Romidepsin-associated cardiac toxicity and ECG changes: A case report and review of the literature.

Background Romidepsin is a novel histone deacetylase inhibitor that is approved for the treatment of cutaneous and peripheral T-cell lymphoma in patients who have had at least one prior therapy. Romidepsin is generally well tolerated, though it comes with a risk of cardiac toxicities. Objective We report a case of electrocardiogram changes in a 64-year-old male with enteropathy-associated T-cell lymphoma, type 2, treated with salvage romidepsin therapy who relapsed after non-myeloablative allogeneic sibling peripheral blood stem cell transplant. Discussion Although histone deacetylase inhibitors have been investigated for many years, they have only recently been translated to clinical use as a therapy for malignancies. Furthermore, given their approval for a rare disease, clinicians often have limited experience with the dosing and side effects of histone deacetylase inhibitors. Conclusion This case report and literature review investigates the cardiac side effects of histone deacetylase inhibitors and illustrates the importance of cardiac monitoring prior to and during treatment.

Rapid Fatal Acute Peripheral T-Cell Lymphoma Associated With IgG Plasma Cell Leukemia and IgA Hypergammaglobulinemia.

Simultaneous occurrence of T-cell and B-cell neoplasms is rare, and etiologic relationships between these 2 malignancies are poorly understood. We describe the case of a 66-year-old woman who was admitted to the hospital because of fever, hemoptysis, lymphadenopathy, and skin rash. Enlarged lymph nodes in axillary, pectoral, paratracheal, and periportal regions as well as slight hepatomegaly and splenomegaly were confirmed. A peripheral blood smear revealed rouleaux formation and numerous circulating plasma cells, with plasmacytoid lymphocytes. Immunofixation-electrophoresis detected a monoclonal band defined as immunoglobulin (IgG)-lambda light chains with broad-band polyclonal IgA. The patient died from abrupt splenic rupture before diagnostic work-up was finished. Postmortem examination revealed infiltration of atypical lymphoid cells exhibiting high proliferative activity admixed with typical and atypical plasma cells in several organs. Thus, plasma cell leukemia (IgG-lambda) as a rare and aggressive variant of plasma cell myeloma in the present case was associated with aggressive peripheral T-cell lymphoma and polyclonal (IgA) plasmacytosis.

Clinical analysis and prognostic significance of lymphoma-associated hemophagocytosis in peripheral T cell lymphoma.

This study aims to retrospectively analyze the clinical characteristics, treatments, and prognosis of aggressive peripheral T cell lymphoma (PTCL) patients with a lymphoma-associated hemophagocytosis syndrome (LAHS). We compared the clinical features and the overall survival (OS) rates of 159 PTCL patients with and without LAHS as well as the treatment outcomes of these patients with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or intensive chemotherapy regimens. We observed that in 23 % (36/159) patients PTCL was associated with LAHS. Different subtypes of PTCL in LAHS patients were diagnosed and peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) was the main subtype (78 %). The median survival rates of the LAHS and non-LAHS groups were 3 and 16 months, respectively. The elevated rates of serum ß2-microglobulin, ferritin, fasting triglycerides, and hypofibrinogen levels were higher in the LAHS group, so were bone marrow involvement, liver dysfunction, hepatosplenomegaly, and B symptoms. Three patients who were treated with a plasma exchange had a longer survival time. There was no statistically significant difference in the OS rates between the intensive chemotherapy and CHOP regimen groups (P > 0.05). PTCL patients with LAHS had a poorer prognosis. Awareness of the clinical symptoms and laboratory findings are crucial in order to diagnose LAHS in an early stage and repeated biopsies of multiple bone marrows from different locations in those patients without enlargement of superficial lymph nodes are necessary to improve the diagnosis. Intensive chemotherapy due to its severe toxicity was not obviously advantageous for the OS rate compared to the CHOP regimen.

New molecular insights into peripheral T cell lymphomas.

Peripheral T cell lymphomas (PTCLs) are heterogeneous neoplasms and represent about 12% of all lymphoid malignancies. They are often regarded as "orphan diseases," a designation that does not reflect their real incidence but rather signifies the difficulties encountered in their classification, diagnosis, and treatment. Here we revise the current understanding of the pathobiological characteristics of the most common nodal PTCLs by focusing on the contribution given by high-throughput technologies and the identification of potential therapeutic targets proposed by translational studies.

Belinostat: clinical applications in solid tumors and lymphoma.

INTRODUCTION: Histone deacetylase (HDAC) inhibitors have recently emerged as a novel and active class of anticancer agents. Belinostat is one member of the class that has been tested as a single agent and in combination with other chemotherapies and biological agents in the treatment of solid tumors and lymphoma. AREAS COVERED: A literature search of pre-clinical and clinical studies of belinostat was performed. The data from these studies were analysed to summarise the progress of belinostat from Phase I to a current pivotal trial in peripheral T-cell lymphoma. The parallel development of appropriate biomarker analysis is also discussed. EXPERT OPINION: Belinostat has demonstrated significant clinical activity in T-cell lymphomas. Although its activity as a single agent in solid tumors has been less compelling, the emerging results from combination trials are promising. However, the basis for the activity of belinostat, like that of other HDAC inhibitors, remains to be truly defined and the identification of predictive and prognostic biomarkers of activity should be established to further progress the development of this compound.

Peripheral T-cell lymphoma: a case-based discussion of recent advances in patient management.

Peripheral T-cell lymphomas (PTCLs) are relatively rare, and data from large, comparative studies are limited. There are several histologic subtypes, which can be difficult to distinguish. Prognosis and management approaches can vary according to subtype. The standard management for PTCL patients is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like regimens. Most patients will respond to CHOP, but a common drawback is the limited durability of response. Several recent trials have examined whether the addition of agents such as etoposide, alemtuzumab, and denileukin diftitox to CHOP can improve outcome. Data appear to suggest that such additions provide only a small amount of benefit, which may be limited to patients who are younger or who have a better prognosis. The newer agent pralatrexate may be beneficial, including when a fast remission is needed prior to a stem cell transplant. Upfront transplants are often used in patients in first remission. In this case-based discussion, Drs. Franco and Popplewell focus on the management of several PTCL subtypes: PTCL-not otherwise specified (PTCL-NOS), PTCL with cutaneous involvement, and angioimmunoblastic lymphoma (AITL).

Activation of T-cell receptor signaling in peripheral T-cell lymphoma cells plays an important role in the development of lymphoma-associated hemophagocytosis.

Peripheral T-cell lymphoma (PTCL) is a biologically diverse lymphoid malignancy. The clinical aggressiveness associated with hemophagocytic syndrome (HS) is a characteristic of PTCL, being more distinctive in CD8(+) PTCL. However, the underlying mechanism of PTCL-associated HS has not yet been fully investigated. We newly established a novel IL-2-dependent CD8(+) PTCL lymphoma cell line (T8ML-1) from a patient with CD8(+) PTCL who suffered recurrent HS accompanying disease flare-up. Focusing on the lymphoma cell T-cell receptor (TCR), we examined the lymphoma cell functions responsible for such clinical manifestations. First, T8ML-1.1 in which endogenous TCR-α/ß chains were silenced by siRNAs, and T8ML-1.2 in which endogenous TCR-α/ß chains were replaced with HLA-A*24:02-restricted and WT1(235-243)-specific TCR-α/ß, were established. T8ML-1 exerted phytohemagglutinin (PHA)-dependent cytotoxicity via granular exocytosis. Additionally, soluble factors produced by PHA-stimulated T8ML-1, which included INF-γ and TNF-α, but not by simple-cultured T8ML-1, caused human monocytes to exhibit erythrophagocytosis and thrombophagocytosis in vitro. PHA binding induced phosphorylation of CD3ζ chain. Furthermore, both cytotoxicity and hemophagocytosis were completely inhibited by T8ML-1.1, but eventually restored by T8ML-1.2. These data suggest that exogenous activation of TCR signaling in PTCL cells might play an important role in the formation of PTCL-associated HS.

Advances in the understanding and management of angioimmunoblastic T-cell lymphoma.

Angioimmunoblastic T-cell lymphoma (AITL) is a distinct peripheral T-cell lymphoma (PTCL) entity with peculiar clinical and pathological features. The recent identification of follicular helper T (T(FH)) cell as the cell of origin of this neoplasm represents a major step in our understanding of the pathobiological characteristics of the disease and should, in the future, clarify the diagnostic criteria for AITL and help to delineate its spectrum, especially from PTCL, not otherwise specified (PTCL, NOS). Deciphering the pathogenesis of the disease is needed to identify targets for new therapies that are expected to improve the poor outcome of AITL patients, when treated with conventional chemotherapy regimens. In this respect, efforts will be needed to evaluate promising innovative therapies in prospective clinical trials.

Peripheral T-cell lymphoma of Lennert type complicated by monoclonal proliferation of large B-cells.

A 69-year-old man presented with lymph node swelling in the right inguinal region. A biopsy was made (LN1) and diagnosed as peripheral T-cell lymphoma. The lesion remitted completely over a period of about 51 months after combination chemotherapy, but erythematous papules, systemic lymphadenopathy, and fever of 38 degrees appeared. Skin (S1) and lymph nodes (LN2) were biopsied. Erythematous papules once disappeared spontaneously, but appeared again and were biopsied (S2). LN1 displayed the typical histologic and immunohistochemical features of Lennert lymphoma, i.e., diffuse proliferation of small to large lymphoid cells of CD3+, CD4+, CD8- immunophenotype accompanied by numerous clusters of epithelioid histiocytes. In LN2, the large cells with CD3+, CD4+, CD8- decreased in number, while numerous CD20+ large cells were discernible. Clonality analysis revealed the persistent presence of an identical T-cell clone in LN1 and LN2. Clonal bands of immunoglobulin heavy (IgH) chain gene were detected in LN2 but not in LN1. S1 and S2 showed diffuse proliferation of small to large lymphoid cells of CD20-, CD3+, CD4+, CD8- in the upper dermis, with obvious epidermotropism. Clonality analysis revealed the presence of a T-cell clone identical to LN1 and LN2 with no B-cell clone, indicating the recurrence of PTCL. In situ hybridization (ISH) for Epstein-Barr virus (EBV) genome revealed that positive signals in the nucleus of large B-lymphoid cells appeared only in LN2. Taken together, EBV-positive large B-cell lymphoma appeared transiently in the course of "Lennert lymphoma".

Novel CD19 expression in a peripheral T cell lymphoma: A flow cytometry case report with morphologic correlation.

BACKGROUND: Peripheral T-cell lymphomas are uncommon lymphomas that show T-cell antigenic loss and clonal T-cell receptor (TCR) gene rearrangement. Rare cases of T-cell lymphomas with aberrant expression of CD20 have been described. However, CD19 coexpression in a mature T-cell neoplasm has not been reported. METHODS: Histology, immunohistochemistry (IHC), and PCR for TCR gene rearrangement were performed on an excised lymph node specimen and a subsequent fine needle aspiration (FNA) of an additional lymph node. Flow cytometry (FC) was performed on FNA and peripheral blood specimen. RESULTS: The lymph node's architecture was effaced by a diffuse atypical lymphoid proliferation that, by IHC, was positive for CD3, CD2, and CD43 and negative for CD4, CD5, CD8, TdT, CD1a, and B-cell-associated antigens PAX-5, CD20, and CD79a. A clonal TCR gene rearrangement was detected. FC was performed on a subsequent FNA, and peripheral blood specimen demonstrated an aberrant T-cell population with expression of CD2, CD3, CD27, TCR alpha/beta, CD52, CD38, CD45, and CD26 (partial expression) and negative for CD4, CD5, CD7, CD8, CD10, CD30, and CD56. The aberrant T-cell population also expressed bright CD19. CONCLUSIONS: Using FC, we describe the first case of peripheral T-cell lymphoma with aberrant coexpression of CD19.

Measurement of pruritus in a Chinese woman with pemphigoid gestationis using a wrist movement detector.

Pemphigoid gestationis (PG) is a rare itching bullous disease of pregnancy and the postpartum period. We describe the use of a new methodology for measuring the nature and intensity of itching in a 21-year-old woman with pemphigoid gestationis. At 19 weeks gestation, she developed an itchy rash over the limbs, which spread to the trunk. Blisters then appeared on the hands which subsequently also involved the feet. Intense nocturnal wrist activities in this patient, measured with a wrist monitor and defined as average acceleration in the early hours of sleep, were even higher than that in patients with severe eczema, with an average value of 181.00 +/- 43.49 (mean +/- standard error) g/min for the first three hours, versus 84.47 +/- 8.53 g/min for the group of 24 eczema subjects. Most wrist activities were slower movements at 0 to 1 Hz. This is in striking contrast to the scratching activities at 0 to 3 Hz in eczema subjects. There have been no therapeutic trials for PG. Topical steroid and oral antihistamines are usually ineffective, but worked in our patient. We also discuss the potential application of the monitor in assessing the nature of various dermatological or systemic itching disorders.

Evaluation and management of angioimmunoblastic T-cell lymphoma: a review of current approaches and future strategies.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare and complex lymphoproliferative disorder, clinically characterized by widespread lymphadenopathy, extranodal disease, immune-mediated hemolysis, and polyclonal hypergammaglobulinemia. Significant progress has been made in the understanding of AITL since its recognition as a clonal T-cell disorder with associated deregulation of B-cells and endothelial cells within a unique malignant microenvironment. However, as the responses to conventional chemotherapy have not been durable, prognosis with current treatment approaches has remained dismal. Here we review the clinical presentation, prognosis, and management of patients with AITL. We discuss recent developments in the understanding of the pathogenesis of AITL at a cellular and molecular level, including the implication of the follicular helper T-cell as the corresponding cell of origin, the roles of Epstein-Barr virus, B-cell deregulation, angiogenesis, and other signaling pathways in AITL, and the therapeutic implications of these findings. Finally, we discuss recent clinical trials and novel treatment approaches in the management of patients with AITL.

Angio-immunoblastic T-cell lymphoma in evolution: a case report.

Angio-immunoblastic T-cell lymphoma (AITL), a rare disease that constitutes 1% to 2% of non-Hodgkin's lymphomas, presents in middle-aged and elderly individuals. This report describes a patient with high-grade fever and lymphadenopathy. An extensive in-hospital work-up that included lymph node biopsy yielded negative results. The patient became asymptomatic for 4 wk, but then symptoms recurred with more pronounced lymphadenopathy. A computed tomography scan documented recurrent diffuse lymphadenopathy. Another lymph node biopsy revealed florid changes that strongly suggested AITL. Flow cytometry confirmed this diagnosis. The patient was treated with hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and achieved complete remission after the first cycle. The patient developed sepsis during the second cycle and expired within 4 mo of diagnosis. The prognosis and natural course of AITL are poor when the classic chemotherapy protocol is administered. When infection has been ruled out, physicians should be wary of aggressive lymphomas that present with diffuse lymphadenopathy and fever.

Pulmonary manifestations of peripheral T-cell lymphoma: case report and review of the literature.

INTRODUCTION: Peripheral T-cell lymphomas (PTCL) represent approximately 10% of non-Hodgkin's lymphomas. Pulmonary involvement is an uncommon manifestation of this heterogeneous group of malignancies. METHODS: Report of a case. RESULTS: This case report describes a 75-year-old man with fever, weight loss, anemia, enlargement of spleen and liver, atypical lymphocytes and pulmonary nodules. Lung biopsy showed lymphocytic infiltration of the lung parenchyma. T-cell receptor gamma gene rearrangement by polymerase chain reaction confirmed the diagnosis of peripheral T-cell lymphoma. Unfortunately, the patient died because of refractory and aggressive disease. CONCLUSION: Pulmonary and pleural involvement are seen in patients with PTCL and usually carry a poor prognosis. The subject of pulmonary involvement in peripheral T-cell lymphoma is discussed.

Magnetic resonance findings of primary central nervous system T-cell lymphoma in immunocompetent patients.

PURPOSE: To describe the MR findings of primary central nervous system T-cell lymphoma (T-PCNSL) in immunocompetent patients. MATERIAL AND METHODS: Seven patients with pathologically proven T-PCNSL were included in our study. The number, location, shape, enhancement pattern, and signal intensity of the tumors were determined. Diffusion-weighted images (DWI) and perfusion-weighted images (PWI) were obtained in four and two patients, respectively. Apparent diffusion coefficients (ADCs) were generated, and regions of interest were defined in each lesion. RESULTS: Four patients with T-PCNSL had a single mass, while the others had multiple lesions (four, three, and two lesions, respectively). All seven cases of T-PCNSL had a supratentorial location: 12 in the subcortical area and 1 in the thalamus. No leptomeningeal involvement was noted. All tumors showed iso- to low T1 and iso- to slightly high T2 signal intensity to the adjacent gray matter. Rim enhancement was seen in 5 of the 7 patients (71.4%), while heterogeneous and homogeneous enhancement was seen in each of two. On DWI and ADC maps, the enhancing lesions showed slight hyperintensity in three patients (mean ADC ratio, 0.92 +/- 0.06) and iso-intensity in the other (ADC ratio, 1.02 +/- 0.05). Cystic areas consistent with necrosis were noted in three patients. High-signal intensity area in the cortex was noted on T1-weighted images in three patients, suggesting hemorrhage. In two patients, the same signal intensity area was noted within the mass. The two masses on the relative cerebral blood volume (rCBV) map demonstrated either similar or slightly higher signal intensity than that of the contralateral white matter. The rCBV ratios of these two masses were 1.27 +/- 0.16 and 1.35 +/- 0.2, respectively. CONCLUSION: T-PCNSLs show a predilection for a subcortical location, a relatively high incidence of cortical or intratumoral hemorrhage, rim enhancement, or cystic-areas consistent with necrosis on magnetic resonance imaging. The lower rCBV ratio of the tumor might be helpful in differentiating T-PCNSL from other brain tumors such as high-grade glioma.