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British Journal of Haematology Mar 2021Relapses involving the central nervous system (CNS) are rare in children and adolescents with ALK+ anaplastic large cell lymphoma (ALCL) treated with regimens including... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Neuro-meningeal relapse in anaplastic large-cell lymphoma: incidence, risk factors and prognosis - a report from the European intergroup for childhood non-Hodgkin lymphoma.
Relapses involving the central nervous system (CNS) are rare in children and adolescents with ALK+ anaplastic large cell lymphoma (ALCL) treated with regimens including CNS prophylaxis. Early identification of patients at high-risk for CNS relapse would enable stratification and better adaptation of initial treatment especially in the light of the upcoming targeted therapies with limited CNS penetration. We analyzed clinical and histological data of all ALK+ALCL patients with CNS relapse registered in ALCL99-database with the aim to describe risk factors and outcome. Characteristics of patients with no relapse, relapse without CNS involvement and CNS relapse were compared. At a median follow-up of 8 years (0.05-18 years), a CNS involvement was reported at first or subsequent relapse in 26/618 patients. Median interval between initial diagnosis and first CNS relapse was 8 months (IQR 5.55-10.61/range 1.31-130.69). The 5-year cumulative risk of CNS relapse was 4% (95% CI 2.9-5.5). Bone marrow involvement, peripheral blasts and CNS involvement at diagnosis were more frequent in patients with CNS relapse than in patients with no relapse or with relapse with no CNS involvement. The treatment of CNS relapse was heterogeneous. The median survival after CNS relapse was 23.7 months. Eleven patients were alive at last follow-up. Three-year overall survival after CNS relapse was 48.70% (95% CI 30.52-67.23).
Topics: Adolescent; Adult; Child; Child, Preschool; Databases, Factual; Disease-Free Survival; Europe; Female; Follow-Up Studies; Humans; Incidence; Infant; Lymphoma, Large-Cell, Anaplastic; Male; Meningeal Neoplasms; Recurrence; Risk Factors; Survival Rate
PubMed: 32648260
DOI: 10.1111/bjh.16755 -
Scientific Reports Dec 2021Central nervous system (CNS) relapse is a significant cause of treatment failure among patients with acute lymphoblastic leukemia. In prior work we found that the...
Central nervous system (CNS) relapse is a significant cause of treatment failure among patients with acute lymphoblastic leukemia. In prior work we found that the meninges, the thin layer of tissue that covers the brain and spinal cord, harbor leukemia cells in the CNS. Importantly, direct interactions between leukemia and meningeal cells enabled leukemia chemoresistance. Herein, we show that an antibody targeting CD99, a transmembrane protein expressed on meningeal cells and many leukemia cells, disrupts adhesion between leukemia and meningeal cells and restores sensitivity of the leukemia cells to chemotherapy. This work identifies a mechanism regulating critical intercellular interactions within the CNS leukemia niche and may lead to novel therapeutic approaches for overcoming niche-mediated chemoresistance.
Topics: 12E7 Antigen; Antibodies, Monoclonal; Drug Resistance, Neoplasm; Humans; Meningeal Neoplasms; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Tumor Cells, Cultured
PubMed: 34934147
DOI: 10.1038/s41598-021-03929-x -
Cureus Apr 2023Sarcoidosis is a systemic disease of unknown etiology with multi-system affection. It typically involves the skin, eyes, hilar lymph nodes, and pulmonary parenchyma....
Sarcoidosis is a systemic disease of unknown etiology with multi-system affection. It typically involves the skin, eyes, hilar lymph nodes, and pulmonary parenchyma. However, as any organ system could be involved, one has to be aware of its atypical manifestations. We present three uncommon manifestations of the disease. Our first case presented with fever, arthralgias, and right hilar lymphadenopathy with a history of tuberculosis in the past. He was treated for tuberculosis but had a relapse of symptoms three months after completion of treatment. The second patient presented with a headache for two months. On evaluation, cerebrospinal fluid examination showed evidence of aseptic meningitis, while an MRI of the brain demonstrated enhancement of the basal meninges. The third patient was admitted with a mass on the left side of the neck for one year. On evaluation, he was found to have left cervical lymphadenopathy, with its biopsy showing non-caseating epitheloid granuloma. Immunofluorescence did not show evidence of leukemia or lymphoma. All the patients had negative tuberculin skin tests and elevated serum angiotensin-converting enzyme levels supporting the diagnosis of sarcoidosis. They were treated with steroids with complete resolution of symptoms and no recurrence at follow-up. Sarcoidosis is an underdiagnosed entity in India. Thus, awareness of the atypical clinical features could lead to early recognition of the disease and its treatment.
PubMed: 37159764
DOI: 10.7759/cureus.37208 -
Indian Journal of Cancer 2021Acute neurological complications occur in 3.6-11% of children treated for acute lymphoblastic leukemia (ALL). This analysis aimed to evaluate the profile of acute...
BACKGROUND
Acute neurological complications occur in 3.6-11% of children treated for acute lymphoblastic leukemia (ALL). This analysis aimed to evaluate the profile of acute neuro-toxicity and its etiology in children with ALL.
METHODS
A retrospective case analysis of central nervous system events in children treated for ALL at our center was performed. Details of events were retrieved from the case records (January 2006-December 2015) and analyzed.
RESULTS
Ninety (9.5%) neurological events occurred in 923 patients treated for ALL. Phase of therapy were: induction (38), consolidation (5), interim maintenance (5), intensification (15) and maintenance (27). Seizures and neurological deficits were the presenting features in 64 and 40 children, respectively. Events included : neuro-infections in 18, posterior reversible encephalopathy syndrome (PRES) in 7, epilepsy in 6, intracranial bleed in 5, systemic infection with neurological complication in 4, hydrocephalus and aseptic meningitis in 3 each, methotrexate encephalopathy and metabolic seizures in 2 children each. Seizures and status epilepticus of unknown etiology and neurological deficits of unknown etiology was observed in 26 and 13 children, respectively. Seizures occurred mainly in induction (12) and intensification phase (9). Status epilepticus transpired in maintenance phase in 9/14 patients. Induction phase was complicated by PRES in 7, intracranial bleed in 5 and cerebral sinus venous thrombosis in 1 patient. Neuroimaging was done in 86% of events. There were 18 (20.6%) deaths: neuro-infections (8), status epilepticus (6), systemic infection (2), bleed (1), and unexplained encephalopathy (demyelination)(1). At last follow-up, 53 patients were well and 7 children persist to have a neurological disability.
CONCLUSION
Ten percent of children on treatment for ALL suffered an acute neuro-toxicity. Morbidity and high-incidence of neuroinfections are major concerns.
Topics: Female; Humans; Male; Nervous System Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Risk Factors; Time Factors
PubMed: 34380827
DOI: 10.4103/ijc.IJC_422_19 -
Scientific Reports Nov 2022To explore the clinical advantages of 3D Slicer combined with Sina/MosoCam multimodal system in preoperative planning of brain lesions surgery. By collecting the data of...
To explore the clinical advantages of 3D Slicer combined with Sina/MosoCam multimodal system in preoperative planning of brain lesions surgery. By collecting the data of brain lesions patients undergoing craniotomy under the preoperative positioning of 3D Slicer combined Sina/MosoCam multimodal system in the people's Hospital of Wuhan University from January 2021 to October 2021, the preoperative planning of patients was introduced, and the size of surgical bone window, operation time, preoperative and postoperative neurological dysfunction were counted. We collected the case data of 35 patients who were reconstructed by 3D Slicer and located by Sina/MosoCam projection. There were 14 cases of malignant tumors (7 cases of glioma, 2 cases of diffuse large B-cell lymphoma, 5 cases of metastatic cancer) and 21 cases of benign tumors (17 cases of meningioma, 1 case of central neurocytoma, 2 cases of cavernous hemangioma and 1 case of arachnoid cyst). All 35 patients were located accurately before operation, the lesions were found quickly during operation, and the postoperative imaging data confirmed that the lesions were removed completely, of which 28 cases (80%) had significantly improved neurological symptoms one month after operation. 3D Slicer combined with Sina/MosoCam multimodal system has many advantages, such as simple and easy to learn, convenient operation, accurate positioning and free. It is considered to be a new technology that is practical, reliable, convenient for diagnosis and preoperative planning. It is suitable for popularization and use in neurosurgery and other operating rooms of all medical institutions.
Topics: Humans; Meningioma; Glioma; Neurosurgical Procedures; Meningeal Neoplasms; Brain; Imaging, Three-Dimensional; Retrospective Studies
PubMed: 36357434
DOI: 10.1038/s41598-022-22549-7 -
Cureus Nov 2021Primary leptomeningeal lymphoma (PLML) is a rare disease, comprising less than 1% of all lymphomas. Clinical manifestations include headache, encephalopathy, ataxia,...
Primary leptomeningeal lymphoma (PLML) is a rare disease, comprising less than 1% of all lymphomas. Clinical manifestations include headache, encephalopathy, ataxia, cranial nerve palsy, and myelitis. Diagnosis requires a combination of magnetic resonance images (MRI), cytology, flow cytometry of cerebrospinal fluid (CSF), and an extensive workup to rule out systemic lymphoma. We describe the case of a 49-year-old man who developed subacute onset headache, encephalopathy, and blindness. Whole-body examinations, including a bone marrow trephine biopsy, excluded systemic lymphoma. Brain MRI showed leptomeningeal enhancement. Cytology and flow cytometry of CSF found a clonal B-cell population making a diagnosis of PLML. He began treatment with rituximab and high-dose methotrexate (HD-MTX), with progressive clinical improvement. CSF analysis after two cycles and one intrathecal methotrexate dose was normal. Brain and spinal MRI images plus CSF analysis, along with an extensive workup to exclude systemic lymphoma, are necessary to diagnose PLM. Early treatment with HD-MTX alone or in combination with rituximab improves clinical outcomes.
PubMed: 34956753
DOI: 10.7759/cureus.19619 -
Clinical Case Reports Jun 2023Primary dural Hodgkin lymphoma (PDHL) is an extremely rare subset of Hodgkin lymphoma (HL). Its existence is controversial, as Hodgkin lymphoma is not traditionally...
Primary dural Hodgkin lymphoma (PDHL) is an extremely rare subset of Hodgkin lymphoma (HL). Its existence is controversial, as Hodgkin lymphoma is not traditionally thought to arise from the central nervous system (CNS) or its meninges and only 0.02% of patients with Hodgkin lymphoma have any CNS involvement. We report a case of a 71-year-old Caucasian man who presented with progressive fatigue and sudden onset slurred speech, disorientation, and memory loss. Brain imaging identified a large extra-axial right frontal mass, and he underwent urgent subtotal resection. Pathology and subsequent workup revealed Stage IAE classical Hodgkin lymphoma of the right frontal dura, with no extra-cranial disease or leptomeningeal spread detected. The patient was subsequently treated with ABVD chemotherapy (completed 2.5 of 4 planned cycles) and 36 Gy in 20 fractions of consolidative involved-site radiotherapy (ISRT). He has been followed for 5 years with no clinical or radiological signs of recurrence. This is the second confirmed case of intracranial PDHL reported in the literature, with the longest follow-up for any case of PDHL.
PubMed: 37361649
DOI: 10.1002/ccr3.7562 -
Frontiers in Pharmacology 2023Zanubrutinib is a Bruton tyrosine kinase (BTK) inhibitor used in B cell malignancy treatment and is generally well tolerated in most patients. Zanubrutinib-induced...
Zanubrutinib is a Bruton tyrosine kinase (BTK) inhibitor used in B cell malignancy treatment and is generally well tolerated in most patients. Zanubrutinib-induced aseptic meningitis is currently not reported. Herein, we present the first case of zanubrutinib-induced aseptic meningitis. A 33-year-old woman was diagnosed with relapsed/refractory follicular lymphoma and subsequently developed aseptic meningitis after receiving zanubrutinib treatment. We reviewed the literature and uncovered the lack of current reports on zanubrutinib or other BTK inhibitor-induced aseptic meningitis. Moreover, we summarized cases on aseptic meningitis induced by common chemotherapy and targeted drugs used for hematological diseases. Drug-induced aseptic meningitis (DIAM) is a drug-induced meningeal inflammation. The possible pathogenesis is the direct stimulation of the meninges via intrathecal injection of chemotherapy drugs and immune hypersensitivity response caused by immunosuppressive drugs. It is more common in women with immune deficiency and mainly manifests as persistent headache and fever. Cerebrospinal fluid examinations mainly demonstrate a significant increase in cells and proteins. DIAM diagnosis needs to exclude bacterial, fungal, viral, and tuberculosis infections; neoplastic meningitis; and systemic diseases involving the meninges. The prognosis of DIAM is usually favorable, and physicians should detect and stop the causative drug. In conclusion, zanubrutinib-induced aseptic meningitis is a rare but serious complication, and physicians should be promptly aware of this adverse event to avoid serious consequences.
PubMed: 37727390
DOI: 10.3389/fphar.2023.1242491 -
International Journal of Molecular... Dec 2023C-X-C-motif chemokine ligand 13 (CXCL13) in cerebrospinal fluid (CSF) is increasingly used in clinical routines, although its diagnostic specificity and divergent...
C-X-C-motif chemokine ligand 13 (CXCL13) in cerebrospinal fluid (CSF) is increasingly used in clinical routines, although its diagnostic specificity and divergent cut-off values have been defined so far mainly for neuroborreliosis. Our aim was to evaluate the value of CSF-CXCL13 as a diagnostic and treatment response marker and its role as an activity marker in a larger disease spectrum, including neuroborreliosis and other neuroinflammatory and malignant CNS-disorders. Patients who received a diagnostic lumbar puncture (LP) ( = 1234) between July 2009 and January 2023 were included in our retrospective cross-sectional study. The diagnostic performance of CSF-CXCL13 for acute neuroborreliosis was highest at a cut-off of 428.92 pg/mL (sensitivity: 92.1%; specificity: 96.5%). In addition, CXCL13 levels in CSF were significantly elevated in multiple sclerosis with clinical ( = 0.001) and radiographic disease activity ( < 0.001). The clinical utility of CSF-CXCL13 appears to be multifaceted. CSF-CXCL13 is significantly elevated in patients with neuroborreliosis and shows a rapid and sharp decline with antibiotic therapy, but it is not specific for this disease and is also highly elevated in less common subacute neuroinfectious diseases, such as neurosyphilis and cryptococcal meningitis or in primary/secondary B-cell lymphoma.
Topics: Humans; Cross-Sectional Studies; Retrospective Studies; Spinal Puncture; Multiple Sclerosis; Neurosyphilis; Syndrome; Chemokine CXCL13
PubMed: 38203597
DOI: 10.3390/ijms25010425 -
Chinese Medical Journal Mar 2021With current chemotherapy treatment, >90% of survival has been obtained for Burkitt lymphoma (BL). In this study, the demographic characteristics and treatment outcomes...
BACKGROUND
With current chemotherapy treatment, >90% of survival has been obtained for Burkitt lymphoma (BL). In this study, the demographic characteristics and treatment outcomes are presented for 78 children in China with central nervous system-positive (CNS+) BL.
METHODS
This retrospective study consecutively enrolled 78 CNS+ BL patients in Beijing Children's Hospital (BCH) from 2007 to 2019 who received the BCH B-cell non-Hodgkin's lymphoma regimen (modified by French-American-British mature lymphoma B-cell 96 [FAB/LMB96] C1 arm ± rituximab). Clinical characteristics, methods of disease detection in the CNS, and outcomes were evaluated. Univariate and multivariate analyses were used to assess prognostic factors.
RESULTS
The median age of 65 boys and 13 girls at the time of diagnosis was 5.7 years (ranging from 1 to 14 years). Patients were followed up for a median time of 34 months (ranging from 1 to 72 months). Bone marrow invasion was found in 38 (48.7%) patients. There were 48 (61.5%), 44 (56.4%), and 25 (32%) patients with cranial nerve palsy, intracerebral mass (ICM), and para-meningeal extension, respectively. Abnormal cerebrospinal fluid (CSF) morphology and CSF immunophenotype appeared in 15 (19.2%) and 15 (19.2%) patients, respectively. There were 69 (88.5%) patients treated with chemotherapy combined with rituximab, and nine patients were treated solely with chemotherapy. Finally, five patients died of treatment-related infection, recurrence occurred for 13, and one developed a second tumor. The 3-year overall survival and event-free survival rates were 78.9% ± 4.7% and 71.4% ± 6.0%, respectively. Treatment with chemotherapy only, ICM positivity, and >4 organs involved at diagnosis were independent risk factors.
CONCLUSIONS
Rituximab combined with a modified LMB96 regimen has greatly increased the efficacy of treatment for Chinese children with CNS+ BL, and with the continuous collection of outcome data, treatment-related complications are decreasing. For further verification, a large sample multicentre randomized controlled study should be performed to explore a treatment scheme for Chinese children with even greater efficacy.
Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Central Nervous System; Child; Child, Preschool; China; Cyclophosphamide; Disease-Free Survival; Female; Humans; Infant; Male; Neoplasm Recurrence, Local; Retrospective Studies; Rituximab; Treatment Outcome
PubMed: 33734131
DOI: 10.1097/CM9.0000000000001386