The Efficacy of Bortezomib-CHOP In Patients with Advanced Stage T or NK/T Cell Lymphomas: The Results of Multicenter Phase II Study.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1791-1791 ◽  
Author(s):  
Seok Jin Kim ◽  
Hyeon-Seok Eom ◽  
Jin Seok Kim ◽  
Hye Jin Kang ◽  
Hyo Jung Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Advanced Stage ◽  
Chop Regimen ◽  
T Cell Lymphomas ◽  
Nk T Cell

Abstract Abstract 1791 Background Advanced stage T-cell or NK/T-cell lymphomas usually show aggressive clinical course and their treatment outcomes are worse than B-cell non-Hodgkin lymphoma. Furthermore, the optimal treatment regimen is not still established for these disease entities. At present, cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) regimen is still used as a primary treatment for advanced stage T or NK/T cell lymphomas although its efficacy is not satisfactory. Thus, more effective treatment regimen is required to improve treatment outcome. The incorporation of new targeted agents into CHOP regimen has been a widely used strategy to develop new regimen for the treatment of lymphoma. Bortezomib, a proteasome inhibitor approved for the use of treatment of multiple myeloma has been tried in many B-cell non-Hodgkin lymphomas. A recent in vitro study results showed that proteasome inhibitor could inhibit the growth of NK/T lymphoma cells. Based on these results, we designed a regimen combining CHOP with. Our previous phase I study determined the maximum tolerated dose of bortezomib as 1.6mg/m2 for combination with CHOP. Thus, we performed the phase II study to evaluate the efficacy of bortezomib plus CHOP chemotherapy. Methods We enrolled patients with newly diagnosed T or NK/T cell lymphoma. All patients were Ann Arbor stage III/IV and had adequate organ function. Patients received bortezomib on days 1 and 8 (weekly schedule, 1.6 mg/m2 per dose) in addition to 750 mg/m2 cyclophosphamide, 50 mg/m2 doxorubicin, 1.4 mg/m2 vincristine on day 1 and 100 mg/day prednisolone on days 1 to 5, every 3 weeks. Six cycles of therapy administered every 21 days were planned. All patients provided written informed consents and this trial was registered at www.ClinicalTrials.gov (NCT00374699). Results 46 patients were enrolled between April 2007 and August 2009. Peripheral T-cell lymphoma, unspecified (n=16) and extranodal NK/T cell lymphoma (n=10) were dominant subtypes while angioimmunoblastic T-cell lymphoma (n=8) and ALK-negative anaplastic large cell lymphoma (n=6) account for 30.4% of all patients. Five patients with cutaneous T-cell lymphoma and one hepatosplenic T-cell lymphoma were also recruited. The median age at diagnosis was 52 years (range 21 – 66 years). Serum LDH elevation (n = 28, 60.9%) and stage IV patients were dominant (n = 32, 69.6%). Thus, the International Prognostic Index risk was dominantly high or high-intermediate (n = 26, 56.5%). Complete response was achieved in 30 patients (65.2%) and partial response was 5 patients (10.9%). As a result, the overall response rate was 76.1%. The comparison of complete response rate based on the subtype demonstrated that the complete response rate of peripheral T-cell lymphoma, unspecified (12/19, 63.2%), angioimmunoblastic T-cell lymphoma (6/8, 75%), anaplastic large cell lymphoma (4/6, 66.7%) and cutaneous T-cell lymphoma (5/5, 100.0%) was better than extranodal NK/T cell lymphoma (3/10, 30.0%). Five patients with extranodal NK/T cell lymphoma progressed during the treatment with bortezomib and CHOP. The hematologic toxicity was the major toxicity of this regimen, thus, grade 3/4 leucopenia and febrile neutropenia were the most frequent toxicity. However, there was no treatment-related mortality. In addition, neurotoxicity was tolerable, so the majority of peripheral neurotoxicity was grade 1 or 2. Conclusion The combined treatment of bortezomib with CHOP is an effective regimen for advanced stage T-cell lymphomas with acceptable toxicity. However, it may not be efficient for advanced stage extranodal NK/T-cell lymphomas. Disclosures: No relevant conflicts of interest to declare.

Brentuximab vedotin in real life, a seven year experience in patients with refractory/relapsed CD30+ T cell lymphoma

2020 ◽  
pp. 107815522096861
Author(s):  
Lucie Oberic ◽  
Faustine Delzor ◽  
Caroline Protin ◽  
Sophie Perriat ◽  
Camille Laurent ◽  
...  
Keyword(s):  
T Cell ◽  
Combination Treatment ◽  
Cell Lymphoma ◽  
Real Life ◽  
Progression Free Survival ◽  
Large Cell ◽  
Complete Response ◽  
Brentuximab Vedotin ◽  
T Cell Lymphoma ◽  
T Cell Lymphomas

Introduction Brentuximab vedotin (Bv) has been approved for the treatment of Refractory/Relapsed (R/R) Anaplastic Large Cell Lymphomas (ALCL) and cutaneous T-Cell Lymphomas, but is also effective in other CD30+ malignancies. We report here the outcomes of patients with various R/R Peripheral T Cell Lymphoma (PTCL) treated with Bv in real life practice. Method This was a retrospective, single-center study based on medical records of patients with R/R PTCL treated either with Bv alone or in combination with chemotherapy. Results Among 27 patients treated with Bv, neutropenia was the main serious adverse event observed in particular when Bv was used as combination treatment. The complete Response Rates (CRR) was 40.7%; it was significantly improved when Bv was used as combination treatment. The majority of eligible patients (7/10) underwent Stem Cell Transplantation. Median Progression Free Survival (PFS) and Overall Survival (OS) were 5.2 months and 12.5 months respectively. Conclusion Our current study shows that Bv used in combination with chemotherapy provides a high CRR and thereby allows SCT in R/R PTCL. The use of Bv treatments in this setting warrants further investigation.

Concurrent Chemo-Radiotherapy Followed by VIDL (Etoposide, Ifosfamide, Dexamethasone, L-asparaginase) Chemotherapy In Stage I/II Extranodal NK/T-Cell Lymphoma of Nasal Cavity/Nasopharynx

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1765-1765
Author(s):  
Seok Jin Kim ◽  
Hyeon-Seok Eom ◽  
Jin Seok Kim ◽  
Jae-Yong Kwak ◽  
Deok-Hwan Yang ◽  
...  
Keyword(s):  
T Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Prognostic Index ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Hematologic Toxicity ◽  
Major Toxicity ◽  
Nk T Cell ◽  
Grade 3

Abstract Abstract 1765 Background Localized extranodal NK/T-cell lymphoma (ENKTL) mainly occurs in nasal and/or nasopharynx. Thus, ENKTL shows a poor response to anthracycline-based chemotherapy because of the frequent expression of a multidrug-resistant p-glycoprotein, radiotherapy for localized disease produces a higher complete response rate than chemotherapy. However, when ENKTL is treated with radiation alone, local and systemic failures are frequently observed. Therefore, our group previously reported the improved outcome of concurrent chemo-radiotherapy (CCRT) with weekly administration of cisplatin followed by systemic chemotherapy VIPD (etoposide, ifosfamide, cisplatin and dexamethasone). However, the grade 3/4 hematologic toxicity was the major toxicity of VIPD. Thus, in consideration of the risk of toxicity of VIPD, we designed VIDL (etoposide, ifosfamide, dexamethasone, and L-asparaginase) as adjuvant to CCRT. Because etoposide and ifosfamide are less affected by p-glycoprotein, and NK lymphoma cells are known as being sensitive to L-asparaginase, we expected VIDL regimen could be more effective and less toxic than VIPD. Methods Thirty-one newly diagnosed stage IE/IIE nasal/nasopharynx ENKTL patients received CCRT (radiation 40–50.4 Gy and cisplatin 30 mg/m2 weekly). Two cycles of VIDL (etoposide 100 mg/m2 D1–D3, ifosfamide 1200 mg/m2 D1–D3, dexamethasone 40 mg D1–D3, and L-asparaginase 4000IU/m2) were scheduled after CCRT. All patients provided informed written consents and this trial was registered at www.ClinicalTrials.gov (NCT01007526). Results The median age was 46.5 years (range, 22–71 years); 78.1% of all patients were younger than 60 years of age, and male (n = 21) to female (n = 11) was 2:1. Twenty-two patients were stage IE and nine were IIE. The majority of patients were in the low (n = 24) or low–intermediate (n = 6) risk categories of the International Prognostic Index. However, when we grouped patients based on the NK/T cell lymphoma prognostic index (NKPI) proposed previously for ENKTL, which includes the presence of B cell symptoms, lesions at stage III or IV, elevated serum LDH concentration, and lymph node involvement, 25 patients belonged to group I or II and 7 patients were group III or IV (those with more than two risk factors). All patients completed CCRT, which resulted in 90.3% overall response rate including 22 complete response (CR) and 6 partial response (PR). Twenty-seven patients completed the planned two cycles of VIDL while four patients did not because three patients progressed during or after CCRT, and one patient is ongoing. The overall response rate of 27 patients completed VIDL was 92.6%, and two patients relapsed after the completion of VIDL chemotherapy. The major toxicity of VIDL was grade 3/4 leucopenia (85.1%), but there was no treatment-related mortality. The non-hematologic toxicity was tolerable, and the hepatic toxicity-associated with the use of L-asparaginase was frequent (55.5%). However, the majority of the hepatic toxicities were grade 1 or 2. Conclusion Concurrent chemo-radiotherapy followed by VIDL chemotherapy can be an effective treatment strategy with acceptable toxicity in stage I/II extranodal NK/T-Cell lymphoma of nasal cavity/nasopharynx. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Final Report on Phase II Trial of L-Asparaginase Plus Concurrent Chemoradiotherapy Followed By Midle (Methotrexate, Ifosfamide, Etoposide, Dexamethasone, and L-asparaginase) Chemotherapy for Patients with Newly Diagnosed Stage I/II Extranodal NK/T-Cell Lymphoma, Nasal Type

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3942-3942
Author(s):  
Dok Hyun Yoon ◽  
Seok Jin Kim ◽  
Seong Hyun Jeong ◽  
Dong-Yeop Shin ◽  
Sung Hwa Bae ◽  
...  
Keyword(s):  
T Cell ◽  
Concurrent Chemoradiotherapy ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Stage I ◽  
Nasal Type ◽  
Nk T Cell ◽  
Grade 3

Abstract Background We previously have shown that concurrent chemoradiotherapy (CCRT) followed by chemotherapy such as VIPD (etoposide, ifosfamide, cisplatin and dexamethasone) or VIDL (etoposide, ifosfamide, dexamethasone and L-asparaginase) is an effective treatment for the management of localized extranodal NK/T-cell lymphoma (ENKTL), nasal type. To further improve efficacy, we designed a new treatment protocol, MIDLE (methotrexate, ifosfamide, dexamethasone, L-asparaginase and etoposide), which incorporates tri-weekly administration of L-asparaginase during CCRT to reduce the probability of systemic progression and high dose methotrexate to intensify chemotherapy based on previous excellent outcomes of methotrexate-containing regimens such as SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide) and MLD (methotrexate, L-asparaginase, dexamethasone). Methods The treatment scheme of CCRT consisted of radiation 36-45 Gy and weekly administration of cisplatin 30 mg/m2 (total: 4 doses). During the CCRT, tri-weekly 4,000 IU of Escherichia coli L-asparaginase was administered intravenously (IV). The chemotherapy, MIDLE (methotrexate 3 g/m2 on day 1, etoposide 100 mg/m2, Ifosfamide 1000 mg/m2 on day 2-3, dexamethasone 40mg on day 1-4, and L-asparaginase 6000 IU/m2 IV on day 4, 6, 8, 10) was repeated every 28 days for two cycles. All patients provided informed written consents and this trial was registered at www.ClinicalTrials.gov(NCT01238159). Results Twenty-eight patients with stage IE/IIE ENKTL were enrolled, and the median age was 51 years (range, 30-77 years). Twenty four patients were male while only four patients were female. Twenty-two patients had stage IE and six IIE disease. Twenty four were classified as low risk group and the other four intermediate group according to PINK-E (Kim SJ et al., EHA 2015 S110). All but two patients completed CCRT, which resulted in 85.7% of overall response rate including 16 complete responses (57.1%) and 8 partial responses (28.6%). One showed stable disease (SD) and the other one showed progressive disease (PD) with development of new distant lymph node involvement after CCRT. Grade 3 or 4 hematologic toxicity was not common. Only two patients experienced G3 neutropenia during or after CCRT. However, grade 3 non-hematologic toxicities were noted including bilirubin elevation (n = 3), mucositis (n = 1), anorexia (n=5) and nausea/vomiting (n = 11) Two could not complete CCRT according to the protocol due to G3 allergic reaction to L-asparaginase (n=1) and prolonged G3 mucositis (n=1). After the completion of CCRT, 23 out of 28 patients entered the MIDLE chemotherapy as five patients including one disease progression and four withdrawal during (n=2) or after (n=2) CCRT due to toxicities. All those who completed the planned two cycles of MIDLE chemotherapy achieved complete response after chemotherapy including those with PR (n=6) and SD (n=1) after CCRT. Three patients dropped out during or after their first cycle of MIDLE due to non-hematologic toxicities (recurrent G3 bilirubinemia (n=1), G3 increased creatinine (n=1), G5 infection (n=1)). The final complete response rate was 82% (23/28). It was associated with a significant rate of grade 3/4 neutropenia (n=21) and febrile neutropenia (n=10). Two patients experienced acute kidney injury (AKI) during the first cycle of MIDLE and one of them died of pneumonia complicated by sepsis. With a median follow-up of 46 months (95% confidence interval: 39 - 47 months), four patients progressed and five patients died with the estimated 3-year progression-free survival rate of 74.1% and overall survival rate of 81.5%. PINK-E could successfully stratify both time-to-progression (p=003) and overall survival (p=0.006) in this study. Conclusion L-asparaginase plus concurrent chemoradiotherapy followed by MIDLE chemotherapy may be an effective treatment strategy for stage I/II extranodal NK/T-Cell lymphoma, nasal type. However, higher numbers of patients were withdrawn during or after CCRT due to toxicity or poor tolerance than previous study. MIDLE chemotherapy was associated with high rate of G3 or 4 hematologic toxicities. Thus, this approach should be reserved for selected patients such as young fit but high risk of relapse. PINK-E can be a useful prognostic index for stage I/II extranodal NK/T-Cell lymphoma, nasal type. Disclosures No relevant conflicts of interest to declare.

Phase I Study of mTOR Inhibitor Everolimus Plus CHOP in Patients with Advanced, Aggressive T-Cell lymphomas

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1642-1642 ◽  
Author(s):  
Seok Jin Kim ◽  
Hye Jin Kang ◽  
Jin Seok Kim ◽  
Hyeon-Seok Eom ◽  
Jooryung Huh ◽  
...  
Keyword(s):  
T Cell ◽  
Mtor Inhibitor ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Hematologic Toxicity ◽  
Advanced Stage ◽  
Chop Regimen ◽  
T Cell Lymphomas ◽  
Level Ii ◽  
Trough Concentrations

Abstract Abstract 1642 Background: Advanced stage T-cell lymphomas usually follow aggressive clinical course and their treatment outcomes are worse than B-cell non-Hodgkin lymphoma. Furthermore, the optimal treatment regimen is still not established for these disease entities. Thus, cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) or CHOP-like regimens are still used as a primary treatment even though their efficacy is not satisfactory. This unmet need of T-cell lymphomas has required the development of more effective regimen. Thus, we incorporated an oral mTOR inhibitor, everolimus (RAD001, Afinitor®) into CHOP regimen to improve its efficacy. The mTOR complex is one of emerging targets in the lymphoma treatment because mTOR signal pathway is used by malignant cells to promote growth and survival. Previous studies demonstrated a single agent activity of mTOR inhibitor against relapsed or refractory lymphomas. Furthermore, several animal study results suggested that the mTOR inhibitor might enhance the effects of vincristine and cyclophosphamide when it was tried in combination with these drugs. Thus, we performed the phase I study to evaluate the feasibility and safety of everolimus plus CHOP chemotherapy for advanced stage, aggressive T-cell lymphomas. Methods: We enrolled patients with newly diagnosed T cell lymphomas including peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), ALK-negative anaplastic large cell lymphoma (ALCL) and cutaneous T-cell lymphoma (CTCL). Extranodal NK/T-cell lymphoma was excluded because it is resistant to anthracycline-based chemotherapy, and mycosis fungoides was also excluded due to its indolent nature. All patients were Ann Arbor stage III/IV and had adequate organ function. Patients received everolimus from day 1 to day 15 (once daily schedule of four dose levels, 2.5, 5, 7.5, and 10mg/dose) in addition to 750 mg/m2 cyclophosphamide, 50 mg/m2 doxorubicin, 1.4 mg/m2 vincristine on day 1 and 100 mg/day prednisolone on days 1 to 5. Six cycles of therapy administered every 21 days were planned. As a pharmacokinetic study, steady state trough concentrations of everolimus were measured at the end of cycle 1 and 2. All patients provided written informed consents and this trial was registered at www.ClinicalTrials.gov (NCT01198665). Results: Fifteen patients were enrolled between October 2010 and April 2011 including PTCL-NOS (n = 8), AITL (n = 4), ALCL (n = 1) and CTCL (n = 2). Ten patients presented as stage IV (66.7%) and the majority of patients showed serum LDH elevation (n = 13, 86.7%). Thus, the International Prognostic Index risk was dominantly high or high-intermediate (n = 9, 60.0%). There was no dose-limiting toxicity (DLT) at the level I (2.5mg/dose of everolimus) while one patient experienced hematologic DLT (grade IV thrombocytopenia) at the level II (5mg/dose). Thus, after patients were enrolled up to six at the level II, dose of everolimus was escalated to 7.5mg (level III). At the level III, two patients experienced DLT (grade IV thrombocytopenia and febrile neutropenia) among six patients enrolled. Therefore, the maximum tolerated dose for everolimus was determined as 5mg. In the evaluation of pharmacokinetic profile, there were no differences in the trough concentrations of everolimus between cycle 1 and 2 for all of these three dose groups. There was no dose-limiting non-hematologic toxicity in the all three dose levels. Although the main toxicity of everolimus was hematologic toxicity and it was overlapped with the toxicity of CHOP regimen, these hematologic toxicities were manageable. Among 15 patients, 14 patients responded to the treatment including 7 complete responses and 7 partial responses. However, five patients relapsed or progressed during follow-up. Conclusions: Everolimus can be safely combined with CHOP chemotherapy and constitutes an active regimen in advanced stage, aggressive T-cell lymphoma patients. The recommended dose for subsequent phase II study of everolimus plus CHOP is 5 mg/dose of everolimus once daily for 15 days as first-line treatment. Disclosures: No relevant conflicts of interest to declare.

Phase II Trial Of L-Asparaginase Plus Concurrent Chemoradiotherapy Followed By Midle (methotrexate, ifosfamide, etoposide, dexamethasone, and L-asparaginase) Chemotherapy For Patients With Newly Diagnosed Stage I/II Extranodal NK/T-Cell Lymphoma, Nasal Type

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3037-3037 ◽  
Author(s):  
Seok Jin Kim ◽  
Dok Hyun Yoon ◽  
Seong Hyun Jeong ◽  
Dong-Yeop Shin ◽  
Sung Hwa Bae ◽  
...  
Keyword(s):  
T Cell ◽  
Concurrent Chemoradiotherapy ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Hematologic Toxicity ◽  
Nasal Type ◽  
Nk T Cell ◽  
Grade 3

Abstract Background The treatment of localized extranodal NK/T-cell lymphoma (ENKTL), nasal type has shifted to non-anthracycline-based intensive chemotherapy with radiotherapy since the poor response of ENKTL to anthracycline due to the expression of a multidrug-resistant (MDR) p-glycoprotein was proven. We previously proposed concurrent chemoradiotherapy (CCRT) followed by chemotherapy which is not affected by MDR and reported a significant improvement of outcomes of localized ENKTL. Based on our accumulated data, we designed a new treatment protocol. First, we added tri-weekly administration of L-asparaginase to reduce the probability of systemic progression during CCRT. Second, we designed MIDLE (methotrexate, ifosfamide, etoposide, dexamethasone, and L-asparaginase) according to previous excellent outcomes of methotrexate-containing regimens such as SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide) and MLD (methotrexate, L-asparaginase, dexamethasone). Methods The treatment scheme of CCRT consisted of radiation 40 Gy and weekly administration of cisplatin 30 mg/m2 (total: 4 doses). During the CCRT, tri-weekly intravenous (IV) administration of 4,000 IU of Escherichia coli L-asparaginase was done. The chemotherapy, MIDLE (methotrexate 3g/m2 on day 1, etoposide 100mg/m2, Ifosfamide 1000mg/m2 on day 2-3, dexamethasone 40mg on day 1-4, and L-asparaginase 6000IU/m2 IV on day 4, 6, 8, 10) was repeated every 28 days up to 2 cycles. All patients provided informed written consents and this trial was registered at www.ClinicalTrials.gov(NCT01238159). Results Twenty-eight patients with stage IE/IIE ENKTL were enrolled, and the median age was 51 years (range, 30–77 years). 24 patients were male while only four patients were female. Twenty-two patients were stage IE and six were IIE. All patients completed CCRT, which resulted in 92.9% of overall response rate including 20 complete responses and 6 partial responses. One patient showed stable disease after CCRT whereas the other patient progressed. No grade 3 or 4 hematologic toxicity was found during CCRT. However, grade 3 non-hematologic toxicities included bilirubin elevation (n = 4), mucositis (n = 1), and nausea/vomiting (n = 6). After the completion of CCRT, 23 patients entered the MIDLE chemotherapy as five patients including one disease progression and four cases of withdrawal could not receive MIDLE. All patients achieved complete response after they completed the planned two cycles of MIDLE chemotherapy whereas two patients dropped out after their first cycle due to non-hematologic toxicity. The final complete response rate of patients enrolled was 92.9% (26/28). The major toxicity of MIDLE was grade 3/4 leucopenia, and the non-hematologic toxicity included mucositis and nausea/vomiting. The hepatic toxicity-associated with L-asparaginase was frequent. However, the majority of the hepatic toxicities were grade 1 or 2. With the median potential follow-up of 25 months (95% confidence interval: 19 – 31 months), four patients relapsed. Conclusion L-asparaginase plus concurrent chemoradiotherapy followed by MIDLE chemotherapy can be an effective treatment strategy with acceptable toxicity in stage I/II extranodal NK/T-Cell lymphoma, nasal type. Disclosures: Kwak: celgene: Research Funding.

The efficacy of PEG-Asp-argase-based chemotherapy for nasal-type extranodal NK/T-cell lymphoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19504-e19504
Author(s):  
Jing-Yun Wen ◽  
Mai Li ◽  
Xing Li ◽  
Qu Lin ◽  
Min Dong ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Cell Lymphoma ◽  
Complete Response ◽  
Invasive Disease ◽  
Bone Marrow Suppression ◽  
T Cell Lymphoma ◽  
Chop Regimen ◽  
Nasal Type ◽  
Nk T Cell

e19504 Background: Nasal-type extranodal NK/T-cell lymphoma (ENKL) is a highly invasive disease with quite poor prognosis.Pegaspargase (PEG-Asp) displays a similar anti-cancer mechanism as that of L-asparaginase (L-ASP), but exhibits lighter antigenicity. The aim of the present research was to evaluate efficacy and safty of PEG-Asp-based regimen in ENKL. Methods: Data were collected from 23 patients with histologically confirmed ENKL who were admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to March 2012. Each patient received PEG-Asp 2500 IU/m2/IM on day 1 of each 21-day chemo-cycle. Among them, 8 received combination chemotherapy with CHOP regimen, 11 with EPOCH, and 4 with a CHOP-like regimen (CHOP + bleomycin). The CHOP regimen consisted of cyclophosphamide 750mg/m2, IV (day 1), pirarubicin 40mg/m2, IV (day 1), vincristine 1.4 mg/m2, IV (day 1), and prednisone 100mg, oral (days 1- 5). The EPOCH regimen consisted of etoposide 50mg/m2, epidoxorubicin 12 mg/m2 and vincristine 0.4mg/m2 dissolved in 500mL saline and administered as a continuous IV drip for 24 hours on days 1- 4. Cyclophosphamide 750mg/m2, IV (day 5) and prednisone 60mg/m2, oral (days 1-5), were also administered. In the CHOP-like regimen, bleomycin 15mg was added on days 1-3. Stage I-II patients received local radiotherapy after the chemotherapy. Results: The patients received the PEG-Asp-based chemotherapy for 2-5 cycles (median, 4 cycles). Eleven (47.8%) achieved complete response (CR), and the overall response rate (ORR) was 82.6%. The median time to progression (TTP) was 5 months (range, 2-6 months) and the median OS was 16 months (range, 5-38 months). The 1-year and 2-year survival rate were 82.6% (19/23) and 56.5% (13/23) , respectively. A minor glutamic-pyruvic transaminase (GPT) elevation was observed in 3 patients (13.0%), slight decrease of albumin in 3 (13.0%), reduced fibrinogen level in 2 (8.7%), grade I-II WBC bone marrow suppression in 8 (34.8%), and grade III-IV WBC bone marrow suppression in 3 (13.0%). No allergic incidences were witnessed. Conclusions: Our results suggested PEG-Asp-based chemotherapy presented potential effects in treating nasal-type ENKL with acceptable side effects profile.

Peripheral T-cell lymphomas unspecified presenting in the skin: analysis of prognostic factors in a group of 82 patients

Blood ◽  
2003 ◽  
Vol 102 (6) ◽  
pp. 2213-2219 ◽  
Author(s):  
Marcel W. Bekkenk ◽  
Maarten H. Vermeer ◽  
Patty M. Jansen ◽  
Ariënne M. W. van Marion ◽  
Marijke R. Canninga-van Dijk ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Size ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Skin Lesions ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
T Cell Lymphomas ◽  
Nor Phenotype ◽  
Peripheral T Cell Lymphomas

Abstract In the present study the clinicopathologic and immunophenotypic features of 82 patients with a CD30– peripheral T-cell lymphoma, unspecified, presenting in the skin were evaluated. The purpose of this study was to find out whether subdivision of these lymphomas on the basis of cell size, phenotype, or presentation with only skin lesions is clinically relevant. The study group included 46 primary cutaneous CD30– large cell lymphomas and 17 small/medium-sized T-cell lymphomas as well as 17 peripheral T-cell lymphomas with both skin and extracutaneous disease at the time of diagnosis. Patients with primary cutaneous small- or medium-sized T-cell lymphomas had a significantly better prognosis (5-year-overall survival, 45%) than patients with primary cutaneous CD30– large T-cell lymphomas (12%) and patients presenting with concurrent extracutaneous disease (12%). The favorable prognosis in this group with primary cutaneous small- or medium-sized T-cell lymphomas was particularly found in patients presenting with localized skin lesions expressing a CD3+CD4+CD8– phenotype. In the primary cutaneous T-cell lymphoma (CTCL) group and in the concurrent group, neither extent of skin lesions nor phenotype had any effect on survival. Our results indicate that peripheral T-cell lymphomas, unspecified, presenting in the skin have an unfavorable prognosis, irrespective of the presence or absence of extracutaneous disease at the time of diagnosis, cell size, and expression of a CD4+ or CD8+ phenotype. The only exception was a group of primary cutaneous small- or medium-sized pleomorphic CTCLs with a CD3+CD4+CD8– phenotype and presenting with localized skin lesions.

Results From a Pivotal, Open-Label, Phase II Study of Romidepsin in Relapsed or Refractory Peripheral T-Cell Lymphoma After Prior Systemic Therapy

2012 ◽  
Vol 30 (6) ◽  
pp. 631-636 ◽  
Author(s):  
Bertrand Coiffier ◽  
Barbara Pro ◽  
H. Miles Prince ◽  
Francine Foss ◽  
Lubomir Sokol ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Systemic Therapy ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Prior Systemic Therapy

Purpose Romidepsin is a structurally unique, potent class 1 selective histone deacetylase inhibitor. The primary objective of this international, pivotal, single-arm, phase II trial was to confirm the efficacy of romidepsin in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Patients and Methods Patients who were refractory to at least one prior systemic therapy or for whom at least one prior systemic therapy failed received romidepsin at 14 mg/m2 as a 4-hour intravenous infusion on days 1, 8, and 15 every 28 days. The primary end point was the rate of complete response/unconfirmed complete response (CR/CRu) as assessed by an independent review committee. Results Of the 131 patients enrolled, 130 had histologically confirmed PTCL by central review. The median number of prior systemic therapies was two (range, one to eight). The objective response rate was 25% (33 of 130), including 15% (19 of 130) with CR/CRu. Patient characteristics, prior stem-cell transplantation, number or type of prior therapies, or response to last prior therapy did not have an impact on response rate. The median duration of response was 17 months, with the longest response ongoing at 34+ months. Of the 19 patients who achieved CR/CRu, 17 (89%) had not experienced disease progression at a median follow-up of 13.4 months. The most common grade ≥ 3 adverse events were thrombocytopenia (24%), neutropenia (20%), and infections (all types, 19%). Conclusion Single-agent romidepsin induced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across all major PTCL subtypes, regardless of the number or type of prior therapies. Results led to US Food and Drug Administration approval of romidepsin in this indication.

Results From a Prospective, Open-Label, Phase II Trial of Bendamustine in Refractory or Relapsed T-Cell Lymphomas: The BENTLY Trial

2013 ◽  
Vol 31 (1) ◽  
pp. 104-110 ◽  
Author(s):  
Gandhi Damaj ◽  
Rémy Gressin ◽  
Krimo Bouabdallah ◽  
Guillaume Cartron ◽  
Bachra Choufi ◽  
...  
Keyword(s):  
T Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Single Agent ◽  
T Cell Lymphoma ◽  
Open Label ◽  
Previous Response ◽  
Angioimmunoblastic Lymphadenopathy ◽  
Prior Chemotherapy ◽  
T Cell Lymphomas

Purpose To determine the efficacy and safety of bendamustine as a single agent in refractory or relapsed T-cell lymphomas. Patients and Methods Patients with histologically confirmed peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma who progressed after one or more lines of prior chemotherapy received bendamustine at 120 mg/m2 per day on days 1 through 2 every 3 weeks for six cycles. The primary end point was overall response rate (ORR). Secondary end points were duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results Of the 60 patients included, 27 (45%) were refractory to their last prior chemotherapy, and the median duration of the best previous response was 6.6 months. Histology was predominantly angioimmunoblastic lymphadenopathy and PTCL not otherwise specified. The disease was disseminated in the majority of patients (87%). The median number of previous lines of chemotherapy was one (range, one to three). Twenty patients (33%) received fewer than three cycles of bendamustine, mostly because of disease progression. In the intent-to-treat population, the ORR was 50%, including complete response in 17 patients (28%) and partial response in 13 patients (22%). Bendamustine showed consistent efficacy independent of major disease characteristics. The median values for DoR, PFS, and OS were 3.5, 3.6, and 6.2 months, respectively. The most frequent grade 3 to 4 adverse events were neutropenia (30%), thrombocytopenia (24%), and infections (20%). Conclusion Bendamustine showed an encouraging high response rate across the two major PTCL subtypes, independent of age and prior treatment, with acceptable toxicity in refractory or relapsed T-cell lymphoma.

The T-Cell Activation Markers CD30 and OX40/CD134 Are Expressed in Nonoverlapping Subsets of Peripheral T-Cell Lymphoma

Blood ◽  
1999 ◽  
Vol 93 (10) ◽  
pp. 3487-3493 ◽  
Author(s):  
Dan Jones ◽  
Christopher D.M. Fletcher ◽  
Karen Pulford ◽  
Aliakbar Shahsafaei ◽  
David M. Dorfman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Tnf Receptor ◽  
T Cell Lymphomas ◽  
Tumor Types ◽  
Tnf Receptor Family ◽  
Receptor Family

The tumor necrosis factor (TNF) receptor family includes several important markers of activation in T cells. We examined expression patterns of two T-cell-associated members of these receptors, namely CD30 and OX40/CD134, in 148 cases of T-cell lymphoma to identify possible objective immunohistochemical criteria for subclassification of these tumors. CD30 expression was characteristic of tumors with an anaplastic (46/47 cases [98%]) or large-cell (10/21 [48%]) morphology and was seen in only scattered cells in other tumor types. In contrast, large numbers of OX40/CD134+ tumors cells were typical of angioimmunoblastic lymphoma (15/16 [94%]), angiocentric lymphoma (4/4), a subset of large-cell lymphomas (10/21 [48%]), and lymphomas with a prominent histiocytic component (6/7 [86%]). Strong OX40/CD134 and CD30 coexpression was seen in only 4% of tumors, typically those with an anaplastic/Hodgkin’s-like appearance. OX40/CD134 expression was characteristic of tumors composed of activated CD4+ T cells and was not seen in small-cell T-cell lymphomas, lymphoblastic lymphomas, or other tumor types, including B-cell lymphomas or carcinomas. These results suggest that immunostaining for OX40/CD134 may be helpful in subclassification of peripheral T-cell lymphomas and that the patterns of TNF receptor family expression in these tumors may parallel those seen within nonneoplastic helper T-cell subsets.

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