Peripheral T-cell non-Hodgkin Lymphoma Research Articles

Long-term survival in patients with peripheral T-cell non-Hodgkin lymphomas after allogeneic hematopoietic stem cell transplant

Peripheral T-cell non-Hodgkin lymphomas (T-NHL) are rare diseases, with a worse prognosis compared to their B-cell counterparts. Allogeneic hematopoietic stem cell transplant may have a role in the treatment of relapsed/refractory disease or high-risk histologies in the upfront setting. However, there is limited information on the efficacy of allogeneic transplant for these diseases, as well as what factors may predict outcomes. We therefore performed a retrospective study of 34 patients who received an allogeneic transplant for the treatment of T-NHL at a single center between 1 January 1992 and 31 December 2009. The median follow-up for survivors was 45 months (range 9–160 months). The 2-year overall survival (OS) was 0.61 (95% confidence interval [CI]: 0.43–0.75) with a plateau at 28 months. Ki-67 expression ≤ 25% was predictive of improved OS (p < 0.01), and transplant in complete remission was predictive of a decreased cumulative incidence of events (p = 0.04). Three patients received a donor leukocyte infusion, and two patients demonstrated a response, supporting a graft-versus-lymphoma effect. These data demonstrate that allogeneic transplant is a viable option for the treatment of T-NHL and merits prospective evaluation.

A Restrospective Review of Peripheral T-Cell Lymphoma in a Single Institution Between 2000 and 2010

Abstract 1623 Background:Peripheral T-cell non-hodgkin lymphomas (NHL) comprise a heterogeneous group of malignancies, characterized by an aggressive disease course and a poor clinical outcome. T-cell lymphomas present in lymph nodes and they also frequently involve extra nodal sites. The first line treatment consists in CHOP-like regimen. Consolidation treatment in first line or in relapse is autologous stem cell transplantation (ASCT) or allogenic stem cell transplantation (SCT).Patients and methods: We retrospectively analysed the data of 189 adults who had received chemotherapy in our institution between 2000 and 2010. Results:Median age at time of presentation was 55 (range 17–89) years, 76% were <65 years. 50% had B symptoms and 50% serum elevated LDH. ECOG was 0–1 in 60% and 2–4 in 40%. According to the Ann Arbor classification, 15% were stage I-II and 85% were stage III-IV. 50% had low IPI (0-1-2) and 50% had elevated IPI (3-4-5). The histologic subtypes were 42% peripheral T-cell NHL unspecified (PTCL-U), anaplastic large cell lymphoma (ALCL), 8% had ALK+ and 10% had ALK-, 24% angioimmunoblastic lymphoma (AILT), 3% transformed mycosis fungoide, 2% instestinal T-cell lymphoma, 2% hepatosplenic γδ T-cell lymphoma and 1% adult T-cell lymphoma/leukemia. Primary extranodal lymphoma represented 17% and 8% were diagnosed with hemophagocytosis.Five-year overall survival (OS) was 28.3% (21.8–36.8%), and five-year progression free survival (PFS) was 18.4% (13.1–25.7%). On multivariate analysis, ALCL-ALK+ (p=0.008), AILT (p<0.001), extranodal involvement (p=0.01), PS>1 (p<0.001), LDH>N (p=0.003) were independent adverse factors for OS. Moreover B symptoms (p<0.01) was a significant factor for PFS.86% received CHOP-like induction treatment. The median number of chemotherapy was 2 (1–7). 59% experienced a complete response during the therapeutic procedure, while 22% were primary refractory. 44% had ASCT and 14% allogenic SCT. Only 28% of patients referred for allogenic SCT received this treatment. Conclusions:This 10-year review of patients treated in a single institution with initial conventional chemotherapy followed by more intensive treatments confirms the poor OS and PFS in the case of T-cell lymphoma. Despite a low incidence, T-cell lymphoma could be a priority area of research for new treatments with a potential to improve OS and PFS. Disclosures:No relevant conflicts of interest to declare.

A large single-center experience with allogeneic stem-cell transplantation for peripheral T-cell non-Hodgkin lymphoma and advanced mycosis fungoides/Sezary syndrome

BackgroundThe prognosis for patients with most forms of T-cell lymphoma is poor. Allogeneic hematopoietic stem-cell transplantation (HSCT) may improve the outcome. Patients and methodsThis study examines the outcome of 52 patients who underwent ablative or nonablative allogeneic HSCT for peripheral T-cell lymphoma (PTCL) or advanced mycosis fungoides/Sezary syndrome over a 12-year period at a single institution. We divided the patients into those with predominantly nodal histologies: peripheral T-cell not otherwise specified (PTCL NOS), angioimmunoblastic (AITL), or anaplastic large cell lymphoma, T/null type (systemic) (ALCL), and predominantly extranodal histologies: natural killer (NK)/T cell, enteropathy type, hepatosplenic, subcutaneous panniculitic, mycosis fungoides, or T cell or NK cell other. ResultsMedian follow-up of survivors is 49 months. Non-relapse mortality and relapse at 3 years was 27% and 43%, respectively. The incidence of grade II–IV acute graft-versus-host disease (GVHD) was 21%. The incidence of extensive chronic GVHD at 2 years was 27%. The 3-year progression-free survival was 30%: 45% in patients with predominantly nodal histologies (PTCL NOS, AITL, and ALCL) and 6% in patients with predominantly extranodal histologies (P=0.016). Overall survival at 3 years was 41% for all patients. ConclusionAllogeneic HSCT can produce long-term remissions in relapsed/refractory T-cell lymphoma, especially those with nodal histologies.

Allogeneic hematopoietic cell transplant for peripheral T-cell non-Hodgkin lymphoma results in long-term disease control

The study analyzed outcomes of a consecutive case series of 37 patients with peripheral T-cell non-Hodgkin lymphoma, from related and unrelated donors, using allogeneic hematopoietic cell transplant (allo-HCT), between the years 2000 and 2007. All patients were pretreated; the majority had either relapsed or progressive disease (n = 25, 68%), 13 had cutaneous histologies (CTCL), and all were ineligible for autologous transplant. Fully ablative conditioning regimens were used in 13 patients while 24 patients underwent reduced intensity conditioning (RIC). At 5 years the overall survival (OS) and progression-free survival (PFS) probabilities were 52.2% and 46.5%, respectively. At the time of analysis, nine (24.3%) patients had either relapsed (n = 6) or progressed (n = 3) post allo-HCT. The cumulative incidences of relapse/progression and non-relapse mortality at 5 years were 24.3% and 28.9%. No statistically significant variables for survival or relapse were discovered by univariate Cox regression analysis of disease and patient characteristics; differences between CTCL and other histologies were not significant. The median follow-up of 64.0 months (range: 16.4–100.4) indicates a mature data-set with probable cure in the survivors. The relapse/progression curves reached and maintained plateaus after 1 year post-transplant, demonstrating that long-term disease control is possible after allo-HCT in patients with peripheral T-cell lymphoma with advanced disease.

Diffuse large B-cell and peripheral T-cell non-Hodgkin's lymphoma in the frail elderly

Abstract Objectives Many frail elderly patients with diffuse large B-cell lymphoma (DLBCL) cannot tolerate standard chemotherapy treatment. The objective of this phase II trial was to assess the efficacy of a cautious COP-based (cyclophosphamide, vincristine, prednisone) regimen with comprehensive geriatric assessment (CGA). Trial registration number: NCT00039351. Materials and methods DLBCL patients aged ≥ 70 years with poor physiological functioning received cyclophosphamide (750 mg/m2 IV at d1), vincristine (1.4 mg/m2 IV at d1, maximum of 2 mg) and prednisone (40 mg/m2 d1 to d5) for six cycles. Comprehensive Geriatric Assessment (CGA) was performed for all patients before and after treatment. Results Thirty-two patients were included, of whom 27 were evaluable for efficacy. Low response rates were observed with only 18.5% complete response and 25.9% partial response leading to the early termination of the trial. Despite strict dose reduction rules, high toxicity rates were observed with four severe toxicities and eight early deaths. CGA data showed that over 90% of patients were depressed, over 80% dependent for instrumental activities of daily living (IADL) and almost half of our patients had severe comorbidities showing that we clearly selected a population of “frail” elderly. Conclusion This adapted COP regimen for vulnerable patients produced an 18.5% complete response rate. Future research will include the addition of rituximab to determine if it can improve treatment efficacy. The geriatric assessment should be part of routine management of frail patients with aggressive lymphomas as it allows us to identify specific issues of vulnerability in this population on which intervention should be focused.

Primary cutaneous peripheral T‐cell non‐Hodgkin lymphoma, not otherwise specified, with cytotoxic features

Primary cutaneous peripheral T‐cell non‐Hodgkin lymphoma, not otherwise specified, with cytotoxic features

Association of serum B7-H1 level and lymphopenia in diffuse large B-cell non-Hodgkin lymphoma.

8080 Background: Activation of the adaptive immune response plays an important role in tumor immune surveillance. Not surprisingly then, lymphopenia has emerged as an adverse prognostic factor in non-Hodgkin lymphoma (NHL). The factors which may contribute to the development of lymphopenia in NHL are incompletely understood. B7-H1, a member of the B7 family of costimulatory/coinhibitory ligands, inhibits T-cell proliferation and promotes the induction of cell death in tumor-specific T cells. We recently described its expression on malignant cells, tumor-infiltrating dendritic cells, and circulating CD14+HLA-DRlo myeloid-derived suppressor cells in NHL (Blood. 2009;114(10): 2149- 58.). Therefore, we have hypothesized that B7-H1 may contribute to the development of lymphopenia in NHL. Methods: Serum samples were collected from normal donors (n=25) and patients with cutaneous T-cell NHL (CTCL, n=24), peripheral T-cell NHL (PTCL, n=29) and diffuse large B-cell lymphoma (DLBCL, n=31) and levels of soluble B7-H1 (sB7-H1) determined by ELISA. Results: Soluble B7-H1 was detected in serum of both normal donors (mean 0.29 ng/mL; 0.09-0.50 95% CI) and CTCL patients (mean 0.44 ng/mL; 0.25-0.63 95% CI), but was found to be significantly elevated in both PTCL (mean 0.84 ng/mL, 0.49-1.20 95% CI, p<0.001) and DLBCL (mean 0.62 ng/mL, 0.49-0.75 95% CI, p<0.001), when compared with that observed in normal donors. In order to determinewhether sB7-H1 may be associated with the development of lymphopenia, sB7-H1 levels at diagnosis were correlated with matched absolute lymphocyte counts (ALC) obtained from DLBCL patients (n=31). An inverse correlation was noted between sB7-H1 and the ALC. Forty-two percent of patients with elevated sB7-H1 (defined as greater than the mean sB7-H1) were lymphopenic (ALC <900/uL) at diagnosis, whereas 16% of the remaining patients were lymphopenic at diagnosis (p=0.1). Following therapy with anthracycline-based chemotherapy, a 39% reduction in sB7-H1 was observed (n=29, p<0.00001, paired t-test) and was associated with an 18% increase in the ALC. Conclusions: Collectively, the data presented demonstrates that sB7-H1 may represent a novel biomarker in NHL that's associated with lymphopenia. No significant financial relationships to disclose.

B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders

AbstractStromal elements present within the tumor microenvironment may suppress host immunity and promote the growth of malignant lymphocytes in B cell–derived non-Hodgkin lymphoma (NHL). In contrast, little is known about the microenvironment's role in T cell–derived NHL. B7-H1 (PD-L1, CD274), a member of the B7 family of costimulatory/coinhibitory ligands expressed by both malignant cells and stromal cells within the tumor microenvironment, has emerged as an important immune modulator capable of suppressing host immunity. Therefore, B7-H1 expression and function were analyzed in cutaneous and peripheral T-cell NHL. B7-H1 was expressed by tumor cells, monocytes, and monocyte-derived cells within the tumor microenvironment in T-cell NHL and was found to inhibit T-cell proliferation and promote the induction of FoxP3+ regulatory T cells. Collectively, the data presented provide the first evidence implicating B7-H1 in the suppression of host immunity in T-cell lymphoproliferative disorders and suggest that the targeting of B7-H1 may represent a novel therapeutic approach.

Clinicopathological study on peripheral T-cell non-Hodgkin lymphoma with bone marrow involvement: a retrospective analysis from China

We reviewed 173 patients with an initial diagnosis of peripheral T-cell non-Hodgkin lymphoma (PTCL) and compared the patients with bone marrow involvement (BMI) to those without to have a better understanding of the clinical characteristics, treatments, survival and prognosis of PTCLs with BMI. We found that 40% (70/173) of the patients had BMI, and its frequency was 64% in angioimmunoblastic T-cell lymphoma (TCL), 46% in PTCL unspecified, 29% in anaplastic large T-cell lymphoma, 23% in extranodal NK/T-cell lymphoma and 13% in enteropathy-type TCL. In the BMI group, 36% of patients had lymphoma-associated hemophagocytic syndrome (LAHS), compared with 8% of the patients without BMI (8/103, P < 0.001). The estimated 1-year overall survival (OS) rates of patients with LAHS in the BMI and non-BMI groups were 5 and 49%, respectively. The increased levels of lactate dehydrogenase, fasting triglycerides and beta(2)-microglobulin between the BMI and non-BMI groups were not significantly different, but ferritin increased significantly and liver dysfunction-related diseases were seen more in the BMI group. As much as 51% of patients of the BMI group had anemia, compared with 27% of the patients without BMI (P = 0.001). The estimated 2-year OS rates in the two groups were 10 and 34%. The estimated 2-year OS rate of the 67 patients with BMI, who did not lose to follow-up, was 22%, compared with 38% in the non-BMI group. The median survival times of the 2 groups were 120 and 356 days. The estimated 2-year OS rate of patients treated by CHOP regimen was 9%, compared with 51% of those with intensive chemotherapy, with a significant difference (log rank P = 0.0008). The median survival time of the 14 patients subjected to chemotherapy combined with L: -asparaginase was 365 days and that of the 7 patients undergoing hemopoietic stem cell transplantation (HSCT) was 575 days. A total of 3 patients in a critical condition underwent plasmapheresis as initial therapy and achieved stable condition. We conclude that patients with PTCLs with BMI on initial diagnosis usually have hemaphagocytic syndrome and poor prognosis. BMI without lymphadenopathy is a patent clinical feature in most PTCLs. Patients with anemia on initial diagnosis in the BMI group usually have poor prognosis than those without. Intense chemotherapy, addition of L: -asparaginase in chemotherapy and HSCT are comparatively efficient treatments of PTCLs. For patients in critical conditions, plasmapheresis before chemotherapy would lower the risk and improve the tolerance to chemotherapy.

Histologic Findings in T-cell Lymphoma Infiltration of the Optic Nerve

To report the clinical and histologic features of lymphomatous infiltration of the optic nerve by systemic T-cell non-Hodgkin's lymphoma (NHL). Interventional case report. A patient with peripheral T-cell NHL. A 39-year-old man with a diagnosis of peripheral T-cell NHL, stage IV, with CNS involvement and decreased vision was found to have lymphomatous infiltration of the optic nerves. Visual acuity. Despite treatment with chemotherapy and an optic nerve sheath fenestration, the patient lost vision in the right eye and subsequently underwent an optic nerve biopsy. The histopathology showed diffuse infiltration with a clonal population of lymphocytic cells that were CD3 positive and CD20 negative, consistent with T-cell NHL. Optic nerve infiltration from systemic B-cell lymphoma is rare and has been reported; we report an unusual case of bilateral optic nerve infiltration secondary to peripheral T-cell NHL.

Peripheral T‐cell lymphomas, unspecified (or not otherwise specified): a review

Peripheral T-cell lymphomas (PTCL) comprises a heterogeneous group of haematological tumours, which originate from mature T-cells, and constitute less than 15% of all non-Hodgkin's lymphomas (NHLs) in adults. The current WHO classification recognizes nine distinct clinicopathologic peripheral T-cell NHLs, being the 'unspecified variant' (PTCL-U) the most common subtype. These neoplasms often present in advanced stage at diagnosis, and most commonly have an aggressive clinical course requiring prompt treatment. The rarity of these tumours requires additional studies to better understand their biology and search for new therapies which may hopefully improve the dismal outcome of most patients. This review aims to describe the pathobiological aspects as well the clinical characteristics and current therapeutic strategies of the PTCLs, with special attention to the group of PTCL-U.

Flow Cytometric Examination of Non-Hematic Body Fluids in Hematologic Malignancies: A Comparison with Cytology.

Introduction: Flow cytometry is well known to detect malignant cells in peripheral blood and bone marrow of patients with hematologic malignancies. However, its role in evaluating non-hematic body fluid contamination by tumor cells is largely unexplored.Patients and Methods: Data detected by flow cytometry in non-hematic body fluid samples drawn between 2002 and 2007 from patients with hematologic neoplasms were retrospectively compared with morphological findings obtained from cytospin slides. Immunophenotyping was carried out by using disease-specific multicolor panels of quadruple monoclonal antibodies, conjugated with the fluorochromes FITC, PE, PerCP, and APC, respectively. Acquisition of information on 1x104 to 1x105 stained cells depending on the whole sample cellularity was assessed on a dual-laser FACSCalibur flow cytometer using the CellQUEST software (Becton Dickinson, San José, CA, USA).Results: Fourty-five samples (bronchoalveolar fluid, n=5; ascites, n=2; hydrocele, n=2; pleural effusion, n=8; and cerebrospinal fluid, n=28) from 32 patients were available for comparison. Diagnoses were as follows: chronic myelomonocitic leukemia (n=1), acute promyelocytic leukaemia (n=2), acute myelomonocytic leukaemia (n=1), B-chronic lymphocitic leukemia (n=4), follicular lymphoma (n=1), acute lymphoblastic leukaemia (n=6), lymphoblastic lymphoma (n=1), high grade non-Hodgkin's lymphoma (NHL), Burkitt-like (n=3), diffuse large B-cell NHL (n=6), peripheral T-cell NHL (n=3), and NHL, unspecified (n=4). Flow cytometry detected neoplastic cells in 24 cases. Of these cases, only 17 were positive also by morphology. In 7 cases, in which tumor cells were detected by flow cytometry but not by morphology, clinical data confirmed the presence of the disease. Flow cytometry did not show neoplastic cells in 21 cases. Of these cases, only 18 were negative also by morphology. In the remaining 3, the suggestion of diffuse large B-cell NHL contamination by morphology was not confirmed by flow cytometry, demonstrating T-reactive lymphocytes that were clearly negative for disease-specific markers.Conclusions: Our data suggest that flow cytometry is a useful tool complementary to morphology for the screening of non-hematic body fluid contamination in patients with hematologic neoplasms.

Management of peripheral T-cell non-Hodgkin's lymphoma

Peripheral T-cell lymphomas are an uncommon and heterogeneous group of non-Hodgkin's lymphomas that are noted for their particularly poor prognosis. Their rarity has resulted in few data being available to allow formulation of optimal treatment approaches. There remains no widely accepted standard therapy. A new and increasing interest in studying these lymphomas is leading to advances in our understanding, which is widening options for management. Historically, peripheral T-cell lymphomas were treated with strategies borrowed from management of aggressive B-cell lymphomas. Investigators have recognized the inadequacy of these approaches, and we are beginning to receive results, often preliminary, of studies specifically designed to evaluate T-cell lymphomas. These range from transplantation approaches, to better prognostic schemes and to attempts at molecular characterization, and new drugs are being developed specifically for their activity against T-cell lymphomas. Research in T-cell lymphomas is still mainly preliminary and studies tend to be small. Nonetheless, our understanding of these disorders is increasing, and data on new and hopefully better approaches are emerging.

Lymphome T révélé par une mononeuropathie multiple : étude d’un cas avec revue de la littérature

Lymphoma occasionally affects the peripheral nervous system. Neuropathy usually appears in patients with known lymphoma but rarely represents the initial manifestation of underlying malignancy. We report a case in which mononeuritis multiplex (MM) was the dominant feature in the clinical presentation of a peripheral T-cell non-Hodgkin lymphoma (NHL). A 32-year-old man suffered from an asymmetric progressive sensory-motor peripheral neuropathy. The left peroneal nerve was affected first, then the left median nerve after one month, followed by the left trigeminal nerve ten months later. The electrophysiological study confirmed the diagnosis of axonal sensory-motor MM. Mediastinal adenopathies, splenomegaly, pancytopenia and inflammatory syndrome were also found. An osteo-medullary biopsy showed a T-cell NHL. Nerve biopsy study found an inflammatory lymphoid infiltration without malignant cell supporting the hypothesis of an inflammatory pathogenic process. Chemotherapy including cyclophosphamide, hydralazine, vincristine and prednisone were administered monthly during 8 months. No improvement was obtained. It must be emphasised that this case is an uncommon one. On the one hand, NHL is rarely associated with MM and on the other hand, it can exceptionally be revealed by a MM. We were able to find 30 reported cases of distal neuropathy revealing a NHL including, 8 mononeuritis simplex, 9 MM and 13 polyneuropathies. Polyradiculoneuritis cases were excluded from this study because the neuropathy is usually caused by a meningeal infiltration. The neuropathy was in the majority of the cases chronic and axonal. The lymphoma was more often B-cell than T-cell. The B-cell lymphoma was frequently associated with a poor prognosis. All mechanisms were present with a predominance of neurolymphomatosis.

Improved Survival in Patients with Peripheral T Cell Lymphoma, Unspecified Following High-Dose Therapy and Stem Cell Transplantation: A Retrospective Review of a Single Institution's Experience.

Background: Peripheral T-cell non-Hodgkin's lymphomas (PTCL) account for approximately 10% of all non-Hodgkin's lymphomas in the U.S. and Europe. PTCL, unspecified (PTCL-U), as classified by the WHO, is the most common subtype. The ability of high-dose therapy (HDT) and stem cell transplantation (SCT) to improve patient outcome was evaluated in the current study.Methods: All patients with PTCL-U evaluated at our institution who had tissue specimens available for review from January, 1994 to December, 2005 were identified and both clinical characteristics and treatment course obtained from the medical record.Results: 89 patients with PTCL-U were identified, with a median follow up of 13 months (range 1 month–12 years). The median age at diagnosis was 56 years (range 24–90). The IPI was low, intermediate or high in 34%, 44% and 22% of patients, respectively. On univariate analysis, age >60 (p<.0001), ECOG performance status >1 (p<.0001), LDH greater than normal (p=.004), Ann Arbor Stage III/IV (p=.01) and the presence of B symptoms (p=.0004) were associated with a poorer overall survival, as was an intermediate or high IPI (p<.0001). In contrast, on multivariate analysis only age >60 (p=.0006) and ECOG performance status >1 (p=.007) were independently associated with poorer overall survival. Fifty-seven percent of patients were treated initially with an anthracycline-based regimen, most commonly CHOP (53%). Patients with a low (0–1), intermediate (2–3) or high (4–5) IPI experienced a 61%, 29% and 18% 5-year overall survival, respectively. Fourteen patients (16%) received HDT and autologous (n=12) or allogeneic (n=2) SCT, either at the time of a first partial or complete response (n=11) or at the time of first relapse (n=3). The median survival in those patients treated initially with an anthracycline-based regimen alone was 11 months (95% CI 0.6–1.6 years). Improvement in both 5-year overall (75% vs 24%, HR=5.6, 95% CI 2.0–23.4, p=.0004) and disease-free (60% vs 26%, HR=3.2, 95% CI 1.3–9.3, p=.008) survival was observed in patients who received HDT/SCT, as compared to patients treated with anthracycline-based therapy alone. Furthermore, improvement in both 5-year overall (80% vs 26%, HR=5.8, 95% CI 1.7–35.7, p=.002) and disease free (72% vs 26%, HR=3.8, 95% CI 1.3–15.8, p=.009) survival was observed in patients who received HDT/SCT at the time of a first partial or complete response when compared to patients who received anthracycline-based therapy. When patients who failed to achieve a first partial or complete response were excluded from the analysis, improved 5-year overall (80% vs 57%, HR=0.5, 95% CI 0.1–2.1, p=.4) and disease-free (72% vs 53%, HR=0.7, 95% CI 0.1–2.3, p=.5) survival were observed in patients who received upfront HDT/SCT, although this failed to reach statistical significance. The improved overall and disease free survival observed in patients receiving HDT/SCT, either at the time of a first response or at the time of relapse, remained significant when accounting for differences in the IPI.In conclusion, selected patients with PTCL-U may benefit from treatment with HDT/SCT following a first response to conventional anthracycline-based chemotherapy.

Benefits of CHOP-14 Followed by Transplantation in Patients with Peripheral T-Cell Lymphoma.

Background: Compared to B-cell lymphomas, peripheral T-cell non-Hodgkin lymphomas (PTCL) represent a subtype that more frequently involve extranodal sites and worse relapse free survival (RFS) and overall survival (OS) with and without risk stratification by the international prognostic index (IPI). Moreover, while traditional anthracycline containing regimens can induce complete remission (CR), they have not significantly improved long-term outcomes for patients (pts) with PTCL and resulted in 5-year OS and failure-free survival of 26% and 20%, respectively. We examined the pathologic features and clinical presentation of pts with PTCL from Emory University Hospital to determine the outcome of PTCL patients treated with anthracycline based regimens and to investigate predictors for RFS.Methods: The Winship Cancer Institute Lymphoma database was screened to retrospectively identify all patients diagnosed with PTCL by the World Health Organization classification system. Patients were excluded if they had cutaneous T- cell lymphoma, anaplastic large cell lymphoma or if the pertinent prognostic and treatment information was incomplete. Review of historical pathology slides occurred when required to classify all cases into a WHO diagnosis category.Results: In total, 32 evaluable pts with PTCL diagnosed between 1994 and 2005 were identified. Median age at diagnosis was 46 years (range 18–74 years). 70%were male. PTCL subtypes were distributed as follows: 20 pts with peripheral T-cell lymphoma unspecified (PTCL-US) (61%), 7 with angioimmunoblastic T-NHL (21%), 4 with extranodal or nasal NK/T-cell lymphoma (12%), and one of each enteropathic and hepatosplenic T- NHL. Ten pts had confirmed gamma/delta T-cell gene rearrangement (30%). Most pts had advanced stage disease (79% stage IV, 9% stage III); 65% had IPI > 2. Fifteen pts had bone marrow involvement at diagnosis (45%) and 4 had biopsy proven skin involvement (12%). Twenty patients were treated with CHOP chemotherapy initially, 4 of whom received CHOP every 14 days with growth factor support (CHOP14), 8 patients received hyperCVAD/Mtx-Ara-C (HCVAD) and 5 received other regimens. Complete remission (CR) was achieved in 50% of pts who received CHOP, in 63% of pts with HCVAD and 17% of pts receiving other therapies. Three of the four pts who received CHOP-14 achieved CR. 50% of pt receiving CHOP21 and 75% of pts receiving HCVAD underwent stem cell transplantation at relapse (n=10) or in CR1 (n=3). All pts who received CHOP14 proceeded to planned SCT. Median RFS and OS were 7months (range 0.9–65) and 24 months (9–59) among patients who received any CHOP regimen, and were 8 months (1–50) and 20 months (5–54) among those who received HCVAD, respectively. Pts who received CHOP14 followed by planned transplantation had the longest RFS of any subgroup: 16 months (0.9–24). Kaplan-Maier OS curves for pts who received CHOP14, CHOP21, HCVAD, and other regimens are shown below.Conclusions: CHOP14 followed by planned stem cell transplantation may provide a platform for achieving CR and sustaining RFS in pts with PTCL. This treatment strategy is a promising one for study in prospective clinical trials of PTCL. [Display omitted]

Mutational Analysis of NOTCH1 Gene in Mature T-Cell Leukemia/Lymphoma.

A somatic mutation of the NOTCH1 gene is frequently observed in T-cell acute lymphoblastic leukemia (T-ALL) of immature T-cell leukemia, but its prevalence in mature T-cell leukemia/lymphoma remains unknown. T-cell non-Hodgkin lymphomas (T-NHL) are relatively uncommon malignancies that represent approximately 12% of all lymphomas. The current WHO/EORTC classification recognizes 9 distinct clinicopathologic peripheral T-NHLs. The identification of genetic abnormalities and chromosomal rearrangements has been helpful in recognizing and defining lymphoma entities according to the WHO classification. However, the molecular changes that could play a role in leukemogenesis and progression remain unknown. NOTCH1 gene mutation was analyzed in 53 mature T-cell leukemia/lymphoma in adults, comprising 21 with adult T-cell leukemia (ATL), 25 with T-cell non-Hodgkin lymphoma (T-NHL), seven with T-cell prolymphocytic leukemia (T-PLL). We analyzed the hotspots of the NOTCH1 activating mutation in T-ALL cases located in exons 26 and 27, which encodes the N-terminal and C-terminal region of the heterodimerization (HD-N, HD-C) domain, and in exon 34, which encodes the PEST domain and terminal activation domain (TAD). Mutation detection in these two locations was performed by means of PCR-based denaturing high-performance liquid chromatography (dHPLC) using a WAVE DNA fragment analysis system followed by sequencing. We detected a nonsense mutation, C7249T, resulting in Q2417X, in an ATL patient, and a missense mutation, A6955G, resulting in M2319V, as well as a 3-bp deletion between 7234 and 7236 that resulted in deletion of the proline at codon 2412 in the same allele in a T-NHL, peripheral T-cell lymphoma, unspecified (PTCL-u), patient. NOTCH1 mutation was infrequent in mature T-cell leukemia/lymphoma, but NOTCH1 may be involved in leukemogenesis associated with a variety of T-cell leukemia/lymphoma rather than only with T-ALL. [Display omitted]

T-cell non-Hodgkin lymphoma

T-cell non-Hodgkin lymphomas (NHLs) are uncommon malignancies. The current WHO/EORTC classification recognizes 9 distinct clinicopathologic peripheral T-cell NHLs. These disorders have unique characteristics and require individualized diagnostic and therapeutic strategies. Tremendous progress has been made in recent years in the understanding of the pathogenesis of these disorders. Specific chromosomal translocations and viral infections are now known to be associated with certain lymphomas. In this review, we describe their clinical and pathologic features. We also discuss the use of molecular studies in the diagnostic work-up of T-cell lymphomas. Because of the rarity of these disorders and the lack of well-designed clinical trials, the treatment of peripheral T-cell NHLs is often challenging. Additional studies are required to learn more about the biology of these diseases, which may lead to more optimal and possibly targeted therapies.

Elevated NF-κB p50 complex formation and Bcl-3 expression in classical Hodgkin, anaplastic large-cell, and other peripheral T-cell lymphomas

Transcription factor nuclear factor kappa B (NF-kappaB) plays a central role in the pathogenesis of classical Hodgkin lymphoma (cHL). In anaplastic large-cell lymphomas (ALCLs), which share molecular lesions with cHL, the NF-kappaB system has not been equivalently investigated. Here we describe constitutive NF-kappaB p50 homodimer [(p50)2] activity in ALCL cells in the absence of constitutive activation of the IkappaB kinase (IKK) complex. Furthermore, (p50)2 contributes to the NF-kappaB activity in Hodgkin/Reed-Sternberg (HRS) cells. Bcl-3, which is an inducer of nuclear (p50)2 and is associated with (p50)2 in ALCL and HRS cell lines, is abundantly expressed in ALCL and HRS cells. Notably, a selective overexpression of Bcl-3 target genes is found in ALCL cells. By immunohistochemical screening of 288 lymphoma cases, a strong Bcl-3 expression in cHL and in peripheral T-cell non-Hodgkin lymphoma (T-NHL) including ALCL was found. In 3 of 6 HRS cell lines and 25% of primary ALCL, a copy number increase of the BCL3 gene locus was identified. Together, these data suggest that elevated Bcl-3 expression has an important function in cHL and peripheral T-NHL, in particular ALCL.

Peripheral T-cell non-Hodgkin's lymphoma NOS: naming of parts

Peripheral T-cell non-Hodgkin's lymphoma NOS: naming of parts