Pattern Of Bone Marrow Infiltration Research Articles

Prominent Bone Marrow Infiltration in the Appendicular Skeleton in a B-cell Acute Lymphoblastic Leukemia Patient Demonstrated by FDG PET-MRI.

Leukemia spread in the bone marrow typically is greater in the axial skeleton than in the appendicular skeleton. We report an unusual pattern of FDG-avid bone marrow infiltration that is more prominent in the appendicular skeleton than the axial skeleton in a pediatric patient with B-cell acute lymphoblastic leukemia.

Visual assessment and quantitative analysis of dual-energy CT virtual non-calcium in imaging diagnosis of multiple myeloma.

To evaluate the reliability and diagnostic performance of dual-energy CT virtual non-calcium imaging in diagnosing bone marrow infiltration in multiple myeloma. Seventy-two patients with multiple myeloma and ten controls were recruited. Patients received dual-energy CT and MRI while controls underwent dual-energy CT only, covering the cervical, thoracic, and lumbar spine and the pelvis. Virtual non-calcium images were compared with magnetic resonance images for confirmation and pattern classification. Fleiss Kappa analysis assessed consistency between virtual non-calcium and MRI classifications. Inter-observer agreement for virtual non-calcium and CT attenuation values was evaluated using Bland-Altman analysis. Diagnostic performances across various sites were evaluated using analysis of variance and receiver operating characteristic curve analysis. Dual-energy CT achieved higher consistency in classifying bone marrow infiltration in multiple myeloma than did MRI (kappa = 0.944). In the overall analysis, the mean virtual non-calcium attenuation values in the bone marrow infiltration group (- 28.3 HU; 95% confidence interval (CI), - 32.1, - 24.6) were higher than those in the non-bone marrow infiltration (- 97.5 HU; 95% CI, - 104.7, - 90.3) and control (- 89.1 HU; 95% CI, - 95.1, - 83.1; F = 172.027, P < 0.001) groups. The optimal cutoff values for virtual non-calcium attenuation varied across the overall (- 42.2 HU), cervical spine (- 21.9 HU), thoracic spine (- 42.8 HU), lumbar spine (- 56.9 HU), and pelvis (- 66.3 HU). Dual-energy CT virtual non-calcium imaging and MRI exhibited good consistency in categorising bone marrow infiltration patterns in multiple myeloma. Different virtual non-calcium attenuation value cutoffs should be used to diagnose bone marrow infiltration in various body regions.

Exploring the role of the combination of FDG PET plus whole body MRI for staging newly diagnosed and relapsed/refractory multiple myeloma: A prospective trial.

7512 Background: The integration of FDG-PET/TC and WB-MRI in the diagnosis of MM may results in higher accuracy to detect bone lesion compared to them alone. This could be translated into better outcomes if early detection of myeloma defining events leads to earlier induction or re-induction treatments. Methods: In our Institution, from January 2021 to January 2023, we performed a prospective trial enrolling 73 consecutive newly diagnosed and relapsed/refractory MM (median age 63 years - range 85-35), according to IMWG, in which WB-MRI was performed according to MY-RADS criteria in combination with FDG PET/CT. 31/73 (42%) had a newly diagnosed MM, 25/73 (34%) were in follow-up after autologous stem cell transplantation and 17/73 (23%) patients were affected by relapsed/refractory MM. Subsequently, in 2 cases WB-MRI were aborted and not diagnostic so patients were excluded from the final analysis. Results: In these 71 patients: 52/71 (73%) cases of concordance of WB-MRI and 18F PET-CT, 18/71 (25%) cases of discordance. In this group 15/18 (83%) cases FDG-PET/CT was negative and WB-MRI showed positive findings according to MYRADS criteria (5 micronodular pattern, 9 diffuse pattern e 1 focal pattern) (Figure 1 Newly diagnosed MM – diffuse pattern in WB-MRI, PET negativity), in 3/18 (17%) FDG-PET/CT was positive for focal lesions and WB-MRI was negative. IMWG criteria showed concordance with WB-MRI data in 16/18 (89 %), in 2/18 (11%) case of follow-up after autologous stem cell transplantation PET-CT showed a relapsed focal lesion while WB-MRI was negative. Accuracy of WB-MRI was 69/71 (97%), whilst PET-CT was 55/71 (77%). These results are in agreement with the literature data about the ability of WB-MRI to depict diffuse and micronodular pattern of bone marrow infiltration. Conclusions: Our preliminary results support a potential complementary role of WB-MRI and FDG PET/CT findings, on the management of patients with MM at both diagnosis and relapse. To date, there is no wide availability of WB-MRI because in concerning about costs and technical issues, but data are consistent with its possible future leading role in MM diagnostic work-up.

Liquid Biopsies as Non-Invasive Tools for Mutation Profiling in Multiple Myeloma: Application Potential, Challenges, and Opportunities.

Over the last decades, the survival of multiple myeloma (MM) patients has considerably improved. However, despite the availability of new treatments, most patients still relapse and become therapy-resistant at some point in the disease evolution. The mutation profile has an impact on MM patients' outcome, while typically evolving over time. Because of the patchy bone marrow (BM) infiltration pattern, the analysis of a single bone marrow sample can lead to an underestimation of the known genetic heterogeneity in MM. As a result, interest is shifting towards blood-derived liquid biopsies, which allow for a more comprehensive and non-invasive genetic interrogation without the discomfort of repeated BM aspirations. In this review, we compare the application potential for mutation profiling in MM of circulating-tumor-cell-derived DNA, cell-free DNA and extracellular-vesicle-derived DNA, while also addressing the challenges associated with their use.

Apparent diffusion coefficient measurements of bone marrow infiltration patterns in multiple myeloma for the assessment of tumor burden - a feasibility study.

The purpose of our study was to explore and compare the tumor burden of different bone marrow infiltration patterns and evaluate the feasibility of apparent diffusion coefficient (ADC) value to identify patterns in multiple myeloma (MM). Ninety-three patients with newly diagnosed multiple myeloma and 23 controls had undergone routine magnetic resonance imaging (MRI) and diffusion-weighted MRI (DWI) from January 2019 to November 2020. Five bone marrow (BM) infiltration patterns were allocated according to routine MRI. The laboratory data and ADC values of patterns were analyzed and compared. ROC analysis was used to establish the best diagnostic ADC threshold value for identifying these patterns and distinguishing normal pattern from controls. Besides, the correlation between the ADC values of diffuse pattern and the plasma cells ratio was assessed. The values of hemoglobin, beta-2 microglobulin (β2-MG), plasma cell, M protein, the percentages of stage, high-risk fluorescence in situ hybridization, and ADC values showed significant difference among patterns. ADCmean at a specific value (368.5×10-6 mm2/s) yielded a maximum specificity (95.5%) and sensitivity (92.0%) in diagnosing MM. A specific value (335.5×10-6mm2/s) yielded a maximum specificity (84.7%) and sensitivity (88.0%) in discriminating visually normal pattern in MM from controls. There was a moderate positive correlation between the plasma cells ratio and ADCs of diffuse infiltration patterns (r = 0.648, P < 0.001). The bone marrow infiltration patterns in MM patients can indicate the tumor burden and ADC value has the ability to discriminate these patterns objectively.

Application of an artificial intelligence-based tool in [18F]FDG PET/CT for the assessment of bone marrow involvement in multiple myeloma

Purpose[18F]FDG PET/CT is an imaging modality of high performance in multiple myeloma (MM). Nevertheless, the inter-observer reproducibility in PET/CT scan interpretation may be hampered by the different patterns of bone marrow (BM) infiltration in the disease. Although many approaches have been recently developed to address the issue of standardization, none can yet be considered a standard method in the interpretation of PET/CT. We herein aim to validate a novel three-dimensional deep learning-based tool on PET/CT images for automated assessment of the intensity of BM metabolism in MM patients.Materials and methodsWhole-body [18F]FDG PET/CT scans of 35 consecutive, previously untreated MM patients were studied. All patients were investigated in the context of an open-label, multicenter, randomized, active-controlled, phase 3 trial (GMMG-HD7). Qualitative (visual) analysis classified the PET/CT scans into three groups based on the presence and number of focal [18F]FDG-avid lesions as well as the degree of diffuse [18F]FDG uptake in the BM. The proposed automated method for BM metabolism assessment is based on an initial CT-based segmentation of the skeleton, its transfer to the SUV PET images, the subsequent application of different SUV thresholds, and refinement of the resulting regions using postprocessing. In the present analysis, six different SUV thresholds (Approaches 1–6) were applied for the definition of pathological tracer uptake in the skeleton [Approach 1: liver SUVmedian × 1.1 (axial skeleton), gluteal muscles SUVmedian × 4 (extremities). Approach 2: liver SUVmedian × 1.5 (axial skeleton), gluteal muscles SUVmedian × 4 (extremities). Approach 3: liver SUVmedian × 2 (axial skeleton), gluteal muscles SUVmedian × 4 (extremities). Approach 4: ≥ 2.5. Approach 5: ≥ 2.5 (axial skeleton), ≥ 2.0 (extremities). Approach 6: SUVmax liver]. Using the resulting masks, subsequent calculations of the whole-body metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in each patient were performed. A correlation analysis was performed between the automated PET values and the results of the visual PET/CT analysis as well as the histopathological, cytogenetical, and clinical data of the patients.ResultsBM segmentation and calculation of MTV and TLG after the application of the deep learning tool were feasible in all patients. A significant positive correlation (p < 0.05) was observed between the results of the visual analysis of the PET/CT scans for the three patient groups and the MTV and TLG values after the employment of all six [18F]FDG uptake thresholds. In addition, there were significant differences between the three patient groups with regard to their MTV and TLG values for all applied thresholds of pathological tracer uptake. Furthermore, we could demonstrate a significant, moderate, positive correlation of BM plasma cell infiltration and plasma levels of β2-microglobulin with the automated quantitative PET/CT parameters MTV and TLG after utilization of Approaches 1, 2, 4, and 5.ConclusionsThe automated, volumetric, whole-body PET/CT assessment of the BM metabolic activity in MM is feasible with the herein applied method and correlates with clinically relevant parameters in the disease. This methodology offers a potentially reliable tool in the direction of optimization and standardization of PET/CT interpretation in MM. Based on the present promising findings, the deep learning-based approach will be further evaluated in future prospective studies with larger patient cohorts.

Bone marrow infiltration by Non-Hodgkin lymphoma: An experience in a tertiary care centre.

To determine the frequency and patterns of bone marrow infiltration in non-Hodgkin lymphoma patients. The cross-sectional study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from April to October 2021, and comprised patients of either gender aged 20-80 years who had been diagnosed with non-Hodgkin lymphoma. Following assessment and as per standard protocol, bone marrow aspirate and trephine biopsy were done on all patients from the posterior superior iliac spine, and slides were prepared and assessed. Data was analysed using SPSS 25. Of the 100 patients, 67(67%) were males and 33(33%) were females. The overall mean age was 54.99±12 years, and mean duration of symptoms was 11.7±1.5 months. Diffuse large B-cell lymphoma was the commonest type 43(43%). Infiltration of marrow occurred in 38(38%) patients, with 12(12%) of them being cases of mantle cell lymphoma. The commonest infiltration pattern was diffuse in 17(17%) cases, followed by focal/nodular in 10(10%). Diffuse large B-cell lymphoma was found to be the commonest type of non-Hodgkin lymphoma, and marrow infiltration occurred most frequently in cases of mantle cell lymphoma.

Patterns of bone marrow infiltration in lymphomas- A retrospective descriptive analysis from a tertiary care centre in Southern India

Bone marrow biopsy (BMB) examination is the gold standard for staging of lymphoma which is interpreted along with other clinical, laboratory and radiological investigations. This study aimed to evaluate the various patterns of BMB infiltration by lymphomas which include Hodgkin and Non Hodgkin lymphoma and the usefulness of BMB compared to bone marrow aspiration (BMA). : In a period of three years, there were 212 cases which showed lymphoma infiltration in bone marrow. We assessed the peripheral blood smear (PBS), BMA and BMB slides and concordance between each was evaluated. BMB slides were assessed for the pattern of involvement. The most frequent subtype was chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (21.70%) followed by Hodgkin lymphoma (HL)(12.73%)and follicular lymphoma (FL)(11.32%). Predominant pattern of infiltration showed by CLL/SLL cases was mixed pattern, by FL was paratrabecular pattern, mantle cell lymphoma(MCL) showed either diffuse or nodular, diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma(BL) showed predominantly diffuse pattern. Hairy cell leukemia (HCL) and peripheral T cell lymphoma (PTCL) showed an interstitial pattern. In HL, the pattern was usually focal nodular however diffuse involvement was seen in a few. Of the 212 cases, 50.94% cases had atypical lymphocytes or lymphocytosis in PBS and 81.14% cases showed infiltration in BMA. Atypical lymphoid cells may not be present at times in peripheral blood or bone marrow aspirate in spite of infiltration in the bone marrow. Different lymphomas show characteristic patterns of marrow involvement.

Clinicopathological Spectrum of Multiple Myeloma: Experience of an Institute in Eastern India

Introduction: Multiple myeloma (MM) is a neoplastic plasma cell disorder characterized by clonal proliferation of malignant plasma cells in the bone marrow. Incidence of MM is increasing rapidly in Asian countries. In a developing country like India diagnosis, risk stratification and access to novel treatment is still a major hurdle Objective: To study the clinico-pathological features of newly diagnosed multiple myeloma patients. Methods: This was a cross sectional hospital based retrospective study conducted in a hospital in eastern India. During the four years of study, 74 cases of multiple myeloma were diagnosed on the basis of International Myeloma Working Group: Criteria for the classification of multiple myeloma and related disorders. The clinical and laboratory characteristics of newly diagnosed patients were studied. Results: Out of the 74 patients, 69% were men and 31% were women. Median age at diagnosis was 55 years (range: 32-81 years). The commonest symptoms observed were fatigue and bone pain. Anemia was present initially in 81% of patients, hypercalcemia in 31.4%, and a serum creatinine level of 2 mg/dL or more in 24.6% patients. The most common monoclonal gammopathy was IgG kappa (44%). Diffuse pattern of bone marrow infiltration, the most common pattern observed in 59% patients. Conclusion: MM patients had male preponderance. Median age of patients was lower compared to western countries with higher percentage of patients with age less than 40 years. Quality of life in MM patients can be improved significantly if there is access to early diagnosis, risk stratification and novel treatment.

CLL-037 The Pattern of Bone Marrow Involvement Among Chronic Lymphocytic Leukemia Patients and Its Impact on the Disease Outcome in Kurdistan Region of Iraq

There are variable degrees of bone marrow (BM) infiltration patterns in chronic lymphocytic leukemia (CLL). Four BM patterns, interstitial, nodular, mixed, and diffuse patterns, were identified. The aim of this study is to assess the effects of BM infiltration patterns on the disease outcome among CLL patients in the Kurdistan Region of Iraq. This study is a cross-sectional, descriptive, retrospective that involved 106 patients with CLL disease. The data were collected from cancer centers in the Kurdistan region of Iraq (including Erbil, Sulaymaniyah, and Duhok) from January 1, 2010 to December 31, 2019. BM histopathology study of all patients was assessed and correlated with the disease outcome. Fifty-three (50.0%) patients had interstitial BM patterns, 17 (16.0%) had nodular BM pattern, 14 (13.2%) had mixed BM patterns, and 22 (20.8%) had diffuse BM pattern. The results showed that patients with interstitial, nodular, and mixed BM patterns had a superior overall survival (OS) and progression-free survival (PFS) rate than diffuse BM pattern. Kaplan-Meier curve illustrates that our CLL patients with interstitial BM patterns had a better mean OS rate (44.0 months) than diffuse BM pattern with a mean of (23.2 months). As well as for PFS, the mean was (35.7 months) for the interstitial BM patterns and (17.6 months) for diffuse BM pattern. We demonstrate that the BM involvement patterns have a prognostic value in our CLL patients and provide more reliable information regarding the clinical outcome.

P27: HUMORAL RESPONSE RATE POST MRNA COVID19 VACCINATION (BNT162B2) IS HIGLY DEPENDENT TO BONE MARROW PLASMACYTOSIS: LONG FOLLOW-UP OF SYMPTOMATIC MULTIPLE MYELOMA PATIENTS

Background: SARS-COV-2 anti-Spike IgG response following mRNA vaccination (BNT162b2) is suboptimal and highly variable in MM patients. Patients and Methods: We report here a single-institution retrospective analysis of 127 consecutive patients with symptomatic MM (71 males, 56 females), [median age 69.5 years (range 45-85)], 63 patients with untreated MM and 64 patients with MM refractory to one or more previous treatment lines. Myeloma therapies included PI+IMiD combos, IMiD-based regimens, PI-based regimens, anti-CD38 mAb-based therapies, antibody-drug conjugates (Belantamab Mafodotin monotherapy), dexamethasone and high dose melphalan. Anti-spike IgG antibody were detected also in 50 healthy volunteers. Patients with symptomatic MM and healthy controls received two dose of COVID-19 mRNA vaccine (Pfizer BioNTech) on days 1 and 21 between 29 April and 15 May 2021. Patients with prior history of SARS-CoV-2 were excluded from analysis. Quantitative determination of anti-spike S1/S2 IgG antibody was performed at 4 weeks from vaccination completion (LIAISON® SARS-COV-2 S1/S2 IgG, LIAISON®). It was previously established a threshold >15 AU/ml of anti-Spike IgG which was related to neutralizing activity of anti-SARS-COV-2 antibodies. Results: Sixty-five out of 127 patients were evaluable for response. Anti-spike IgG antibody were detected in 50/65 (76.9%) MM patients, defined as responders [177 AU/mL (range 26.4 – 1430)]. 23.1% of MM patients, defined as non-responders, failed to respond at two doses of COVID-19 mRNA vaccine [3.8 AU/mL (range 0.65 – 9.33)]. Seroprotection rate at cutoff of 15 AU/mL was 100% in controls [249 AU/mL (range 104 - 2430)]. No statistically significant differences were found between the two subgroups of patients for myeloma disease phase (relapse/refractory MM vs. untreated symptomatic MM), LDH, residual gammaglobulin levels, WBC, ANC, lymphocytic response, age and sex (Tab. 2). Conversely, plasmacytosis, B2M and haemoglobin concentration were associated with a different response to vaccine. Patients with extreme plasmacytosis (60.0 ± 20.3 vs. 28.2 ± 18.8 mean ± SD; p <0.001) (Tab. 2) had a mean titer less than 15 AU/ml of anti-Spike IgG compared with patients with a low plasmacytosis, who, conversely, showed significantly higher mean titers of anti-Spike IgG. B2M was significantly higher in non-responders compared to responders (4.6 ± 4.1 vs. 3.2 ± 3.6 mean ± SD; p = 0.006) (Tab. 2). Haemoglobin value was significantly lower in non-responders compared to responders (10.8 ± 1.8 vs. 12.1 ± 1.8 mean ± SD; p = 0.008) (Tab. 2). Multivariate analysis confirmed the bone marrow infiltration pattern and haemoglobin value as statistically significant variables. In addition, in the present cohort, the myeloma treatment, including high-dose melphalan and autologous stem cell transplantation, have not been associated with SARS-CoV-2 infection. Conclusions: In our experience, significant fraction of MM patients (23.1%) does not developed any detectable anti-Spike IgG after two dose of COVID-19 mRNA vaccine. Lack of IgG response associated with three statistically significant variables: extreme plasmacytosis, B2M, and haemoglobin concentration. In the subgroup of patients with good response to vaccine, after a median follow-up of 7 months from second dose of COVID-19 mRNA vaccine, no cases of COVID-19 occurred.

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.

Skeletal changes in plasma cell dyscrasias

Plasma cell dyscrasias are aspectrum of diseases characterized by clonal plasma cell proliferation. Important entities within this group are monoclonal gammopathy of unknown significance, smoldering multiple myeloma, and symptomatic multiple myeloma. The goal of this review is to illustrate plasma cell dyscrasia imaging findings of bone and bone marrow as seen on whole-body computed tomography (CT) and magnetic resonance imaging (MRI) and to discuss the relevance of imaging for management of patients with plasma cell dyscrasias. Selective literature search with analysis of dedicated original research articles and reviews and discussion of clinical guidelines. Diagnostic classification of plasma cell dyscrasias is based on the SLiM-CRAB criteria. CT primarily represents imaging of mineralized bone to show osseous end organ damage by detecting osteodestruction. MRI is primarily used for bone marrow imaging to detect diffuse or focal bone marrow infiltration, even in the absence of bone destruction. Different patterns of bone marrow infiltration can be distinguished. Treatment response is associated with characteristic imaging signs of lesion regression. Imaging plays aprominent role in treatment stratification of patients with plasma cell dyscrasia at first diagnosis and during follow-up.

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.

The pattern of bone marrow involvement among chronic lymphocytic leukemia patients and its impact on the disease outcome in Kurdistan Region of Iraq

OBJECTIVES : There are the variable degrees of bone marrow (BM) infiltration patterns in chronic lymphocytic leukemia (CLL). Four BM patterns: Interstitial, nodular, mixed, and diffuse patterns were identified. The aim of this study is to assess the effects of BM infiltration patterns on the disease outcome among CLL patients in Kurdistan Region of Iraq.METHODS: This study is a cross-sectional, descriptive, retrospective involved 106 patients with CLL disease. The data are collected in the Kurdistan region of Iraq (including Erbil, Sulaymaniyah, and Duhok) cancer centers. Through the period from January 1, 2010 to December 31, 2019. BM histopathology study of all patients was assessed and correlated with the disease outcome.RESULTS: Fifty-three (50.0%) patients had interstitial BM patterns, 17 (16.0%) had nodular BM pattern, 14 (13.2%) had mixed BM patterns, and 22 (20.8%) had diffuse BM pattern. The results showed that patients with interstitial, nodular, and mixed BM patterns had a superior overall survival (OS) and progression-free survival (PFS) rate than diffuse BM pattern. Kaplan–Meier curve illustrates that our CLL patients with interstitial BM patterns had a better mean OS rate (44.0 months) than diffuse BM pattern with a mean of (23.2 months). As well as for PFS, the mean was (35.7 months) for the interstitial BM patterns and (17.6 months) for diffuse BM pattern.CONCLUSIONS: We demonstrate that the BM involvement patterns have a prognostic value in our CLL patients and provide more reliable information regarding the clinical outcome.

Evaluation of Whole-Body MRI (WB-MRI) in Smoldering Multiple Myeloma (SMM)

Introduction Whole-body magnetic resonance imaging (WB-MRI), including multiplanar multisequence technique with diffusion weighted images, is a novel imaging technique being evaluated for patients with multiple myeloma (MM). WB-MRI is ideal for this population due to its high sensitivity for bone marrow signal changes and full anatomic coverage from vertex to mid-thighs. It is well established that patients with unequivocal focal lesions on MRI have worse outcomes. Currently the IMWG recommends that all patients with smoldering multiple myeloma (SMM) undergo WB-MRI (or whole spine MRI if WB-MRI is not available) to rule out two or more focal lesions which would classify the patient as having symptomatic myeloma requiring treatment. There is a clear benefit of using MRI for the detection of early focal myeloma lesions however less is known about findings in the SMM population. Detection of subtle findings such as one small focal lesion or heterogeneous bone marrow in WB-MRI has unknown clinical significance that needs to be further evaluated. This study aimed to evaluate the sensitivity of WB-MRI compared to other highly sensitive functional imaging modalities in patients with SMM both at baseline and after treatment. Methods Imaging of patients with WB-MRI performed at the National Institutes of Health Clinical Center Myeloma Program were reviewed and compared to whole spine MRI and 18F-FDG PET/CT completed at the same timepoint. The majority of patients were being evaluated for enrollment on clinical trials. Patients had undergone a WB-MRI with a 3-Tesla system either as a baseline study, after completion of induction treatment, or during follow up determined by the time DWI became available at our institution. The imaging protocol included sagittalT1 weighted (W) and Short tau inversion recovery (STIR) for spine and coronal, axial T1W and axial T2 TSE pulse sequences. The functional component included diffusion weighted imaging in the axial plane (b=0 and 900sec/mm2). Radiological interpretation was performed by two readers using myeloma response assessment and diagnosis system (My-RADS) {Messiou, 2019 #340}. WB-MRIs were categorized as positive if focal lesions or diffuse/heterogenous pattern of bone marrow infiltration were present. Similarly, 18F-FDG PET/CTs and whole spine MRIs were classified as positive if focal lesions or diffuse/heterogenous pattern of bone marrow were present. Results A total of 34 patients with SMM and 5 patients with relapsed refractory multiple myeloma (RRMM) had sequential WB-MRI and 18F-FDG PET/CT. Figure 1 summarizes the radiological data of the SMM population. Eleven of these patients had PET/CT, whole spine MRI, and WB-MRI at baseline. Twenty-five patients had PET/CT and WB-MRI completed after at least 8 cycles of treatment. Thirteen patients had consistently negative imaging at baseline, 7 of which also had negative imaging after treatment, while 2 patients were found to have new lesions seen on WB-MRI after treatment. Six patients had resolution of positive imaging seen at baseline after treatment. Among the 17 patients with a positive WB-MRI, 12 (71%; 95% CI 47% - 87%) had a negative correlating PET/CT. Among 5 patients with positive PET/CT at the same time point as a WB-MRI, only 1 (20%; 95% CI 2% - 64%) correlated to a negative WB-MRI. Figure 2 depicts findings from patients with RRMM for comparison. All imaging modalities showed multiple focal findings in all 5 patients. Conclusions This study depicts the high sensitivity of WB-MRI in the SMM population. Such a high sensitivity is especially needed in SMM and early myeloma when disease burden is lower and the decision for treatment is being considered. In comparison to the RRMM population where all three imaging modalities easily detect multiple focal lesions, WB-MRI tends to identify myeloma involvement in the SMM patients more than the other imaging techniques. This suggests the importance of utilizing WB-MRI when diagnosing SMM. In the SMM population, the prognostic significance of lesions that are discrepant between MRI and FDG PET/CT is not yet known. Further follow up is needed to evaluate any difference in hard endpoints such as progression free survival between patients with positive findings described by WB-MRI. Disclosures No relevant conflicts of interest to declare.

Quantitative bone marrow magnetic resonance imaging through apparent diffusion coefficient and fat fraction in multiple myeloma patients.

Quantitative bone marrow (BM) MR sequences, as DWI and CSI, were used to evaluate BM water-fat composition. The aim of the study was to assess the potential usefulness of fat fraction (FF) and ADC, calculated by CSI or DWI, in diagnosing and classifying myeloma (MM) patients according to their different BM infiltration patterns. The study group included 43 MM patients (19F; 24M; mean age 64years), 15 asymptomatic, 15 symptomatic with diffuse BM infiltration and 13 symptomatic with focal lesions (FLs). The control group was made up of 15 healthy subjects (7F; 8M; mean age 64years). MRI examinations consisted of sagittal T1w TSE on the spinal column, axial DWI (b 50-400-800mm2/s) and coronal T2 Dixon, on the whole body. Mean ADC and FF were calculated placing 1 ROI on 6 vertebras and 2 ROIs on either the pelvis or FL. ANOVA with Bonferroni's correction showed a significant difference in ADC values among the different groups of MM patients (P < 0.05), while FF was only significantly different between patients with diffuse infiltration and patients with FL (P = 0.002). ADC allowed distinguishing MM patients from normal BM patients with diffuse BM infiltration (cutoff value: 0.491 × 10-3mm2/s; sensitivity 73%, specificity 80%). FF helped better discriminate healthy controls from normal BM patients (cutoff = 0.33, sensitivity 73%, specificity 92%) and patients with diffuse BM infiltration from those with FL (cutoff = 0.16, sensitivity 82%, specificity 92%). ADC and FF are potentially useful parameter for the quantitative evaluation of BM infiltration in MM patients.

Bone marrow infiltration pattern in patients with intravascular large B-cell lymphoma diagnosed by random skin biopsy.

We retrospectively analyzed bone marrow (BM) infiltration pattern in consecutive 30 intravascular large B‐cell lymphoma (IVLBCL) patients diagnosed by random skin biopsy (RSB). BM infiltration of lymphoma was observed in 18 patients (60.0%), including five patients with the intrasinusoidal pattern with minimal extravasation, eight patients with the mixed of intrasinusoidal and scattered/interstitial or nodular infiltration, and five patients with the nodular/diffuse pattern. Twelve patients were negative for lymphoma infiltration. BM histology of patients with IVLBCL were diverse and frequently discordant with those of other site of IVLBCL lesions. BM biopsy had a poorer diagnostic performance for detecting intravascular features.

Spectrum of magnetic resonance imaging findings in transplanted multiple myeloma patients with hip/pelvic pain (according to MY-RADS): A single center experience

PurposeThe aim of our study is to evaluate the spectrum of MRI findings in transplanted Multiple Myeloma (MM) patients with hip/pelvic pain and to correlate these findings with standard prognostic clinical outcomes. MethodsA retrospective interpretation of the MRI findings of 54 MM patients with hip/pelvic pain were done according to MY-RADS guidelines. MRI findings included: type of bone marrow involvement and incidental findings (osteonecrosis and fractures). Inter- and intra-reader agreement were calculated using Cohen’s kappa test. Survival and relapse rates, type of transplantation and days of hospitalization were correlated with MRI findings. Results1/52 patient presented normal bone marrow pattern, 10/52 focal pattern, 26/52 diffuse pattern and 15/52 mixed. No cases of micronodular was reported. Among the incidental findings, n = 6 osteonecrosis and n = 5 pathological fractures were found, with average length of stay higher. The intra- and inter-reader agreement assessing MY-RADS, were good (k value between 0.61−0.8). Focal pattern was most represented in patients with osteonecrosis and the worst survival rate. Diffuse pattern was most represented in relapses. No statistically significant correlations were found between bone marrow infiltration patterns and the type of transplantation. ConclusionMRI can recognize different infiltration patterns and complications in transplanted MM patients with hip/pelvic pain, correlating with clinical parameters.

Age- and BMI-related variations of fat distribution in sacral and lumbar bone marrow and their association with local muscle fat content

This analysis investigated the age- and BMI-related variations of fat distribution in sacral and lumbar bone marrow and their association with local muscle fat content in order to detect fat distribution patterns and variations in healthy adults using proton density fat fraction (PDFF) measurements. A six-echo 3D spoiled gradient-echo sequence was used for chemical shift encoding-based water-fat separation at the sacral and lower lumbar region in 103 healthy volunteers. PDFF values of the sacrum, 5th lumbar vertebral body, the gluteal and paraspinal muscles were determined. Correlation with age was significant (p < 0.05) for PDFF of the sacrum (men (m): r = 0.58; women (w): r = 0.54), L5 (m: r = 0.58; w: r = 0.54), the gluteal (m: r = 0.51; w: r = 0.44) and paraspinal (m: r = 0.36; w: r = 0.49) muscles in both genders. BMI correlated significantly with the paraspinal musculature in men (r = 0.46) and women (r = 0.33). Correlation testing revealed significant correlations (p < 0.05) between the two osseous (m: r = 0.63, w: r = 0.75) and the muscle compartments (m: r = 0.63, w: r = 0.33) in both genders. Bone marrow and muscle fat infiltration patterns were not significantly associated with each other at the sacral and lower lumbar spine region. The presented data suggest that the two compartments may have distinct pathophysiological fat infiltration patterns. However, further clinical studies are needed to support the results.