From empiric to mechanism-based therapy for peripheral T cell lymphoma

Intlekofer, Andrew M.; Younes, Anas

doi:10.1007/s12185-014-1521-2

Cited by 17 publications

(18 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some studies have recently described the efficacy of ALK inhibition in ALCL, both in murine models [40] and in preliminary clinical studies: in one trial 2 ALK+ ALCL patients reported complete remission of the disease within 1 month of treatment with Crizotinib, the response being sustained 5–6 months later [8]. A later clinical trial with 9 ALK+ ALCL patients treated with Crizotinib showed an objective response rate of 100%, a complete remission rate of 100%, a median duration of response of 10 months and 3-year progression-free survival of 63% with a plateau in the curve after 6 months [9]. In fact, Crizotinib has been approved by the FDA for the treatment of ALK+ non-small cell lung cancer [3].…”

Section: Discussionmentioning

confidence: 99%

“…Although different histological subtypes of PTCL have been identified, the treatment approach has been essentially based on the application of anthracycline-based combination chemotherapy, resulting in poor outcomes [9]. To date, only 3 agents have been recently approved by the FDA for the treatment of relapsed or refractory PTCL: pralatrexate, romidepsin and brentuximab vedotin [9], [10].…”

Section: Introductionmentioning

confidence: 99%

“…To date, only 3 agents have been recently approved by the FDA for the treatment of relapsed or refractory PTCL: pralatrexate, romidepsin and brentuximab vedotin [9], [10]. Nevertheless, the development of new, efficiently targeted therapies is of great importance to PTCL patients [9], [11], [12].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

PIM Kinases as Potential Therapeutic Targets in a Subset of Peripheral T Cell Lymphoma Cases

et al. 2014

View full text Add to dashboard Cite

Currently, there is no efficient therapy for patients with peripheral T cell lymphoma (PTCL). The Proviral Integration site of Moloney murine leukemia virus (PIM) kinases are important mediators of cell survival. We aimed to determine the therapeutic value of PIM kinases because they are overexpressed in PTCL patients, T cell lines and primary tumoral T cells. PIM kinases were inhibited genetically (using small interfering and short hairpin RNAs) and pharmacologically (mainly with the pan-PIM inhibitor (PIMi) ETP-39010) in a panel of 8 PTCL cell lines. Effects on cell viability, apoptosis, cell cycle, key proteins and gene expression were evaluated. Individual inhibition of each of the PIM genes did not affect PTCL cell survival, partially because of a compensatory mechanism among the three PIM genes. In contrast, pharmacological inhibition of all PIM kinases strongly induced apoptosis in all PTCL cell lines, without cell cycle arrest, in part through the induction of DNA damage. Therefore, pan-PIMi synergized with Cisplatin. Importantly, pharmacological inhibition of PIM reduced primary tumoral T cell viability without affecting normal T cells ex vivo. Since anaplastic large cell lymphoma (ALK+ ALCL) cell lines were the most sensitive to the pan-PIMi, we tested the simultaneous inhibition of ALK and PIM kinases and found a strong synergistic effect in ALK+ ALCL cell lines. Our findings suggest that PIM kinase inhibition could be of therapeutic value in a subset of PTCL, especially when combined with ALK inhibitors, and might be clinically beneficial in ALK+ ALCL.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

PIM Kinases as Potential Therapeutic Targets in a Subset of Peripheral T Cell Lymphoma Cases

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Non-anaplastic peripheral T cell lymphoma (PTCL) is a heterogeneous group of diseases that accounts for 0.9-1.8 % of all childhood non-Hodgkin's lymphoma (NHL) [1][2][3][4][5]. In the 2008 World Health Organization (WHO) classification, PTCL comprised 21 subtypes, including a leukemic/disseminated group, an extranodal group, a cutaneous lymphoma group, and a nodal group [6].…”

Section: Introductionmentioning

confidence: 99%

Non-anaplastic peripheral T cell lymphoma in children and adolescents—an international review of 143 cases

et al. 2016

View full text Add to dashboard Cite

Peripheral T cell lymphomas (PTCL) are rare in children and adolescents, and data about outcome and treatment results are scarce. The present study is a joint, international, retrospective analysis of 143 reported cases of non-anaplastic PTCL in patients <19 years of age, with a focus on treatment and outcome features. One hundred forty-three patients, between 0.3 and 18.7 years old, diagnosed between 2000 and 2015 were included in the study. PTCL not otherwise specified was the largest subgroup, followed by extranodal NK/T cell lymphoma, hepatosplenic T cell lymphoma (HS TCL), and subcutaneous panniculitis-like T cell lymphoma (SP TCL). Probability of overall survival (pOS) at 5 years for the whole group was 0.56 ± 0.05, and probability of event-free survival was (pEFS) 0.45 ± 0.05. Patients with SP TCL had a good outcome with 5-year pOS of 0.78 ± 0.1 while patients with HS TCL were reported with 5-year pOS of only 0.13 ± 0.12. Twenty-five percent of the patients were reported to have a pre-existing condition, and this group had a dismal outcome with 5-year pOS of 0.29 ± 0.09. The distribution of non-anaplastic PTCL subtypes in pediatric and adolescent patients differs from what is reported in adult patients. Overall outcome depends on the subtype with some doing better than others. Pre-existing conditions are frequent and associated with poor outcomes. There is a clear need for subtype-based treatment recommendations for children and adolescents with PTCL.

show abstract

“…Overall response rate [ORR, CR plus PR (partial remission)] was 60 % (CR 2 cases, PR 4 cases and 1 case omitted because of no description). ORR with R-CHOP and R-CHOP-like regimens was 75 %, which was slightly inferior to 79 through 84 % of ORR in CD20-negative PTCL-NOS treated with CHOP or CHOP-like regimens [30]. More scrutinizing the relationship between the intensity of CD20 immunostaining and the efficacy of rituximab-based chemotherapy, we found that ORR was 100 % in cases in strong staining (n = 3), while 33.3 % in cases in variable staining (n = 6).…”

Section: Discussionmentioning

confidence: 77%

CD20-positive primary gastric T-cell lymphoma poorly responding to initial treatment with rituximab plus CHOP, and a literature review

et al. 2015

View full text Add to dashboard Cite

There have been rare reported cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) that co-expressed CD20. A 44-year-old Japanese male was initially misdiagnosed as CD20-positive diffuse large B-cell lymphoma with a background of reactive CD3-positive T-cells in the stomach. After four cycles of R-CHOP [rituximab plus cyclophosphamide (CY), doxorubicin, vincristine, and prednisolone (PSL)], total gastrectomy with regional lymph node dissection was performed due to the poor response to R-CHOP. A final diagnosis of CD20-positive primary gastric PTCL-NOS was made based on the immunohistochemical, flow cytometric, and molecular genetic findings. In the present case, CD20 immunostaining for T-cell lymphoma cells in tumor tissue varied; in a large part, these were strong to weak-positive, and in some parts, absent. We additionally reviewed the literature focusing on CD20-positive PTCL-NOS treated with rituximab. The administration of rituximab has been performed as an initial treatment in 11 cases, including the case reported here. The response was good in cases with high expression of CD20, while it was poor in cases with variable intensity in CD20 staining, which is consistent with our experience in the present case. The efficacy of rituximab may be associated with intensity of CD20 expression in T cells and its homogeneity in the tumor tissue.

show abstract

From empiric to mechanism-based therapy for peripheral T cell lymphoma

Cited by 17 publications

References 115 publications

PIM Kinases as Potential Therapeutic Targets in a Subset of Peripheral T Cell Lymphoma Cases

PIM Kinases as Potential Therapeutic Targets in a Subset of Peripheral T Cell Lymphoma Cases

Non-anaplastic peripheral T cell lymphoma in children and adolescents—an international review of 143 cases

CD20-positive primary gastric T-cell lymphoma poorly responding to initial treatment with rituximab plus CHOP, and a literature review

Contact Info

Product

Resources

About