Assessment Of Bone Marrow Infiltration Research Articles

Quantitative assessment of bone marrow infiltration and characterization of tumor burden using dual-layer spectral CT in patients with multiple myeloma.

The aim of the study was to evaluate whether virtual calcium subtraction (VNCa) image extracted from dual-layer spectral CT could estimate bone marrow (BM) infiltration with MRI as the reference standard and characterize tumor burden in patients with multiple myeloma (MM). Forty-seven patients with newly diagnosed MM were retrospectively enrolled. They had undergone whole-body low-dose dual-layer spectral CT (DLCT) and whole-body MRI within one week. VNCa images with calcium-suppressed (CaSupp) indices ranging from 25 to 95 at an interval of 10 and apparent diffusion coefficient (ADC) maps were quantitatively analyzed on vertebral bodies L1-L5 at the central slice of images. The optimal combination was selected by correlation analysis between CT numbers and ADC values. Then, it was used to characterize tumor burden by correlation analysis and receiver operating characteristic (ROC) curves analysis, including plasma cell infiltration rate (PCIR), high serum-free light chains (SFLC) ratio and the high-risk cytogenetic (HRC) status. The most significant quantitative correlation between CT numbers of VNCa images and ADC values could be found at CaSupp index 85 for averaged L1-L5 (r = 0.612, p < 0.001). It allowed quantitative evaluation of PCIR (r = 0.835, p < 0.001). It could also anticipate high SFLC ratio and the HRC status with area under the curve (AUC) of 0.876 and 0.760, respectively. The VNCa measurements of averaged L1-L5 showed the highest correlation with ADC at CaSupp index 85. It could therefore be used as additional imaging biomarker for non-invasive assessment of tumor burden if ADC is not feasible.

Comparison of bone marrow biopsy and fluorodeoxyglucose-positron emission tomography for the assessment of bone marrow infiltration in children with Hodgkin's lymphoma.

To compare bone marrow biopsy (BMB) with [18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (PET/CT) imaging in the demonstration of bone marrow involvement in children with Hodgkin's Lymphoma (HL) and to investigate the effectiveness of PET/CT imaging and thus the necessity for BMB at staging. Pediatric patients with HL, who underwent both bilateral iliac BMB and PET/CT imaging at disease staging were retrospectively analyzed. In determining bone marrow involvement (BMinv), BMB and/or first/follow-up PET/CT imaging were eligible for review. Fifty-six patients were included. BMinv was detected by PET/CT imaging in 6/56 (10.7%), whereas the proportion was 3/56 (5.3%) in BMB specimens. Bone marrow biopsies and PET/CT images were concordant in 53/56 (94.6%) patients with BMB specimens missing three cases of BMinv detected by PET/CT. When diagnostic accuracy was calculated, sensitivity, specificity, positive predictive value and negative predictive values for PET/CT were 100%, 100%, 100%, 100%, respectively, and the same values for BMB were 50%, 100%, 100%, 94.3%, respectively. The results of PET/CT and BMB for staging of pediatric HL patients were compatible, and PET/CT imaging was found to provide high diagnostic performance in determining BMinv. In keeping with earlier research, the current study showed that BMB may not be necessary in every patient at staging, and should be reserved for cases where PET/CT is inconclusive.

Feasibility of artificial intelligence\u2013supported assessment of bone marrow infiltration using dual-energy computed tomography in patients with evidence of monoclonal protein \u2014 a retrospective observational study

ObjectivesTo demonstrate the feasibility of an automated, non-invasive approach to estimate bone marrow (BM) infiltration of multiple myeloma (MM) by dual-energy computed tomography (DECT) after virtual non-calcium (VNCa) post-processing.MethodsIndividuals with MM and monoclonal gammopathy of unknown significance (MGUS) with concurrent DECT and BM biopsy between May 2018 and July 2020 were included in this retrospective observational study. Two pathologists and three radiologists reported BM infiltration and presence of osteolytic bone lesions, respectively. Bone mineral density (BMD) was quantified CT-based by a CE-certified software. Automated spine segmentation was implemented by a pre-trained convolutional neural network. The non-fatty portion of BM was defined as voxels > 0 HU in VNCa. For statistical assessment, multivariate regression and receiver operating characteristic (ROC) were conducted.ResultsThirty-five patients (mean age 65 ± 12 years; 18 female) were evaluated. The non-fatty portion of BM significantly predicted BM infiltration after adjusting for the covariable BMD (p = 0.007, r = 0.46). A non-fatty portion of BM > 0.93% could anticipate osteolytic lesions and the clinical diagnosis of MM with an area under the ROC curve of 0.70 [0.49–0.90] and 0.71 [0.54–0.89], respectively. Our approach identified MM-patients without osteolytic lesions on conventional CT with a sensitivity and specificity of 0.63 and 0.71, respectively.ConclusionsAutomated, AI-supported attenuation assessment of the spine in DECT VNCa is feasible to predict BM infiltration in MM. Further, the proposed method might allow for pre-selecting patients with higher pre-test probability of osteolytic bone lesions and support the clinical diagnosis of MM without pathognomonic lesions on conventional CT.Key Points• The retrospective study provides an automated approach for quantification of the non-fatty portion of bone marrow, based on AI-supported spine segmentation and virtual non-calcium dual-energy CT data.• An increasing non-fatty portion of bone marrow is associated with a higher infiltration determined by invasive biopsy after adjusting for bone mineral density as a control variable (p = 0.007, r = 0.46).• The non-fatty portion of bone marrow might support the clinical diagnosis of multiple myeloma when conventional CT images are negative (sensitivity 0.63, specificity 0.71).

Diagnostic performance of 18F-2-fluoro-2-deoxy-D-glucose PET/computerized tomography in identifying bone marrow infiltration in new patients with diffuse large B-cell lymphoma and Hodgkin lymphoma.

To compare between F-2-fluoro-2-deoxy-D-glucose PET/computerized tomography (F-FDG PET/CT) and routine iliac bone marrow biopsy (BMB) in assessment of bone marrow infiltration (BMI) in Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL) patients at initial presentation. A retrospective analysis of 138 patients (50 Hodgkin lymphomas, 88 DLBCLs). The study included 70 males and 68 females with median age of 43 years. All patients underwent F-FDG PET/CT and iliac crest BMB before treatment. Any focal or patchy FDG uptake in the bone marrow, superior-to hepatic uptake was interpreted as abnormal with or without corresponding CT changes. Treatment response was evaluated clinically with each cycle of chemotherapy, radiologically after three cycles and at the end of treatment. The overall diagnostic performance showed significant higher sensitivity of F-FDG PET/CT than that of BMB (73.9 versus 62.5%, P = 0.046), while the specificity was higher in BMB than in F-FDG PET/CT (100% in BMB versus 93.5% in F-FDG PET/CT). In Hodgkin lymphoma, sensitivity, negative predictive value (NPV) and accuracy were significantly higher in F-FDG PET/CT compared with BMB, being 87.5, 94.4 and 96% versus 50, 81 and 84% (P = 0.02, 0.03, 0.04, respectively). However, for DLBCL patients, almost comparable results were found between both tests in terms of sensitivity, NPV and accuracy (66.7, 83.9 and 81.8% versus 68.8, 84.9 and 88.6%, respectively). After PET/CT scan, 12 patients (8.6%) were upstaged to stage IV, eight of them were negative by BMB. F-FDG PET/CT seemed to be an excellent diagnostic test in assessment of BMI at initial assessment and staging of Hodgkin lymphoma and DLBCL patients.

Gaucher disease status and treatment assessment: pilot study using magnetic resonance spectroscopy bone marrow fat fractions in pediatric patients

ObjectiveTo assess magnetic resonance spectroscopy (MRS) bone marrow fat fractions' ability to discern between untreated Gaucher disease patients and healthy controls based on assessment of bone marrow infiltration and evaluate response to enzyme replacement therapy (ERT) on serial imaging. MethodsThis retrospective case-controlled study compared conventional MRI and bone marrow MRS findings in six pediatric and young adult Gaucher disease patients with age- and sex-matched controls, examining femoral neck and lumbar spine bone marrow fat fractions and bone marrow burden (BMB) scores. Separate analysis of six patients with serial imaging on ERT was performed with analysis of fat fractions, BMB scores, organ volumes, and serum chitotriosidase. ResultsUntreated patients had significantly lower femoral and lumbar spine fat fractions than controls (0.32 versus 0.67, p = 0.041 and 0.17 versus 0.34, p = 0.041, respectively). Total BMB scores were significantly higher in patients (8.0 versus 3.5, p = 0.015). In patients on ERT with average follow-up of 3.5 years, femoral neck fat fraction was the sole significant predictor of treatment duration (R square: 0.804, p < 0.001) when adjusted for age. Femoral neck fat fraction also correlated with lumbar spine fat fraction, liver volume and chitotriosidase (p < 0.05). MRS test-retest reliability was excellent (Pearson correlations: 0.96, 0.99; p-values <0.001). BMB inter-rater reliability was good overall with an intra-class correlation coefficient of 0.79 for total score, although lumbar spine score reliability was poor at 0.45. ConclusionMRS-derived bone marrow fat fractions appear capable of detecting Gaucher disease severity and monitoring treatment-related changes as a predictor of ERT duration in pediatric and young adult patients.

1013PD - A comparative study of 18F-FDG PET/CT with bilateral bone marrow trephine biopsy for assessment of bone marrow infiltration by lymphoma

1013PD - A comparative study of 18F-FDG PET/CT with bilateral bone marrow trephine biopsy for assessment of bone marrow infiltration by lymphoma

Assessment of Bone Marrow Infiltration and Minimal Residual Disease by Multidimensional Flow Cytometry in Patients With Diffuse Large B-Cell Lymphoma (DLBCL)

Assessment of Bone Marrow Infiltration and Minimal Residual Disease by Multidimensional Flow Cytometry in Patients With Diffuse Large B-Cell Lymphoma (DLBCL)

The assessment of bone marrow infiltration with 18FDG-PET in non-haematopoietic solid tumors

The assessment of bone marrow infiltration with 18FDG-PET in non-haematopoietic solid tumors

Evaluation of Bone Marrow Infiltration in Non-Neuropathic Gaucher Disease Patients with Use of Whole-Body MRI--A Retrospective Data Analysis.

To evaluate whole-body magnetic resonance imaging (WB-MRI) for the assessment of bone marrow infiltration in patients with confirmed Gaucher disease type 1 under long-term enzyme replacement therapy (ERT). This retrospective data analysis included 38 patients in two subgroups. Group A: 10 females, 9 males, 15-29 years, mean age 22 years and Group B: 11 females, 8 males, 29-77 years, mean age 49 years, all treated with alglucerase or imiglucerase for at least 12.5 years. Whole-body MRI was carried out in all patients using a standard MRI protocol. Two radiologists assessed all MR images retrospectively with the use of three different MRI score systems: The bone marrow burden (BMB) score, the Düsseldorf-Gaucher score (DGS) and the vertebra disc ratio (VDR). As a clinical component, severity score index type 1 (GD-DS3) was determined. In both groups the MR scores showed low to moderate pathologic levels but no statistically significant difference was found between both groups. The median scores in group A/group B were 7.00/9.00 for the BMB score (p=0.07), 4.00/3.00 for the DGS score (p=0.062) and 1.54/1.62 for the VDR score (p=0.267). The GD-DS3 score was statistically significantly different between both groups (1.6/3.9, p=0.000) and osseous Gaucher disease complications were only found in group B. Bone marrow involvement and typical clinical manifestations are reduced to a minimum, when ERT starts immediately after the confirmed diagnosis of Gaucher disease type 1. The applied MR scores are useful markers to control bone marrow infiltration under enzyme replacement therapy in older patients. Pathologic MR scores in young patients may reflect postponed fat conversion of the juvenile bone marrow. This issue has to be examined in further studies. Whole-body MRI is valuable for the staging of Gaucher disease type 1. Osseous complications are reduced to a minimum in early treated patients. MR score systems have to be adjusted in young Gaucher patients.

Correlation of FDG-PET-CT with Bone Marrow Aspiration and Biopsy at the Initial Staging in Follicular Lymphoma: Can We Omit Bone Marrow Biopsy in Some?

Introduction: The role of FDG PET-CT in follicular lymphoma is limited to accurate assessment of disease extent in early stage patients and selection of biopsy site in cases of suspected high- grade transformation. Despite the known FDG avidity of follicular lymphoma, FDG PET-CT has not yet been included as part of standard staging procedures in these patients. FDG PET-CT has shown significant correlation with bone marrow biopsy in Hodgkin and diffuse large B-cell lymphomas. In this retrospective analysis we have assessed the correlation of PET-CT with that of bone marrow biopsy, the reference standard for assessment of bone marrow infiltration in follicular lymphoma.Methods: We retrospectively analyzed electronic medical records and database of patients with newly diagnosed follicular lymphoma registered at Tata Memorial Centre from July 2009 to Jun 2014, who underwent complete staging workup as per the current recommendations along with whole body 18FDG-PET/CT. The demographic features, performance status, stage, LDH, nodal sites, haemoglobin, follicular lymphoma international prognostic index (FLIPI), FDG PET-CT findings (bone marrow involvement, pattern of involvement- focal or diffuse, sites of marrow involvement, liver and spleen uptake, SUVmax of most FDG avid lesion) and bone marrow aspiration/biopsy (morphology, immunohistochemistry and immunophenotyping on aspirate, where available) findings were recorded. Focal uptake in marrow on baseline PET-CT was considered as marrow involvement if post therapy PET-CT showed resolution of these lesions. The sensitivity, specificity, negative and positive predictive value of PET-CT in detecting bone marrow infiltration was assessed taking bone marrow biopsy as gold standard. The factors responsible for discordant results were analyzed.Results: A total of 54 patients (males-38, females-16) were included in analysis with median age of 50 years, (range 22-73 years). At diagnosis 83% (45 patients) had stage III or IV disease and 57% patients had high-risk FLIPI score. Approximately 88% patients had good performance status (ECOG-<2). Bone marrow showed infiltration in approximately 60% (32 patients) on biopsy and immunophenotyping. PET-CT showed bone marrow involvement in 18 patients (focal-12, diffuse -6). In 4 patients with focal PET-CT positivity, bone marrow was uninvolved. However, post therapy these lesions showed resolution, thus confirming the presence of disease pretherapy. The sensitivity, specificity, positive and negative predictive value of PET/CT with respect to biopsy was 43.7%, 81.2%, 77.8% and 50% respectively. However, if we include the above mentioned 4 cases as true positives, then specificity and positive predictive value improves to 100% each. In addition, PET-CT could accurately predict absence of bone marrow involvement in stage I and stage II disease (100% concordance). The median SUVmax of most FDG avid lesion was 13.1 (5.25-34.93). However the SUVmax did not correlate with grade of lymphoma as the node biopsy was not done based on PET-CT results.Conclusion: This study shows that in patients with advanced stage follicular lymphoma bone marrow biopsy can be omitted if PET-CT shows focal or diffuse bone marrow uptake. Similarly, patients with early stage disease with no bone marrow uptake on PET-CT can be spared from bone marrow biopsy. DisclosuresNo relevant conflicts of interest to declare.

Assessment of bone marrow infiltration diagnosed by flow cytometry in canine large B cell lymphoma: Prognostic significance and proposal of a cut-off value

The aims of this study were to assess the prognostic significance of bone marrow (BM) infiltration in canine large B cell lymphoma (LBCL) and to establish cut-off values for designating the BM as infiltrated by lymphoid blasts. The degree of BM infiltration by large CD21 positive cells in dogs with LBCL was assessed by flow cytometry (FC) and related to time to progression (TTP) and lymphoma-specific survival (LSS). Forty-six dogs were prospectively enrolled, staged and treated with a dose-intense chemotherapeutic protocol. BM infiltration was directly correlated with peripheral blood infiltration (P=0.001), high lactate dehydrogenase activity (P=0.0024) and substage b disease (P<0.001). In the univariate analysis, there was a significant association between BM infiltration diagnosed by FC and both TTP (P=0.001) and LSS (P<0.001). Substage was the only factor associated with TTP in the multivariate analysis (P=0.002), whereas substage (P<0.001) and anaemia (P=0.008) were associated with LSS. A cut-off of 3% BM infiltration had the strongest prognostic value, since it discriminated between dogs with a poorer prognosis (median TTP 69days; median LSS 155days) and dogs with a better prognosis (median TTP 149days; median LSS 322days). BM analysis is an essential step in the staging of LBCL. The presence of BM infiltration by FC at diagnosis is a negative prognostic indicator in canine LBCL.

Intravoxel incoherent motion imaging for assessment of bone marrow infiltration of monoclonal plasma cell diseases

Modern imaging techniques have demonstrated that monoclonal plasma cell diseases infiltrate the bone marrow in a diffuse, focal, mixed pattern. While focal lesions can be easily counted and measured, the diffuse lesions of the infiltration are hard to assess. We therefore investigated 31 patients with monoclonal plasma cell diseases of all stages with intravoxel incoherent motion imaging of the same region of the pelvis from where afterwards a biopsy was obtained. We found a significant correlation between plasma cell percentage in bone marrow histology and the imaging parameters "apparent diffusion coefficient" and the diffusion coefficient D. Furthermore, those parameters correlated with other factors of disease activity, e.g., monoclonal protein, hemoglobin, and immunoparesis. In summary, we found that the non-invasively acquired imaging parameters correlated with the degree of plasma cell infiltration in the bone marrow.

Aspectos óseos de la enfermedad de Gaucher

The exposition aims, is to review the pathophysiological mechanisms of bone marrow involvement and the patterns of marrow infiltration by Gaucher cells. We have reviewed the different methods of assessment of bone marrow infiltration and its temporal development. Qualitative methods include simple radiography, magnetic resonance imaging (MRI), computed tomography (CT) and radioisotope. The simple radiography is the basic element, but its sensitivity is limited and only allows for assessing changes and trabecular bone remodeling MRI allows us to appreciate the bone marrow infiltration, detection of complications and response to therapy. Radioisotopes can contribute to the differential diagnosis of osteomyelitis and bone crises. Among the quantitative methods are the QCSI (quantitative chemical shift imaging) and the dual-energy X-ray absorptiometry (DEXA), as well as new quantitative techniques of CT, MRI and ultrasound densitometry. The QCSI performed an assessment of fat content of bone marrow in the spine. DEXA quantifies bone density by measuring the attenuation coefficient. The semiquantitative methods have various “scores” to establish criteria for generalized bone disease endpoints of disease progression and response to therapy.

Whole-Body Imaging of Bone Marrow

For bone marrow screening, multimodality algorithms including conventional radiographs, bone scintigraphy, multislice computed tomography CT (MS-CT) scan, and dedicated magnetic resonance imaging (MRI) are widely established in clinical routine. Although radiographs are used as a basic imaging procedure for clarification of suspected focal bone pathologies, low sensitivity has been reported for the detection of limited osteolytic bone marrow destruction. Therefore, skeletal scintigraphy often is used as a more sensitive and integrated method in patients with suspected malignant bone marrow disease. MS-CT scan is the method of choice in the assessment of bone stability and allows for evaluation of fracture risk. Hybrid imaging concepts, such as positron emission tomography-computed tomography (PET-CT) scan, have been established as an effective tool for the detection of skeletal metastases, using the additional metabolic information of a PET scan for the assessment of tumor viability and therapy response. MRI is an imaging technique that allows direct visualization of bone marrow components with high spatial resolution. The unique soft-tissue contrast of MRI enables precise assessment of bone marrow infiltration before osteolytic changes become visible in MS-CT or metabolic changes occur in bone scintigraphy or a PET scan. Furthermore it can depict tumor expansion into adjacent paraosseous structures, such as the spinal canal. The development of multichannel whole-body MRI (WB-MRI) systems has enabled bone marrow screening without use of ionizing radiation at high diagnostic accuracy. Parallel imaging techniques in combination with global matrix coil concepts, as well as the introduction of high-field whole-body scanners, have substantially reduced acquisition times without compromises in spatial resolution. WB-MRI has successfully been applied for screening of bone metastases and hematologic bone marrow diseases, like multiple myeloma, lymphoma, and histiocytosis X. Furthermore, it has recently been proposed for the assessment of primarily benign bone diseases predisposing for malignancy (e.g., multiple cartilaginous exostoses). This article provides an overview of state-of-art whole-body imaging of the bone marrow and highlights present and potential future applications, especially in the field of WB-MRI.

Whole-body imaging of the musculoskeletal system: the value of MR imaging.

In clinical practice various modalities are used for whole-body imaging of the musculoskeletal system, including radiography, bone scintigraphy, computed tomography, magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT). Multislice CT is far more sensitive than radiographs in the assessment of trabecular and cortical bone destruction and allows for evaluation of fracture risk. The introduction of combined PET-CT scanners has markedly increased diagnostic accuracy for the detection of skeletal metastases compared with PET alone. The unique soft-tissue contrast of MRI enables for precise assessment of bone marrow infiltration and adjacent soft tissue structures so that alterations within the bone marrow may be detected before osseous destruction becomes apparent in CT or metabolic changes occur on bone scintigraphy or PET scan. Improvements in hard- and software, including parallel image acquisition acceleration, have made high resolution whole-body MRI clinically feasible. Whole-body MRI has successfully been applied for bone marrow screening of metastasis and systemic primary bone malignancies, like multiple myeloma. Furthermore, it has recently been proposed for the assessment of systemic bone diseases predisposing for malignancy (e.g., multiple cartilaginous exostoses) and muscle disease (e.g., muscle dystrophy). The following article gives an overview on state-of-the-art whole-body imaging of the musculoskeletal system and highlights present and potential future applications, especially in the field of whole-body MRI.

MRI and 18FDG-PET in the assessment of bone marrow infiltration of the spine in cancer patients

The aim of this study was to evaluate the diagnostic value of MRI and (18)FDG-PET in bone marrow infiltration of the spine due to metastases of solid tumours and lymphoma in cancer patients. In 35 cancer patients (solid tumours n = 26, lymphoma n = 9) MRI of the spine and (18)FDG-PET were reviewed and the detectability of metastases, infiltration of the spine, extent of disease, and therapeutic implications were compared. In 8/35 cases (23%) imaging technique showed concordantly no bone marrow infiltration. In 19/35 patients (54%), both MRI and (18)FDG-PET revealed bone marrow infiltration of the axial skeleton. In 12/19 patients (63%), MRI showed more extensive disease which lead to subsequent therapy. The imaging findings of MRI and (18)FDG-PET were discordant in 8/35 cases (23%). (18)FDG-PET was false positive in two patients. In six patients, (18)FDG-PET failed to detect bone metastases and bone marrow infiltration of the spine, which was detected by MRI and proven by clinical follow-up with subsequent therapy in two cases. MRI is more sensitive and specific than (18)FDG-PET detecting bone marrow metastases and infiltration of the spine and has a great impact in staging cancer patients.

A comparison of flow cytometry, bone marrow biopsy, and bone marrow aspirates in the detection of lymphoid infiltration in B cell disorders

Aims: To evaluate the diagnostic value of bone marrow aspirates, trephine biopsies (BMB), and flow cytometry (FC) in the assessment of bone marrow infiltration in chronic lymphoid disorders. Methods: Investigations...

Bone marrow assessment in B‐cell chronic lymphocytic leukaemia: aspirate or biopsy? A comparative study in 258 patients

To evaluate the relative merits and prognostic value of bone marrow aspirate and bone marrow biopsy in the assessment of bone marrow infiltration in B-cell chronic lymphocytic leukaemia (CLL), two observers independently reviewed the percentage of lymphocytes in bone marrow aspirate (lymphocytic infiltration, LI) and the bone marrow histological pattern (BMP) in 258 patients. The inter-observer reproducibility and agreement was higher for BMP than for LI. BMP was an independent prognostic factor for survival in the whole series, whereas LI only had independent predictive value in stage A patients. In the entire series, disease progression was predicted by either BMP and LI, whereas in stage A patients only by BMP. Regarding low-risk CLL (smouldering CLL or A"1 substage), BMP led to a more reproducible identification of these clinical forms than LI. In conclusion, although both BMP and LI are of value to estimate bone marrow infiltration in CLL and to predict the outcome of the disease, BMP is more reliable and reproducible than LI.

Assessment of bone marrow infiltration in B-cell non-Hodgkin's lymphoma (NHL)

A study is currently in progress at St Bartholomew's Hospital in which patients with B-cell lymphoma receive cyclophosphamide and total body irradiation supported by autologous bone marrow transplantation. The marrow is being treated in vitro with the monoclonal antibody anti-B1 (Coulter Immunology) and baby rabbit complement (PelFreez) before re-infusion (Rohatiner et al., 1986). Anti-B1 is an antibody that defines a 35 kDa B-cell differentiation antigen (CD20) which is expressed on more than 95% of normal B-cells isolated from peripheral blood