Discrepancy of Blast Percentage between the Bone Marrow Aspirate and Flow Cytometry and Its Impact on Survival Outcomes in Patients with Myelodysplastic Syndromes Excess Blast (MDS-EB)

Background MDS is a heterogeneous disease and the revised International Prognostic Scoring System (IPSS-R) is utilized in prognostication. The percentage (%) of blasts in the bone marrow is determined in the aspirate morphologically. Though the former is the standard of care the blast percentage is also reported by flow cytometry and biopsy which can many times be inconsistent. We previously presented the utilization of biopsy based blast percentage which showed meaningful prognostic groups compared to aspirate. In this study we compare the blasts as reported by the aspirate and flow cytometry in MDS-EB in calculating IPSS-R. Methods The MDS database was reviewed for cases of MDS-EB after due IRB approval at the Mayo clinic. We calculated IPSS-R scores based on the aspirate blast % (IPSS-RAsp) and flow blast% (IPSS-Rfl). The aspirate blast percentage was reported morphologically. Suboptimal aspirates were excluded from the study. The flow blast percentage was determined by immunophenotyping. The overall survival (OS) was determined by IPSS-RAsp and IPSS-RFl. OS estimates were calculated by Kaplan-Meier curves and log-rank testing using JMP v.13. Uno's concordance statistic was used to compare the 2 risk scoring systems. Results Of 1322 patients, 431 (33%) cases were identified with MDS-EB out of which 120 (29%) cases had blasts reported in the aspirate and flow. Based on aspirate MDS EB1: 54% (n=65), MDS EB2 46% (n=55). The hematological, cytogenetic and R-IPSS categories were compared between MDS-EB1 and MDS- EB 2. The blast percentage and hemoglobin levels was significantly different between MDS-EB1 and EB2 as seen in table 1, however the IPSS-R risk groups were not significantly different. The flow cytometry was concordant with aspirate in 66/120 (55%) cases. Out of the dis-concordant cases only 20% (11/54) was upstaged by flow cytometry with most of the patients being down staged as expected by the techniques used in processing the blood and hence not reliable when reported low (Figure 1). The OS outcomes based on the IPSS- R asp, IPSS-Rfl areshown in figure 2A,2B .The p value with aspirate based R-IPSS was more significant than flow cytometry based R-IPSS (p= 0.0007 vs 0.0174). We compared the two models for observed OS differences using the Uno model which was not statistically significant. (p= 0.6) Conclusions Both models did not show a difference which is likely due to the very small sample size. However flow cytometry did down stage more patients when disconcordant and may have less value in that setting. It would be ideal to compare all 3 models aspirate, biopsy and flow cytometry however we did not have enough number of patients to do the comparison. Disclosures Patnaik: Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees. Al-Kali:Astex Pharmaceuticals, Inc.: Research Funding.

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Discrepancy of blast percentage between the bone marrow aspirate and biopsy and its impact on survival outcomes in patients with myelodysplastic syndromes excess blast (MDS-EB).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.7053 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 7053-7053

Author(s):

Meera Yogarajah ◽

Phuong L. Nguyen ◽

Rong He ◽

Hassan Alkhateeb ◽

Mithun Vinod Shah ◽

...

Keyword(s):

Bone Marrow ◽

Scoring System ◽

Small Sample Size ◽

Scoring Systems ◽

Standard Of Care ◽

Small Sample ◽

International Prognostic Scoring System ◽

Increased Risk ◽

Significant Difference ◽

Impact On Survival

7053 Background: The revised International Prognostic Scoring System (IPSS-R) aids in prognosticating MDS. The percentage (%) of blasts in the bone marrow is one of the major determinants of the scoring system. The aspirate blast % is utilized as the standard of care, but there could be discrepancies in the blast % reported by the aspirate and the biopsy. We aim to study the possible use of bone marrow biopsy blasts in MDS-EB in calculating IPSS-R. Methods: The MDS database was reviewed for cases of MDS-EB after due IRB approval. We calculated IPSS-R scores based on the aspirate blast % (IPSS-RAsp) and biopsy blast % (IPSS-RBx). The biopsy blast % was reported morphologically or by the CD34 stain. Whenever a range was reported the highest value was utilized as the blast %. Suboptimal aspirates were excluded from the study. The overall survival (OS) was determined by IPSS-RAsp, IPSS-RBx and IPSS-R highest blast (IPSS-RHi). OS estimates were calculated by Kaplan-Meier curves and log-rank testing using JMP v.13. Uno’s concordance statistic was used to compare all 3 risk scoring systems. Results: Of 1322 patients, 431 (33%) cases were identified with MDS-EB; out of which 173 cases had both blasts reported in the biopsy and the aspirate. Out of 173 cases, 35 (20%) had MDS-EB1, and 61 (35%) had MDS EB-2 based on both biopsy and aspirate (concordant cases). Seventy seven (45%) patients changed from EB-1 to EB2 or vice versa based on the biopsy blast (44/77 (57%) cases were upstaged). The OS outcomes based on the IPSS-RBx biopsy showed a clear and meaningful separation with median OS decreasing with increased risk but IPSS-RAsp and IPSS-RHi did not (Table). We compared the 3 models for observed OS differences using the Uno model and there was no statistically significant difference. Conclusions: IPSS-RBx (but not IPSS-RAsp and IPSS-RHi) identified prognostic groups for OS with median OS decreasing with increased risk. The small sample size may have led to an insignificant effect on model power by Uno model. This finding needs to be validated by other centers. [Table: see text]

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Prognostic Significance of BCL-2 Expression in Patients with Multiple Myeloma.

Blood ◽

10.1182/blood.v104.11.4840.4840 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4840-4840

Author(s):

Mehmood Hashmi ◽

Kiarash Kojouri ◽

Jian Yang ◽

Sunil Patel ◽

Mohammad Khan ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Overall Survival ◽

Median Survival ◽

Small Sample Size ◽

Prognostic Significance ◽

Chemotherapeutic Agents ◽

Small Sample ◽

Rank Test ◽

Number Of Patients

Abstract Background: multiple myeloma (MM) remains an incurable disease that accounts for approximately 10% of all hematologic cancers. Patients (pts) with MM treated with conventional chemotherapy have a median overall survival of 36–42 months. Various adverse prognostic factors have been described in MM, including elevated B2 microglobulin, hypoalbuminemia, cytogenetic abnormalities of chromosome 13 (13q14 del, monosomy 13), and elevated CRP among others. BCL-2 mediates anti-apoptotic pathways and its expression has been implicated with lack of response to certain chemotherapeutic agents and unfavorable prognosis in different human malignancies. Objective: to evaluate the prognostic significance of BCL-2 expression in patients with MM. Methods: adult pts who were diagnosed with MM at our institution since 1/1/90 were retrospectively analyzed. Expression of BCL-2 was determined by immunohistochemistry (IHC) staining of deparafinized bone marrow specimens. Median survival was calculated for BCL-2 (+) and BCL-2 (−) groups. Survival curves were estimated according to the Kaplan-Meier method, and were compared with the use of the log-rank test. Median survivals were also compared by using Wilcoxon-Mann-Whitney test. Two-tailed alpha level of 0.05 was considered statistically significant. SAS® software (Cary, NC) was used for statistical analysis. Results: sixty-six patients were initially identified. Forty-four pts were excluded because bone marrow samples were not available for IHC staining. Twenty-two pts (11 males, 11 females), with a median age at the time of diagnosis of 64 years (range: 46 to 83 years) were included for this analysis. Fourteen pts (64%) had positive BCL-2 bone marrow specimens, including 4 mild, 3 moderate, and 7 strong staining, while for 8 pts (36%), bone marrow specimens did not stain for BCL-2. Twelve pts (86%) from BCL-2 (+) group and 4 pts (50%) from BCL-2 (−) group died during the period of follow-up; 8 pts are still alive at the time of this analysis, 23 to 71 months (median: 39 months) after diagnosis. The median survival among BCL-2 (+) pts was 35 months (95% CI: 24 – 69 months) and among BCL-2 (−) pts was 47 months (95% CI: 13 months - N/A). Overall survival did not differ between the two groups (p-values for log-rank and Wilcoxon-Mann-Whitney tests, 0.8256 and 0.7072, respectively). Conclusion: although our study did not show correlation between BCL-2 expression and overall survival, median survival among BCL-2 (−) pts with MM was 34% longer than BCL-2 (+) pts. The authors recognize the limitations associated with this analysis including the retrospective nature of the study, small sample size, and exclusion of a large number of patients. This study highlights the need for prospective evaluation of the prognostic significance of BCL-2 expression among pts with MM.

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Abstract W P224: Higher Pre-Hospital Blood Pressure Prolongs Door to Needle Thrombolysis Times

Stroke ◽

10.1161/str.46.suppl_1.wp224 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Digvijaya Navalkele ◽

Chunyan Cai ◽

Mohammad Rahbar ◽

Renganayaki Pandurengan ◽

Tzu-Ching Wu ◽

...

Keyword(s):

Blood Pressure ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Small Sample Size ◽

Heart Association ◽

Small Sample ◽

Categorical Variables ◽

Continuous Variables ◽

Intravenous Tissue Plasminogen Activator ◽

Number Of Patients

Background: Per American Heart Association guidelines, blood pressure (BP) should be < 185/110 to be eligible for intravenous tissue plasminogen activator (tPA). It is shown that door to needle (DTN) time is prolonged in patients who require anti-hypertensive medications prior to thrombolysis in the emergency department (ED). To our knowledge, no studies have focused on pre-hospital BP and its impact on DTN times. We hypothesize that DTN times are longer for patients with higher pre-hospital BP. Methods: We conducted a retrospective review of acute ischemic stroke patients who presented between 1/2010 and 12/2010 to our ED through Emergency Medical Services (EMS) within 3-hrs of symptom onset. Patients were identified from our registry and categorized into two groups: Pre-hospital BP ≥ 185/110 (Pre-hsp HBP) and < 185/110 (Pre-hsp LBP). BP records were abstracted from EMS sheets. Two groups were compared using two-sample t-test or Wilcoxon rank sum test for continuous variables and Chi-square test or Fisher’s exact test for categorical variables. Results: A total of 107 consecutive patients were identified. Out of these, 75 patients (70%) were treated with tPA. Among the patients who received thrombolysis, 35% had pre-hospital BP ≥ 185/110 (n= 26/75). Greater number of patients required anti-hypertensive medications in ED in high BP group compared to low BP group (Pre-hsp HBP n= 14/26, 54%; Pre-hsp LBP n= 13/49, 27%, p < 0.02). Mean door to needle times were significantly higher in Pre-hsp HBP group. (mean ± SD 87.5± 34.2 Vs. 59.7±18.3, p<0.0001). Analysis of patients only within the Pre-hsp HBP group (n= 26) revealed that DTN times were shorter if patients received pre-hsp BP medications compared to patients in the same group who did not receive pre-hsp BP medication (n= 10 vs 16; mean ± SD 76.5 ± 25.7 Vs. 94.3 ± 37.7, p = 0.20) Conclusion: Higher pre-hospital BP is associated with prolonged DTN times and it stays prolonged if pre-hospital high BP remains untreated. Although the later finding was not statistical significant due to small sample size, pre-hospital blood pressure control could be a potential area for improvement to reduce door to needle times in acute ischemic stroke.

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The feasibility of same day pegfilgrastim-cbqv administration in breast cancer patients receiving myelosuppressive chemotherapy regimens at a northern Virginia cancer center.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18687 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18687-e18687

Author(s):

Maya Leiva ◽

Angela Pennisi ◽

Kathleen Kiernan Harnden ◽

Patricia Conrad Rizzo ◽

Lauren Ann Mauro

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Small Sample Size ◽

Standard Of Care ◽

Secondary Prophylaxis ◽

Small Sample ◽

Cancer Center ◽

Breast Cancer Patients ◽

Curative Intent ◽

Myelosuppressive Chemotherapy

e18687 Background: The long-acting injectable G-CSF, pegfilgrastim and its biosimilars have historically been given to patients 24 hours following the administration of myelosuppressive chemotherapy for either primary or secondary prophylaxis of febrile neutropenia (FN). Previous literature has indicated that pegfilgrastim administration prior to 24 hours post chemotherapy, may result in a deepened and prolonged neutropenia due to the increase in circulating granulocytes exposed to chemotherapy. With the onset of the COVID-19 pandemic and to reduce potential SAR-CoV-2 exposure to cancer patients on therapy, we implemented same day administration of injectable pegfilgrastim-cbqv among select breast cancer patients receiving myelosuppressive chemotherapy regimens from March 2020 – February 2021. Methods: Utilizing retrospective EHR chart reviews, 55 patients among 4 medical oncologists in our breast cancer group were identified as meeting the criteria of same day pegfilgrastim-cbqv administration. Inclusion was based on completion of at least 2 consecutive cycles of same day pegfilgrastim-cbqv 6 mg subcutaneous injection for primary or secondary prophylaxis. The selected patient charts were reviewed for the incidence and severity of FN. Among the patients who had documented FN, further subgroup analyses were done regarding baseline characteristics, timing of neutropenia, regimens, regimen sequence, and reported ADRs associated with pegfilgrastim-cbqv. Results: 9 (16.4%) of the 55 patients experienced FN (Grades 3-4) and 6 (10.9%) patients were hospitalized. There were no Grade 5 events and none had therapy discontinued due to FN. 8 (88.9%) of the patients experienced FN between cycles 1 and 2. Of note, there were no cases of COVID-19 among the 9 patients who had an episode of FN. 52 (94.5%) of the 55 patients received treatment with curative intent and 3 (5.5%) had metastatic disease on a subsequent line of therapy. The median age was 49.1 years (range 29-71) and patients were 56.4% Caucasian, 18.1% Black or African American, 12.7% Asian, and 12.7% Hispanic/Latina. Conclusions: Based on the retrospective data analysis, same day pegfilgrastim-cbqv appears to be a safe and effective option in the primary and secondary prophylaxis of FN with myelosuppressive standard of care chemotherapy used in breast cancer treatment. Though our review was limited by a relatively small sample size and confined to younger (49.1 median age) breast cancer patients, this opens the door to further re-evaluation of same day pegfilgrastim-cbqv administration in other patient populations. In a post pandemic treatment world, this slight change in practice has the potential to reduce patient financial toxicity associated with multiple medical visits, provide an alternative to on-body injector formulations, and ensure treatment adherence.

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Retrospective, observational study on usage of evogliptin in T2DM patients: A real-World experience in Indian patients

Indian Journal of Pharmacy and Pharmacology ◽

10.18231/j.ijpp.2021.035 ◽

2021 ◽

Vol 8 (3) ◽

pp. 205-207

Author(s):

Abhijit Trailokya ◽

Amol Aiwale ◽

Roshan Pawar ◽

Suhas Erande

Keyword(s):

Real World ◽

Small Sample Size ◽

Small Sample ◽

Hypoglycemic Agents ◽

P Value ◽

Base Line ◽

Oral Hypoglycemic Agents ◽

Naive Patient ◽

Indian Patients ◽

Treatment Naïve

This study aimed to assess effectiveness and safety of Evogliptin 5 mg in patients with T2DM who were prescribed Evogliptin alone or with other oral hypoglycemic agents in real world scenario. Overall 20 patients who received Evogliptin as routine clinical practice in management of T2DM were analyzed retrospectively from single center. Data collected from past medical records. Primary endpoint was mean changes in HbA1c from baseline to weeks 24 and secondary endpoints were Change in HbA1c from baseline to weeks 12 Change from baseline in FPG & PPG at weeks 12 & 24.Significant reduction in HbA1c at the end of 12 and 24 weeks of Evogliptin therapy was - 0.9% and -1.45% respectively from the baseline of HbA1c 8.6% (p value <0.001). At the end of 12 and 24 weeks of addition of Evogliptin, significant reduction in FBG were seen i.e -49.5 mg/dl and -90.7mg/dl respectively from base line of 182 mg/dl and reduction in PPG was -79.4mg/dl and -116.6mg/dl respectively from base line 277 mg/dl (p value <0.001). Evogliptin was found to be effective when added to the patients who were uncontrolled on dual / triple oral anti-diabetic medications and even in treatment naïve patient. It effectively showed reduction in HbA1c, FBG and PPG and the end of 12 and 24 weeks when added to existing anti-diabetic medications & well tolerated in type 2 diabetes Indian patients.Small sample size and retrospective study

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Hodgkin lymphoma arising in patients with chronic lymphocytic leukemia: outcomes from a large multi-center collaboration

Haematologica ◽

10.3324/haematol.2020.256388 ◽

2020 ◽

pp. 0-0

Author(s):

Deborah M. Stephens ◽

Ken Boucher ◽

Elizabeth Kander ◽

Sameer A. Parikh ◽

Erin M. Parry ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Hodgkin Lymphoma ◽

Hematopoietic Cell Transplantation ◽

Small Sample Size ◽

Case Series ◽

Standard Of Care ◽

Median Number ◽

Small Sample ◽

Lymphocytic Leukemia ◽

Treatment Type

Chronic lymphocytic leukemia (CLL) patients who develop Hodgkin lymphoma (HL) have limited survival. No current therapeutic standard of care exists. We conducted a multi-center retrospective study of patients with Hodgkin Transformation (HT) of CLL. Clinicobiologic characteristics, treatment type, and survival outcomes were analyzed and compared with historic case series. Ninety-four patients were identified. Median age at HT was 67 years (range, 38-85). Median time from CLL diagnosis to HT was 5.5 years (range, 0-20.2). Prior to HT, patients received a median of 2 therapies for CLL (range, 0-12). As initial therapy for HT, 61% (n=62) received ABVD-based regimens (adriamycin, bleomycin, vinblastine, and dacarbazine). Seven (7%) patients received hematopoietic cell transplantation (HCT) while in first complete remission (CR1). The median number of treatments for HT per patient was 1 (range, 0-5) with 59 (61%) patients only receiving one line of therapy. After HT, patients had a median follow-up of 1.6 years (range, 0-15.1). Two-year overall survival (OS) after HT diagnosis was 72% (95%CI 62-83%). The patients who received standard ABVD-based therapy had a median OS of 13.2 years. Although limited by small sample size, the patients who underwent HCT for HT in CR1 had a similar 2-year OS (n=7; 67%) compared to patients who did not undergo HCT for HT in CR1 (n=87; 72%; p=0.46). In this multi-center study, HT patients treated with ABVD-based regimens had prolonged survival supporting the use of these regimens as standard of care for these patients.

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Evaluation of the Intra-LABORATORY Reproducibility of Percentage of Blast Counting In MYELODYSPLASIA

Blood ◽

10.1182/blood.v118.21.4901.4901 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4901-4901

Author(s):

Soraya Wuilleme ◽

Marion Eveillard ◽

Sophie Barillet ◽

Françoise Accard ◽

Hervé Avet-Loiseau ◽

...

Keyword(s):

Bone Marrow ◽

Scoring System ◽

Who Classification ◽

Conflicts Of Interest ◽

Scoring Systems ◽

Poor Quality ◽

International Prognostic Scoring System ◽

Inter Observer Variability ◽

Morphological Criteria ◽

Blast Cells

Abstract Abstract 4901 In the two International Prognostic Scoring Systems of Myelodysplastic Syndrom (MDS), the percentage of BLAST cells in the Bone Marrow is the most important parameter implicated in score: either directly in the IPSS (International Prognostic Scoring System) (1) or indirectly in the WPSS (Who classification-based prognostic scoring system) (2). In these two systems, as in the recommendations of the WHO 2001 (3), the morphological criteria defining blasts cells compared to promyelocyte cells are not specified. In 2005, the IWGM-MDS (International Working Group on Morphology of myelodysplastic syndrome) (4-6) has established morphological criteria defining Blasts cells. Our objective in this study is to evaluate the reproducibility, among five observers of our laboratory, of the counting of the marrow blasts of 73 myelodysplasia. This study was conducted in several stages. 1st step was to test the implementation of the MDS-Foundation (www.mds-foundation.org/virtualmicroscopy) by 5 observers. The 2nd step was to perform correlation test of the selected cells from RAEB (selected and stained in our laboratory conditions), for the 5 observers. Finally Step 3 was to assess the correlation of blast percentage of 73 bone marrow smears from MDS patients, selected due to the presence of an excess of blast cells in the first reading on the bone aspiration. Our results show that the correlation on counting blasts is generally satisfactory (percentage agreement: Test 1 = 86% and test 2 = 94%), while the concordance on the counting blasts of bone marow smears of 73 MDS patients and concordance on the WHO classification seems less satisfactory (agreement 3/5 observers. = 95% but agreed to 4–5/5 observers = 64%). These results can be explained partly by the inter-observer variability and by the variability of some parameters specific to smear marrow (poor quality smears, the staining and/or poverty of smears). In conclusion, the evaluation of the blasts in the MDS must be achieved: (i) at least 500 cells counted (ii) by at least two different observers (iii) by a third observer in discordant case. Despite these recommendations, the assessment of the blasts in myelodysplasia is difficult to achieve in many cases. Disclosures: No relevant conflicts of interest to declare.

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Mutation Analysis in 200 Cases of Newly Diagnosed Myelodysplastic Syndrome By Next Generation Sequencing: Association with Established Prognostic Variables and IPSS-R

Blood ◽

10.1182/blood.v126.23.1703.1703 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1703-1703

Author(s):

Kankana Ghosh ◽

Parsa Hodjat ◽

Priyanka Priyanka ◽

Beenu Thakral ◽

Keyur P. Patel ◽

...

Keyword(s):

Bone Marrow ◽

Next Generation Sequencing ◽

Myelodysplastic Syndrome ◽

Mutation Analysis ◽

Conflicts Of Interest ◽

International Prognostic Scoring System ◽

P Value ◽

Newly Diagnosed ◽

Next Generation ◽

Generation Sequencing

Abstract INTRODUCTION Myelodysplastic syndrome (MDS) is known to have numerous genomic aberrations that predict response to treatment and overall survival. We aimed to assess various mutations in newly diagnosed MDS cases by next generation sequencing (NGS) and their association with various well-established clinicopathologic parameters and the Revised International Prognostic Scoring System (IPSS-R). MATERIALS AND METHODS We performed molecular studies on DNA extracted from bone marrow aspirate specimens in 200 newly diagnosed treatment naïve MDS patients presenting at a single institution from 08/2013 to 03/2015 as part of routine clinical work up in a CLIA certified molecular diagnostics laboratory. Cases met criteria for MDS per WHO 2008 criteria. The entire coding sequences of 28 genes (ABL1, ASXL1, BRAF, DNMT3A, EGFR, EZH2, FLT3, GATA1, GATA2, HRAS, IDH1, IDH2, IKZF2, JAK2, KIT, KRAS, MDM2, MLL, MPL, MYD88, NOTCH1, NPM1, NRAS, PTPN11, RUNX1, TET2, TP53, WT1) were sequenced using a NGS-based custom-designed assay using TruSeq chemistry on Illumina MiSeq platform. FLT3 internal tandem duplications (ITD) and codon 835/836 point mutation were detected by PCR followed by capillary electrophoresis. CEBPA mutation analysis was performed by PCR followed by Sanger sequencing on 186 patients. RESULTS Median age was 67 years. Patients included 139 males (69.5%) and 61 females (30.5%). Hematologic parameters are as follows [median (range)]: Hb 9.6 g/dL (5-16.7), platelets 75 K/μ L (5-652), WBC: 2.8 K/μ L (0.4-20.8), ANC 1.3 K/μ L (0.0 -12.0), AMC 0.2 K/μ L (0.0-3). Bone marrow (BM) blasts [median (range)] were 4% (0-19). Of 192 patients with cytogenetic analysis performed, 65 (33.85%) had diploid karyotype, 53 (27.6%) had one, 21 (10.93%) had two, 13 (6.77%) had three, 40 (20.83%) had > three abnormalities. IPSS-R risk categorization of the 200 cases is as follows: very low (17 cases, 8.5%), low (46, 23%) intermediate (42, 21%), high (47, 23.5%), very high (48, 24%). Mutations identified by NGS are as detailed in Table 1. Of the 4 patients with FLT mutations detected, the breakdown is as follows: FLT3 ITD (3, 75%), FLT3 D835 (1, 25%), FLT3, ITD + D835 (0, 0%). CEBPA mutation was detected in 12 of 186 (6.45%) cases assessed. CEBPA was detected in 12 (6.45%). Sixty three (31.5%) cases had no mutations detected in the genes analyzed by NGS or PCR, 80 (40%) had mutations in one, 42 (21%) had mutations in two, 8 (4%) in three and 7 (3.5%) in > three genes. We found positive associations between mutated genes and various parameters as detailed in Table 2. No association was found between frequency of any particular mutation and the IPSS-R score. CONCLUSIONS: MDS is a heterogeneous group of myeloid neoplasms at the genetic level. Multiple genetic mutations in a large subset of cases likely indicate clonal evolution. A subset of mutations has significant association with well-established clinico-pathologic parameters like WBC and BM blast percentage. With longer follow-up, we could use this data to refine IPSS-R. Table 1. Number of cases % cases TP53 46 23 TET2 33 16.5 RUNX1 27 13.5 ASXL1 25 12.5 DNMT3A 17 8.5 EZH2 12 6 IDH2 8 4 IDH1 7 3.5 NRAS 7 3.5 JAK2 5 2.5 FLT3 4 2 PTPN11 3 1.5 EGFR 2 1 MPL 2 1 WT1 2 1 GATA2 1 0.5 KIT 1 0.5 KRAS 1 0.5 MYD88 1 0.5 NPM1 1 0.5 BRAF 1 0.5 Table 2. Mutated genes p value WBC ASXL1 <0.042 AEC TET2 <0.016 BM blast % RUNX1, CEBPA <0.008, p<0.02 BM myelocyte % TP53, TET2, RUNX1, DNMT3A <0.014, <0.014, <0.015, <0.038 AEC: absolute eosinophil count, BM: bone marrow Disclosures No relevant conflicts of interest to declare.

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A study of atherosclerosis in patients after radiation for early breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.27_suppl.260 ◽

2011 ◽

Vol 29 (27_suppl) ◽

pp. 260-260

Author(s):

V. G. Kirtani ◽

M. Chang ◽

A. M. Dobrescu ◽

S. Zeldis ◽

J. A. Haas ◽

...

Keyword(s):

Breast Cancer ◽

Coronary Arteries ◽

Background Radiation ◽

Small Sample Size ◽

Screening Method ◽

Calcium Score ◽

Small Sample ◽

Left Hemithorax ◽

Asymptomatic Patients ◽

Number Of Patients

260 Background: Radiation therapy (RT) is widely used as part of curative treatment of breast cancer. However, older studies have shown increased cardiac morbidity and mortality from breast RT. A screening method is needed to detect early cardiac damage in this population. Recent data have shown that Electron beam computed tomography (EBCT) can detect early atherosclerosis in coronary arteries by identifying the amount of calcification in the coronaries. In our study we employed this tool to detect occult atherosclerosis caused by breast RT. Methods: We evaluated 20 asymptomatic patients, less than 60 years of age, treated with RT at least 5 years prior to enrollment. Nine received RT to the left and 11 to the right hemithorax. Average interval between RT and CT was 7.7 years (5-14). All patients were treated with external beam RT using tangential technique. The breast was treated to a dose of 4500-5040 cGy and the tumor bed was boosted to a total dose of 6000-6600 cGy. All patients underwent EBCT to compute the volumetric and agatston calcium scores in the coronary arteries and the aorta. Results: Of the 11 patients who had RT to right hemithorax, 8 had calcium score of 0, 2 had very minimally elevated scores and 1 had significantly elevated score (patient 19, interval -14 years). Of the 9 patients who had RT to left hemithorax, 7 had calcium score of 0. None had significantly elevated scores. In the aorta, 11 patients had score of 0 and 8 had minimally elevated scores. Conclusions: Occult atherosclerosis was not detected using EBCT calcium scores in coronaries and aorta in a significant number of patients treated with RT for breast cancer. However, the study is limited by a small sample size. [Table: see text]

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Role of an extended pathology exam in risk classification of testicular germ cell tumors (GCTs).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e15032 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e15032-e15032

Author(s):

Mihai Vasile Marinca ◽

Irina Draga Caruntu ◽

Ludmila Liliac ◽

Simona Eliza Giusca ◽

Andreea Marinca ◽

...

Keyword(s):

Sample Size ◽

Small Sample Size ◽

Germ Cell Tumors ◽

Disease Free Survival ◽

Developed Countries ◽

Small Sample ◽

P Value ◽

Testicular Germ Cell ◽

Therapeutic Decisions ◽

The Impact

e15032 Background: The 1997 IGCCCG Consensus classification provides clinicians with enough information to efficiently choose between treatment options for most GCT patients. Nevertheless, therapy is ineffective in 5-10% of cases (even more in less developed countries), and about the same numbers experience severe side effects. This exploratory study aims to assess the impact of more rigorous and detailed pathology examination on improving the assignation of these patients to prognostic groups and, consequently, making optimal therapeutic decisions. Methods: Predefined features were reviewed on histology slides from 39 GCT patients followed-up for a median of 48.28 months. We designed a uniform pathology protocol, focused on identifying potential new prognostic factors. Categorical and continuous variables were quantified using light microscopy and computer-aided morphometry and, due to the small sample size, their statistical correlation was analyzed by exact tests and Spearman’s rho, respectively. Significant (2-sided p-value <0.05, under sample size reserve) coefficient values were entered in hierarchical cluster analysis (HCA). Results: Favorable IGCCCG group, presence of seminoma, glandular tissue pattern, presence and histoarchitecture of lymphocytic infiltrate associated better survival rates and lower risk of progression. Invasion of the epididymis and spermatic cord, presence of teratoma, choriocarcinoma and yolk-sac elements, papillary pattern and cell pleomorphism predicted poorer outcomes. HCA yielded 2 significantly distinct patient groups in terms of overall survival (p=0.018) and time to progression (p=0.080), but not disease-free survival (p=0.614). Conclusions: Quantification of tumor subtypes and other histology features of GCTs (e.g. necrosis, tissue patterns, inflammation) is feasible and, if standardized, may prove useful in optimal selection of risk groups, when performed by an experienced pathologist.

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