B-lymphoblastic Lymphoma Research Articles

Comprehensive analysis of constitutional mismatch repair deficiency-associated non-Hodgkin lymphomas in a global cohort.

Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare childhood cancer predisposition syndrome associated with a broad spectrum of malignancies, including non-Hodgkin lymphomas (NHL). Most patients die due to cancer before the age of 20years. Limited data exist on CMMRD-associated lymphomas and their outcome. We conducted a retrospective study including all CMMRD-associated NHL patients registered before 2020 in the European and North American databases or reported by members of the European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL). Events considered to define event-free survival included relapse/progression, second malignancy (SML), or death, whichever occurred first. The analysis included 74 patients, with 20 having multiple metachronous NHL. The median age at diagnosis was 9.4years. Previous malignancies were reported in 36% of the patients, café au lait spots in 96%, and consanguinity in 54%. The initial lymphoma subtypes were 53 T-cell lymphoblastic lymphomas (T-LBL), four B-lymphoblastic lymphomas, and 17 mature B-cell non-Hodgkin lymphoma (B-NHL). All patients were treated with curative intent, with current chemotherapy regimens adapted to their subtype. The median follow-up was 8.7years. After the first lymphoma, the 5-year event-free and overall survival rates were, respectively, 23.5% [95% confidence interval (CI): 14.9-35.1] and 61.5% [95% CI: 49.6-72.1]. The 5-year cumulative risk of progression/relapse, SML or death as a first event was 20.8%, 52.9%, and 2.7%. Standard treatments for sporadic NHL are effective in most CMMRD-associated NHL cases, but multiple malignancies, including lymphomas, impair prognosis. Future strategies should evaluate the potential of less genotoxic therapies, including immunotherapy, in preventing SMLs while maintaining effective control of NHL.

Non-Hodgkin lymphoma presenting with spinal cord compression: A population-based analysis of the NHL-BFM study group.

Spinal cord compression is a rare presentation of non-Hodgkin lymphoma (NHL) in children. We aimed to describe the prevalence, histological subtypes, clinical presentation, therapy, and outcome of those children in a population-based cohort. The chemotherapy regimen remained comparable over time. We retrospectively identified all children and adolescents with paresis as initial manifestations of the NHL between January 1990 and December 2020 from the NHL-BFM database. Characteristics, therapy, and outcome data were gathered from the database and patient files. Fifty-seven of 4779 children (1.2%) presented with initial paresis due to spinal cord compression. The median age was 10.3 years (range, 3.1-18.0 years), and 33% were female. Initial symptoms were paresis/weakness (n=50, 88%), back pain (n=33, 58%), paresthesia (n=23, 40%), and bladder dysfunction and/or constipation (n=22, 39%), persisting for a median of 14 days before diagnosis. Subtype distribution was mature B-NHL (n=41, 72%), precursor B-lymphoblastic lymphoma (LBL) (n=12, 21%), anaplastic large cell lymphoma (ALCL) (n=3, 5%), and T-LBL (n=1, 2%). Initial emergency therapy included surgery (70%) and/or chemotherapy/steroids (63%). Five-year event-free survival and overall survival (80%±5% and 82%±5%, respectively) were comparable with all other NHL patients. Neurological symptoms persisted in approximately one-third of surviving patients at the last follow-up. 1.2% of pediatric NHL patients presented with paresis from spinal cord compression mainly due to B-cell lymphomas. Neurological sequelae were observed in one-third of surviving patients.

B-NHL Cases in a Tertiary Pediatric Hematology-Oncology Department: A 20-Year Retrospective Cohort Study.

Non-Hodgkin lymphoma (NHL) is among the five most common pediatric cancer diagnoses in children and adolescents and consists of a heterogeneous group of lymphoid tissue malignancies -with B-cell-derived NHL accounting for nearly 80% of cases. Novel and high-throughput diagnostic tools have significantly increased our understanding of B-NHL biology and molecular pathogenesis, leading to new NHL classifications and treatment options. This retrospective cohort study investigated 17 cases of both mature B-cell NHL (Burkitt lymphoma or BL; Diffuse large B-cell lymphoma or DLBCL; Primary mediastinal large B-cell lymphoma or PMBCL; Follicular lymphoma or FL) and immature B-cell progenitor NHL (B-lymphoblastic lymphoma or BLL) that were treated in a tertiary Pediatric Hematology-Oncology Department during the last 20 years. Modern NHL protocols for children, adolescents, and young adults, along with the addition of rituximab, are safe and efficient (100% overall survival; one relapse). Elevated ESR was more prevalent than elevated LDH. Analyses have focused on immune reconstitution (grade ≥3 infections, lymphocyte and immunoglobulin levels recovery) and body-mass-index changes post-treatment, late effects (in 53% of patients), and the presence of histology markers BCL2, BCL6, CD30, cMYC, and Ki-67%. One patient was diagnosed with a second malignant neoplasm (papillary thyroid cancer).

Renal B-lymphoblastic lymphoma with hematuria as the first symptom diagnosed in urine cytology: A case report and literature review.

Cytological examination of urine sediment is a helpful diagnostic tool for identifying renal involvement by hematological malignancies. We present the case of a 47-year-old man who was diagnosed with extranodal B-lymphoblastic lymphomas after presenting with gross hematuria as his first symptom. The presence of lymphoma cells in the urine led to a diagnosis confirmed through an immunophenotypic study using cell block sections of urine centrifuge sediment and core needle biopsy histology of the right renal pelvis mass. This case highlights the usefulness of a urine cytological study in diagnosing lymphoma involvement in the genitourinary tract. Furthermore, this paper reviews relevant literature on diagnosing lymphoma involvement from urine sediment.

Paediatric cutaneous lymphomas including rare subtypes: A 40-year experience at a tertiary referral centre.

Primary cutaneous lymphomas are neoplasms of the immune system with a distinct tropism for the skin and an absence of extracutaneous manifestations at the time of diagnosis. Studies focusing on cutaneous lymphomas in children and adolescents remain scarce and often do not encompass the rare subtypes. To address this knowledge gap by describing the clinical, histological and molecular characteristics of a large group of paediatric patients affected by primary cutaneous lymphoma. We also provided the Paediatric Primary Cutaneous Lymphoma Atlas that illustrates the clinicopathological spectrum of observed presentations, in the hope of supporting other physicians in the diagnostic process. Retrospective chart review of paediatric patients diagnosed with primary cutaneous lymphomas between 1980 and 2022 at the Paediatric Dermatology Unit of Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan. A total of 101 patients (58 males, 43 females) met the inclusion criteria. The most common subtypes were lymphomatoid papulosis (n = 48) and mycosis fungoides (n = 31). These were followed by primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorders (n = 7), primary cutaneous anaplastic large-cell lymphomas (n = 5), primary cutaneous marginal zone B-cell lymphomas (n = 3), primary cutaneous follicle centre lymphomas (n = 2), subcutaneous panniculitis-like T-cell lymphomas (n = 2), primary cutaneous peripheral T-cell lymphoma not otherwise specified (n = 1), primary cutaneous precursor B-lymphoblastic lymphoma (n = 1) and Sézary syndrome (n = 1). Clinical follow-up data covering a median of 70.8 months (range 1-324) were available for 74 patients, of whom three died due to cutaneous lymphoma. Our findings shed light on the peculiar aspects and long-term outcomes of paediatric cutaneous lymphomas, particularly emphasizing their distinctive features in comparison to their adult counterparts and exploring the less common subtypes. Further larger-scale studies are warranted to better characterize these entities and to achieve a more rapid and accurate diagnosis.

B-Lymphoblastic Lymphoma in Children: A Case Series From a Single Institution.

Pediatric B-lymphoblastic lymphoma is an uncommon subtype of non-Hodgkin lymphoma. Studies regarding the biology, clinical course, and approach to relapse are limited. We present a series of children with B-lymphoblastic lymphoma to describe the clinical course at diagnosis and relapse as well as the role of tumor cytogenetics, immunotherapy, and hematopoietic stem cell transplant. The prognostic significance of cytogenetic changes in B-lymphoblastic lymphoma is not well described but may offer improved risk stratification. Immunotherapy may offer salvage options for relapsed disease and can serve as a bridge to transplant.

FLI-1 is expressed in a wide variety of hematolymphoid neoplasms: a special concern in the differential diagnosis

Friend Leukemia Virus Integration 1 (FLI-1) is a member of E26 transformation-specific family of transcription factors that participates in hematopoietic and vascular endothelial cell development. Immunohistochemical detection of FLI-1 has been widely used to diagnose vascular tumors or, more evidently, Ewing’s sarcoma. However, the expression pattern of FLI-1 in hematolymphoid neoplasms remains unclear. Therefore, in this study, we aimed to investigate the expression of FLI-1 in these tumors, focusing on high-grade lesions, which presents a diagnostic challenge by mimicking Ewing’s sarcoma. We evaluated the expression FLI-1 in various types of lymphoid and plasmacytic tumors, including 27 plasmablastic lymphomas, 229 diffuse large B-cell lymphomas, 22 precursor T- or B-lymphoblastic lymphomas, 24 angioimmunoblastic-type nodal T-follicular helper cell lymphomas, 52 peripheral T-cell lymphomas, NOS, 18 Burkitt lymphomas, 18 non-gastric lymphomas of mucosa-associated lymphoid tissue, 38 chronic lymphocytic leukemia/small lymphocytic lymphomas, 15 mantle cell lymphomas, 23 gastric MALT lymphomas, 50 plasma cell myelomas, and 38 follicular lymphomas. We calculated the H-scores of FLI-1 immunostaining, ranging from 0 to 200, and used the scores to analyze the clinicopathological significance of FLI-1 statistically. FLI-1 was expressed to varying degrees in all types of hematological tumors. FLI-1 expression was detected in 84.1% of patients (466/554). FLI-1 was highly expressed in precursor T- or B-lymphoblastic lymphomas. Follicular lymphomas exhibited low FLI-1 expression. In plasmablastic lymphoma, 85.2% of the patients were focally positive for FLI-1. FLI-1 expression did not correlate with clinicopathological variables, such as demographic data or disease stage, in patients with plasmablastic lymphoma and diffuse large B-cell lymphoma. However, FLI-1 overexpression was associated with poorer overall survival in patients with plasmablastic lymphoma. This study demonstrates that FLI-1 is expressed in various hematolymphoid neoplasms. FLI-1 expression can lead to diagnostic confusion, especially in small blue round cell tumors, such as lymphoblastic lymphoma, plasmablastic lymphoma, and plasma cell myeloma, when distinguishing tumors positive for CD99 and CD56 without CD3, CD20, or CD45. Our findings also suggested the possibility of FLI-1 as a potential prognostic biomarker for plasmablastic lymphoma.

Lymphoblastic lymphoma presenting as soft-tissue swelling – A single-center experience

Abstract: BACKGROUND: Lymphoblastic lymphomas (LBL) are a rare, aggressive type of non-Hodgkin lymphomas and constitute 2% of all lymphomas. It is classified as T-lymphoblastic lymphoma (T-LBL) and B lymphoblastic lymphoma (B-LBL) and resembles acute lymphoblastic leukemia (ALL), with no or limited bone-marrow involvement. LBL rarely present as soft-tissue swellings. Soft-tissue involvement is more common in B-LBL than in T-LBL. They occur predominantly in adolescents and young adults and have a prognosis similar to ALL. OBJECTIVE: p>The aim was to study the clinical characteristics, treatment response, and survival of patients with lymphoblastic lymphoma presenting with soft-tissue swelling. SETTINGS AND DESIGN: This was a retrospective study of eight adolescent and adult patients with lymphoblastic lymphoma presenting with soft-tissue swelling conducted in the Department of Medical Oncology at a tertiary cancer center in India. STATISTICAL ANALYSIS: The baseline patient characteristics, treatment details, and response assessment were analyzed using descriptive statistics. Overall survival (OS) and progression-free survival were obtained by the Kaplan–Meier method, using the SPSS version. 11. MATERIALS AND METHODS: We present the clinical features, imaging, diagnosis, treatment, and outcome of eight cases of lymphoblastic lymphoma presenting with soft-tissue swellings. Patients above 14 years of age treated over 12 years were included in the study. RESULTS: There were five males and three females. The median age at diagnosis was 24 years. Common presenting complaints were swelling, pain, and paraparesis. The sites of involvement were the epidural mass, thigh, calf, breast, and anterior chest wall. The diagnosis was confirmed by immunohistochemistry. Seven patients were diagnosed with B-LBL and one with T-LBL. They were treated with intensive chemotherapy (six patients with Berlin–Frankfurt–Munster protocol and two with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone). Three patients received consolidation radiotherapy and one received palliative radiotherapy. Seven patients attained remission after induction chemotherapy and four of them are currently alive at a median follow-up of 48 months. The 2-year OS was 71.4%. CONCLUSION: Even though rare, lymphoblastic lymphoma should be considered a differential diagnosis in patients presenting with soft-tissue swelling and should be managed with systemic chemotherapy similar to ALL.

Disparities in Clinical Outcomes of B-Lymphoblastic Lymphoma: A National Cancer Database Study with Focus on Hispanic Populations in the United States

BACKGROUND Lymphoblastic lymphoma, a rare non-Hodgkin's lymphoma subtype, exhibits striking cytological and histological parallels with acute lymphoblastic leukemia (ALL). Such similarities have led to its classification as precursor B and T lymphoblastic lymphoma/leukemia by the World Health Organization. Exhibiting a modest global incidence of 1 to 5 cases per 100,000 population, it is notable that two-thirds of cases of ALL cases are of B-cell phenotype (PMID 15698386). To deepen our comprehension of this rare disease, it becomes essential to understand its behavior across various demographics, particularly among Hispanic (HI) and Non-Hispanic (NH) populations in the United States (US). To bridge this knowledge gap, this pioneering nationwide study endeavors to unravel how demographic, clinical, and survival outcomes vary between HI and NH patients with this disease. METHODS: Data were analyzed on B-Lymphoblastic lymphoma patients in the US reported to the National Cancer Database (NCDB) between 2004 and 2019. Demographic and treatment characteristics were compared between ethnic groups. Kaplan-Meier and Cox regression analyses were used to compare OS between Hispanic and Non-Hispanic populations. Multivariate analysis and propensity score matching was performed with adjustment for age, stage, co-morbidity score, and insurance status, type of facility and great circle distance. RESULTS Of 989 B-Lymphoblastic Lymphoma patients, 16 were HI, and 81% NH. 53% of HI were male, compared to 57% of NH. At diagnosis, HI patients were younger (40 years vs. 56 years) (p=<0.001); the majority of HI 84% and NH 68% were diagnosed in the age bracket of < 65 (p=<0.001). With respect to race, most of both HI and NH were whites (87% vs 85%), followed by blacks (1% vs 10%). Examining the stage, most of both HI 45% and NH 47% were stage IV (p= 0.260). When looking at insurance type; private insurance was the most prevalent type in HI vs NH (42% vs 51%), followed by government-sponsored (40% vs 44%). The most uninsured group was HI 16% vs NH 3%. Considering Census Median Income (2008-2012), the most prevalent bracket for HI was Less than $38,000 (29%) and NH was $63,000+ (34%). When it comes to median income of less than $38,000, HI were 29% vs NH 16%. As for Charlson-Deyo Score (comorbidities score), HI had 10% =/> 2 scores, vs NH 8%. In terms of Academic/Research Programs, including NCI-designated comprehensive cancer centers, it was the most prevalent type of facility providing care for both HI 55% and NH 50%. Regarding the median distance in miles between the patient's residence and the hospital that reported the case (Great Circle Distance), HI lived at a median of 9.3 miles, vs NH at a median of 12.4 miles. On survival analysis; the survival probability at 2, 5, and 10 years of HI vs NH were (0.624 vs 0.552), (0.516 vs 0.435), and (0.458 vs 0.362), respectively. The median survival time (MS) was 10.0 years for HI, vs 3.1 years for NH; and there was an overall survival (OS) difference favoring HI with (p=0.017). On multivariate analysis, there were no independent variables associated with better or worse OS; however, the propensity matched analysis showed a striking MS difference between HI vs NH (3.02 y vs. 1.43 y). CONCLUSION This groundbreaking study provides crucial insights into the distinct demographic and clinical characteristics of HI and NH patients with B-Lymphoblastic Lymphoma in the US. Importantly, we found that HI patients were significantly younger at diagnosis, and despite having a higher percentage of uninsured individuals and lower median income, showed better survival outcomes compared to NH. These findings highlight the critical role ethnicity plays in disease presentation and prognosis, thus emphasizing the importance of culturally sensitive, tailored healthcare approaches. This study underscores the urgent need for further research to understand intrinsic biologic factors contributing to these disparities and enhance health equity in lymphoma care.

Efficacy and Safety of Avatrombopag in the Treatment of Chemotherapy-Induced Thrombocytopenia Refractory to Rhtpo in Patients with Lymphoma

Background: Chemotherapy-induced thrombocytopenia (CIT) is a common cause of chemotherapy dose reductions and treatment delays. With applications of recombinant human interleukin 11 (rhIL-11) and recombinant human thrombopoietin (rhTPO), outcomes of patients with CIT have improved significantly. however，some patients with severe thrombocytopenia still have poor responses to the above therapies. Avatrombopag is an orally administered thrombopoietin receptor agonist and can stimulate thrombopoiesis in haematopoietic stem cells. Avatrombopag has been approved in the USA, Europe, and China for thrombocytopenia in patients with chronic liver disease who are scheduled to undergo a surgery. It also has been approved for patients with chronic immune thrombocytopenia who are unresponsive to previous treatments in the USA and Europe. The aim of this study is to evaluate the efficacy and safety of avatrombopag in the treatment of refractory CIT. Methods: The clinical data of 23 lymphoma patients with grade 3/4 CIT unresponsive to rhTPO treatment for 7-10 days were collected from April 2022 to May 2023. All patients received avatrombopag orally at a dose of 40 to 60 mg / day combined with subcutaneous injection of rhTPO (300 U/kg/day). Response (R) was defined as a platelet count≥ 50 × /L, or doubling of the baseline platelet count, and absence of bleeding. Platelet transfusion was allowed when the platelet count was less than 10×109/L or with bleeding events. When the platelet count recovered to ≥100 ×10 9/L or increased 50 ×10 9/L from baseline, treatments of avatrombopag and rhTPO were stopped. Results: The median age of the 23 patients with refractory CIT was 57 (range 17‒83) years. The pathological subtypes were diffuse large B cell lymphoma (DLBCL) (n=10), Burkitt lymphoma (n=4), angioimmunoblastic T-cell lymphoma (AITL) (n=3), follicular lymphoma (FL) (n=2), extranodal NK/T cell lymphoma (ENKTL) (n=1), anaplastic large cell lymphoma (ALCL) (n=1), B-lymphoblastic lymphoma (n=1), and mantle cell lymphoma (MCL) (n=1). The treatment consisted of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) (n=11), Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone), high-dose methotrexate with cytarabine (n=6), liposomal mitoxantrone-containing regimen (n=4), bendamustine-containing regimen (n=1), and peg-asparaginase-based regimens (n=1). At baseline, 19 patients experienced grade 3 and 4 patients experienced grade 4 thrombocytopenia after chemotherapy. The median lowest platelet level was 12×10 9/L (range 2‒44×10 9/L). Two patients developed grade 1 bleeding events and one patient occurred grade 2 bleeding events. Nineteen patients received platelet transfusion. After receiving the combination therapy of avatrombopag, 73.9% (17/23)of patients achieved the primary end point of corrected platelet counts (≥50×10 9/L )and were free from platelet transfusion. The median time to response was 11 (range 5‒25) days. No treatment-related adverse events such as elevated aminotransferases, thrombosis, fatigue, fever and dizziness were noticed during administration. Two patients received avatrombopag as secondary prophylactic treatment, and there were no grade 4 thrombocytopenia or bleeding events during subsequent cycles of chemotherapy. Conclusion: Avatrombopag is effective and safe in the management of CIT for lymphoma and it can be used as an alternative / combination treatment for the patients who refractory to rhTPO. The further clinical research is still needed to confirm this conclusion.

The Universal Antitumor Activity of TAS0612, a Triple Inhibitor for RSK, AKT, and S6K, in B-Cell Lymphomas Regardless of Disease Subtype

B-cell lymphomas (BCLs) are the most common disease entity among hematological malignancies and have various genetically and molecularly distinct subtypes. Although the prognosis of most BCL subtypes has been greatly improved by the advancements of disease subtype-oriented molecular-targeted therapeutics, there remain patients who are incurable with currently available therapeutics. Therefore, further development of new therapies that are effective regardless of disease subtypes is still awaited. 3-phosphoinositide dependent protein kinase 1 (PDPK1) is the master serine-threonine kinase of >20 AGC kinases, including RSK family proteins, AKT, S6K, and several non-AGC kinases. By regulating a series of downstream molecules and mediating the RAS/ERK/RSK2 and PI3K/AKT pathways, PDPK1 plays a pivotal role in disease development and progression in various malignancies. We have also shown that PDPK1/RSK2 axis plays pivotal roles in the pathophysiology of multiple myeloma and mantle cell lymphoma (MCL) (Chinen Y, Cancer Res 2014; Shimura Y, Mol Cancer Ther 2012; Matsumura-Kimoto Y, Cancer Med 2020). In the search for novel molecular targeted therapy for BCLs, these provoked us to investigate the role of PDPK1 and its effector molecules as the therapeutic targets in a broad range of BCLs. We first revealed that the blockade of phosphoinositide-dependent kinase-1 (PDPK1) using its specific inhibitor BX-912 induces a growth inhibition via G2/M cell cycle arrest and the induction of apoptosis in all 8 BCL-derived cell lines examined, including two from activated B-cell-like diffuse large B cell lymphoma (DLBCL), two from double expressor DLBCL, two from Burkitt lymphoma, and two from follicular lymphoma (FL). By using specific inhibitors for the downstream kinases of PDPK1, we also demonstrated that RSK2, AKT, and S6K, but not other PDPK1 substrates, such as PLK1, SGK, or PKC, plays critical roles for cell survival and proliferation as target molecules of PDPK1 in these cell lines examined. In addition, RSK2 plays a central role and AKT and S6K play subsidiary functional roles as the downstream effectors of PDPK1. Following these results, we next investigated the anti-BCL efficacy of TAS0612 which is the triple inhibitor for total RSK, including RSK2, AKT, and S6K, by inhibiting the binding of its target RSK, AKT, and S6K with their substrate molecules (Shibata T, Mol Cancer Ther 2020). As the results, TAS0612 showed the antiproliferative effect in all 8 BCL-derived cell lines examined with IC80s ranging from 1.18 to 8.46 µM, leading to G1 or G2/M cell cycle blockade, and induced apoptosis. At the protein level, TAS0612 caused the accumulation of its direct substrates p-total RSK Ser380, p-AKT Ser473, and p-S6K Thr389 in most cell lines examined as the results of the inhibition of binding to their respective substrates, and the subsequent inactivation through dephosphorylation of their respective target substrates in all cell lines examined. The 72-hour treatment with TAS0612 at 2.5 and 5.0 µM also showed the ex vivo antiproliferative effect in 25 patients-derived lymphoma cells of various disease subtypes, including nine DLBCLs, seven FLs, three MCLs, one mucosa-associated lymphoid tissue lymphoma, one splenic marginal zone B cell lymphoma, one chronic lymphocytic leukemia, and three B-lymphoblastic lymphomas. We finally examined the global molecular effects of TAS0612 using gene expression profiling. Among several tumor suppressor genes upregulated by TAS0612, we found the increased expression of tumor protein 53 inducible nuclear protein 1 (TP53INP1) in cell lines regardless of disease subtypes. Moreover, gene set enrichment analysis identified that TAS0612 significantly downregulated the gene sets driven by the upregulation of MYC and mTORC1, reactive oxygen species, and the unfolded protein response. Thus, this study revealed that the concomitant blockade of RSK2, AKT, and S6K, which are the pivotal downstream substrates of PDPK1, is a novel universally active therapeutic target for the various disease subtypes of BCLs, and line up TAS0612 as an attractive candidate agent for BCLs for future clinical development.

Lymphoma of Nervous System or the Great Imitator in Neurology

Background: Lymphoma of the central nervous system (CNS), both primary and secondary, represents a very rare part of patients with non-Hodgkin lymphoma. Methods: Exams included a neurological exam, laboratory blood tests, МRI, biopsy, and electromyography. Results: Three different clinical cases of patients with lymphoma of the nervous system are presented. The first patient is a 44-year-old male admitted to the emergency room because of neck stiffness, with MRI data for a tumour in the left cavernous sinus area. Biopsy was performed 3 months prior to hospitalisation, showing connective tissue, partially hyalinised. Lumbar tap was performed to exclude CNS infection. Cerebrospinal fluid (CSF) examination showed lymphocytic pleocytosis, atypical cells in different phases of mitosis, and the result did not confirm lymphocytic choriomeningitis. Flow cytometric measurement (FCM) of CSF led to the diagnosis of T-lymphoblastic lymphoma of CNS. The second patient is a 50-year-old female hospitalised in the authors’ neurological department because of lower limb weakness and decreased sensation, dysphagia, and facial nerve palsy. Brain MRI showed no abnormal lesions. Guillain–Barré syndrome was considered after performing electromyography and electroneurography. CSF showed lymphocytic pleocytosis and 47% of them were atypical. FCM of CSF helped the authors diagnose the patient with B-lymphoblastic lymphoma. The third case presents a 63-year-old male with right sided hemiparesis and progressive cognitive impairment. Previously performed CTs and MRIs of the brain showed both hemispheres and left cerebellar peduncle diffuse lesions. Ischaemic stroke, tumour, and CNS infectious disease were considered. Most of these were excluded because CSF showed no pathological findings. Brain tissue biopsy of one of the lesions was performed, and the patient was diagnosed with diffuse large B cell lymphoma. Conclusion: Lymphoma of the CNS is rare disease. Differential diagnoses include different conditions. FCM of CSF and biopsy could be useful in complicated patients and unknown diagnosis affecting the CNS.

Real-world use of tisagenlecleucel in children and young adults with relapsed or refractory B-cell lymphomas.

10031 Background: Survival for pediatric B-cell lymphomas (BCL) exceeds 90% with modern regimens, however outcomes remain poor for patients with relapsed or refractory (R/R) disease. Tisagenlecleucel is a CD19-directed CAR T-cell therapy (CART) that is FDA approved for adults with R/R BCL. No data exists for use of tisagenlecleucel in R/R pediatric BCL. Methods: We surveyed 48 sites in the Pediatric Real-World CAR Consortium to retrospectively describe use and outcomes of tisagenlecleucel for pediatric patients with R/R BCL. This cohort included 10 patients from 7 centers aged ≤25 years who were infused between 2019-2022 and were ≥3 months from CART. We aimed to describe response rates, as determined by each institution based on positron emission tomography, bone marrow evaluation, and/or cerebrospinal fluid (CSF) studies, along with toxicity and outcomes in this population. Results: Ten patients received CART with a median age at infusion of 19 (range, 7-24) years. Five patients had B-lymphoblastic lymphoma (B-LLy), 2 had primary mediastinal BCL, and 1 each had Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), and post-transplant lymphoproliferative disorder related DLBCL. Five patients had primary refractory disease, and 5 were in ≥2nd relapse. Three had received prior hematopoietic stem cell transplant (HSCT). Two had CSF involvement, and 1 had central nervous system parenchymal disease at time of infusion. CART was well tolerated with 1 patient experiencing grade 3 cytokine release syndrome and 2 patients experiencing neurotoxicity (grade 2 n = 1, grade 3 n = 1), both of whom had CSF involvement at time of CART infusion. Best overall response was complete response (CR) for 6, partial response (PR) for 2, and refractory disease for 2. Two patients, both with B-LLy, underwent allogeneic HSCT while in CART-mediated CR with B-cell aplasia. Both patients with PR (1 DLBCL, 1 Burkitt) subsequently relapsed with CD19-negative disease; the patient with DLBCL subsequently achieved CR with salvage immuno-chemotherapy and HSCT. All 6 CR patients remain in remission at a median time to follow-up of 31 (range, 14-47) months. Conclusions: This multicenter case series of CD19-directed CART for R/R pediatric BCL suggests that tisagenlecleucel may be safe and active in this population with all CR patients currently in sustained remission. Larger studies are needed to understand how best to incorporate CART into treatment for R/R pediatric BCL. [Table: see text]

How I approach B-lymphoblastic lymphoma in children.

There are limited data pertaining to the prognostic features and optimal therapeutic approach for the 20%-25% of children with lymphoblastic lymphoma (LLy) who have the B-lymphoblastic subtype. Outcomes are favorable following treatment modeled after acute lymphoblastic leukemia (ALL) regimens, but prognosis is dismal after relapse, and there are no established features for predicting therapy response. Ongoing US and international trials will include the largest cohort of uniformly treated patients with B-LLy to date, providing an opportunity to define clinical and molecular predictors of relapse and to establish a standard of care for treatment to improve outcomes for this rare pediatric cancer.

Pediatric Non-Hodgkin Lymphoma: Ten-Year Experience with Berlin-Frankfurt-Munster (BFM) Protocols from a Tertiary Care Hospital in Turkey

Objective: Progress in therapy of childhood non-Hodgkin lymphoma (NHL) is one of the stunning success stories of the past two decades. In developed countries, more than 80% of children with NHL can now be cured with modern therapy, even patients with widely disseminated disease. The aim of this study is to analyze all NHL patients who were treated in a single tertiary center in Turkey. Methods: An analysis of data of children with NHL, diagnosed and treated between 2003 and 2012 according to the original Berlin-Frankfurt-Munster (BFM) protocol in Kocaeli University Pediatric Oncology Department was carried out. 
 Results: Forty-seven children were eligible for analysis. Mean age at diagnosis was 9.6 years with a male: female ratio of 1.9. Thirty-one patients (66%) were mature B-cell NHL with 23 patients (48.9%) Burkitt lymphoma, 7 patients (14.8%) diffuse large B-cell lymphoma, 1 patient (%2) primary mediastinal large B-cell lymphoma; 13 patients (27.6%) were lymphoblastic lymphoma with 11 patients (23.3%) T-lymphoblastic lymphoma and 2 patients (4.2%) B-lymphoblastic lymphoma, and also 3 patients (6.3%) were mature-T cell lymphoma-anaplastic large cell lymphoma. Four-year event-free survival was 78.7% and overall survival was 80.8%. 
 Conclusion: These results with BFM protocol administration reflect good treatment outcome in our patients.

B Lymphoblastic Lymphoma of Thigh: A Case of an Unusual Location

B-Lymphoblastic Lymphoma (B-LBL) is a malignancy of immature B lymphoid cells. They have a low propensity for bone marrow involvement. They typically present as generalised lymphadenopathy, bone lesions, mediastinal or skin lesions. They present with more skin and soft tissue involvement than acute lymphatic leukaemias. They are treated with systemic chemotherapy similar to their leukaemic counterparts. They have a favourable prognosis with a survival of 90%, although it worsens with age. Here, we present the case of a 23-year-old gentleman who was evaluated for a swelling in the posterior aspect of right thigh clinically resembling a sarcoma. Imaging studies showed a lesion in the posterior compartment of right thigh which showed contrast enhancement and hyperintensity in T2 images. Pelvic and inguinal node was enlarged. Ultrasound guided biopsy from the lymph node was suggestive of B-LBL. There was no bone marrow involvement. He was treated according to Berlin-Frankfurt-Munster (BFM) 95 protocol and attained remission post induction. He completed induction, consolidation and reinduction and is currently on maintenance treatment.

Reduced Expression of the Tissue-Specific Oct-IL Isoform Exerts an Antitumor Effect on Namalwa Burkitt's Lymphoma Cells

Increased expression levels of the Oct-1 transcription factor is considered to be one of the key markers of poor cancer prognosis. In addition to the ubiquitous Oct-1A isoform, which is found in all cells, there also exists a tissue-specific Oct-1L isoform, which is expressed in hematopoietic cells. Oct-1L increases cell resistance to different stresses and also regulates the expression of genes controlling differentiation of hematopoietic and immune system cells. The tissue-specific Oct-1L isoform levels are significantly increased in the B-cell lymphoblastoma Namalwa and Raji lines and the T-cell lymphoblastoma Jurkat line compared to normal B and T cells. Apparently, aberrant Oct-1L overexpression not only enhances stress resistance but also leads to the disruption of developmental pathways in the cells promoting their malignant transformation. We report here that targeted suppression of the tissue-specific Oct-1L isoform expression reduces the proliferation rate of Namalwa B-lymphoblastic Burkitt's lymphoma cells, significantly increases cell death rate under hypoxic conditions, and makes cells more sensitive to chemotherapeutic agents such as docetaxel and doxorubicin. These results indicate that targeted therapy aimed at the suppression of the Oct-1 isoforms with increased expression levels in tumor cells rather than the total Oct-1, thus avoiding the traumatic effects of total Oct-1 knockdown, may be promising. Selective suppression of Oct-1 isoforms is a promising strategy in the treatment of lymphoid tumors and may contribute to mitigating the disease course and increasing survival rates in cancer patients.

Malignant Lymphoproliferative Disorders of the Oral and Maxillofacial Region: Report of Two Institutions.

BackgroundReport of the incidence of malignant hematologic neoplasms in the oral cavity according to the experience of the two oral and maxillofacial pathology institutions in North Carolina, USA.MethodsA 10-year retrospective review was carried out in the records of patients at ECU SoDM and UNC Adams SoD. Age, sex, location of the lesion, clinical impression, initial diagnosis, and the expression immunohistochemical and molecular markers were recorded for each subject. All diagnoses were reviewed according to the 2016 revision of the WHO classification of lymphoid neoplasms.ResultsA total of 318 records from both institutions were reviewed. Seventy males and 68 females with an average age of 60.7 comprised the study population. The most common neoplasm encountered was plasma cell myeloma, followed by diffuse large B-cell lymphoma, B-lymphoblastic lymphoma, and follicular lymphoma. We encountered primarily intraosseous tumors, with the posterior mandible and posterior maxilla being the most common locations. Twelve cases were identified initially as a periapical radiolucency.ConclusionOur findings are concurrent with the existing literature regarding epidemiologic data. However, the type and location of tumors encountered do not, as the most common lymphoma in the oral cavity is diffuse large B-cell lymphoma, typically present in soft tissue. To aid in diagnosis and treatment, the collection of data should continue over time so that eventually, a more specific diagnostic profile of North Carolina residents with these neoplasms can be made.

B-lymphoblastic lymphoma presenting as the gallbladder tumor: a case report

B-lymphoblastic lymphoma presenting as the gallbladder tumor: a case report

Solitary manifestations of primary B-lymphoblastic lymphoma of the spine: Systematic literature review with case illustration

BackgroundGiven the locally destructive osteolytic nature of primary B-cell lymphoblastic lymphoma (B-LBL) of the spine, careful attention is needed to identify clinical signs and symptoms as well as radiological findings of spinal instability because these lesions may warrant resection, decompression, and instrumentation with posterolateral fusion. Our objective was to summarize the presenting symptoms, clinical features, potential treatment modalities, and clinical outcome of cases described in the literature. MethodsWe undertook a systematic literature review to identify all relevant cases and case series describing primary manifestations B-LBL of the spine using Pubmed/Medline. We summarized the findings in accordance with the PRISMA guidelines. We also present a case illustration. ResultsTogether with our case, 9 cases of primary B-LBL of the spine were identified in 6 male and 3 female patients (age 8–58 years, median 31 years). Back pain was the most common symptom, and five patients also had neurological signs of spinal cord compression. T1-weighted MRI contrast enhancement was seen in 5 cases. Surgery was performed in 5 patients with progression of neurological deficits. Steroid treatment was also given in 3 patients preoperatively. Seven patients had chemotherapy after diagnosis. During follow-up of 1 month to 1 year, 2 cases of recurrence and 4 cases of complete remission were noted; however, with the short follow-up time, patient prognosis overall remains unclear. ConclusionsPrimary B-LBL of the spine represents a rare clinical entity whose management mandates a multidisciplinary approach. Careful attention must be paid to the neurological status of the patient, as well as to imaging that may highlight potential local instability of the spine.