Primary cutaneous peripheral T-cell lymphoma, not otherwise specified with mammalian target of rapamycin mutation: A novel finding for targeted treatment

Primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS) is a rare, progressive, and often fatal disease with no specific treatment regimen that presents as rapidly enlarging plaques or nodules. Here, we present a case of progressive pcPTCL-NOS with mammalian target of rapamycin (mTOR) mutation and variable T-cell antigen expression. mTOR mutation in pcPTCL-NOS may represent a new therapeutic target

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Cutaneous T-cell lymphomas (including rare subtypes) : current concepts. II

Background. Cutaneous T-cell lymphomas (CTCL) represent about the 80% of skin lymphomas and comprise a heterogeneous group of diseases with respect to clinical presentation, outcome, histologic and immunophenotypic features. In the recent years, data have been accumulated indicating that clinical and biological differences exists between primary nodal and primary extranodal lymphomas. Information Sources. On such bases, the cutaneous lymphoma classification by the EORTC (European Organization for Cancer Research and Treatment) but also the recent general lymphoma classification, by the WHO (World Health Organization), have dedicated special attentions to the cutaneous lymphomas including the T and NK-cell subtypes. This paper reviews the most significative subtypes of T-cell lymphoma that affect the skin primarily or secondarily. State of the Art. Apart from mycosis fungoides with its variants forms and the Sezary's syndrome, we have focused on the CD30(+) primary cutaneous lymphoproliferative disorders (PCLD) (25% of all CTCL), a fascinating spectrum of disease, extending from lymphomatoid papulosis (LyP) trough to CD30(+) large cell lymphoma. These disorders have in common large atypical CD30(+) cells and a frequent spontaneous regression of the skin lesions associated with a relatively favourable outcome (excellent in LyP). The identification of this group of skin disorders is crucial for the patients since most of CD30(+) PCLD are indolent diseases that do not warrant aggressive treatment. Others types of CTCL include the heterogeneous category of peripheral T-cell lymphoma not otherwise specified (NOS), subcutaneous panniculitis-like T-cell lymphoma and the still controversial group of the cytotoxic lymphomas. Perspectives. Notably, the latter two subtypes have special relevance to the clinicians because (i) subcutaneous panniculitis-like T-cell lymphoma may be associated with the hemophagocytic syndrome; (ii) skin lesions in cytotoxic lymphomas may represent the first mainifestation of an otherwise systemic disease

Romidepsin for the treatment of relapsed/refractory peripheral T cell lymphoma: prolonged stable disease provides clinical benefits for patients in the pivotal trial.

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 \u3e3 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

Mycosis fungoides with CD20 expression: report of two cases and review of the literature

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107359/1/cup12299.pd

Peripheral T-cell lymphomas: a review of current approaches and hopes for the future.

Peripheral T-cell lymphomas (PTCL) are a diverse group of lymphoproliferative disorders, which share a common denominator of overall poor prognosis, with few exceptions. In this article, the authors review current standard of care approaches for the treatment of PTCLs, the role of stem-cell/bone marrow transplantation, and current developments in novel targeted therapies

Gastric cancer is the leading cause of death in Italian adult patients with common variable immunodeficiency

An increased prevalence of malignant lymphoma and of gastric cancer has been observed in large cohorts of patients with common variable immunodeficiency (CVID), the most frequently symptomatic primary immunodeficiency. Surveillance strategies for cancers in CVID should be defined based on epidemiological data. Risks and mortality for cancers among 455 Italian patients with CVID were compared to cancer incidence data from the Italian Cancer Registry database. CVID patients showed an increased cancer incidence for all sites combined (Obs = 133, SIR = 2.4; 95%CI = 1.7\u20133.5), due to an excess of non-Hodgkin lymphoma (Obs = 33, SIR = 14.3; 95%CI = 8.4\u201322.6) and of gastric cancer (Obs = 25; SIR = 6.4; 95%CI = 3.2\u201312.5). CVID patients with gastric cancer and lymphoma had a worse survival in comparison to cancer-free CVID (HR: 4.8, 95%CI: 4.2\u201344.4 and HR: 4.2, 95%CI: 2.8\u201344.4). Similar to what observed in other series, CVID-associated lymphomas were more likely to be of B cell origin and often occurred at extra-nodal sites. We collected the largest case-series of gastric cancers in CVID subjects. In contrast to other reports, gastric cancer was the leading cause of death in CVID. Standardized mortality ratio indicated a 10.1-fold excess mortality among CVID patients with gastric cancer. CVID developed gastric cancer 15 years earlier than the normative population, but they had a similar overall survival. Only CVID diagnosed at early stage gastric cancer survived >24 months. Stomach histology from upper endoscopy performed before cancer onset showed areas of atrophic gastritis, intestinal metaplasia or dysplasia. CVID patients might progress rapidly to an advanced cancer stage as shown by patients developing a III-IV stage gastric cancer within 1 year from an endoscopy without signs of dysplasia. Based on high rate of mortality due to gastric cancer in Italian CVID patients, we hereby suggest a strategy aimed at early diagnosis, based on regular upper endoscopy and on Helicobacter pylori infection treatment, recommending an implementation of national guidelines

Anaplastic large cell lymphoma in paediatric and young adult patients.

Anaplastic large cell lymphoma (ALCL) is a heterogeneous disease of debateable origin that, in children, is largely anaplastic lymphoma kinase (ALK) positive with aberrant ALK activity induced following the formation of chromosomal translocations. Whilst the survival rates for this disease are relatively high, a significant proportion (20-40%) of patients suffer disease relapse, in some cases on multiple occasions and therefore suffer the toxic side-effects of combination chemotherapy. Traditionally, patients are treated with a combination of agents although recent data from relapse patients have suggested that low risk patients might benefit from single agent vinblastine and, going forward, the addition of ALK inhibitors to the therapeutic regimen may have beneficial consequences. There are also a plethora of other drugs that might be advantageous to patients with ALCL and many of these have been identified through laboratory research although the decision as to which drugs to implement in trials will not be trivial.Supported in part by the Pediatric Cancer Research Foundation and Fondazione Giacomo Ascoli. S.D.T. is supported with funding from BloodwiseThis is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1111/bjh.1395

Long-term complete remission with belinostat in a patient with chemotherapy refractory peripheral t-cell lymphoma

Peripheral T/NK-cell lymphomas (PTCL) are rare malignancies with a poor prognosis. Due to the lack of randomised studies, standard therapy has not been established. First-line treatment with anthracycline-based polychemotherapy followed by consolidation with high-dose therapy and autologous stem cell transplant in responding patients has demonstrated good feasibility with low toxicity in prospective studies and is widely used in eligible patients. In relapsed and refractory patients, who are not candidates for transplant approaches, therapeutic options are limited and are usually palliative. Several new agents are currently under investigation to improve the outcome of PTCL in the first line and salvage settings. Belinostat, a histone deacetylase (HDAC) inhibitor, has demonstrated broad antineoplastic activity in preclinical studies, and promising results in advanced relapsed/refractory lymphomas. Here, we report the case of a 73 year old patient with heavily pre-treated refractory PTCL in complete remission with belinostat for 39 months