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T-cell lymphomas (TCLs) constitute a rare subset of non-Hodgkin lymphomas, with mycosis fungoides/Sézary syndrome (MF/SS) being the most common subtype of cutaneous TCLs (CTCLs). Considered an incurable but treatable disease, MF/SS management presents several challenges including diagnostic delays, debilitating effect on patients' quality of life, need for several lines of therapies, multidisciplinary care and cumulative drug toxicities limiting duration of use. The present review intends to provide an overview of the recent advances in our understanding of the biology of CTCL and how these are being leveraged to provide additional treatment options for management of advanced and recurrent disease. In addition, the discussion of the different modalities of treatment is summarised to further outline the importance of multidisciplinary care and early referral to CTCL centres., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Study Objectives: Mogamulizumab is an important treatment for T-cell leukemia and lymphoma. Adverse cardiovascular events (ACE) after mogamulizumab therapy have not been investigated. The aim of the study is to investigate ACE occurrence after mogamulizumab therapy., Methods: The International World Health Organization database, VigiBase, was analyzed from January 2013 to August 2019 for all adverse events, including ACE, that occurred after mogamulizumab treatment. ACE was defined as: cardiac death, myocardial infarction, heart failure, myocarditis, arrhythmia, vasculitis, thrombosis, palpitations and new hypertension., Results: ACE after mogamulizumab therapy affected 28 out of 650 unique patients (4.3%). Heart failure (42.8%) and ventricular arrhythmias (17.85%) were most common. ACE accounted for 10% of all fatal adverse outcomes, and 25% of all ACE were fatal. Time to fatal outcome was significantly shorter for patients with ACE compared to non-cardiovascular events, with a mean of 7.7 days (SD 6.91) vs 73 days (SD 90.7), p  = 0.017, respectively. There was an increased total number of adverse cardiovascular events in patients greater than 65 and in Asian countries., Conclusions: Cardiovascular toxicity with mogamulizumab is a possible early occurring adverse outcome associated with high mortality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Introduction: The most common types of CTCL are mycosis fungoides (MF) and Sézary syndrome (SS). In both MF and SS, complete responses to treatment are uncommon. Recent developments and understanding of the biology of MF/SS have led to novel agents which may offer prolonged responses with less toxicity compared to conventional chemotherapy approaches., Areas Covered: In this review, we discuss the efficacy and safety of new nonchemotherapy treatment options including antibody agents, small molecule inhibitors, fusion proteins, and CAR T-cell therapy. We also reflect on older immunomodulatory treatments including retinoids and histone deacetylase inhibitors., Expert Opinion: Patients with MF/SS who require systemic therapy often progress through multiple agents sequentially, thus the need for additional novel agents in the treatment armamentarium. Antibody-based therapies such as alemtuzumab are highly effective in the blood compartment of disease, while brentuximab vedotin has shown higher activity in skin and lymph nodes. Checkpoint inhibitors may play a role in treating MF/SS but may induce hyperprogression, and engineered T cells and bispecific antibodies recruiting immune effectors are being developed and may show promise in the future.

Purpose: Intravenous immune globulin (IVIG) therapy is used in patients with hypogammaglobulinemia to lower the risk of infections. IVIG and subcutaneous IVIG (SCIG) therapy have been to shown to be safe and effective when administered as clinic-based infusions. Concern from both patients and providers for increased transmission of the coronavirus disease 2019 (COVID-19) virus to immunosuppressed patients with scheduled medical visits and procedures made it necessary for us to reassess our process of how we manage patient care in general and chronic clinic infusions in particular. Here we describe our experience of transitioning patients from clinic-based to home based IVIG and/or SCIG infusions to decrease the risk of COVID-19 exposure., Methods: Criteria were developed to identify high-risk immunosuppressed patients who would be appropriate candidates for potential conversion to home based IVIG infusions. Data were collected via chart review, and cost analysis was performed using Medicare Part B reimbursement data. A patient outcome questionnaire was developed for administration through follow-up phone calls., Results: From March to May 2020, 45 patients met criteria for home-based infusion, with 27 patients (60%) agreeing to home-based infusion. Posttransition patient outcomes assessment, conducted in 26 patients (96%), demonstrated good patient understanding of the home-based infusion process. No infusion-related complications were reported, and 24 patients (92%) had no concerns about receiving future IVIG and/or SCIG doses at home. No patient tested positive for COVID-19 during the study period. Clinic infusion visits decreased by 26.6 visits per month, resulting in a total of 106 hours of additional available infusion chair time per month and associated cost savings of $12,877., Conclusion: Transition of clinic based to home based IVIG/SCIG infusion can be successfully done to decrease potential exposure during a pandemic in a high-risk immunosuppressed population, with no impact on patient satisfaction, adherence, or efficacy. The home-based infusion initiative was associated with a reduction in costs to patients and an increase in available chair time in the infusion clinic., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Despite decades of work, much remains elusive about molecular events at the interplay between physiological and structural changes underlying neuronal plasticity. Here, we combined repetitive live imaging and expansion microscopy in organotypic brain slice cultures to quantitatively characterize the dynamic changes of the intracellular versus surface pools of GluA2-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) across the different dendritic spine types and the shaft during hippocampal homeostatic plasticity. Mechanistically, we identify ephrinB2 and glutamate receptor interacting protein (GRIP) 1 as mediating AMPAR relocation to the mushroom spine surface following lesion-induced denervation. Moreover, stimulation with the ephrinB2 specific receptor EphB4 not only prevents the lesion-induced disappearance of mushroom spines but is also sufficient to shift AMPARs to the surface and rescue spine recovery in a GRIP1 dominant-negative background. Thus, our results unravel a crucial role for ephrinB2 during homeostatic plasticity and identify a potential pharmacological target to improve dendritic spine plasticity upon injury., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

We report results on 23 patients with cutaneous T cell lymphoma (7 primary cutaneous γδ T cell lymphoma [PCGDT], 16 mycosis fungoides/Sézary syndrome [MF/SS]) who underwent allogeneic stem cell transplantation. All pts had skin involvement, 14 had total skin electron beam before conditioning. Donors were 10/10 HLA matched related (13), 5/10 haploidentical (4), and matched unrelated (5) or mismatched unrelated (1). Thirteen were in a clinical complete remission at the time of transplant. The 100-day transplant related mortality for the MF/SS and PCGDT patients was 12% and 29%, respectively. At a median follow up of 5.5 years, the overall survival and disease-free survival for MF/SS patients was 75% and 64%, respectively, and 6 of 10 MF/SS pts in long term complete response had a partial response at the time of transplant. Of seven PCGDT patients, four of seven are alive at a median follow up of 5 years and three are disease-free.

A recent phase II trial showed that use of polatuzumab vedotin in combination with bendamustine plus rituximab (Pola-BR) in transplant-ineligible patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) resulted in longer progression-free survival and overall survival compared to bendamustine plus rituximab (BR) alone. In this study, we constructed a Markov model to assess the cost-effectiveness of Pola-BR versus BR in transplant-ineligible R/R DLBCL. We calculated the incremental cost-effectiveness ratio (ICER) of each treatment strategy from a US payer perspective, using a lifetime horizon and a willingness-to-pay threshold of $100,000 per quality-adjusted life-year (QALY). Use of Pola-BR was associated with an incremental cost of $92,641 compared to BR alone ($200,905 vs $108,265, respectively), an incremental effectiveness of 1.76 QALYs (2.35 vs 0.59 QALYs, respectively), and an ICER of $52,519/QALY. These data suggest that use of Pola-BR for R/R DLBCL is likely to be cost-effective compared to BR alone.

Cellular senescence is a key component of human aging that can be induced by a range of stimuli, including DNA damage, cellular stress, telomere shortening, and the activation of oncogenes. Senescence is generally regarded as a tumour suppressive process, both by preventing cancer cell proliferation and suppressing malignant progression from pre-malignant to malignant disease. It may also be a key effector mechanism of many types of anticancer therapies, such as chemotherapy, radiotherapy, and endocrine therapies, both directly and via bioactive molecules released by senescent cells that may stimulate an immune response. However, senescence may contribute to reduced patient resilience to cancer therapies and may provide a pathway for disease recurrence after cancer therapy. A new group of drugs, senotherapies, (drugs which interact with senescent cells to interfere with their pro-aging impacts by either selectively destroying senescent cells (senolytic drugs) or inhibiting their function (senostatic drugs)) are under active investigation to determine whether they can enhance the efficacy of cancer therapies and improve resilience to cancer treatments. Senolytic drugs include quercetin, navitoclax, and fisetin and preclinical and early phase clinical data are emerging of their potential role in cancer treatments, although none are yet in routine use clinically. This article provides a review of these issues.

Purpose: To assess the efficacy of pembrolizumab in patients with advanced relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS)., Patients and Methods: CITN-10 is a single-arm, multicenter phase II trial of 24 patients with advanced MF or SS. Patients were treated with pembrolizumab 2 mg/kg every 3 weeks for up to 24 months. The primary end point was overall response rate by consensus global response criteria., Results: Patients had advanced-stage disease (23 of 24 with stage IIB to IV MF/SS) and were heavily pretreated with a median of four prior systemic therapies. The overall response rate was 38% with two complete responses and seven partial responses. Of the nine responding patients, six had 90% or more improvement in skin disease by modified Severity Weighted Assessment Tool, and eight had ongoing responses at last follow-up. The median duration of response was not reached, with a median response follow-up time of 58 weeks. Immune-related adverse events led to treatment discontinuation in four patients. A transient worsening of erythroderma and pruritus occurred in 53% of patients with SS. This cutaneous flare reaction did not result in treatment discontinuation for any patient. The flare reaction correlated with high PD-1 expression on Sézary cells but did not associate with subsequent clinical responses or lack of response. Treatment responses did not correlate with expression of PD-L1, total mutation burden, or an interferon-γ gene expression signature., Conclusion: Pembrolizumab demonstrated significant antitumor activity with durable responses and a favorable safety profile in patients with advanced MF/SS.

Patients with AIDS have increased risk of developing lymphomas, such as anaplastic large cell lymphoma (ALCL), which generally carry a poor prognosis. The DUSP-IRF4 genetic rearrangement in ALCL confers a favourable prognosis in HIV-negative patients; it is unknown how this interacts clinically with HIV/AIDS. A man aged 53 years presented with subcutaneous nodules on the scalp and axillae, and diffuse lymphadenopathy. Biopsy of subcutaneous nodule and lymph node showed large atypical anaplastic lymphocytes which were CD30+ and anaplastic lymphoma kinase-negative, consistent with primary systemic ALCL. In addition, he was found to be HIV-positive and diagnosed with AIDS. Genetic testing of the tissue revealed a DUSP22-IRF4 rearrangement. Complete remission was achieved with HyperCVAD and subsequent brentuximab vedotin monotherapy. We report a case of AIDS-associated primary systemic ALCL with a DUSP22-IRF4 rearrangement. AIDS-associated ALCL is an aggressive lymphoma, with a poor prognosis. However, the presence of the genetic rearrangement, previously unseen in this disease, drastically altered the disease course. This case highlights the value of genetic testing and identifies DUSP22-IRF4- associated ALCL in the setting of HIV-associated lymphoproliferative disorders., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction : Cutaneous T-cell lymphomas (CTCL) are rare non-Hodgkin lymphomas of skin-homing T-cells that initially or mainly manifest cutaneously. Treatment of CTCL is challenging given the disease states' varying presentation and prognosis. Systemic treatment options often lack comparative evidence and have relatively low response rates and short duration of response. The recent Food and Drug Administration (FDA) approval of mogamulizumab in adult patients with relapsed or refractory (R/R) CTCL after at least one prior line of therapy provided a new treatment option to patients with advanced disease. Areas covered : The authors discuss basic information about CTCL and mogamulizumab's mechanism of action. Then, the authors discuss the agent's efficacy. Finally, the authors evaluate the safety of mogamulizumab in comparison to other agents available in CTCL. Expert opinion : Mogamulizumab has been shown to be an effective and well tolerated therapy for patients with relapsed and refractory MF/SS with excellent activity in the circulating component of the disease.

To correctly transfer information, neuronal networks need to continuously adjust their synaptic strength to extrinsic stimuli. This ability, termed synaptic plasticity, is at the heart of their function and is, thus, tightly regulated. In glutamatergic neurons, synaptic strength is controlled by the number and function of AMPA receptors at the postsynapse, which mediate most of the fast excitatory transmission in the central nervous system. Their trafficking to, at, and from the synapse, is, therefore, a key mechanism underlying synaptic plasticity. Intensive research over the last 20 years has revealed the increasing importance of interacting proteins, which accompany AMPA receptors throughout their lifetime and help to refine the temporal and spatial modulation of their trafficking and function. In this review, we discuss the current knowledge about the roles of key partners in regulating AMPA receptor trafficking and focus especially on the movement between the intracellular, extrasynaptic, and synaptic pools. We examine their involvement not only in basal synaptic function, but also in Hebbian and homeostatic plasticity. Included in our review are well-established AMPA receptor interactants such as GRIP1 and PICK1, the classical auxiliary subunits TARP and CNIH, and the newest additions to AMPA receptor native complexes.

Background: Current guidelines recommend adding vancomycin to empiric treatment of FN in patients who meet specific criteria. After 48 hours, the guidelines recommend discontinuing vancomycin if resistant Gram-positive organisms are not identified. Based on these recommendations, a vancomycin stewardship team defined criteria for discontinuation of vancomycin at 48 hours and increased surveillance of vancomycin usage through a multimodal approach. The purpose of this retrospective analysis is to assess the impact of this multimodal approach on the discontinuation of empiric vancomycin at 48 hours in FN., Methods: This retrospective analysis included a pre- and post-intervention cohort of 200 HSCT recipients with FN from 2015 to 2018. Criteria for continued vancomycin use beyond 48 hours included culture-documented resistant Gram-positive infection, positive Methicillin-Resistant S aureus (MRSA) nasal swab with evidence of pneumonia, or hemodynamic instability with concern for sepsis. The following patient characteristics were collected: previous MRSA infection, MRSA nasal swab collection and results, culture results, duration of vancomycin use, rationale for continuation of vancomycin beyond 48 hours, and re-initiation of vancomycin., Results: In the post-intervention cohort, vancomycin discontinuation at 48 hours increased from 31% (95% CI 21.94-40.05) to 70% (95% CI 61.02-78.97; P < 0.0001). An additional 23% of vancomycin orders were discontinued at 72 hours. Off criteria vancomycin use decreased from 33% in pre to 1% in the post-implementation cohort., Conclusion: Establishing define criteria for vancomycin use in FN patients with a multimodal approach of physicians from hematology and infectious diseases, clinical pharmacists and the antibiotic stewardship team significantly improved vancomycin discontinuation., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: The aim of this open-label, first-in-setting, randomized phase III trial was to evaluate the efficacy of alisertib, an investigational Aurora A kinase inhibitor, in patients with relapsed/refractory peripheral T-cell lymphoma (PTCL)., Patients and Methods: Adult patients with relapsed/refractory PTCL-one or more prior therapy-were randomly assigned 1:1 to receive oral alisertib 50 mg two times per day (days 1 to 7; 21-day cycle) or investigator-selected single-agent comparator, including intravenous pralatrexate 30 mg/m 2 (once per week for 6 weeks; 7-week cycle), or intravenous gemcitabine 1,000 mg/m 2 or intravenous romidepsin 14 mg/m 2 (days 1, 8, and 15; 28-day cycle). Tumor tissue (disease subtype) and imaging were assessed by independent central review. Primary outcomes were overall response rate and progression-free survival (PFS). Two interim analyses and one final analysis were planned., Results: Between May 2012 and October 2014, 271 patients were randomly assigned (alisertib, n = 138; comparator, n = 133). Enrollment was stopped early on the recommendation of the independent data monitoring committee as a result of the low probability of alisertib achieving PFS superiority with full enrollment. Centrally assessed overall response rate was 33% for alisertib and 45% for the comparator arm (odds ratio, 0.60; 95% CI, 0.33 to 1.08). Median PFS was 115 days for alisertib and 104 days for the comparator arm (hazard ratio, 0.87; 95% CI, 0.637 to 1.178). The most common adverse events were anemia (53% of alisertib-treated patients v 34% of comparator-treated patients) and neutropenia (47% v 31%, respectively). A lower percentage of patients who received alisertib (9%) compared with the comparator (14%) experienced events that led to study drug discontinuation. Of 26 on-study deaths, five were considered treatment related (alisertib, n = 3 of 11; comparator, n = 2 of 15). Two-year overall survival was 35% for each arm., Conclusion: In patients with relapsed/refractory PTCL, alisertib was not statistically significantly superior to the comparator arm.

Hepatosplenic T-cell lymphoma (HSTL) is a rare variant of extranodal peripheral T-cell lymphomas (PTCL), associated with aggressive disease course and a relentless track record for lethal outcomes. HSTL presents commonly in young men in their third or fourth decade. Of the known causes, immune dysregulation and immunosuppression are the key players in the pathogenesis of HSTL. Clinical manifestation includes hepatosplenomegaly, fevers, and weakness. Bone marrow involvement or organomegaly can cause cytopenias. Anthracycline-based regimens provide modest responses with most individuals dying within a year of diagnosis. Hematopoietic stem cell transplant (HSCT) can be offered to fit and eligible patients to prolong remissions. Disease relapse post chemotherapy has an aggressive phenotype, with limited salvage options available in the setting of declining performance status. Understanding the disease biology further to identify mechanistic-driven drug discovery could overcome the current limitations of existing therapeutic armamentarium.

Background: Primary cutaneous aggressive epidermotropic cytotoxic CD8 positive T-cell lymphoma (CD8 + PCAETL) is a rare subtype of peripheral T-cell lymphoma with poor outcomes and without a standardized treatment strategy. Allogeneic hematopoietic stem cell transplantation (HSCT) has been suggested as a potential curative therapy., Patients and Methods: We conducted a retrospective case series. We identified 8 patients with the diagnosis of CD8 + PCAETL, 4 of whom also underwent allogeneic HSCT., Results: Eight patients were treated at our center with combination chemotherapy and several novel agents, including histone deacetylase inhibitors, brentuximab, and pralatrexate. Patients underwent a median of 8.5 treatments before HSCT. Six of the 8 patients examined, including all 4 who received an HSCT, were alive at their last follow-up., Conclusion: Allogeneic HSCT is a promising treatment modality for CD8 + PCAETL. Because of the aggressive nature of this disease and lack of sustained remission with currently available therapies, HSCT should be considered early in the course of treatment. Two novel agents, brentuximab and pralatrexate, showed significant activity against CD8 + PCAETL, and may be incorporated earlier in the treatment course., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Recognizing the significant biological and clinical heterogeneity of mature T cell and natural killer (NK)/T cell lymphomas, the American Society for Blood and Marrow Transplantation invited experts to develop clinical practice recommendations related to the role of autologous hematopoietic cell transplantation (auto-HCT) and allogeneic HCT (allo-HCT) for specific histological subtypes. We used the GRADE methodology to aid in moving from evidence to decision making and ultimately to generating final recommendations. Auto-HCT in front-line consolidation is recommended in peripheral T cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T cell lymphoma (AITL), anaplastic large cell lymphoma-anaplastic lymphoma kinase (ALCL-ALK)-negative, NK/T cell (disseminated), enteropathy-associated T cell lymphoma (EATL), and hepatosplenic lymphomas. Auto-HCT in relapsed-sensitive disease is recommended for NK/T cell (localized and disseminated), EATL, subcutaneous panniculitis-like T cell, and ALCL-ALK-positive lymphomas. Auto-HCT is also recommended for PTCL-NOS, AITL, and ALCL-ALK-negative lymphomas if not performed as front-line therapy. Auto-HCT in refractory (primary or relapsed) disease is not recommended for any of the histological subtypes discussed. Allo-HCT in front-line consolidation is recommended for NK/T cell (disseminated), adult T cell leukemia/lymphoma (ATLL; acute and lymphoma type), and hepatosplenic lymphomas. Allo-HCT for relapsed-sensitive disease is recommended for PTCL-NOS, AITL, ALCL-ALK-negative, ALCL-ALK-positive, NK/T cell (localized and disseminated), ATLL (acute, lymphoma type, smoldering/chronic), mycosis fungoides/Sezary syndrome (advanced stage IIB-IVB or tumor stage/extracutaneous), EATL, subcutaneous panniculitis-like T cell, and hepatosplenic lymphoma. Allo-HCT in refractory (primary or relapsed refractory) disease is recommended for any aforementioned histological subtypes. Emerging novel therapies will likely be incorporated into the pretransplantation, peritransplantation, and post-transplantation algorithms (auto-HCT or allo-HCT) with the goals of optimizing efficacy and improving outcomes. We acknowledge that there are unique clinical scenarios not covered by these recommendations that may require individualized decisions., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking in response to neuronal activity is critical for synaptic function and plasticity. Here, we show that neuronal activity induces the binding of ephrinB2 and ApoER2 receptors at the postsynapse to regulate de novo insertion of AMPA receptors. Mechanistically, the multi-PDZ adaptor glutamate-receptor-interacting protein 1 (GRIP1) binds ApoER2 and bridges a complex including ApoER2, ephrinB2, and AMPA receptors. Phosphorylation of ephrinB2 in a serine residue (Ser-9) is essential for the stability of such a complex. In vivo, a mutation on ephrinB2 Ser-9 in mice results in a complete disruption of the complex, absence of ApoER2 downstream signaling, and impaired activity-induced and ApoER2-mediated AMPA receptor insertion. Using compound genetics, we show the requirement of this complex for long-term potentiation (LTP). Together, our findings uncover a cooperative ephrinB2 and ApoER2 signaling at the synapse, which serves to modulate activity-dependent AMPA receptor dynamic changes during synaptic plasticity., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive non-Hodgkin lymphomas typically associated with poor prognosis. Most patients with PTCL receive chemotherapy as first-line treatment, but many experience rapid relapse. For patients with relapsed/refractory PTCL, responses to treatment and long-term outcomes tend to worsen with increasing lines of therapy. Romidepsin is a potent class I histone deacetylase inhibitor approved by the US Food and Drug Administration for the treatment of PTCL in patients who have received ≥1 prior therapy. A pivotal phase 2 trial of romidepsin in patients with relapsed/refractory PTCL demonstrated an objective response rate of 25% (33/130), including 15% with confirmed/unconfirmed complete response, and a median duration of response of 28 months. In the analysis presented herein, romidepsin was shown to have similar responses and long-term outcomes in patients with 1, 2, and ≥3 prior lines of treatment, including in patients with disease refractory to the last prior therapy. Although adverse events increased with increasing lines of treatment, the rate of dose modifications and discontinuations due to adverse events was not significantly different. These data support the use of romidepsin as salvage treatment for PTCL irrespective of the number of prior therapies., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Carmustine (BCNU) is used in the conditioning regimens BEAM and CBV for autologous stem cell transplantation. Carmustine-related infusion reactions, while not described in the BEAM literature, occurred in 95 % of patients who received CBV. The most common symptoms include flushing, facial pain, headache, and hypotension. These reactions have been attributed to the absolute ethanol that is used in the reconstitution process or alternatively by a direct effect of carmustine. It is currently recommended that carmustine 300 mg/m 2 be infused over at least 100 min (3-5 mg/m 2 /min). Prior to October 2014, carmustine infusions were given over 90 min but were changed to 120 min based on the above recommendation. We compared the two infusion rates in patients receiving BEAM to see if lengthening the infusion decreased the frequency of reactions., Methods: Overall, 100 patients received BCNU as part of BEAM or Zevalin BEAM and were equally divided between 90 and 120 min infusion times. The primary outcome was the incidence of infusion-related reactions which were graded based on CTCAE 4.03 descriptions of flushing and infusion-related reactions. We also evaluated the impact of premedication as well as the efficacy of medications used to treat infusion reactions., Results: Between the years 2013-2016, there were 50 patients who received BCNU over 90 min and 50 patients over 120 min. There were no significant differences observed for diagnosis, age and gender between the two groups. Twenty-eight (56 %) in the 90-min and 26 (52 %) in the 120-min infusion intervals developed a reaction (p = 0.6882). Of the patients that developed a reaction, 19 patients (67 %) in the 90-min and all 26 patients (100 %) in the 120-min infusion were given premedications predominately acetaminophen, in addition to dexamethasone. Among reacting patients, 57 % of the 90-min and 65 % of the 120-min groups received additional intervention (p = 0.53)., Conclusion: Infusion reactions during high-dose BCNU are common and are not clearly reduced by modestly extending the duration of infusion or giving premedications.

Background: Tumor stage and folliculotropic mycosis fungoides are uncommon subtypes of cutaneous T-cell lymphoma (CTCL) with an aggressive disease course. Romidepsin is a histone deacetylase inhibitor approved by the US Food and Drug Administration for patients with CTCL who have received ≥ 1 previous systemic therapy. In the present study, we examined the efficacy and safety of romidepsin in patients from the pivotal, single-arm, open-label, phase II study of relapsed or refractory CTCL with cutaneous tumors and/or folliculotropic disease involvement., Materials and Methods: Patients with CTCL who had received ≥ 1 previous systemic therapy received romidepsin at 14 mg/m 2 on days 1, 8, and 15 of 28-day cycles. Responses were determined by a composite endpoint (assessments of the skin, blood, and lymph nodes). Patients with cutaneous tumors and/or folliculotropic disease involvement were identified by review of diagnosis and histology reports., Results: The objective response rate to romidepsin was 45% in patients with cutaneous tumors (n = 20) and 60% in patients with folliculotropic disease involvement (n = 10)., Conclusion: Romidepsin is active in subtypes of CTCL with less favorable outcomes, such as tumor stage and folliculotropic mycosis fungoides., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Diffuse invasion of the surrounding brain parenchyma is a major obstacle in the treatment of gliomas with various therapeutics, including anti-angiogenic agents. Here we identify the epi-/genetic and microenvironmental downregulation of ephrinB2 as a crucial step that promotes tumour invasion by abrogation of repulsive signals. We demonstrate that ephrinB2 is downregulated in human gliomas as a consequence of promoter hypermethylation and gene deletion. Consistently, genetic deletion of ephrinB2 in a murine high-grade glioma model increases invasion. Importantly, ephrinB2 gene silencing is complemented by a hypoxia-induced transcriptional repression. Mechanistically, hypoxia-inducible factor (HIF)-1α induces the EMT repressor ZEB2, which directly downregulates ephrinB2 through promoter binding to enhance tumour invasiveness. This mechanism is activated following anti-angiogenic treatment of gliomas and is efficiently blocked by disrupting ZEB2 activity. Taken together, our results identify ZEB2 as an attractive therapeutic target to inhibit tumour invasion and counteract tumour resistance mechanisms induced by anti-angiogenic treatment strategies.

Background: Autologous stem cell transplantation remains important in the treatment of myeloma and relapsed lymphoma. Plerixafor has been shown to significantly enhance stem cell mobilization but is very expensive., Patients and Methods: We evaluated plerixafor use in the 3-year period after its approval in December 2008., Results: A total of 277 patients with myeloma and lymphoma had stem cell mobilization; 97.5% were successfully mobilized, including 41.5% who received plerixafor. Plerixafor was generally used for rescue after suboptimal granulocyte-colony stimulating factor (G-CSF) mobilization ("just in time") or for remobilization after an unsuccessful attempt with chemotherapy plus G-CSF. In addition, 10% of patients received planned G-CSF plus plerixafor because of high risk factors for inadequate collection. Rescue plerixafor was more effective in patients with myeloma than lymphoma as after 1 dose of plerixafor; 85% versus 55% collected a minimum number of stem cells (2 × 10E6 CD34 cells/kg) for 1 transplant and 51% versus 15% collected > 5 × 10E6 CD34 cells/kg. After transplantation, there were no significant differences in engraftment as a consequence of plerixafor use. Among all patients, there were less platelet transfusions in patients provided ≥ 3.5 × 10E6 CD34(+) cells/kg., Conclusion: With the judicious use of plerixafor, nearly all patients can collect enough stem cells to proceed to transplantation. Further studies, including hematologic tolerance to posttransplantation therapy, are required to determine the cost-effectiveness of using plerixafor to convert adequate to more optimal mobilizers., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Accurate quantification of malignant cells in the peripheral blood of patients with cutaneous T-cell lymphoma is important for early detection, prognosis, and monitoring disease burden., Objective: We sought to determine the spectrum of current clinical practices; critically evaluate elements of current International Society for Cutaneous Lymphomas (ISCL) B1 and B2 staging criteria; and assess the potential role of T-cell receptor-Vβ analysis by flow cytometry., Methods: We assessed current clinical practices by survey, and performed a retrospective analysis of 161 patients evaluated at Yale (2011-2014) to compare the sensitivity, specificity, positive predictive value, and negative predictive value of parameters for ISCL B2 staging., Results: There was heterogeneity in clinical practices among institutions. ISCL B1 criteria did not capture 5 Yale cohort cases with immunophenotypic abnormalities that later progressed. T-cell receptor-Vβ testing was more specific than polymerase chain reaction and aided diagnosis in detecting clonality, but was of limited benefit in quantification of tumor burden., Limitations: Because of limited follow-up involving a single center, further investigation will be necessary to conclude whether our proposed diagnostic algorithm is of general clinical benefit., Conclusion: We propose further study of modified B1 criteria: CD4/CD8 ratio 5 or greater, %CD4(+) CD26(-) 20% or greater, or %CD4(+) CD7(-) 20% or greater, with evidence of clonality. T-cell receptor-Vβ testing should be considered in future diagnostic and staging algorithms., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Achievement of durable responses in patients with relapsed/refractory peripheral T cell lymphoma (PTCL) is challenging with current therapies, and there are few data regarding the potential benefits of continuing treatment in patients with the best response of stable disease (SD). Histone deacetylase inhibitors are a novel class of drugs with activity in T cell malignancies. Romidepsin was approved by the US Food and Drug Administration for the treatment of relapsed/refractory PTCL based on a pivotal trial demonstrating an objective response rate of 25% (33/130), including 15% with confirmed/unconfirmed complete response and a median duration of response of 28 months. Our objective was to further study the clinical benefits of romidepsin in patients that had the best response of SD., Methods: Patients with PTCL relapsed/refractory to ≥1 prior therapy were treated with the approved dose of 14 mg/m(2) romidepsin on days 1, 8, and 15 of six 28-day cycles; patients with SD or response after cycle 6 were allowed to continue on study until progression. By protocol amendment, patients treated for ≥12 cycles could receive maintenance dosing twice per cycle; after cycle 24, dosing could be further reduced to once per cycle in those who had received maintenance dosing for ≥6 months., Results: Of the 32 patients (25%) with the best response of SD, 22 had SD for ≥90 days (SD90; cycle 4 response assessment). The longest SD was >3 years in a patient who received maintenance dosing of 14 mg/m(2) on days 1 and 15 beginning in cycle 13. Patients with the best response of SD90 or partial response achieved similar overall and progression-free survival. Prolonged dosing of romidepsin was well tolerated., Conclusions: We concluded that patients who achieve SD may consider continuing treatment because the clinical benefits of romidepsin may extend beyond objective responses., Trial Registration: NCT00426764.

After allogeneic stem cell transplant, severe grade III-IV gastrointestinal (GI) acute GvHD is associated with significant morbidity and mortality, and generally results in poor outcomes. Salvage therapy for patients who fail steroid therapy is not well defined in the literature. In the current retrospective study, we reviewed our experience with the combination of basiliximab and infliximab in 21 patients with severe, grade III-IV GI acute GvHD of whom 16 met the definition for steroid-refractory disease. The overall response rate was 76%, with 43% CR at a median time of 21 days after beginning treatment. The survival at 1 year was 24%, with most deaths due to complications from GvHD and recurrence of primary disease. All five of the long-term survivors have chronic GvHD. On the basis of a review of the literature, this regimen does not seem to be significantly more effective than other strategies for severe GI GvHD and seems to be worse than the results reported for basiliximab alone. Future studies of single-agent basiliximab and newer agents are required.

Remyelination in multiple sclerosis (MS) lesions often remains incomplete despite the presence of oligodendrocyte progenitor cells (OPCs). Amongst other factors, successful remyelination depends on the phagocytic clearance of myelin debris. However, the proteins in myelin debris that act as potent and selective inhibitors on OPC differentiation and inhibit CNS remyelination remain unknown. Here, we identify the transmembrane signalling protein EphrinB3 as important mediator of this inhibition, using a protein analytical approach in combination with a primary rodent OPC assay. In the presence of EphrinB3, OPCs fail to differentiate. In a rat model of remyelination, infusion of EphrinB3 inhibits remyelination. In contrast, masking EphrinB3 epitopes using antibodies promotes remyelination. Finally, we identify EphrinB3 in MS lesions and demonstrate that MS lesion extracts inhibit OPC differentiation while antibody-mediated masking of EphrinB3 epitopes promotes it. Our findings suggest that EphrinB3 could be a target for therapies aiming at promoting remyelination in demyelinating disease.

Peripheral T-cell lymphomas (PTCL) have suboptimal outcomes using conventional CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. The anti-folate pralatrexate, the first drug approved for patients with relapsed/refractory PTCL, provided a rationale to incorporate it into the front-line setting. This phase 2 study evaluated a novel front-line combination whereby cyclophosphamide, etoposide, vincristine and prednisone (CEOP) alternated with pralatrexate (CEOP-P) in PTCL. Patients achieving a complete or partial remission (CR/PR) were eligible for consolidative stem cell transplantation (SCT) after 4 cycles. Thirty-three stage II-IV PTCL patients were treated: 21 PTCL-not otherwise specified (64%), 8 angioimmunoblastic T cell lymphoma (24%) and 4 anaplastic large cell lymphoma (12%). The majority (61%) had stage IV disease and 46% were International Prognostic Index high/intermediate or high risk. Grade 3-4 toxicities included anaemia (27%), thrombocytopenia (12%), febrile neutropenia (18%), mucositis (18%), sepsis (15%), increased creatinine (12%) and liver transaminases (12%). Seventeen patients (52%) achieved a CR. The 2-year progression-free survival and overall survival, were 39% (95% confidence interval 21-57) and 60% (95% confidence interval 39-76), respectively. Fifteen patients (45%) (12 CR) received SCT and all remained in CR at a median follow-up of 21·5 months. CEOP-P did not improve outcomes compared to historical data using CHOP. Defining optimal front line therapy in PTCL continues to be a challenge and an unmet need., (© 2015 John Wiley & Sons Ltd.)

Peripheral T cell lymphomas (PTCLs) are a heterogeneous group of lymphoid malignancies that portend a poor prognosis and have an undefined optimal therapeutic strategy. Data on best practices stem from prior studies that have generally included B cell lymphomas. However, the enhanced ability to diagnose PTCLs, the development of newer agents specific for PTCLs, and its increased incidence have called the scientific community to develop better strategies to combat these neoplasms. To that end, T cell lymphoma registries were developed in an attempt to answer relevant questions on the prognosis and management of PTCLs. The largest registries currently enrolling patients are the Comprehesive Oncology Measures for PeripheraL T-cEll Lymphoma TrEatment (COMPLETE) and the T-Cell Project. Despite the inherent limitations of these studies, valuable information are being collected to refine our management approaches and to aid in designing future clinical trials. This review illustrates the value of these registries and describes the critical questions that need to be answered.

Purpose: Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers., Patients and Methods: Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS)., Results: Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%)., Conclusion: To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value, which, used together in a prognostic index, may be useful to stratify advanced-stage patients., (© 2015 by American Society of Clinical Oncology.)

Purpose: Peripheral T-cell lymphomas (PTCLs) represent a diverse group of non-Hodgkin lymphomas with a poor prognosis and no accepted standard of care for patients with relapsed or refractory disease. This study evaluated the efficacy and tolerability of belinostat, a novel histone deacetylase inhibitor, as a single agent in relapsed or refractory PTCL., Patients and Methods: Patients with confirmed PTCL who experienced progression after ≥ one prior therapy received belinostat 1,000 mg/m(2) as daily 30-minute infusions on days 1 to 5 every 21 days. Central assessment of response used International Working Group criteria. Primary end point was overall response rate. Secondary end points included duration of response (DoR) and progression-free and overall survival., Results: A total of 129 patients were enrolled, with a median of two prior systemic therapies. Overall response rate in the 120 evaluable patients was 25.8% (31 of 120), including 13 complete (10.8%) and 18 partial responses (15%). Median DoR by International Working Group criteria was 13.6 months, with the longest ongoing patient at ≥ 36 months. Median progression-free and overall survival were 1.6 and 7.9 months, respectively. Twelve of the enrolled patients underwent stem-cell transplantation after belinostat monotherapy. The most common grade 3 to 4 adverse events were anemia (10.8%), thrombocytopenia (7%), dyspnea (6.2%), and neutropenia (6.2%)., Conclusion: Monotherapy with belinostat produced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across the major subtypes, irrespective of number or type of prior therapies. These results have led to US Food and Drug Administration approval of belinostat for this indication., Competing Interests: Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article., (© 2015 by American Society of Clinical Oncology.)

Background: The panniculitic T-cell lymphomas (TCLs) comprise 2 distinct entities, αβ subcutaneous panniculitis-like TCL (SPTCL) and the γδ cutaneous TCLs with pannicular involvement primary cutaneous γδ (PCGD)-TCL. Although outcomes for most patients with SPTCL are favorable, those with PCGD-TCLs generally have an inferior outcome, and treatment strategies have not been well defined. Allogeneic hematopoietic stem cell transplantation (HSCT) has been shown to be a potentially curative strategy in aggressive TCLs and in refractory and advanced-stage mycosis fungoides., Objective: We sought to analyze the outcomes of HSCT for panniculitic cutaneous TCL., Results: Fourteen patients (4 SPTCL, 10 PCGD-TCL) presented with primarily pannicular T-cell infiltrates. Seven patients underwent allogeneic HSCT from matched-related donors and matched-unrelated donors of which 4 (57%) are alive (1 SPTCL, 3 PCGD-TCL) at 7.8, 6.9, 6.2, and 0.25 years. Two patients underwent autologous HSCT (1 SPTCL, 1 PCGD-TCL) and both are alive at a median follow-up of 1.91 years., Limitations: This study is limited by its retrospective nature and small sample size because of the rarity of SPTCL and PCGD-TCL., Conclusion: Aggressive therapy followed by allogeneic HSCT is a promising treatment modality for patients with PCGD-TCL., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: For patients with peripheral T-cell lymphoma (PTCL), the value of (18)fluoro-deoxyglucose positron emission tomography (FDG-PET) scans for assessing prognosis and response to treatment remains unclear. The utility of FDG-PET, in addition to conventional radiology, was examined as a planned exploratory end point in the pivotal phase 2 trial of romidepsin for the treatment of relapsed/refractory PTCL., Patients and Methods: Patients received romidepsin at a dose of 14 mg/m(2) on days 1, 8, and 15 of 28-day cycles. The primary end point was the rate of confirmed/unconfirmed complete response (CR/CRu) as assessed by International Workshop Criteria (IWC) using conventional radiology. For the exploratory PET end point, patients with at least baseline FDG-PET scans were assessed by IWC + PET criteria., Results: Of 130 patients, 110 had baseline FDG-PET scans, and 105 were PET positive at baseline. The use of IWC + PET criteria increased the objective response rate to 30% compared with 26% by conventional radiology. Durations of response were well differentiated by both conventional radiology response criteria [CR/CRu versus partial response (PR), P = 0.0001] and PET status (negative versus positive, P < 0.0001). Patients who achieved CR/CRu had prolonged progression-free survival (PFS, median 25.9 months) compared with other response groups (P = 0.0007). Patients who achieved PR or stable disease (SD) had similar PFS (median 7.2 and 6.3 months, respectively, P = 0.6427). When grouping PR and SD patients by PET status, patients with PET-negative versus PET-positive disease had a median PFS of 18.2 versus 7.1 months (P = 0.0923)., Conclusions: Routine use of FDG-PET does not obviate conventional staging, but may aid in determining prognosis and refine response assessments for patients with PTCL, particularly for those who do not achieve CR/CRu by conventional staging. The optimal way to incorporate FDG-PET scans for patients with PTCL remains to be determined., Trial Registration: NCT00426764., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

CD4 + primary cutaneous small/medium-sized pleomorphic T-cell lymphoma (CD4 + PCSM-TCL) is a rare T-cell lymphoma associated with a favorable prognosis. A retrospective study of 23 patients with CD4 + PCSM-TCL as defined by World Health Organization-European Organisation for Research and Treatment of Cancer (WHO-EORTC) and WHO classifications was conducted. Median age was 63 years. The head and neck were the most commonly affected locations, followed by the trunk. Two patients had evidence of systemic involvement at relapse. All tumors were CD3 + and CD4+. CD5 and CD7 loss occurred in 52% and 84%, respectively. The median follow-up was 33.6 months. Eleven patients had excisional biopsy only, six had localized radiotherapy and two received excision and localized radiation. Cytotoxic chemotherapy and localized radiation were used in one patient with aggressive and invasive features. All patients had a complete remission but one developed systemic involvement. Our case series demonstrates that CD4 + PCSM-TCL is an indolent T-cell lymphoma that can be treated with local modalities and raises the question of its current classification as a lymphoma.

Belinostat is a pan-histone deacetylase inhibitor with antitumour and anti-angiogenic properties. An open label, multicentre study was conducted in patients with peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) who failed ≥1 prior systemic therapy and were treated with belinostat (1000 mg/m(2) intravenously ×5 d of a 21-d cycle). The primary endpoint was objective response rate (ORR). Patients with PTCL (n = 24) had received a median of three prior systemic therapies (range 1-9) and 40% had stage IV disease. Patients with CTCL (n = 29) had received a median of one prior skin-directed therapy (range 0-4) and four prior systemic therapies (range 1-9); 55% had stage IV disease. The ORRs were 25% (PTCL) and 14% (CTCL). Treatment-related adverse events occurred in 77% of patients; nausea (43%), vomiting (21%), infusion site pain (13%) and dizziness (11%) had the highest incidence. Treatment-related serious adverse events were Grade 5 ventricular fibrillation; Grade 4 thrombocytopenia; Grade 3 peripheral oedema, apraxia, paralytic ileus and pneumonitis; and Grade 2 jugular vein thrombosis. Belinostat monotherapy was well tolerated and efficacious in patients with recurrent/refractory PTCL and CTCL. This trial was registered at www.clinicaltrials.gov as NCT00274651., (© 2014 John Wiley & Sons Ltd.)

Tumours exploit their hypoxic microenvironment to induce a more aggressive phenotype, while curtailing the growth-inhibitory effects of hypoxia through mechanisms that are poorly understood. The prolyl hydroxylase PHD3 is regulated by hypoxia and plays an important role in tumour progression. Here we identify PHD3 as a central regulator of epidermal growth factor receptor (EGFR) activity through the control of EGFR internalization to restrain tumour growth. PHD3 controls EGFR activity by acting as a scaffolding protein that associates with the endocytic adaptor Eps15 and promotes the internalization of EGFR. In consequence, loss of PHD3 in tumour cells suppresses EGFR internalization and hyperactivates EGFR signalling to enhance cell proliferation and survival. Our findings reveal that PHD3 inactivation provides a novel route of EGFR activation to sustain proliferative signalling in the hypoxic microenvironment.

Solid tumours are exposed to microenvironmental factors such as hypoxia that normally inhibit cell growth. However, tumour cells are capable of counteracting these signals through mechanisms that are largely unknown. Here we show that the prolyl hydroxylase PHD3 restrains tumour growth in response to microenvironmental cues through the control of EGFR. PHD3 silencing in human gliomas or genetic deletion in a murine high-grade astrocytoma model markedly promotes tumour growth and the ability of tumours to continue growing under unfavourable conditions. The growth-suppressive function of PHD3 is independent of the established PHD3 targets HIF and NF-κB and its hydroxylase activity. Instead, loss of PHD3 results in hyperphosphorylation of epidermal growth factor receptor (EGFR). Importantly, epigenetic/genetic silencing of PHD3 preferentially occurs in gliomas without EGFR amplification. Our findings reveal that PHD3 inactivation provides an alternative route of EGFR activation through which tumour cells sustain proliferative signalling even under conditions of limited oxygen availability.

Background: Histone deacetylase inhibitor romidepsin has demonstrated durable clinical responses and tolerability in patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma (PTCL, CTCL). Selection of novel drug therapies for patients with relapsed/refractory aggressive lymphoma requires not only considerations regarding efficacy but also careful evaluation of toxicities as well as overall clinical benefit. The purpose of this analysis was to examine common adverse events (AEs) reported in pivotal trials of romidepsin in relapsed/refractory PTCL or CTCL and to more clearly define the overall AE profile in these populations., Methods: Patients with relapsed/refractory PTCL or CTCL were treated with romidepsin at 14 mg/m(2) as a 4-hour intravenous infusion on days 1, 8, and 15 of 28-day cycles for up to 6 cycles; patients with at least stable disease could extend therapy until progressive disease or another withdrawal criterion was met. All enrolled patients who received ≥ 1 dose of romidepsin were included in the AE analyses., Results: Overall, safety profiles of common AEs were similar, although patients with relapsed/refractory PTCL had more frequent hematologic toxicities and grade ≥ 3 infections. In both patient populations, the greatest incidence of grade ≥ 3 AEs and the majority of discontinuations due to AEs occurred during cycles 1-2. Early discontinuations were primarily related to infection, thrombocytopenia, or electrocardiogram abnormalities, confirming the need to closely monitor patients with poor bone marrow reserve or other comorbidities. Despite this, 28% of patients with relapsed/refractory PTCL and 36% of patients with relapsed/refractory CTCL continued on romidepsin treatment for ≥ 6 cycles., Conclusions: This study demonstrates that patients with relapsed/refractory PTCL or CTCL have similar AE profiles with romidepsin treatment, although patients with PTCL experienced more frequent and more severe hematologic toxicities and more frequent grade ≥ 3 infections. The greatest incidence of grade ≥ 3 AEs and the majority of discontinuations due to AEs occurred during treatment cycles 1-2. Extended dosing of romidepsin can be tolerated in responding patients., Trial Registration: NCT00426764,NCT00106431.