scholarly journals Casitas B-cell lymphoma mutation in childhood T-cell acute lymphoblastic leukemia

2012 ◽  
Vol 36 (8) ◽  
pp. 1009-1015 ◽  
Author(s):  
Yuka Saito ◽  
Yoko Aoki ◽  
Hideki Muramatsu ◽  
Hideki Makishima ◽  
Jaroslaw P. Maciejewski ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Lymphoblastic Leukemia ◽  
B Cell Lymphoma ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals Optimizing the Clinical Impact of CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia: Looking Back While Moving Forward

2021 ◽  
Vol 12 ◽  
Author(s):  
Pouya Safarzadeh Kozani ◽  
Pooria Safarzadeh Kozani ◽  
Fatemeh Rahbarizadeh
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Lymphoblastic Leukemia ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Alternative Treatment Option ◽  
Car T ◽  
Cell Acute Lymphoblastic Leukemia

Chimeric antigen receptor T-cell (CAR-T) therapy has been successful in creating extraordinary clinical outcomes in the treatment of hematologic malignancies including relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). With several FDA approvals, CAR-T therapy is recognized as an alternative treatment option for particular patients with certain conditions of B-ALL, diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, or multiple myeloma. However, CAR-T therapy for B-ALL can be surrounded by challenges such as various adverse events including the life-threatening cytokine release syndrome (CRS) and neurotoxicity, B-cell aplasia-associated hypogammaglobulinemia and agammaglobulinemia, and the alloreactivity of allogeneic CAR-Ts. Furthermore, recent advances such as improvements in media design, the reduction of ex vivo culturing duration, and other phenotype-determining factors can still create room for a more effective CAR-T therapy in R/R B-ALL. Herein, we review preclinical and clinical strategies with a focus on novel studies aiming to address the mentioned hurdles and stepping further towards a milestone in CAR-T therapy of B-ALL.

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.

Concurrent Subcutaneous Panniculitis-like T-Cell Lymphoma and B-Cell Acute Lymphoblastic Leukemia in 2 Pediatric Patients

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Geoffrey A. Smith ◽  
Anya L. Levinson ◽  
Robert T. Galvin ◽  
Leah E. Lalor ◽  
Timothy McCalmont ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
Pediatric Patients ◽  
Cell Lymphoma ◽  
Lymphoblastic Leukemia ◽  
T Cell Lymphoma ◽  
Cell Acute Lymphoblastic Leukemia

CD200: a New Target for Immunotherapy in Hematologic Malignancies.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1598-1598 ◽  
Author(s):  
Lorenzo Brunetti ◽  
Giovanna Abate ◽  
Marisa Gorrese ◽  
Maddalena Raia ◽  
Caterina Pascariello ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
Fluorescence Intensity ◽  
Mean Fluorescence Intensity ◽  
Cytokine Production ◽  
Cell Lymphoma ◽  
Lymphoblastic Leukemia ◽  
Cytotoxic Response ◽  
Cell Acute Lymphoblastic Leukemia

Abstract CD200 is a transmembrane glycoprotein expressed on several tissues in rats and humans. It plays an immunoregulatory function by switching cytokine production from a TH1 to TH2 pattern, thus reducing cytotoxic response while indirectly enabling tumor escape and growth. Interestingly, CD200 is also a target for a novel humanized monoclonal antibody (Anti-CD200 MoAb, Alexion Pharmaceuticals, Cheshire, CT, USA). Anti-CD200 inhibits CD200 binding to its receptor, so modifying cytokine production and improving T-cell mediated cytotoxic response. Expression of CD200 has been already described in chronic lymphocytic leukemia/small lymphocyte lymphoma (CLL/SLL), multiple myeloma (MM) and acute myeloid leukemia (AML). Moreover, CD200 expression is considered an unfavorable prognostic factor in MM and AML. The goal of this work was to study, using flow cytometry, CD200 expression on a large number of onco-hematological samples, with the aim to exactly describe conditions in which anti-CD200 MoAb could be a therapeutic option. Analysis was conduced using a six-color FACSCanto II cytometer (Becton Dickinson, BD, San Jose, CA, USA) equipped with the FACSDiva software (BD). CD200 expression was evaluated by using CD200-PE-conjugated antibody (BD/Pharmingen). During the last year we analyzed CD200 expression in 184 samples: 131 bone marrow aspirates (BM), 33 peripheral blood specimens (PB) and 20 fine needle aspiration cytology samples (FNAC). One hundred and four were lymphoproliferative disorders, 12 MM, 16 myelodysplastic syndromes (MDS) and 52 acute leukemias. CD200 positivity was assigned to every single case when CD200 mean fluorescence intensity (MFI) was higher then 256 arbitrary units, a channel close to the cut-off point between positive and negative cells, in our experience. All results concerning our analysis are showed in the table. Three classes of hematologic neoplasms displayed a constant positivity for CD200 with a high level of MFI: CLL/SLL, hairy cell leukemia (HCL) and B-cell acute lymphoblastic leukemia (B-ALL). Lymphoplasmacytic lymphoma (LPL) was positive in 100% of cases but with lower MFI as compared to CLL/SLL, HCL and B-ALL (p<0.001). MM/MGUS plasma cells showed CD200 positivity in 80% of cases. CD200 was also expressed in cases of marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), T-non Hodgkin lymphoma (T-NHL), AML, acute hybrid leukemia (AHL) and T-cell acute lymphoblastic leukemia (T-ALL). Follicular Lymphoma (FL) samples were always negative but one, which expressed the antigen with a very low MFI. In AML we also compared CD200 expression with that of a large number of antigens (n=40), finding a statistically significant inverse correlation with myeloperoxidase (MPO-7) (Spearman’s r= −0.54; p<0.001). Difference in MFI between AML and B-ALL was statistically significant (p=0.003). No case of acute promyelocytic leukemia (APL) was positive for CD200. In conclusion, CD200 is candidate as a new specific target for immunotherapy with anti-CD200 in all cases of CLL/SLL, B-ALL and HCL as well as in selected cases of MZL, DLBCL, MCL, LPL, MM, T-NHL, AML, AHL and T-ALL. Disease N Positive N (%) PPC (mean) PPC (25°–75° percentile) MFI (median) MFI (25°–75° percentile) PPC= percent positive cells MFI= mean fluorescence intensity AML 38 24 (63) 32.9 8–57 294 138–695 APL 2 0 (0) 2.5 - 33 - MDS 16 12 (75) 34.2 15–57 516 263–1122 AHL 5 4 (80) 60.2 27–87 420 238–1194 ALL 7 6 (86) 63.6 57–85 1099 288–1444 CLL/SLL 47 47 (100) 98.4 98–99 3410 2300–4733 LPL 5 5 (100) 54.8 41–65 492 377–715 MCL 11 8 (72) 43 3–71 665 20–835 FL 10 1 (10) 4.7 2–8 46 30–83 DLCL 12 6 (50) 29.8 3–71 204 66–754 MZL 9 6 (66) 39.2 4–85 352 47–864 HCL 6 6 (100) 87 72–98 3841 1271–7527 MM 12 11 (92) 52.7 18–79 2956 979–5937 T-NHL 4 2 (50) 23.5 2–62 287 23–2477

scholarly journals Preclinical development of CD37CAR T-cell therapy for treatment of B-cell lymphoma

2019 ◽  
Vol 3 (8) ◽  
pp. 1230-1243 ◽  
Author(s):  
Hakan Köksal ◽  
Pierre Dillard ◽  
Sarah E. Josefsson ◽  
Solrun Melkorka Maggadottir ◽  
Sylvie Pollmann ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Cell Lymphoma ◽  
Lymphoblastic Leukemia ◽  
Xenograft Model ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Cell Acute Lymphoblastic Leukemia

Abstract T cells modified to express chimeric antigen receptor (CAR) targeting CD19 (CD19CAR) have produced remarkable clinical responses in patients with relapsed/refractory B-cell acute lymphoblastic leukemia. CD19CAR T-cell therapy has also demonstrated prominent effects in B-cell non-Hodgkin lymphoma (B-NHL) patients. However, a subset of patients who relapse after CD19CAR T-cell therapy have outgrowth of CD19− tumor cells. Hence, development of alternative CARs targeting other B-cell markers represents an unmet medical need for B-cell acute lymphoblastic leukemia and B-NHL. Here, we confirmed previous data by showing that, overall, B-NHL has high expression of CD37. A second-generation CD37CAR was designed, and its efficacy in T cells was compared with that of CD19CAR. In vitro assessment of cytotoxicity and T-cell function upon coculture of the CAR T cells with different target B-cell lymphoma cell lines demonstrated comparable efficacy between the 2 CARs. In an aggressive B-cell lymphoma xenograft model, CD37CAR T cells were as potent as CD19CAR T cells in controlling tumor growth. In a second xenograft model, using U2932 lymphoma cells containing a CD19− subpopulation, CD37CAR T cells efficiently controlled tumor growth and prolonged survival, whereas CD19CAR T cells had limited effect. We further show that, unlike CD19CAR, CD37CAR was not sensitive to antigen masking. Finally, CD37CAR reactivity was restricted to B-lineage cells. Collectively, our results demonstrated that CD37CAR T cells also can effectively eradicate B-cell lymphoma tumors when CD19 antigen expression is lost and support further clinical testing for patients with relapsed/refractory B-NHL.

Neuropsychiatric disorders in hospitalized patients undergoing chimeric antigen receptor T-cell therapy for aggressive lymphomas and acute lymphoblastic leukemia: A national study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 12118-12118
Author(s):  
Josephine Emole ◽  
Odunayo Susan Lawal ◽  
Oleksandra Lupak ◽  
Itoro Udo
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Chimeric Antigen Receptor ◽  
Cell Lymphoma ◽  
Lymphoblastic Leukemia ◽  
B Cell Lymphoma ◽  
Female Gender ◽  
T Cell Therapy

12118 Background: Chimeric antigen receptor T cell therapy (CART) has shown efficacy in acute lymphoblastic leukemia (ALL), diffuse large B cell lymphoma (DLBCL), and primary mediastinal B cell lymphoma (PMBCL). While neurological toxicities of CART are known, neuropsychiatric disorders (NPD) in patients undergoing CART has not been well described. Our study assessed the prevalence of NPD in hospitalized patients (pts) undergoing CART, and explored association of NPD with clinical variables. Methods: Using the National Inpatient Sample database, we conducted a retrospective study of pts with ALL, DLBCL and PMLCL aged ≥ 18 years who underwent CART in 2018. Hospitalizations were selected using International Classification of Disease, Tenth Revision (ICD-10) codes. NPD of interest included anxiety, depression, adjustment disorder, insomnia, psychosis, dementia, bipolar disorder. Delirium was not included in the inventory of NPD since delirium is a neurotoxicity of CART, and inclusion of delirium as NPD would confound results. Patient, disease, and CART complications were extracted from hospitalization records. Regression analyses were used to assess association of NPD with clinical variables. Results: 945 CART procedures met the inclusion criteria (56 % males and 60% Caucasians). Majority of CART (88%) were performed for DLBCL and PMBCL. NPD was diagnosed in 31 % of pts. Anxiety was the most common NPD, followed by insomnia and depression. ALL pts were more likely to have NPD compared to pts with lymphoma (52% versus 28%, p<0.05). More females had NPD compared to males (40% versus 25%, p<0.05). Univariable analysis showed association of NPD with female gender [Odds ratio (OR)=2.03, 95% CI = 1.05-3.93] and ALL (OR=2.76, 95% CI = 1.03-7.43). In a multivariable model, NPD was associated with ALL (OR =3.57, 95% CI= 1.01-12.55), while the association of NPD with female gender was less certain (OR =1.41, 95% CI=0.73 - 2.74). There was no association between NPD and mortality, neurotoxicity, systemic inflammatory response syndrome or hemophagocytic lymphohistiocytosis. Conclusions: One in every 3 pts who underwent in-hospital CART for ALL or aggressive B cell lymphoma in 2018 had comorbid NPD. Females and ALL pts were at higher risk for NPD. As CART pts transition into longer follow up and survivorship, ours and similar results should inform the planning and allocation of psychosocial services.

scholarly journals Tisagenlecleucel Immunogenicity in Relapsed/Refractory Acute Lymphoblastic Leukemia and Diffuse Large B-Cell Lymphoma

2021 ◽  
Author(s):  
Karen Thudium Mueller ◽  
Stephan A. Grupp ◽  
Shannon L. Maude ◽  
John E Levine ◽  
Michael A Pulsipher ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Lymphoblastic Leukemia ◽  
T Cell Responses ◽  
B Cell Lymphoma ◽  
Cell Responses ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Tisagenlecleucel is indicated for pediatric and young adult patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) and adult patients with r/r diffuse large B-cell lymphoma (DLBCL). The tisagenlecleucel chimeric antigen receptor (CAR) contains a murine single-chain variable fragment domain; hence, we examined the effects of humoral and cellular immune responses to tisagenlecleucel on clinical outcomes using 2 validated assays. Data were pooled from ELIANA (NCT02435849) and ENSIGN (NCT02228096) trials in r/r B-ALL (N=143) and the JULIET trial (NCT02445248) in r/r DLBCL (N=115). Humoral responses were determined by flow cytometric measurement of anti-murine CAR19 (mCAR19) antibodies in serum. Cellular responses were determined using T-cell production of interferon gamma in response to 2 different pools of mCAR19 peptides. Pretreatment anti-mCAR19 antibodies were detected in 81% of patients with r/r B-ALL and 94% of patients with r/r DLBCL. Posttreatment anti-mCAR19 antibodies were higher than patient-specific baseline in 42% of r/r B-ALL and 9% of r/r DLBCL patients. Pretreatment and posttreatment anti-mCAR19 antibodies did not affect tisagenlecleucel cellular kinetics including Cmax and persistence (r2&lt;0.05), clinical response (day 28 response, duration of response, event-free survival), or safety. T-cell responses were consistent over time, with net responses &lt;1% at baseline and posttreatment time points in the majority of patients with no effect on transgene expansion and persistence or outcomes. Presence of baseline and/or posttreatment anti-mCAR19 antibodies or T-cell responses did not alter the activity of tisagenlecleucel in patients with r/r B-ALL or r/r DLBCL.

Sign in / Sign up

Export Citation Format

Share Document