scholarly journals Novel Therapies Potentially Available for Pediatric B-Cell Non-Hodgkin Lymphoma

2020 ◽  
Vol 18 (8) ◽  
pp. 1125-1134
Author(s):  
Paul D. Harker-Murray ◽  
Lauren Pommert ◽  
Matthew J. Barth
Keyword(s):  
T Cell ◽  
B Cell ◽  
Targeted Therapies ◽  
Burkitt Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Acute Leukemias ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Antibody Drug

Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), and primary mediastinal B-cell lymphoma are the most common aggressive pediatric mature B-cell non-Hodgkin lymphomas (B-NHLs). Despite excellent survival with current chemotherapy regimens, therapy for Burkitt lymphoma and DLBCL has a high incidence of short- and long-term toxicities. Patients who experience relapse generally have a very poor prognosis. Therefore, novel approaches using targeted therapies to reduce toxicities and improve outcomes in the relapse setting are needed. The addition of rituximab, a monoclonal antibody against CD20, to upfront therapy has improved survival outcomes for high-risk patients and may allow decreased total chemotherapy in those with low-risk disease. Antibody–drug conjugates have been combined with chemotherapy in relapsed/refractory (R/R) NHL, and multiple antibody–drug conjugates are in development. Additionally, bispecific T-cell–engaging antibody constructs and autologous CAR T-cells have been successful in the treatment of R/R acute leukemias and are now being applied to R/R B-NHL with some successes. PD-L1 and PD-L2 on tumor cells can be targeted with checkpoint inhibitors, which restore T-cell–mediated immunity and antitumor responses and can be added to conventional chemotherapy and immune-directed therapies to augment responses. Lastly, trials of small molecule inhibitors targeting cell signaling pathways in NHL subtypes are underway. This article reviews many of the targeted therapies under development that could be considered for future trials in R/R pediatric mature B-NHL.

Development of novel anti-CD19 antibody-drug conjugates for B-cell lymphoma treatment

2018 ◽  
Vol 62 ◽  
pp. 299-308 ◽  
Author(s):  
Zhuanglin Li ◽  
Mingxue Wang ◽  
Xuejing Yao ◽  
Huanzhao Li ◽  
Shenjun Li ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Lymphoma Treatment ◽  
Antibody Drug

scholarly journals Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes

Leukemia ◽  
2015 ◽  
Vol 29 (7) ◽  
pp. 1578-1586 ◽  
Author(s):  
M Pfeifer ◽  
B Zheng ◽  
T Erdmann ◽  
H Koeppen ◽  
R McCord ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Antibody Drug

scholarly journals Mikosis Fungoides Folikulotropik Disertai Ko-Ekspresi Pan B-Cell Markers Dengan Manifestasi Klinis Berupa Facies Leonina

2019 ◽  
Vol 45 (4) ◽  
Author(s):  
Eva Krishna Sutedja ◽  
Dia Febrina ◽  
Erfina Rohana ◽  
Nina Roslina ◽  
Jono Hadi Agusni ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Targeted Therapies ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Ki 67 ◽  
Cell Markers ◽  
Cutaneous B Cell Lymphoma

Mikosis fungoides folikulotropik (MFF) merupakan varian dari mikosis fungoides (MF)  dengan perjalanan klinis yang lebih agresif dan prognosis lebih buruk dibandingkan MF klasik. Facies leonina (FL) merupakan manifestasi klinis yang sangat jarang ditemukan pada MFF. CD20 dan CD79a merupakan pan B-cell markers yang sangat jarang ditemukan pada kasus cutaneous T-cell lymphoma (CTCL), termasuk di dalamnya MFF. Dilaporkan satu kasus MFF pada seorang laki-laki berusia 51 tahun dengan manifestasi klinis FL dan madarosis disertai papula folikel menyerupai lesi keratosis pilaris pada dada, punggung, kedua lengan, dan paha. Diagnosis MFF pada pasien ini ditegakkan berdasarkan pemeriksaan histopatologis sediaan biopsi kulit wajah yang menunjukkan gambaran folikulotropisme. Pada pemeriksaan imunohistokimia ditemukan fenotipe CD3 yang dominan, CD4, CD8, CD30, dan Ki-67 lebih dari 40% sel tumor. Penanda sel-B juga ditemukan positif pada beberapa sel yaitu CD20, CD79a, dan bcl-2. Setelah dua bulan diterapi dengan kortikosteroid topikal tidak didapatkan pendataran pada lesi FL. Pasien direncanakan pemberian regimen kemoterapi siklofosfamid, doxorubicin, vincristine, dan prednison. Mikosis fungoides folikulotropik  dapat bermanifestasi klinis FL. Fenotipe CD20 dan CD79a pada kasus ini bukan merupakan cutaneous B-cell lymphoma karena fenotipe CD3, CD4, dan CD8 yang ditemukan lebih dominan. Folikulotropisme menyebabkan MFF kurang responsif terhadap skin-targeted therapies sehingga membutuhkan terapi yang lebih agresif. Kata kunci: facies leonina, mikosis fungoides folikulotropik, pan-B cell markers

scholarly journals Promising Immunotherapeutic Modalities for B-Cell Lymphoproliferative Disorders

2021 ◽  
Vol 22 (21) ◽  
pp. 11470
Author(s):  
Jana Mihályová ◽  
Katarína Hradská ◽  
Tomáš Jelínek ◽  
Benjamin Motais ◽  
Piotr Celichowski ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
T Cell Therapy ◽  
Antibody Drug Conjugates ◽  
Car T Cell ◽  
Drug Conjugates ◽  
Car T Cell Therapy ◽  
Car T ◽  
Antibody Drug

Over the last few years, treatment principles have been changed towards more targeted therapy for many B-cell lymphoma subtypes and in chronic lymphocytic leukemia (CLL). Immunotherapeutic modalities, namely monoclonal antibodies (mAbs), bispecific antibodies (bsAbs), antibody-drug conjugates (ADCs), and chimeric antigen receptor T (CAR-T) cell therapy, commonly use B-cell-associated antigens (CD19, CD20, CD22, and CD79b) as one of their targets. T-cell engagers (TCEs), a subclass of bsAbs, work on a similar mechanism as CAR-T cell therapy without the need of previous T-cell manipulation. Currently, several anti-CD20xCD3 TCEs have demonstrated promising efficacy across different lymphoma subtypes with slightly better outcomes in the indolent subset. Anti-CD19xCD3 TCEs are being developed as well but only blinatumomab has been evaluated in clinical trials yet. The results are not so impressive as those with anti-CD19 CAR-T cell therapy. Antibody-drug conjugates targeting different B-cell antigens (CD30, CD79b, CD19) seem to be effective in combination with mAbs, standard chemoimmunotherapy, or immune checkpoint inhibitors. Further investigation will show whether immunotherapy alone or in combinatory regimens has potential to replace chemotherapeutic agents from the first line treatment.

scholarly journals T cell/histiocyte rich B-cell lymphoma: A difficult diagnosis to make

2020 ◽  
Vol 2 ◽  
pp. 100041
Author(s):  
Olutayo A. Sogunro ◽  
Rachael Steinhauer ◽  
Eugene Lewis
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Difficult Diagnosis

scholarly journals Tumor staging in a Beagle dog with concomitant large B-cell lymphoma and T-cell acute lymphoblastic leukemia

2021 ◽  
pp. 104063872110110
Author(s):  
Alessandro Ferrari ◽  
Marzia Cozzi ◽  
Luca Aresu ◽  
Valeria Martini
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Tumor Staging ◽  
Lymphoblastic Leukemia ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Cell Acute Lymphoblastic Leukemia

An 8-y-old spayed female Beagle dog was presented with peripheral lymphadenomegaly. Lymph node cytology and flow cytometry led to the diagnosis of large B-cell lymphoma (LBCL). We detected minimal percentages of LBCL cells in peripheral blood and bone marrow samples. However, a monomorphic population of neoplastic cells different from those found in the lymph node was found in the bone marrow. T-cell acute lymphoblastic leukemia was suspected based on flow cytometric immunophenotyping. PCR for antigen receptor rearrangement (PARR) revealed clonal rearrangement of both B-cell and T-cell receptors, and the presence of both neoplastic clones in the lymph node, peripheral blood, and bone marrow. The dog was treated with multi-agent chemotherapy but died 46 d following diagnosis. Tumor staging and patient classification are needed to accurately establish a prognosis and select the most appropriate therapeutic protocol.

scholarly journals Use of immune repertoire sequencing to resolve discordant microscopic and immunochemical findings in a case of T cell-rich large B cell lymphoma in a young dog

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Gary Kwok Cheong Lee ◽  
Dorothee Bienzle ◽  
Stefan Matthias Keller ◽  
Mei-Hua Hwang ◽  
Nikos Darzentas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Immune Repertoire ◽  
Large B Cell Lymphoma ◽  
Repertoire Sequencing ◽  
Reactive Lymphocytes ◽  
Large B Cell

Abstract Background Lymphocytic neoplasms with frequent reactive lymphocytes are uncommonly reported in dogs, and can pose a diagnostic challenge. Different diagnostic modalities such as cytology, flow cytometry, histopathology, immunohistochemistry, and clonality testing, are sometimes required for a diagnosis. This report illustrates the value of using a multi-modal diagnostic approach to decipher a complex lymphocytic tumor, and introduces immune repertoire sequencing as a diagnostic adjunct. Case presentation A 10-month-old Great Dane was referred for marked ascites. Cytologic analysis of abdominal fluid and hepatic aspirates revealed a mixed lymphocyte population including numerous large lymphocytes, yielding a diagnosis of lymphoma. Flow cytometrically, abdominal fluid lymphocytes were highly positive for CD4, CD5, CD18, CD45, and MHC II, consistent with T cell lymphoma. Due to a rapidly deteriorating clinical condition, the dog was euthanized. Post mortem histologic evaluation showed effacement of the liver by aggregates of B cells surrounded by T cells, suggestive of hepatic T cell-rich large B cell lymphoma. Immune repertoire sequencing confirmed the presence of clonal B cells in the liver but not the abdominal fluid, whereas reactive T cells with shared, polyclonal immune repertoires were found in both locations. Conclusions T cell-rich large B cell lymphoma is a rare neoplasm in dogs that may be challenging to diagnose and classify due to mixed lymphocyte populations. In this case, the results of histopathology, immunohistochemistry and immune repertoire sequencing were most consistent with a hepatic B cell neoplasm and reactive T cells exfoliating into the abdominal fluid. Immune repertoire sequencing was helpful in delineating neoplastic from reactive lymphocytes and characterizing repertoire overlap in both compartments. The potential pitfalls of equating atypical cytomorphology and monotypic marker expression in neoplasia are highlighted.

scholarly journals T-Cell/Histiocyte-Rich Large B-Cell Lymphoma Presenting as a Primary Central Nervous System Lymphoma

Rare Tumors ◽  
2015 ◽  
Vol 7 (4) ◽  
pp. 160-162 ◽  
Author(s):  
Pooja Advani ◽  
Jason Starr ◽  
Abhisek Swaika ◽  
Liuyan Jiang ◽  
Yushi Qiu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell
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