The combination of chidamide with the CHOEP regimen in previously untreated patients with peripheral T-cell lymphoma: a prospective, multicenter, single arm, phase 1b/2 study

Objective:To assess the efficacy and safety of the novel histone deacetylase inhibitor,chidamide,in combination with cyclophosphamide,doxorubicin,vincristine,etoposide,and prednisone(Chi-CHOEP)for untreated peripheral T-cell lymphoma(PTCL).Methods:A prospective,multicenter,single arm,phase 1 b/2 study was conducted.A total of 128 patients with untreated PTCL(18–70 years of age)were enrolled between March 2016 and November 2019,and treated with up to 6 cycles with the Chi-CHOEP regimen.In the phase 1 b study,3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximumtolerated dose and recommended phase 2 dose(RP2 D).The primary endpoint of the phase 2 study was 2-year progression-free survival(PFS).Results:Fifteen patients were enrolled in the phase 1 b study and the RP2 D for chidamide was determined to be 20 mg,twice a week.A total of 113 patients were treated at the RP2 D in the phase 2 study,and the overall response rate was 60.2%,with a complete response rate of 40.7%.At a median follow-up of 36 months,the median PFS was 10.7 months,with 1-,2-,and 3-year PFS rates of 49.9%,38.0%,and 32.8%,respectively.The Chi-CHOEP regimen was well-tolerated,with grade 3/4 neutropenia occurring in approximately two-thirds of the patients.No unexpected adverse events(AEs)were reported and the observed AEs were manageable.Conclusions:This large cohort phase 1 b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.

Acute liver failure as a rare initial manifestation of peripheral T-cell lymphoma

Acute liver failure(ALF) is an uncommon disease in the United States,affecting more than 2 000 people each year.Of all the various causes,malignant infiltration is one of the least well known and carries with it a high mortality.We describe a case of ALF as the presenting manifestation of peripheral T-cell lymphoma in an elderly woman.By reporting this case,we hope to increase early recognition of this disease process in order to potentially improve treatment outcomes.

Noncirrhotic portal hypertension due to peripheral T-cell lymphoma,not otherwise specified:A case report

BACKGROUND Peripheral T-cell lymphoma(PTCL),an aggressive and rare disease that belongs to a heterogeneous group of mature T-cell lymphomas,develops rapidly and has a poor prognosis.Early detection and treatment are essential to improve patient cure and survival rates.Here,we report a rare case of PTCL with clinical presentation of noncirrhotic portal hypertension,which provides a basis for early vigilance of lymphomas in the future.CASE SUMMARY A 65-year-old Chinese woman was admitted to our hospital because of abdominal distension for 3 months and pitting oedema of both lower limbs for 2 months.Physical examinations and associated auxiliary examinations showed the presence of hepatosplenomegaly,and her hepatic venous pressure gradient was 10 mmHg.Immunohistochemical analysis of the liver biopsy confirmed the diagnosis of PTCL.The patient underwent combination therapy with dexamethasone,VP-16,and chidamide.Unfortunately,after 41 days of chemotherapy,the patient died of multiple organ failure.CONCLUSION PCTL accompanied by noncirrhotic portal hypertension is rarely reported.This case report discusses the diagnosis of a patient according to the literature.

Secondary peripheral T-cell lymphoma and acute myeloid leukemia after Burkitt lymphoma treatment:A case report

BACKGROUND Multiple primary cancer refers to more than one synchronous or sequential cancer in the same individual.Multiple primary cancer always presents as solid cancer or acute myeloid leukemia(AML)secondary to lymphoma.Here,we report a rare case of secondary peripheral T-cell lymphoma and AML after Burkitt lymphoma treatment.CASE SUMMARY A 54-year-old female patient was admitted to our hospital complaining of edema on her left lower limb.Physical examination revealed multiple superficial lymphadenectasis on her neck and pelvis.Color ultrasonography examination showed multiple uterine fibroids and a solid mass at the lower left side of the abdomen.Pathological biopsy revealed Burkitt lymphoma.After three hyper-CVAD(A+B)regimens,she achieved complete remission.Two years later,lymphadenectasis reoccurred.A relevant biopsy confirmed the diagnosis of peripheral T-cell lymphoma,which was accompanied by gastrointestinal invasion and hemocytopenia.Meanwhile,bone marrow examination revealed AML.On the second day of scheduled treatment,she developed gastrointestinal bleeding,peptic ulcers,and hemorrhagic shock and was critically ill.She was then discharged from the hospital due to financial concerns.CONCLUSION This is the first report of secondary peripheral T-cell lymphoma and AML after Burkitt lymphoma treatment with heterochronous and synchronal multiple primary cancers.

Therapeutic Efficacy of L-asparaginase in the Treatment of Refractory Midfacial Peripheral T-Cell Non-Hodgkin’s Lymphoma

Objective: To improve the efficacy of refractory midfacial peripheral T-cell non-Hodgkin’s lymphoma (MPTC-NHL) with L-asparaginase (L-ASP) based salvage chemotherapy. Methods: 21 patients with refractory MPTC-NHL were analyzed. 11patients (L-ASP group) received L-asparaginase based salvage chemotherapy consisting of L-asparaginase, vincristine and dexame-thosone. 10 patients (control group) received salvage combination chemotherapy without L-asparaginase. Results: Complete remission rates were 45.6% for L-ASP group and 0.0% for control group (p<0.05). Overall response rates (CR+PR) were 63.6% for L-ASP group and 10.0% for control group, respectively (p<0.05). 2-year survival rates were 45.5% for L-ASP group and 0.0% for control group (p<0.05). The major adverse effects of L-ASP were leukopenia, elevation of serum bilirubin and hyperglycemia. Conclusion: The preliminary clinical study shows that the L-ASP based salvage chemotherapy may improve the response rate and 2-year survival rate of the patients with refractory MPTC-NHL. It is necessary to continue the study further.

Primary sino-orbital peripheral T-cell lymphoma presenting as unilateral periorbital swelling: a case report

Dear Editor,My name is Ahmad Al Omari and I am currently working as an otorhinolaryngology assistant professor at Jordan University of Science and Technology. I am writing this letter to present a case of a primary sino-orbital peripheral T-cell

Peripheral T-Cell Lymphoma of Cervical Spine

Peripheral T-cell lymphoma is a rather uncommon non-Hodgkin’s lymphoma with the initial manifestation of spinal cord compression. Herein, we reported a 74-year-old woman with sustained neck pain radiating into the right shoulder and arm and weakness of the right upper extremity. A mass that had invaded the C5 and C6 vertebral bodies, causing a kyphotic curvature and compressing the spinal cord, was discovered with magnetic resonance imaging. The patient then underwent anterior corpectomy at C5 and C6, and reconstruction with a titanic rod and bone cement. The pathology confirmed a diagnosis of peripheral T-cell lymphoma after serial H & E and immunohistochemical staining. She recovered well from her profound neurological deficit. Both chemotherapy and radiotherapy were used postoperatively. Surgical intervention is indicated in these cases to decompress the cord, remove the majority of the tumor mass, stabilize the spine and obtain tissue for pathological diagnosis.

Treatment of Peripheral T-cell Lymphoma by Chidamide and Literature Analysis

[Objectives] To analyze the dosage,curative effect,and adverse effect of Chidamide in treating peripheral T-cell lymphoma( PTCL). [Methods]A case of treating peripheral T-cell lymphoma by Chidamide was reported,including the treatment process,dosage,curative effect,and adverse effect. Literature review was made and searched in Wanfang Digital Database,China National Knowledge Infrastructure( CNKI),and Pubmed database,using the key word chidamide in Chinese and English separately. Disease and case number of patients,Chidamide observation indicator,curative effect,and adverse effects were recorded in detail. The search was carried out as of September,2016. [Results] It searched 3 articles related to clinical application and 111 cases of patients. [Conclusions] Chidamide has excellent curative effect in treating peripheral T-cell lymphoma and is suitable for clinical application.

Chidamide plus prednisone,cyclophosphamide,and thalidomide for relapsed or refractory peripheral T-cell lymphoma:A multicenter phase II trial

Background:Although the treatment of peripheral T-cell lymphoma(PTCL)has undergone advancements during the past several years,the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory(R/R)patients.This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone,cyclophosphamide,and thalidomide(CPCT)for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons.Methods:We conducted a multicenter phase II clinical trial in which we combined chidamide(30 mg twice weekly)with prednisone(20 mg daily after breakfast),cyclophosphamide(50 mg daily after lunch),and thalidomide(100 mg daily at bedtime)(the CPCT regimen)for a total of fewer than 12 cycles as an induction-combined treatment period,and then applied chidamide as single-drug maintenance.Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers.Our primary objective was to assess the overall response rate(ORR)after the treatment with CPCT.Results:Of the 45 enrolled patients,the optimal ORR and complete response(CR)/CR unconfirmed(CRu)were 71.1%(32/45)and 28.9%(13/45),respectively,and after a median follow-up period of 56 months,the median progression-free survival(PFS)and overall survival(OS)were 8.5 months and 17.2 months,respectively.The five-year PFS and OS rates were 21.2%(95%confidence interval[CI],7.9-34.5%)and 43.8%(95%CI,28.3-59.3%),respectively.The most common adverse event was neutropenia(20/45,44.4%),but we observed no treatment-related death.Conclusion:The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons.Trial Registration:ClinicalTrials.gov,NCT02879526.

Peripheral T-cell Lymphomas： Updates in AIIogeneic Hematopoietic Stem Cell Transplantation

Objective： Peripheral T-cell lymphomas （PTCLs） confer dismal prognosis and no consensus has been established on the role of allogeneic hematopoietic stem cell transplantation （allo-HSCT） due to its rarity and heterogeneity. The purpose was to review key points ofallo-HSCT for PTCLs, including indication, times of transplantation, conditioning regimen, graft versus host disease prophylaxis, and treatment of relapse.Data Sources： A comprehensive search in PubMed and Cochrane up to February 28, 2018, with the keywords ＂Peripheral＂, ＂T＂, ＂Lymphoma＂, and ＂Transplantation＂ was done. Study Selection： Relevant articles including HSCT for PTCLs were carefully reviewed. Results： Promising data have been reported from advances in transplant technology and more and more PTCLs patients with poor prognosis could benefit from allo-HSCT. Conclusion： Allo-HSCT is a useful choice for patients with refractory/relapsed PTCLs or high-risk new diagnosed PTCLs.

A multicenter retrospective study on the real-world outcomes of autologous vs. allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphoma in China

Background:There were few studies on real-world data about autologous hematopoietic stem cell transplantation(auto-HSCT)or allogeneic HSCT(allo-HSCT)in peripheral T-cell lymphoma(PTCL).This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.Methods:From July 2007 to June 2017,a total of 128 patients who received auto-HSCT(n=72)or allo-HSCT(n=56)at eight medical centers across China were included in this study.We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.Results:Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease(95%vs.82%,P=0.027),bone marrow involvement(42%vs.15%,P=0.001),chemotherapy-resistant disease(41%vs.8%,P=0.001),and progression disease(32%vs.4%,P<0.001)at transplantation than those receiving auto-HSCT.With a median follow-up of 30(2–143)months,3-year overall survival(OS)and progression-free survival(PFS)in the auto-HSCT group were 70%(48/63)and 59%(42/63),respectively.Three-year OS and PFS for allo-HSCT recipients were 46%(27/54)and 44%(29/54),respectively.There was no difference in relapse rate(34%[17/63]in auto-HSCT vs.29%[15/54]in allo-HSCT,P=0.840).Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63)compared with 27%(14/54)for allo-HSCT recipients(P=0.004).Subanalyses showed that patients with lower prognostic index scores for PTCL(PIT)who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores(3-year OS:85%vs.40%,P=0.003).Patients with complete remission(CR)undergoing auto-HSCT had better survival(3-year OS:88%vs.48%in allo-HSCT,P=0.008).For patients beyond CR,the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group(3-year OS:51%vs.46%,P=0.300).Conclusions:Our study provided real-world data about auto-HSCT and allo-HSCT in China.Auto-HSCT seemed to be associated with better survival for patients in good condition(lower PIT score and/or better disease control).For patients possessing unfavorable characteristics,the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.

The peripheral T-cell lymphoma:can we pivot from the chemotherapy-predicated paradigm?

Peripheral T-cell lymphomas(PTCL)are uncommon and aggressive diseases that are difficult to study.Combination chemotherapy such as cyclophosphamide,doxorubicin,vincristine,and prednisone has been the mainstay of treatment for almost 30 years,but outcomes remain poor.The development of new targeted therapies is changing the landscape of how we treat patients with these difficult diseases.For instance,the addition of brentuximab vedotin to combination chemotherapy enhanced the outcomes in patients with CD30-positive anaplastic large cell lymphomas,but there is still a need for better therapies in the other numerous subtypes.Here we discuss the data for the existing treatment paradigm of PTCL as well as the merits of shifting toward a chemotherapy-free approach.

Hyper-CVAD chemotherapy or autologous stem cell transplantation in patients with peripheral T cell lymphomas： a single centre report

Background Peripheral T-cell lymphoma （PTCL） is generally characterized by poor prognosis after conventional chemotherapy. The place for high-dose chemotherapy and autologous stem cell transplantation （ASCT） in these patients is still not clear. In this study, we presented the outcomes of PTCL patients followed these treatments in our centre. Methods We retrospectively analyzed the outcomes of 39 patients with PTCL received the two treatments between 1999 and 2010. Results The 3-year overall survival （OS） of 61.9% and 3-year progression free survival （PFS） of 35.7% were observed in the 39 patient. Twenty-one patients received Hyper-CVAD chemotherapy with 3-year OS of 46.2% and 3-year PFS of 27.9%. Eighteen patients received ASCT with 3-year OS of 70.3% and 3-year PFS of 44.2%. Further analysis revealed that patients with elevated lactate dehydrogenase, at least 2 international prognostic index （IPI） points, and extranodal involvement had a poorer outcome compared with the control group. Conclusion These findings might suggest that Hyper-CVAD chemotherapy and ASCT could offer a durable survival benefit for patients with aggressive PTCL.

CTOP与CHOP方案治疗外周T细胞淋巴瘤的疗效比较

目的:比较含吡喃阿霉素(THP)的CTOP方案与含阿霉素(ADM)的CHOP方案治疗外周T细胞性非霍奇金氏淋巴瘤-非特异性(PTCL-U)的疗效和不良反应。方法:采用两种方案治疗PTCL-U患者共130例,THP组49例,ADM组81例。结果:两组患者临床特征指标相似(P>0.05)。可评价疗效129例,两组有效率分别为71.6%和72.8%,CR率分别为43.2%和39.5%(P>0.05)。骨髓抑制、胃肠道反应、脱发为主要不良反应。Ⅲ～Ⅳ度白细胞降低、血小板和血红蛋白降低发生率两组无明显差异;脱发ADM组高于THP组(31.1%:14.0%,P<0.001);ADM组心脏毒性稍高于THP组(11.1%%:6.1%,P=0.522)。中位随访24个月(1～88个月),两组预计5年生存率分别为22.0%和42.2%(P<0.01)。结论:采用含THP的CTOP方案治疗PTCL-U疗效较好,毒性较低,远期生存率较高,值得临床进一步研究。

肠道复合性弥漫性大B细胞淋巴瘤及周围T细胞淋巴瘤临床病理观察

目的探讨罕见的肠道复合性淋巴瘤的临床病理特征。方法采用形态学、免疫组化及分子遗传学方法对1例肠道复合性弥漫性大B细胞淋巴瘤及周围T细胞淋巴瘤进行临床病理分析并复习文献。结果本例肠道复合性B与T细胞淋巴瘤在形态上有弥漫性大B细胞淋巴瘤和非特殊性周围T细胞淋巴瘤的两种区域,免疫组化CD20和CD3(+),分子遗传学上同时有IgH和TCR基因重排。结论肠道复合性淋巴瘤罕见,诊断需结合形态、免疫表型和分子遗传学特征。

不一致性淋巴瘤临床病理观察

目的探讨不一致性淋巴瘤的临床病理特征。方法采用形态学观察、免疫组化及分子病理学方法,对1例不一致性颈部淋巴结弥漫大B细胞淋巴瘤和鼻咽非特异性外周T细胞淋巴瘤进行临床病理分析,并复习文献。结果患者以鼻咽部肿物为首发症状,第1次鼻咽肿物活检诊断为非霍奇金淋巴瘤,T细胞性;之后进行颈部淋巴结活检,诊断为弥漫大B细胞淋巴瘤。进行了8个疗程的R-CHOP方案化疗后患者病情进展,重新取鼻咽肿物活检,诊断为非特异性外周T细胞淋巴瘤。最终诊断为同时发生的不一致性淋巴瘤。结论不一致性B细胞和T细胞淋巴瘤非常罕见,从每一个病变部位取活检有助于避免漏诊,从而选择正确的治疗方案。

CHOP及高强度方案EPOCH、HyperCVAD、硼替佐米联合化疗治疗外周T细胞淋巴瘤-非特指型的临床效果及预后因素分析

目的探讨不同化疗方案对外周T细胞淋巴瘤-非特指型（PTCL-NOS）患者的近期临床疗效及预后因素。方法回顾性分析安徽省肿瘤医院2009年1月~2012年12月收治的45例PTCL-NOS患者的临床资料。根据患者肿瘤负荷情况、体能状况评分（ECOG）、疾病临床分期情况,采用CHOP及高强度方案[EPOCH、HyperCVAD（A、B方案）及硼替佐米联合化疗]治疗,评价治疗效果及分析预后因素。结果 45例PTCL-NOS患者经治疗后10例完全缓解（22.2%）,25例部分缓解（55.6%）,总有效率为77.8%,第1、2、3年的总生存率分别为84.4%、60.0%、33.3%。45例患者中Ki-67表达〉80%的患者2年生存率小于Ki-67表达≤80%的患者2年生存率,差异有统计学意义（P〈0.05）。中位生存时间25.5个月,单因素分析β2微球蛋白水平、外周T细胞淋巴瘤预后指数（PIT）、骨髓侵犯、临床分期、乳酸脱氢酶水平、体能状况评分与预后生存有关。PIT是PTCL-NOS患者的预后的影响因素,临床分期是影响患者近期疗效的重要因素。结论 PTCL-NOS目前尚无统一的标准方案,对常用的一线方案近期疗效较好,但多数患者很快出现复发、耐药、疾病进展。对于年龄较轻,体能状况评分较好、肿瘤负荷较大的患者建议采用高强度方案组方案和新药的运用争取尽早达到CR,延长总生存时间。

EPOCH方案和CHOP方案一线治疗非特殊性外周T细胞淋巴瘤回顾性临床对照研究

目的:比较EPOCH方案和CHOP方案一线治疗非特殊性外周T细胞淋巴瘤(PTCL-U)的疗效及不良反应。方法:A组:2008年1月至2010年4月,24例经病理确诊的PTCL-U患者,采用EPOCH方案化疗:足叶已甙50mg/(m2·d),长春新碱0.4mg/(m2·d),表阿霉素15mg/(m2·d),上述三种药物持续静脉滴注96h,环磷酰胺750mg/m2,静脉滴注,d5;强的松60mg/(m2·d),口服,d1-5。每3周为1周期。B组:2005年1月至2007年4月PTCL-U患者35例,采用CHOP方案化疗:环磷酰胺750mg/m2,静脉滴注,d1,表阿霉素75mg/m2,静脉滴注,d1,长春新碱1.4mg/m2,静脉滴注,d1,强的松60mg/(m2·d),口服,d1-5,每3周为1周期。对两组的近期疗效、疾病进展时间、不良反应进行分析比较。结果:A组和B组的完全缓解效率分别为66.7%(16/24)和40.0%(14/35),有显著性差异(P=0.0441),有效率分别为79.2%(19/24)和65.7%(23/35),无显著差异(P=0.2624)。A组和B组的中位疾病进展时间12.0月(1-27月)、10月(1-28月)(P=0.2045)。主要不良反应白细胞减少、神经毒性、脱发、心脏毒性等指标均无显著性差异(P>0.05)。轻度口腔炎的发生率A组高于B组:24.8%∶13%(P<0.05)。结论:一线治疗PTCL-U,EPOCH方案近期疗效较CHOP方案具有一定的优势,不良反应相近,耐受性好。

外周T细胞淋巴瘤的研究进展

外周T细胞淋巴瘤(peripheral T-cell lymphomas,PTCL)为异质性血液学肿瘤组,起源于成熟的T细胞,约占全部成人非霍奇金淋巴瘤(NHLs)15%。现今的WHO分类包括9种临床病理学外周T细胞NHLs,其中非特异变异型(PTCL-U)最常见。在诊断时常处于进展期,最常呈侵袭性临床经过,需立即治疗。为更好理解其生物学特性和探索新的治疗方法,本文综述PTCLs(特别着重PTCL-U亚组)的病理学、临床特征和目前的治疗策略。

外周T细胞淋巴瘤-非特指型2例并文献复习

目的报告2例外周T细胞淋巴瘤-非特指型(peripheral T lymphocytes unspecified,PTCL-U)患者的临床、实验室指标及诊治和预后,以提高对该类疾病的认识。方法对2例PTCL-U患者的病例资料进行分析,并结合国内外相关文献进行复习。结果 PTCL-U临床特点为发热、淋巴结肿大,易侵犯肝、脾、骨髓、皮肤等结外部位和并发噬血细胞综合征。病情进展快,对化疗不敏感,2例均死亡。结论 PTCL-U恶性程度高,进展快,侵袭性强,预后极差,需提高对该病的识别,以期早期诊断和积极治疗。