Mature T-/NK-cell lymphomas: Prognostic factors and treatment outcome of patients treated on studies of the German High-Grade Lymphoma Study Group (DSHNHL)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8564-8564
Author(s):  
N. Schmitz ◽  
M. Ziepert ◽  
M. Nickelsen ◽  
S. P. Wolf ◽  
L. Truemper ◽  
...  
Keyword(s):  
T Cell ◽  
Prospective Studies ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
High Dose ◽  
T Cell Lymphomas ◽  
Improved Outcomes ◽  
Alk Positive ◽  
Lymphoma Study Group

8564 Background: T-cell lymphomas represent a heterogeneous group of malignancies difficult to diagnose and to treat. We evaluated patients (pts) diagnosed according to WHO standards and treated on prospective studies of the DSHNHL. Chemotherapy regimens (CHOP-14 and CHOEP) had significantly improved outcomes of patients with aggressive B-NHL. Methods: Between 1993 and 2006 we treated 329 pts with ALK-positive ALCL (73 pts), ALK-negative ALCL (108 pts), PTCL, NOS (68 pts), AITL (28 pts), NK-/T-cell lymphoma (18 pts), and rare T-cell lymphomas on prospective studies. All pts received CHOP ± etoposide (E) every 2 or 3 weeks; in pts <=60 yrs C, H, and E were escalated to further improve outcomes. Results: The majority of pts with ALK-positive ALCL presented with IPI 0, 1 (62%) or IPI 2 (26%) and had an excellent overall survival (OS) of 89 % and event-free survival (EFS) of 75% at 3 yrs. E significantly improved TTTF for pts <=60 yrs (p=0.007). Pts with other histologies did significantly worse (OS 58%, EFS 44 % at 3 yrs). The IPI discriminated between pts with a favorable (IPI 0, 1: OS 73%), moderate (IPI 2: OS 55%), and poor prognosis (IPI 3: OS 35%; IPI 4, 5: OS 19%) at 3 yrs. OS, EFS were significantly better for ALK-positive ALCL but did not significantly differ for pts in other histological subgroups. Neither shortening of the treatment interval (CHOP-14) nor the addition of E (CHOEP-21 or -14) significantly improved outcome of elderly pts. In younger pts (ALK-positive ALCL were excluded) and good-risk disease (LDH <= N) there was a trend for better EFS after the addition of E to CHOP (EFS 63% vs. 48%, p = 0.065). The MegaCHOEP protocol (Schmitz et al., CANCER 2006) failed to improve treatment results for younger pts with poor-risk disease (EFS at 3 yrs: 25.9%, 95% CI: 10.4–41.4); the prospective study comparing MegaCHOEP with CHOEP-14 was stopped for pts with T-cell lymphoma. Conclusions: CHO(E)P results in excellent OS of pts with ALK-positive ALCL and selected pts with other histologies and low IPI. All other pts did poorly; CHOP-14 or the addition of E failed to significantly improve outcomes. Notably, also the MegaCHOEP protocol characterized by repetitive high-dose therapy and ASCT did not result in significant improvement. No significant financial relationships to disclose.

scholarly journals An Update in Management of Noncutaneous T-Cell Lymphomas

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Y. Y. Hwang ◽  
R. H. S. Liang
Keyword(s):  
T Cell ◽  
Treatment Approach ◽  
Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Conventional Chemotherapy ◽  
High Dose Therapy ◽  
T Cell Lymphomas ◽  
Alk Positive

T-cell lymphoma is a heterogeneous group of diseases. Except for ALK positive anaplastic large cell lymphoma, T-cell lymphoma responds to conventional chemotherapy unfavourably, and most patients carry poor prognosis. In recent years, efforts have been made to improve the outcome of T-cell lymphoma patients. Novel agents, high-dose therapy, and allogeneic stem cell transplantation are studied, and various results are reported in literature. This paper looks into the prognostication and treatment approach of different entities of noncutaneous T-cell lymphoma and would focus on the latest updates in its management.

A Retrospective Comparison of Autologous Vs. Allogeneic Transplantation for Peripheral T-Cell Lymphoma: A Single Institution Experience

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4392-4392
Author(s):  
Frederick Lansigan ◽  
Stuart Seropian ◽  
Dennis Cooper ◽  
Francine Foss
Keyword(s):  
T Cell ◽  
Complete Remission ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Unrelated Donor ◽  
T Cell Lymphomas ◽  
First Remission

Abstract Peripheral T-cell Lymphomas (PTCL) are a heterogenous group of malignanices that represent 10–15% of non-Hodgkin lymphoma (NHL). This group has a worse prognosis with conventional chemotherapy compared to B-cell lymphomas. Both autologous (AutoSCT) and allogeneic stem cell transplantation (AlloSCT) have been used as consolidation in first remission and at relapse, but the role of transplantation has not been clearly defined. We report a retrospective analysis of 42 patients with PTCL who underwent AutoSCT (24) or AlloSCT (18) between 8/1997 and 12/2007. The AlloSCT group consisted of 4 PTCL unspecified (PTCLu), 3 angioimmunoblastic T-cell lymphomas (AITL), 2 panniculitic T-cell lymphomas, 2 cutaneous T-cell lymphomas (CTCL) with large cell transformation, 2 NK-cell lymphomas, 2 anaplastic large cell lymphomas (ALCL, 1 Alk+, 1 Alk unknown), 1 hepatosplenic T-cell lymphoma, 1 enteropathic T-cell lymphoma, and 1 refractory CTCL. The AutoSCT group consisted of 6 PTCLu, 12 ALCL (5 Alk+, 5 Alk−, 2 Alk unknown), 4 AITL, 1 CTCL with transformation, and 1 T-lymphoblastic lymphoma. The median age of the AlloSCT and AutoSCT groups was 51 (range 29–72) and 52 years (range 19–67), respectively. The median number of prior treatments of the AlloSCT and AutoSCT groups were 3 (range 1 to 5) and 1 (range 1 to 5), respectively. Within the AlloSCT group there were 14 matched-related donor transplants, and 4 matched-unrelated donor transplants; 7 were ablative and 11 were reduced-intensity transplants; the AlloSCT conditioning regimens varied. The AutoSCT group predominantly received BEAM as their conditioning regimen. Median time from diagnosis to AlloSCT or AutoSCT was 18.4 (range 6.9 to 109) and 7.5 (range 3.9 to 25) months, respectively. Median follow-up times for the AlloSCT and AutoSCT groups were 28.6 and 23.5 months, respectively. The day 100 transplant-related mortality rates in the AlloSCT and AutoSCT groups were 11% and 0%, respectively. Within the AlloSCT group the relapse and non-relapse mortalities were 11% and 33%, respectively. In the AutoSCT group, the relapse mortality was 33%. The 1- and 2-year overall survival (OS) rates were similar within the AlloSCT and AutoSCT groups (78% vs 74%, and 67% vs 60%, respectively). The 1- and 2-year progression-free survival (PFS) rates for the AlloSCT vs AutoSCT groups were 68% vs 52%, and 53% vs 45%, respectively (p = 0.28). Within the AutoSCT group, 14 patients (58%) were transplanted in first complete remission (CR1), and 10 (42%) in second complete remission (CR2), beyond CR2, or partial remission (PR). Patients in CR1 had significantly better PFS (57 vs 17 months, p=0.007) and OS (76 vs 29 months, p=0.004) than those in CR2, PR2, or beyond. Within the AlloSCT group, there was a trend toward poorer OS in 6 patients (33%) who had prior AutoSCT (32 vs 60 months, p=0.15). One patient (6%) was transplanted in CR1, and is still alive. We conclude that outcomes for AutoSCT are best in CR1. For patients with resistant or relapsed disease, AlloSCT should be strongly considered rather than AutoSCT. Prior AutoSCT may affect the outcome of AlloSCT. These results suggest that a prospective randomized trial comparing AutoSCT and AlloSCT for aggressive PTCL in first remission is warranted.

Second-Line Therapy with ICE Followed by High Dose Therapy and Autologous Stem Cell Transplantation for Relapsed/Refractory Peripheral T-Cell Lymphomas: Minimal Benefit When Analyzed by Intent To Treat.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2679-2679 ◽  
Author(s):  
Steven Horwitz ◽  
Craig Moskowitz ◽  
Tarun Kewalramani ◽  
Paul Hamlin ◽  
David Straus ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Refractory Disease ◽  
Second Line ◽  
High Dose Therapy ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

Abstract Background: Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin’s lymphomas with a poorer prognosis than their B-cell counterparts. Second -line chemotherapy (SLT) followed by high dose therapy and autologous stem cell transplantation (HDT/ASCT) is a common approach to patients (pts) with relapsed PTCL. Reports evaluating this approach have analyzed the outcome of transplanted patients. Our goal was to identify pts with relapsed or refractory disease, treated in a uniform manner, with the intent to induce a remission and proceed to HDT/ASCT. Patients and Methods: From our ICE database we identified 40 pts with a diagnosis of a mature T or NK lymphoma who received ICE as SLT therapy prior to planned HDT/ASCT. Histologic subtypes were as follows: PTCL NOS (n=15), anaplastic large cell lymphoma (n=11), angioimmunoblastic T-cell lymphoma (n=5), NK/T cell lymphoma (n=4), subcutaneous panniculitis-like T-cell lymphoma (n=2), and one each of hepatosplenic γ/δ T-cell lymphoma, enteropathy associated T-cell lymphoma, and transformed mycosis fungoides. Median age was 48 years (24–73), five pts were ≥ 60 years. Twenty-five men and 15 women were treated. Initial chemotherapy regimens included: CHOP/CHOP-like (n=32), NHL-15 (n=5), and other (n=4). Twenty-two pts responded to their initial therapy and 18 had primary refractory disease. At time of relapse, 24 pts had stage IV disease, 23 had elevated LDH, and 9 had a performance status ≤ 70%. Thirty-one pts had at least one extranodal site. Complete second line International Prognostic Index (IPI) factors (AA stage, LDH, PS) were available for 36 pts. IPI scores were LR (n=3), LIR (n=12), HIR (n=13), and HR (n=8). Results: All pts received at least one cycle of ICE, 36 received all three planned cycles. Fourteen patients (35%) achieved a complete response, 14 (35%) had a partial response, four (10%) had stable disease, and eight (20%) progressed on therapy. Twenty-seven (68%) pts went on to receive HDT/ASCT. Median follow-up for surviving pts was 45 months (range 7–104). By 3 years, 33/40 (83%) of pts had relapsed with a median progression free survival (PFS) of 6 months from last ICE treatment. Twenty-eight (70%) pts relapsed within 1 year. Neither second-line IPI nor histologic subtype was predictive of continuous remission. Relapsed pts had a superior 3 year PFS compared to primary refractory pts 20% vs 6% (p=0.0005). Despite high relapse rate, 18/40 (45%) of pts were alive at last follow-up. Conclusion: SLT and HDT/ASCT is a common treatment strategy for pts with relapsed PTCL. However, when examined by intention to treat from initiation of SLT and not from time of transplant few pts have durable benefit from this approach. Despite the high response rate to SLT, consolidation with HDT/ASCT provides little clinically meaningful benefit for most pts. The number of pts alive with other therapies despite early relapse underscores the need to study alternative or maintenance strategies for those who achieve remissions.

Allogeneic Stem Cell Transplantation (Allo-SCT) for Relapsed/Refractory T Cell Lymphomas in Adults: A Survey from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3020-3020
Author(s):  
Steven Le Gouill ◽  
Jean-noël Milpied ◽  
Jean-paul Vernant ◽  
Norbert Ifrah ◽  
Françoise Mechinaud ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
Disease Status ◽  
T Cell Lymphoma ◽  
Myeloablative Conditioning ◽  
Prognosis Factors ◽  
T Cell Lymphomas

Abstract Background: Adult mature T-cell and NK-cell neoplasms include several lymphomas entities. Taken together, T- and NK- cell lymphomas represent 10–15 % of non-Hodgkin’s lymphoma in adults, presenting with aggressive behaviour and poor outcome (except for ALCL ALK positif lymphomas). Despite intensive chemotherapy including or not autologous stem cell transplantation upfront, a majority of patients experience relapse. Therefore, allo-SCT is an attractive second-line strategy. We retrospectively analyzed T-cell lymphomas patients (lymphoblastic lymphomas were systematically excluded) reported to the SFGM-TC registry and transplanted from an HLA identical sibling donor with or without myeloablative conditioning regimen. Results: In the present intermediate report, we analysed 24 patients. Because of misdiagnosis, we excluded two cases. Among the 22 remaining patients, there were peripheral T-cell lymphoma NOS (PTCL) in 5 cases, angioimmunoblastic T-cell lymphoma (AITL) in 3 cases, anaplastic large cell lymphoma (ALCL) in 10 cases (ALK positif in 3 cases; negative in 2 cases and unknown in 5 cases; respectively), hepatosplenic g/d lymphoma (HSL) in 2 cases, T-cell granular lymphocytic leukemia (GLL) in 1 case and localized nasal NK/T cell lymphoma (NK/L) in one case. There were 15 males and 7 females. Median age was 38.5 years (15.5–54). All patients have been considered eligible for allo-SCT because of poor prognosis factors: HSL diagnosis in 2 cases, relapsed/refractory disease in 16 cases (including all ALCL cases) and/or failure to reach CR in 8 cases. Disease status at the time of transplantation was CR in 9 cases, PR in 7 cases and PD/refractory in 3 cases; respectively. All patients but 2 underwent myeloablative conditioning regimen prior to transplantation (TBI/EDX in 70%). The majority of patients (86%) received BMSC graft from related HLA-matched sibling donor. Median overall survival (OS) was 70 months for the all cohort. Median OS was not reached in the ALCL subgroup compared to 20 months for the non-ALCL subgroup. According to disease status, 7 out of 9 patients in CR at the time of transplantation are alive and in CR at the time of the analysis compared to 6 out of 13 in non-CR patients. Cause of death was AGVH in 2 cases, bacterial or fatal infections in 4 cases and relapse in 2 cases, respectively. Conclusion: these preliminary results show that allo-SCT is a treatment of choice for refractory/relapsed T-cell lymphomas. Results are very encouraging in relapsed/refractory ALCL patients and highlight the role of graft versus T-cell lymphoma effect. Further analysis are required to identify prognosis factors and additional cases will be analyzed at the time of the meeting.

Assessment of FDG-PET Imaging in T-Cell and NK-Cell Lymphomas

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5305-5305
Author(s):  
Juan Chalapud-Revelo ◽  
Pedro Sobrevilla-Calvo ◽  
Cadena-Eumaña Carlos ◽  
Rivas-Vera Silvia ◽  
Lopez-Navarro Omar ◽  
...  
Keyword(s):  
T Cell ◽  
Fdg Pet ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Histological Subtypes ◽  
Cutaneous Lesions ◽  
Nasal Type ◽  
T Cell Lymphomas ◽  
Nasal Region

Abstract BACKGROUND: Malignant T-cell lymphomas are a heterogeneous group of disorders that frequently involve extranodal regions. Treatment and prognosis depend on accurate staging and histological evaluation. PET is widely used in staging and response evaluation of B-cell lymphomas, however, the use of FDG-PET have not been well studied for T-cell and natural killer cell lymphomas, and there is controversy if PET can detect accurately extranodal tumor activity. PATIENTS AND METHODS: We retrospectively evaluated FDG-PET in 38 patients with active T-cells, and T/NK-cells lymphoma diagnosed according to the World Health Organization (WHO) classification, from May 2007 to May 2008. We also evaluated the Standard Uptake values (SUV) according the different subtypes and the accuracy of PET in detecting tumor activity in the skin and nasal region. RESULTS: Histological subtypes included were extranodal NK/T-cell lymphoma nasal type (ENKL, n=12); Anaplastic T-cell lymphoma (ATCL, n=11); peripheral T-cell lymphoma (PTL, n=7); mycosis fungoides and Sezary syndrome (MF/SS, n=5), angioimmunoblastic (An=3). FDG-PET detected a lymphoma lesion in at least one site in 35 out of 38 patients (91%). The positivity rate was high in all histological subtypes ENKL 92%, ATCL 100%, PTL 86%, MF/SS 80%, A 100%. Among 13 patients who had cutaneous lesions only 7 had FDG-avid skin lesions (sensitivity =53.8% and specificity=100%) and among 11 patients with nasal region lesions, 91% had FDG-avid cutaneous lesions (sensibility = 91%, specificity=100%). The SUV Value in the different subtypes is shown in the table and there was not statistical differences between the groups (p= 0.067) Lymphoma N Mean SD(+/−) Range An 3 4.1 1.7 2.7–6 MF/SS 5 4.2 3.0 1.9–8.6 ATCL 11 8.3 5.3 1.6–20.8 PTL 7 3.5 1.6 2.2–6.0 ENKL 12 7.2 4.1 2.2–13.8 Total 38 6.35 4.3 1.6–20.8 CONCLUSIONS: Most of the T and T/NK cell lymphomas were detected by FDGPET. All cases, except one, of ENKL nasal type were FDG-avid, but only half of cutaneous lesions were detected by PET. In the whole T-Cell lymphomas group the mean SUV was 6.35, ATCL had the highest SUV, and we did not find any statistically differences between the groups. We conclude that PET has a high sensitivity for detection of active ENNK nasal type lymphomas and this information should be the basis for designing further studies to assess its value in staging, tumor response and as a prognostic factor.

scholarly journals Histone Deacetylase Inhibitors Downregulate CCR4 Expression and Decrease Mogamulizumab Efficacy in CCR4-Positive Mature T-Cell Lymphomas

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 720-720
Author(s):  
Akihiro Kitadate ◽  
Sho Ikeda ◽  
Fumito Abe ◽  
Naoto Takahashi ◽  
Norio Shimizu ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Research Funding ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Selective Inhibitor ◽  
T Cell Lymphoma ◽  
Lymphoma Cell ◽  
Class I ◽  
T Cell Lymphomas

Abstract Background: Histone deacetylase inhibitors (HDACis) are promising agents for various T-cell lymphomas, including cutaneous T-cell lymphoma (CTCL), peripheral T-cell lymphoma (PTCL), and adult T-cell lymphoma/leukemia (ATLL). CCR4 is an important therapeutic target molecule because mogamulizumab, an anti-CCR4 antibody, has shown promising efficacy against CTCL, PTCL, and ATLL. However, their combined effects and interactions have not been examined thus far. We previously showed that CCR6, a chemokine receptor, is overexpressed in cutaneous T-cell lymphomas (Ito et al., 2014 Blood). Moreover, we recently demonstrated that HDACis downregulate CCR6 expression in advanced cutaneous T-cell lymphomas (Abe et al., 2017 Oncotarget). These reports lead us to hypothesize that HDACis might also downregulate CCR4 in various T-cell lymphomas. In this study, we clarify the effect of the combined use of mogamulizumab and HDACis on various T-cell and NK-cell lymphomas. Based on our findings, we discuss what benefits or adverse effects might be assumed for patients if these molecular targeting agents are used in clinical practice. Methods: We evaluated changes in CCR4 expression and antibody-dependent cell-mediated cytotoxicity (ADCC) activities against mogamulizumab- and HDACi-treated T-cell and NK-cell lymphoma lines and primary cases. To determine which HDAC mainly regulated CCR4 expression, we used isoform-specific HDACis and induced knockdown of respective HDACs for T-cell lymphoma cell lines. To examine the effect of CCR4 downregulation by HDACis in clinical cases, we examined the CCR4 expression of CTCL skin samples, which were obtained from the same patients before and after HDACi treatment (n = 6). Results: We first examined the expression of CCR4 for 15 T-cell and NK-cell lymphoma cell lines and a peripheral blood mononuclear cell (PBMC) sample derived from healthy donors to investigate the effect of vorinostat, a pan-HDACi, on CCR4 expression. The expression of CCR4 was mostly expressed in the (11 out of 15) cell lines: ATLL (MT-1, MT-2, MT-4, and TL-Su), CTCL (My-La, HH, and MJ), and NK/T-cell lymphoma cell lines (Kai3, SNK6, HANK1, and SNK10). We found that vorinostat decreases mRNA expression and surface expression of CCR4 except for the cell lines without CCR4 expression. Next, we used isoform-specific HDACis to examine which isoform of HDAC is involved in the regulation of CCR4. We used the following class-specific HDACis: romidepsin as a class I selective HDACi, CI-994 as an HDAC1/HDAC2-selective inhibitor, RGFP966 as an HDAC3-selective inhibitor, ricolinostat as an HDAC6-selective inhibitor, and PCI-34051 as an HDAC8-selective inhibitor. When these drugs were exposed to T-cell lymphoma cells, romidepsin and CI-994 strongly suppressed CCR4 expression. These results suggest that class I HDACs might controls CCR4 expression. We further performed knockdown experiments using siRNAs against HDAC1, HDAC2, and HDAC3. When we compared the expression change of CCR4 in HDAC-knockdown cells, HDAC2 knockdown cells showed the most significantly decreased expression of CCR4. These results suggest that class I HDACs, especially HDAC2, might be deeply involved in CCR4 expression regulation. When we examined the CCR4 expression in skin samples from primary CTCL, obtained from the same patients before and after vorinostat treatment, we found that CCR4 expression was greatly reduced after vorinostat treatment. Finally, when we conducted an ADCC assay with mogamulizumab by using various lymphoma cell lines and primary T-cell lymphoma samples, we found that the efficacy of mogamulizumab was significantly reduced by pre-treatment with vorinostat. Conclusion: Our results suggest that the primary use of HDACis before treatment of mogamulizumab might not be suitable to obtain synergistic effects. Moreover, these results provide potential implications for optimal therapeutic sequences in various CCR4 positive T-cell and NK-cell lymphomas. Disclosures Kitadate: Kyowa Kirin: Research Funding; Fujimoto: Research Funding; Eisai: Research Funding; Otsuka: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Asahi Kasei: Research Funding; Chugai: Research Funding; Toyama kagaku: Research Funding. Abe: Kyowa Kirin: Research Funding; Fujimoto: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Otsuka: Research Funding; Toyama Kagaku: Research Funding; Chugai: Research Funding; Asahi Kasei: Research Funding; Eisai: Research Funding. Tagawa: TaNeDS (Daiichi Sankyo): Research Funding.

scholarly journals Progress in the treatment of NK-cell lymphoma/leukemia

2021 ◽  
Author(s):  
Ayumi Fujimoto ◽  
Ritsuro Suzuki
Keyword(s):  
T Cell ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Genetic Alterations ◽  
T Cell Lymphoma ◽  
Barr Virus ◽  
T Cell Lymphomas ◽  
Previous Decade ◽  
Nk T Cell ◽  
Epstein Barr

Natural killer (NK)/T cell lymphoma includes two major subtypes of disease, specifically extranodal NK/T cell lymphoma, nasal type (ENKL) and aggressive NK cell leukemia (ANKL). Both are strongly associated with Epstein-Barr virus and are prevalent in East Asia and Latin America. Except for that of limited-stage ENKL, the prognosis of both diseases was poor in the previous decade. The advent of non-anthracycline-based chemoradiotherapy has contributed to an improvement in ENKL prognosis, but there is still room for further treatment progress. Recently, the high efficacy of PD-1 antibody was reported in relapsed or refractory ENKL patients. This was later supported by the finding that PD-L1/PD-L2 genetic alterations are frequently observed in ENKL and ANKL patients. Due to the rarity of the disease, a standard treatment for ANKL remains to be established. Currently, allogeneic stem cell transplantation is the only curative treatment, and this is even applicable to chemo-resistant ANKL patients. In this review, we focus on recent treatment approaches for NK/T cell lymphomas including novel agents.

Disappointing Outcomes of Peripheral T Cell Lymphoma after Autologous Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5428-5428
Author(s):  
Stephen D. Smith ◽  
John William Sweetenham ◽  
Lisa Rybicki ◽  
Stacey Brown ◽  
Robert M. Dean ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Cell Lymphoma ◽  
Patient Characteristics ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Peripheral T Cell Lymphoma ◽  
First Remission ◽  
Alk Positive

Abstract The role of high dose therapy and autologous stem cell transplantation (ASCT) for patients with peripheral T-cell lymphoma (PTCL) is poorly defined. Comparisons of outcomes between PTCL and B-cell NHL following HDT have yielded conflicting results, in part due to the rarity and heterogeneity of PTCL. Older retrospective studies found comparable survival rates after ASCT for pts with T-cell and B-cell NHL.1,2 In this study, we report our single center experience over one decade using a uniform high-dose regimen for patients with PTCL. Patients and Methods The transplant database of the BMT program at Cleveland Clinic was reviewed, and 32 patients undergoing ASCT for PTCL between 1996 and 2005 were identified. Twenty-one patients (66%) had anaplastic large cell lymphoma (ALCL), and 11 (34%) had peripheral T cell, not otherwise specified (PTCL-NOS). Patient characteristics are summarized in table 1. Stem cell mobilization with VP16 and GCSF priming provided a median CD34 cell dose of 5.01× 106/kg (range 2.05–29.69). Patients received a preparative regimen consisting of busulfan (either 1 mg/kg orally or 0.8mg/kg IV for 14 doses), followed by VP16 60 mg/kg IV continuous infusion, then cyclophosphamide 60mg/m2 IV daily for two days. Standard supportive care measures were employed. Results Recovery to 500 neutrophils/uL occurred at a median of 10 days post transplant (range 9–12 days) and platelet recovery to 20 000 at a median of 14 (range 7–60) days. Kaplan-Meier 5 year overall survival and relapse-free survival for all patients is 34% and 18%, respectively; median survival for all patients is 36 months (see figure 1). Median follow-up of 10 survivors is 25 months. No obvious plateau was observed on the overall or relapse fee survival curves. No significant difference in outcomes based on subgroup (ALCL versus PTCL-NOS) was observed. Staining for anaplastic lymphoma kinase (ALK) was available for 11 (of 21 total) anaplastic T cell lymphoma patients: 4/5 ALK-positive patients are alive compared to 2/6 ALK-negative patients at last follow-up. Four of five patients undergoing ASCT as consolidation following initial therapy are alive at a median 25 months. Based on this small patient population, and in contrast to some recent studies, our results suggest a poor outcome for patients with PTCL after ASCT. The outcome for pts undergoing ASCT in first remission, and for ALK-positive (versus ALK-negative) ALCL, requires prospective investigation. Table 1: Patient Characteristics Characteristic N (%) ALCL 21 (66) PTCL NOS 11 (34) Male 21 (66) Age: median(range) 44 (16-69) 2 prior chemo regimens 22 (69) 3 or more prior chemo regimens 7 (22) Transplant in first remission 5 (16) Relapsed/Refractory 25 (78) Figure Figure

scholarly journals STAT3 Dysregulation in Mature T and NK Cell Lymphomas

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1711 ◽  
Author(s):  
Seffens ◽  
Herrera ◽  
Tegla ◽  
Buus ◽  
Hymes ◽  
...  
Keyword(s):  
T Cell ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Ex Vivo ◽  
T Cell Lymphoma ◽  
Inflammatory Microenvironment ◽  
Stat3 Signaling ◽  
T Cell Lymphomas ◽  
Models Of Disease ◽  
Hodgkin's Lymphomas

Abstract: T cell lymphomas comprise a distinct class of non-Hodgkin’s lymphomas, which include mature T and natural killer (NK) cell neoplasms. While each malignancy within this group is characterized by unique clinicopathologic features, dysregulation in the Janus tyrosine family of kinases/Signal transducer and activator of transcription (JAK/STAT) signaling pathway, specifically aberrant STAT3 activation, is a common feature among these lymphomas. The mechanisms driving dysregulation vary among T cell lymphoma subtypes and include activating mutations in upstream kinases or STAT3 itself, formation of oncogenic kinases which drive STAT3 activation, loss of negative regulators of STAT3, and the induction of a pro-tumorigenic inflammatory microenvironment. Constitutive STAT3 activation has been associated with the expression of targets able to increase pro-survival signals and provide malignant fitness. Patients with dysregulated STAT3 signaling tend to have inferior clinical outcomes, which underscores the importance of STAT3 signaling in malignant progression. Targeting of STAT3 has shown promising results in pre-clinical studies in T cell lymphoma lines, ex-vivo primary malignant patient cells, and in mouse models of disease. However, targeting this pleotropic pathway in patients has proven difficult. Here we review the recent contributions to our understanding of the role of STAT3 in T cell lymphomagenesis, mechanisms driving STAT3 activation in T cell lymphomas, and current efforts at targeting STAT3 signaling in T cell malignancies.

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