Bone Marrow Involvement Research Articles

Modified Endothelial Activation and Stress Index: A New Predictor for Survival Outcomes in Classical Hodgkin Lymphoma Treated with Doxorubicin-Bleomycin-Vinblastine-Dacarbazine-Based Therapy

Background: Although the cure rates of classical Hodgkin Lymphoma (cHL) are as high as 90% using the current treatment protocols, the prognosis is poor for primary refractory patients. Thus, a biomarker that can predict patients with early progression at the time of diagnosis is an unmet clinical need. Endothelial activation and stress index (EASIX) and its variant modified EASIX (mEASIX) is a scoring system currently used for the prediction of prognosis in hematologic malignancies. This study aimed to investigate the prognostic value of the mEASIX score in newly diagnosed cHL patients. Methods: Data from 206 patients who underwent positron emission tomography (PET)-guided doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) therapy for cHL between January 2007 and November 2023 were retrospectively analyzed. The prognostic value of the mEASIX score was evaluated using the receiver operating characteristic (ROC) analysis, Cox regression analysis, and the Kaplan–Meier method, and then compared with standard risk assessment methods. Results: The median age at diagnosis was 33 years, and the rate of patients in the advanced stage was 67%. ROC analysis determined an optimal mEASIX score cut-off of 17.28, categorizing patients into mEASIXhigh (47%) and mEASIXlow (53%) groups. The 5-year progression-free survival (PFS) (60% vs. 84.3%) and overall survival (OS) (79.6% vs. 95.8%) were significantly lower in the mEASIXhigh group (p < 0.001). Additionally, multivariate analysis showed that the independent variables affecting PFS included the nodular sclerosing subtype (HR: 0.4), bone marrow involvement (HR: 2.6), and elevated mEASIX (HR: 3.1). Independent variables, which had an effect on OS included elevated mEASIX (HR:3.8) and higher IPS-3 scores (HR:1.9). Furthermore, a higher mEASIX score (≥17.28) was identified as an independent variable indicating primary refractory disease (OR: 6.5). Conclusions: mEASIX is a powerful and easy-to-access marker for the detection of primary refractory disease and prognosis in newly diagnosed cHL cases.

Clinical characteristics of lymphoma patients presenting with fever of unknown origin misdiagnosed with connective tissue diseases.

Recognizing and diagnosing lymphoma in patients with fever of unknown origin (FUO) can be challenging, and misdiagnosis is not uncommon. To improve understanding of the clinical characteristics of lymphoma patients presenting with FUO who were misdiagnosed with autoimmune diseases. A retrospective, observational study of 140 consecutive patients with FUO and lymphoma presenting to a tertiary center between January 2017 and December 2023. Patients were divided into those who were correctly diagnosed and those misdiagnosed as connective tissue diseases (CTD) and the clinical features compared. Of 140 lymphoma patients with FUO, 21 patients (15.0%) were misdiagnosed as CTD. The median time between symptom onset and diagnosis was significantly longer in the misdiagnosed group than in the non-misdiagnosed group (11.0 (IQR 6.0, 22.5) months vs. 4.0 (2.5, 9.0) months; p = 0.001). The misdiagnosed group had significantly less lymph node and bone marrow involvement and more skin rashes than the non-misdiagnosed group (47.6% vs. 70.6%, p = 0.039; 23.8% vs. 47.9%, p = 0.040; 47.6% vs. 25.2%, p = 0.036), as well as significantly lower ESR (p = 0.026) and hsCRP (p = 0.049). The misdiagnosed group had higher frequency of ANA/ANCA (57.1% vs. 27.7%; p = 0.008) and anti-phospholipid antibody (42.9% vs. 6.1%; p = 0.008) positivity. The distribution of lymphoma subtypes was different between groups (p = 0.058). Lymphoma patients with an atypical presentation and FUO suggesting inflammatory systemic disease are easily misdiagnosed. Autoantibody positivity is not rare in lymphoma patients with an atypical presentation and FUO, so close follow-up and repeated histopathological examination may be helpful to establishing a correct diagnosis.

The Role of [18F]FDG PET and Clinicopathologic Factors in Detecting and Predicting Bone Marrow Involvement in Non-Hodgkin Lymphoma

Background/Objectives: This study evaluates the diagnostic accuracy of [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) using bone marrow biopsy (BMB) and clinical follow-up as reference standards. It further identifies predictive factors for bone marrow involvement (BMI) in non-Hodgkin lymphoma (NHL) patients. Methods: NHL patients who underwent [18F]FDG PET and BMB at diagnosis in a tertiary cancer center were included in this study. Diagnostic accuracy was analyzed, and logistic regression was performed to identify BMI predictors using Stata software version 17. A retrospective analysis of 262 NHL patients was conducted. Results: Concordance rates between [18F]FDG PET and BMB and between [18F]FDG PET and clinical follow-up were 75.6% and 88.1%, respectively. The primary cause of discordance between [18F]FDG PET and BMB was the detection of extra-iliac focal hypermetabolic bone marrow lesions by [18F]FDG PET, which were negative on BMB. The sensitivity, specificity, and accuracy of [18F]FDG PET were 62.9%, 80%, and 75.6%, respectively, with BMB as a reference, and 74.1%, 97.5%, and 88.2%, respectively, with clinical follow-up as a reference. The focal bone marrow [18F]FDG pattern was the most reliable indicator of BMI. Univariate logistic regression showed that advanced NHL stage, elevated alkaline phosphatase, thrombocytopenia, leukopenia, and elevated lactate dehydrogenase were significant predictors of BMI. Multivariate analysis revealed advanced NHL stage and thrombocytopenia as clinical predictors. Conclusions: [18F]FDG PET is a reliable tool for assessing BMI, providing comprehensive total-body evaluation and identifying extra-iliac involvement beyond the scope of BMB. The collective interpretation of molecular imaging, clinical, and biochemical factors is crucial for predicting BMI.

Clinical Characteristics and Outcomes of Pediatric Systemic Anaplastic Large Cell Lymphoma.

Anaplastic large cell lymphomas (ALCLs) present unique challenges due to their clinical and genetic heterogeneity. This study investigated the clinical characteristics of children diagnosed with systemic ALCL. Retrospective data from 14 pediatric patients diagnosed with systemic ALCL at Valme University Hospital were studied. Demographic, clinical, and treatment data were collected and statistically analyzed. The mean age at diagnosis was 8.5 years, with a male predominance (78.6%). Cutaneous presentation occurred in 35.7% of cases, with characteristic rapidly growing subcutaneous nodules. B symptoms were present in 57.1% of patients, while 100% exhibited nodal involvement. Visceral and bone marrow involvement was observed in 71.4% and 7.1% of patients, respectively. Central nervous system (CNS) involvement was absent. Anaplastic lymphoma kinase (ALK) rearrangement was positive in all cases. Anthracycline-based chemotherapy resulted in 100% 5- and 10-year overall survival rates. Systemic ALCL in children often presents with advanced-stage disease, with cutaneous involvement in a significant proportion of cases. Prompt recognition of skin lesions is vital to expedite diagnosis and treatment initiation, ultimately improving patient outcomes. This study underscores the importance of vigilance and early intervention in managing pediatric ALCL.

ALK-positive large B-cell lymphoma: A study of six cases from an oncopathology center in North India.

ALK-positive large B-cell lymphoma (ALK+ LBCL) is a rare neoplasm with an aggressive course and poor therapeutic response to the standard R-CHOP regimen. Owing to its negativity for usual B- and T-cell markers and immunopositivity for epithelial markers, it can be easily misdiagnosed if it is not contemplated. To study the clinicopathological parameters of cases of ALK+ LBCL diagnosed at our institution. A retrospective observational study of ALK+ LBCL was conducted at a tertiary cancer center of North India with cases diagnosed over a period of 3 years. Six cases of ALK+ LBCL were identified. The clinical findings at presentation included mean age of 38.8 years, male-to-female ratio of 5:1, extranodal presentation (1/6 cases), concurrent extranodal and nodal involvement (3/6), nodal presentation (2/6), high serum LDH (5/5), and bone marrow involvement (1/5). Histomorphology of diffuse (100%), alveolar/nested (16.6%), and sinusoidal pattern (1 case upon relapse) and immunoblastic and plasmablastic morphology (100%) and immunopositivity in all cases for ALK-1 protein (100%), CD138 (100%), MUM1 (100%), LCA (100%) along with negativity for EBER-ISH/EBV-LMP1 immunohistochemistry clinched the diagnosis. Fluorescence in situ hybridization analysis for ALK gene rearrangement was detected in 4/4 cases. Four patients received chemotherapy demonstrating relapse in 2 cases: residual disease and no response in one case each, along with death in 2 cases. A high degree of diagnostic suspicion is required for accurate recognition of ALK+ LBCL. Awareness of its histology, immunohistochemistry, and cytogenetics is pivotal for precise identification of this rare entity.

Characterization of bone marrow aspirate reports in dogs and cats: A retrospective study

Background: Bone Marrow Aspirate (BMA) allows the study, staging and monitoring of multiple conditions with bone marrow involvement. The BMA report is a crucial component of the post-analytical stage and significantly influences the veterinarian's understanding and decision-making process. Objective: To describe the zoographic, clinical, and quality characteristics of BMA reports, as well as the frequency of diagnoses and associated factors in dogs and cats treated at veterinary centers in Colombia from 2012 to 2023. Methods: This was a cross-sectional descriptive study. Data on zoographic and clinical variables were extracted from BMA reports and consultations; the frequency of diagnoses and associated factors were determined. Adherence to reporting quality was evaluated using established guidelines for BMA in dogs, cats, and humans. Results: A total of 135 BMA reports were reviewed from eight veterinary institutions: 116 for dogs and 19 for cats, with a mean age of 5.22 ± 3 years; 53% were males. The most common indication for BMA was anemia, alone or with other abnormalities. The least adhered-to reporting elements were puncture site (91.9%), relevant clinical data (85.2%), and morphological evaluation by cell line (52.6%). Additionally, 27.4% of the reports were excluded due to poor sample quality. The most frequent diagnosis in dogs was hypoplasia (36.1%), while in cats, it was neoplasia (40.0%). Erythroid hyperplasia and neoplasms were more prevalent in males, whereas granulocytic hypoplasia was more common in females. Conclusions: BMA as a diagnostic tool in dogs and cats in Colombia is rare. A significant proportion of samples did not meet quality criteria, and there was low adherence to reporting guidelines.

Sporadic Burkitt Lymphoma First Presenting as Painful Gingival Swellings and Tooth Hypermobility: A Life-Saving Referral

Background: Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma (NHL), subdivided into endemic, sporadic, and immunodeficiency-associated forms. While jaw lesions are common in endemic BL, they are infrequent in sporadic cases, only rarely constituting the first manifestation of the disease. The aim of this study is to present a rare pediatric case of sporadic BL first manifesting as gingival swellings and tooth hypermobility and provide a review of all the published sporadic BL case reports as the first sign of disease. Case report: An 11-year-old Caucasian female was referred for the evaluation of hypermobility of posterior lower teeth, associated with painful gingival swellings of 20 days duration. Clinical examination revealed right facial asymmetry and bilateral prominent swellings of the posterior lower gingiva. A panoramic radiograph revealed ill-defined radiolucent lesions in the posterior mandible bilaterally. On computed tomography, soft-tissue masses were identified along the mandibular ramus extending into the maxillary sinus bilaterally. The histopathologic and immunohistochemical analyses of the lesions led to a diagnosis of Burkitt lymphoma (BL). The patient underwent a full staging work-up, revealing bone marrow involvement and widespread disease. A multi-chemotherapy regimen was initiated with the regression of oral lesions and symptoms within a few weeks and complete disease remission after nine chemotherapy cycles. The patient remains free of disease 11 years later. Conclusions: This case underscores the critical importance of the timely diagnosis and life-saving referral of rapidly growing jaw lesions, which may represent the first sign of an underlying lymphoreticular malignancy with aggressive course, such as BL.

Clinical and splenectomy-based treatment outcomes in 40 cases of hepatosplenic T-cell lymphoma: a comprehensive analysis

Background/aimThis research study was conducted to examine the clinical characteristics and post-splenectomy survival outcomes of patients diagnosed with hepatosplenic T-cell lymphoma (HSTCL).Materials and methodsA total of 10 cases of HSTCL patients admitted to the Hematology Department of Fudan University Affiliated Huadong Hospital between January 2012 and December 2021 were included. In addition, we also included 30 other cases reported from domestic and international sources. All pathological specimens were stained with hematoxylin and eosin (H&E) and immunohistochemistry, with color development using DAB staining. Survival analysis was conducted using Kaplan-Meier curves and log-rank tests.ResultsIn the 10 HSTCL patients, Epstein-Barr virus (EBV) infection was confirmed. Six patients had died, with 5 of them within 1 year of disease onset. Survival analysis showed poorer prognosis in patients with hemophagocytic syndrome and thrombocytopenia. Patients who underwent splenectomy followed by chemotherapy had a higher median and average survival time compared to those who only received chemotherapy. The study included a total of 40 HSTCL patients, with 29 males and 11 females, and an average age of onset at 42.3 years. All patients presented with fever, with some exhibiting emaciation and/or hemophagocytic syndrome. Splenomegaly, hepatomegaly, lymphadenopathy, and bone marrow involvement were found in the patients. Common laboratory findings included leukopenia, anemia, and thrombocytopenia. All patients exhibited elevated ferritin levels and decreased blood calcium levels.ConclusionThose patients suffering from hemophagocytic syndrome at the onset of this disease face greater treatment-related difficulties and a higher risk of mortality. Combined chemotherapy after splenectomy may improve HSTCL patient survival.

Cutaneous plasmacytosis in a dog (Caninus familiaris)

AbstractCutaneous plasmacytosis is rarely reported in veterinary medicine, but far more described in human medicine. Extramedullary plasmacytomas are plasma cell tumours without bone marrow involvement. This study aimed to report a case of a 7‐year‐old, mixed‐breed dog with a presumptive diagnosis of cutaneous plasmacytosis. At clinical examination, the dog presented 15 cutaneous nodules disseminated through the body. Cytopathological analysis revealed plasmacytoma in 13 out of 15 nodules. Thoracic radiography revealed radiopaque structures suggestive of pulmonary nodules, and abdominal ultrasonography indicated suspicion of a hepatic neoplastic process. The animal died during the diagnostic screening period, with a survival of 16 days from the initial consultation. Thus, further confirmatory tests such as histopathology and immunohistochemistry were not performed, and the pulmonary and hepatic lesions were not assessed. This report demonstrates the importance of cytopathology in the presumptive diagnosis of cutaneous plasmacytosis in a dog, considering the absence of other complementary examinations.

Characterizing Nodal Gamma-Delta T-Cell Lymphoma: Clinicopathological and Molecular Insights.

Peripheral T-cell lymphomas with gamma-delta phenotype (GDTCL) are rare lymphoid malignancies. Beyond the well-recognized entities of extranodal lymphomas with gamma-delta phenotype as defined by the 5th edition of the WHO Classification of Hematolymphoid Tumors and 2022 International Consensus Classification, there is a group of poorly-defined gamma-delta T-cell lymphomas with predominantly nodal presentation, termed as nodal GDTCL (nGDTCL). In this study, we present a series of 12 cases of EBV-negative nGDTCL, highlighting the clinical, histopathological and molecular features of this rare entity. Seven cases reported in the literature were included for the analysis. Of the 12 cases, nGDTCL shows an increased incidence in elderly males with a median age of 65.5 years. All cases presented primarily with enlarged lymph nodes and 4 cases (4/12; 33.3%) showed involvement of extranodal sites, including skin, liver, spleen and bone marrow. Histologically, 9 cases showed a diffuse and monomorphic proliferation of mostly medium to large lymphoid cells while 3 cases demonstrated a lymphoepithelioid morphology. All cases (12/12, 100%) were positive for CD3 and TCRγδ. CD4, CD8 and CD56 were positive in 66.7% (8/12), 25% (3/12) and 8.3% (1/11) of cases, respectively. Most cases (8/12, 66.7%) showed a non-cytotoxic phenotype. Using immunohistochemistry, the majority of cases (6/8, 75.0%) belonged to the PTCL-GATA3 subtype with GATA3 and/or CCR4 expression and a non-cytotoxic CD4-positive phenotype. Two cases (2/8, 25%) belonged to the PTCL-TBX21 subtype, of which 1 displayed a cytotoxic CD8-positive phenotype. Next-generation sequencing was performed on 9 cases and TP53 mutation was detected in 66.7% (6/9) of cases. Mutations of ATM and KSR2 were identified in 2 cases each. It remains uncertain if nGDTCL represents a distinct entity, and further studies are needed for better characterization. Nonetheless, nodal-based GDTCL should be distinguished from secondary nodal involvement by other extranodal GDTCL and EBV-positive T/NK-cell lymphoproliferative diseases.

Comparison of Bone Marrow Biopsy and Flow Cytometry in Demonstrating Bone Marrow Metastasis of Neuroblastoma.

This study aimed to compare bone marrow aspirate (BMA) multicolor flow cytometry (MFC) analysis and bone marrow biopsy (BMB) in detecting bone marrow (BM) involvement in children with neuroblastoma (NB) at diagnosis and during follow-up. A total of 132 BM samples from 39 patients (M/F ratio: 19/20; median age: 38 months) with neuroblastoma were simultaneously obtained for evaluation. The samples were investigated for BM involvement using BMB and MFC. A comparison between MFC (n: 60) and BMB (n: 60) was possible for 120 samples. When BMB was considered as the reference standard, MFC had diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of 86%, 58%, 54%, and 88%, respectively, and values of 90%, 57%, 60%, and 89%, respectively, at diagnosis. The median proportion of CD45-/CD56+ cells in MFC was 0.028% (range 0-35%). The event-free survival (EFS) rates for MFC (+) and MFC (-) patients according to the analysis results of the BM samples at the time of diagnosis were 70.6% and 81.8%, respectively (p = 0.607), and the overall survival (OS) rates were 88.2% in MFC (+) patients and 90.9% in MFC (-) patients (p = 0.583). Multicolor flow cytometry may be used as an adjunct to cytomorphology to achieve more sensitive and accurate results as an objective, quantitative method with fast results in detecting bone marrow involvement in children with NB.

Clinical Manifestations, Prognostic Factors, and Outcomes of Extranodal Natural Killer T-Cell Lymphoma: A Single-Center Experience in Thailand.

Background/Objectives: The primary objective of this study was to investigate clinical manifestations, time to diagnosis, and number of biopsies in patients with extranodal natural killer T-cell lymphoma (ENKTL). The secondary objectives were to determine response rates, survival outcomes, prognostic factor for overall survival (OS), and validation of the Prognostic Index of Natural Killer Lymphoma (PINK), Ann Arbor staging system (AASS), and the CA system. Methods: This retrospective study included data pertaining to patients with newly diagnosed ENKTL in Chiang-Mai University Hospital from 2004 to 2020. Comparisons between the areas under the receiver operating characteristic curve (AUC) of prognostic models (PINK, AASS, and CA system) were made. Results: Sixty patients were enrolled (n = 60) with a mean age of 49.1 ± 13.4 years. The most frequent symptom of ENKTL was nasal obstruction (66%). The median time to diagnosis was 22 days (ranging from 3 to 84 days), with 36.7% requiring more than one biopsy for diagnosis. Most patients presented with limited stage disease (75%). The median OS was 49 months. Factors associated with increased mortality were advanced stage, bone marrow involvement, gastrointestinal tract involvement, and receiving chemotherapy. Following prognostic model validation, the CA system model scored the highest level of accuracy (AUC 0.61), followed by AASS (AUC 0.58) and PINK (AUC 0.54). Conclusions: Patients with ENKTL commonly presented with nasal obstruction, with 36.7% requiring more than one biopsy for diagnosis. An advanced stage, bone marrow involvement, or gastrointestinal tract involvement were associated with poor OS. The CA system model has the highest level of accuracy for prognostic determination.

Overall manifestations and survival of pediatric patients with Langerhans cell histiocytosis. A middle-income country (mic) national multicenter study.

Langerhans cell histiocytosis (LCH) is a rare neoplastic disease characterized by clonal proliferation of den-dritic cells. It is Mexico's ninth most frequent malignancy in patients under 18 years of age. The aim of the study was to determine the clinical characteristics, treatment, and survival of Mexican pediatric patients diagnosed with LCH treated from January 2010 to December 2018. We conducted a retrospective study of LCH using data from 19 accredited hospitals throughout the Mexican Republic. Patients < 18 years who were diagnosed with LCH between January 2010 and December 2018 were included (253 patients) in the study. All patients had a histopathological diagnosis, and extension studies were performed at their treatment centers. The median age at diagnosis was 19 months. The most frequently affected sites included the bone (178 cases; 70%) and the skin (131 cases; 51.7%). Of the patients in Group 1, 48 (42%) had bone marrow involvement, 62 (53%) had splenomegaly, and 39 (34.8%) had liver involvement. Of the patients who underwent chemotherapy treatment, 61.2% exhibited a complete response, and 36 patients (14.2%) relapsed after complete remission. The most frequent sites of relapse were the skin, bone, lymph nodes, and liver. The overall survival rate was 91.3% and was lower for patients in Group 1 (77%) compared with those in Groups 2 (97%) and 3 (100%), p = 0.001. The current report aims to demonstrate the findings of a multicenter study conducted on Mexican children with LCH; consequently, these treatment results for a relatively infrequent disease merit further research.

The Impact of Bone Marrow Involvement on Prognosis in Diffuse Large B-Cell Lymphoma: An 18F-FDG PET/CT Volumetric Segmentation Study.

This study assessed the prognostic value of tumor burden in bone marrow (BM) and total disease (TD), as depicted on 18F-FDG PET/CT in 140 DLBCL patients, for complete remission after first-line systemic treatment (iCR) and 3- and 5-year overall survival (OS3 and OS5). Baseline 18F-FDG PET/CT scans of 140 DLBCL patients were segmented to quantify metabolic tumor volume (MTV), total lesion glycolysis (TLG), and SUVmax in BMI, findings elsewhere (XL), and TD. Bone marrow involvement (BMI) presented in 35 (25%) patients. Median follow-up time was 47 months; 79 patients (56%) achieved iCR. iCR was significantly associated with TD MTV, XL MTV, BM PET positivity, and International Prognostic Index (IPI). OS3 was significantly worse with TD MTV, XL MTV, IPI, and age. OS5 was significantly associated with IPI, but not with MTVs and TLGs. Univariate factors predicting OS3 were XL MTV (hazard ratio [HR] = 1.29), BMI SUVmax (HR = 0.56), and IPI (HR = 1.92). By multivariate analysis, higher IPI (HR = 2.26) and BMI SUVmax (HR = 0.91) were significant independent predictors for OS3. BMI SUVmax resulted in a negative coefficient and hence indicated a protective effect. Baseline 18F-FDG PET/CT MTV is significantly associated with survival. BMI identified on 18F-FDG PET/CT allows appropriate treatment that may improve survival.

Neuroblastoma plasticity during metastatic progression stems from the dynamics of an early sympathetic transcriptomic trajectory.

Despite their indisputable importance in neuroblastoma (NB) pathology, knowledge of the bases of NB plasticity and heterogeneity remains incomplete. They may be rooted in developmental trajectories of their lineage of origin, the sympatho-adrenal neural crest. We find that implanting human NB cells in the neural crest of the avian embryo allows recapitulating the metastatic sequence until bone marrow involvement. Using deep single cell RNA sequencing, we characterize transcriptome states of NB cells and their dynamics over time and space, and compare them to those of fetal sympatho-adrenal tissues and patient tumors and bone marrow samples. Here we report remarkable transcriptomic proximities restricted to an early sympathetic neuroblast branch that co-exist with phenotypical adaptations over disease progression and recapitulate intratumor and interpatient heterogeneity. Combining avian and patient datasets, we identify a list of genes upregulated during bone marrow involvement and associated with growth dependency, validating the relevance of our multimodal approach.

Pediatric Mature B-Cell Non-Hodgkin Lymphomas in India: A Retrospective Multicenter Pooled Analysis of Treatment Approaches and Outcomes

BackgroundPublished data on outcomes ofpediatric mature B-cell non-Hodgkin lymphoma (B-NHL) from India is limited and difficult to interpret due to small sample size and non-uniform treatment protocols.This study aims to do a pooled analysis of published patient data from multiplecenters across India to provide a clearer understanding of survival rates and treatment-related toxicities with respect to the treatment protocols in this population. MethodsA pooled analysis of patient-level data from 505 children with mature B-NHL, including Burkitt lymphoma (n=395), diffuse large B-cell lymphoma (DLBCL, n=52), and other subtypes (n=58), treated from 2000 to 2022 at seven major cancer centers in India, was conducted. Outcomes assessed were grade 3/4 toxicities, toxic deaths, relapse/progression, and survival rates. ResultsMost patients (401/505) presented with advanced disease; bone marrow and CNS involvement were observed in 13.9% and 6.9% of cases, respectively. Treatment protocols primarily included LMB (n=208), BFM (n=191), and MCP (n=61). Grade 3/4 toxicities were reported in 79.2% of patients, with higher rates observed with LMB protocol (92.1%) compared to BFM (70.8%) and MCP (70.1%) (p<0.001). Toxic death rates were similar across protocols. Overall survival (OS) and event-free survival (EFS) at a median follow-up of 17 months were 69.4±2.2% and 64.9±2.2%, respectively, with no significant differences in relapse/progression rates or stage-specific OS between protocols (p=0.28 and 0.51). ConclusionsThis pooled analysis shows that although treatment-related toxicities differ by protocol, overall survival outcomes were similar across the LMB, BFM, and MCP regimens, despite being lower than those reported in Western studies.Uniform standardized protocols may further improve outcomes for pediatric B-NHL in India.

Pediatric B-cell Non-Hodgkin Lymphoma: The Impact of Therapy Response and Relapse on Outcome. A Single-center Analysis.

Pediatric patients with primary refractory or relapsed B-cell non-Hodgkin lymphoma (B-NHL) have highly unfavorable prognosis. In this study, we retrospectively analyzed outcomes in pediatric B-NHL patients treated in a single center in Poland from 1995 to 2022, with emphasis on therapy results in patients with progression or relapse. The primary objectives were a 5-year probability of overall survival (pOS) and a 5-year probability of event-free survival (pEFS). The secondary objectives involved the assessment of prognostic factors. A total of 76 children were eligible for the analysis. The 5-year pOS was 76.7%, and the 5-year pEFS was 72.9%. At diagnosis, elevated lactate dehydrogenase activity, the presence of B symptoms, bone marrow, skeletal or mediastinal involvement, and stage IV disease were associated with inferior outcomes. Nine children experienced progression and four relapse. The 5-year pOS for patients with progression was 38.1%. Two patients treated with hematopoietic stem cell transplantation (HSCT) as part of salvage therapy survived. However, only one out of seven patients who were treated without HSCT survived. The 5-year pOS was 0.0% in patients with relapsed disease. The most significant factor related to outcomes in pediatric B-NHL is therapy response, with a high mortality rate in children with refractory disease and relapse. There is no consensus on the salvage therapy approach; however, HSCT appears to be the optimal choice.

CNS relapse in high-grade B-cell lymphoma with MYC and BCL2 rearrangements and dark-zone signature–expressing DLBCL

AbstractHigh-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-DH-BCL2), or “double-hit lymphoma,” has been associated with a high risk of central nervous system (CNS) relapse. However, historic estimates are impacted by selection bias. We report CNS relapse rates associated with HGBCL-DH-BCL2 from a population-based cohort with complete fluorescence in situ hybridization testing, as well as diffuse large B-cell lymphoma morphology (DLBCL) tumors expressing the dark-zone gene expression signature (DZsig), which was originally derived from HGBCL-DH-BCL2. The 2-year CNS relapse risk in HGBCL-DH-BCL2 was 6.8%. CNS relapses were early, predominantly leptomeningeal (73%), and co-occurred with systemic relapse (64%). High-risk CNS International Prognostic Index (CNS-IPI) and concordant bone marrow involvement were associated with an elevated CNS relapse risk in HGBCL-DH-BCL2. The “refined cell-of-origin” classification assigned 20% of DLBCL morphology tumors with germinal center B-cell–like phenotype (GCB-DLBCL) into a distinct subgroup based on DZsig expression (DZsig+). CNS relapse risk in DZsig+ (2 year: 6.4%) was independent of HGBCL-DH-BCL2 status and was further stratified by the CNS-IPI. CNS relapse in DZsig-negative GCB-DLBCL was rare (2-year risk, 1.4%; P = .04 vs DZsig+) and exclusively parenchymal. Altogether, the CNS relapse risk in HGBCL-DH-BCL2 is lower than previously reported, and DZsig refines risk stratification in GCB-DLBCL.

Myeloid Sarcoma: Novel Advances Regarding Molecular Pathogenesis, Presentation and Therapeutic Options

Myeloid sarcoma (MS), an extramedullary form of acute myeloid leukemia (AML) is a rare tumor mass of myeloid blasts. It can disseminate to any one or multiple anatomical sites, with (synchronous MS) or without (isolated MS) bone marrow (BM) involvement. The aim of this review is to describe the most recent advances in MS regarding diagnosis, molecular background, various clinical manifestations from several organs, and treatment approaches. Due to the lack of prospective, randomized clinical trials, therapeutic decisions are a challenge for the clinician. In the era of novel targeted AML treatments, a critical analysis of how to decide the best option for individual patients, also covering the possible central nervous system (CNS) prophylaxis is provided. For the majority of the patients, AML induction chemotherapy, followed by hematopoietic stem cell transplantation (HSCT) is generally recommended. This paper discusses the role of radiotherapy, the treatment of refractory and relapsed disease, along with the therapeutic approach of difficult-to-treat patients, due to specific problems related to different anatomical sites of MS.

Isolated intracranial myeloid sarcoma as an acute myeloid leukemia relapse: A case report

Abstract Introduction/Objective Adequate assessment during intraoperative consultation on a patient with a brain mass is imperative to provide critical information that will direct the therapeutic approach during surgery. Methods/Case Report The patient is a 67-year-old female with acute myeloid leukemia (AML) on maintenance therapy and in remission for the past 2 years that developed altered mental status and seizures. Imaging revealed a diffuse intra-axial mass within the corpus callosum and right hypothalamic region. A brain stereotactic biopsy was performed. Blood work showed mild leukopenia (3.63x109/L), thrombocytopenia (platelet count of 82x109/L), and an essential normal hemoglobin level of 11.9 g/dL. A frozen section assessment during intraoperative consultation revealed an infiltration of small blue cells, suggesting a hematolymphoid process. Further histological assessment showed small to intermediate-sized monomorphic cells in sheets and around the vessels with open fine chromatin, prominent nuclei, and scant cytoplasm admixed with tingible body macrophages. Differential diagnoses included high- grade B-cell lymphoma, Burkitt lymphoma, mantle cell lymphoma blastoid variant, lymphoblastic lymphoma, and myeloid sarcoma (MS). The tumor cells were positive for CD34, CD43, and MPO (subset) and negative for CD20, PAX5, TdT, CD3, and AE1/AE3 by immunohistochemical staining, consistent with MS. Concurrent bone marrow biopsy with flow cytometric evaluation showed progressive trilineage hematopoiesis without evidence of residual leukemia. Results (if a Case Study enter NA) NA Conclusion Intracranial MS is extremely rare, and literature reviews are limited to primarily case reports. MS can occur before, during, or after the initial presentation of AML. Interestingly, this patient had an isolated intracranial myeloid sarcoma as an AML relapse without bone marrow involvement. We aim to increase the awareness of isolated recurrence of AML in the form of an intracranial MS; this disease warrants consideration in patients with a history of a myeloid neoplasm who present with neurological symptoms despite the absence of peripheral disease.