scholarly journals Impact of Epstein-Barr Virus on Peripheral T-Cell Lymphoma Not Otherwise Specified and Angioimmunoblastic T-Cell Lymphoma

2022 ◽  
Vol 11 ◽  
Author(s):  
Tong-Yoon Kim ◽  
Gi-June Min ◽  
Young-Woo Jeon ◽  
Sung-Soo Park ◽  
Silvia Park ◽  
...  

PurposeThe significance of Epstein-Barr virus (EBV) infections for the prognosis of patients with peripheral T-cell lymphomas (PTCLs), specifically angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (PTCL-NOS), remains unclear. The Epstein-Barr encoding region can be used to detect EBV in tissue sections by in situ hybridization (ISH) and by polymerase chain reaction (PCR) assays of peripheral blood samples from patients with PTCLs. This study compared the outcomes patients with AITL or PTCL-NOS for whom the presence of EBV infection was assessed by these two methods.Patients and MethodsThis was a retrospective study of patients newly diagnosed with AITL or PTCL-NOS. All patients were selected from a single transplantation center. EBV-positive lymphomas were detected at the time of diagnosis in tissue sections by ISH or in the blood by PCR.ResultsOut of a cohort of 140 patients with histologically confirmed AITL or PTCL-NOS, 105 were EBV-positive. The 3-year overall survival of patients with EBV-positive TCL was 43.3% compared to 68.6% in patients with EBV-negative TCL (p = .01). Patients who were treated with autologous or allogeneic hematopoietic stem cell transplantation (n = 28 and n = 11, respectively) or chemotherapy alone (n = 66) had 3-year survival rates of 67.0%, 62.3%, and 30.2%, respectively (p <.02). Patients with EBV-positive TCL had a better prognosis after treatment with hematopoietic stem cell transplantation compared to chemotherapy alone, but no difference was seen among patients with EBV-negative TCL.ConclusionsEBV infection was shown to negatively affect the clinical outcomes of patients with TCL. Stem cell transplantation has been found to be an effective treatment for EBV-associated lymphomas. Further investigations are warranted to determine the optimal treatment for these patients.

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5438-5438
Author(s):  
Andrei R. Shustov ◽  
Haifa Kathrin Al-Ali ◽  
Gerald Wulf ◽  
Pamela Hsu ◽  
Mi Rim Choi ◽  
...  

Abstract Background: PTCL is a heterogeneous group of hematologic malignancies associated with a poor prognosis for most subtypes. In the relapsed setting, hematopoietic stem cell transplantation (HSCT) is the only potentially curative option for patients with PTCL. However, many patients are not able to achieve an adequate response to allow for HSCT. Belinostat (Beleodaq) is a potent pan-histone deacetylase inhibitor that was recently approved in the US for the treatment of patients with R/R PTCL. Approval was based on data from the pivotal Phase 2 BELIEF study that enrolled 129 patients with R/R PTCL (N = 120 evaluable), and demonstrated durable clinical benefit and tolerability. This analysis presents data for 12 of the enrolled patients (9 evaluable) who proceeded to HSCT following belinostat treatment. Methods: Patients with R/R PTCL received belinostat as a 1000 mg/m2IV infusion on Days 1-5 of a 21-day cycle. The primary endpoint of the study was Objective Response Rate (ORR; Complete Response [CR] + Partial Response [PR]) determined by an Independent Review Committee (IRC). We present efficacy and safety data for the subset of 12 patients who subsequently went on to HSCT. Results: Among 12 patients who subsequently proceeded to HSCT, 4 went on to receive an autologous HSCT and 8 received an allogeneic HSCT; 8 patients (67%) were female and 4 (33%) were male, and the median age was 54.5 (range 31-71) years. The median number of prior anticancer therapies was 2 (range 1-8), including 3 patients with prior autologous HSCT. The median number of belinostat treatment cycles was 2.5 (range 1-14) compared to the median of 2.0 (range 1-8) in the overall study population. Most patients in this subgroup had PTCL-Not Otherwise Specified (58.3%), angioimmunoblastic T-cell lymphoma (16.7%), or anaplastic large cell lymphoma (16.7%); 41.7% of patients had Stage IV disease. Three of the 12 patients were not evaluable for response due to insufficient histological material for confirmation by central pathologic analysis. The IRC-confirmed ORR for the 9 evaluable patients was 33.3% vs 25.8% in the study overall, and included 2 CRs, 1 PR, 2 patients with stable disease (SD) and 3 patients with progressive disease (PD). Duration of Response after transplant ranged from 41-261 days for the 3 belinostat responders. At last study contact, 2 patients had died from cardiac events (unrelated to belinostat) and 10 remained alive, with Overall Survival (OS) ranging from 8-23+ months. Most adverse events (AEs) were Grade 1-2, with two treatment-related Grade ≥3 AEs (neutropenia and prolonged QT interval); 3 serious AEs (arthralgia, lower limb fracture, and pyrexia) were reported in this subgroup. Conclusions: Belinostat was well tolerated in previously treated patients with R/R PTCL and enabled some patients to proceed to HSCT. Three patients responded and went on to HSCT following belinostat; the remaining patients had HSCT following SD (2), PD (4) or were not evaluable (3). OS was prolonged when compared to historical controls. Summary of Patients Treated with Belinostat Who Subsequently Went on to Hematopoietic Stem Cell Transplantation Sorted by Subtype and Response Table 1PatientSubtype(Stage)Prior RegimensECOGPSBelinostat CyclesIRC ResponseOS(months)DoR(days) Evaluable Patients931-003^PTCL-NOS (IIIB)3114CR11.56261907-006PTCL-NOS (IIA)5 + auto SCT02SD13.93-907-007^PTCL-NOS (IVA)402SD12.09-907-005^PTCL-NOS (IIIA)202PD13.63-140-002PTCL-NOS (IVA)817PD17.64-914-006PTCL-NOS (IIIA)4 + auto SCT02NE13.73-245-001AITL (UNK)106PR19.9141221-003ALCL ALK– (IA)2 + auto SCT011CR20.4173907-001ALCL ALK– (IVA)204PD22.87- Non-Evaluable Patients*914-002PTCL-NOS (IVB)102PD7.75-147-002^AITL (IIIB)221NE9.43-147-001Hepatosplenic TCL (IVA)103NE10.22- AITL = angioimmunoblastic T-cell lymphoma; ALCL = anaplastic large cell lymphoma; ALK = alkaline phosphatase; auto = autologous; CR = complete response; DoR = duration of response; ECOG = Eastern Cooperative Oncology Group; IRC = independent review committee; NE = not evaluable; NOS = not otherwise specified; OS = overall survival; PD = progressive disease; PR = partial response; PS = performance status; PTCL = peripheral T-cell lymphoma; SCT = stem cell transplantation; SD = stable disease; TCL = T-cell lymphoma *Lack of central pathologic confirmation resulted in exclusion from the evaluable population ^Autologous hematopoietic SCT Disclosures Al-Ali: Novartis: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Hsu:Spectrum Pharmaceuticals: Employment. Choi:Spectrum Pharmaceuticals: Employment. Allen:Spectrum Pharmaceuticals: Employment. Visser:Sanofi: Membership on an entity's Board of Directors or advisory committees. Horwitz:Celgene: Consultancy, Research Funding; Millenium: Consultancy, Research Funding; Infinity: Research Funding; Kiowa-Kirin: Research Funding; Seattle Genetics: Consultancy, Research Funding; Spectrum: Consultancy, Research Funding; Amgen: Consultancy; Bristol-Myers Squibb: Consultancy; Jannsen: Consultancy.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5857-5857
Author(s):  
Caixia Li ◽  
Dan Yang ◽  
Xiaochen Chen ◽  
Tong Wang ◽  
Qiu Zou ◽  
...  

Abstract Objective To investigate the effect of hematopoietic stem cell transplantation in the treatment of T cell lymphoma. Methods The clinical data of 98 patients with T cell lymphoma (T-NHL) treated by hematopoietic stem cell transplantation from June 2001 to December 2015 in our center were retrospectively analyzed. Results (1) 98 T-NHL patients, 62 males and 36 females, aged 7-64 years (median age 27 years). Disease subtypes: 30 cases of T-cell lymphoblastic lymphoma, 24 cases of NK / T cell lymphoma, 22 cases of peripheral T-cell lymphoma (PTCL, NOS), 19 cases of variable large cell lymphoma (ALCL), and 3 cases of subcutaneous panniculitic T cell lymphoma. Transplantation type: 55 cases of autologous transplantation, 43 cases of allogeneic transplantation. The follow-up was ended in April 2016, the duration of following-up ranged from 2 to 178 months (median follow-up time was 20 months). (2) 55/98 patients with autologous hematopoietic stem cell transplantation (auto-HSCT), 31 males and 24 females, aged 7-64 years (median age 27 years). Disease subtypes: 19 cases of anaplastic large cell lymphoma (ALCL) , 15 cases of NK / T cell lymphoma, 13 cases of peripheral T-cell lymphoma (PTCL, NOS), 5 cases of T cell lymphoblastic lymphoma, and 3 cases of subcutaneous panniculitic T cell lymphoma. The 3 year overall survival (OS) and disease-free survival (EFS) were 79.6% and 58.4%, respectively. (3) 43/98 patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT), 31 males and 12 females, aged 8-52 years (median age 27 years). Disease subtypes: 25 cases of T lymphoblastic lymphoma, 9 cases of NK / T cell lymphoma, and 9 cases of peripheral T cell lymphoma (PTCL, NOS). Transplant subtypes: 23 cases of haploidentical transplantation, 12 cases of HLA-identical sibling donor transplantation, 6 cases of HLA-identical unrelated donor transplantation, and 2 cases of umbilical cord blood transplantation. The 3 year EFS and OS of allo-HSCT were 58.3% and 56.7%, respectively. (4) 38/55 patients with CR1 status before auto-SCT, 3 year OS and EFS were 82.8% and 60.7% respectively. 17/55 patients with non-CR1 status before auto-HSCT, 3 year OS and EFS were 57.2% and 47.8%. Compared with non-CR1 group, the OS and PFS of CR1 group were better, but failed to show significant statistical difference (p>0.05), which may be related to the less number of cases and sub types of the two groups do not match the correlation. (5) 31/98 cases were young and high-risk patients (age < 60 years, IPI score ≥3).16/31 cases treated with allo-HSCT, the 3 year OS and EFS were 73.1% and 70.5%. 15/31 cases treated with auto-HSCT, the 3 year OS and EFS were 48.4% and 27.8%. The OS and EFS of the two groups were significantly different (P=0.001). Conclusion Hematopoietic stem cell transplantation can improve the efficacy of T cell lymphoma. Auto-HSCT in first complete remission (CR1) enables T-NHL patients with greater benefit. Allo-HSCT can cure some T-NHL patients, which can be considered for the treatment of young and high-risk T-NHL patients. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4849-4849
Author(s):  
Ikuo Shimizu ◽  
Wataru Takeda ◽  
Takehiko Kirihara ◽  
Keijiro Sato ◽  
Yuko Fujikawa ◽  
...  

Abstract Abstract 4849 Background: Peripheral T-cell lymphoma (PTCL) is an intractable entity with limited response to CHOP-like regimens or more intensive regimens. Although some relapsed or refractory patients may benefit from allogeneic stem cell transplantation, management of elderly patients remains problematic. Sobuzoxane (MST-16) is an oral topoisomerase II inhibitor developed and approved in Japan (Narita T et al. Cancer Chemother Pharmacol 1990). Some anecdotal reports revealed its activity against refractory or relapsed PTCLs as a single-drug regimen or in combination regimens. Patients and Methods: We retrospectively reviewed consecutive cases of patients with angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) who were refractory to or relapsed after CHOP-like chemotherapy during the period spanning January 1990 to March 2012 at Nagano Red Cross Hospital (Nagano, Japan). Diagnosis was performed by certified pathologists based on biopsy samples and flow cytometry. We compared efficacy, safety, and survival time between patients who underwent MST-16-containing regimens and other salvage regimens, including autologous or allogeneic stem cell transplantation. Results: Among 40 patients with AITL or PTCL-NOS, 27 (median age, 65 years; range, 48–86) were administered salvage chemotherapy. The MST-16 group (n=13) received MST-16 alone (9), MST-16 and etoposide (3), or MTX-HOPE (methotrexate, hydrocortisone, vincristine, MST-16, and etoposide) (1). The median number of previous regimens was 3 (range 1–4). The non-MST-16 group (n=14) consisted of multiple regimens including EPOCH (2), ESHAP (2), CEPP (cyclophosphamide, etoposide, procarbazine, and prednisolone) (1), IVAM (2), DeVIC (1), DHAP (1), ABEP (doxorubicin, bleomycin, etoposide, and prednisolone) (1), or high dose therapy with autologous or allogeneic stem cell transplantation (3). Patients in the MST-16 group were of significantly higher age (p=0.027) and had less hepatosplenomegaly (p=0.028) compared to those in the non-MST-16 group. No significant difference was observed in patient performance status, B symptoms, LDH, immunoglobulin values, International Prognostic Index (IPI) scores, and Prognostic Index for T-cell lymphoma (PIT) scores between the two groups. Among MST-16 group, overall response rate was 62.1% (CR 31.0%, PR 31.0%). Notably, additional patients (14.3%) achieved durable SD by palliative MST-16 chemotherapy. With a median observation period of 25 months, median survival time was significantly longer in the MST-16 group compared to the non-MST-16 group (23 months vs. 4 months, respectively; p=0.027). Those with a longer remission period over 6 months due to a CHOP-like regimen tended to respond better to MST-16 salvage regimens (p=0.059). With respect to adverse events, two deaths occurred (one patient with pulmonary aspergillosis following ABEP, and one patient with pneumocystis pneumonia following MST-16). Conclusions: Although this study was of a small scale and retrospective, it supports the notion that MST-16-containing regimens may present a promising approach for relapsed/refractory AITL or PTCL-NOS patients, particularly for those who relapse following a long remission of over 6 months due to a CHOP-like regimen, those not indicated for SCT, and those for whom steroid use is difficult. Given the pleomorphic nature of these entities, there remains the possibility that selection bias may have accounted for the difference observed between the two arms. Further prospective studies with other approaches (e.g., biological or immunohistopathological) may lead to the identification of pathologies other than hepatosplenomegaly that benefit from MST-16. Disclosures: No relevant conflicts of interest to declare.


2017 ◽  
Vol 44 (9) ◽  
pp. 1038-1042 ◽  
Author(s):  
Hiroshi Saruta ◽  
Chika Ohata ◽  
Ikko Muto ◽  
Taichi Imamura ◽  
Eijiro Oku ◽  
...  

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