Bone Marrow Involvement In Patients Research Articles

Pre-treatment 18f-FDG PET/CT for Assessing and Predicting Bone Marrow Involvement in Patients with Newly Diagnosed Peripheral T-Cell Lymphoma

Objective: To explore the value of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in assessing and predicting bone marrow involvement (BMI) in patients with newly diagnosed peripheral T-cell lymphoma (PTCL) prior to treatment. Methods: This retrospective study included 201 eligible patients of PTCL who received bone marrow biopsy (BMB) and PET/CT between January 2017 and December 2022. Extra subgroup analysis was designed considering the variation of avidity of FDG in different distinct entities. The status of bone marrow (BM) by PET was assessed using a visual examination and a quantitative index (the highest SUV of BM divided by the mean SUV of the liver [M/L]). Prognostic value of BM findings was also evaluated regarding progression free survival (PFS) and overall survival (OS). Results: The sensitivity and specificity of PET/CT for patients with confirmed PTCL by BMB were 43.2% and 90.2%, respectively. As for subgroup analysis, the kappa value reflecting the agreement between BMB and visual analysis in angioimmunoblastic T-cell lymphoma (AITL), peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), anaplastic large cell lymphoma (ALCL) as well as nodal T-follicular helper (TFH) cell lymphoma (PTCL-TFH) was 0.315, 0.307, 0.426 and 0.581, respectively. (Give the number of cases in each lymphoma group) PET score was an independent factor for PFS (P =0.011) but not for OS (P =0.840). In addition, 25 patients with stage I to II disease had no evidence of BMI by either PET/CT or BMB. Image-guided biopsy was also recommended when PET/CT showed a focal FDG uptake outside the iliac crest. Quantitative analysis revealed the differences in the two-level of M/L; however, they were not statistically significant for both PFS and OS (P =0.246 and P =0.227). Conclusion: PET/CT has a complementary role in assessing BMI and prognosis in PTCL patients.

Use of IDEAL-IQ in Quantifying Femoral Bone Marrow Involvement in Gaucher Disease.

To quantitatively measure femoral bone marrow involvement in patients with Gaucher disease (GD) by using fat fraction (FF) derived from the iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation (IDEAL-IQ) technique. Bilateral femora of 23 patients with type 1 GD receiving low-dose imiglucerase treatment were prospectively scanned using structural magnetic resonance imaging sequences and an IDEAL-IQ sequence. Femoral bone marrow involvement was evaluated by both semiquantification (bone marrow burden [BMB] score based on magnetic resonance imaging structural images) and quantification (FF derived from IDEAL-IQ) methods. These patients were further divided into subgroups according to whether they underwent splenectomy or had bone complications. The interreader agreement of measurements and the correlation between FF and clinical status were statistically analyzed. In patients with GD, both BMB and FF evaluation of femora showed good interreader concordance (intraclass correlation coefficient = 0.98 and 0.99, respectively), and FF highly correlated with BMB score ( P < 0.001). The longer the duration of disease, the lower the FF ( P = 0.026). Femoral FF was lower in subgroups with splenectomy or bone complications than those without splenectomy or bone complications (0.47 ± 0.08 vs 0.60 ± 0.15, 0.51 ± 0.10 vs 0.61 ± 0.17, respectively, both P < 0.05). Femoral FF derived from IDEAL-IQ could be used to quantify femoral bone marrow involvement in patients with GD, and low bone marrow FF may predict worse outcomes of GD patients in this small-scale study.

FDG-PET/CT Provides Clues on Bone Marrow Involvement in Follicular Lymphoma and Carries Important Prognostic Information.

Objectives: To compare the diagnostic efficacy of PET-CT and bone marrow biopsy (BMB) in the detection of bone marrow involvement (BMI) in newly diagnosed patients with follicular lymphoma (FL), as well as their prognostic implications in such patients. Methods: Retrospective analysis was conducted on clinical data from 165 newly diagnosed FL patients. The benefits and drawbacks of PET-CT and BMB in assessing BMI in FL patients were compared and evaluated. Moreover, the prognostic outcomes and factors affecting the survival of FL patients were examined. Results: Among 165 patients, bone marrow involvement (BMI) was diagnosed by PET-CT (PET+) in 54 cases (32.7%), by bone marrow biopsy (BMB+) in 50 cases (30.3%), and by either PET+ or BMB+ in 80 cases (48.5%). PET-CT scans upgraded 32 patients (19.4%) to stage IV, including 1 stage I and 4 stage II cases. Four patients were elevated to stage IV by BMB, all of whom had a previous stage III diagnosis. No patients with previous stages I or II were elevated to stage IV by BMB. The median follow-up time was 6.6 years (range,0-11.0 years). The 5-year OS was 86.7%, and the 5-year PFS was 44.8%. Multivariate analysis revealed that BMI by PET-CT was the only independent predictor of PFS reduction. Regarding OS, grade 3a and BMI by PET-CT were independent predictors of decreased survival. Conclusion: PET-CT enables a thorough evaluation of bone marrow involvement in patients with FL, and BMI identified by PET-CT can have substantially implications for patient prognosis. PET-CT obtains vital data for the diagnosis, treatment, and prognosis of FL patients. By contrast, BMB seldom augments crucial data.

Correlation of flow cytometry and bone marrow biopsy in marrow involvement of lymphoma patients

Introduction: Non-Hodgkin’s lymphomas (NHLs) are hematolymphoid malignancies. Bone marrow biopsy (BMB) is performed for staging. BMB findings are an important indicator of prognosis and treatment planning. In this study, we compared flow cytometry and BMB in marrow involvement of lymphoma patients. Objectives: This study aimed to compare the frequency of involvement in bone marrow in flow cytometry and biopsy, compare the frequency of involvement in bone marrow in flow cytometry based on gender, compare frequency of bone marrow involvement in biopsy based on gender, compare mean age between two groups with bone marrow involvement and without bone marrow involvement in biopsy, compare mean age between two groups struggling with bone marrow involvement and without bone marrow involvement in flow cytometry, and compare mean ages between all genders struggling with bone marrow involvement and without bone marrow involvement in flow cytometry and biopsy. Patients and Methods: This study was cross-sectional, and the population included all patients affected by NHL, which bone marrow flow cytometry and biopsy performed for disease staging referred to Seyed Al-Shohada hospital affiliated with Isfahan University of medical sciences during 2016-2020. Four color flow cytometry devices (PARTEC CyFlow Space, Germany) with EXBIO antibody kits (Spain) were used. Results: In this study, the number of samples was 107, of which 68 (63.6%) were male, and the mean (standard deviation) of the total age was 40.87 (18.98) years. All samples were diagnosed as lymphoma and were examined by bone marrow flow cytometry and biopsy. Flow cytometry frequency of bone marrow involvement was 14 (13.1%), and biopsy frequency of bone marrow involvement was 22 (20.6%). In 97 cases (90.6%), the diagnosis of both methods was the same. Nine patients (8.4%) had bone marrow involvement in biopsy only, and one case (1%) had bone marrow involvement in flow cytometry only. As a result, bone marrow involvement in patients with lymphoma who participated in this project is about 21.5%. Conclusion: We concluded that evaluation of bone marrow involvement using combined methods is more efficient than biopsy or flow cytometry alone. We also recommended physicians use both methods at the same time.

Might periostin serve as a marker of bone marrow involvement in patients with diffuse large B-cell lymphoma?

Abstract Objectives We measured the serum periostin levels in patients with DLBCL and determined whether the levels reflected the clinical findings. Methods This was a case-control study. DLBCL patients diagnosed between March 2021 and October 2021 (n=36) and healthy volunteers (n=36) (Control group) were included. The serum periostin levels of the two groups were compared. Moreover, subgroup analyses were conducted in the patient group. Results The serum periostin level was significantly higher in the patient than the control group (28.8 ± 3.2 vs. 15.1 ± 7.5 ng/mL, p=0.017). On subgroup analyses, the median serum periostin level of nine (25%) patients with bone marrow involvement was higher than that of the 27 (75%) lacking bone marrow involvement (12.7 vs. 21.7 ng/mL, p=0.018). On ROC analysis, the optimal periostin cutoff for bone marrow involvement was 17.3 ng/mL (sensitivity 77%, specificity 67%, AUC 0.765; 95% CI; 0.606–0.924, p=0.018). By the disease stage, the periostin level was higher in stage 4 patients than in those of other stages (21.3 vs. 12.0 ng/mL, p=0.029). Conclusions The periostin level correlated with such involvement; periostin may serve as a novel prognostic marker of DLBCL.

Diagnostic Accuracy of Positron Emission Tomography-Computed Tomography (PET-CT Scan) In Detecting Bone Marrow Involvement in Patients with Diffuse Large B cell Lymphoma

Objective: To evaluate the diagnostic accuracy of positron emission tomography combined with CT scan (PET-CT Scan) in detecting bone marrow involvement in patients with diffuse large B-cell lymphoma, keeping bone marrow biopsy as gold standard. Methodology: From November 2017 to May 2018, a cross sectional validation study was carried out at the Aga Khan University in Karachi Department of Oncology's Section of Clinical Hematology. The study comprised a total of 112 patients who were identified as having diffuse large B cell lymphoma after a lymph node was implicated was histopathologically examined. All patients had a PET-CT scan and bone marrow biopsy technique as part of the staging workup. With bone marrow biopsy acting as the gold standard, the diagnostic efficacy of a PET-CT scan for identifying bone marrow involvement was evaluated. Results: Of 112 patients, there were 71(63.39%) males and 41(36.61%) females. The mean age was 45.09±17.36 years. The mean duration of diagnosis was 17.19±6.02 days. Through biopsy, bone marrow involvement was identified in 40 (35.7%) cases. Through a PET-CT scan, bone marrow involvement was identified in 47 (41.9%) cases. The PET- CT scan in comparison with bone marrow biopsy for detecting bone marrow involvement in patients with DLBCL had a sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of 95%, 87.7%, 80.85%, 96.92% and 90.18% respectively. Conclusion: PET-CT scan can accurately detect bone marrow involvement in patients with DLBCL so it can be used in most patients instead of invasive bone marrow biopsy procedure for staging of DLBCL patients.

Deep learning-based virtual noncalcium imaging in multiple myeloma using dual-energy CT.

Dual-energy CT with virtual noncalcium (VNCa) images allows the evaluation of focal intramedullary bone marrow involvement in patients with multiple myeloma. However, current commercial VNCa techniques suffer from excessive image noise and artifacts due to material decomposition used in synthesizing VNCa images. In this work, we aim to improve VNCa image quality for the assessment of focal multiple myeloma, using an Artificial intelligence based Generalizable Algorithm for mulTi-Energy CT (AGATE) method. AGATE method used a custom dual-task convolutional neural network (CNN) that concurrently carries out material classification and quantification. The material classification task provided an auxiliary regularization to the material quantification task. CNN parameters were optimized using custom loss functions that involved cross-entropy, physics-informed constraints, structural redundancy in spectral and material images, and texture information in spectral images. For training data, CT phantoms (diameters 30 to 45cm)withtissue-mimicking inserts were scanned on a third generation dual-source CT system. Scans were performed at routine dose and half of the routine dose. Small image patches (i.e., 40 × 40 pixels) of tissue-mimicking inserts with known basis material densities were extracted for training samples. Numerically simulated insert materials with various shapes increased diversity of training samples. Generalizability of AGATE was evaluated using CT images from phantoms and patients. In phantoms, material decomposition accuracy was estimated using mean-absolute-percent-error (MAPE), using physical inserts that were not used during the training. Noise power spectrum (NPS) and modulation transfer function (MTF) were compared across phantom sizes and radiation dose levels. Five patients with multiple myeloma underwent dual-energy CT, with VNCa images generated using a commercial method and AGATE. Two fellowship-trained musculoskeletal radiologists reviewed the VNCa images (commercial and AGATE) side-by-side using a dual-monitor display, blinded to VNCa type, rating the image quality for focal multiple myeloma lesion visualization using a 5-level Likert comparison scale (-2=worse visualization and diagnostic confidence, -1=worse visualization but equivalent diagnostic confidence, 0=equivalent visualization and diagnostic confidence, 1=improved visualization but equivalent diagnostic confidence, 2=improved visualization and diagnostic confidence). A post hoc assignment of comparison ratings was performed to rank AGATE images in comparison to commercial ones. AGATE demonstrated consistent material quantification accuracy across phantom sizes and radiation dose levels, with MAPE ranging from 0.7% to 4.4% across all testing materials. Compared to commercial VNCa images, the AGATE-synthesized VNCa images yielded considerably lower image noise (50-77% noise reduction) without compromising noise texture or spatial resolution across different phantom sizes and two radiation doses. AGATE VNCa images had markedly reduced area under NPS curves and maintained NPS peak frequency (0.7 lp/cm to 1.0 lp/cm), with similar MTF curves (50% MTF at 3.0 lp/cm). In patients, AGATE demonstrated reduced image noise and artifacts with improved delineation of focal multiple myeloma lesions (all readers comparison scores indicating improved overall diagnostic image quality [scores 1 or 2]). AGATE demonstrated reduced noise and artifacts in VNCa images and ability to improve visualization of bone marrow lesions for assessing multiple myeloma.

Bone marrow involvement in patients with metastatic castration sensitive prostate cancer.

The clinical significance of bone marrow (BM) metastasis in prostate cancer as well as impact on oncological prognosis is unclear. We aim to assess the prevalence and clinical outcomes of BM metastasis at initial presentation of metastatic castrate sensitive prostate cancer (CSPC). Retrospective chart review of newly diagnosed metastatic CSPC patients was performed with collection of clinicopathologic and radiologic characteristics. Descriptive univariate and multivariate analysis was performed as well as survival measures (OS and PFS), which was done using the Kaplan-Meier survival and the Log-rank test. 189 patients were eligible, of which, eleven patients (6%) had biopsy proven BM involvement at diagnosis. There was a trend to poorer PFS and OS in patients with BM involvement but not statistically significant; however, factors that correlated with inferior PFS and OS in the multivariate analysis included ECOG PS, ALP, and Hb. BM metastasis in prostate cancer may lead to poorer survival. Clinical features including poor performance status, anemia, and elevated ALP, could guide bone marrow biopsies in the future to diagnose bone marrow metastasis at an earlier stage.

Impact of bone marrow involvement in patients with peripheral T-cell lymphoma undergoing autologous stem cell transplant.

7550 Background: Nodal-based T-cell lymphomas (PTCL) are treated with induction therapy and consideration for autotransplant (autoSCT) in first remission. The impact of bone marrow (BM) involvement at diagnosis and at autoSCT is unclear. Methods: We performed a retrospective review of consecutive patients with PTCL-NOS, AITL, and ALCL who received autoSCT in first remission at Memorial Sloan Kettering Cancer Center from 1997-2021. For BM involvement at baseline, patients were classified as positive (≥5% by histology), any involvement (by histology and/or at least 1 high-sensitivity [HS] assay, referring to flow or clonal TCR gene rearrangement), or negative (no involvement by histology and at least 1 negative HS assay). Patients with no baseline BM biopsy were excluded. At end of therapy (EOT, after induction but prior to autoSCT), BM involvement was considered positive (≥5% by histology), minimal residual disease positive (MRD+, no histological involvement but at least 1 positive HS assay), and MRD- (no histological involvement and at least 1 negative HS assay). Patients with no EOT BM but negative baseline BM were included as a separate cohort. Patients with no baseline BM and no EOT BM were excluded, as were those with baseline BM involvement and no EOT BM. The Kaplan-Meier method was used to estimate survival and compared using log-rank tests. Results: A total of 135 patients were included. Median follow-up after autoSCT for survivors was 56 months. The 5-year PFS/OS for the entire cohort was 45% and 65%, respectively. By histology, 5-year PFS/OS for PTCL-NOS (N = 27), AITL (N = 78), ALK+ (N = 8) and ALK- (N = 21) ALCL was 36%, 37%, 75%, 74% (p = 0.005), and 51%, 59%, 100%, 85% (p = 0.01). Among those with adequate baseline BM evaluation (N = 98), 31 were positive, 52 had any involvement, and 44 were negative. Five-year PFS and OS in the positive, any involvement, and negative groups was 46%, 42%, 44% (p = 0.82), and 63%, 61%, 74% (p = 0.27). Of those with adequate EOT BM evaluation (N = 72), 1 was positive, 17 were MRD+, and 43 were MRD-; 32 patients had no EOT BM but negative baseline BM. Five-year PFS and OS by the EOT positive, MRD+, MRD-, and no EOT BM but negative baseline groups was 0%, 37%, 45%, 45% (p = 0.86), and 0%, 92%, 59%, 71% (p = 0.39). Of the 17 patients with MRD+ EOT BM, 14 (82%) had AITL. Two-year PFS/OS in the AITL only cohort by EOT BM was 0%, 54%, 48%, 33%, and 0%, 90%, 75%, 72%, for the positive, MRD+, MRD-, and no EOT BM but negative baseline groups (PFS: p = 0.4; OS: p = 0.3). Conclusions: In patients treated with upfront induction and autoSCT in first remission, neither BM involvement at diagnosis nor the presence of MRD at the time of autoSCT resulted in worse survival outcomes compared to those with no BM involvement. For patients with PTCL-NOS, AITL, or ALCL in first remission, baseline BM involvement or pre-autoSCT BM MRD+ should not dissuade use of autoSCT consolidation.

Diagnostic Accuracy and Prognostic Relevance of Immunoglobulin Heavy Chain Rearrangement and 18F-FDG-PET/CT Compared With Unilateral Bone Marrow Trephination for Detecting Bone Marrow Involvement in Patients With Diffuse Large B-Cell Lymphoma.

BackgroundIn diffuse large B-cell lymphoma (DLBCL), bone marrow involvement (BMI) has an important clinical implication as a component of staging and International Prognostic Index. This study aimed to determine whether molecular analysis of immunoglobulin heavy chain (IgH) genes and positron emission tomography-computed tomography (PET/CT) could overcome the limitation of defining morphologic BMI by trephination biopsy and could increase the diagnostic accuracy or prognostic prediction.MethodsA total of 94 de novo patients with DLBCL underwent PET/CT, polymerase chain reaction (PCR) test for detection of IgH gene rearrangement, and unilateral bone marrow (BM) trephination at diagnosis.ResultsA total of 9 patients (9.6%) were confirmed to present morphologic BMI (mBMI) based on trephination biopsy. On the other hand, 21 patients (22.3%) were confirmed to have IgH clonality (IgH BMI), while 16 (17.0%) were classified with BMI based on the assessment of PET/CT (PET BMI). Each IgH rearrangement PCR and PET/CT showed the high negative predictive value of detecting the BMI. However, the combined assessment of IgH rearrangement and PET/CT could increase the diagnostic accuracy and specificity with 87.2% and 97.0%, respectively. The survival outcome of patients with double positive PET BMI and IgH BMI was significantly worse than that with either single positive PET BMI or IgH BMI, and even less than patients with neither PET BMI nor IgH BMI (3-year PFS: 50.0% vs. 75.4% vs. 97.9%, P = 0.007, 3-year OS: 50.0% vs. 75.6% vs. 80.1%, P = 0.035, respectively).ConclusionThis study suggests that the combined evaluation of PET/CT and IgH rearrangement could give additional information for predicting therapeutic outcomes in patients with negative morphologic BMI as an important part of the prognosis.

Incidence and Prognostic Implication of Bone Marrow Involvement in Hodgkin’s Lymphoma

Introduction- : Conducting Bone marrow examination in a Hodgkin's Lymphoma (HL) patient at the time of diagnosis is done routinely to determine the stage of the disease. The aim of this study was to analyze the incidence and prognosis of bone marrow involvement in patients with Hodgkins lymphoma, retrospectively.&#x0D; Materials and Patients: Ten patients of Hodgkins lymphoma were incorporated in the current study. Bone marrow aspiration and biopsy was done in all ten cases as part of staging procedure.&#x0D; Results: Three patients showed involvement of bone marrow by Hodgkin’s lymphoma and both the patients had clinically poor outcome.&#x0D; Discussion and Conclusion: Bone marrow examination is important in stage II and III of Hodgkin”s lymphoma because positive result will upstage the disease. Also, bone marrow involvement indicates an aggressive disease and poor prognosis for the patient.

Aberrant expression of CD54 detected by flow cytometry is a characteristic of B-lymphoma cells in bone marrow specimens

BackgroundFlow cytometry (FC) is a popular method to detect bone marrow (BM) involvement in patients with B-cell non-Hodgkin lymphoma (B-NHL). The majority of screen panels of FC still rely on finding monoclonal B-cells, e.g., B-cells with immunoglobin (Ig) light-chain restriction, which has many limitations. Therefore, exploring new markers is warranted.MethodsA total of 52 cases of B-NHL with BM involvement were collected. The median age was 60 years. Out of these 52 cases, 34 were male, and 18 were female. A 10-color FC panel was used to detect the expression of CD54 on lymphoma cells. The expression of CD54 was calculated as the mean fluorescence index ratio (MFIR) and was described as the mean ± standard error of the mean (SEM).ResultsUp to 18/52 (34.62%) of BM specimens abnormally expressed an increased level of CD54, including 1/10 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 9/13 cases of mantle cell lymphoma (MCL), 2/14 cases of follicular lymphoma (FL), 5/9 cases of marginal zone lymphoma (MZL), and 1/3 cases of high-grade B-NHL (HG B-NHL). The expression level of CD54 was significantly increased in MCL cases (53.41 ± 11.04) compared with CLL/SLL cases (11.66 ± 2.79) and FL cases (13.49 ± 2.81). The lowest percentage of CD54-positive B-cells attained 0.13%. In 5/9 cases of MZL and 1/3 cases of HG B-NHL, increased expression of CD54 was the only abnormal immunophenotype detected besides Ig light-chain restriction. No aberrant CD54 expression was identified by FC in lymphoplasmacytic lymphoma (LPL) (0/2) and Burkitt lymphoma (BL) (0/1) cases. Aberrant expression of CD54 was not related to plasma cell differentiation.ConclusionLymphoma cells, especially in MCL and MZL cases, frequently show increased expression of CD54. Such aberrant expression is not related to plasma cell differentiation. We highly recommend adding CD54 to the FC screening panel to detect BM involvement in patients with B-NHL.

The role of microscopic bone marrow examination and [123I]MIBG scintigraphy in detection of bone marrow involvement in patients with neuroblastoma

ABSTRACT Objectives For the detection of bone marrow (BM) metastases in patients with neuroblastoma, microscopic BM examination and [123I]MIBG scintigraphy are advised. The aims of this study were to assess the concordance of [123I]MIBG and microscopic BM examination (aspirate and biopsy) in detecting BM involvement and to compare invasive disease in BM biopsies and aspirates, both at diagnosis and before autologous stem cell collection (ASCC). Methods Fifty-five patients with stage 4 or stage 4S disease were included, and 37 of them received an autologous hematopoietic stem cell transplantation (AHSCT). The concordance rate was measured and paired binary data were analysed by the McNemar test to look for a systematic difference between diagnostic tests. Results At diagnosis and before ASCC, we found acceptable concordance rates for [123I]MIBG versus microscopic BM examination (77.1% and 85.3% respectively). Discordant results were found in both directions and at both time points. The concordance rate for biopsy versus aspirate at diagnosis was 80.6%, however, before ASCC a much higher concordance rate between both microscopic examinations was found (94.1%). While none of the aspirates showed neuroblastoma cells before ASCC, two biopsies still showed tumor invasion. Conclusion For patients with neuroblastoma, a [123I]MIBG scintigraphy and a microscopic examination of BM aspirate and its biopsy should be used as complementary tools in the evaluation of BM involvement, and this both at diagnosis and during treatment (before ASCC).

Comparison of three different methods to detect bone marrow involvement in patients with neuroblastoma

PurposeNeuroblastoma (NB) is the most frequent extracranial tumor in children. The detection of bone marrow (BM) involvement is crucial for correct staging and risk-adapted treatment. We compared three methods regarding the detection of NB involvement in BM.MethodsEighty-one patients with NB were included in this retrospective study. BM samples were obtained at designated time points at study entry and during treatment or follow-up. The diagnostic tools for BM analysis included cytomorphology (CM), flow cytometry (FCM) and automatic immunofluorescence plus fluorescence in situ hybridization (AIPF).ResultsWe analyzed 369 aspirates in 81 patients in whom AIPF, CM, and FCM were simultaneously available. During the observation period, NB cells were detected in 86/369 (23.3%) cases, by CM in 32/369 (8.7%), by FCM in 52 (14.1%), and by AIPF in 72 (19.5%) samples. AIPF and/or FCM confirmed all positive results obtained in CM and detected 11 additional positive BM aspirates in 294 CM negative samples (p < 0,001). Survival of patients with BM involvement at study entry identified solely by FCM/AIPF was 17.4% versus 0% for patients in whom BM involvement was already identified by CM.ConclusionThe combination of AIPF/FCM yielded the highest detection rate of NB cells in BM. AIPF was the single, most sensitive method in detecting these cells. Although CM did not provide any additional positive results, it is still a useful, readily available and cost-effective tool. The prognostic significance of FCM and AIPF should be confirmed in a prospective study with a larger number of patients.

Application of CD54 in diagnosing bone marrow involvement by using flow cytometry in patients with diffuse large B-cell lymphoma

BackgroundFlow cytometry plays a key role in detecting bone marrow (BM) involvement in patients with diffuse large B-cell lymphoma (DLBCL). To improve its detection sensitivity, we need to explore novel markers. In this study, we detected the expression CD54 on lymphoma cells in BM specimens from DLBCL patients and clarified its diagnostic significance in BM involvement by DLBCL.MethodsWe collected BM specimens from 76 patients with DLBCL (germinal center B-cell (GCB) = 25, non-GCB = 51) and 10 control patients without lymphoma. We detected and compared the expression of CD54 on lymphoma cells and normal mature B cells by using 10-color panels.ResultsNormal plasma cells expressed a higher level of CD54 as compared with hematogones (p < 0.05) and normal mature B cells (p < 0.05). Among 76 patients, 23 of them (GCB = 12, non-GCB = 11) had BM involvement. Lymphoma B cells from 12 cases (GBC = 4, non-GCB = 8) expressed a higher level of CD54 compared to normal mature B cells (p < 0.05). Additionally, lymphoma cells of the non-GCB subtype frequently expressed a higher level of CD54 in comparison to the GCB subtype (p < 0.05). And the high expression of CD54 was not related to plasmacytoid differentiation.ConclusionAberrant expression of CD54 on lymphoma cells is frequently seen in patients’ BM specimens involved by DLBCL, especially in the non-GCB subtype. CD54 could be used as a new marker to gate on lymphoma cells and improve the detection sensitivity of BM involvement in patients with DLBCL.

The Efficacy of PET-CT in Detecting Bone Marrow Involvement in Patients with Newly Diagnosed Lymphoma: A Retrospective Study

Background: Patients diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) undergo various investigations to determine disease stage. This includes Positron Emission Tomography with Computed Tomography (PET-CT) scan and bone marrow biopsy (BMB), which has historically been considered the gold standard for detecting involvement of the bone marrow (BM) by lymphoma. Recent studies have suggested that PET-CT scans can detect BM involvement in most patients with lymphoma. As such, there is growing interest into whether or not PET-CT scans may replace the need for BMB in staging patients with lymphoma.Objective: We conducted a retrospective chart review of patients newly diagnosed with lymphoma at our local cancer centre to evaluate the diagnostic performance of PET-CT scans in detecting BM involvement.Methods: Patients were eligible for inclusion if they were age 18 or older, had previously untreated HL or NHL diagnosed from January 2012 to August 2016, and underwent both BMB and PET-CT scan at time of staging. We collected the results of BM aspirate, flow cytometry, cytogenetics and biopsy. Patients were considered to have BM involvement if they had a positive BMB. PET-CT scans were retrospectively re-analyzed by two readers from the Division of Nuclear Medicine. Both were blinded to the patients' clinical information, including lymphoma diagnosis and BMB results. BM positivity by PET-CT scan was characterized as being either diffuse (relatively uniform increase in tracer uptake in the BM) or focal (localized increase in tracer uptake to one or more demarcated regions of BM). We performed sensitivity and specificity analyses of PET-CT scans.Results: The study included 110 patients: 102 patients with NHL and 8 with HL. The most common NHL subtype was diffuse large B-cell lymphoma (DLBCL) (n=40). For the entire cohort of patients with NHL, the sensitivity and specificity of PET-CT scan for diagnosing BM involvement were 78% (95% CI: 52-93%) and 86% (95% CI: 76-92%), respectively (Table 1). For patients with DLBCL, the sensitivity and specificity of PET-CT scan were 100% (95% CI: 52-100%) and 79% (95% CI: 63-91%), respectively. In this group, none of the patients with a negative PET-CT scan had a positive BMB. Five of the 7 patients with positive PET-CT scans but negative BMB had focal BM involvement on PET-CT scan.Conclusions: Although limited by small sample size, our data suggests that PET-CT scan is particularly adept at detecting BM involvement in patients with DLBCL and may detect focal BM involvement missed by BMB. The high sensitivity of PET-CT scan may lend support to clinicians foregoing BMB in patients with newly diagnosed lymphoma if imaging with PET-CT scan does not show involvement of the BM by lymphoma. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Diagnostic Value of Whole-Body MRI Short Protocols in Bone Lesion Detection in Multiple Myeloma Patients.

The aim of the study is to evaluate the effectiveness of short whole-body magnetic resonance imaging (WBMRI) protocols for the overall assessment of bone marrow involvement in patients with multiple myeloma (MM), in comparison with standard whole-body MRI protocol. Patients with biopsy-proven MM, who underwent a WBMRI with full-body coverage (from vertex to feet) were retrospectively enrolled. WBMRI images were independently evaluated by two expert radiologists, in terms of infiltration patterns (normal, focal, diffuse, and combined), according to location (the whole skeleton was divided into six anatomic districts: skull, spine, sternum and ribs, upper limbs, pelvis and proximal two-thirds of the femur, remaining parts of lower limbs) and lytic lesions number (<5, 5–20, and >20). The majority of patients showed focal and combined infiltration patterns with bone lesions predominantly distributed in the spine and pelvis. As skull and lower limbs are less frequently involved by focal bone lesions, excluding them from the standard MRI protocol allows to obtain a shorter protocol, maintaining a good diagnostic value.

Whole Body Low Dose Computed Tomography (WBLDCT) Can Be Comparable to Whole-Body Magnetic Resonance Imaging (WBMRI) in the Assessment of Multiple Myeloma.

Aim of the study is to compare the agreement between whole-body low-dose computed tomography (WBLDCT) and magnetic resonance imaging (WBMRI) in the evaluation of bone marrow involvement in patients with multiple myeloma (MM). Patients with biopsy-proven MM, who underwent both WBLDCT and WBMRI were retrospectively enrolled. After identifying the presence of focal bone involvement (focal infiltration pattern), the whole skeleton was divided into five anatomic districts (skull, spine, sternum and ribs, pelvis, and limbs). Patients were grouped according to the number and location of the lytic lesions (<5, 5–20, and >20) and Durie and Salmon staging system. The agreement between CT and MRI regarding focal pattern, staging, lesion number, and distribution was assessed using the Cohen Kappa statistics. The majority of patients showed focal involvement. According to the distribution of the focal lesions and Durie Salmon staging, the agreement between CT and MRI was substantial or almost perfect (all κ > 0.60). The agreement increased proportionally with the number of lesions in the pelvis and spine (κ = 0.373 to κ = 0.564, and κ = 0.469–0.624), while for the skull the agreement proportionally decreased without reaching a statistically significant difference (p > 0.05). In conclusion, WBLDCT showed an almost perfect agreement in the evaluation of focal involvement, staging, lesion number, and distribution of bone involvement in comparison with WBMRI.

DETECTION OF DISSEMINATED TUMOR CELLS IN THE BONE MARROW OF PATIENTS WITH NON-SMALL CELL LUNG CANCER

Introduction. There is evidence that disseminated tumor cells (DOCs) in the bone marrow (BM) are precursors of subsequent distant metastases. The detection of DOCs in non-small cell lung cancer (NSCLC) will provide important information about the features of metastasis, as well as the possibilities of identifying new targets for the treatment of NSCLC. Purpose of the study is to evaluate the possibility of detection DOCs in BM and to identify the frequency of BM involvement in patients with NSCLC. Materials and methods . Morphological and immunological methods studied 62 BM samples from patients with NSCLC. DOCs analysis was performed using flow cytometry (FACSCanto II, USA, Kaluza Analysis v 2.1 software), monoclonal antibodies to CD45, cytokeratins directly labeled with various fluorochromes were used. Results . DOCs (EPCAM+CD45–) in the BM were found in 43.5 % of patients (threshold level: 1 cell per 10 million myelocaricytes). The presence of DOCs did not correlate with tumor size, lymph node status, stage of the tumor process. The highest detection rates of DOCs were observed at stages IA and IIA: 60.7 % (3/5) and 58.3 % (7/12) respectively. BM involvement in adenocarcinoma was observed in 45 % (15/33) cases, in squamous cell carcinoma – in 37 % (10/27) samples (p = 0.501). It was found that DOCs are more often detected in more differentiated tumors (p = 0.023). Significant correlations between the presence of DOCs in the BM and myelogram parameters have not been established. A decrease in the number of granulocyte germ cells was observed in 4 % of BM involvement (p = 0.036). Conclusion. The possibility of detecting DOCs in the BM of NSCLC patients has been established. BM involvement was 43.5 %. DOCs are detected even in the early stages of NSCLC. Relationship between BM involvement and the degree of tumor differentiation was found. More frequent BM involvement was observed in adenocarcinoma compared with squamous cell carcinoma of the lung. Compliance with patient rights and principles of bioethics The study protocol was approved by the biomedical ethics committee of N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia. All patients gave written informed consent to participate in the study.

Diagnosis and Prognosis Value of Bone Marrow Aspirate Detection for the Bone Marrow Involvement in Non-Hodgkin's Lymphoma Patients

To compare and evaluate the sensitivity, specificity, and prognostic value of various assays for bone marrow involvement in patients with non-Hodgkin's lymphoma (NHL). A total of 351 patients with NHL who underwent concurrent bone marrow biopsy in Third Hospital of Peking University from January 2013 to November 2017 were selected. Bone marrow biopsy (BMB), flow cytometry (FCM), gene rearrangement detection, and bone marrow morphology examination were performed for evaluation of bone marrow involvement. Bone marrow biopsy was used as the gold standard, the sensitivity and specificity of FCM, gene rearrangement and bone marrow morphology of bone marrow aspirate were analyzed, and their ROC curves were drawn. In the survival analysis of 77 patients with NHL, the overall survival (OS) time, progression-free survival (PFS) time, and complete remission rate (CRR) were counted. The survival of patients in the FCM positive group, the gene rearrangement positive group, the positive control group (BMB positive group) and the negative control group were compared. The detection rate of flow cytometry and gene rearrangement of bone marrow aspirate both were higher than that of bone marrow biopsy and bone marrow morphological examination, showing better diagnostic efficacy. The sensitivity of the combined method of flow cytometry and gene rearrangement was 82.5%, while the specificity was 90% and the AUC was 0.863. The gene rearrangement detection of bone marrow aspirate possessed the role suggesting the poor prognosis for NHL patients. The 3-year survival rate of patients in the gene rearrangement-positive group (RG group) was lower than that of patients in the no-bone involvement group (All negative group) (P＜0.05). Although the survival curve of patient in RG group was not significantly different from that of patients in All negative group (P＜0.1), it still showed a poor prognosis for NHL patients. And the significance of predicting death risk was reflected in Cox regression model (P＜0.05). There was no statistical difference in the prognosis of patients in the FCM-positive group (FCM group). In the bone marrow aspirate tests, flow cytometry and gene rearrangement detection have good diagnostic efficiency, and gene rearrangement can suggest the prognosis of patients. The combined detection efficacy of two methods is better.