Comparison of peripheral T-cell lymphomas and diffuse large B-cell lymphoma

17566 Background: The clinicopathologic characteristics of malignant lymphomas vary according to geography. The aim of this study was to determine the relative frequency of cutaneous lymphomas and to examine the clinical relevance of the new WHO/EORTC classification in Peruvian cases of cutaneous lymphoma. Methods: We conducted a clinicopathologic retrospective study of a collection of 68 primary cutaneous lymphomas, diagnosed from 1997 to 2004 in a National General Hospital. The clinical records, haematoxylin & eosin-stained slides and immunohistochemical stains from 67 patients with malignant lymphomas of the skin were reviewed. HTLV-1 serology was made using ELISA and Western Blot methods. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method. Results: Mean age at presentation was 62 years and the female/male ratio 1.5:1. T cell lymphomas were 88.6% and 11.4% were B-cell lymphomas. The most frequent cutaneous lymphoma was mycosis fungoides (MF) 30/67 (44.7%), Adult T-cell leukemia/lymphoma (ATLL) 13/67 (19.4%), unspecified peripheral T-cell lymphoma 4/67 (6%), lymphomatoid papulosis 2/67 (3%), leg-type diffuse large B-cell lymphoma 2/67 (3%), diffuse large B-cell lymphoma 2/67 (3%), subcutaneous panniculitis-like T-cell lymphoma 2/67 (3%), anaplastic large cell lymphoma 1/67 (1.4%), Sézary síndrome 1/67 (1.4%), nasal type extranodal NK/T-cell lymphoma 1/67 (1.4%), marginal zone B-cell lymphoma 1/67 (1.4%), follicle center lymphoma 1/67 (1.4%), intravascular lymphoma 1/67 (1.4%) and unclassifiable 5/67 ( 7.4%). Clinical stages of MF were: 60% stage I; 30% stage II; 3% stage III and 7% stage IV. 5-year survival was 77%. In ATLL group, 3 had smouldering type and 10 had cutaneous type. 5-year survival was 18%. Conclusions: In this retrospective analysis, cutaneous T cell lymphomas were prevalent; both MF and ATLL had the most frequency among primary cutaneous lymphomas in our hospital. ATLL had a poor 5-year survival. No significant financial relationships to disclose.

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Comparison of clinical outcome after autologous stem cell transplantation between patients with peripheral T-cell lymphomas and diffuse large B-cell lymphoma

Bone Marrow Transplantation ◽

10.1038/bmt.2009.29 ◽

2009 ◽

Vol 44 (5) ◽

pp. 287-293 ◽

Cited By ~ 4

Author(s):

B S Sohn ◽

I Park ◽

E K Kim ◽

D H Yoon ◽

S S Lee ◽

...

Keyword(s):

Stem Cell ◽

Clinical Outcome ◽

Stem Cell Transplantation ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

T Cell Lymphomas ◽

Large B Cell ◽

Peripheral T Cell Lymphomas

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Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study

Journal of Clinical Oncology ◽

10.1200/jco.2015.65.9789 ◽

2016 ◽

Vol 34 (23) ◽

pp. 2698-2704 ◽

Cited By ~ 493

Author(s):

Alexander M. Lesokhin ◽

Stephen M. Ansell ◽

Philippe Armand ◽

Emma C. Scott ◽

Ahmad Halwani ◽

...

Keyword(s):

Multiple Myeloma ◽

T Cell ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

T Cell Lymphoma ◽

Peripheral T Cell Lymphoma ◽

Large B Cell Lymphoma ◽

T Cell Lymphomas ◽

Large B Cell

Purpose Cancer cells can exploit the programmed death-1 (PD-1) immune checkpoint pathway to avoid immune surveillance by modulating T-lymphocyte activity. In part, this may occur through overexpression of PD-1 and PD-1 pathway ligands (PD-L1 and PD-L2) in the tumor microenvironment. PD-1 blockade has produced significant antitumor activity in solid tumors, and similar evidence has emerged in hematologic malignancies. Methods In this phase I, open-label, dose-escalation, cohort-expansion study, patients with relapsed or refractory B-cell lymphoma, T-cell lymphoma, and multiple myeloma received the anti–PD-1 monoclonal antibody nivolumab at doses of 1 or 3 mg/kg every 2 weeks. This study aimed to evaluate the safety and efficacy of nivolumab and to assess PD-L1/PD-L2 locus integrity and protein expression. Results Eighty-one patients were treated (follicular lymphoma, n = 10; diffuse large B-cell lymphoma, n = 11; other B-cell lymphomas, n = 10; mycosis fungoides, n = 13; peripheral T-cell lymphoma, n = 5; other T-cell lymphomas, n = 5; multiple myeloma, n = 27). Patients had received a median of three (range, one to 12) prior systemic treatments. Drug-related adverse events occurred in 51 (63%) patients, and most were grade 1 or 2. Objective response rates were 40%, 36%, 15%, and 40% among patients with follicular lymphoma, diffuse large B-cell lymphoma, mycosis fungoides, and peripheral T-cell lymphoma, respectively. Median time of follow-up observation was 66.6 weeks (range, 1.6 to 132.0+ weeks). Durations of response in individual patients ranged from 6.0 to 81.6+ weeks. Conclusion Nivolumab was well tolerated and exhibited antitumor activity in extensively pretreated patients with relapsed or refractory B- and T-cell lymphomas. Additional studies of nivolumab in these diseases are ongoing.

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Asparagine Synthetase Expression and L-Asparaginase Sensitivity in Aggressive Lymphomas

Blood ◽

10.1182/blood.v124.21.5494.5494 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5494-5494 ◽

Cited By ~ 1

Author(s):

Willy Berlier ◽

Karine Aguera ◽

Anne-Marie Chevrier ◽

Fanny Gallix ◽

Alexandra Traverse-Glehen ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Cell Lines ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

T Cell Lymphoma ◽

Large B Cell Lymphoma ◽

T Cell Lymphomas ◽

Large B Cell

Abstract L-asparaginase (L-ASPA) displays a strong clinical benefit in the treatment of acute lymphoblastic leukemia (ALL), where it is included in most of current chemotherapy regimen. L-ASPA depletes plasmatic asparagine (ASN), an amino acid essential for the proliferation of leukemic cells. Since these cells are deficient in asparagine synthetase (ASNS), they rely on external (plasmatic) source of ASN and can be starved to death by L-ASP treatment. Several studies evidenced the potential of ASN depletion to treat lymphomas. Indeed, many animal and human lymphoma cell lines have been shown to be sensitive to L-ASPA in vitro. In veterinary medicine, L-ASPA is routinely administered to treat effectively both feline and canine lymphomas (Wypig et al., 2013). L-ASPA regained attention in the treatment of human lymphomas since its adjunction in current chemotherapy regimens significantly improved the outcome of patients with NK/T cell lymphoma (Zou et al., 2014). Some studies also evidenced its benefit in combined chemo or monotherapy for the treatment of B-cell and T-cell lymphomas (Sun et al., 2006; Takahashi et al., 2010). In this study, we assessed the in vitro sensitivity to L-ASPA of 6 lymphoma cell lines and we analyzed ASNS expression in biopsies from 166 cases of lymphomas (130 B-cell lymphomas and 17 T-cell lymphomas). Sensitivity to L-ASPA (expressed as an IC50) was assessed in vitro by measuring the cell viability in the presence of various concentrations of E.coliL-ASPA. ASNS expression in biopsies (TMA, USBiomax, Rockville, MD) was assessed with a validated immunohistochemistry (IHC) method attributing a score to each tumor based on ASNS labeling intensity from 0 (no expression) to 3 (strong expression). Tumors expressing no/low ASNS (scores 0 and 1) were considered potentially sensitive to asparagine depletion. As shown in the following table, all cell lines were proved to be sensitive to L-ASPA. Their in vitrosensitivity exceeded cell lines MOLT-4 (ALL) and HL-60 (AML). Table 1Cell lineSensitivity to L-ASPA (IC50 in IU/mL)HuT-78 (Peripheral T-cell lymphoma,PTCL)0.11 ± 0.02Toledo (Diffuse large B-cell lymphoma, DLBCL)0.19 ± 0.03SU-DHL-8(Diffuse large B-cell lymphoma, DLBCL)0.10 ± 0.04SU-DHL-10(Diffuse large B-cell lymphoma, DLBCL)0.10 ± 0.01REC-1 (Mantle cell lymphoma, MCL)0.15 ± 0.03KHYG-1 (NK/T-cell lymphoma)0.16 ± 0.06MOLT-4 (acute lymphoid leukemia, ALL)0.19 ± 0.07HL-60 (acute myeloid leukemia, AML)0.23 ± 0.02 As shown in the following table, ASNS expression was null/low in 85% in the entire population of patients with B-cell lymphomas. Considering DLBCL, 63% of patients displayed no ASNS expression at all. ASNS expression was also null/low in 88% of patients with T-cell lymphomas (n=17). Table 2ASNS expression (IHC score)Type of lymphoma(% of cases)DLBCL (n=110)Others BCL (n=20)PTCL (n=3)Others TCL (n=14)MCL(n=3)Hodgkin (n=16)Negative (0)62,770,00,057,133,343,8Low positive (1)21,825,066,635,766,656,3Positive (2)7,35,033,37,10,00,0Highly positive (3)8,20,00,00,00,00,0 Globally, these results suggest that L-ASPA is potentially effective for the treatment of several lymphomas. Indeed, B-cell as well as T-cell lymphoma cell lines are sensitive to L-ASP in vitroand the majority of lymphoma tissues express no/low ASNS. Based on our results on ASNS expression in lymphoma biopsies, L-ASPA therapy may be beneficial for up to 85% of patients with DLBCL. Up to 90% of patients with other B-cell lymphomas or T-cell lymphomas may be sensitive to L-ASPA treatment as well. However, L-ASPA has only been used scarcely in the treatment of lymphomas despite promising clinical responses. Its well known serious side-effects (hypersensitivity, coagulation disorders, pancreatitis, and liver failure) render its use hazardous, particularly in older or frail patients. Therefore, the development of a new formulation of L-ASPA with safer profile has to be considered in order to allow the clinical development of L-ASPA in the treatment of aggressive lymphomas. Disclosures Berlier: ERYTECH: Employment, Equity Ownership. Aguera:ERYTECH: Employment. Chevrier:ERYTECH: Employment. Gallix:ERYTECH: Employment. Godfrin:ERYTECH Pharma: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

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Negative Interim FDG-PET Scan Is Predictive of Superior Outcome in T Cell Lymphoma.

Blood ◽

10.1182/blood.v114.22.1956.1956 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1956-1956 ◽

Cited By ~ 1

Author(s):

Carla Casulo ◽

Andrew D. Zelenetz ◽

Craig H Moskowitz ◽

Steven M. Horwitz

Keyword(s):

T Cell ◽

B Cell ◽

Fdg Pet ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

T Cell Lymphoma ◽

Large B Cell Lymphoma ◽

T Cell Lymphomas ◽

Pet Scans ◽

Large B Cell

Abstract Abstract 1956 Poster Board I-979 Background: Fluoro-deoxy-glucose positron emission tomography (FDG-PET) is a required staging study for diffuse large B-cell lymphoma and Hodgkin lymphoma. Numerous studies have demonstrated that FDG-PET performed after one to four cycles of multiagent chemotherapy (interim restaging) is predictive of outcome, with relapse rates much higher in patients with positive FDG-PET scans at interim restaging. The prognostic role of FDG-PET in T-cell lymphoma however is unclear and has yet to be well defined. Small retrospective studies have demonstrated FDG-PET avidity of T-cell lymphoma. Our experience confirms that the great majority of patients with mature T or NK lymphomas have FDG-PET avid disease. We hypothesized that the interim FDG-PET (int FDG-PET) may have prognostic importance in patients with T-cell lymphomas as they do in diffuse large B-cell lymphoma and Hodgkin lymphoma. Methods: We reviewed our T-cell lymphoma database to identify patients with mature T or NK lymphomas who had FDG-PET scans as part of complete staging at initial diagnosis as well as repeat PET imaging as part of restaging. Inclusion criteria required FDG-PET avid disease at baseline and treatment administered with curative intent. Results: We reviewed fifty four patients who met the above criteria. Histologies were as follows: peripheral T-cell lymphoma NOS (N=18), angioimmunoblastic T-cell lymphoma (N=5), anaplastic large cell lymphoma ALK-1- (N=15), anaplastic large cell lymphoma ALK-1+ (N=3), and other subtypes (N=13). Patients received a variety of initial chemotherapy regimens including CHOP (N=18), EPOCH (N=6), CHOP/ICE (N=20) or other treatments provided with curative intent. Twenty two patients were consolidated with high dose therapy and either autologous (N=18), or allogeneic (N=4) SCT. Fifty nine percent were PET negative at interim restaging (32/54), 7.4% were positive (4/54), 22 % were not available (12/54), and 11% had equivocal scans (6/54). Median follow up was 17 months. Median PFS for the entire group was 15 months. Median OS for the entire group was 40 months. The median OS of patients with negative int FDG-PET has not been reached, compared to the OS of patients with positive int FDG-PET of 10.2 months (p<.001). Patients with equivocal int FDG-PET had a median OS of 62 months, which was statistically superior to patients with positive int FDG-PET (p=.02). There was no significant difference in median OS in patients with negative versus equivocal int FDG-PET. Similar to what was observed in OS, the median PFS of patients with negative int FDG-PET has not yet been reached, compared to the PFS of patients with a positive int FDG-PET of 4.8 months (p=<.001). Patients with equivocal int FDG-PET had a statistically improved PFS of 16 months when compared to those with a positive int FDG-PET (p<.01). Patients with equivocal int FDG-PET had similar outcomes to patients with a negative int FDG-PET, and superior to those with a positive int FDG-PET, whose results were very poor. Conclusions: In this dataset, interim PET scans are strongly predictive of outcome. Patients with negative int FDG-PET enjoyed significantly longer remissions and better overall survival. Patients with negative int FDG-PET were more likely to receive consolidative therapy, which may contribute to their superior outcomes. This may be a potentially confounding factor. Nonetheless, achievement of a negative int FDG-PET appears to be a reliable predictor of outcome in patients with T-cell lymphomas and may have similar prognostic importance in these patients as they do in diffuse large B-cell lymphoma and Hodgkin lymphoma. It is reasonable to consider int FDG-PET in the restaging of patients with T-cell lymphomas. Disclosures: Zelenetz: Millenium Advisory board: Membership on an entity's Board of Directors or advisory committees. Horwitz:Allos Therapeutics, Inc: Consultancy, Research Funding.

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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

BMC Veterinary Research ◽

10.1186/s12917-021-02783-3 ◽

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.

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