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.

Bone marrow biopsy in geriatric patients above the age of 85 years: invaluable or unnecessary? A retrospective analysis.

Bone marrow biopsy (BMB) is a well-established diagnostic tool for various hematological, oncological, and other medical conditions. However, treatment options for geriatric patients (pts) facing these diseases are often constrained. In this single-center, retrospective analysis we assessed the diagnostic value of BMB in geriatric pts aged ≥ 85 years and examined its impact on therapeutic decisions. We examined 156 BMB procedures in 129 pts, extracting data from the electronic patient records and applying descriptive statistical methods. Nearly half of the primary diagnostic procedures (26; 44.1%) resulted in a modification of the initially suspected diagnosis. Notably, 15 (25.4%) of these procedures, led to changes in both the diagnosis and planned interventional treatment. Among the 15 follow-up procedures (36.6%), disease progression was initially suspected based on symptoms, but BMB results excluded such progression. In lymphoma staging biopsies, only 2 (3.6%) prompted a change in therapeutic intervention. Importantly, no BMB-related complications, such as bleeding, infection or nerve damage, were reported. Median survival after BMB was 16.1 months across all pts, yet it varied based on the diagnosis and comorbidity score. The survival of pts with a change in therapy based on BMB results did not significantly differ from those who did not undergo a therapy change. In conclusion, BMB proved to be generally safe and beneficial in this geriatric cancer patient cohort beyond the age of 85 years. However, the advantages of lymphoma staging in this patient population warrant further consideration.

Value of hemophagocytosis in the diagnosis of hemophagocytic lymphohistiocytosis in critically ill patients.

BACKGROUND: Ferritin is an established biomarker in the diagnosis of secondary hemophagocytic lymphohistiocytosis (HLH), which is diagnosed by the HLH-2004 criteria. Among these criteria, detection of hemophagocytosis through invasive procedures may delay early life saving treatment. Our aim was to investigate the value of hemophagocytosis in diagnosing HLH in critically ill patients. METHODS: In this secondary analysis of a retrospective observational study, we included all patients aged ≥18 years and admitted to any adult ICU at Charité-Universitätsmedizin Berlin between January 2006 and August 2018, who had hyperferritinemia (≥500 µg/L) and underwent bone marrow biopsy during their ICU course. RESULTS: Two hundred fifty-two patients were included, of whom 31 (12.3%) showed hemophagocytosis. In multivariable logistic regression analysis, maximum ferritin was independently associated with hemophagocytosis. By removing hemophagocytosis from HLH-2004 criteria and HScore, prediction accuracy for HLH diagnosis was only marginally decreased compared to the original scores. CONCLUSIONS: Our results strengthen the diagnostic value of ferritin and underline the importance of considering HLH diagnosis in patients with high ferritin but only four fulfilled HLH-2004 criteria, when hemophagocytosis was not assessed or not detectable. Proof of hemophagocytosis is not required for a reliable HLH diagnosis.

Erythroid Predominance in Bone Marrow Biopsies of Acute Myeloid Leukemia Patients after Decitabine Treatment Correlates with Mutation Profile and Complete Remission.

INTRODUCTION: Acute myeloid leukemia (AML) patients may receive hypomethylating agents such as decitabine (DAC) as part of their treatment. Not all patients respond to this therapy, and if they do, the clinical response may occur only after 3-6 courses of treatment. Hence, early biomarkers predicting response would be very useful. METHODS: We retrospectively analyzed a cohort of 22 AML patients who were treated with DAC. Histology of the bone marrow biopsy, pathogenic mutations, and methylation status were related to the treatment response. RESULTS: In 8/22 (36%) patients, an erythroid dominant response (EDR) pattern, defined as a ratio of myeloid cells/erythroid cells <1, was observed. In the remaining 14 cases, a myeloid predominance was preserved during treatment. No difference in the hypomethylating effect of DAC treatment was observed in patients with and without EDR, as global 5-methylcytosine levels dropped similarly in both groups. Mutational analysis by NGS using a panel of commonly mutated genes in AML showed that patients with an early EDR harbored on average less mutations, with U2AF1 mutations occurring more frequently, whereas RUNX1 mutations were underrepresented compared to non-EDR cases. Interestingly, the development of an EDR correlated with complete remission (7/8 cases with an EDR vs. only 2/14 cases without an EDR). CONCLUSION: We conclude that early histological bone marrow examination for the development of an EDR may be helpful to predict response in AML patients during treatment with DAC.

Artificial Intelligence in Bone Marrow Histological Diagnostics: Potential Applications and Challenges.

The expanding digitalization of routine diagnostic histological slides holds a potential to apply artificial intelligence (AI) to pathology, including bone marrow (BM) histology. In this perspective, we describe potential tasks in diagnostics that can be supported, investigations that can be guided, and questions that can be answered by the future application of AI on whole-slide images of BM biopsies. These range from characterization of cell lineages and quantification of cells and stromal structures to disease prediction. First glimpses show an exciting potential to detect subtle phenotypic changes with AI that are due to specific genotypes. The discussion is illustrated by examples of current AI research using BM biopsy slides. In addition, we briefly discuss current challenges for implementation of AI-supported diagnostics.

Quantitative interpretation of bone marrow biopsies in MPN-What's the point in a molecular age?

The diagnosis of myeloproliferative neoplasms (MPN) requires the integration of clinical, morphological, genetic and immunophenotypic findings. Recently, there has been a transformation in our understanding of the cellular and molecular mechanisms underlying disease initiation and progression in MPN. This has been accompanied by the widespread application of high-resolution quantitative molecular techniques. By contrast, microscopic interpretation of bone marrow biopsies by haematologists/haematopathologists remains subjective and qualitative. However, advances in tissue image analysis and artificial intelligence (AI) promise to transform haematopathology. Pioneering studies in bone marrow image analysis offer to refine our understanding of the boundaries between reactive samples and MPN subtypes and better capture the morphological correlates of high-risk disease. They also demonstrate potential to improve the evaluation of current and novel therapeutics for MPN and other blood cancers. With increased therapeutic targeting of diverse molecular, cellular and extra-cellular components of the marrow, these approaches can address the unmet need for improved objective and quantitative measures of disease modification in the context of clinical trials. This review focuses on the state-of-the-art in image analysis/AI of bone marrow tissue, with an emphasis on its potential to complement and inform future clinical studies and research in MPN.

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes: A workshop report with focus on novel entities and a literature review including paediatric cases.

Myeloid/lymphoid neoplasms with eosinophilia (M/LN-eo) and tyrosine kinase (TK) gene fusions are a rare group of haematopoietic neoplasms with a broad range of clinical and morphological presentations. Paediatric cases have increasingly been recognised. Importantly, not all appear as a chronic myeloid neoplasm and eosinophilia is not always present. In addition, standard cytogenetic and molecular methods may not be sufficient to diagnose M/LN-eo due to cytogenetically cryptic aberrations. Therefore, additional evaluation with fluorescence in-situ hybridisation and other molecular genetic techniques (array-based comparative genomic hybridisation, RNA sequencing) are recommended for the identification of specific TK gene fusions. M/LN-eo with JAK2 and FLT3-rearrangements and ETV6::ABL1 fusion were recently added as a formal member to this category in the International Consensus Classification (ICC) and the 5th edition of the WHO classification (WHO-HAEM5). In addition, other less common defined genetic alterations involving TK genes have been described. This study is an update on M/LN-eo with TK gene fusions with focus on novel entities, as illustrated by cases submitted to the Bone Marrow Workshop, organised by the European Bone Marrow Working Group (EBMWG) within the frame of the 21st European Association for Haematopathology congress (EAHP-SH) in Florence 2022. A literature review was performed including paediatric cases of M/LN-eo with TK gene fusions.

Update on follicular lymphoma.

The past two decades have seen remarkable progress in both biological understanding and optimizing treatment of follicular lymphoma. Historically considered an incurable disease, long-term follow-up of several induction approaches demonstrates that up to 40% of patients enjoy remission durations of 10 or more years, and risk of dying of lymphoma continues to fall. This update will focus on progress in follicular lymphoma over the past 3 years, which has included refinements in staging and prognosis, novel immunotherapy treatment approaches for relapsed and refractory disease, and long-term follow-up of pivotal trials. Ongoing trials will define the optimal sequence for these novel treatments, including whether earlier incorporation of these approaches may result in definitive cure of this disease. Through ongoing and planned correlative studies, we are poised to ultimately achieve the goal of a precision management approach to follicular lymphoma.

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.

(Smoldering) multiple myeloma: mismatch between tumor load estimated from bone marrow biopsy at iliac crest and tumor load shown by MRI.

In multiple myeloma and its precursor stages, precise quantification of tumor load is of high importance for diagnosis, risk assessment, and therapy response evaluation. Both whole-body MRI, which allows to investigate the complete bone marrow of a patient, and bone marrow biopsy, which is commonly used to assess the histologic and genetic status, are relevant methods for tumor load assessment in multiple myeloma. We report on a series of striking mismatches between the plasma cell infiltration estimating the tumor load from unguided biopsies of the bone marrow at the posterior iliac crest and the tumor load assessment from whole-body MRI.

Diagnostic Accuracy of 18F-FDG PET - CT Imaging in determining the bone marrow involvement (BMI) in pediatric Hodgkin's Lymphoma (HL).

Objective: To determine diagnostic accuracy of 18F-FDG PET - CT imaging in determining Bone marrow involvement in pediatric HL by taking bone marrow biopsy as standard. Method: This descriptive cross-sectional study was conducted in the Department of Pediatric Hematology/Oncology, Indus Hospital and Health Network, Karachi from July 2021 to December 2022. Treatment naïve histologically proven pediatric HL patients of both gender and aged between two to 16 years with both 18F-FDG PET - CT and bone marrow biopsy imaging were included. Basic demographics such as age, gender, height, weight, as well as classification and staging of HL was obtained. Results were assessed by expert reviewers who were blinded to clinical outcome. Sensitivity, specificity, positive and negative predictive value, and diagnostic precision were assessed. The data was analyzed via SPSS 26.0. Results: Total 131 participants were included with a male predominance i.e. 104 (79.6%). The mean (±SD) age was 8.7 ± 3.4 years. The present study reported PET/CT to have a sensitivity, specificity diagnostic accuracy, PPV and NPV of 94.1%, 92%, 92%, 64% and 99% respectively. Conclusion: Our findings support the idea that BMB should not be routinely conducted in all patients but rather can be reserved exclusively for patients with dubious 18F-FDG bone marrow findings, as this test has strong diagnostic potential for evaluating BMI involvement in HL.

Frequency of benign neutropenia among Black versus White individuals undergoing a bone marrow assessment.

Healthy individuals in the United States identified as having Black race have lower neutrophil counts, on average, than individuals identified as having White race, which could result in more negative diagnostic evaluations for neutropenia. To test this hypothesis, the proportion of evaluations where the final diagnosis was clinically insignificant neutropenia for Black and White individuals who underwent an evaluation by a haematologist that included a bone marrow (BM) biopsy to investigate neutropenia was assessed. 172 individuals without prior haematological diagnoses who underwent a haematological evaluation to investigate neutropenia. Individuals diagnosed with clinically insignificant neutropenia between Black and White individuals were compared using a propensity-score-adjusted logistic regression. Of 172 individuals, 42 (24%) were classified as Black race, 86 (50%) were males, and the 79 (46%) were over 18 years old. A BM biopsy did not identify pathology in 95% (40 of 42) of Black individuals and 68% (89 of 130) of White Individuals. Black individuals (25 of 42 [60%]) received a final diagnosis of clinically insignificant neutropenia, compared to White individuals (12 of 130 [9%]) (adjusted odds ratio =7.9, 95% CI: 3.1 - 21.1). We conclude that black individuals were more likely to receive a diagnosis of clinically insignificant neutropenia after haematological assessment.

Of drills and bones: Giovanni Ghedini and the origin of bone marrow biopsy.

Bone marrow (BM) studies are pivotal for the diagnosis of haematological disorders. Their introduction into clinical haematology dates back to the work of Giovanni Ghedini (1877-1959), an Italian physician who first conceived BM sampling in 1908. Ghedini's proposal stemmed from his clinical experience and from the scientific developments that characterised his epoch. By presenting selected passages of Ghedini's publications, this report considers the theoretical and historical bases of his work and analyses its practical implications for modern haematology.

Management of bone marrow biopsy related bleeding risks: a retrospective observational study.

Bone marrow biopsies are largely used for the diagnosis and prognostic of various hematological diseases. Complications are rare but can be as serious as hemorrhage. However, little is known about management of patients deemed at high hemorrhagic risk like thrombocytopenic patients or patients receiving antithrombotic drugs. The aim of the study was to describe the management of patients regarding their laboratory profile and antithrombotic treatment prior to bone marrow biopsy and the short-term outcomes, notably hemorrhage. We conducted a retrospective observational study between February 2007 and March 2018. A standardized form was used to collect data from patients' records, blood tests results, management of antiplatelet and anticoagulant treatment before biopsy and complications including bleeding and thromboembolic events until 3 months after the biopsy. A total of 524 bone marrow biopsies were performed. No major bleeding events were reported. The incidence of clinically relevant non-major bleeding was 0.19% (CI 95% 0.00-1.20) and was linked to low platelets counts (p = 0.002) and not to abnormal coagulation profile or antithrombotic therapy, whether or not a bridging therapy has been used. Anticoagulants were temporarily stopped before biopsy in most cases without subsequent thrombotic complications. Our data suggest that thrombocytopenic patients have a non-negligible bleeding risk. Coagulation profiling seems irrelevant. We propose an algorithm to assist the management of those patients, notably when receiving antithrombotic drugs.

Complications associated with improper palpation-guided iliac bone marrow biopsy tracts identified on follow-up imaging.

OBJECTIVE: Bone marrow biopsy complications are rare. Our aim is to study the association of improper palpation-guided iliac biopsy tract with complications. MATERIALS AND METHODS: This is a retrospective study of adult patients who underwent iliac bone marrow biopsy without image guidance at our hospital from January 2019 to January 2021, and have cross-sectional radiologic imaging of the pelvis within 30 days following the procedure. Electronic health records were reviewed for clinical data. Two radiologists reviewed images of the pelvis for assessment of biopsy tract and complications. RESULTS: A total of 443 procedures were included in 309 patients, mean age 53.4 ± 18.1 years, 112 females (36.2%). In addition, 332 tracts were proper (75%), 97 improper (22%), and 14 unidentified (3%). All 11 complications occurred in procedures with improper tracts; nine bleeding, one fracture, and one facet joint injury. Improper tract was significantly associated with complications (p < .001). There was no statistically significant association between platelet count, international normalized ratio, antiplatelet use and anticoagulant use, and presence of complications (p > .05). Body mass index and subcutaneous fat thickness overlying posterior superior iliac spine were not associated with improper tract (p > .05). Procedures performed by providers with ≤ 12 months' experience were significantly associated with improper tract (p < .001) and hence associated with complications (p = .007). CONCLUSION: Improper tracts were common in palpation-guided iliac bone marrow biopsy and significantly associated with complications. No complications were encountered in proper tract procedures. Procedures performed by providers with ≤ 12 months' experience were significantly associated with improper tract and complications.

Bone marrow aspiration and biopsy: techniques and practice implications.

Bone marrow aspiration and biopsy (BMAB) is a valuable diagnostic procedure commonly performed for evaluation of a wide spectrum of diseases including hematologic abnormalities, nonhematologic malignancies, metabolic abnormalities, and tumor treatment response such as chemotherapy and bone marrow transplantation, hematologic tumor staging, and suspected infection in patients with fever of unknown origin. This minimally invasive intervention offers excellent safety profile and a high diagnostic yield. Radiologists should be familiar with clinical implications of BMAB for patient care and be able to implement various technical armamentarium available to achieve a safe intervention while maximizing procedure yield.

Comparison of bone marrow trephine sample quality between a drill-powered system and a manual needle system.

CONTEXT: Bone marrow biopsy (BMB) is a common procedure in haematology used for the diagnosis and evaluation of response treatment. Because the procedure is difficult for haematologists to perform, patients often experience pain and stress. On Control, a system device, was introduced in the 2000s and uses a drill-powered needle to perform BMB. OBJECTIVE: The aim of this study was to compare the quality of BMB, based on the length of the trephine, the number of interosseous spaces and the interpretability of the examination, obtained from manual BMB vs. drill-powered BMB. The secondary objectives were to evaluate the patient's pain and anxiety, and the haematologist's perceived difficulty in performing BMB. DESIGN: This was a retrospective study conducted between June 2016 and June 2017 in the Henri Becquerel Cancer Centre in Rouen, France. RESULTS: A total of 439 patients were included in the study; the sex ratio (M:F) was 1.34 and 70.2% underwent a drill-powered BMB. A significant difference was observed concerning trephine length (14.30 ± 5.58 mm with the drill-powered system vs. 11.18 ± 4.43 mm with manual BMB, p < 0.0001) and the number of interosseous spaces (9.49 ± 5.35 vs. 7.93 ± 4.01, respectively, p = 0.01). The interpretability of the examination did not differ between the two procedures (p = 0.9). CONCLUSIONS: On Control, the drill-powered system for BMB, is widely distributed in North America and Europe, but this procedure is not yet generally applied. Although this procedure is costly, the ongoing development of this technique, because of its performance, is beneficial especially to obese patients.

Patients with mast cell activation symptoms and elevated baseline serum tryptase level have unique bone marrow morphology.

BACKGROUND: Patients with mast cell (MC) activation symptoms and elevated baseline serum tryptase level (MCAS-T) may not necessarily have a clonal MC disorder. Many are diagnosed with hereditary α-tryptasemia (HαT), a genetic trait characterized by autosomal dominant inheritance of multiple copies of TPSAB1 encoding α-tryptase and increased risk for severe anaphylaxis. OBJECTIVE: The aim of our study was to identify and characterize bone marrow MC histopathologic features specific for MCAS-T. METHODS: A total of 43 patients with MCAS-T underwent evaluation, including bone marrow biopsy, for a MC disorder. The results of the work-up for clonal MC disorders such as systemic mastocytosis and monoclonal MC activation syndrome were negative. Bone marrow MC histopathology was reviewed to identify characteristic features of MCAS-T. A subgroup of patients was available for tryptase genotyping. RESULTS: Patients with MCAS-T showed unique morphologic and histologic features when compared with controls. MCs were larger (P < .01), hypogranular (P < .01), frequently detected in paratrabecular (P < .05) and perivascular (P < .01) locations, and associated with bone marrow eosinophilia (P < .01). A total of 10 patients who were available for tryptase genotyping were all confirmed to have HαT. This subgroup was representative of the larger MCAS-T cohort. CONCLUSION: We report unique bone marrow MC phenotypic and histopathologic changes in patients with MCAS-T. These morphologic changes are associated with an elevated tryptase level that has been confirmed to be caused by HαT in all patients available for testing.

Diagnostic importance of bone marrow aspiration evaluation: A single-center study.

Background & Objective: Early diagnosis can be made based on the morphological examination of bone marrow aspiration (BMA) until the bone marrow biopsy (BMB) result is reported. This allows for treatment to be started immediately, especially in hematological malignancies for which urgent treatment is indicated. This study aimed to determine the sensitivity and importance of bone marrow aspiration in the diagnosis of hematological malignancies. Methods: In this study, the data of patients who underwent bone marrow aspiration and bone marrow biopsy in Van Yuzuncu Yil University hospital between 2017 and 2019 were retrospectively analyzed. A total of 500 patients who simultaneously underwent BMA and BMB were included in the study. Data were obtained from electronic medical records. Results: Indication for bone marrow evaluation was abnormalities in complete blood count in 270 (54%) of patients. The diagnosis was made based on the evaluation of BMA in 475 (95%). In 456 (96%) of the 475 patients diagnosed with BMA, the diagnosis was consistent with that of BMB. Agreement of BMB with BMA was 100% in acute and chronic leukemias, while BMA was not sufficient for the diagnosis of lymphoma and solid organ metastasis. Conclusion: Our study showed that the evaluation of BMA was highly sensitive in the diagnosis of hematological malignancies, such as acute leukemias, chronic leukemias, and multiple myeloma.

FDG PET/CT to detect bone marrow involvement in the initial staging of patients with aggressive non-Hodgkin lymphoma: results from the prospective, multicenter PETAL and OPTIMAL>60 trials.

PURPOSE: Fluorine-18 fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET/CT) is the standard for staging aggressive non-Hodgkin lymphoma (NHL). Limited data from prospective studies is available to determine whether initial staging by FDG PET/CT provides treatment-relevant information of bone marrow (BM) involvement (BMI) and thus could spare BM biopsy (BMB). METHODS: Patients from PETAL (NCT00554164) and OPTIMAL>60 (NCT01478542) with aggressive B-cell NHL initially staged by FDG PET/CT and BMB were included in this pooled analysis. The reference standard to confirm BMI included a positive BMB and/or FDG PET/CT confirmed by targeted biopsy, complementary imaging (CT or magnetic resonance imaging), or concurrent disappearance of focal FDG-avid BM lesions with other lymphoma manifestations during immunochemotherapy. RESULTS: Among 930 patients, BMI was detected by BMB in 85 (prevalence 9%) and by FDG PET/CT in 185 (20%) cases, for a total of 221 cases (24%). All 185 PET-positive cases were true positive, and 709 of 745 PET-negative cases were true negative. For BMB and FDG PET/CT, sensitivity was 38% (95% confidence interval [CI]: 32-45%) and 84% (CI: 78-88%), specificity 100% (CI: 99-100%) and 100% (CI: 99-100%), positive predictive value 100% (CI: 96-100%) and 100% (CI: 98-100%), and negative predictive value 84% (CI: 81-86%) and 95% (CI: 93-97%), respectively. In all of the 36 PET-negative cases with confirmed BMI patients had other adverse factors according to IPI that precluded a change of standard treatment. Thus, the BMB would not have influenced the patient management. CONCLUSION: In patients with aggressive B-cell NHL, routine BMB provides no critical staging information compared to FDG PET/CT and could therefore be omitted. TRIAL REGISTRATION: NCT00554164 and NCT01478542.