PROGNOSTIC IMPACT OF IMMUNOHISTOCHEMICAL P53 EXPRESSION IN BONE MARROW BIOPSY IN HIGHER RISK MDS: A PILOT STUDY

Background and objectives: Mutations of the TP53 gene have an unfavorable prognosis in Myelodysplastic Syndromes (MDS). The product of the TP53gene is the p53 protein. Most of TP53mutations entail the accumulation of the protein in the nucleus of tumor cells. The immunohistochemical (IHC) staining for p53 can be a surrogate suggesting a mutational status and, if overexpressed, seems to be of prognostic value by itself. The best prognostic cut-off value of overexpression is controversial. The aim of this pilot study is to investigate about the correct value from a homogenous group of patients with higher IPSS-R risk MDS. Methods: In sixty consecutive patients diagnosed with MDS and categorized as IPSS-R risk “intermediate”, “high” and “very high”, the bone marrow biopsies performed at the diagnosis were retrospectively re-examined for IHC p53 expression. The result of p53 expression was subsequently related to survival. Results: A worst overall survival was observed both in patients whose IHC p53 expression was ≥5% and ≥ 10% compared to the patients with a p53 expression respectively below 5% (p= 0.0063) or 10% (p=0.0038). Conclusions: The ICH p53 expression in bone marrow biopsy in higher risk MDS was confirmed to have prognostic value. These results indicate more than 10% expression as the best cut off value.

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The Immunohistochemical Expression of p53 in Bone Marrow Biopsy Has Unfavorable Prognostic Impact in Higher Risk Myelodysplastic Syndromes If It Is at Least 10%

Blood ◽

10.1182/blood.v128.22.5546.5546 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5546-5546

Author(s):

Alfredo Molteni ◽

Emanuele Ravano ◽

Laura Bandiera ◽

Marta Riva ◽

Michele Nichelatti ◽

...

Keyword(s):

Bone Marrow ◽

Overall Survival ◽

Risk Score ◽

Myelodysplastic Syndromes ◽

Prognostic Value ◽

Patient Survival ◽

P53 Protein ◽

Prognostic Impact ◽

P53 Expression ◽

Very High

Abstract Background The p53 protein is an onco-suppressor protein encoded by the TP53 gene, which is mutated in 5-10% of cases of de novo myelodysplastic syndromes (MDS). In 75% of cases TP53 mutations lead to store the p53 protein within the nucleus of the neoplastic cells. TP53 mutations were shown to have an unfavorable prognostic impact in patients with MDS. The immunohistochemical (IHC) expression of p53 in bone marrow (BM) biopsy has in itself negative impact on prognosis in low risk MDS, especially in MDS with isolated del(5q) category. However, the p53 cut-off value related to prognosis has not been established with accuracy, ranging between 1 and 5% in different reports. Moreover, no data are available on the possible prognostic impact of p53 BM expression and cut-off levels in patients with higher risk MDS. Aim To evaluate the prognostic value of IHC expression of p53in BM biopsies from patients with intermediate, high and very high R-IPSS risk MDS Methods BM biopsies performed at diagnosis in patients with intermediate, high and very high R-IPSS risk MDS with a follow up of at least three years were revised and screened for IHC p53 expression. Percentage of p53 expression was evaluated by two independent pathologists (L.B.; M.T.), and related to patient survival. Only cells with strong p53 staining were counted as positive. The statistical evaluations were carried out with the logistic analysis and the influence of p53 expression on survival was analyzed by Cox regression. A ROC analysis was carried out using theYouden method to analyze the optimal cut-off value influencing the survival. The verification was performed with the positive and negative predictive values (respectively PPV and NPV), the sensibility and the specificity with their respective 95% confidence intervals (95%CI). Survivorships were estimated with the Kaplan-Meier product limit method, followed by the logrank test, and by the Cox proportional-hazard regression. The association among categorical variables was evaluated by Fisher exact test. Results A total of 60 BM biopsies performed at MDS diagnosis were screened for p53 expression. Themedian age of these 60 patients was 67 years (range 19 - 82). Diagnoses, according to WHO, were RCMD in 26/60 (43.3%) cases; RAEB1 in 21/60 (35%) cases; RAEB2 in 13/60 (21.7%) cases. The IPSS-R was intermediate in 43 (71.7%) cases; high in 9 (15%) cases and very high in 8 (13.3%) cases. Cytogenetic risk according to the IPSS-R stratification was: very low in 1(1.6%) case; low in 30 (50%) cases; intermediate in 10 (16.7%) cases; high in 12 (20%) cases; very high in 7 (11.7%) cases. Median overall survival was 41 months. The p53 expression was: < 1% in 39 cases (65.0%), 1% in 5 cases (8.3%), 2% in 6 cases (10.0%), 3% in 2 cases (3.3%), 5% in 3 cases (5.0%),at least 10% in 5 cases (8.3%). Upon analysis, a significant association between percentage of p53 expression and patient survival was found (p=0.013; Hazard Ratio 1.067; 95%CI: 1.014 - 1.124). A cut-off value of 10% p53 expression was associated with outcome (specificity 100%; sensibility 13.5%;PPV 100%; NPV 41.8%). Specifically, as shown in figure 1, a significantly better overall survival was observed in the 55 (91.7%) patients whose BM p53 expression was < 10% compared to the 5 (8.3 %) patients with a BM p53 expression at least 10% (p=0.0038). No association was found between either BM blast countor BM grade of fibrosis and p53 expression.A significant association between the cytogenetic risk according to R-IPSS stratification and the expression of p53was instead found: any single unitary arbitrary increase in the cytogenetic risk score rises by 1600% the odds of a BM p53 expression at least 10% (p=0.015). Conclusion In our study population we confirm the unfavorable prognostic significance of BM p53 expression in higher risk MDS patients. Contrary to the reported cut-off values of p53 expression in low risk MDS, in our cohort of higher risk MDS the levels related to prognosis were greater (10% compared with 1 to 5% according to different reports). A tentative explanation for this difference may be that factors other than p53 expression strongly impact on survival in patients with higher risk MDS. Thus the negative prognostic value of p53 only emerges at higher levels of expression. The association between p53 expression and the IPSS-R cytogenetic risk score, if confirmed on a larger cohort, should be evaluated in specific biologic investigations. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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CD34-Positive Blast Count and p53 Expression in Bone Marrow Biopsies of Patients with Low-Risk Myelodysplastic Syndromes: Potential Predictive Tools of Response to Erythropoietin Stimulating Agents

Pathobiology ◽

10.1159/000512700 ◽

2021 ◽

pp. 1-9

Author(s):

Francesca Boggio ◽

Alessandro Del Gobbo ◽

Marco Barella ◽

Giorgio Croci ◽

Ramona Cassin ◽

...

Keyword(s):

Bone Marrow ◽

Myelodysplastic Syndromes ◽

Therapeutic Option ◽

P53 Protein ◽

Low Risk ◽

Histological Evaluation ◽

Bone Marrow Biopsies ◽

P53 Expression ◽

Erythropoietin Stimulating Agents

Introduction: The first-line therapy for patients with low-risk myelodysplastic syndromes (MDSs) commonly consists of erythropoietin stimulating agents (ESAs), with a response rate ranging from 34 to 62%. For nonresponder patients, outside clinical trials, blood transfusions are the most frequent therapeutic option, with detrimental effect on the quality of life and with risks of iron-overload. Since no studies have been yet conducted on this topic, we investigated the potential predictive role of bone marrow (BM) histological evaluation in patients treated with ESAs. Materials and Methods: We performed a morphological and immunohistochemical retrospective analysis of BM biopsies of 96 patients with low-risk MDSs subsequently treated with ESAs. Results: In our series, substantial morphological overlap was found between responder and nonresponder patients. On the contrary, patients with a percentage of CD34-positive blasts >3% or with p53 protein expression <1% responded with a significantly higher frequency to ESAs. Conclusions: Our study reinforces the role of BM biopsy as diagnostic tool in MDSs, being also able to supply information related to response to ESAs and to its loss over time.

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Hairy Cell Leukemias (HCL) with Unmutated V-Genes Have a Poorer Response to Single Agent 2CdA Than HCL with Mutated V-Genes.

Blood ◽

10.1182/blood.v108.11.2327.2327 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2327-2327 ◽

Cited By ~ 1

Author(s):

Francesco Forconi ◽

Elisa Sozzi ◽

Donatella Raspadori ◽

Francesca Toraldo ◽

Marzia Defina ◽

...

Keyword(s):

Bone Marrow ◽

B Cell ◽

Single Agent ◽

Prognostic Impact ◽

Hairy Cell ◽

Bone Marrow Biopsies ◽

Mutational Status ◽

Cell Neoplasm ◽

V Genes ◽

Vh Genes

Abstract Hairy cell leukemia (HCL) is a rare B-cell neoplasm highly responsive to purine analogues 2Chlorodeossiadenosine (2CdA) or Desossicoformicin or Interferons as single agents, and only a minority are refractory. Patients who obtain any response (either complete or partial) tend to have survivals as normal healthy subjects and/or will benefit from repeating the treatments in case of relapse. Conversely, the minority of patients who do not respond to one of the drugs often do not respond to the others and have a poor prognosis. We have recently observed that the majority of HCL have mutated VH genes, while a minority have unmutated VH genes. In the most common B-cell neoplasm chronic lymphocytic leukemia (CLL), VH gene status has prognostic impact and correlates with progression, treatment-response and surivival. In the process of identifying prognostic parameters of responsiveness to 2CdA, we prospectively investigated the VH and VL genes expressed by the tumor cells and response to treatment in patients receiving subcutaneous 2CdA. In newly diagnosed HCL requiring treatment, enrolled in an Italian multicenter trial (ICGHCL2004), peripheral blood mononuclear cells were obtained prior to treatment, and the expressed tumor VH and VL transcripts were identified by RT-PCR and cloning. Tumor sequences with > 98% homology to germline VH and VL genes were defined as “unmutated”. Patients received 0.1 mg/kg subcutaneous 2CdA (Litak) for 5 or 7 consecutive days and responses were evaluated by immunohistochemistry of trephine bone marrow biopsies 2 and/or 6 months after the end of treatment. Of 56 patients recruited, 22 patients were evaluable for response. Definition of response was according to consensus resolution criteria. We observed that 19/22 patients responded to subcutaneous 2CdA (15 CR, 4 PR), while 3/22 patients demonstrated refractory or progressive disease, indicating similar efficacy of subcutaneous to intravenous administration. Leukocytosis was observed in 2/3 refractory, but also in 2/21 responsive patients. In one of one patient in CR, molecular remission was also documented in the bone marrow by PCR and capillary electrophoresis. Most remarkably, the 3/3 refractory HCL shared the common feature of expressing unmutated VH and VL genes, in contrast to the responsive patients that all carried mutated VH and/or VL genes. From our series, there are indications that mutational status may relate with tumor burden (leukocytosis) and, more importantly, with response to 2CdA. Overall, the interim data suggest that HCL patients with unmutated VH genes may not benefit from single agent subcutaneous 2CdA and provide elements to build new clinical trials with combined strategies in cases of refractory/non responsive HCL where the immunogenenetic tumor profile is provided.

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The Certainty of a Post-Bone Marrow Diagnosis: A Study of the Yield of Bone Marrow Biopsies in a Community Hospital Setting

Blood ◽

10.1182/blood-2020-142032 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 34-35

Author(s):

Manasi M. Godbole ◽

Peter A. Kouides

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Bone Marrow Biopsy ◽

Fever Of Unknown Origin ◽

Conflicts Of Interest ◽

Diagnostic Yield ◽

Hospital Setting ◽

Unknown Origin ◽

Nutritional Deficiencies ◽

Bone Marrow Biopsies

Introduction: Most studies on the diagnostic yield of bone marrow biopsy including the one by Hot et al. have focused on the yield of bone marrow biopsies in diagnosing the source of fever of unknown origin. However, there have not been any studies performed to our knowledge looking at overall practice patterns and yield of bone marrow biopsies for diagnoses other than fever of unknown origin. We aim to determine the most common indications for performing bone marrow biopsies in a community-based teaching hospital as well as the yield of the biopsies in patients with specified and unspecified pre-test indications to estimate the rate of uncertain post-test diagnoses. Methods: We performed a retrospective data collection study at Rochester General Hospital, NY. A comprehensive search was conducted in our electronic medical data to identify all patients who underwent bone marrow biopsies over a 5 year period from January 2011 - December 2016 for indications other than fever of unknown origin. Patient data including demographics, pre-bone marrow biopsy diagnosis and post-bone marrow diagnosis was obtained. All patients above the age of 18 who underwent bone marrow biopsy for indications other than fever of unknown origin or follow up treatment of a hematological malignancy were included. Results: A total of 223 biopsies were performed. The median age was 59 years (age range- 23-95). One hundred and sixteen patients were male and 107 were female. The most common indications for performing bone marrow biopsy were evaluation of the following possible conditions: multiple myeloma (n=54), myelodysplastic syndrome [MDS] (n=47), lymphoma (n=28) and leukemia (n=18) as well as non-specific indications such as pancytopenia (n=40), anemia (n=22) and thrombocytopenia (n=11). The proportion of cases confirmed by bone marrow biopsy was 45/54 (83%) with the pre-marrow diagnosis of multiple myeloma, 34/47 cases (72%) with the pre-marrow diagnosis of MDS, 15/18 (83%) with the pre-marrow diagnosis of leukemia and 13/28 (46%) in those with the pre-marrow diagnosis of rule out lymphoma. Thirteen cases (18%) with possible MDS had post-bone marrow diagnoses of leukemia, anemia of chronic disease, myelofibrosis or medication-related changes. Five out of twenty two cases (23%) for anemia and 3/11 cases (27%) for thrombocytopenia without otherwise specified pre-bone marrow etiology had uncertain diagnosis after bone marrow biopsy. Conclusion: In about a fifth of patients necessitating a bone marrow, the diagnosis is discordant and can be surprising. It is also worth reporting that in these discordant results, non-hematological causes such as medications, anemia due to chronic diseases or conditions such as cirrhosis or splenomegaly from other etiologies were among the final diagnoses. Interestingly, 20% of the patients with unspecified pre-bone marrow diagnoses such as anemia or thrombocytopenia in our study had an unclear post-bone marrow diagnosis despite undergoing bone marrow biopsy. Our findings are a reminder that the bone marrow exam does not always lead to a definitive diagnosis and the need by exclusion to include in the differential non-hematological etiologies such as nutritional deficiencies, chronic kidney disease or autoimmune disorders. Disclosures No relevant conflicts of interest to declare.

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Mutational Status of the TP53 Gene As a Predictor of Response and Survival in Patients With Chronic Lymphocytic Leukemia: Results From the LRF CLL4 Trial

Journal of Clinical Oncology ◽

10.1200/jco.2010.32.0838 ◽

2011 ◽

Vol 29 (16) ◽

pp. 2223-2229 ◽

Cited By ~ 170

Author(s):

David Gonzalez ◽

Pilar Martinez ◽

Rachel Wade ◽

Sarah Hockley ◽

David Oscier ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Survival Data ◽

Prognostic Value ◽

Gene Mutations ◽

Progression Free Survival ◽

Tp53 Gene ◽

Lymphocytic Leukemia ◽

Tp53 Mutations ◽

Mutational Status ◽

Gene Tp53

Purpose TP53 mutations have been described in chronic lymphocytic leukemia (CLL) and have been associated with poor prognosis in retrospective studies. We aimed to address the frequency and prognostic value of TP53 abnormalities in patients with CLL in the context of a prospective randomized trial. Patients and Methods We analyzed 529 CLL samples from the LRF CLL4 (Leukaemia Research Foundation Chronic Lymphocytic Leukemia 4) trial (chlorambucil v fludarabine with or without cyclophosphamide) at the time of random assignment for mutations in the TP53 gene. TP53 mutation status was correlated with response and survival data. Results Mutations of TP53 were found in 40 patients (7.6%), including 25 (76%) of 33 with 17p deletion and 13 (3%) of 487 without that deletion. There was no significant correlation between TP53 mutations and age, stage, IGHV gene mutations, CD38 and ZAP-70 expression, or any other chromosomal abnormality other than 17p deletion, in which concordance was high (96%). TP53 mutations were significantly associated with poorer overall response rates (27% v 83%; P < .001) and shorter progression-free survival (PFS) and overall survival (OS; 5-year PFS: 5% v 17%; 5-year OS: 20% v 59%; P < .001 for both). Multivariate analysis that included baseline clinical variables, treatment, and known adverse genetic factors confirmed that TP53 mutations have added prognostic value. Conclusion TP53 mutations are associated with impaired response and shorter survival in patients with CLL. Analysis of TP53 mutations should be performed in patients with CLL who have progressive disease before starting first-line treatment, and those with mutations should be selected for novel experimental therapies.

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Clinical Relevance of Bone Marrow Biopsy in Staging and Follow-Up of Breast Cancer

Tumori Journal ◽

10.1177/030089168306900210 ◽

1983 ◽

Vol 69 (2) ◽

pp. 143-150 ◽

Cited By ~ 2

Author(s):

Giorgio Cruciani ◽

Gian Maria Fiorentini ◽

Giovanni Rosti ◽

Amelia Tienghi ◽

Daniele Bardella ◽

...

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Bone Metastases ◽

Bone Marrow Biopsy ◽

Clinical Relevance ◽

Bone Biopsy ◽

Bone Marrow Biopsies ◽

Female Patients

Bone marrow biopsies by Jamshidi needle were performed in 106 breast cancer female patients. Sixty-four of them were in follow-up after mastectomy, and neoplastic involvement of marrow was found in 21 patients (32.8%). Among the 42 women undergoing staging before mastectomy, the incidence of marrow involvement was 11.9% (5 women, all with radiographic positivity). Of the 37 women, either in follow-up or in the staging phase, with bone metastases detected by roentgenographic and isotopic examination, the bone biopsy was positive in 23 (62.1%), and 7 histologically had micrometastases. Three women, without any radiographic or isotopic sign of metastases, had positive biopsies. A good correlation was found between the hydroxyproline:creatinine ratio and neoplastic involvement of bone marrow.

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Bone Effect of Botezomib in Patients with Relapse and Smoldering Myeloma; A Computer Assisted Image Analysis Study of Bone Marrow Core Biopsies,

Blood ◽

10.1182/blood.v118.21.3996.3996 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3996-3996

Author(s):

Mohamed E Salama ◽

Graham E. Wagner ◽

Tamara Berno ◽

Jessica Kohan ◽

Fenghuang Zhan ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Image Analysis ◽

Bone Marrow Biopsy ◽

Computer Assisted ◽

Weekly Dose ◽

Bone Marrow Biopsies ◽

Bortezomib Treatment ◽

Smoldering Myeloma ◽

Bone Effect

Abstract Abstract 3996 Background: Bone loss and related complications including bone pains, fractures and hypercalcemia are major causes of morbidity and mortality in multiple myeloma (MM) patients. Bone growth/loss (Bone mineral densitometry) can be monitored by dual x-ray absorptiometry (DXA) in patients with smoldering myeloma (SMM). We previously reported a novel quantitative method to asses trabecular volume (TV) using whole scanned slides and image analysis (WSI) obtained from bone marrow biopsy (Teman et al. 2010). This method provides a low cost reproducible mean to assess TV in archival paraffin embedded biopsy materials. Velcade has been shown to produce an anabolic bone effect in relapsed/refractory MM patients and in this study, we examine the effect of low-dose bortezomib (Velcade) in SMM patients using the WSI methodology. Methods: Bone marrow biopsy slides obtained before, during and after bortezomib treatment were used to evaluate TV. H&E stained core biopsy slides were scanned using Scan Scope XT system (Aperio Technologies, Vista, CA) into digital whole slide images that is viewable on Aperio Image Scope. We developed classifier algorithms using Genie (Aperio) pattern recognition image analysis software (PRIA) that were adept at identifying bone, hematopoietic tissue, and clear glass. The calculated bone area (TV) was represented as a ratio of the total hematopoietic area for each biopsy event. Slides were excluded if the analysis available area was less than 6mm2 or could not be classified correctly to the satisfaction of the pathologist Mixed-effects models were used to compare bone TV/hematopoietic ratios (HR) over time and between the different groups, as well as assess any correlation with that ratio and light chain, B-2-microglobulin, and plasma cell levels. Results were considered statistically significant if p<0.05. Results: Slides from 253 consecutive biopsies composed the study materials. 45 were excluded due to significant artifacts or small analysis areas (<6mm2). 208 bone marrow biopsies from 43 patients were included in the analysis. The group included 26 maintenance, 12 relapsed, and 5 smoldering patients; The relapsed and maintenance patients received Bortezomib alone or in combination for a minimum of three cycles; smoldering patients received bortezomib as part of a phase 2 study at the weekly dose of 0.7mg/kg. All maintenance and relapsed, patients had previously received bone marrow transplant with a median 68 years of age 29 were male. Median baseline TV/HR was 32.9%for maintenance 29.8% for relapse and 33.1% smoldering groups. A median increment of TV/RH (17%) was observed after Bortezomib treatment in all groups of patients (p<0.0001). Conclusion: Analysis of bone associated changes after Bortezomib exposure in patients with multiple myeloma by Scan Scope XT demonstrate a post treatment overall gain in bone formation. Monitoring bone indices in patients with multiple myeloma with PRIA may provide a valid tool to assess treatment associated bone effect. Disclosures: No relevant conflicts of interest to declare.

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N-Cadherin Immunoexpression In Patients With Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v122.21.4976.4976 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4976-4976

Author(s):

Rahul D Pawar ◽

Tara L. Lin ◽

Wei Cui ◽

Omar S. Aljitawi

Keyword(s):

Bone Marrow ◽

Bone Marrow Biopsy ◽

Myeloid Leukemia ◽

Statistical Difference ◽

Culture Conditions ◽

Bone Marrow Biopsies ◽

Biopsy Specimens ◽

Control Bone ◽

Grade 3 ◽

Acute Myeloid

Abstract Introduction N-cadherin is a member of the cadherin family which is involved in calcium ion dependent adhesion between cells by interaction with catenin on other cells. In our previous work, we have shown differential patterns of N-cadherin expression in acute myeloid leukemia (AML) cell lines when cultured in traditional 2-dimensional (2-D) culture conditions (over monolayer of stromal cells) compared to 3-D culture conditions. In addition, we have observed that AML cell lines which are more resistant to chemotherapy in vitro had higher expression of N-cadherin, suggesting potential translational applications to patients with AML. In order to further examine the role of N-cadherin in AML, we studied patterns of N-cadherin immunoexpression in bone marrow samples taken from patients with untreated AML and compared them to control bone marrow samples. Methods In this retrospective study, we evaluated bone marrow biopsy specimens of 10 AML patients for N-cadherin expression by immunohistochemistry. Bone marrow biopsy specimens from 10 negative staging lymphoma patients were used as control. Automated Cellular Imaging system (ACIS) was used to quantify and grade N-cadherin immunoexpression in the nucleus as well as in the cytoplasm of evaluated cells. ACIS uses advanced color detection software in order to evaluate N-cadherin positive cells and measure the intensity of staining. Grades of N-cadherin positivity were subclassified as grade 0 (no staining) 1+, 2+, 3+. 10 different areas of each sample were evaluated in order to estimate the median intensity of staining per slide. Student’s t-test was used to compare the generated medians and a P-value of <0.05 was considered statistically significant. Results Nuclear N-cadherin staining was graded and compared between bone marrow biopsy specimens of patients with AML and control bone marrow biopsies from patients with negative staging bone marrow examinations for lymphoma. Interestingly, the percentage of N-cadherin grade 0 (negative) cells was higher in controls than AML samples (54% vs. 37%, p=0. 01). Also, the percentage of grade 1 and grade 2 expressing cells was significantly higher in AML cases compared to controls (grade 1: 39% vs. 29%, p=0.005; grade 2: 21% vs. 13%, p=0.029). However, there was no statistical difference seen in between AML cases and controls in terms of levels of grade 3 expression. Similarly, cytoplasmic N-cadherin staining was quantified. Grade 0 expressing cells were significantly higher in control samples compared to AML samples (34% vs. 16%, p=0.01). There was no statistical difference seen in terms of levels of grade 1 expression. However, grade 2 and 3 expression levels quantifying the higher levels of N-cadherin expression were significantly higher in bone marrow biopsies from patients with AML versus those from negative staging bone marrows (grade 2: 26% vs. 9%, P=0.01; grade 3: 4% vs. 1%, p=0.04). Conclusion Based on these results, we conclude that cytoplasmic N-cadherin expression is significantly increased in AML bone-marrow samples compared to control samples. These results should be further evaluated in the future to determine the prognostic significance of N-cadherin expression in AML. Disclosures: No relevant conflicts of interest to declare.

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Do patients with MGUS require a bone marrow biopsy?

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.8117 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 8117-8117

Author(s):

J. Singh ◽

A. K. Malani ◽

C. H. Huang ◽

M. Hashmi ◽

S. C. Mathur ◽

...

Keyword(s):

Bone Marrow ◽

Regression Analysis ◽

Bone Marrow Biopsy ◽

Plasma Cell ◽

Linear Correlation ◽

Plasma Cells ◽

Bone Marrow Biopsies ◽

Cell Percentage ◽

Serum Igg ◽

Immunoglobulin Levels

8117 Monoclonal gammopathy of undetermined significance (MGUS) increase in prevalence with age and it is associated with risk of progression to plasma cell disorder. According to ASH guidelines, patients (pts) should have a complete blood count (CBC), creatinine, calcium, and a complete bone survey and periodic follow up. There has been no clear-cut guideline regarding the role of bone marrow biopsy in these patients. There is suggestion in the literature that bone marrow aspiration and biopsy is indicated if the M protein is 1.5 g/dL. Hypothesis We hypothesize that the increase in serum immunoglobulin is correlated with an increase in plasma cell in the bone marrow biopsy. Methods: We performed a retrospective chart review of 327 MGUS veteran patients seen from 2002 to 2005. Diagnostic criteria for MGUS were defined as <3 g/dL serum monoclonal protein, <10 % plasma cells in the bone marrow and absence of radiographic or laboratory abnormality related to the plasma cell proliferative process. Patients with smoldering myeloma were excluded. Bone marrow biopsies were available on 97/327 patients. Bone marrow biopsy with plasma cell percentage, serum protein electrophoresis (SPEP) and immunofixation (SFE), and immunoglobulin levels of these patients were retrieved and statistical analysis was performed by using Pearson correlation coefficient and linear regression analysis to detect the correlation between plasma cell percentage and immunoglobulin levels. Results: Of the 97 patients whom the bone marrow biopsy was available, 66 patients had IgG, 15 had IgA and 16 had IgM monoclonal paraprotein. There was linear correlation between serum IgG and IgA levels with the percentage of plasma cells in the bone marrow. (p< 0.001 and < 0.02 respectively. By regression analysis, using a cut off value of 10% plasma cells in the bone marrow, the predicted level of IgG and IgA immunoglobulin was 2124 mg /dl and 1564 mg/dl respectively. There was no correlation between IgM immunoglobulin and plasma cell percentage in the marrow. Conclusion: There is a linear correlation between serum IgG and IgA immunoglobulin with plasma cell percentage in the bone marrow. Bone marrow biopsy with plasma cell percentage of 10% or higher may be predicted in patients with MGUS with IgG or IGA above 2g/dl and 1.5g/dl respectively. No significant financial relationships to disclose.

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Comparison of a powered bone marrow biopsy device with a manual system: results of a prospective randomised controlled trial

Journal of Clinical Pathology ◽

10.1136/jclinpath-2012-201167 ◽

2012 ◽

Vol 66 (1) ◽

pp. 24-28 ◽

Cited By ~ 16

Author(s):

Christoph Marcus Bucher ◽

Thomas Lehmann ◽

André Tichelli ◽

Alexander Tzankov ◽

Stephan Dirnhofer ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Biopsy ◽

Conscious Sedation ◽

Control Group ◽

Hospital System ◽

Bone Marrow Biopsies ◽

Skin Contact ◽

Patient Reported ◽

Biopsy Device ◽

Median Pain

The diagnostic and clinical usefulness of a powered bone marrow biopsy device (OnControl()) versus a standard manual device (TRAP Hospital System) was studied. Primary endpoints were biopsy quality and patient pain during the procedure. Fifty patients underwent a total of 60 procedures by three expert operators in a randomised stratified fashion. Baseline demographic and clinical parameters were similar in both groups. The usage of conscious sedation, dosage of lidocaine/pethidin was similar between groups. Biopsy quality was rated ‘sufficient for diagnosis’ in 24/30 in the control group and 25/30 in the powered group (p=0.74). Biopsy cylinder length, procedure time (from skin contact of the biopsy needle to placement of the biopsy cylinder in the formalin container) and patient reported pain during the procedure (T1), 15 min after the procedure (T2) and 3–5 days after the procedure (T3) there were comparable between groups. In the small subgroup of patients that did not receive conscious sedation (n=15; manual 6, powered 9) significantly lower median pain scores were observed with the powered system (median pain score 3 vs 7; p=0.015). Patients were satisfied with either device whether sedation was used (sedation: median 9 for both groups, range 3–10 (manual) and 0–10 (powered)) no sedation (median 8 (manual) vs 9 (powered)). In summary bone marrow biopsies taken with the manual or powered device produce similar technical and clinical results. If no conscious sedation is used, pain during the procedure appears to be lower with the powered system. The use of a powered system seems to be justified in selected patients.

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