Bone Marrow Infiltration In Patients Research Articles

Direct comparison of bone marrow biopsy and PET/CT for the detection of bone marrow infiltration in patients with non-Hodgkin lymphoma: a meta-analysis.

The diagnostic utility of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) compared to bone marrow biopsy (BMB) in patients with non-Hodgkin lymphoma (NHL) remained to be confirmed. This study aimed to compare BMB and PET/CT for bone marrow infiltration (BMI) in patients with NHL. PubMed, Embase, and the Cochrane library were searched for papers published up to October 2021. The outcomes were the true positive and negative and false positive and negative rates for BMB and PET/CT. The summarized sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratios (DOR) were calculated. Thirteen studies with a total of 2396 patients were included. Significant differences are observed between BMB and PET/CT for sensitivity (relative ratio: 0.749; 95% CI: 0.586-0.956; P=0.020) and NLR (relative ratio: 1.839; 95% CI: 1.106-3.058; P=0.019), but not for specificity (P=0.819), PLR (P=0.802), and DOR (P=0.150). The summary area under the receiver operating characteristic curves for BMB is 0.692 (SE: 0.170) and 0.977 (SE: 0.021) for PET/CT. PET/CT presents a better sensitivity and NLR for the detection of BMI in patients with NHL, whereas no differences are found regarding specificity, PLR, and DOR compared with BMB.

Clonal Hematopoiesis and Bone Marrow Infiltration in Patients With Follicular Helper T-Cell Lymphoma of Angioimmunoblastic Type

Follicular helper T-cell (TFH) lymphoma harbors recurrent mutations of RHOAG17V, IDH2R172, TET2, and DNMT3A. TET2 and DNMT3A mutations are the most frequently affected genes in clonal hematopoiesis (CH). The aim of our study was to investigate the frequency of CH in bone marrow biopsies (BMB) of TFH/angioimmunoblastic T-cell lymphoma (TFH-AITL) patients and its association with myeloid neoplasms. A total of 29 BMB from 22 patients with a diagnosis of TFH–AITL were analyzed by next-generation sequencing (NGS) with a custom panel. Morphologically, 5 BMB revealed that TFH–AITL infiltrates of >5% of bone marrow (BM) cellularity confirmed in 4 cases by NGS-based T-cell clonality. IDH2R172 was demonstrated only in 1 (3%) of 29, and RHOAG17V in 2 (7%) of 29 samples. TET2 and DNMT3A were identified in 24 (83%) of 29 and 17 (59%) of 29 BMB, respectively. In the parallel lymph node the frequencies of mutations were 27% (IDH2R172), 64% (RHOAG17V), 86% (TET2), and 50% (DNMT3A). TET2 and/or DNMT3A mutations identical in lymph node and BMB were present in 18 (82%) of 22 patients, regardless of BM infiltration. In 3 cases the CH mutations were detected 13, 41, and 145 months before TFH–AITL diagnosis. Cases with TET2/DNMT3A mutations and BM variant allele frequencies >40% (7/18, 39%) showed lower blood counts. However, only low platelet count was statistically significant (P = .024). Myeloid neoplasms and/or myelodysplastic syndrome-related mutations were identified in 4 cases (4/22; 18%); all with high TET2 variant allele frequencies (>40%; P = .0114). In conclusion, CH is present in 82% of TFH–AITL and can be demonstrated up to 145 months before TFH–AITL diagnosis. NGS T-cell clonality analysis is an excellent tool to confirm TFH–AITL BM infiltration. Concurrent myeloid neoplasms were identified in 18% of the cases and were associated with TET2 mutations with high allelic burden (>40%). We demonstrated that myeloid neoplasms might occur simultaneously or precede the diagnosis of TFH lymphoma.

Comparison of reduced field-of-view DWI and conventional DWI techniques for the assessment of lumbar bone marrow infiltration in patients with acute leukemia.

To compare the imaging quality, apparent diffusion coefficient (ADC), and the value of assessing bone marrow infiltration between reduced field-of-view diffusion-weighted imaging (r-FOV DWI) and conventional DWI in the lumbar spine of acute leukemia (AL). Patients with newly diagnosed AL were recruited and underwent both r-FOV DWI and conventional DWI in the lumbar spine. Two radiologists evaluated image quality scores using 5-Likert-type scales qualitatively and measured signal-to-noise ratio (SNR), contrast-to-noise (CNR), signal intensity ratio (SIR), and ADC quantitatively. Patients were divided into hypo- and normocellular group, moderately hypercellular group, and severely hypercellular group according to bone marrow cellularity (BMC) obtained from bone marrow biopsies. The image quality parameters and ADC value between the two sequences were compared. One-way analysis of variance followed by LSD post hoc test was used for the comparisons of the ADC values among the three groups. The performance of ADC obtained with r-FOV DWI (ADCr) and conventional DWI(ADCc) in evaluating BMC and their correlations with BMC and white blood cells (WBC) were analyzed and compared. 71 AL patients (hypo- and normocellular: n=20; moderately hypercellular: n=19; severely hypercellular: n=32) were evaluated. The image quality scores, CNR, SIR, and ADC value of r-FOV DWI were significantly higher than those of conventional DWI (all p<0.05), and the SNR of r-FOV DWI was significantly lower (p<0.001). ADCr showed statistical differences in all pairwise comparisons among the three groups (all p<0.05), while ADCc showed significant difference only between hypo- and normocellular group and severely hypercellular group (p=0.014). The performance of ADCr in evaluating BMC (Z=2.380, p=0.017) and its correlations with BMC (Z=-2.008, p = 0.045) and WBC (Z=-2.022, p = 0.043) were significantly higher than those of ADCc. Compared with conventional DWI, r-FOV DWI provides superior image quality of the lumbar spine in AL patients, thus yielding better performance in assessing bone marrow infiltration.

Diagnostic and Prognostic Evaluation Value of 18f-FDG PET-CT for Bone Marrow Infiltration in Primary Treated Follicular Lymphoma

Objective ：The purpose of this paper is to evaluate the value of 18F-FDG PET-CT in the diagnosis of bone marrow infiltration in patients with primary treated follicular lymphoma and whether it provides valuable information for staging and prognosis. Methods ：This is a retrospective analysis of 199 hospitalized patients with primary 1-3a follicular lymphoma diagnosed by pathological examination from January 01, 2014 to September 31, 2022 in Fujian Medical University's Union Hospital. The recorded clinical characteristics, bone marrow examination, the result of 18F-FDG PET-CT for bone marrow involvement, treatment regimen, efficacy, and survival status were analyzed. univariate analysis and multivariate analysis were performed for clinical features, laboratory results. Results ： 1.Among the 199 patients with FL , the median age was 54.1 years old, including 88 males and 111 females Stage III-IV patients accounted for 82.9%.The Number in high-risk groups was 70（35.2%）according to FLIPI score and was 33（16.6%）according to FLIPI-2 score. The median OS in all cases was not reached. The cumulative OS rates at 1, 3, and 5 years were 93.5%90.0% and 88.8%,respectively The median PFS in all cases was not reached. The cumulative PFS rates at 1, 3, and 5 years were 87.3%72.0% and 67.8%,respectively. PET-CT images showed increased bone marrow uptake FDG in a total of 42 patients (21.1%), of which 17 patients (8.54%) had focal increased bone marrow uptake FDG (6 unifocal; 3 bifocal; 8 multifocal), 6 patients (3.02%) had focal with diffuse increased bone marrow uptake FDG, and 19 patients (9.55%) had diffuse bone marrow FDG uptake was elevated in 19 patients (9.55%).Bone marrow infiltration was detected by PET-CT alone in 16 patients (8.04%),and by BMB alone in 19 patients (9.54%), and by both PET-CT and BMB in 26 patients (13.63%), Bone marrow infiltration was detected by PET-CT and BMB in a total of 26 patients (13.61%). 45 patients (22.6%) had bone marrow infiltration detected by BMB and 42 patients (21.1%) had bone marrow infiltration detected by PET-CT. Using BMB results as the gold standard for bone marrow infiltration, the paired chi-square design corrected chi-square test yielded c 2=0.11， P=0.735, so it can be considered that the results of the two methods for testing bone marrow infiltration were consistent, and the difference was not statistically significant, and the agreement between PET-CT and BMB diagnostic results was general (Kappa=0.485, P&amp;lt;0.05), using BMB as the gold standard , the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET-CT for detecting bone marrow infiltration were 57.78%, 89.61%, 82.41%, 61.90%, and 87.90%, respectively.The initial staging of 199 patients with FL was based on PET-CT findings of lesions outside of the bone marrow, and 22 patients with initial stage III were up-staged to stage IV by restaging with PET-CT findings of bone marrow lesions; similarly, 1 patient with initial stage II was up-staged to stage IV by restaging with BMB findings of bone marrow lesions, and 23 patients with initial stage III were up-staged to stage IV by BMB. Eight patients with stage III were upstaged to stage IV by PET-CT alone, one patient with stage II and nine patients with stage III were upstaged to stage IV by BMB alone, and 14 patients were upstaged to stage IV by BMB and PET-CT together, making a total of 32 patients upstaged to stage IV by BMB or PET-CT. 5 patients were upstaged to stage IV by BMB and PET-CT. Five patients changed their treatment plan due to up-staging of BMB bone marrow infiltration, and five patients had up-staging of BMB bone marrow infiltration but were unable to change their standard treatment due to symptoms or high tumor load.The result of univariate analysis showed that BMB positivity, PET-CT detection of bone marrow infiltration, Ann Arbor staging based on PET-CT, PET-CT combined with Ann Arbor staging of BMB,were factors associated with OS ( P &amp;lt; 0.05)Multifactorial results showed thatPET-CT detection of bone marrow infiltration were risk factors for OS (P&amp;lt;0.05) Conclusion ： Combined PET-CT and marrow biopsy has higher accuracy than bone marrow biopsy alone.PET-CT detection of bone marrow infiltration were risk factors for OS and was associated with poor prognosis. Keywords: bone marrow biopsy, positron emission tomography/computed tomography，follicular lymphoma, prognostic factor

Diagnostic Efficacy of 18F-FDG PET/CT in Detecting Bone Marrow Infiltration in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma*

ObjectiveDiffuse large B-cell lymphoma (DLBCL) is often associated with bone marrow infiltration, and 2-deoxy-2-(18F) fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has potential diagnostic significance for bone marrow infiltration in DLBCL. MethodsA total of 102 patients diagnosed with DLBCL between September 2019 and August 2022 were included. Bone marrow biopsy and 18F-FDG PET/CT examinations were performed at the time of initial diagnosis. Kappa tests were used to evaluate the agreement of 18F-FDG PET/CT with the gold standard, and the imaging features of DLBCL bone marrow infiltration on PET/CT were described. ResultsThe total detection rate of bone marrow infiltration was not significantly different between PET/CT and primary bone marrow biopsy (P = 0.302) or between the two bone marrow biopsies (P = 0.826). The sensitivity, specificity, and Youden index of PET/CT for the diagnosis of DLBCL bone marrow infiltration were 0.923 (95% CI, 0.759–0.979), 0.934 (95% CI, 0.855–0.972), and 0.857, respectively. Conclusion18F-FDG PET/CT has a comparable efficiency in the diagnosis of DLBCL bone marrow infiltration. PET/CT-guided bone marrow biopsy can reduce the misdiagnosis of DLBCL bone marrow infiltration.

Bone marrow biopsy can be omitted in the diagnostic workup of CNS lymphoma of DLBCL origin: a population-based retrospective study in the PET-CT era

Currently, bone marrow (BM) biopsy (BMB) is recommended in the initial staging of patients with the presumed primary central nervous system (CNS) lymphoma (PCNSL). However, the added value of BMB in the era of positron emission tomography (PET-CT) has been challenged in other lymphoma subtypes. We analyzed BM findings in patients with biopsy-proven CNS lymphoma and a negative PET-CT scan for disease outside CNS. A comprehensive Danish population-based registry search was performed to identify all patients with CNS lymphoma of diffuse large B cell lymphoma (DLBCL) histology with available BMB results and staging PET-CT without systemic lymphoma. A total of 300 patients fulfilled the inclusion criteria. Of them, 16% had a previous history of lymphoma, while 84% were diagnosed with PCNSL. None of the patients had DLBCL in the BM. A minority (8.3%) had discordant BMB findings, mainly low-grade histologies that did not influence treatment choice in any case. In conclusion, the risk of overlooking concordant BM infiltration in patients with CNS lymphoma of DLBCL histology and negative PET-CT scan is negligible. As we did not find any patient with DLBCL in the BMB, our results suggest that BMB can be safely omitted in the diagnostic workup in patients with CNS lymphoma and a negative PET-CT.

Diagnostic Value of Dual-Energy CT Virtual Non-Calcium and Rho/Z Images for Bone Marrow Infiltration in Primary Malignant Bone Tumors

We investigated the diagnostic performance of dual-energy CT (DECT) virtual non-calcium (VNCa) and Rho/Z images for bone marrow infiltration of primary malignant bone tumors (PMBTs). We retrospectively analyzed 65 patients with PMBT who underwent DECT and MRI within 2 weeks. DECT was used to evaluate the presence and extent of marrow involvement surrounding PMBTs using the SCT, VNCa, and Rho/Z images. MRI was used as the reference standard for measurements. CT values of normal and involved bone marrow areas were measured on VNCa images, and Zeff values were measured on Rho/Z images. The statistical methods used were the 2*C chi-square test, ANOVA test, paired samples t test, and diagnostic performance of the different variables were evaluated using receiver operating characteristic curves. VNCa and Rho/Z images showed higher accuracy (91%, 92% vs. 67%) and sensitivity (90%, 92% vs. 69%) than SCT images for diagnosing bone marrow infiltration in patients with PMBT. The maximum longitudinal diameter of tumor involvement measurements was statistically different between VNCa and SCT, Rho/Z and SCT, MRI, and SCT (all p < 0.05, p=0.047, p=0.049, and p=0.023, respectively). The maximum transverse diameter was statistically significant between SCT and MRI, VNCa and MRI, Rho/Z and MRI (all p < 0.05, and p=0.015, and p=0.044, and p=0.047, respectively). The HU or Zeff values based on the area of interest of VNCa and Rho/Z images differed significantly between the normal and infiltrated bone marrow area (p < 0.001). Receiver operating characteristic curve analysis revealed area under the curves of 0.995 and 0.988, respectively, with cut-off values of -31.57 HU and 7.8, and the sensitivity of both was 96.9%. DECT-VNCa and Rho/Z images have good diagnostic value when evaluating bone marrow infiltration in PMBTs.

Prediction Model of Bone Marrow Infiltration in Patients with Malignant Lymphoma Based on Logistic Regression and XGBoost Algorithm.

Objective The prediction model of bone marrow infiltration (BMI) in patients with malignant lymphoma (ML) was established based on the logistic regression and the XGBoost algorithm. The model's prediction efficiency was evaluated. Methods A total of 120 patients diagnosed with ML in the department of hematology from January 2018 to January 2021 were retrospectively selected. The training set (n = 84) and test set (n = 36) were randomly divided into 7 : 3, and logistic regression and XGBoost algorithm models were constructed using the training set data. Predictors of BMI were screened based on laboratory indicators, and the model's efficacy was evaluated using test set data. Results The prediction algorithm model's top three essential characteristics are the blood platelet count, soluble interleukin-2 receptor, and non-Hodgkin's lymphoma. The area under the curve of the logistic regression model for predicting the BMI of patients with ML was 0.843 (95% CI: 0.761~0.926). The area under the curve of the XGBoost model is 0.844 (95% CI: 0.765~0.937). Conclusion The prediction model constructed in this study based on logistic regression and XGBoost algorithm has a good prediction model. The results showed that blood platelet count and soluble interleukin-2 receptor were good predictors of BMI in ML patients.

Wnt signaling pathway inhibitor, sclerostin, correlates with bone pain and bone marrow infiltration in patients with Gaucher disease

Wnt signaling pathway inhibitor, sclerostin, correlates with bone pain and bone marrow infiltration in patients with Gaucher disease

Informative value of whole-body magnetic resonance imaging with diffusion-weighted images for the detection of bone marrow infiltration in patients with multiple myeloma (literature review)

Magnetic resonance imaging (MRI) is increasingly being used to diagnose bone marrow lesions in patients with multiple myeloma (MM). Since 2014, the results of MRI have been included in the updated criteria of the International Myeloma Working Group. The presence of &gt;1 bone marrow lesion larger than or equal to 5 mm on MRI is considered sufficient for the diagnosis of symptomatic MM, requiring initiation of treatment. MRI assessment of bone marrow is also possible with functional sequences such as diffusion-weighted imaging (DWI), which provide additional information about the bone marrow. This article provides an overview of the possibilities of MRI with anatomical sequences and with DWI for diagnosing, monitoring and evaluating the response to treatment in patients with MM. In patients with monoclonal gammopathy of undetermined significance and smoldering myeloma, in some cases, pathological changes in the bone marrow can be detected by MRI. The presence of &gt;1 bone marrow lesion on MRI is a cut-off value as a prognostic factor for the progression of monoclonal gammopathy of undetermined significance or smoldering myeloma to symptomatic MM. In symptomatic MM, there are four patterns of bone marrow infiltration on MRI – focal, diffuse, “salt-and-pepper” infiltration, and combined diffuse and focal pattern, which have prognostic significance. Patients with diffuse pattern of infiltration on MRI had a 3-year overall survival of 35 % versus 92 % in patients with normal MRI bone marrow. During treatment of MM patients, residual bone marrow lesions are often identified on MRI. MRI residual bone marrow lesions increase the risk of MM relapse. In the group of patients who had residual bone marrow lesions on MRI on the 100th day after autologous hematopoietic stem cell transplant, 2-year progression-free survival was 50 % versus 89 % in patients without bone marrow lesions at the same time. The addition of DWI to the scan protocol helps to differentiate persistent focal bone marrow lesions that can lead to MM relapse after the treatment phase. Apparent diffusion coefficient is a quantitative indicator of DWI. MRI can serve as a valuable tool for assessing the treatment response in patients with MM.

Bone marrow burden score is not useful as a follow-up parameter in stable patients with type 1 Gaucher disease after 5 years of treatment

IntroductionGaucher disease (GD) is one of the most prevalent lysosomal disorders, with an estimated incidence of 1 in 40,000 live births worldwide. Skeletal involvement is one of the main features of GD, causing morbidity and impacting long-term quality of life in patients with type 1 GD. ObjectivesTo characterize bone marrow infiltration in patients with type 1 GD followed at the Gaucher Disease Referral Center of Porto Alegre, Brazil, and to assess whether the Bone Marrow Burden score (BMB) correlates with clinical or laboratory parameters. We also evaluated whether the BMB score is a suitable parameter for long-term follow-up of patients with type 1 GD. MethodsAll included patients underwent magnetic resonance imaging for BMB score calculation at baseline, 1 year, and every other year thereafter or as clinically indicated from 2012 to 2018. ResultsThe BMB score tended to decrease during the first 5 years of treatment, at a rate of −1.08 points per year; after the 5-year mark, BMB tended to remain stable. ConclusionsThe BMB score is useful for response monitoring in the first five years of treatment. We recommend that, after 5 years of treatment, MRI for BMB evaluation should only be performed in non-adherent patients or in those who develop symptoms of acute skeletal disease.

Quantitative evaluation of bone marrow infiltration using dual-energy spectral computed tomography in patients with multiple myeloma

To explore the potential value of quantitative parameters derived from dual-energy spectral computed tomography (DESCT) as comparing to the parameters derived from magnetic resonance imaging (MRI) in detecting bone marrow (BM) infiltration and distinguishing different patterns of BM infiltration in patients diagnosed with Multiple myeloma (MM). This study involved 35MM patients and 15 healthy control subjects who had undergone spinal DESCT and MRI. Pattern assignment was based on visual assessment of MR images, and the regions of interest were defined on both DESCT and apparent diffusion coefficient maps. Quantitative values of DESCT parameters were measured and compared between infiltrated and healthy bone marrow. Receiver operating characteristic (ROC) analysis was performed to determine potential utility of DESCT parameters in identifying BM infiltration and different patterns defined by MRI. Sensitivity and specificity under the optimal thresholds determined by the Youden Index were also calculated. Statistical differences were observed between the DESCT parameters including Ca(Water), Water(Ca), HAP(Fat), Fat(HAP) and Effective atomic number (Eff-Z) but not for the 70-keV CT value between the infiltrated and healthy BM (all P < 0.001). The 70keV CT value and Ca(Water), HAP(Fat) and Eff-Z values were also found to be statistically different in comparing different infiltration patterns (all P < 0.05). Performance of the model-based parameter Ca/Water was superior in differentiating between infiltrated and healthy BM in which the area under ROC curve, AUC = 0.856 [95% CI, 81.4-89.1%] with sensitivity = 0.841 and specificity = 0.768, as well as between MM patients and control subjects (AUC = 0.910 [95% CI, 79.5-97.3%], sensitivity = 0.829 and specificity = 1.000). Analysis of DESCT offers potential as a quantitative method to detect infiltrated BM and evaluate infiltration patterns of BM in patients diagnosed with MM.

Evaluation of bone marrow infiltration in multiple myeloma using whole-body diffusion-weighted imaging and T1-weighted water-fat separation Dixon.

Multiple myeloma (MM) is a blood cancer caused by the unlimited proliferation of intramedullary plasma cells. The presence of focal lesions (FLs) is presumed to be a more relevant factor for patient outcomes and risk distribution than diffuse bone marrow signal abnormalities. Signal changes in these FLs also have a good correlation with prognosis. As the cell density increased, a lower apparent diffusion coefficient (ADC) value was found with the diffusion-weighted imaging (DWI) sequence. Therefore, whole-body magnetic resonance imaging (MRI) with DWI sequences is sensitive to cell density and viability and may be vital for disease detection and therapy response assessments. However, the correlation between the DWI signal and the degree of bone destruction and the proportion of bone marrow plasma cells (BMPC) was still unclear in patients with MM. Water-fat separation MRI is used mainly for evaluating liver and bone marrow fat quantification, and fat quantification in other diseases. Meanwhile, it is also possible to assess the extent of bone marrow invasion in medullary lesions. This study aimed to investigate the correlation between ADC values from whole-body DWI and water/fat MRI signals from T1-weighted water-fat separation in evaluating bone marrow infiltration in patients with MM. The study included 35 patients with MM who underwent whole-body DWI and T1-weighted water-fat separation Dixon examinations before therapy. The ADC values, normalized fat signal intensity (nMfat), normalized water molecular signal intensity (nMwater), and normalized fat fraction (nFF) of the thoracolumbar spine was measured in FLs and the normal-appearing bone marrow (NABM). The differences in values were compared using the independent-samples t-test. The correlation between ADC values and water-fat MRI signals was estimated using the Pearson or Spearman correlation test. The correlation between the MRI above parameters and proportions of BMPC was also explored. Statistically significant differences were found between the mean ADC values in FLs and NABM (0.72 vs. 0.33 mm2/s, P<0.0001). Significantly elevated nMwater values and decreased nMfat and nFF values were observed in FLs; no correlations were found in NABM (P>0.05). The ADC value highly correlated with nMfat and nFF values and moderately with the nMwater value in FLs (r=-0.899, -0.834, 0.642, respectively, P<0.0001). Correlations were also observed between the proportion of BMPC and MRI parameters in MM (r=0.984, 0.716, -0.938, and -0.905, respectively, P<0.05). The ADC value combined with water-fat separation parameters could be used for evaluating thoracolumbar bone marrow infiltration in MM. All parameters correlated with the proportion of BMPC, which helped assess the early response in MM therapy.

The Role of Texture Analysis and Radiomics in Prediction of Bone Marrow Infiltration in Patients with Lymphoma

Purpose. To explore the ability of image-based parameters with texture parameters in the differentiation of bone marrow infiltration by positron emission tomography-computed tomography (PET/CT). Procedures. We retrospectively evaluated the baseline PET/CT scan of 44 patients with histologically proven lymphoma. Seventy-three of features were extracted using CGITA software and statistical analysis were carried out on SPSS program. Results. Spearman correlation analysis revealed a strong positive correlation between conventional PET metrics and texture features (19 significant association features) and inverse correlation was found (one parameter significant association feature). Area under the curve and p-value of receive operating characteristics showed that (HILRE (4-bin), HILZE (64-bin), LRE (64-bin), LZE (64-bin), max spectrum (8-bin), busyness (64-bin),code similarity (32-bin & 64-bin)) were significant discriminator of bone marrow infiltration among other features (AUC>0.682, p < 0.05). Univariate analyses of texture features showed that code similarity and LRE (both 64 bin) has significant prediction to BMI. Multivariate analyses revealed that LRE (64 bin) p= 0.031; odds ratio: 1.022; 95% CI, 1.002-1.043) were independent variables for bone marrow infiltration. Conclusions. Significant associations emerged between PET features and bone marrow infiltration in lymphoma. Texture analysis on PET/CT shows potential to differentiate between bone marrow infiltration in patients with Lymphoma.

Biological Features and Prognostic Impact of Bone Marrow Infiltration in Patients with Diffuse Large B-Cell Lymphoma.

The biology and clinical impact of bone marrow (BM) infiltration in patients with diffuse large B-cell lymphoma (DLBCL) remains unclear in the rituximab era. We retrospectively analyzed 232 patients diagnosed with DLBCL at our center between 1999 and 2014. Concordant-presence of large cells similar to those of the lymph node biopsy- and discordant-infiltration by small cells forming lymphoid aggregates, lacking cytological atypia-BM infiltration was defined by histological criteria and further characterized by flow cytometry (FCM). Cell of origin (COO) was determined using Hans’ algorithm. For the clonal relationship between tumor and discordant BM, the VDJH rearrangement was analyzed. Survival analyses were restricted to 189 patients treated with rituximab and chemotherapy. Thirty-six (16%) had concordant, and 37 (16%) discordant BM infiltration. FCM described different indolent lymphomas among discordant cases, clonally related with DLBCL in 10/13 available samples. Median follow-up was 58 months. 5-year-progression-free survival (PFS) for non-infiltrated, discordant and concordant groups was 68%, 65% and 30%, respectively (p < 0.001). Combining COO and BM infiltration, patients with discordant BM and non-germinal center B-cell COO also had decreased 5-year-PFS (41.9%). In multivariate analysis, concordant BM had an independent effect on PFS (HR 2.5, p = 0.01). Five-year cumulative incidence of central nervous system (CNS) relapse was 21%, 4% and 1% in concordant, discordant and non-infiltrated groups, respectively (p < 0.001). In conclusion, concordant BM infiltration represents a subset with poor prognosis, whereas the prognostic impact of discordant BM infiltration could be limited to non-CGB cases.

Improvement in bone marrow infiltration in patients with type I Gaucher disease treated with taliglucerase alfa

Preliminary data suggest a positive effect of taliglucerase alfa on the bone marrow infiltration of Gaucher cells. In this investigator-initiated study, we report the impact of taliglucerase alfa on the bone marrow fat fraction (FF) in 26 patients assessed by quantitative chemical shift imaging (QCSI). Of 15 treatment-naïve patients (median age 48 [range 24–68] years), eight had baseline FF ≤ 0.3, six of those with a FF ≤ 0.23 (‘bone at risk’). All significantly improved from a median baseline FF of 0.24 (0.15–0.32) to 1st year FF of 0.37 (0.25–0.54) and 2nd year FF of 0.42 (0.27–0.59) (p = 0.01). Among the 11 ‘switch-over’ patients (median age 42 [range 33–69] years; median imiglucerase exposure 8 [range 1–17] years), eight had baseline FF ≤ 0.3, five of those with FF < 0.23. All, but one, significantly improved from a median baseline FF of 0.17 (0.08–0.28) to 1st year FF of 0.3 (0.05–0.34) and 2nd year FF of 0.34 (0.08–0.44) (p = 0.03). Two elderly female patients (age 43 and 58 years, with 17 years imiglucerase exposure) who remained at the same enzyme replacement therapy dose, increased from baseline FF of 0.13 and 0.19 to 0.26 at 1 year. Although the number of observations is small, we hypothesize that switching to taliglucerase may result in an improved bone marrow response. A larger study is needed to assess the early benefit of taliglucerase alfa in adult patients with type 1 Gaucher disease on the bone marrow compartment.

Multiple Myeloma and Dual-Energy CT: Diagnostic Accuracy of Virtual Noncalcium Technique for Detection of Bone Marrow Infiltration of the Spine and Pelvis

Purpose To determine the diagnostic performance of dual-energy computed tomography (CT) for detection of bone marrow (BM) infiltration in patients with multiple myeloma by using a virtual noncalcium (VNCa) technique. Materials and Methods In this prospective study, 34 consecutive patients with multiple myeloma or monoclonal gammopathy of unknown significance sequentially underwent dual-energy CT and magnetic resonance (MR) imaging of the axial skeleton. Two independent readers visually evaluated standard CT and color-coded VNCa images for the presence of BM involvement. MR imaging served as the reference standard. Analysis on the basis of the region of interest (ROI) of VNCa CT numbers of infiltrated (n = 75) and normal (n = 170) BM was performed and CT numbers were subjected to receiver operating characteristic analysis to calculate cutoff values. Results In the visual analysis, VNCa images had an overall sensitivity of 91.3% (21 of 23), specificity of 90.9% (10 of 11), accuracy of 91.2% (31 of 34), positive predictive value of 95.5% (21 of 22), and a negative predictive value of 83.3% (10 of 12). ROI-based analysis of VNCa CT numbers showed a significant difference between infiltrated and normal BM (P < .001). Receiver operating characteristic analysis revealed an area under the curve of 0.978. A cutoff of -44.9 HU provided a sensitivity of 93.3% (70 of 75), specificity of 92.4% (157 of 170), accuracy of 92.7% (227 of 245), positive predictive value of 84.3% (70 of 83), and negative predictive value of 96.9% (157 of 162) for the detection of BM infiltration. Conclusion Visual and ROI-based analyses of dual-energy VNCa images had excellent diagnostic performance for assessing BM infiltration in patients with multiple myeloma with precision comparable to that of MR imaging. © RSNA, 2017 Online supplemental material is available for this article.

Identification of Bone Marrow Involvement of FL: Comparison of PET-CT and Bone Marrow Biopsy.

IntroductionIn malignant lymphoma, bone marrow involvement is considered as clinical stage IV which adversely affects International Prognostic Index resulting in poor outcome. Detecting bone marrow lesion is therefore important in staging of newly diagnosed malignant lymphoma. Bone marrow biopsy (BMB) of unilateral or bilateral iliac crest has been a classical method to detect bone marrow infiltration. However, BMB in rare instance, induce some complications including excessive bleeding, infections, or lasting pain. Recently, positron emission tomography combined with computed tomography (PET-CT) became a routine tool in staging of malignant lymphoma. Although PET-CT shows high sensitivity of detecting viable nodal and extra-nodal lesions in aggressive lymphoma, its role in low-grade, indolent lymphoma such as follicular lymphoma (FL) remains controversial.The aim of this study is to retrospectively evaluate the diagnostic accuracy of PET-CT in detecting bone marrow infiltration in patients with newly diagnosed FL.Patients and Methods:We collected data of all patients who were newly diagnosed with FL from January 2005 to October 2015 at Yokohama City University Hospital and Yokohama City University Medical Center. Patients with FL who underwent both PET-CT and BMB prior to the initiation of treatments were finally included in the analysis.Results of unilateral or bilateral BMB of posterior iliac crest were collected from written reports. BMB specimens were evaluated by hemato-pathologists of each institution. The presence of lymphoma cells in the bone marrow was based on morphological and immune-histochemical findings.Written reports were used to collect PET-CT data. Interpretation of images was made by radiologists of each institution where PET-CT scans were performed. Bone marrow involvement in PET-CT was defined as greater intensity of FDG uptake in the bone marrow than those in liver or those in mediastinum.This study was approved by the Internal Review Board of Yokohama City University School of Medicine.Results:In total, 184 patients were newly diagnosed with FL from January 2005 to October 2015. Of 184 patients, 117 who underwent both PET-CT and BMB before treatment were evaluated in the further analysis. The patients included 53 males and 64 female with a median age at diagnosis of 53 years (range: 25 - 82). The distributions of histological FL grading were grade 1-2 in 3 patients, grade 1 in 41, grade 2 in 47, grade 3 in 7, grade 3a in 12, and grade unknown in 7.Bone marrow FDG uptake was elevated according to the defined criteria in 22 patients (19%), while the infiltration of lymphoma cells in the bone marrow was detected by BMB in 35 patients (30%).Of 22 patients with elevated FDG uptake in the bone marrow, 6 (32%) were diagnosed as negative for bone marrow infiltration by BMB. Among the 6 patients who were positive for PET-CT and negative for BMB, the pattern of bone marrow FDG uptake was focal in 2, diffuse in 3, and unknown in 1.Among the 35 patients positive for BMB, bone marrow FDG uptake was increased in 16 (65%). Of the16 patients positive for both BMB and PET-CT, the pattern of FDG uptake in the bone marrow was diffuse in 12, and focal in 4. The remaining 19 BMB positive patients were negative for PET-CT. Of these 19 patients positive for BMB and negative for PET-CT, the grading of FL was grade 1 or 2 in 16, and grade 3a in 3.DiscussionIn conclusion, our study revealed that significant number of patients showed discrepancy between the results of PET-CT and BMB in detecting bone marrow involvement of lymphoma. Although PET-CT is highly sensitive for detecting viable lymphoma cells and is commonly used for staging in routine practice, our data indicated that PET-CT still cannot replace BMB for identifying lymphoma cells in the bone marrow in patients with FL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Standardization of MRI and Scintigraphic Scores for Assessing the Severity of Bone Marrow Involvement in Adult Patients With Type 1 Gaucher Disease.

MRI and (99m)Tc-sestamibi scintigraphy are used to estimate bone marrow infiltration in patients with Gaucher disease (GD), but comparison of data obtained at different institutions is difficult because different scores are employed for semiquantitative assessment. We developed normalized scores for comparing data both within a single method (MRI) and between different methods (MRI versus scintigraphy). We evaluated 51 patients with type 1 GD (26 women, 25 men; mean age ± SD, 36.3 ± 10.9 years old). T1- and T2-weighted turbo spin-echo sequences at 1.5 T served to derive the bone marrow burden score (0-16), the vertebra-disk ratio (VDR), the Terk score (0-3), and the Spanish-MRI score (S-MRI, 0-24). Scintigraphy was scored between 0 and 8. Each score was normalized into four categories: 0 = normal, 1 = mild, 2 = intermediate, 3 = severe involvement. Interobserver and intraobserver agreements were evaluated by kappa statistics; nonparametric statistics with Bonferroni correction assessed correlations among the various original and normalized scores. Interobserver agreement was excellent for the original scores (κ = 0.730-0.843) and even more so for the normalized scores (κ = 0.775-0.940). Intraobserver agreement kappa values ranged from 0.753 to 0.937 for the original scores and 0.851 to 1.000 for the normalized scores. Highly significant correlations were found among the various original scores (r = 0.42-0.86, p values between 0.0296 and < 0.0001), except for VDR versus S-MRI and Terk. Normalization generally induced marginal reductions in statistical significance, whereas S-MRI versus VDR reached statistical significance with the normalized scores. Our data indicate no significant loss of statistical information is caused by the normalization we employed. Our approach therefore facilitates comparison of different scores obtained in different institutions with different imaging modalities.

Prognostic Impact, Phenotypic and Molecular Characterization of Concordant and Discordant Bone Marrow Involvement in Patients with Diffuse Large b-Cell Lymphoma

INTRODUCTIONIn the rituximab era, the prognostic influence of bone marrow (BM) infiltration in patients with diffuse large B-cell lymphoma (DLBCL) has been hardly studied. In this retrospective observational study, we aim to investigate the prognostic influence of concordant and discordant BM infiltration in patients with histological diagnosis of DLBCL. In addition, we analyzed the possible clonal relationship between BM and lymph node tumor cells in the cases with discordant histology. PATIENTS AND METHODSAll patients diagnosed of DLBCL in our center from January 1, 1999 were included in the study. Histological BM infiltration pattern was classified as concordant (DLBCL infiltration) or discordant (small or low-grade B-cell lymphoma) based on the diagnostic reports from the Pathology department. All cases were reviewed for this purpose by an expert pathologist. To further characterize the discordant cases, flow cytometry (FCM) reports of BM infiltration were reviewed. In the discordant cases, the clonal IGH rearrangement was studied in both BM and lymphadenopathy, by amplification of the VDJ genes as recommended in the BIOMED-2 protocol. For survival analysis, only patients treated with R-CHOP or similar were included. RESULTS236 patients diagnosed of DLBCL were included in the study; of them, 31 (13%) had concordant histological BM infiltration and 18 (7.6%) discordant. Phenotypic characterization by FCM of the discordant cases was heterogeneous: chronic lymphocytic leukemia (N = 2), follicular lymphoma (N = 5), marginal zone lymphoma (N = 2), non-specific phenotype (N = 5) or non-infiltration (N = 2). Clonality studies were performed in the discordant cases. Good quality DNA was obtained in 17 out of 18 patients. We confirmed the same clone in both BM and lymphadenopathy in 12 patients (70%); different clones were observed in two, and a polyclonal pattern was obtained in the remaining three patients. Survival analyzes were conducted only in the 186 patients treated with R-CHOP or similar. With a median follow up of 58 (1-135) months, PFS was significantly worse in patients with concordant (35% at 5 years, p = 0.001) or discordant (35% at 5 years, p = 0.04) histology, compared to patients without infiltration (64% at 5 years) (Figure 1). OS was significantly lower in patients with concordant histology (53% at 5 years, p = 0.05), whereas there was no significant difference between patients with discordant infiltration (62% at 5 years, p = 0.8) and non-affected BM (75% at 5 years). In the multivariate analysis, concordant BM infiltration (HR = 2.25, 95% CI 1.2 to 4.3, p = 0.01) had a negative influence on PFS (but not on OS), independently of the age, ECOG and LDH, while discordant histology was close to statistical significance (RR = 2; 95% CI 0.95 to 3, p = 0.1) CONCLUSIONSOur results indicate that BM infiltration, both concordant and discordant, is associated with a lower PFS in DLBCL patients treated with R-CHOP or similar. Cases with discordant BM infiltration have a very heterogeneous phenotype, but we found a clonal relationship between the two different histologies in a high proportion of cases, indicating a probable histologic transformation from a low-grade lymphoma. Further studies are needed to determine the sequence of biological events that might be involved in this transformation. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.