scholarly journals P53 and CD34 Immunohistochemical Expression on Bone Marrow Biopsy As Predictive Marker of Response to Erythropoietin in Low Risk Myelodysplastic Syndrome

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5511-5511
Author(s):  
Gianluigi Reda ◽  
Francesca Boggio ◽  
Ramona Cassin ◽  
Marta Riva ◽  
Marco Barella ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Treatment Response ◽  
Bone Marrow Biopsy ◽  
Univariate Analysis ◽  
Low Risk ◽  
P Value ◽  
P53 Expression ◽  
Loss Of Response

Abstract Introduction: Erythropoietin stimulating agents (ESAs) are first-line therapy for International Prognostic Scoring System (IPSS)-low risk myelodysplastic syndrome (MDS) when symptomatic anaemia (Hb <10 g/dl) is associated with serum erythropoietin (EPO) <500 mU/mL. Treatment response rate, according to international working group (IWG) response criteria (1- 5), ranges from 40 to 60%. Attempts have been made to build prognostic scores (integrating transfusion need, erythropoietin level, R-IPSS and ferritin) able to predict response to ESAs (6-7). No data concerning the predictive value of morphological and immunohistochemical analysis on bone marrow biopsy in low risk MDS patients are emerged till now. Methods: We retrospectively examined 96 IPSS low/int-1 MDS patients treated with ESAs in order to evaluate the morphological and immunohistochemical features of the bone marrow biopsies performed at baseline. All the patients had hemoglobin (Hb) ≤10 g/dL and serum EPO <500 mU/mL and received EPO alfa or β 40 000-80 000 IU/week for at least 12 weeks. Response to ESAs treatment was evaluated according to IWG 2006 criteria. A detailed analysis of the morphological features (including quantitative and qualitative changes in the erythroid, myeloid and megakariopoyetic lineages) was performed, together with an immunohistochemical evaluation of p53 expression and CD34-positive blasts percentage. Results: Sixty-eight percent of the patients were classified as responder while 32% as non-responder. The morphologic profiles of the responder and non-responder did not differ significantly. A significant correlation was found between the response to the therapy and a percentage of CD34-positive blasts > 3% (univariate analysis: p= .0211). Moreover p53 expression in less than 1% of the nucleated cells correlated with the treatment response (univariate analysis: p = .0086). These results were also confirmed on multivariate analysis (p= .002). Fifty-eight percent of patients maintained response to ESAs for the entire duration of the follow up while 42% lost the response (median follow up: 35 months). More than 3% CD34-positive blasts was associated with a higher probability to lose the response to ESAs (p = .00003). Kaplan-Meier method was than applied to estimate the response duration. Patients with more than 3% CD34-positive blasts showed earlier loss of response in comparison with those with a lower percentage of blasts (p value= .0003; HR=3.9, IC 95% 1.8154-8.6238). Finally, the expression of p53 in more than ≥ 1% of the nucleated cells correlated with the loss of response before 24 mounts (p value= 0.029). Conclusions: Our study identifies 2 well-known parameters that could be useful to better predict outcome of ESAs therapy in low risk MDS patients. Therefore role of bone marrow biopsy together with its diagnostic contribution in the clinical evaluation of MDS patients (cellularity, morphologic dysplasia, percentage of CD34-positive blasts, grading of bone marrow fibrosis) could be helpful as a predictive tool in ESAs candidate patients. Further studies based on larger series of patients are needed to confirm these preliminary results. Disclosures Reda: Gilead: Consultancy; ABBVIE: Consultancy; Janssen and Cilag: Consultancy; Celgene: Consultancy. Riva:Jannsen and Cilag: Consultancy; Novartis: Consultancy; Celgene: Consultancy. Molteni:Janssen and Cilag: Consultancy; Novartis: Consultancy; Italfarmaco: Consultancy; Celgene: Consultancy; AMGEN: Consultancy. Cortelezzi:abbvie: Consultancy; novartis: Consultancy; roche: Consultancy; janssen: Consultancy.

Blood Flow Cytometry Allows Us To Dispense with Bone Marrow Biopsy in the Evaluation of Treatment Response in CLL.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4769-4769
Author(s):  
Karim Maloum ◽  
Frederic Charlotte ◽  
Marine Divine ◽  
Bruno Cazin ◽  
Stephane Lepretre ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Blood Flow ◽  
Complete Remission ◽  
Treatment Response ◽  
Bone Marrow Biopsy ◽  
Predictive Value ◽  
Response Evaluation ◽  
Sensitivity Specificity

Abstract Aims: To evaluate the diagnostic value of bone marrow biopsy (BMB) with immunohistochemistry studies compared to blood flow cytometry (FC) in response evaluation after treatment in CLL. Patients and methods: 75 previously untreated patients with stage B and C-CLL were treated with oral Fludarabine (30mg/m2/d) + Cyclophosphamide (200mg/m2/d) combination, day 1 through 5, repeated every 28 days for 6 courses. Response evaluation was performed 2 months after the completion of therapy, according to NCI criteria. Sixty patients out of 75 achieved partial or complete remission and underwent BMB. Minimal residual disease (MRD) was simultaneously evaluated on paraffin-embedded BMB by anti-CD5, -CD20 and -CD3 immunostaining and in the peripheral blood using a very high sensitive FC method (Maloum et al, Br J Haematol, 2002, 119:970–5). BMB immunostaining was considered positive for MRD in case of concurrent expression of CD20 and CD5 by the same cells assessed on consecutive sections. Twenty nine patients could have been analyzed so far. The median follow-up was of 49 months [range 19–56]. Results: In all these 29 patients, BMB was considered histologically normal according to the NCI criteria. In 23/29 cases, bone marrow immunostaining did not show expressing CD20 cells. Fifteen out of 23 were in phenotypic remission using blood FC (PhR), of whom only 2 relapsed (at 31 and 37 months). The remaining 8/23 patients did not achieve PhR and all relapsed (at 22, 27, 37, 40, 45 and 51 months). In 6/29 patients, immunochemistry on BMB showed persistent B CD5+ cells : 3 did not achieve PhR of whom 2 relapsed (at 32 and 37 months) while 3 were in complete PhR and displayed a persistent clinical complete remission with a follow-up of 39, 47 and 47 months respectively. Interestingly, in the latter 3 cases, FC analysis showed an expansion of polyclonal BCD5+ cells in blood as assessed, which could explain the presence of such normal BCD5+ cells in the bone marrow. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy (ACC) to predict relapse for BMB and FC are given in the following table: Sensitivity (%) Specificity (%) PPV (%) NPV (%) ACC (%) BMB 16.7 76.5 33.3 56.3 51.7 FC 83.3 94.1 90.9 88.9 89.7 Conclusion: These results strongly suggest that BMB should not be indicated in the evaluation of treatment response and is not useful for relapse prediction. In contrast, blood flow cytometry constitutes the best method in routine laboratory to predict clinical outcome and should be included in response treatment criteria in CLL.

scholarly journals A Clinical Review of the Co-Occurrence of Myeloproliferative and Lymphoproliferative Neoplasms

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4285-4285
Author(s):  
Spencer Krichevsky ◽  
Erica B Bhavsar ◽  
Richard R. Furman ◽  
Ruben Niesvizky ◽  
Ellen K. Ritchie ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Polycythemia Vera ◽  
Bone Marrow Biopsy ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Low Risk ◽  
Diagnostic Code ◽  
Intermediate Risk ◽  
Early Stage Disease

Abstract The co-occurrence of myeloproliferative (MPN) and lymphoproliferative neoplasms (LPN) is rare and many publications have been limited to small case reports. Others have involved a considerable number of patients, but the coexistence remains underreported and inadequately studied. A recent retrospective review reported that a MPN patients have a 2.8-fold higher relative risk of developing LPN. A database developed at Weill Cornell Medicine (WCM) was queried for patients with ≥3 visits between 1998-2018 with a diagnostic code for a MPN and lymphoma or myeloma subtype. Patients identified were verified to ensure that study inclusion criteria were satisfied. Observed co-occurrence was compared to nation-wide reported prevalence. Demographic and clinical details of 24 patients with a MPN and LPN were recorded (Table 1). The ratio of males to females was 1.7. Essential thrombocythemia and polycythemia vera, and chronic lymphocytic leukemia (CLL) were the leading MPN and LPN subtypes, respectively. Patients were assigned to risk or staging categories at diagnosis based on subtype-specific criteria (Table 2). Median values for diagnostic bone marrow biopsy findings in 14 patients were 2% [0-5] for myeloblasts and 80% [15-100] for cellularity. Additionally, 10 patients had evaluated reticulin fibrosis: 5 (50.0%) presented as MF-0, 4 (40.0%) as MF-1, and 1 (10.0%) as MF-2. Progression to myelofibrosis was confirmed by morphology in 1 (4.2%) patient 10.1 years after a polycythemia vera diagnosis and 5.4 years after a diffuse large B-cell lymphoma (DLBCL) diagnosis. Progression to acute myeloid leukemia was confirmed by morphology in 1 (4.2%) patient 2.4 years after a chronic myelomonocytic leukemia diagnosis and 1.2 years after a smoldering myeloma (SM) diagnosis. Interphase fluorescence in situ hybridization (iFISH) detected cytogenetic abnormalities in 5/8 (62.5%) CLL patients: 2/5 (40.0%) and 5/5 (100.0%) patients harbored deletions in trisomy 12 and 13q14, respectively. Immunoglobulin heavy chain variable region gene (IGVH) status was unmutated in 2 (25.0%) patients. One (12.5%) patient was CD38+ and 2/6 (33.0%) patients were ZAP-70+. At diagnosis, all 8 patients presented with early stage disease (Rai stage 0-II). Based on the CLL-specific international prognostic index (IPI), 3/8 (37.5%) and 5/8 (62.5%) presented as low-risk and intermediate-risk, respectively. Of the 6 lymphoma patients: 5 (83.0%) patients presented with Ann Arbor stage-IV disease at diagnosis. Four (66.7%) patients presented as low/intermediate-risk, and 2 (33.3%) presented as high-risk based on disease-specific IPIs. One patient presented with -17p by iFISH. All 4 patients that were evaluated for Ki-67 had moderate/high expression. Of the 7 multiple myeloma (MM) patients, 6 (85.7%) presented as stage 1 and 1 (14.3%) as stage 3. Of the 3 SM patients, all 3 presented as low risk [12]. In addition, these patients were categorized as IgG-K (4; 40.0%), IgG-L (2; 20.0%), IgA-K (1; 10.0%), IgA-L (1; 10.0%), IgM (1; 10.0%), and biclonal IgG-L/IgA-L (1; 10.0%) [13]. Mutation statuses were identified by commercially tested myeloid or lymphoid molecular panels. As expected in this MPN subtype distribution, 11 (45.8%) are JAK2+, 2 (8.3%) are MPL+, 1 (4.2%) is BCR-ABL+, and 1 (4.2%) is CALR+ (Table 3). The risk of a co-occurrent MPN and LPN is higher than expected if they are mutually exclusive (Table 4A-4B, 5). Of interest, 13 (54.2%) patients were diagnosed with a MPN 11.8±18.8 years prior to a LPN; conversely, 11 (45.9%) were diagnosed with a LPN 6.5±6.2 years prior to a MPN. In addition, MPN therapy was started 2.0±2.3 years after a MPN diagnosis, and LPN therapy was started 2.6±4.0 years after a LPN diagnosis. A review of survival analysis requires larger subtype populations since the degree of survival can vary greatly, but it has been reported that patients with a MPN or LPN have significantly reduced life expectancy when compared to the general population. Median follow-up for our patient is 8.2 years (1.5-28.0) with 17/24 (70.8%) patients still being actively followed at our institution, 6 (25.0%) are been lost to follow-up, and 1 (4.2%) is deceased. The significant prevalence of these hematologic malignancies in combination emphasizes the importance of performing a bone marrow biopsy, which we espouse at our institution, cytogenetic analysis, and myeloid and lymphoid molecular testing to identify mutations. Disclosures Furman: Loxo Oncology: Consultancy; Gilead: Consultancy; Verastem: Consultancy; Acerta: Consultancy, Research Funding; TG Therapeutics: Consultancy; Incyte: Consultancy, Other: DSMB; Pharmacyclics LLC, an AbbVie Company: Consultancy; Genentech: Consultancy; Sunesis: Consultancy; Janssen: Consultancy; AbbVie: Consultancy. Niesvizky:Amgen Inc.: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Ritchie:Bristol-Myers Squibb: Research Funding; Novartis: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Astellas Pharma: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau; Pfizer: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; ARIAD Pharmaceuticals: Speakers Bureau.

Disease Characteristics and Prognosis of Myelodysplastic Syndrome Presenting with Isolated Thrombocytopenia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3477-3477 ◽  
Author(s):  
Julie B Waisbren ◽  
Shira N. Dinner ◽  
Irene Helenowski ◽  
Juehua Gao ◽  
Brandon McMahon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Bone Marrow Biopsy ◽  
Major Bleeding ◽  
Low Risk ◽  
Hypomethylating Agents ◽  
Bleeding Events ◽  
Major Bleeding Events ◽  
Very High

Abstract Background Myelodysplastic syndrome (MDS) presenting with isolated thrombocytopenia (TCP) represents a rare subset of this heterogenous malignancy. Prior small studies have suggested an indolent course. However, because this presentation is uncommon, there are clinical challenges in diagnosis and management. The aim of this study is to better define the morphologic, cytogenetic, and prognostic features of MDS presenting with isolated TCP. Methods Using the Northwestern University Electronic Data Warehouse, MDS patients were selected between 2004 and 2014 using ICD-9 codes and billing data. The diagnosis of MDS was determined by a practicing hematologist/oncologist according to World Health Organization criteria and confirmed with bone marrow biopsy results. Inclusion criteria were patients with isolated thrombocytopenia as defined by (PLT) <100×109/L, absolute neutrophil count (ANC) > 1.5×109/L and hemoglobin (Hgb) > 10 g/dl. Those with rapidly progressive TCP, confounding bone marrow disorders or those with suspected secondary causes of cytopenia were excluded. Data obtained from patient charts included demographics, peripheral blood counts, bone marrow biopsy results, bleeding complications, treatment history, and disease progression. IPSS-R scores were calculated on all patients. Overall survival rate and acute myeloid leukemia (AML) free event rates were determined via the Kaplan Meier method and compared between risk groups using the log-rank test. A P-value < 0.05 was considered statistically significant. Results Baseline characteristics: Of 404 MDS patients, 50 (12%) presented with isolated TCP. Among these 50, the median age was 72 and 34 were men (68%). Fourteen patients had TCP for greater than 2 years before diagnosis. Idiopathic thrombocytopenic purpura (ITP) was the presumed diagnosis in 17 patients. Median cell counts at the time of diagnosis were hemoglobin 12.0 g/dl, WBC 4.4 x 109/L and PLT 64 x 109/L. The most common cytogenetic profile was normal (n=28), and del 20q was the most common mutation seen in isolation (n=4) or in combination (n=3). Seven patients had complex cytogenetic profiles. Twenty-four patients fell into IPSS-R low or very low risk categories, 18 patients were IPSS-R intermediate (Int) risk and 7 patients were IPSS-R high or very high risk. Treatment + outcomes: Ten patients developed AML, 3 with low risk disease, 4 with Int-risk disease, 4 with high or very high-risk disease and 1 with an unknown IPSS-R score. Twenty-three patients were treated with hypomethylating agents including 5-Azacitidine or Decitabine. Three patients received thrombopoietin (TPO) receptor agonists. It is unclear by retrospective chart analysis if treatment resulted in improved outcomes. Fourteen of the 50 MDS patients presenting with isolated TCP died. Causes of death included AML (n=6), sepsis (n=4), intracranial bleeding (n=1), and unknown (n=1). Nine of the 14 patients who died were treated with hypomethylating agents, TPO agonists or both. There were 2 cases of major bleeding events, each intracranial and each in patients with PLT counts over 50. Discussion In our tertiary care center, the prevalence of isolated TCP in MDS was 12%. Patients with isolated TCP and MDS had similar demographics compared to patients with MDS at large. There were 17 patients (34%) that were first diagnosed with ITP. Need for bone marrow biopsy in asymptomatic patients with isolated TCP and normal peripheral smears is not clearly defined, however may be indicated in patients with demographics more typical of MDS (older male). The patients in this study distributed across all IPSS-R categories and many had an aggressive course. This is in contrary to previous studies that have suggested that MDS with isolated TCP has a relatively favorable prognosis. Next generation sequencing may uncover additional mutations in these patients that would help with risk stratification and development of targeted therapies. For example RUNX1 mutation carriers have been shown to present with thrombocytopenia and an increased risk of MDS/AML, and GATA2 mutants present with rapid onset MDS and often have a poor prognosis. Despite varying degrees of thrombocytopenia, incidence of major bleeding events was low. Treatment remains uncertain in this unique MDS subgroup. More studies are needed to address treatment options, including safety and efficacy of TPO agonists for this patient population. Disclosures Stein: Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees.

CLINICO-PATHOLOGICAL AND RADIOLOGICAL PROGNOSTIC FACTORS IN CANCER CERVIX TREATED WITH CONCURRENT CHEMORADIATION

2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Manraj S. Kang ◽  
Kamal Sahni ◽  
Piyush Kumar ◽  
Rajneesh Madhok ◽  
Ratna Saxena ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Mitotic Index ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Concurrent Chemoradiation ◽  
P Value ◽  
Publication Date ◽  
Cancer Cervix ◽  
Stage Ib

<bold>Introduction:</bold> Cervical cancer is most common cancer in the rural and second most common in urban areas of our country. It accounts for 16% of all cancers. There are various clinical, Paper Submission Datepathological and radiological factors which dictate the prognosis of these cancer cervix patients. The present study evaluates clinical, pathological and radiological prognostic factors in cancer cervix treated with concurrent chemoradiation. <bold>Material and Methods:</bold> A total of 32 patients seen between 2012 and 2014 patients planned concurrent chemoradiation were evaluated in terms of clinical (age, stage, Hb% and HPV Paper Publication Date infection), pathological (histopathology type and subtype, grade, mitotic index, lymph-July 2016 vascular invasion and necrosis) and radiological (parametrial extension, disease dimension, lymph node, hydronephrosis and vascularity of tumour) prognostic factors. After pre-DOI treatment evaluation patient was planned for 3 Dimentional-Conformal Radiotherapy (50Gy/25#/5 weeks) with concurrent chemotherapy (Cisplatin 35mg/m<sup>2</sup>) followed by 3 applications of Intracavitary radiotherapy (6Gy/fraction) with 6 months follow up. Response was accessed according to WHO response criteria and univariate analysis was done using chi-square test. <bold>Results:</bold> Clinical factors: Age – better disease free survival in older patients (p value=0.003), stage - Lower stage had better survival (for stage Ib-IIa vs stage IIb p value = 0.003 and for stage Ib vs. IIIb p value = 0.0005), Hb% - 57% patients with Hb <10g/dl had recurrence at end of 6 months (p value=0.00001), HPV – High recurrence with HPV presence. Pathological factors like high Mitotic Index had more residual disease (p=0.0009), grade - No statistical significance. Radiological factors- volume of disease - 35 % patients with volume of disease > 6 cm had disease at end of 6 months, hydronephrosis - 40 % patient with hydronephrosis had recurrence (p value = 0.0005) at end of 6 months follow up and vascularity of tumour showed statistically no difference. <bold>Conclusion:</bold> Hb <10%, HPV infection, Mitotic index (3-5/HPF), stage IIIB, pelvic nodes were concluded as the independent poor prognostic factors.

Reduced expression of FLIPSHORT in bone marrow of low risk myelodysplastic syndrome

2007 ◽  
Vol 31 (6) ◽  
pp. 853-857 ◽  
Author(s):  
Paula de Melo Campos ◽  
Fabíola Traina ◽  
Adriana da Silva Santos Duarte ◽  
Irene Lorand-Metze ◽  
Fernando F. Costa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Low Risk

scholarly journals Mutational Characteristics and Changing Pattern from Idiopathic Cytopenia of Undetermined Significance to High-Risk Myelodysplastic Syndrome Stratified By IPSS-R

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3009-3009
Author(s):  
Eun-Ji Choi ◽  
Young-Uk Cho ◽  
Seongsoo Jang ◽  
Chan-jeoung Park ◽  
Han-Seung Park ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Rna Splicing ◽  
Conflicts Of Interest ◽  
Low Risk ◽  
International Prognostic Scoring System ◽  
Intermediate Risk ◽  
Sequencing Data ◽  
Undetermined Significance

Background: Unexplained cytopenia comprises a spectrum of hematological diseases from idiopathic cytopenia of undetermined significance (ICUS) to myelodysplastic syndrome (MDS). Revised International Prognostic Scoring System (IPSS-R) is the standard tool to assess risk in MDS. Here, we investigated the occurrence, characteristics, and changing pattern of mutations in patients with ICUS and MDS stratified by IPSS-R score. Methods: A total of 211 patients were enrolled: 73 with ICUS and 138 with MDS. We analyzed the sequencing data of a targeted gene panel assay covering 141 genes using the MiSeqDx platform (Illumina). The lower limit of variant allele frequency (VAF) was set to 2.0% of mutant allele reads. Bone marrow components were assessed for the revised diagnosis according to the 2016 WHO classification. Lower-risk (LR) MDS was defined as those cases with very low- or low-risk MDS according to the IPSS-R. Higher-risk (HR) MDS was defined as those cases with high- or very high-risk MDS according to the IPSS-R. Results: Patients with ICUS were classified as very low-risk (39.7%), low-risk (54.8%), and intermediate-risk (5.5%) according to the IPSS-R. Patients with MDS were classified as LR (35.5%), intermediate-risk (30.4%), and HR (34.1%). In the ICUS, 28 (38.4%) patients carried at least one mutation in the recurrently mutated genes in MDS (MDS mutation). The most commonly mutated genes were DNMT3A (11.0%), followed by TET2 (9.6%), BCOR (4.1%), and U2AF1, SRSF2, IDH1 and ETV6 (2.7% for each). IPSS-R classification was not associated with mutational VAF and the number of mutations in ICUS. In the 49 LR MDS, 28 (57.1%) patients carried at least one MDS mutation. The most commonly mutated genes were SF3B1 (20.4%), followed by TET2 (12.2%), U2AF1 (10.2%), DNMT3A (10.2%), ASXL1 (10.2%), and BCOR (6.1%). Higher VAF and number of mutations were observed in LR MDS compared to ICUS patients. In the 42 intermediate-risk MDS, 27 (64.3%) patients carried at least one MDS mutation. The most commonly mutated genes were ASXL1 (23.8%), followed by TET2 (21.4%), RUNX1 (16.7%), U2AF1 (14.3%), DNMT3A (14.3%), SF3B1 (9.5%), and SRSF2, BCOR, STAG2 and CBL (7.1% for each). In the 47 HR MDS, 36 (76.6%) patients carried at least one MDS mutation. The most commonly mutated genes were TET2 (25.5%), followed by DNMT3A (14.9%), TP53 (14.9%), RUNX1 (12.8%), U2AF1 (10.6%), ASXL1 (10.6%), and SRSF2 and KRAS (6.4% for each). As the disease progressed, VAF and number of the MDS mutations gradually increased, and mutations involving RNA splicing, histone modification, transcription factor or p53 pathway had a trend for increasing frequency. Specifically, ASXL1, TP53, and RUNX1 mutations were the most striking features in patients with advanced stage of the disease. Cohesin mutations were not detected in ICUS, whereas these mutations were detected at a relatively high frequency in HR MDS. Our data were summarized in Table 1. Conclusions: We demonstrate that on disease progression, MDS mutations are increased in number as well as are expanded in size. Furthermore, a subset of mutations tends to be enriched for intermediate- to HR MDS. The results of this study can aid both diagnostic and prognostic stratification in patients with unexpected cytopenia. In particular, characterization of MDS mutations can be useful in refining bone marrow diagnosis in challenging situations such as distinguishing LR MDS from ICUS. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Platelet Millionaire: A Rare Cause of Thrombocytosis in an Adolescent

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5391-5391
Author(s):  
Ritika Walia ◽  
Theresa Sepulveda ◽  
Sharon Wretzel ◽  
Philip H Brandt
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Primary Care Physicians ◽  
Conflicts Of Interest ◽  
Abdominal Ultrasound ◽  
Cell Transplant ◽  
Peripheral Smear ◽  
Hematopoietic Stem ◽  
Marrow Fibrosis

Objectives: Primary myelofibrosis is rare in pediatrics, often manifesting as persistent idiopathic thrombocytosis.Transitions from pediatric to adult medical care can be complicated by workup requiring invasive procedures. J.M., an 18-year-old healthy male, presented for excessive gingival bleeding after wisdom tooth extraction. Workup revealed persistent thrombocytosis to 1,165K, prompting a referral to hematology-oncology. A peripheral smear was notable for many platelets but normal RBC morphology. He had splenomegaly on abdominal ultrasound and a decreased von-Willebrand's activity to antigen ratio, suggesting acquired vWD. A bone marrow biopsy was advised; however, J.M. became lost to follow up for over 9 months owing to self-reported anxiety about the procedure. He remained asymptomatic in this interim until he re-presented to clinic for easy bruising, with no other evidence of bleeding at the time. The biopsy was pursued, revealing hypercellular marrow for age with left shifted granulocytic and erythroid maturation, abnormal megakaryocytes, and 3% blasts. This was consistent with primary early myelofibrosis (PMF), positive for MF-1, CALR, and TP53 mutations and negative for JAK2 and BCR-ABL. He was transitioned to adult hematology, maintained on baby aspirin, and referred for potential allogeneic hematopoietic stem cell transplant (HSCT). PMF is characterized by marrow fibrosis due to secretion of fibroblast growth factor by clonally proliferative megakaryocytes. It is a disease of adulthood, with 67 years being the median age at diagnosis. Only 100 cases have been reported in children, most of which are secondary to AML, ALL or other malignancies.1 Most patients present with complications of extramedullary hematopoiesis or bleeding.2 Diagnosis is suggested by a leukoerythroblastic picture on peripheral smear and confirmed with a bone marrow biopsy "dry tap" revealing marrow fibrosis.3 Prognosis in pediatric PMF is difficult to predict but outcomes tend to be worse;4 TP53 mutation is rare and based on limited adult studies may portend a poorer prognosis.5 Our young patient with this rare mutation was therefore referred for HSCT evaluation. Further complicating this case was J.M.'s anxiety, which delayed definitive diagnosis by biopsy. He only agreed to it when, at the med-peds clinic, the concept of local pain management was discussed. Anticipation of upcoming procedures by primary care physicians and close follow-up is especially important for patients transitioning from pediatric to adult providers. Disclosures No relevant conflicts of interest to declare.

Indolent Neuroendocrine Tumor Involving the Bone Marrow

2003 ◽  
Vol 127 (4) ◽  
pp. 488-491
Author(s):  
Ellen Schlette ◽  
L. Jeffrey Medeiros ◽  
Miloslav Beran ◽  
Carlos E. Bueso-Ramos
Keyword(s):  
Bone Marrow ◽  
Neuroendocrine Tumor ◽  
Bone Marrow Biopsy ◽  
Clinical Symptoms ◽  
Eosinophilic Cytoplasm ◽  
Hydroxyindoleacetic Acid ◽  
History Of ◽  
Cardiac Valve Disease ◽  
Immunohistochemical Studies

Abstract We report a unique case of a patient with a neuroendocrine tumor localized to the bone marrow. The patient had a history of hairy cell leukemia, and the neuroendocrine tumor was detected in a bone marrow biopsy specimen obtained to assess response to 2-chlorodeoxyadenosine therapy. The neuroendocrine tumor was present as nodules that replaced approximately 15% of the bone marrow medullary space and was composed of round cells with fine chromatin, indistinct nucleoli, and relatively abundant, granular, eosinophilic cytoplasm. Histochemical stains showed cytoplasmic reactivity with Grimelius and Fontana-Masson stains, and immunohistochemical studies showed positivity for keratin and chromogranin. The histologic, cytochemical, and immunohistochemical features resembled a carcinoid tumor, and metastasis to the bone marrow was considered initially. The patient was asymptomatic without diarrhea, flushing, or cardiac valve disease. Serotonin production, assessed by the measurement of serum 5-hydroxyindoleacetic acid and substance P levels, was normal. Extensive clinical and radiologic work-up and endoscopy of the gastrointestinal tract to detect a primary site other than the bone marrow were negative. Follow-up bone marrow biopsy 7 years after the initial diagnosis was positive for persistent neuroendocrine tumor. The patient has not received any therapy specific for the neuroendocrine tumor and has had no clinical symptoms or evidence of progression after 9 years of clinical follow-up. We suggest that this neuroendocrine tumor may have arisen in the bone marrow.

P1018Evolution of atrioventricular conduction disorders after TAVI

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Irles ◽  
F Salerno ◽  
R Cassagneau ◽  
R Eschallier ◽  
C Maupain ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Primary Endpoint ◽  
Univariate Analysis ◽  
P Value ◽  
Conduction Disorders ◽  
Av Conduction ◽  
One Year ◽  
The One ◽  
Valve Implantation

Abstract Background The evolution of atrioventricular block (AVB) after Trans Aortic Valve Implantation (TAVI) is poorly understood, and indications of pacemaker (PM) implantation after TAVI not well defined. Modern PM algorithms can help studying the evolution of these AV conduction disorders after TAVI. SafeR® mode (Sorin® PM) allows to monitor precisely the AV conduction and to store AVB episodes in the PM memory as intracardiac electrograms, which can be re-read and validated afterwards. Methods From November 2015 and January 2017, all patients implanted in one of the 19 French enrolling centers with a Sorin® PM set in SafeR® mode after TAVI could be prospectively included in the study. All the PM interrogation files were centrally collected. The primary endpoint (PE) was the presence of at least one episode of high grade AVB (HG-AVB) beyond day 7 (D7) to one year after the TAVI. It could be validated either by the presence of a HG-AVB on EKG or telemetry, or by the confirmation of a HG-AVB in the PM memory files. Results 273 patients were included in the study, the PE was assessable in 197 patients. PE was validated in 74.6% patients. In univariate analysis, the use of an oversized prothesis or balloon, and all early episodes of HG-AVB (all those occurring up to D7) influence the validation of the PE. Other AV conduction disorders have no influence on the PE (Table). In multivariate analysis, only HG-AVB occurring between D2 and D7 has a significant influence on the PE. Factors influencing HG-AVB after TAVI Studied factor HG-AVB episode(s) during the one year follow up No HG-AVB episode during the one year follow up p value RBBB before TAVI (%) 41 34 0,346 Low implantation (>6mm) (%) 59 37 0,156 Use of Autoexpansive Valve (%) 62 62 0,990 Oversizing (%) 19 6 0,022 HG-AVB per TAVI (%) 56 30 0,001 HG-AVB D0-D1 (%) 53 24 0,001 HG-AVB D2-D7 (%) 68 34 0,001 New or wiser LBBB and improvement of PR interval after TAVI (%) 30 39 0,253 Influence of predefined factors on the Primary Endpoint. Conclusion The analysis of the SafeR® algorithm files in patients implanted with a PM after TAVI show a high incidence of HG-AVB during the one year follow up. In multivariate analysis, only HG-AVB occurring between D2 and D7 significantly influence the PE, confirming that AV conduction disorders occurring during the first 24 hours may spontaneously normalize. Acknowledgement/Funding Microport CRM

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