scholarly journals Outcomes of GDPT (gemcitabine, cisplatin, prednisone, thalidomide) versus CHOP in newly diagnosed peripheral T-cell lymphoma patients

2020 ◽  
Vol 12 ◽  
pp. 175883592092382 ◽  
Author(s):  
Yuanyuan Sun ◽  
Ling Li ◽  
Xin Li ◽  
Lei Zhang ◽  
Xinhua Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
The Other ◽  
Newly Diagnosed ◽  
Peripheral T Cell Lymphoma ◽  
Angioimmunoblastic T Cell Lymphoma ◽  
Significant Difference ◽  
Gene Expression Levels

Aim: To compare the outcomes of GDPT [gemcitabine (G), cisplatin (D), prednisone (P), thalidomide (T)] versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in treating newly diagnosed PTCL (peripheral T-cell lymphoma). Methods: An open-label prospective clinical trial with 153 newly diagnosed PTCL patients conducted between January 2010 and December 2018 was designed. Patients were randomly assigned to the GDPT (77 cases) and CHOP (76 cases) groups. Patients in each group were further divided into four subgroups: PTCL, not otherwise specified (PTCL-NOS); anaplastic large cell lymphoma (ALCL), angioimmunoblastic T cell lymphoma (AITL), and other types subgroup, in accordance with pathological patterns. Based on expression of RRM1, TOP2A, TUBB3, and ERCC1, patients were divided into groups with high and low gene expression levels. Clinical characteristics, side effects, efficacy, progression-free survival (PFS), and overall survival (OS) were compared. Results: There were no significant differences in the basic clinical features or side effects between the GDPT and CHOP groups. The overall response rate (ORR) of the GDPT group was better than that of the CHOP group (66.3% versus 50.0%, p = 0.042), as was the complete remission (CR) rate (42.9% versus 27.6%, p = 0.049). Patients in the GDPT group had a longer PFS and OS than the CHOP group. The 4-year PFS and OS rates in the GDPT group were both superior to those in the CHOP group (63.6% versus 53.0% for PFS, p = 0.035; 66.8% versus 53.6% for OS, p = 0.039). In the GDPT group, the difference in CR between the four subgroups was statistically significant ( p = 0.046). In the CHOP group, differences in both CR and ORR among the four subgroups were statistically significant ( p < 0.001 and p = 0.005, respectively). There were also statistically significant differences in CR between patients treated with CHOP and GDPT in the PTCL-NOS subgroup, AITL subgroup, and the other types subgroup ( p = 0.015; p = 0.003; p = 0.005, respectively). The data also showed a significant difference in OS among the four subgroups within the GDPT group ( p = 0.001). The OS of AITL was shorter than that of the other three subgroups. Four subgroups of CHOP showed a significant difference in PFS ( p = 0.019). There was no statistical association between responses and the gene expression levels of RRM1, ERCC1, TUBB3, and TOP2A. Conclusion: The GDPT group had better response rates and prolonged patient PFS and OS. As a promising new regimen, GDPT is expected to become the first-line therapy for PTCL. New agents should be applied to patients who do not achieve good responses with previous treatment, such as those diagnosed with angioimmunoblastic T cell lymphoma. Trial registration: This open randomized prospective clinical trial was registered at ClinicalTrials.gov (NCT01664975).

Outcomes of GDPT (gemcitabine, cisplatin, prednisone,thalidomide) versus CHOP in newly diagnosed peripheral T-cell lymphoma patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8018-8018
Author(s):  
Ling Li ◽  
Yuanyuan Sun ◽  
Xin Li ◽  
Lei Zhang ◽  
Xinhua Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
The Other ◽  
Newly Diagnosed ◽  
Peripheral T Cell Lymphoma ◽  
Significant Difference ◽  
Gene Expression Levels

8018 Background: Peripheral T-cell lymphoma(PTCL) is highly heterogeneous invasive NHL.There is no consensus standard treatment for it now. So outcomes of GDPT versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in treating newly diagnosed PTCL were compared. Methods: An open-label prospective clinical trial with 153 newly diagnosed PTCL patients conducted between January 2010 and December 2018 was designed. Patients were randomly assigned to the GDPT group (77 cases) and CHOP group (76 cases). Patients in each group were further divided into four subgroups: PTCL-NOS, ALCL, AITL, and an other types, in accordance with pathological patterns. Based on expression of RRM1, TOP2A, TUBB3 and ERCC1, patients were divided into groups with high and low gene expression levels. Clinical characteristics, side effects, efficacy, PFS and OS were compared. Results: There were no significant differences in the basic clinical features or side effects between the GDPT and CHOP groups. The ORR of the GDPT group was better than that of the CHOP group (66.3%vs. 50.0%, P= 0.042), as was the CR rate (42.9% vs. 27.6%, P= 0.049). Patients in the GDPT group had a longer PFS and OS than the CHOP group. The 4-year PFS and OS rates in the GDPT group were both superior to those in the CHOP group (63.6% vs. 53.0% for PFS, P= 0.035; 66.8% vs. 53.6% for OS, P= 0.039).In the GDPT group, the difference in CR between the four subgroups was statistically significant (P = 0.046).In the CHOP group, differences in both CR and ORR among the four subgroups were statistically significant ( P= < 0.001 and P= 0.005, respectively).There were also statistically significant differences in CR between patients treated with CHOP and GDPT in the PTCL-NOS subgroup, AITL subgroup, and the other types subgroup( P= 0.015; P= 0.003; P= 0.005, respectively).The data also showed a significant difference in OS among the four subgroups within the GDPT group ( P= 0.001).The OS of AITL was shorter than that of the other three subgroups. Four subgroups of CHOP showed a significant difference in PFS ( P= 0.019). There was no statistical association between responses and the gene expression levels of RRM1, ERCC1, TUBB3 and TOP2A. Conclusions: The GDPT group had better response rates and prolonged the patients’ PFS and OS. As a promising new regimen, GDPT is expected to become the first-line therapy for PTCL. New agents should be applied to patients who do not achieve good responses with previous treatment, such as those diagnosed with angioimmunoblastic T cell lymphoma. Clinical trial information: NCT01664975 .

The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells

Blood ◽  
2007 ◽  
Vol 109 (11) ◽  
pp. 4952-4963 ◽  
Author(s):  
Laurence de Leval ◽  
David S. Rickman ◽  
Caroline Thielen ◽  
Aurélien de Reynies ◽  
Yen-Lin Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Gene Set Enrichment Analysis ◽  
Molecular Profile ◽  
Peripheral T Cell Lymphoma ◽  
Angioimmunoblastic T Cell Lymphoma ◽  
Tfh Cells ◽  
Follicular Helper

Abstract The molecular alterations underlying the pathogenesis of angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, unspecified (PTCL-u) are largely unknown. In order to characterize the ontogeny and molecular differences between both entities, a series of AITLs (n = 18) and PTCLs-u (n = 16) was analyzed using gene expression profiling. Unsupervised clustering correlated with the pathological classification and with CD30 expression in PTCL-u. The molecular profile of AITLs was characterized by a strong microenvironment imprint (overexpression of B-cell– and follicular dendritic cell–related genes, chemokines, and genes related to extracellular matrix and vascular biology), and overexpression of several genes characteristic of normal follicular helper T (TFH) cells (CXCL13, BCL6, PDCD1, CD40L, NFATC1). By gene set enrichment analysis, the AITL molecular signature was significantly enriched in published TFH-specific genes. The enrichment was higher for sorted AITL cells than for tissue samples. Overexpression of several TFH genes was validated by immunohistochemistry in AITLs. A few cases with molecular TFH-like features were identified among CD30− PTCLs-u. Our findings strongly support that TFH cells represent the normal counterpart of AITL, and suggest that the AITL spectrum may be wider than suspected, as a subset of CD30− PTCLs-u may derive from or be related to AITL.

scholarly journals GATA 3 Gene Overexpression Is A Biomarker of Adverse Prognosis for Peripheral T-Cell Lymphoma, Not Otherwise Specified and for ALK-Negative Anaplastic Large Cell Lymphoma: An Exploratory Analysis of 80 Latin American Cases of nodal PTCLs

2020 ◽  
Author(s):  
Luís Alberto de Pádua Covas Lage ◽  
Cláudio Vinícius Brito ◽  
Débora Levy ◽  
Hebert Fabrício Culler ◽  
Samuel Campanelli Freitas Couto ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Not Otherwise Specified ◽  
Large Cell Lymphoma ◽  
Alk Positive ◽  
Gene Expression Levels

Background: Nodal peripheral T-cell lymphomas (nPTCLs) encompass a heterogeneous group of mature and aggressive lymphoid malignancies, including peripheral T-cell lymphoma, not otherwise specified (PTCL/NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL) ALK-positive and ALK-negative. Their differential diagnosis and prognosis are an issue in the clinical practice. Accurate biomarkers to refine the different subtypes of nPTCLs and to stratify their prognosis are essential to improve their treatment approach. The aim of this study was to test the prognostic impact of GATA3 gene expression, and its capability to discriminate the different subtypes of nPTCLs. Patients and Methods: From 2000 to 2017, 80 patients with nPTCLs were eligible for GATA3 gene expression analysis that was assessed retrospectively by quantitative real time PCR (qRT-PCR) of neoplastic biopsies in Formalin-Fixed Paraffin-Embedded samples (FFPE). Results: Median age was 49 years old (IqR 34-59), 43/80 (53.7%) were male. Median follow-up was 1.72 years. Of them, 36.3% were classified as PTCL/NOS, 31.2% ALK-negative ALCL, 21.2% ALK-positive ALCL and 11.3% AITL. The majority of cases had advanced stage (III/IV). Two-year estimated overall survival (OS) and progression-free survival (PFS) were 52.2% and 39.5%, respectively. The median GATA3 gene expression level was 0.49% (range 0 &ndash; 7.07) in all cohort, it was 0.11% for ALK-positive ALCL, 0.46% for ALK-negative ALCL, 0.86% for PTCL/NOS and 0.67% for AITL. The difference of GATA3 gene expression among distinct variants of nPTCLs was statistically significant (p &lt; 0.001). GATA3 gene expression levels &ge; 0.71% discriminate PTCL/NOS from ALK-negative ALCL and AITL with sensitivity of 62% and specificity of 80.3%. GATA3 gene expression levels &ge; median was associated with poor 2-year OS for PTCL/NOS (46.7% x 21.4%, p=0.04) and for ALK-negative ALCL (85.7% x 54.5%, p=0.04). Conclusion: Despite the relative small and heterogeneous group of patients with nPTCLs, GATA3 gene overexpression may be an important biomarker associated with poor prognosis in PTCL/NOS and ALK-negative ALCL. Moreover it may also discriminate different subtypes of nPTCLs. Further studies with larger series of patients should confirm our findings.

scholarly journals Bone marrow transplantation for peripheral T-cell lymphoma in children and adolescents

Blood ◽  
1992 ◽  
Vol 80 (11) ◽  
pp. 2938-2942 ◽  
Author(s):  
BG Gordon ◽  
PI Warkentin ◽  
DD Weisenburger ◽  
JM Vose ◽  
WG Sanger ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Phase I ◽  
Children And Adolescents ◽  
Marrow Transplantation ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
The Other ◽  
Peripheral T Cell Lymphoma

Abstract We report nine children with relapsed (n = 8) or high-risk (n = 1) peripheral T-cell lymphoma (PTCL) who underwent autologous (n = 6) or allogeneic (n = 3) bone marrow transplantation (BMT). These children received transplants as part of a prospective phase I/II study of thioTEPA (TT) and total body irradiation (TBI) with escalating doses of VP-16. The median age of these patients at time of BMT was 6.5 years (range 2.5 years to 14 years). Three were transplanted with active disease after failing salvage chemotherapy. Of the other six, one was transplanted in first complete remission (CR) and five in second or subsequent CR. Of these nine patients, eight are free of disease a median of 25 months after BMT (range, 6 to 48 months), with an estimated 2-year relapse-free survival (RFS) of 89%. Six of these eight patients have been followed for 12 or more months after BMT, and in each their current remission exceeds their longest previous remission duration. The toxicity of the TT/TBI +/- VP-16 regimens was significant but manageable, predominantly consisting of severe mucositis. For a comparison, we reviewed retrospective data on the six additional children and adolescents with PTCL who underwent BMT during the 3-year period preceding this phase I/II study. The median age at BMT of these six patients was 19 years (range 15.5 years to 20 years). These patients were prepared for BMT with a variety of other regimens. One had no response to BMT and the other five relapsed at 1.5 to 5 months after BMT (median, 3 months) with an RFS of 0%. Our data suggest that thioTEPA plus TBI, with or without VP-16, is an effective preparative regimen for BMT for young patients with relapsed or high-stage PTCL and leads to prolonged RFS.

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