Diffuse Bone Marrow Uptake Research Articles

Prognostic significance of diffuse increased fluorine-18-fluorodeoxyglucose (18F-FDG) uptake within the reticuloendothelial system in lymphoma patients.

As constituents of the reticuloendothelial system, the spleen and bone marrow (BM) have been recognized as integral components of the systemic inflammatory response in cancer contexts, thereby serving as predictive indicators for assessing cancer prognosis. Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) has attained widespread utilization for staging, assessing treatment response, and prognostication in lymphoma patients. Several investigations have proposed that focal increased 18F-FDG uptake in the BM or spleen may correlate with malignant involvement in lymphoma. However, scant data exist regarding the implications of diffuse BM and splenic uptake. This study aimed to explore the relationships between metabolic parameters of the spleen and BM on 18F-FDG PET/CT and inflammatory markers, and to assess their prognostic value in patients with lymphoma. A retrospective analysis was conducted on 118 patients newly diagnosed with malignant lymphoma, who underwent 18F-FDG PET/CT and exhibited diffuse increased splenic or BM uptake in 18F-FDG PET/CT imaging. The mean standardized uptake value (SUV) of the spleen, BM, and liver was calculated. The association between metabolic variables and systemic inflammatory markers was investigated, and the prognostic significance of clinicopathological and PET parameters was assessed using overall survival (OS) and progression-free survival (PFS). A statistically significant correlation was found between the spleen-to-liver SUV ratio (SLR) and inflammatory markers such as C-reactive protein (r=0.264, P=0.007) and platelet-to-lymphocyte ratio (r=0.227, P=0.021). No significant correlation was observed between BM-to-liver SUV ratio (BLR) and hematologic parameters, while concordance analysis revealed a fair agreement between BLR and bone marrow biopsy (BMB) (Cohen's Kappa-κ =0.271, P=0.002). In patients with aggressive non-Hodgkin lymphoma, both SLR [P=0.017, HR 2.715, 95% confidence interval (CI): 0.875-8.428] and BLR (P=0.044, HR 0.795, 95% CI: 0.348-1.813) were significantly linked to OS, while SLR (P=0.019, HR 2.223, 95% CI: 1.139-4.342) emerged as a significant prognostic factor for PFS. This study highlighted that diffuse increased splenic 18F-FDG uptake in lymphoma patients was closely associated with inflammation, whereas diffuse BM uptake was likely attributable to BM infiltration rather than inflammatory changes. Furthermore, both parameters held promise as prognostic indicators for patients with aggressive lymphoma.

Importance of FDG-PET (Fluorodeoxyglucose Positron Emission Tomography) in Staging and Response Assessment of Hairy Cell Leukemia (HCL)

Alessandro Mancini and Luca De Carolis are Co-first authors. Nicodemo Baffa, Brunangelo Falini and Enrico Tiacci are Co-last authors. INTRODUCTION HCL is an indolent BRAF-mutated leukemia usually presenting with cytopenias, splenomegaly, little or no lymphadenopathy, heavy bone marrow (BM) infiltration and few circulating leukemic cells. Imaging exams for staging include abdominal echography and computed tomography (CT), while the role of PET is largely unknown. METHODS 84 patients (pts) with relapsed/refractory HCL participating to our clinical trials of BRAF inhibitor-based therapies prospectively underwent PET/CT pre- and post-treatment, in addition to usual examinations for response assessment. Since FDG uptake is normally higher in liver than spleen, BM and lymph nodes, uptake in the latter tissues was considered abnormal if equal to or higher than the liver. Splenomegaly was defined by a longest spleen diameter >13 cm on PET/CT. The standard definition of complete remission (CR) in HCL just requires no palpable splenomegaly on physical examination, in addition to resolution of cytopenias as well as no hairy cells visible in the blood smear and the BM biopsy by non-immunological stains. RESULTS Pre-therapy, 58/77 (75%) non-splenectomized pts showed abnormal splenic FDG uptake (maximal standardized uptake value/SUVmax: median 4.8, vs 3.9 for the liver), which was always diffuse without focal lesions. Conversely, focal splenic uptake is not infrequent in splenic marginal zone lymphoma (18%, 7/39 pts - Abdom Radiol 2018;43:2721; vs of 0/58 HCL pts, p=0.0003), which may aid in the differential diagnosis with this HCL-mimicker. Moreover, 14/58 (24%) HCL pts. with a PET+ spleen did not have splenomegaly, and splenic uptake returned to normal in 10/11 evaluable cases (91%) achieving at least a partial response post-therapy, which suggests leukemic spleen involvement even without splenomegaly. Abnormal diffuse BM uptake was observed in 41/82 evaluable pts (50%; median SUVmax 5, vs 3.4 for the liver). In these cases, leukemic involvement in the BM biopsy was greater (median 80%) than in the other 41 pts (median 65%; p-value <0.01), pointing to HCL infiltration as the cause of abnormal BM uptake rather than to reactive hyperplasia of non-involved BM. Post-therapy, pathologic spleen uptake normalized in 46/51 evaluable pts (90%), and their CR rate was higher (32/46 pts, 70%) than in the other 5 pts remaining PET+ (1/5, 20%; p=0.047). Among the 46 PET- cases, 31 (67%) were not splenomegalic while 15 (33%) had residual splenomegaly (up to 17 cm; Fig. 1A); interestingly, within PET- cases relapse-free survival (RFS) was similar not only in conventionally defined CR cases with (n=8) vs without (n=24) residual non-palpable splenomegaly (p=0.84 after a median follow-up of 19 months), but also when the 6 cases meeting all conventional CR criteria except for still palpable splenomegaly were added to the 8 CR pts with residual non-palpable splenomegaly (p=0.7 after a median follow-up of 20.5 months - Fig. 1B). These findings suggest that metabolic status reflects splenic HCL involvement more reliably than spleen size or palpability, a concept that could improve the current definition of CR in HCL. Abnormal BM uptake resolved after treatment in 34/37 evaluable pts (92%), and their CR rate was again higher (23/34, 68%) than in the other 3 pts remaining PET+ (0/3; p=0.047). Leukemic infiltration of the BM biopsy was lower in the 34 PET- vs the 3 PET+ pts (median 5% vs 70%-80%, respectively; p=0.0004), indicating that BM abnormal uptake reflects HCL infiltration load rather than reactive BM hyperplasia post-therapy. Finally, abnormal lymph node uptake was observed pre-therapy in 9/84 (11%) pts (median SUVmax 7.1, vs 3.4 for the liver) and normalized after treatment in 7/8 evaluable pts (88%), including one case with residual lymph node enlargement (2.2 cm); all these 7 pts had achieved a CR while the remaining pt had no response to therapy. CONCLUSIONS PET is potentially useful in the differential diagnosis with splenic marginal zone lymphoma and may aid in the clinical management of HCL pts by detecting metabolic involvement of the main disease sites even in the absence of organomegaly. Importantly, PET signal tracks with response to therapy even in case of persistent organomegaly, which may lead to refine the definition of CR in HCL.

The relationship between bone marrow involvement on 18F-FDG PET/CT and bone marrow biopsy in patients with multiple myeloma and other plasma cell neoplasms

Background: Bone marrow biopsy (BMB) plays a crucial role in the diagnosis and assessment of treatment response in patients with multiple myeloma (MM). 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has been shown to be a complimentary measure of marrow involvement in patients with Hodgkin and diffuse large B cell lymphomas. However, only limited information is available on its relationship with BMB in MM.Aim: To assess the association between bone marrow involvement on 18F-FDG PET/CT, and BMB in patients with MM and other plasma cell neoplasms.Setting: Cape Town, South Africa.Methods: Hundred and three patients undergoing 18F-FDG PET/CT and BMB were included. Plasma cell infiltration (PCI) on BMB was compared for three visual patterns of 18F-FDG bone marrow uptake (irregular, diffuse less than or equal to the liver and diffuse greater than liver).Results: Eighty-four patients had diffuse bone marrow uptake. Of these, 25/84 had uptake greater than liver, all having PCI ≥ 60% and a median value of 85%. Of the 84 patients, the 59 patients with uptake less than or equal to liver had PCI 10% in 57.6% (34/59), and ≥ 10% in 42.4% (25/59) with a median value of 8%. Nineteen patients had irregular bone marrow uptake. Of these, 4/19 (21.1%) had PCI of 10% and 15/19 (78.9%) had PCI ≥ 10%, with the median value of 23%. The median percentage of PCI across the three described patterns of FDG uptake was significantly different (p = 0.0001).Conclusion: 18F-fluorodeoxyglucose positron emission tomography/computed tomography might avoid the need of repeat BMB in most of the patients with diffuse and irregular patterns of 18F-FDG uptake.

11C-acetate positron emission tomography is more precise than 18F-fluorodeoxyglucose positron emission tomography in evaluating tumor burden and predicting disease risk of multiple myeloma

The optimal method of tumor burden evaluation in newly diagnosed multiple myeloma (NDMM) is yet to be determined. This study aimed to compare the value of 11C-acetate positron-emission tomography (PET)/computed tomography (CT) (AC-PET and 18F-fluorodeoxyglucose PET/CT (FDG-PET) in the assessment of tumor burden in NDMM.This study evaluated 64 NDMM patients between February 2015 and July 2018. AC-PET and FDG-PET were used to assess myeloma lesions. The clinical data, imaging results, and their correlations were analyzed. Diffuse bone marrow uptake in AC-PET was significantly correlated with biomarkers for tumor burden, including serum hemoglobin (P = 0.020), M protein (P = 0.054), the percentage of bone marrow plasma cells (P < 0.001), and the Durie–Salmon stage of the disease (P = 0.007). The maximum standard uptake value (SUVmax) of focal lesions and high diffuse bone marrow uptake in AC-PET showed stronger correlations with high-risk disease (P = 0.017, P = 0.013) than those in FDG-PET. Moreover, the presence of diffuse bone marrow uptake, more than ten focal lesions, and an SUVmax of focal lesions of > 6.0 in AC-PET, but not in FDG-PET, predicted a higher probability of disease progression and shorter progression-free survival (P < 0.05). AC-PET outperformed FDG-PET in tumor burden evaluation and disease progression prediction in NDMM.

Prognostic value of bone marrow (18)F-FDG uptake pattern of pretreatment PET-CT in extranodal NK/T cell lymphoma

Objective: To investigate the prognostic value of bone marrow (BM) (18)F-fluorodeoxyglucose ((18)F-FDG) uptake pattern of pretreatment positron emission tomography/computed tomography (PET-CT) in extranodal NK/T cell lymphoma (ENKTL) patients. Methods: We retrospectively collected clinical data from a series of 63 ENKTL patients with stageⅡ~Ⅳ, who have received both (18)F-FDG PET-CT and bone marrow biopsy (BMB) prior to treatment. According the BM (18)F-FDG uptake pattern of PET-CT, the patients were divided into three groups: focal BM FDG uptake higher than liver (fPET+ ), diffuse BM uptake higher than liver (dPET+ ) and normal BM uptake (lower than liver) (nPET). The Kaplan-Meier method and Log-rank test were respectively used for survival analysis and univariate analysis, and COX proportional hazards model for multivariate analysis. Results: Among the 63 patients, 22 patients had nPET, 24 patients showed dPET+ , and 17 patients had fPET+ . BMB positive was found in 8 patients, and negative in 55 patients. Thirty-seven patients had disease progression or relapse, and 31 patients died. The 3-years progression free survival (3y-PFS) rates of fPET+ patients and nPET patients were 14.7% and 63.6% (P=0.006). The 3-years overall survival (3y-OS) rates were 18.8% and 64.8% (P=0.005). The 3y-PFS of dPET+ patients and nPET patients were 35.6% and 63.6% (P=0.161), 3y-OS were 47.9% and 64.8% (P=0.280). Univariate analysis showed that lactate dehydrogenase (LDH) level, Epstein-Barr virus DNA (EBV-DNA), Korean prognostic index (KPI) and BM (18)F-FDG were related with PFS and OS (all P<0.05). Multivariate analysis showed EBV-DNA and BM (18)F-FDG were independent predictors for PFS (P<0.05). EBV-DNA was also an independently predictor for OS (P<0.05). Conclusions: PET/CT-directed BM patterns are meaningful in predicting prognosis of newly diagnosed ENKTL patients. Focal BM (18)F-FDG uptake pattern is an independent predictor for PFS.

Diagnostic and Clinical Impact of Staging 18F-FDG PET/CT in Mantle-Cell Lymphoma: A Two-Center Experience

IntroductionThe diagnostic accuracy of fluorine-18–fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in staging mantle-cell lymphoma has not yet investigated. The aim of this 2-center retrospective study was to investigate the utility of 18F-FDG PET/CT in assessing nodal, splenic, bone marrow (BM), and gastrointestinal (GI) disease compared to CT, BM, and GI endoscopy; and to assess its clinical impact. Patients and MethodsOne hundred twenty-two patients with histologically proven mantle-cell lymphoma were included. PET/CT BM findings were considered positive if isolated/multiple focal uptake in the BM not explained by benign findings and/or diffuse BM uptake higher than liver with/without focal uptakes were present. PET/CT findings were considered positive for GI involvement in the presence of isolated/multiple focal uptake in the GI organ. ResultsAll patients had positive PET/CT showing the presence of at least one hypermetabolic lesion, with the exception of one case. PET/CT results, compared to CT, detected more nodal and/or splenic lesions in 26 patients. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT for BM were 52%, 98%, 97%, 65%, and 74%; for GI 64%, 91%, 69%, 90%, and 85%; and for GI excluding diabetic patients, 78%, 92%, 72%, 94%, and 89%. PET/CT permitted upstaging of 21 cases and downstaging of 2. Conclusion18F-FDG PET/CT showed excellent detection rate in nodal and splenic disease—a rate better than CT. For BM and GI evaluation, in order to reach good accuracy, the selection of patients and the use of specific criteria for evaluation of these organs seems to be crucial. Moreover, PET/CT altered the management and therapeutic approach in about 20% of patients.

18F-FDG PET/CT Radiomic Analysis with Machine Learning for Identifying Bone Marrow Involvement in the Patients with Suspected Relapsed Acute Leukemia

18F-FDG PET / CT is used clinically for the detection of extramedullary lesions in patients with relapsed acute leukemia (AL). However, the visual analysis of 18F-FDG diffuse bone marrow uptake in detecting bone marrow involvement (BMI) in routine clinical practice is still challenging. This study aims to improve the diagnostic performance of 18F-FDG PET/CT in detecting BMI for patients with suspected relapsed AL.Methods: Forty-one patients (35 in training group and 6 in independent validation group) with suspected relapsed AL were retrospectively included in this study. All patients underwent both bone marrow biopsy (BMB) and 18F-FDG PET/CT within one week. The BMB results were used as the gold standard or real “truth” for BMI. The bone marrow 18F-FDG uptake was visually diagnosed as positive and negative by three nuclear medicine physicians. The skeletal volumes of interest were manually drawn on PET/CT images. A total of 781 PET and 1045 CT radiomic features were automatically extracted to provide a more comprehensive understanding of the embedded pattern. To select the most important and predictive features, an unsupervised consensus clustering method was first performed to analyze the feature correlations and then used to guide a random forest supervised machine learning model for feature importance analysis. Cross-validation and independent validation were conducted to justify the performance of our model.Results: The training group involved 16 BMB positive and 19 BMB negative patients. Based on the visual analysis of 18F-FDG PET, 3 patients had focal uptake, 8 patients had normal uptake, and 24 patients had diffuse uptake. The sensitivity, specificity, and accuracy of visual analysis for BMI diagnosis were 62.5%, 73.7%, and 68.6%, respectively. With the cross-validation on the training group, the machine learning model correctly predicted 31 patients in BMI. The sensitivity, specificity, and accuracy of the machine learning model in BMI detection were 87.5%, 89.5%, and 88.6%, respectively, significantly higher than the ones in visual analysis (P < 0.05). The evaluation on the independent validation group showed that the machine learning model could achieve 83.3% accuracy.Conclusions: 18F-FDG PET/CT radiomic analysis with machine learning model provided a quantitative, objective and efficient mechanism for identifying BMI in the patients with suspected relapsed AL. It is suggested in particular for the diagnosis of BMI in the patients with 18F-FDG diffuse uptake patterns.

FDG and FCH PET/CT of Multiple Myeloma at Various Clinical Situations: Lesion Detection, Proposal for a Patient-Based “Summ” Score and Reproducibility of Scoring

Introduction: In a previous pilot study, PET/CT performed for suspected relapsing or progressive multiple myeloma (MM) revealed more lesions with FCH than with FDG. We then launched a prospective comparison of FDG and FCH PET/CT in MM at initial staging, restaging and during therapeutic follow-up. The IMPeTUs scoring system was proposed in 2016 by Nanni et al. to summarize the results of FDG PET/CT. However, the IMPeTUs scoring system is not designed to reflect by one single patient-based score the extent of the disease, as determined on radiotracer uptake. To compare the performance of those two PET radiotracers, we set a single patient-based score, derived from the IMPeTUs approach, and we applied it to the comparison of FDG and FCH PET/CT at various clinical situations of MM.Aim: To compare (1) the reproducibility of reading and scoring of FDG and FCH PET/CT in initial staging, restaging and therapeutic follow-up of MM, (2) the correlation between the scores on FDG or on FCH PET/CT and serum concentration of M-protein, a quantitative criterion reflecting the secretory activity of MM, recommended at diagnosis and as a part of evaluation of therapeutic response.Patients and methods: FDG and FCH PET/CT were performed in 105 patients (20 at initial staging, 37 at relapse and 48 during follow-up).The FDG and FCH PET/CTs were read in a random order with a wash out period by two experienced readers blinded to any patient's clinical data. They scored according to IMPeTUs scoring system, evaluating the number and intensity of foci of radiotracer uptake in 5 sites (spine, skull, extraspinal, visceral and nodal), the presence of diffuse axial and/or appendicular bone marrow uptake, of PET-positive lytic lesions, or of fractures. According to the number of visible foci in each site, the site-score was: 1: 0 focus, 2: 1-3 foci, 3: 4-10 foci or 4: >10 lesions. In case of diffuse bone marrow uptake by the axial or appendicular skeleton, the site-score 4 was attributed to the corresponding site, to integrate this pattern in one single score per site. A “SUMM” score, theoretically ranging from 5 to 20, was obtained by summing up the site-scores of the 5 sites. The kappa coefficient was calculated to evaluate the inter-reader agreement in determining the SUMM score.A consensus reading was finally performed, to solve discordances in scoring between the two readers. The paired Wilcoxon test was used to compare the consensual SUMM scores of PET/CT with FDG and FCH; the correlation coefficient between the consensual SUMM scores and M-protein level was calculated.Results:Before final consensus, the inter-reader agreement in determining the SUMM score was better with FCH (Kappa=0.90; CI=0.85-0.95) than with FDG (Kappa=0.75; CI=0.64-0.86). The analysis was then continued on the data of consensus reading. FCH showed more foci in 28 patients (4 at initial staging, 13 at relapse, 11 during follow up) and FDG in 14 patients (3 at initial staging, 4 at relapse, 7 during follow up). The SUMM score was significantly greater with FCH than with FDG (p=0.0027).M-protein was present in the serum of 95/105 patients. The correlation with serum M-protein level was significantly >0 for both SUMM scores, but loose for FDG (r=0.3, p=0.0029) and stronger for FCH (r=0.7, p<0.001), the difference being significant (p=0.0001).Among 8 patients without M-protein detected in their serum, a negative PET/CT with FDG (SUMM FDG=5) but positive with FCH (SUMM FCH>5) was observed in 2 patients (1 referred for evaluation of relapsing MM and in one referred during therapeutic follow-up of MM).Conclusion: A patient-based “SUMM” score is proposed to characterize the extension and the number of foci on PET/CT imaging of MM. Using this SUMM score, a better inter-reader reproducibility, lesion detectability and correlation with serum M-protein was observed for FCH than for FDG, confirming FCH as a potential tracer in MM deserving further research. DisclosuresGarderet:Celgene: Consultancy; Amgen: Consultancy; Takeda: Consultancy.

A predicting model of bone marrow malignant infiltration in 18F-FDG PET/CT images with increased diffuse bone marrow FDG uptake.

Purpose: To demonstrate the relationship between the etiologies of increased diffuse bone marrow (BM) 18F-FDG uptake and PET/CT imaging/clinical features, as well as to explore a predicting model of BM malignant infiltration (MI) based on decision tree.Methods: 84 patients with increased diffuse BM uptake were retrospectively enrolled. Their complete case record and PET/CT images were reviewed, with the maximal standardized uptake values of bone marrow (SUVmaxBM) and other imaging/clinical features were noted. At the same time, the differences in imaging/clinical features between bone marrow MI and non-MI groups were compared. The decision tree for predicting MI was established by C5.0 component of SPSS Clementine.Results: In patients with homogenously increased BM uptake, 21 patients had MI resulted from leukemia, lymphoma and small cell lung cancer (SCLC). MI group had higher SUVmaxBM than non-MI group (6.7±3.1 vs 4.2±0.9, p=0.001). However, a considerable proportion of MI patients had similar SUVmaxBM to non-MI patients, which were mainly seen in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM), chronic myeloid leukemia (CML) and multiple myeloma (MM). There were significant differences in other factors between the two groups. MI patients were highly associated with SUVmaxAP/AX≥1 (the ratio of SUVmaxBM of appendicular skeleton to that of axial skeleton), hepatosplenomegaly, older age and lower rate of fever. The decision tree combining SUVmaxBM, SUVmaxAP/AX, fever and hepatosplenomegaly achieved a sensitivity of 81.0%, a specificity of 98.4% and an accuracy of 94.0% for predicting MI.Conclusion: Increased diffuse BM 18F-FDG uptake can be attributed to both bone marrow MI and benign etiologies. A decision tree based on C5.0 algorithm, combining PET/CT imaging and clinical features, is of potential use in discriminating BM malignant infiltration from patients with increased diffuse BM uptake.

FDG PET/CT for Initial Staging of Diffuse Large B-Cell Lymphoma: Is Diffuse Bone Marrow Uptake a Reflection of Disease Involvement?

Objectives: Bone marrow assessment is a diagnostic challenge in staging diffuse large B-cell lymphoma (DLBCL). Diffuse bone marrow uptake (BMU) can be observed on FDG PET/CT performed for initial staging of DLBCL, but remains difficult to analyze. The aim of this study was to evaluate the meaning of this diffuse BMU, and especially to assess its correlation with bone marrow involvement (BMI). Methods: Patients who underwent FDG PET/CT for initial staging of DLBCL were analyzed. Diffuse BMU was assessed using a visual qualitative analysis according to liver uptake (grade 1=below liver uptake, 2=equal to liver uptake, 3=above liver uptake), and a semi-quantitative analysis, by measurement of maximum standardized uptake value (SUV) in the sacral promontory. We compared the BMU with BMI, parameters of disease extension and inflammatory markers. Results: 86 patients (median age 59, range: 19-91, 54 men, 32 women) were included. BMU grade was 1, 2 and 3 in 45, 28 and 13 cases respectively. Bone marrow was considered involved in 13 patients. No statistical correlation was found between diffuse BMU and BMI, using qualitative (p=0.594) or semi-quantitative method (p=0.116). Diffuse BMU visual grading was correlated with inflammatory markers: biological systemic symptoms (p=0.003), CRP (p=0.002) and fibrinogen (p=0.020). Conclusions: Our study suggests that a diffuse BMU seen on FDG PET/CT at initial staging of DLBCL is not representative of bone marrow involvement, but can be due to inflammatory changes.

Hyperfixation ostéomédullaire diffuse de la 18F-fluorocholine et hémopathies chroniques

We report here the cases of three patients presenting with prostate cancer history and chronic hemopathies in whom 18F-FCH PET/CT showed diffuse bone marrow uptake. All three patients had rising PSA. Diffuse bone marrow uptake was attributed to bone marrow involvement, caused by hemopathy. In our knowledge, similar 18F-FCH bone marrow uptake has not yet been described in chronic hemopathies. This pattern should not be mistaken with any metastatic bone involvement. Furthermore, attention has to be paid to detect coexisting skeletal metastases, which could be missed among the diffuse bone marrow uptake.

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.

Guidelines for the first line management of classical Hodgkin lymphoma

The guideline group was selected to be representative of UK-based medical experts and patients’ representatives. MEDLINE and EMBASE were searched systematically for publications in English from January 1990 to June 2013 using the key words Hodgkin, Lymphoma, Treatment, Chemotherapy and Radiotherapy. References from relevant publications were also searched. The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemato-Oncology Task Force of the British Committee for Standards in Haematology (BCSH). The guideline was then reviewed by a sounding board of approximately 50 UK haematologists and the BCSH and comments incorporated where appropriate. The ‘GRADE’ system was used to quote levels and grades of evidence, details of which can be found in Appendix I. The objective of this guideline is to provide healthcare professionals with clear guidance on the management of patients with classical Hodgkin Lymphoma (HL). The guidance may not be appropriate for all patients with HL and in all cases individual patient circumstances may dictate an alternative approach.

Diffuse bone marrow uptake of fluorodeoxyglucose in a patient with aleukaemic acute lymphoblastic leukaemia

Diffuse bone marrow uptake of fluorodeoxyglucose in a patient with aleukaemic acute lymphoblastic leukaemia

11C-Acetate as a new biomarker for PET/CT in patients with multiple myeloma: initial staging and postinduction response assessment

We investigated the potential value of (11)C-acetate (ACT) PET/CT in characterizing multiple myeloma (MM) compared with (18)F-FDG PET/CT. Bone marrow histological and whole-body (WB) MRI findings served as the reference standards. In this prospective study, 15 untreated MM patients (10 men and 5 women, age range 48-69 years) underwent dual-tracer (11)C-ACT and (18)F-FDG PET/CT and WB MRI for pretreatment staging, and 13 of them had repeated examinations after induction therapy. Diffuse and focal bone marrow uptake was assessed by visual and quantitative analyses, including measurement of the maximum standardized uptake value (SUVmax). Between-group differences and correlations were assessed with the Mann-Whitney U test and the Pearson test. At staging, all 15 patients had diffuse myeloma involvement upon bone marrow examination with 30-90 % of plasma cell infiltrates. Diffuse infiltration was detected in all of them (100 %) using (11)C-ACT with a positive correlation between bone marrow uptake values and percentages of plasma cell infiltrates (r = +0.63, p=0.01). In contrast, a diagnosis of diffuse infiltration could be established using (18)F-FDG in only six patients (40 %). Focal lesions were shown in 13 patients on both (11)C-ACT PET/CT and WB MRI, and in 10 patients on (18)F-FDG PET/CT. Focal lesions demonstrated (11)C-ACT uptake with a mean SUVmax of 11.4 ± 3.3 (range 4.6-19.6, n=59), which was significantly higher than the (18)F-FDG uptake (mean SUVmax 6.6 ± 3.1, range 2.3-13.7, n=29; p<0.0001). After treatment, the diffuse bone marrow (11)C-ACT uptake showed a mean SUVmax reduction of 66 % in patients with at least a very good partial response versus 34 % in those with at most a partial response only (p=0.01). PET/CT using (11)C-ACT as a biomarker showed a higher detection rate for both diffuse and focal myeloma lesions at diagnosis than using (18)F-FDG, and may be valuable for response assessment.

Unremitting pyrexia, pancytopenia, hepatosplenomegaly, and extreme hyperferritinemia

Unremitting pyrexia, pancytopenia, hepatosplenomegaly, and extreme hyperferritinemia

Diffuse Homogeneous Bone Marrow Uptake of FDG in Patients With Acute Lymphoblastic Leukemia

PET (positron emission tomography) using FDG (¹⁸F-fluorodeoxyglucose) has been widely used in the evaluation of various malignancies, but its clinical application to leukemia remains limited. We report a case of leukemia in which diffuse bone marrow uptake of FDG was observed, and bone marrow aspiration subsequently revealed acute lymphoblastic leukemia. It is not easy to differentiate between physiological and pathologic uptake when diffuse homogeneous uptake in bone marrow is observed.

A Japanese case of familial Mediterranean fever presenting diffuse bone marrow uptake of FDG-PET and high levels of neutrophil membrane CD64 expression

A Japanese case of familial Mediterranean fever presenting diffuse bone marrow uptake of FDG-PET and high levels of neutrophil membrane CD64 expression

Prognostic Relevance of 18F-FDG PET/CT In Newly Diagnosed Multiple Myeloma Patients Treated with up-Front Autologous Transplantation: A Prospective Study

AbstractAbstract 369F-18-fluorodeoxyglucose positron emission tomography integrated with computed tomography (FDG-PET/CT) has been reported to be a careful technique for a widespread screening of myelomatous lesions, both medullary and extramedullary, at the onset of multiple myeloma (MM). By the opposite, the role of FDG-PET/CT in assessing and monitoring response to therapy and the prognostic value of this imaging technique is less explored.Aim of the present study was to prospectively evaluate the prognostic significance of FDG-PET/CT at diagnosis and after therapy in an homogeneous population of patients with newly diagnosed MM who received up-front single or double autologous stem cell transplantation (ASCT). By study design, all patients were studied with FDG-PET/CT at baseline, 3 months after ASCT, every year during the maintenance/follow-up phase and at time of relapse. Bone marrow involvement was described as negative, diffuse or focal. The number of focal lesions (FL), as well as their size and associated standardized uptake values (SUV) were recorded. Extramedullary disease, if present, was described by location, size, number of lesions and SUV.A total of 146 patients who actually received the planned treatment program and were followed for a median of 39 months were analyzed. Their median age was 58 years. ISS stage was as follows: 48% stage I, 31% stage II, 14% stage III. Six per cent of the patients had renal failure, related to the presence of hypercalcemia at diagnosis. Del (13q), t(4;14) and del(17p), detected by FISH, were present in 47%, 25% and 10% of the patients, respectively. Induction treatment prior to ASCT included an IMiD in 55% of the patients, bortezomib in 34% and chemotherapy in 11% of the cases.The best overall response rate, including CR and at least VGPR, was 56% and 82%, respectively. Median PFS of the entire population was 55 months and the 5-year projected OS rate was 85%.At baseline, 22% of the patients had a negative PET/CT, 27% presented less than 3 FL and 51% 3 or more FL or a diffuse bone marrow uptake of FDG. In 44% of the cases the SUV was low (< 3.9) while in 56% was 4 or more. In 6% of the patients extramedullary disease was present.No significant differences between patients with positive or negative PET/CT were found regarding baseline characteristics and response to therapy. The entity of PET/CT involvement at baseline influenced clinical outcomes. In particular, patients with more than 3 FL and/or SUV > 3.9 had a significantly shorter OS in comparison with patients with FL < 3 and/or SUV < 3.9 (5-year projected OS: 92% vs 75%, respectively, P=0.04).After 3 months from ASCT, PET/CT was negative in 65% of the patients and remained positive, either unchanged or with a reduction in the SUV, in 35% of them. A correlation between PET/CT findings and response to ASCT was evident; in particular, among patients with negative PET/CT the rate of CR and VGPR was significantly higher than among patients with positive PET/CT (CR: 68% vs 38%; P= 0.001) (VGPR: 90% vs 76%; P= 0.008). Complete FDG suppression at PET/CT after ASCT conferred superior PFS and OS than persistence of FL (PFS: median 58 vs 45 months, respectively, P=0.05; 5-year projected OS: 92% vs 79%, respectively, P=0.004).In conclusion, involvement of PET/CT at diagnosis in terms of number of FL and intensity of tumour metabolism (SUV) predicted survival outcome. Complete FDG suppression after ASCT was strictly related with achievement of high-quality response and was prognostically relevant for durable disease control and longer OS. Disclosures:Cavo:Jansen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, no; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, no; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, no.

18F-FDG-PET findings of rare case of nonsecretory plasmablastic myeloma

A 61-year-old woman presented with pancytopenia and underwent a bone marrow biopsy. The patient was diagnosed with nonsecretory myeloma (plasmablastic type) based on both the bone marrow biopsy findings and her laboratory data. Fluorine-18 fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET) was performed prior to chemotherapy showing diffuse bone marrow uptake, splenic uptake, and focal uptake of the right anterior chest wall. The patient underwent an (18)F-FDG-PET examination to evaluate the curative effects after three cycles of chemotherapy, and no abnormal uptake on (18)F-FDG-PET was found. Bone marrow biopsy to evaluate the curative effect showed no viable tumor cells. We present a rare case of nonsecretory plasmablastic myeloma detected by (18)F-FDG-PET.