Consolidation therapy with autologous stem cell transplantation after remission of induction chemotherapy prolongs the survival of patients with peripheral T-cell lymphoma.

Background: There was little evidence of autologous stem cell transplantation (ASCT) as consolidation therapy after remission of induction for patients with Peripheral T-cell lymphoma (PTCL). In this study, we conducted a comparative analysis of real-world survival outcomes between consolidation therapy and observation in patients with PTCL. Methods: A total of 92 patients with peripheral T-cell lymphoma (PTCL) who were admitted to the Department of Hematology, Huadong Hospital Affiliated with Fudan University from January 2013 to April 2019 were divided into two groups based on whether they were treated with high-dose therapy (HDT) followed by autologous hematopoietic stem cell transplantation (ASCT): ASCT as consolidation therapy (n=30) and observation (n=62). Clinical characteristics, treatment patterns, and survival outcomes were analyzed between the two groups. Univariate and Cox multivariate regression analyses were also performed to detect prognostic factors of survival. Results: With a median follow-up time of 41 months, the median overall survival (OS) of peripheral T-cell lymphoma patients treated with ASCT was not reached; the median progression-free survival (PFS) was 77.0 months, which was much higher than that of patients without ASCT (p<0.003 for OS, p=0.015 for PFS). Subgroup analysis found that patients with high risks benefited more from ASCT. Combination with hemophagocytic lymphohistiocytosis (HLH) (p<0.001), clinical stage more than III (p=0.014), IPI score above 3 (p=0.049), and bone marrow involvement (p=0.010) were the independent prognostic factors significantly associated with worse OS and PFS. Additionally, pegylated liposomal doxorubicin (PLD)-containing chemotherapy regimen could bring a higher overall response rate (ORR) and prolong the survival of patients with PTCL who underwent ASCT. Conclusion: ASCT may improve the long-term survival of patients with PTCL as consolidation therapy after achieving complete or partial remission of induction treatment, particularly for those with high risks. The chemotherapy regimen containing pegylated liposomal doxorubicin may induce deeper remission than traditional doxorubicin in PTCL. It is crucial to identify the specific groups most likely to benefit from upfront ASCT.

Role of upfront autologous transplant for peripheral T-cell lymphoma patients achieving a complete remission with first-line therapy: a systematic review and meta-analysis.

There is currently no consensus on the role of upfront autologous transplantation (ASCT) for patients with peripheral T-cell lymphomas (PTCL), especially in patients achieving first complete remission (CR1) following chemotherapy, and data in the literature is conflicting. A systematic review and meta-analysis was performed to address this question. We searched key databases from January 2000 to February 2022. Six prospective and eleven retrospective studies were included among 2959 unique records. Median follow up in these studies ranged from 22 to 94 months. There was a trend towards benefit in PFS (HR = 0.80, 95% CI 0.62-1.05, p = 0.11) and OS (HR = 0.79, 95% CI 0.57-1.09, p = 0.15) in the ASCT compared to chemotherapy only group. Importantly, in transplant eligible patients in CR1, a significant benefit was demonstrated in both OS (HR = 0.59, 95% CI 0.36-0.95, p = 0.03) and PFS (HR = 0.61, 95% CI 0.47-0.81, p = 0.0004) in the ASCT group. Amongst the nodal PTCL subgroups, ASCT showed a significant PFS benefit for the AITL subgroup (HR = 0.43, 95% CI 0.20-0.94, p < 0.03) but not PTCL-NOS or ALK-ve ALCL subgroups. Our findings support upfront ASCT for transplant eligible PTCL patients achieving CR1 post chemotherapy. In particular, patients with AITL exhibited a significantly better PFS after upfront ASCT.

Hematopoietic stem cell transplantation for pediatric patients with non-anaplastic peripheral T-cell lymphoma. An EBMT pediatric diseases working party study.

Peripheral T-cell lymphomas (PTCL) other than anaplastic large-cell lymphoma are rare in children, and the role of hematopoietic stem cell transplantation (HSCT) has not been clarified yet. In a retrospective analysis of registry-data of the European Society for Blood and Marrow Transplantation we analyzed 55 patients aged < 18 years who received allogeneic (N = 46) or autologous (N = 9) HSCT for PTCL. Median age at HSCT was 13.9 years; 33 patients (60%) were in first remission, and 6 (19%) in progression at HSCT. Conditioning was myeloablative in 87% of the allogeneic HSCTs and in 27 (58.7%) based on total body irradiation. After allogeneic HSCT the 5-year overall- and progression-free survival was 58.9% (95% CI 42.7-71.9) and 52.6% (95% CI 36.8-66.1), respectively. 5-year relapse incidence was 27.6% (95% CI 15.1-41.6), the non-relapse mortality rate was 19.8% (95% CI 9.7-32.6). Five of the six patients with progression at HSCT died. Seven of nine patients after autologous HSCT were alive and disease-free at last follow-up. Our data suggest a role of allogeneic HSCT in consolidation-treatment of patients with high-risk disease, who reach at least partial remission after primary- or relapse-therapy, whereas patients with therapy-refractory or progressive disease prior to transplantation do not profit from HSCT.

Romidepsin Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Versus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Final Analysis of the Ro-CHOP Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The primary analysis of the Ro-CHOP phase III randomized controlled trial (ClinicalTrials.gov identifier: NCT01796002) established that romidepsin (Ro) plus cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) did not yield an increased efficacy compared with CHOP alone as first-line treatment of peripheral T-cell lymphoma. We report the planned final analysis 5 years after the last patient enrolled. With a median follow-up of 6 years, median progression-free survival (PFS) was 12.0 months compared with 10.2 months (hazard ratio [HR], 0.79 [95% CI, 0.62 to 1.005]; P = .054), while median overall survival was 62.2 months (35.7-86.6 months) and 43.8 months (30.1-70.2 months; HR, 0.88 [95% CI, 0.68 to 1.14]; P = .324) in the Ro-CHOP and CHOP arms, respectively. In an exploratory analysis, the median PFS in the centrally reviewed follicular helper T-cell lymphoma subgroup was significantly longer in the Ro-CHOP arm (19.5 v 10.6 months, HR, 0.703 [95% CI, 0.502 to 0.985]; P = .039). Second-line treatments were given to 251 patients with a median PFS2 and OS2 after relapse or progression of 3.3 months and 11.5 months, respectively. Within the limits of highly heterogeneous second-line treatments, no specific regimen seemed to provide superior disease control. However, a potential benefit was observed with brentuximab vedotin in association with chemotherapy even after excluding anaplastic large-cell lymphoma subtype or after adjusting for histology and international prognostic index in a multivariate model (HR for PFS, 0.431 [95% CI, 0.238 to 0.779]; P = .005).

Prognostic impact of pretreatment cell-free DNA concentration in newly diagnosed peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) have a poor prognosis and, to date, there are no reliable predictive biomarkers of response. In this work we explored the prognostic impact of cell-free DNA (cfDNA) concentration in 75 newly diagnosed patients enrolled in a prospective multicenter study. Pre-treatment cfDNA was strongly associated with clinical risk factors and was identified as a superior predictor for shorter progression-free survival in multivariable analysis, outweighing canonical risk parameters. Furthermore, we identified a cfDNA value above which survival worsens. In conclusion, pre-treatment cfDNA concentration represents an easily usable predictive biomarker that is highly associated with survival of PTCL patients.

Romidepsin Plus CHOP Versus CHOP in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Results of the Ro-CHOP Phase III Study (Conducted by LYSA).

PURPOSE: Romidepsin, a histone deacetylase inhibitor, has demonstrated activity in relapsed or refractory peripheral T-cell lymphoma (PTCL) as a single agent. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy is widely used as first-line treatment of PTCL; however, it has limited efficacy. Results from a phase Ib and II study showed the feasibility of combining romidepsin with CHOP (Ro-CHOP). METHODS: This study is a randomized phase III study of Ro-CHOP versus CHOP in adult patients with previously untreated PTCL. All patients received CHOP in 3-week cycles for six cycles. Romidepsin, 12 mg/m2, was administered intravenously over a 4-hour period on days 1 and 8 of each 3-week cycle for six cycles. The primary end point was progression-free survival (PFS) according to International Working Group 1999 criteria. RESULTS: Between January 2013 and December 2017, 421 patients were enrolled (Ro-CHOP, n = 211; CHOP, n = 210). The median PFS for Ro-CHOP versus CHOP was 12.0 months (95% CI, 9.0 to 25.8) versus 10.2 months (95% CI, 7.4 to 13.2) with a hazard ratio of 0.81 (P = .096). In the Ro-CHOP versus CHOP arms, the median overall survival was 51.8 versus 42.9 months and the objective response rate was 63% versus 60% with complete response plus unconfirmed complete response rates of 41% versus 37% (P > .1 in all comparisons), respectively. Grade 3 or 4 treatment-emergent adverse events occurring in ≥ 30% of patients in the Ro-CHOP arm included thrombocytopenia (50% v 10% in the Ro-CHOP v CHOP arms, respectively), neutropenia (49% v 33%), anemia (47% v 17%), and leukopenia (32% v 20%). CONCLUSION: The addition of romidepsin to CHOP did not improve PFS, response rates, nor overall survival and increased the frequency for grade ≥ 3 treatment-emergent adverse events. Ro-CHOP does not represent a significant advance in the standard of care for patients with previously untreated PTCL.

Expression of telomerase reverse transcriptase in peripheral T-cell lymphoma.

Telomere length is maintained by the activation of telomerase, which causes continuous cell division and proliferation in many carcinomas. A catalytic reverse transcriptase protein (TERT) encoded by the TERT gene plays a critical role in the activation of telomerase. We performed a molecular and pathological analysis of the TERT against three different peripheral T-cell lymphoma (PTCL) subtypes: PTCL, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and adult T-cell leukemia/lymphoma (ATLL). Immunohistochemical analysis demonstrated TERT expression in 31% of AITL, 11% of PTCL-NOS, and 5% of ATLL. Among them, AITL frequently showed high TERT expression with statistical significance. TERT promoter mutation analysis and genomic copy number evaluation were performed. TERT promoter mutation was observed in two cases of PTCL-NOS (2/40) and not in other PTCLs. Genome copy number amplification was detected in 33% of PTCL-NOS, 33% of AITL, and 50% of ATLL cases. We evaluated the relationship between the analyzed TERT genomic abnormalities and protein expression; however, no apparent relationship was observed. Furthermore, immunostaining showed TERT expression in the PTCL cytoplasm, suggesting the existence of mechanisms other than the maintenance of telomere length. Statistical analysis of the effect of TERT expression on the prognosis in PTCL cases revealed that TERT expression tended to have a poor prognosis in PTCL-NOS. Since TERT expression was not an independent factor in multivariate analysis, further research will be needed to clarify the poor prognosis of PTCL-NOS in TERT expression.

How to Sequence Therapies in Peripheral T Cell Lymphoma.

OPINION STATEMENT: Peripheral T cell lymphoma (PTCL) represents a heterogeneous group of rare lymphoproliferative disorders. Historically, there has been a lack of pathobiological understanding of PTCL. With the exception of ALK-positive anaplastic large cell lymphoma, patients with PTCL have less favorable outcomes, with most patients relapsing shortly after conventional anthracycline-containing multi-agent chemotherapy. The standard management approach for PTCL involves induction therapy followed by autologous stem cell transplantation. Patients with relapsed/refractory PTCL have dismal outcomes and limited treatment options despite the available novel agents, therefore remaining a critical unmet need. By virtue of advancement in cancer biology over the recent years, the treatment landscape of PTCL has gradually evolved from conventional chemotherapy based on solely morphological diagnosis toward more individualized therapies by integrating molecular attributes of PTCL to the traditional treatment paradigm. We are at the edge of witnessing a paradigm shift in PTCL management.

What's new in peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) are a rare, heterogeneous group of hematological malignancies with extremely poor prognosis for almost all subtypes. The diverse clinicopathological features of PTCLs make accurate diagnosis, prognosis, and choice of optimal treatment strategies difficult. Moreover, the best therapeutic algorithms are still under debate due to the extrapolated approaches developed for B-cell lymphomas and to the absence of few treatment protocol specifically developed for PTCLs. Some advances have been made with CD30 monoclonal antibody, mainly for anaplastic large-cell lymphomas, with improvements in progression-free survival and overall survival. Several new drugs are under evaluation in clinical trials, although not all the results are as encouraging as expected. In this review, we briefly present the most updated information on diagnosis, prognostication, and treatment strategies in PTCLs.

The value of complete remission according to positron emission tomography prior to autologous stem cell transplantation in lymphoma: a population-based study showing improved outcome.

BACKGROUND: Chimeric antigen-receptor T-cell and bispecific antibody therapies will likely necessitate a reconsideration of the role of autologous stem-cell transplantation (ASCT) in lymphoma. Patients who are likely to profit from ASCT need to be better identified. METHODS: Here, we investigated the value of positron emission tomography/computerized tomography (PET/CT) before ASCT. All 521 patients transplanted for lymphoma 1994-2019 at Karolinska (497 conditioned with BEAM) were included. RESULTS: Outcome improved over three calendar periods 1994-2004, 2005-2014, 2015-2019 (2-year overall survival [OS]: 66, 73, 83%; P = 0.018). Non-relapse mortality (NRM) at 100 days over the three periods were 9.8, 3.9, 2.9%, respectively. The OS improvement between 1994 and 2004 and 2005-2014 was due to lower NRM (P = 0.027), but the large OS advance from 2015 was not accompanied by a significant reduction in NRM (P = 0.6). The fraction of PET/CT as pre-ASCT assessment also increased over time: 1994-2004, 2%; 2005-2014, 24%; 2015-2019, 60% (P < 0.00005). Complete responses (PET/CT-CR) were observed in 77% and metabolically active partial responses (PET/CT-PR) in 23%. PET/CT-CR was a predictor for survival in the entire population (P = 0.0003), also in the subpopulations of aggressive B-cell (P = 0.004) and peripheral T-cell (P = 0.024) lymphomas. Two-year OS and progression-free survival (OS/PFS) for patients in PET/CT-CR were in relapsed/refractory aggressive B-cell lymphoma 87%/75% and peripheral T-cell lymphoma 91%/78%. The corresponding figures in PET/CT-PR were 43%/44 and 33%/33%. Patients with solitary PET/CT-positive lesions showed acceptable outcome with ASCT followed by local irradiation (2-year OS/PFS 80%/60%). CT was less discriminative: 2-year OS/PFS: CT-CR, 76%/66%; CT-PR, 62%/51%. Outcome was inferior after BEAC compared with BEAM conditioning. CONCLUSIONS: We conclude that the improved outcome reflects better, PET/CT-informed, identification of patients who should proceed to ASCT. The excellent survival of patients in PET/CT-CR indicates that ASCT should remain part of standard therapy for lymphoma.

Conditional survival and hazards of death for peripheral T-cell lymphomas.

Typically, peripheral T-cell lymphoma (PTCLs) prognosis is estimated using overall survival before treatment. However, these estimates cannot show how prognosis evolves with the changing hazard rate over time. Patients (n = 650) with newly diagnosed PTCLs were enrolled retrospectively. After a median follow-up of 5.4 years, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) and NK/T cell lymphoma had initially lower 3-year conditional overall survival (COS3; i.e., the 3-year conditional overall survival was defined as the probability of surviving an additional 3 years) and higher hazards of death (26-44.3%). However, after 2 years, the COS3 increased and the death risk decreased over time, whereas anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma constantly had a lower risk over time (0-19.5%). For patients with complete remission after initial treatment, prognosis varied by histological subtypes, with PTCL, NOS having a negative impact. Our data suggested that the risk stratification using the International Prognostic Index might not accurately predict the COS3 for survivors of PTCLs. The COS3 provided time-dependent prognostic information for PTCLs, representing a possible surrogate prognosis indicator for long-term survivors after systemic chemotherapy.

Clinicopathological characterization of follicular helper T-cell-derived peripheral T-cell lymphoma involving Waldeyer's ring.

Follicular helper T-cell-derived peripheral T-cell lymphoma (TFH-derived PTCL) initially present in the Waldeyer's ring is a rare condition with a challenging diagnosis. This study aimed to evaluate the clinicopathological characteristics and diagnosis of Waldeyer's ring TFH-derived PTCL and raise awareness of this type of lymphoma. A series of 13 cases of Waldeyer's ring TFH-derived PTCL were retrospectively analyzed. Clinically, most patients presented with localized manifestations, such as painless cervical lymphadenopathy (7/13), pharyngalgia (6/13), and nasal obstruction (3/13), and systemic symptoms were uncommon. Macroscopically, plump mass (9/13) and nodular lesions (3/13) covered with intact and tense mucosa were the main findings on fiberoptic laryngoscopy examination. Pathologically, diffuse infiltration with atypical lymphocytes in the lamina propria (10/13) was the most common growth pattern. Clear cells (9/13) and vascular proliferation (11/13) within a polymorphic inflammatory background (11/13) were frequently observed. All cases expressed at least two TFH markers: PD-1 in 92.3% (12/13), BCL6 in 69.2% (9/13), CXCL13 in 53.8% (7/13), and CD10 in 46% (6/13). Targeted next-generation sequencing analysis identified frequent mutations, including TET2 (10/11), RHOA (6/11), DNMT3A (3/11), and IDH2 (2/11). The overall survival rate at 2 years was 35.5%, and survival analysis revealed that patients with localized disease showed better overall survival (P = 0.022). In conclusion, careful morphological observation combined with immunohistochemistry and molecular analysis would help in diagnosis of TFH-derived PTCL involving the Waldeyer's ring, which is a rare condition that frequently presents with atypical clinical manifestations.

Analysis of clinical characteristics and prognosis of patients with peripheral T-cell lymphoma.

BACKGROUND: This study aimed to explore the clinical characteristics, therapeutic efficacy and prognostic factors of peripheral T-cell lymphoma (PTCL). METHODS: The clinical data of 119 PTCL patients who were admitted to the Xinjiang Medical University Affiliated Tumor Hospital from January 2010 to December 2017 were retrospectively analyzed, including the clinical characteristics, therapeutic efficacy, prognosis-related factors and treatments. Among the patients, 98 patients received antharcyclines-based therapeutic protocols, including Cyclophosphamide, Pirarubicin, Vincristine, Prednisone (CHOP) protocol and Cyclophosphamide, Pirarubicin, Vincristine, Prednisone, Etoposide (CHOPE) protocol, with median follow-up time of 32.5 months (2-166 months). The patients' clinical characteristics were analyzed, and COX ratio risk regression model was adopted to analyze the prognostic factors related with the survival rate of PTCL patients. RESULTS: The 5-year overall survival (OS) rate was 46.4% and progression-free survival (PFS) rate was 42.7% in the 98 patients, and there were insignificant differences between patients with CHOP protocol and those with CHOPE protocol in the 5-year OS and PFS rates (OS: P = 0.197, PFS: P = 0.663). The univariate analysis results showed that different pathological types, Ann Arbor stage, Eastern Cooperative Oncology Group (ECOG) score ≥ 2, the number of extranodal lymphomas involved, Lactic dehydrogenase (LDH) level, presence/absence of bone marrow involved, international prognostic index (IPI) score, ß2 microglobulin (ß2-MG) level and hemoglobin (Hb) level were poor prognosis factors influencing patients' OS and PFS rates (P all < .05). Multivariate analysis demonstrated that different pathological types, Ann Arbor stage, presence/absence of bone marrow involved and Hb level were independent prognostic indicators influencing patients' OS and PFS rates (P all < .05). CONCLUSION: PTCL is poor in therapeutic efficacy and prognosis, and different pathological types, Ann Arbor stage, presence/absence of bone marrow involved and Hb level are related with the prognosis of PTCL patients. Anemia occurring before the treatment is an important predictive indicator influencing the prognosis of PTCL patients and patients who experience anemia will be poor in prognosis.

Advances in Frontline Management of Peripheral T-cell Lymphoma.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphomas that are frequently associated with a poor prognosis. For many decades, the standard-of-care has been CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone)-based therapy, but it is well-recognized that survival outcomes are unsatisfactory, especially when compared with B-cell lymphomas. Major recent advances in cancer diagnosis and management have the potential to significantly improve PTCL outcomes. These include: (1) improved diagnostic techniques that incorporate molecular genetic data to further refine diagnosis and subtyping; (2) the development of novel agents; and (3) improved monitoring modalities, such as 18F-fluorodeoxyglucose positron emission tomography-computed tomography scans and circulating tumor DNA. In this review, we aim to explore these 3 advances in the context of frontline management of PTCL.

Low serum cholesterol levels predict inferior prognosis and improve prognostic index scoring for peripheral T-cell lymphoma, unspecified.

Peripheral T-cell lymphomas, unspecified (PTCL-U) is a heterogeneous group of non-Hodgkin lymphomas, arising from the transformation of mature, post-thymic T-cells. Prognostic index for PTCL-U (PIT) is based on Europeans and may not be applicable for Chinese PTCL-U patients. Besides, low circulating cholesterol concentration is associated with elevated cancer incidence and mortality. The purpose of our study was to assess the prognostic value of serum lipid levels in PTCL-U and improve PIT. We screened the prognostic factors associated with progression-free survival (PFS) and overall survival (OS) by multivariate Cox regression analysis in ninety-one enrolled patients. The results showed that low-level high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were associated with unfavorable OS. Furthermore, we developed a new risk model, PITC, based on low-level HDL-C, LDL-C and PIT. In Chinese PTCL-U, PITC was superior to PIT in PFS and OS. In conclusion, serum cholesterol levels may be good candidates for predicting prognosis in PTCL-U.

Combination of brentuximab-vedotin and ifosfamide, carboplatin, etoposide in relapsed/refractory peripheral T-cell lymphoma.

OBJECTIVES: Relapsed/refractory peripheral T-cell lymphomas (PTCL) have a poor prognosis. We aimed at assessing efficacy of ifosfamide, carboplatin, etoposide (ICE) regimen, a known therapeutic option, to which we added brentuximab-vedotin (BV). METHODS: In this study, we retrospectively analyzed patients with PTCL treated with BV-ICE in our center between July 2014 and March 2018. RESULTS: Fourteen patients received BV-ICE. Median age was 62 years (range, 31-73). Main histological subtypes were PTCL-not otherwise specified (29%), angioimmunoblastic T-cell lymphoma (21%), follicular-T helper (21%), or anaplastic large-cell (15%) lymphomas, all were CD30 positive. Overall response was seen in four (29%) patients, and complete response (CR) in two (14%). Most frequent adverse events were infections, and cytopenia. 2-year progression-free and overall survival were 14% and 17.5%, respectively. CONCLUSION: Patients with relapsed/refractory PTCL treated with BV-ICE can achieve CR, but few had a sustained response. This association should preferably be used as a bridge to stem cell transplant or be followed by maintenance therapy.

Increased incidence of adult T cell leukemia-lymphoma and peripheral T cell lymphoma-not otherwise specified with limited improvement in overall survival: a retrospective analysis using data from the population-based Osaka Cancer Registry.

Peripheral T cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin lymphomas with poor outcomes. Adult T cell leukemia-lymphoma (ATL) and PTCL-not otherwise specified (PTCL-NOS)-are 2 common mature T cell lymphomas in Japan. Since it is unclear whether novel agents and treatment strategies incorporating hematopoietic cell transplantation have contributed to improved clinical outcomes in the real world, we performed a retrospective analysis using data from the population-based Osaka Cancer Registry. From 1977 to 2014, 1274 and 1143 patients were diagnosed with ATL or PTCL-NOS, respectively. Recently, the incidence of both diseases has gradually increased, and the age at diagnosis has risen. The 3-year overall survival (OS) rates in ATL patients were 12.0% in era 1 (1977-1999), 12.4% in era 2 (2000-2008), and 17.5% in era 3 (2009-2014) (P < 0.001). The 3-year OS rates in PTCL-NOS patients were 27.6% in era 1, 36.2% in era 2, and 35.0% in era 3 (P = 0.049). In conclusion, the incidences of ATL and PTCL-NOS have been increasing, particularly in elderly individuals. Clinical outcomes have improved in recent decades but are still unsatisfactory in both diseases. Thus, effective new treatment strategies incorporating novel agents are needed to further improve clinical outcomes in patients with ATL and PTCL-NOS.

Alemtuzumab plus CHOP versus CHOP in elderly patients with peripheral T-cell lymphoma: the DSHNHL2006-1B/ACT-2 trial.

PTCL patients exhibit poor survival with existing treatments. We investigated the efficacy of CHOP combined with alemtuzumab in 116 PTCL patients age 61-80 in an open-label, randomized phase 3 trial. Alemtuzumab was given on day 1, to a total of 360 mg in 21 patients, or 120 mg in 37. Hematotoxicity was increased with A-CHOP resulting in more grade ≥3 infections (40% versus 21%) and 4 versus 1 death due to infections, respectively. CR/CRu rate was 60% for A-CHOP and 43% for CHOP, and OR rate was 72% and 66%, respectively. Three-year-EFS, PFS and OS were 27% [15%-39%], 28% [15%-40%], and 37% ([23%-50%] for A-CHOP, and 24% [12%-35%], 29% [17%-41%], and 56% [44%-69%] for CHOP, respectively, showing no significant differences. Multivariate analyses, adjusted for strata and sex confirmed these results (hazard ratio HREFS: 0.7 ([95% CI: 0.5-1.1]; p = 0.094), HRPFS: 0.8 ([95% CI: 0.5-1.2]; p = 0.271), HROS: 1.4 ([95% CI: 0.9-2.4]; p = 0.154). The IPI score was validated, and male sex (HREFS 2.5) and bulky disease (HREFS 2.2) were significant risk factors for EFS, PFS, and OS. Alemtuzumab added to CHOP increased response rates, but did not improve survival due to treatment-related toxicity.

Comparison of clinicopathological features and treatment outcomes in aggressive primary intestinal B- and T/NK-cell lymphomas.

BACKGROUND: Primary intestinal lymphomas (PILs) are rare, and this study compared the clinical outcomes of aggressive primary intestinal B-cell lymphomas (aB-PILs) and T/natural killer-cell lymphomas (T/NK-PILs). METHODS: The clinical information of patients diagnosed with aggressive PILs at our institution between 1995 and 2015 were retrospectively investigated. Pathological subtypes were confirmed according to the 2016 revision of the World Health Organization classification. The correlation between clinicopathological features and overall survival (OS) was determined using univariate and multivariate analyses. RESULTS: Cases of T/NK-PILs had higher initial bowel perforation incidence (67% vs. 7%, P < 0.001) and lower complete response rate to first-line chemotherapy regimens (22% vs. 69%, P = 0.009) than aB-PILs. Patients with aB-PILs had a better 5-year event-free survival rate (55.8% vs. 13.9%, P = 0.026) and a 5-year OS rate (74.3% vs. 29.6%, P = 0.036) than those with T/NK-cell lymphomas. Multivariate analysis identified that female gender and stage III/IV were unfavorable prognostic factors. Among the 54 patients with diffuse large B-cell lymphoma (DLBCL), those with International Prognostic Index (IPI) scores of 0-2 had a better 5-year OS rate than those with scores of 3-5 (84.2% vs. 46.8%, P = 0.002). IPI scores of 3-5 (P = 0.026) and tumors located in the large intestine (P = 0.015) were poor prognostic factors based on the multivariate analysis. CONCLUSION: The prognosis of T/NK-PILs was less favorable than that of aB-PILs. Female gender, stage III/IV disease, DLBCL with IPI scores of 3-5, or tumors in the large intestine were poor prognostic factors.