Bone Marrow Infiltration Research Articles

Bone marrow infiltration in diffuse large B-cell lymphoma: impact of 18FDG-PET/CT in detection and prediction of therapy outcome

Bone marrow infiltration in diffuse large B-cell lymphoma: impact of 18FDG-PET/CT in detection and prediction of therapy outcome

Prevalence of hypersensitivity reactions in various forms of mastocytosis: A pilot study of 2485 adult patients with mastocytosis collected in the ECNM registry.

Hypersensitivity reactions (HR) are common in mastocytosis. However, little is known about triggers and risk factors. The registry of the European Competence Network on Mastocytosis (ECNM) enables reliable studies in a larger cohort of mastocytosis patients. We assessed prevalence, triggers and risk factors of HR in adults with mastocytosis in the ECNM registry. Data were collected in 27 ECNM centers. We analyzed potential triggers (Hymenoptera venoms, food, drug, inhalant and others) and risk factors at diagnosis and during follow-up. The study group consisted of 2485 adults with mastocytosis, 1379 women (55.5%) and 1106 men (44.5%). Median age was 48.2 years (range 18-91 years). Nine hundred and forty eight patients (38.1%) reported one or more HR`. Most common triggers were Hymenoptera venoms in cutaneous mastocytosis (CM) and indolent systemic mastocytosis (ISM), whereas in advanced SM (advSM), most common elicitors were drugs, including nonsteroidal anti-inflammatory agents and penicillin. In multivariate analyses, tryptase level < 90 ng/mL, <15% infiltration by mast cells in bone marrow biopsy-sections, and diagnosis of ISM were identified as independent risk factors for HR. For drug-induced HR, prominent risk factors were advSM and high tryptase levels. New reactions were observed in 4.8% of all patients during 4 years follow-up. HR are mainly triggered by Hymenoptera venoms in patients with CM and ISM and by drugs in patients with advSM. Tryptase levels <90 ng/mL, mast cell bone marrow infiltration <15%, and WHO category ISM are predictors of HR. New HR occur in 4.8% of all patients within 4 years.

Endocrinological and metabolic profile of Gaucher disease patients treated with enzyme replacement therapy.

Gaucher disease (GD) is a lysosomal storage disease caused by glucocerebrosidase (GCase) enzyme deficiency. Gaucher cells transformed from the macrophages by progressive sphingolipid accumulation and infiltrate bone marrow, spleen, liver, and other organs. The accumulation of substrate causes inflammation, compromised cellular homeostasis, and disturbed autophagy. It has been hypothesized that this proinflammatory state of GD leads cytokines and chemokines release. As a result of inflammatory process, the cellular dysfunction caused by disruption of cellular signaling, organelle dysfunction, or autoimmune antibodies may affect endocrine profile of GD patients such as hormone levels, lipid profile, and bone mineral density status. A total of 13 patients confirmed to have GD, 12 non-neuronopathic type and one subacute neuronopathic type, were enrolled in our study. The median treatment duration in the enzyme therapy was 13.33 years (9-26 years). At least one endocrinological abnormality was detected in blood tests of nine patients. Hyperinsulinism was the most common finding although fasting blood glucose levels HgbA1c levels were normal in all patients. Two patients had osteopenia, and osteoporosis was detected in two patients. Low HDL levels were detected in six patients, but HDL levels below 23 mg/dL associated with disease severity have been detected in two patients who have not receiving enzyme replacement therapy. None of patients had thyroidal dysfunction. This study had revealed endocrinological abnormalities in GD patients that have not led any severe morbidity in our patients. However, thyroid hormone abnormalities, insulin resistance, or lipid profile abnormalities may cause unpredictable comorbidities. Endocrinological assessment in GD patients in routine follow-up may prevent possible clinical manifestation in long term as well as can define efficacy of ERT on endocrine abnormalities.

Targeting foamy macrophages by manipulating ABCA1 expression to facilitate lesion healing in the injured spinal cord

Spinal cord injury (SCI) triggers a complex cascade of events, including myelin loss, neuronal damage, neuroinflammation, and the accumulation of damaged cells and debris at the injury site. Infiltrating bone marrow derived macrophages (BMDMϕ) migrate to the epicenter of the SCI lesion, where they engulf cell debris including abundant myelin debris to become pro-inflammatory foamy macrophages (foamy Mϕ), participate neuroinflammation, and facilitate the progression of SCI. This study aimed to elucidate the cellular and molecular mechanisms underlying the functional changes in foamy Mϕ and their potential implications for SCI. Contusion at T10 level of the spinal cord was induced using a New York University (NYU) impactor (5 g rod from a height of 6.25 mm) in male mice. ABCA1, an ATP-binding cassette transporter expressed by Mϕ, plays a crucial role in lipid efflux from foamy cells. We observed that foamy Mϕ lacking ABCA1 exhibited increased lipid accumulation and a higher presence of lipid-accumulated foamy Mϕ as well as elevated pro-inflammatory response in vitro and in injured spinal cord. We also found that both genetic and pharmacological enhancement of ABCA1 expression accelerated lipid efflux from foamy Mϕ, reduced lipid accumulation and inhibited the pro-inflammatory response of foamy Mϕ, and accelerated clearance of cell debris and necrotic cells, which resulted in functional recovery. Our study highlights the importance of understanding the pathologic role of foamy Mϕ in SCI progression and the potential of ABCA1 as a therapeutic target for modulating the inflammatory response, promoting lipid metabolism, and facilitating functional recovery in SCI.

18F-FDG PET/CT versus bone marrow biopsy in detecting bone marrow infiltration in initial staging of pediatric lymphoma.

To evaluate the efficacy of PET/CT using18F-FDG (18F-fluorodeoxyglucose) as a radiotracer compared to conventional bone marrow biopsy (BMB) in detecting infiltration to bone marrow (BM) in pediatric patients with lymphoma at the time of initial diagnosis. 66 pediatric patients with lymphoma (47Hodgkin's and 19non-Hodgkin's lymphoma) were referred for initial staging by18F-FDG PET/CT study. All patients underwent bilateral iliac BMB and 18F-FDG PET/CT scan with no more than 2 weeks interval in-between. Follow-up for at least 6 months was used as a reference standard to compare diagnostic performance between two modalities in detecting bone marrow infiltration (BMI). Sensitivity, specificity, accuracy, as well as positive and negative predictive values of 18F-FDG PET/CT in detecting BMI were (80%, 86%, 85%, 63%, and 94%) in contrast to BMB (80%, 53%, 59%, 33%, and 90%) respectively. 18F-FDG PET/CT was concordant to BMB in 39/66 patients (59%). 18F-FDG PET/CT was more accurate and specific, with higher predictive values than BMB in detecting BMI during initial staging of pediatric lymphoma. In most pediatric lymphoma patients, 18F-FDG PET/CT can be used instead of BMB to determine BMI during their initial staging process.

Infiltration of Round Blue Cell Tumors in Bone Marrow

Objective: To identify different types of round blue cell tumors on bone marrow biopsy and their pattern of marrow infiltration. Methodology: This cross-sectional descriptive study was conducted at the Department of Hematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from July 2021 to December 2021. A total of 60 diagnosed cases of round blue cell tumors were included. Patients with acute lymphoblastic leukemia (ALL) and those receiving treatment for round blue cell tumors were excluded. Bone marrow aspiration and biopsy were performed. Peripheral film results, clinical observations, and patterns of marrow infiltration of round blue cell malignancies were analyzed using Statistical Package for the Social Sciences (SPSS) version 23. Results: The study revealed a male to female ratio of 2:1, with 40 (66.6%) males and 20 (33.3%) females. The overall average age was 5.69 ± 5.0 years. Ewing sarcoma and rhabdomyosarcoma patients did not exhibit infiltration, while three instances of retinoblastoma (9.37%) and two cases of neuroblastoma (10.52%) did. Immunohistochemistry (IHC) results for synaptophysin and chromogranin were positive for retinoblastoma and neuroblastoma, while S100 results were positive for neuroblastoma infiltration and negative for retinoblastoma. Both retinoblastoma and neuroblastoma showed diffuse, focal, and interstitial patterns of infiltration on trephine biopsy. Conclusion: Small round blue cell tumors were noted in bone marrow infiltration in 5 (8.33%) cases. Early detection of malignant cancers necessitates appropriate medical care, and in more severe cases, the need for neoadjuvant chemotherapy.

The Value of Baseline PET/CT Imaging of Bone Marrow 18F-FDG Uptake Pattern in Predicting Prognosis of DLBCL

To investigate the prognostic value of bone marrow uptake pattern in 18F-deoxyglucose (18F-FDG) PET/CT imaging before diffuse large B-cell lymphoma (DLBCL) treatment. The clinical data of 156 patients with DLBCL were retrospectively analyzed. All patients underwent bone marrow biopsy, bone marrow smear, flow cytometry and 18F-FDG PET/CT scan before treatment. Taking normal liver 18F-FDG uptake as the standard, the bone marrow uptake patterns of patients were divided into three types: focal increased bone marrow uptake (fPET+), diffusely increased bone marrow uptake (dPET+), and normal bone marrow uptake (nPET). Survival analysis was performed using the Kaplan-Meier method, log-rank test was used for comparison of differences between groups, and multivariate Cox regression analysis was used to identify risk factors associated with prognosis. Among the 156 patients, 17 cases were fPET+, 28 cases were dPET+, and 111 cases were nPET. Clinical diagnosis of bone marrow infiltration (BMI) was positive in 21 cases and negative in 135 cases. There were 62 cases of recurrence and progression, and 18 cases of death. Univariate analysis showed that Ann Arbor stage III/IV, B symptoms, NCCN-IPI score, lactate dehydrogenase (LDH), BMI+ and fPET+ were associated with progression-free survival (PFS) (all P < 0.05), while Ann Arbor stage III/IV, NCCN-IPI score, LDH, BMI+ and fPET+ were associated with overall survival (OS) (all P < 0.05). Multivariate analysis showed that Ann Arbor stage III/IV, LDH and fPET+ were independent predictors of PFS (all P < 0.05). There were no independent predictors of OS in multivariate analysis. The bone marrow uptake pattern of 18F-FDG imaging in DLBCL patients before treatment has a predictive value for DLBCL, while fPET+ is an independent risk factor for PFS.

FLT3 and IRAK4 Inhibitor Emavusertib in Combination with BH3-Mimetics in the Treatment of Acute Myeloid Leukemia.

Targeting the FLT3 receptor and the IL-1R associated kinase 4 as well as the anti-apoptotic proteins MCL1 and BCL2 may be a promising novel approach in the treatment of acute myeloid leukemia (AML). The FLT3 and IRAK4 inhibitor emavusertib (CA4948), the MCL1 inhibitor S63845, the BCL2 inhibitor venetoclax, and the HSP90 inhibitor PU-H71 were assessed as single agents and in combination for their ability to induce apoptosis and cell death in leukemic cells in vitro. AML cells represented all major morphologic and molecular subtypes, including FLT3-ITD and NPM1 mutant AML cell lines and a variety of patient-derived AML cells. Emavusertib in combination with MCL1 inhibitor S63845 or BCL2 inhibitor venetoclax induced cell cycle arrest and apoptosis in MOLM-13 cells. In primary AML cells, the response to emavusertib was associated with the presence of the FLT3 gene mutation with an allelic ratio >0.5 and the presence of NPM1 gene mutations. S63845 was effective in all tested AML cell lines and primary AML samples. Blast cell percentage was positively associated with the response to CA4948, S63845, and venetoclax, with elevated susceptibility of primary AML with blast cell fraction >80%. Biomarkers of the response to venetoclax included the blast cell percentage and bone marrow infiltration rate, as well as the expression levels of CD11b, CD64, and CD117. Elevated susceptibility to CA4948 combination treatments with S63845 or PU-H71 was associated with FLT3-mutated AML and CD34 < 30%. The combination of CA4948 and BH3-mimetics may be effective in the treatment in FLT3-mutated AML with differential target specificity for MCL1 and BCL2 inhibitors. Moreover, the combination of CA4948 and PU-H71 may be a candidate combination treatment in FLT3-mutated AML.

DETERMINATION OF SERUM INTERLEUKIN-36 ALPHA, BETA, GAMMA AND INTERLEUKIN-17 LEVELS IN PATIENTS WITH MULTIPLE MYELOMA

Multiple myeloma (MM) is a hematologic malignancy characterized by bone marrow infiltration of clonal plasma cells. Today, there is no treatment for obtaining a complete cycle for MM. IL-36 is a cytokine composed of three agonists named alpha, beta, and gamma. Its increase in inflammation has been proven in the literature. It is also reported that IL-17 plays a role in some rheumatologic and malignant diseases together with inflammation. &#x0D; The aim of the study is to figure out the roles, if any, of IL-36 and IL-17 in the pathogenesis of multiple myeloma depending on their known physiology and to contribute to the literature to find new treatment options.&#x0D; 33 newly diagnosed MM patients who had never received any treatment and 33 healthy volunteers were included in the study. Basic laboratory parameters and interleukin levels in myeloma patient group and healthy group were included in the study.&#x0D; In the study, it was found that IL-36 alpha, beta, gamma, and IL-17 levels were statistically significantly lower in the disease group when compared to the healthy group. A negative correlation was found between IL-17 measurement and beta-2 microglobulin. Therefore, it was thought that IL-17 may be a marker to predict prognosis.&#x0D; In conclusion, we think that IL-36 and IL-17 may play a role in the etiopathogenesis of myeloma and IL-36 alpha and IL-17 may be associated with prognosis. However, there is a need for more comprehensive studies.

Comparative Review of the Current and Future Strategies to Evaluate Bone Marrow Infiltration at Diffuse Large B-Cell Lymphoma Diagnosis.

Diffuse large B-cell lymphoma (DLBCL) requires a complete staging at diagnosis that may have prognostic and therapeutic implications. The role of bone marrow (BM) biopsy (BMB) is controversial in the era of nuclear imaging techniques. We performed a comparative review of 25 studies focused on BM evaluation at DLBCL diagnosis, including at least two of the following techniques: BMB, flow cytometry, and positron emission tomography (PET-FDG). The report about BM involvement (BMi), diagnostic accuracy, and prognostic significance was collected and compared among techniques. A concordance analysis between BMB, FCM, and PET was also performed, and we deeply evaluated the implications of the different types of BMi: concordant by LBCL or discordant by low-grade B-cell lymphoma for both BMB and FCM, and focal or diffuse uptake pattern for PET. As a main conclusion, BMB, FCM, and PET are complementary tools that provide different and clinically relevant information in the assessment of BMi in newly diagnosed DLBCL.

Hairy cell leukemia 2024: Update on diagnosis, risk-stratification, and treatment-Annual updates in hematological malignancies.

Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogenous group of mature lymphoid B-cell disorders characterized by the identification of hairy cells, a specific genetic profile, a different clinical course and the need for appropriate treatment. Diagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11c, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral bone marrow infiltration and the presence of BRAFV600E somatic mutation. Progression of patients with HCL is based on a large splenomegaly, leukocytosis, a high number of hairy cells in the peripheral blood, and the immunoglobulin heavy chain variable region gene mutational status. VH4-34 positive HCL cases are associated with a poor prognosis, as well as HCL with TP53 mutations and HCL-V. Patients should be treated only if HCL is symptomatic. Chemotherapy with risk-adapted therapy purine analogs (PNAs) are indicated in first-line HCL patients. The use of chemo-immunotherapy combining cladribine (CDA) and rituximab (R) represents an increasingly used therapeutic approach. Management of relapsed/refractory disease is based on the use of BRAF inhibitors (BRAFi) plus R, MEK inhibitors (MEKi), recombinant immunoconjugates targeting CD22, Bruton tyrosine kinase inhibitors (BTKi), and Bcl-2 inhibitors (Bcl-2i). However, the optimal sequence of the different treatments remains to be determined.

Unpredicted transformation of acute myeloid leukemia with translocation (16;16) (p13; q22): a case report and review of the literature

IntroductionThe transformation of acute myeloid leukemia with translocation (16;16) (p13; q22) from AML M2 to acute monocytic leukemia (AML M5) during therapy is a rare clinical occurrence, and this is the first time it has been reported.Clinical complainA 19-year-old male patient was admitted for severe fatigue with anemic manifestation and weight loss, for more than 1 month, with exacerbation of the condition in the last 2 days.DiagnosisA primary diagnosis was made for AML M2 with t (16;16) (p13; q22) established on bone marrow (BM) morphology. A consequential detection of FLT-3 ITD mutation was done. At day 28 follow-up after induction and maintenance therapy, the diagnosis of AML M2 was maintained with a high bone marrow (BM) blast count, prompting the initiation of a more aggressive treatment protocol. After 1 month of implementing the recent protocol, the patient remains morphologically resistant with a notable transformation of bone marrow infiltration by an abnormal monocytic population (monoblasts and promonocytes). The final diagnosis of transforming FLT3-mutated AML with t (16;16) (p13; q22) was established.InterventionAfter the initial diagnosis of AML M2 with t (16;16) (p13; q22), the patient received the 3 + 7 induction protocol. The 2nd induction protocol initiated after the second evaluation and morphological resistance was the FLAG Adrian protocol. The 3rd protocol after transformation to AML M5 was 1 cycle of the MEC protocol. Anti-FLT3 treatment was considered.OutcomesThe patient was maintained on the 3rd protocol of chemotherapy. Unfortunately, he was admitted to the ICU unit complaining of neutropenic fever and severe sepsis where he died before final re-evaluation and the anti-FLT3 treatment initiation.ConclusionAML with t (16;16) (p13; q22) characterized by favorable outcome. However, identifying additional chromosome abnormality or genetic aberration, especially FLT3 gene mutation, is recognized as an important factor influencing final disease outcome. Therefore, early detection of FLT3 mutations will allow comprehensive disease course prediction and targeted therapy that might achieve longer and more durable remissions.

Current Approaches in the Management of Monoclonal Gammopathies: an approach to Waldenström Macroglobulinemia

Monoclonal gammopathies encompass a spectrum of disorders characterized by the abnormal proliferation of plasma cells, leading to the production of monoclonal immunoglobulins. Waldenström macroglobulinemia (WM) is a rare, indolent lymphoproliferative disorder characterized by the presence of an IgM monoclonal gammopathy, bone marrow infiltration by lymphoplasmacytic cells, and clinical features such as hyperviscosity, lymphadenopathy, and hepatosplenomegaly. Recent advances in understanding the pathogenesis of WM have led to the development of novel therapeutic strategies, including targeted therapies and immunomodulatory agents, which have significantly improved outcomes for patients. This article provides an overview of the current understanding of WM pathophysiology, clinical presentation, diagnostic approach, and recent advancements in its management.

Detecting bone marrow infiltration in nonosteolytic multiple myeloma through separation of hydroxyapatite via the two-material decomposition technique in spectral computed tomography.

Conventional computed tomography (CT) has low sensitivity for the diagnosis of bone marrow infiltration in nonosteolytic multiple myeloma (NOL-MM). This study aimed to compare the performance of the two-material decomposition technique of spectral CT with the removal of X-ray absorption components of calcium (Ca) versus that of hydroxyapatite (HAP) for diagnosis of NOL-MM. From October 2022 to March 2023, a total of 41 consecutive patients with MM without focal bone lesions undergoing chest spectral CT and thoracic spine magnetic resonance imaging (MRI) in Fujian Medical University Union Hospital were prospectively enrolled; meanwhile, another set of 41 age- and sex-matched healthy consecutive participants were selected as a comparison group. Based on MRI findings, patients with MM were classified with a diffuse infiltration pattern MM (DP-MM) or a normal pattern MM (NP-MM). Regions of interest (ROIs) were manually drawn on vertebrae. CT values of 70-keV images and basic material density within the ROIs were stored. The basic two-material pairs included a Ca-related pair (Ca-X) and an HAP-related pair (HAP-X), with X referring to fat, water, or muscle. Material density values DCa(X), DX(Ca), DHAP(X), and DX(HAP) were each used to diagnose MM, and the area under the receiver operating characteristic curve (AUC) was used to assess diagnostic performance. The 41 patients with NOL-MM included 30 with DP-MM and 11 with NP-MM. CT value, DCa(X), and DHAP(X) were comparable between the NOL-MM, DP-MM, NP-MM, and comparison groups. DX(HAP) was better than DX(Ca) for distinguishing the NOL-MM group from the comparison group {AUC [95% confidence interval (CI)], 0.874 (0.800, 0.949) vs. 0.737 (0.630, 0.844); P=0.02}, the DP-MM group from the comparison group [AUC (95% CI), 0.933 (0.878, 0.989) vs. 0.785 (0.677, 0.894); P=0.01], the NP-MM group from the comparison group [AUC (95% CI), 0.714 (0.540, 0.888) vs. 0.605 (0.429, 0.782); P=0.03], and the DP-MM group from the NP-MM group [AUC (95% CI), 0.809 (0.654, 0.964) vs. 0.736 (0.566, 0.907); P=0.049]. The diagnostic performance of DX(HAP) and DX(Ca) was influenced only by the removed material, while the X material had no influence. The spectral CT two-material decomposition technique with removal of X-ray absorption components of HAP is useful for diagnosis of NOL-MM, irrespective of the paired material.

Multicentric lymphoma in a donkey with intestinal and bone marrow involvement

BackgroundLymphoma is a common neoplasm in horses but is reported much less commonly in donkeys. In this case report, we describe the macroscopic, microscopic and immunohistochemical features of a multicentric lymphoma with intestinal and bone marrow involvement.Case presentationA geriatric female donkey with history of chronic lameness was found dead. Post-mortem examination revealed advanced emaciation, periodontal disease, left front foot laminitis and multiple, soft, white to yellow tan intestinal transmural masses, up to 12 cm in diameter. Cytology suggested a round cell intestinal neoplasm. The femur of the left hint limb was double the size of the normal contralateral, with suspected neoplastic infiltration and replacement of bone marrow and bone. Histologically we diagnosed a lymphoma in the intestine and left femur. Immunohistochemically, the neoplastic cells showed CD3 immunolabelling, supporting a diagnosis of a multicentric T-cell lymphoma.ConclusionsTo the authors’ knowledge, this is the first time multicentric lymphoma is diagnosed in donkeys. Further studies of the genetic background, clinical, laboratory, histopathologic, and immunohistochemical, as well as the pathogenesis of lymphoma, is needed to better understand the uniquely low frequency of this neoplasm in donkeys.

Development of a whole spinal MRI-based tumor burden scoring method in participants with multiple myeloma: a pilot study of prognostic significance.

The aim of the study was to develop a new whole spinal MRI-based tumor burden scoring method in participants with newly diagnosed multiple myeloma (MM) and to explore its prognostic significance. We prospectively recruited participants with newly diagnosed MM; performed whole spinal MRI (sagittal FSE T1WI, sagittal IDEAL T2WI, and axial FLAIR T2WI) on them; and collected their clinical data, early treatment response, progression-free survival (PFS), and overall survival (OS). We developed a new tumor burden scoring method according to the extent of bone marrow infiltration in five MRI patterns. All participants were divided into good response and poor response groups after four treatment cycles. Univariate, multivariate analyses, and ROC were used to determine the performance of independent predictors. Thresholds for PFS and OS were calculated using X-tile, and their prognostic significance were assessed by Kaplan-Meier. The Kruskal-Wallis H test was used to compare the differences of tumor burden score between the revised International Staging System (R-ISS) stages. The new tumor burden scoring method was used in 62 participants (median score, 12; range, 0-18). The tumor burden score (OR 1.266, p = 0.002) was an independent predictor of poor response and the AUC was 0.838. Higher tumor burden scores were associated with shorter PFS (p = 0.002) and OS (p = 0.011). The tumor burden score was higher in R-ISS-III than in R-ISS-I and R-ISS-II (p = 0.016 and p = 0.006, respectively). The tumor burden score was an excellent predictor of prognosis and may serve as a supplemental marker for R-ISS.

Lymphoma-associated hemophagocytic lymphohistiocytosis (LA-HLH): a scoping review unveils clinical and diagnostic patterns of a lymphoma subgroup with poor prognosis.

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome driven by pathologic activation of cytotoxic T-lymphocytes and macrophages. Despite advances in diagnostics and management, adult patients with lymphoma-associated HLH (LA-HLH) harbor particularly poor prognosis and optimal treatment remains challenging. As systematic data on LA-HLH are scarce, we aimed to synthesize research evidence by thorough analysis of the published literature in PubMed (MEDLINE-database) within the context of a scoping review. Of 595 search results, 132 articles providing information on 542 patients were reviewed and analyzed. Median patient age was 60 years (range, 18-98) with male predominance (62.7%). B- and T-NHL were equally represented (45.6% and 45.2%), Hodgkin's lymphoma was reported in 8.9% of the cases. The majority of patients (91.6%) presented in Ann-Arbor-Stages III and IV, and bone marrow infiltration was observed in a significant proportion of patients (61.5%). Soluble CD25 levels were markedly elevated (median 10,000 U/ml), with levels beyond 10,000 U/ml indicating unfavorable prognosis for 30-day and overall survival. 66.8% of the patients died after median 5.1 months. LA-HLH remains a clinical challenge requiring specialized management. Timely diagnosis and appropriate lymphoma-specific treatment are of utmost importance to enhance patient outcomes.

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

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

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

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

Long-term Survival in a Patient With Transformation of Waldenström's Macroglobulinemia into DLBCL.

Waldenström's macroglobulinemia (WM) is a rare slow-growing B-cell lymphoma that is characterized by lymphoplasmacytic bone marrow infiltration and the production of monoclonal immunoglobulin M (IgM) paraprotein. In 5-10% of patients, WM undergoes transformation into diffuse large B-cell lymphoma (DLBCL), which is more aggressive, with poor prognosis and a low survival rate. Α 69-year-old woman was diagnosed with WM in 2009. She received six cycles of chemoimmunotherapy and a remarkable remission was achieved. However, in 2013 the disease transformed into DLBCL. The patient received chemotherapy and after the completion of the first cycle of therapy, the disease was significantly minimized. At the end of the therapy, there was no evidence of disease, and the patient remains disease-free. The cytogenetic profile of the patient did not reveal expression of BCL2 apoptosis regulator, BCL6 transcription repressor, Epstein-Barr virus small RNA, syndecan 1 nor cyclin D1. According to a staging system based on the platelet count, lactate dehydrogenase and previous treatment for WM, the described patient was classified as being at intermediate risk with an expected 2-year survival probability of 47% after WM transformation into DLBCL. However, the patient unexpectedly exceeded these prognostic indications. The findings for this patient are of great interest compared with the existing literature which suggests that the survival and prognosis for patients with transformed DLBCL are not favorable.