a good percentage of CR, according to other similar regimens of chemotherapy reported. However, toxicity and relapses are still elevated. The research of a related or unrelated HLA-identical donor must be done from the diagnosis, specially in those forms of recognized bad prognosis. Disclosures: No relevant conflicts of interest to declare.

BCR-ABLIS Expression at Diagnosis and After 3 or 6 Months of Treatment Predicts CML Response to IMATINIB Therapy.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3426-3426 ◽  
Author(s):  
Paolo Vigneri ◽  
Fabio Stagno ◽  
Stefania Stella ◽  
Alessandra Cupri ◽  
Michele Massimino ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Chronic Phase ◽  
Rapid Identification ◽  
Response To Therapy ◽  
Molecular Characteristics ◽  
Correlated Response ◽  
Molecular Responses ◽  
Transcript Levels ◽  
Optimal Response ◽  
Intention To Treat

Abstract Abstract 3426 Imatinib mesylate (IM) has shown remarkable efficacy for the treatment of Chronic Myeloid Leukemia (CML) patients (pts) in the chronic phase of the disease. However, while most individuals achieve an optimal response to conventional IM therapy, approximately 30% either fail IM or develop intolerance to the drug. Thus, there is a growing need for biological parameters predictive of IM response (at diagnosis or during the first months of therapy) in order to recognize pts with a more aggressive disease that should receive alternative treatments. We examined the outcomes of the first 193 CML pts accrued to the observational SCREEN (Sicily and Calabria CML REgional ENterprise) multicenter non-sponsored study, and analyzed the responses of this unselected population. Pts characteristics were as shown in Table 1. All subjects received IM 400 mg daily. Median follow-up was 26 months (range 3–60). Complete hematological (CHR), cytogenetic (CCyR) and major molecular responses (MMR) were rated according to the European Leukemia Net 2006 guidelines. Peripheral blood samples were used for BCR-ABL determination by quantitative real-time polymerase chain reaction according to the International standardized Scale (IS). To identify parameters predictive of IM response, pts were stratified according to clinical and molecular responses or BCR-ABL transcript levels at diagnosis and analyzed for their outcome on an intention to treat basis. At 12 months, cumulative incidences of CHRs, CCyRs and MMRs were 100%, 82% and 43%, respectively. At 24 months, incidences of CCyR and MMR increased to 87% and 67%. According to the ELN criteria, 121 pts (62%) achieved an optimal response; 36 pts (19%) had a suboptimal response; 32 pts (17%) failed IM because of either primary (20 pts) or secondary (12 pts) resistance. Only 4 pts (2%) were intolerant to IM. Kaplan-Meyer estimates for overall, progression-free, event-free and failure-free survival at 60 months were 99%, 96% 80% and 72%. When we clustered all subjects in optimal responders (ORs) and suboptimal/resistant (S/R) pts and correlated response to therapy with various molecular characteristics we found that the amount of BCR-ABLIS transcripts at diagnosis predicted response to IM. Indeed, the median amount of BCR-ABLIS at diagnosis displayed by patients that failed IM or achieved a suboptimal response was significantly higher (104.154IS) than that of patients obtaining an optimal response (53.478IS; p=0.000611). As WBC counts were not significantly different between ORs and S/R pts (p=0.2065), increased amounts of BCR-ABLIS transcripts were probably representative of the aggressiveness of the leukemic clone. We also observed that pts displaying >10% BCR-ABLIS after 3 or 6 months of IM had a significantly lower chance of achieving a CCyR compared to pts with BCR-ABLIS levels lower than 10% (p<0.001). IM is a highly effective and well-tolerated treatment for most chronic phase CML pts, producing high rates of CHR, CCyR and MMR. However, 35–40% of newly diagnosed CML pts will either fail IM or obtain a suboptimal response. High levels of BCR-ABLIS transcripts at diagnosis may allow the rapid identification of CML pts that are likely to fail IM or to achieve a suboptimal response. Furthermore, failing to achieve BCR-ABLIS transcript levels <10% after 3 or 6 months of IM treatment significantly reduces the probability of subsequently obtaining a CCyR. Table 1. Characterisitics of CML pts included in the SREEN study Age (median yrs) 54 (range 24–90) Sex (M/F) 108/85 WBC × 109/L (median) 64.8 (range 3.4–718.0) Hb (g/dL) 12.1 (range 7.5–17.0) PLT × 109/L (median) 330.0 (range 67.0–1690.0) Organomegaly % 58 Sokal risk stratification % 49 Low/36 Intermediate/15 High Ph+ % (diagnosis) 96 ACA % (diagnosis) 7 BCR-ABL transcript variants % 38 e13a2/53 e14a2/9 other BCR-ABLIS % (median at diagnosis) 58.641 Disclosures: No relevant conflicts of interest to declare.

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