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Frontiers in Immunology 2023Burkitt lymphoma (BL) is the most common tumor of non-Hodgkin's lymphoma (NHL) in children, accounting for about 40% of cases. Although different combined short-course...
Case Report: Unedited allogeneic chimeric antigen receptor T cell bridging to conditioning-free hematopoietic stem cell transplantation for a child with refractory Burkitt lymphoma.
PURPOSE
Burkitt lymphoma (BL) is the most common tumor of non-Hodgkin's lymphoma (NHL) in children, accounting for about 40% of cases. Although different combined short-course chemotherapies have achieved a good effect, refractory/relapsed BL has a poor prognosis with cure rates less than 30%. Chimeric antigen receptor T cell (CAR-T) therapy has developed rapidly in recent years and achieved excellent results in acute lymphoblastic leukemia (ALL). However, in some cases, there is a failure to produce autologous CAR-T cells because of T-cell dysfunction. In such cases, allogeneic CAR-T therapy has to be considered.
METHODS
A 17-year-old boy with stage II BL did not respond to extensive chemotherapy and sequential autologous CAR-T therapy. Lentiviral vectors containing anti-CD20-BB-ζ (20CAR) and anti-CD22-BB-ζ (22CAR) transgenes were used to modify the T cells from an HLA-identical matched unrelated donor. Flow cytometry was used to assess the cytokine analyses and CAR-T cell persistence in peripheral blood, enumerated by qPCR as copies per ug DNA. Informed consent for autologous/allogeneic CAR-T therapy was obtained from the patient and his legal guardian.
RESULTS
Unedited HLA-matched allogeneic CD20 and CD22 CAR-T cells were infused after lymphodepletion chemotherapy with cyclophosphamide and fludarabine. The patient experienced Grade IV cytokine release syndrome (CRS) and went into complete remission (CR) after anti-inflammatory treatment including tocilizumab. Because of persistent pancytopenia and full donor chimerism, the same donor's conditioning-free peripheral blood stem cells were successfully transplanted 55 days post CAR-T. Neutrophils were engrafted at day +11 and platelets were rebuilt at day +47 without obvious acute graft-versus-host disease (GVHD), but there was mild chronic GVHD in the skin and eyes. Currently, active anti-rejection therapy is still underway.
CONCLUSION
Unedited HLA-matched allogeneic CAR-T cell therapy could be an innovative, effective, and safe treatment for children with refractory/relapse BL without obvious acute GVHD. Conditioning-free allogeneic hematopoietic stem cell transplantation (HSCT) from the same donor is feasible for a patient with full donor T-cell chimerism after allogeneic CAR-T. It cannot be ignored that close GVHD monitoring is needed post HSCT.
Topics: Male; Humans; Child; Adolescent; Receptors, Chimeric Antigen; Burkitt Lymphoma; T-Lymphocytes; Hematopoietic Stem Cell Transplantation; Immunotherapy, Adoptive
PubMed: 37736096
DOI: 10.3389/fimmu.2023.1219872 -
Journal of Cancer Research and... 2021Rituximab is a chimeric monoclonal antibody against CD20. It is an established immunotherapeutic agent for non-Hodgkin's lymphoma. Even though rituximab has been used in...
BACKGROUND
Rituximab is a chimeric monoclonal antibody against CD20. It is an established immunotherapeutic agent for non-Hodgkin's lymphoma. Even though rituximab has been used in clinics for decades, only 50% of the patients respond to rituximab therapy. To enhance the in vitro effect of rituximab, it was labeled with Iodine-131 (I) and combined effect of I-rituximab and camptothecin (CPT) was studied on a tumor cell line expressing CD20.
OBJECTIVE
The aim is to study the magnitude of cell killing and the underlying mechanism responsible for enhancing in vitro therapeutic efficacy.
METHODS
Rituximab was labeled with I by the iodogen method. Raji cells were pretreated with CPT (250 nM) for an hour followed by I-rituximab (0.37 and 3.7 MBq) and incubated for 24 h in a humidified atmosphere of CO incubator at 37°C. Subsequently, Raji cells were harvested and thoroughly washed to carry out studies of cellular toxicity, apoptosis, cell cycle, and mitogen-activated protein kinase (MAPK) pathways.
RESULTS
Maximal inhibition of cell proliferation and enhancement of apoptotic cell death was observed in the cells treated with the combination of CPT and I-rituximab, compared to controls of CPT-treated and I-rituximab-treated cells. Raji cells undergo G1 arrest after I-rituximab treatment, which leads to apoptosis and was confirmed by the downregulation of bcl protein. Expression of p38 was decreased while an increase in phosphorylation of p38 was observed in the combination treatment of CPT and I-rituximab.
CONCLUSIONS
It was concluded from the findings that CPT enhanced I-rituximab-induced apoptosis, G1 cell cycle arrest and p38 MAPK phosphorylation in Raji cells.
Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Burkitt Lymphoma; Camptothecin; Cell Proliferation; G1 Phase Cell Cycle Checkpoints; Gene Expression Regulation, Neoplastic; Humans; Radioimmunotherapy; Rituximab; Tumor Cells, Cultured; p38 Mitogen-Activated Protein Kinases
PubMed: 34528546
DOI: 10.4103/jcrt.JCRT_1012_19 -
The American Journal of Case Reports Jun 2022BACKGROUND Burkitt lymphoma (BL) is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL) rarely affecting the central nervous system (CNS) as a primary disease.... (Review)
Review
Primary Central Nervous System Burkitt Lymphoma, Presenting with Long-Term Fluctuating Level of Consciousness: A Case Report and Literature Review on Challenges in Diagnosis and Management.
BACKGROUND Burkitt lymphoma (BL) is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL) rarely affecting the central nervous system (CNS) as a primary disease. Over the past years, only a few cases of primary CNS Burkitt lymphoma were reported. There is a challenge in early recognition and diagnosis of this type of brain lymphoma. Furthermore, there is no specific treatment protocols for primary CNS Burkitt lymphoma, which adds to the difficulty in managing those patients. We introduce a case of a 65-year-old who presented with fluctuating memory disturbance diagnosed as cerebral Burkitt lymphoma. CASE REPORT A 65-year-old man developed a gradual decrease in his level of consciousness over a span of 4 days, associated with fluctuating memory disturbances. A CT scan showed a hyperdense mass in the region of the trigon of the left lateral ventricle and marked obstructive hydrocephalus involving the temporal, occipital horns, and the left lateral ventricle, with no evidence of other suspicious lesions. A brain biopsy of the lesion revealed features of encephalitis initially, but the patient presented later with worsening symptoms, and a repeated brain biopsy showed features of Burkett lymphoma, with normal pan-CT scan. CONCLUSIONS Primary CNS Burkitt lymphoma (PCNSBL) is a rare disease with no clear evidence in the literature of how to deal with it. Reporting such cases provides a better understanding of how to approach such unusual presentations. Treatment of PCNSBL is challenging and even with the currently adopted approaches, the disease still has a very poor outcome.
Topics: Aged; Biopsy; Burkitt Lymphoma; Central Nervous System; Consciousness; Humans; Male; Tomography, X-Ray Computed
PubMed: 35727738
DOI: 10.12659/AJCR.936401 -
Proceedings of the Royal Society of... Sep 1971
Review
Topics: Africa; Burkitt Lymphoma; Hemoglobinopathies; Herpesvirus 4, Human; Humans; Infectious Mononucleosis; Insect Vectors; Malaria; New Guinea; Tropical Climate; Viral Vaccines
PubMed: 4329792
DOI: No ID Found -
BMC Research Notes Oct 2017Burkitt's lymphoma (BL) is a common aggressive non-Hodgkin's lymphoma in East and Central Africa among children. Persistent infections with Epstein Barr virus or...
OBJECTIVE
Burkitt's lymphoma (BL) is a common aggressive non-Hodgkin's lymphoma in East and Central Africa among children. Persistent infections with Epstein Barr virus or Plasmodium falciparum are associated with immune hyperstimulation. It is hypothesised that inadvertent cytokine responses to infections indirectly or directly influence B cell neoplastic transformation through c-myelocytomatosis (c-myc) gene translocation. We sought to describe cytokines in children and adolescents with BL. Participants were recruited from western Kenya with parental consent, diagnosis confirmed using histology and consensus panel of immunohistochemistry antibodies. T helper1/2/17A and transforming growth factor-β1 (TGF-β1) cytokines were estimated using cytometric bead array in plasma. Complete blood counts (CBC) were determined by Beckman Coulter.
RESULTS
Out of 104 enrolled participants, 32% were confirmed BL and 68% grouped as non-BL. Mean (pg/ml) levels of cytokines in BL and non-BL were: interleukin (IL)-6 100.3 and 39.4 p = 0.152; IL-10 11.5 and 12.5 p = 0.363; IL-17A 17.8 and 64.9 p = 0.094 respectively. Expressions of interferon-γ, IL-2 and tumour necrosis factor-α were low and TGF-β1 undetectable in both groups. Mean CBC differed between the two groups before and after chemotherapy, WBC being significantly so. Interleukin-6, IL-17A and IL-10 responses to infections in the study area may be associated with pathogenesis and be potential therapeutic targets.
Topics: Burkitt Lymphoma; Child, Preschool; Cytokines; Female; Humans; Immunohistochemistry; Kenya; Male
PubMed: 29078819
DOI: 10.1186/s13104-017-2841-0 -
Ear, Nose, & Throat Journal Oct 2023Extraganglionic Burkitt's lymphoma is rare. Primary thyroid localization accounts for 1% to 5% of malignant tumors of the thyroid gland. The association of Burkitt's...
Extraganglionic Burkitt's lymphoma is rare. Primary thyroid localization accounts for 1% to 5% of malignant tumors of the thyroid gland. The association of Burkitt's lymphoma and pregnancy is even rarer. Our patient was pregnant at 36 weeks. She was brought to the emergency department with anterior cervical swelling, rapidly increasing in volume and becoming compressive for 15 days, in addition to dysphonia and inspiratory dyspnea. Cervical ultrasound and computed tomography scan revealed a compressive and plunging goiter. Surgery attempted after fetal extraction proved impossible due to massive tumor infiltration into adjacent structures shielding the cervical region. Accordingly, the act was limited to a glandular biopsy. The newborn was healthy. Histological examination confirmed the diagnosis of Burkitt's lymphoma. Given the poor general condition of the patient, chemotherapy was not administered and the patient died after 15 days of stay in intensive care unit.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Burkitt Lymphoma; Pregnant Women; Thyroid Neoplasms; Dyspnea
PubMed: 34107797
DOI: 10.1177/01455613211024877 -
American Journal of Clinical Pathology Dec 2017The latest revision of lymphoma's World Health Organization classification describes the new provisional entity "Burkitt-like lymphoma with 11q aberration" (BLL, 11q) as...
The 11q-Gain/Loss Aberration Occurs Recurrently in MYC-Negative Burkitt-like Lymphoma With 11q Aberration, as Well as MYC-Positive Burkitt Lymphoma and MYC-Positive High-Grade B-Cell Lymphoma, NOS.
OBJECTIVES
The latest revision of lymphoma's World Health Organization classification describes the new provisional entity "Burkitt-like lymphoma with 11q aberration" (BLL, 11q) as lacking MYC rearrangement, but harboring the specific11q-gain/loss aberration. We report genetic characteristics of 11 lymphoma cases with this aberration.
METHODS
Classical cytogenetics, fluorescence in situ hybridization (FISH), and single nucleotide polymorphism/array comparative genomic hybridization.
RESULTS
The 11q aberrations were described as duplication, inversion, and deletion. Array comparative genomic hybridization showed two types of duplication: bigger than 50 megabase pairs (Mbp) and smaller than 20 Mbp, which were associated with bulky tumor larger than 20 cm and amplification of the 11q23.3 region, including KMT2A. Six cases revealed a normal FISH status of MYC and were diagnosed as BLL,11q. Five cases showed MYC rearrangement and were diagnosed as Burkitt lymphoma (BL) or high-grade B-cell lymphoma, not otherwise specified (HGBL, NOS).
CONCLUSIONS
The 11q-gain/loss is not specific for BLL, 11q, but occurs recurrently in MYC-positive BL and MYC-positive HGBL.
Topics: Adult; Aged; Burkitt Lymphoma; Chromosomes, Human, Pair 11; Comparative Genomic Hybridization; Gene Rearrangement, B-Lymphocyte; Humans; In Situ Hybridization, Fluorescence; Lymphoma, B-Cell; Male; Middle Aged; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins c-myc; Young Adult
PubMed: 29272887
DOI: 10.1093/ajcp/aqx139 -
British Journal of Haematology Mar 2012The two major epidemiological clues to the pathogenesis of Burkitt lymphoma (BL) are the geographical association with malaria--BL incidence relates to the malaria... (Review)
Review
The two major epidemiological clues to the pathogenesis of Burkitt lymphoma (BL) are the geographical association with malaria--BL incidence relates to the malaria transmission rate--and early infection by Epstein-Barr virus (EBV). Both agents cause B cell hyperplasia, which is almost certainly an essential component of lymphomagenesis in BL. The critical event in lymphomagenesis is the creation of a MYC translocation, bringing the MYC gene into juxtaposition with immunoglobulin genes and causing its ectopic expression, thereby driving the proliferation of BL cells. It is highly likely that such translocations are mediated by the activation-induced cytidine deaminase (AID) gene, which is responsible for hypervariable region mutations as well as class switching. Stimulation of the Toll-like receptor 9 by malaria-associated agonists induces AID, providing a mechanism whereby malaria could directly influence BL pathogenesis. EBV-containing cells must reach the memory cell compartment in order to survive throughout the life of the individual, which probably requires traversal of the germinal centre. Normally, cells that do not produce high affinity antibodies do not survive this passage, and are induced to undergo apoptosis. EBV, however, prevents this, and in doing so may also enhance the likelihood of survival of rare translocation-containing cells.
Topics: Acquired Immunodeficiency Syndrome; B-Lymphocytes; Burkitt Lymphoma; Environment; Epstein-Barr Virus Infections; Humans; Malaria; Proto-Oncogene Proteins c-myc
PubMed: 22260300
DOI: 10.1111/j.1365-2141.2011.09013.x -
The American Journal of Case Reports Aug 2016BACKGROUND Non-neoplastic causes such as infections and thrombi account for most intracardiac masses. Primary tumors such as myxomas and metastasis from breast cancer,... (Review)
Review
BACKGROUND Non-neoplastic causes such as infections and thrombi account for most intracardiac masses. Primary tumors such as myxomas and metastasis from breast cancer, lung cancer, or melanomas account for many of the remaining cases. Burkitt lymphoma manifesting as an intracardiac mass is a rare entity, with 21 cases reported in the English literature. CASE REPORT We report the case of a man infected with human immunodeficiency virus (HIV) who presented with non-specific cardiac symptoms and was later found to have intracardiac mass caused by Burkitt lymphoma. His rapid decline with unexpected complications was reversed with prompt management. Subsequent to induction, the patient achieved a near complete response with considerable improvement in his condition. CONCLUSIONS Lymphoma should be considered in the differential diagnosis of intracardiac masses. Associated cardiac symptoms are frequently non-specific and can often be overlooked or underappreciated. Burkitt lymphoma has a short doubling time and an intracardiac lesion can become life-threatening in a matter of days. Early recognition and prompt treatment are crucial to achieving optimal outcomes.
Topics: Adult; Burkitt Lymphoma; Echocardiography, Three-Dimensional; HIV Infections; Heart Neoplasms; Humans; Male; Tomography, X-Ray Computed
PubMed: 27484990
DOI: 10.12659/ajcr.899022 -
Medicine Jun 2019Individuals infected with human immunodeficiency virus (HIV) have higher morbidity and mortality due to cancer, which is the third most common cause of death in this... (Observational Study)
Observational Study
Individuals infected with human immunodeficiency virus (HIV) have higher morbidity and mortality due to cancer, which is the third most common cause of death in this group, despite the high effectiveness of antiretroviral therapy (ART). We describe the clinical and laboratory characteristics, initial staging and outcome of HIV-related lymphoma.We included 18 patients in the study, of whom 61.1% were male, mean age 41 years. Nine of the 18 patients (50%) had a diagnosis of HIV infection concurrent with the diagnosis of lymphoma.The most common histological types were diffuse non-Hodgkin B-cell lymphoma, 8 patients (44.4%); and Burkitt lymphoma, 5 (27.8%) cases. The Cotswold revision of the Ann Arbor staging classification in 14 patients (77.7%) was between III and IV. B Symptoms were present in 11 patients (61.1%), bulky mass was observed in 11 cases (61.1%) and had extra-nodal involvement in 8 patients (44.4%).Of the 18 cases analyzed, 8 followed on to second-line treatment, wherein the CODOX-M/IVAC scheme (cyclophosphamide, adriamycin, vincristine, methotrexate/ifosfamide, etoposide, and cytosine arabinoside) was used in 3 of the cases. The second most common scheme was etoposide, doxorubicin, vincristine and cyclophosphamide (EPOCH), used in 2 cases (25%), while in single cases (12.5% each) cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP), ifosfamide, etoposide, and carboplatin (ICE) and dexamethasone, cisplatin, and cytarabine (DHAP) were used.In this series, we observed very high mortality, equivalent to 44.4%, and a complete response in only 11.1%, much lower than that observed by other authors.We found that patients diagnosed with lymphoma associated with HIV had an advanced early clinical staging, and evolved with low response rates to chemotherapy.
Topics: Adult; Antineoplastic Agents; Burkitt Lymphoma; Female; Humans; Lymphoma, AIDS-Related; Lymphoma, Non-Hodgkin; Male; Neoplasm Staging; Retrospective Studies
PubMed: 31261533
DOI: 10.1097/MD.0000000000016129