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.

肠型恶性组织细胞增生症的再探讨——兼论肠型中线外周T细胞淋巴瘤

报道7例肠型恶性组织细胞增生症(简称IMH),其中4例为中小多形T细胞淋巴瘤,1例为Tr-ML,2例为组织细胞性淋巴瘤。4例中小多形T细胞淋巴瘤临床表现为腹痛、腹泻、反复便血伴发热,肠壁出血坏死形成溃疡甚至穿孔。病理形态:溃疡表面坏死形成肉芽样血管增生,异形淋巴细胞浸润而无明确肿块。经免疫组化证实LCA、UCHL_1呈阳性,电镜显示异形淋巴细胞多形性。作者建议将此特殊类型T细胞淋巴瘤称肠型中线外周T细胞淋巴瘤,以区别子肠道形成明确肿块的T、B和组织细胞恶性淋巴瘤,有助于治疗和预后的判断。

中线外周T细胞淋巴瘤

目的 总结 13例中线外周T细胞淋巴瘤 (MPTL)探讨其特征、治疗及预后。方法 用病理、免疫酶标方法对 13例MPTL进行确诊 ,采用CHOP方案化疗并观察其预后。结果 8例CR ,2例PR ,其中 2例CR后复发 ,另 3例NR死亡。结论CHOP方案对MPTL有效。血和尿 β2 MG升高和血清LDH升高应视为预后不良因素。

Truth lies below: A case report and literature review of typical appearing polyps yet with an atypical diagnosis

BACKGROUND Enteropathy associated T-cell lymphoma(EATL) is a rare form of peripheral Tcell lymphoma and makes up less than 5% of gastrointestinal lymphomas. EATL can be divided into type 1 which is associated with celiac disease, and monomorphic epitheliotropic intestinal T-cell lymphoma(MEITL), formally type 2, which is not associated with celiac disease.CASE SUMMARY We present a 60-year-old African American female, without celiac disease, who presented with abdominal pain, diarrhea, and 30 lb. weight loss over a 3 month period. She was subsequently diagnosed with EATL throughout her entire gastrointestinal tract. She is currently undergoing chemotherapy with EOCH(Etoposide, Oncovin, Cyclophosphamide, and Hydroxydaunorubicin). EATL is most common in the Asian and Hispanic population yet the incidence in African Americans is uncertain and emphasizes the rarity of this case. A literature review was included to further emphasize similarities and differences between our case and previously reported cases of MEITL.CONCLUSION The patient was diagnosed with EATL, immunochemical testing was not conclusive for MEITL however was suggestive of the disease.

左旋门冬酰胺酶治疗难治性中线外周T细胞淋巴瘤

目的 提高难治性中线外周T细胞淋巴瘤 (MPTCL)的疗效。方法 左旋门冬酰胺酶 (L ASP)组为 11例难治性MPTCL患者 ,给予L ASP为主的挽救化疗 (由L ASP、长春新碱和地塞米松组成 )。对照组为 10例难治性MPTCL患者 ,给予不含L ASP的联合化疗。观察比较两组的有效率和 2年生存率。结果 有效 (完全缓解加部分缓解 )率L ASP组为 6 3 .6 % ,对照组为 10 .0 % (P <0 .0 5 )。 2年生存率L ASP组为 45 .5 % ,对照组为 0 (P <0 .0 5 )。本组L ASP治疗的不良反应主要表现为白细胞减少、血清胆红素升高和高血糖症。结论 L ASP为主的挽救化疗可能提高难治性MPTCL的疗效和 2年生存率 ,值得进一步研究。