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The poor prognosis of acute T‐cell lymphoblastic leukemia (T‐ALL) and T‐cell lymphoblastic lymphoma (T‐LBL) in older adults and patients with relapsed/refractory illness is an unmet clinical need, as there is no defined standard of care and there are few treatment options. Abnormally elevated CD38 expression in T‐ALL and T‐LBL is associated with tumor expansion and disease development, making CD38 a potential target for anti‐T‐ALL and T‐LBL treatment. Isatuximab is a monoclonal antibody that binds to a specific epitope on CD38. The purpose of the study was to assess the efficacy and safety of isatuximab monotherapy in a phase 2, multicenter, one‐arm, open‐label study in patients with relapsed or refractory T‐ALL or T‐LBL (Clinical Trials.gov identifier NCT02999633). The primary endpoint was to assess the efficacy of isatuximab by overall response rate (ORR). An interim analysis based on the efficacy and safety of isatuximab in the first 19 patients enrolled was scheduled, however only 14 patients were enrolled in the study. No patient achieved complete response (CR) or CR with incomplete peripheral recovery. Most patients (11 [78.6%]) developed progressive disease and had progressive disease as their best response. A total of 10 (71.4%) patients had treatment emergent adverse events considered treatment‐related, with infusion reactions as the most frequent drug‐related TEAE, occurring in 8 (57.1%) patients. Despite the low efficacy of isatuximab in the current study, it is likely that the use of immunotherapy medication in T‐ALL will be expanded through logically targeted approaches, together with advances in the design of T‐cell therapy and clinical experience and will provide restorative options beyond chemotherapy and targeted treatments. [ABSTRACT FROM AUTHOR]

Summary: A few prospective trials in HIV‐positive patients with Burkitt lymphoma (BL) or high‐grade B‐cell lymphoma (HGBL) have been reported. Investigated therapies have shown good efficacy but relevant safety problems, with high rates of interruptions, severe mucositis, septic complications, and fungal infections. Here, we report the results of a multicentre phase II trial addressing a new dose‐dense, short‐term therapy aimed at maintaining efficacy and improving tolerability. The experimental programme included a 36‐day polychemotherapy induction followed by high‐dose cytarabine‐based consolidation and response‐tailored BEAM (carmustine, etoposide, cyatarabine, and melphalan)‐ conditioned autologous stem cell transplantation (ASCT). This therapy would be considered active if ≥11 complete remissions (CR) after induction (primary endpoint) were recorded among 20 assessable patients. HIV‐positive adults (median age 42, range 26–58; 16 males) with untreated BL (n = 16), HGBL (n = 3) or double‐hit lymphoma (n = 1) were enrolled. All patients had high‐risk features, with meningeal and bone marrow infiltration in five and nine patients respectively. The experimental programme was safe and active in a multicentre setting, with only two episodes of grade 4 non‐haematological toxicity (hepatotoxicity and mucositis), and no cases of systemic fungal infections; two patients died of toxicity (bacterial infections). Response after induction (median duration: 47 days; interquartile range 41–54), was complete in 13 patients and partial in five [overall response rate = 90%; 95% confidence interval (CI) = 77–100]. All responders received consolidation, and five required autologous stem cell transplant. At a median follow‐up of 55 (41–89) months, 14 patients are relapse‐free and 15 are alive, with a five‐year progression‐free survival and an overall survival of 70% (95% CI = 60–80%) and 75% (95% CI = 66–84) respectively. No patient with cerebrospinal fluid (CSF)/meningeal lymphoma experienced central nervous system recurrence. With respect to previously reported regimens, this programme was delivered in a shorter period, and achieved the main goal of maintaining efficacy and improving tolerability. [ABSTRACT FROM AUTHOR]

Summary: Optimal treatment for transformed follicular lymphoma (tFL) is not fully defined. Clinical characteristics and treatments that impact on post‐transformation outcome of 176 biopsy‐proven tFL were analysed. Transformation occurred at initial diagnosis in 52% (Group 1) and after a FL diagnosis in 48% (Group 2). Five‐year overall survival was 84% for Group 1 and 51% for Group 2 (P < 0·001). In Group 1, 5‐year progression‐free survival was superior after rituximab maintenance compared to observation only (94% vs. 53%, P = 0·024). In Group 2, an inverse trend was found between survival and both a higher number of pre‐transformation treatment lines and a short time‐to‐transformation. [ABSTRACT FROM AUTHOR]

Patients infected with human immunodeficiency virus (HIV) are at increased risk for developing both non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). Even if this risk has decreased for NHL after the introduction of combination antiretroviral therapy (cART), they remain the most common acquired immune deficiency syndrome (AIDS)-related cancer in the developed world. They are almost always of B-cell origin, and some specific lymphoma types are more common than others. Some of these lymphoma types can occur in both HIV-uninfected and infected patients, while others preferentially develop in the context of AIDS. HIV-associated lymphoma differs from lymphoma in the HIV negative population in that they more often present with advanced disease, systemic symptoms, and extranodal involvement and are frequently associated with oncogenic viruses (Epstein-Barr virus and/or human herpesvirus-8). Before the introduction of cART, most of these patients could not tolerate the treatment strategies routinely employed in the HIV-negative population. The widespread use of cART has allowed for the delivery of full-dose and dose-intensive chemotherapy regimens with improved outcomes that nowadays can be compared to those seen in non-HIV infected patients. However, a great deal of attention should be paid to opportunistic infections and other infectious complications, cARTchemotherapy interactions, and potential cumulative toxicity. In the context of relatively sparse prospective and randomized trials, the optimal treatment of AIDS-related lymphomas remains a challenge, particularly in patients with severe immunosuppression. This paper will address epidemiology, pathogenesis, and therapeutic strategies in HIV-associated NHL and HL. [ABSTRACT FROM AUTHOR]

Follicular lymphoma (FL) is an indolent non-Hodgkin's lymphoma that remains an incurable disease for most patients. It is responsive to a variety of different treatments, however it follows a pattern of relapsing and remitting disease. Traditional therapeutic options for patients with untreated FL include a "watchful waiting" approach for asymptomatic and low tumor burden and multiagent cytotoxic chemotherapy for symptomatic and/or high tumor burden. The life expectancy of patients with FL has been extended with the use of rituximab, but there remains a group of patients who fail to respond to chemoimmunotherapy. So there is a need for useful novel prognostic factors and scoring systems for prediction of the disease course of single patients to individualize therapy, especially in the new era of chemoimmunotherapy. The identification of novel targeted agents, use of stem cell transplantation, and new treatment combinations provide the opportunity to enhance patient outcomes. [ABSTRACT FROM AUTHOR]

Clinical trial results indicate that lenalidomide, an immunomodulatory drug, is a promising treatment in relapsed/refractory non-Hodgkin lymphoma (NHL). This retrospective multicenter study was conducted in patients with relapsed/refractory NHL treated with lenalidomide monotherapy through a Named Patient Program in Italy. Principal endpoints were overall response rate (ORR), safety and overall survival (OS). The ORR in 64 evaluable patients was 42.2% and was similar among patients receiving 10, 15 or 25 mg/day lenalidomide. Response rates in patients with mantle cell, diffuse large B-cell and follicular lymphoma were 45.5%, 42.1% and 20%, respectively. Among patients who responded to most recent prior therapy, ORR was 50.0% versus 36.8% in patients with refractory NHL. Mean duration of response in patients receiving any lenalidomide dose was 10.5 months; 1-year progression-free survival and OS were 50.3% and 82.6%, respectively. These findings suggest that lenalidomide is effective and safe for heavily pretreated patients with NHL in the clinical setting. [ABSTRACT FROM AUTHOR]

We performed a multicenter study to validate the concept that a simple comprehensive geriatric assessment (CGA) can identify elderly, non-fit patients with diffuse large B-cell lymphoma (DLBCL) in whom curative treatment is not better then palliation, and to analyze potential benefits of treatment modulation after further subdividing the non-fit category by CGA criteria. One hundred and seventy-three patients aged > 69 treated with curative or palliative intent by clinical judgement only were grouped according to CGA into fit (46%), unfit (16%) and frail (38%) categories. Two-year overall survival (OS) was significantly better in fit than in non-fit patients (84% vs. 47%; p < 0.0001). Survival in unfit and frail patients was not significantly different. Curative treatment slightly improved 2-year OS in unfit (75% vs. 45%) but not in frail patients (44% vs. 39%). CGA was confirmed as very efficient in identifying elderly patients with DLBCL who can benefit from a curative approach. Further efforts are needed to better tailor therapies in non-fit patients. [ABSTRACT FROM AUTHOR]

The article presents case study of a 38-year-old Jamaican woman who was diagnosed with adult T-cell leukaemia lymphoma (ATLL) Human T-Lymphotropic Virus (HTLV+) was treated with combination chemotherapy. It mentions information on NUP98 positive acute myeloid leukemia which originates from multiple chromosomal translocations involving homeobox and non-homeobox genes. It also presents information on extraction of RNA usingTrizol reagent.

The article presents information that the treatment of human immunodeficiency virus infection in patients with the Burkitt lymphoma (HIV-BL) is a difficult challenge which requires multidisciplinary efforts and demanding strategies. It informs that the use of highly active antiretroviral therapy (HAART) has resulted in improved tolerability and efficacy of standard chemotherapy in the HIV-positive patients with diffused large B-cell lymphomas.

Alemtuzumab is a humanized monoclonal antibody that recognizes the CD52 antigen expressed on malignant and normal B lymphocytes. It has come to be used therapeutically in B-cell malignancies and, in addition, it shows interesting activity also in T-cell lymphomas. Published literature and abstract proceedings were scanned, and a systematic review of phase II studies administering alemtuzumab in patients with T-cell lymphomas was performed. Alemtuzumab is an effective alternative option for patients with peripheral T-cell lymphomas and cutaneous T-cell lymphomas. Alemtuzumab may belong to the current standard of care for nodal and cutaneous T-cell lymphomas. [ABSTRACT FROM AUTHOR]

We conducted a prospective study to compare epirubicin, cyclophosphamide, vinblastine, prednisone and rituximab (R-miniCEOP) with cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab (R-CHOP) for the treatment of 'fit' elderly patients with diffuse large B-cell lymphoma (DLBCL). Patients over the age of 65 with stage II-IV DLBCL were screened with a comprehensive geriatric assessment. Patients were randomized to receive six courses of R-miniCEOP ( n == 114) or R-CHOP ( n == 110). Overall, the rate of complete remission was 70% ( p == 0.466). After a median follow-up of 42 months, 5-year event-free survival (EFS) rates were 46% and 48% for R-miniCEOP and R-CHOP, respectively ( p == 0.538). Patients older than 72 years and with low-risk disease had a better outcome when treated with R-miniCEOP ( p == 0.011). Overall R-CHOP and R-miniCEOP are similarly effective for elderly 'fit' patients with DLBCL. The less intense R-miniCEOP may be an acceptable option for the treatment of relatively older patients with low-risk disease. [ABSTRACT FROM AUTHOR]

Summary: Extranodal marginal zone B-cell lymphomas are linked to bacterial infections that vary according to the anatomical site. The occurrence of these lymphomas in the central nervous system is a very rare event, and the identification of specific bacteria in this setting has not been previously addressed. Herein, we report for the first time a case of primary central nervous system marginal zone B-cell lymphoma involving the choroid plexus associated with Chlamydophila psittaci infection. No concomitant ocular involvement was detected. C psittaci was identified with 3 independent methods, and through immunohistochemistry, it was visualized in the cytoplasm of monocytes/macrophages present within lymphomatous tissues. This observation points toward the opportunity to investigate the prevalence of C psittaci infection in central nervous system lymphomas, particularly in those with low-grade histologic features. [Copyright &y& Elsevier]

Objectives. Rituximab is an anti-CD20 monoclonal antibody that promotes better treatment outcomes in patients with non-Hodgkin's lymphoma (NHL). Case series of progressive multifocal leukoencephalopathy (PML) in patients receiving rituximab within polychemotherapy regimens have led to the introduction of a black box warning, but no risk estimation has ever been provided. Methods. We performed a retrospective, monocentric cohort study on 976 NHL patients diagnosed in 1994-2008, including 517 patients who received at least one dose of rituximab. Results. Inclusion of rituximab into standard chemotherapy regimens for NHL caused a significantly higher incidence of PML cases (rate difference, 2.2 every 1,000 patient-years; 95% confidence interval, 0.1- 4.3). Interpretation. Based on this finding, clinical surveillance of PML-related symptoms is recommended in NHL patients exposed to rituximab. [ABSTRACT FROM AUTHOR]

The article reports on the study conducted to analyze whether comprehensive geriatric assessment (CGA) can identify elderly patients with diffuse large cell lymphoma (DLCL) who can be treated with anthracycline-containing immunochemotherapy. The study includes 84 consecutive patients with DLCL aged below 65 years. It shows that CGA can be an efficient method to identify elderly DLCL patients treated with anthracycline-containing immunochemotherapy.

Some case reports and a Japanese series suggest benefit from the use of rituximab in patients with intravascular large B-cell lymphoma (IVL). Rituximab efficacy was evaluated in Western patients with IVL, comparing outcome of 10 patients treated with rituximab + chemotherapy (R-CT) and of 20 patients treated with chemotherapy alone (CT). There were no significant differences in patients’ characteristics between the two subgroups. The addition of rituximab was associated with improved complete remission rate (90% vs. 50%; P = 0·04), event-free survival (3-year: 89% vs. 35%; P = 0·003) and overall survival (3-year: 89% vs. 38%; P = 0·01). In conclusion, rituximab may substantially change the dismal prognosis of IVL. [ABSTRACT FROM AUTHOR]

Despite its recognition as a distinct, extremely rare entity, no large studies of intravascular lymphoma (IVL) have been reported. The clinico-pathological characteristics of 38 human immunodeficiency virus-negative patients with IVL diagnosed in Western countries were reviewed to better delineate clinical presentation, clinical variants, natural history and optimal therapy. The IVL is an aggressive and usually disseminated disease (Ann Arbor stage IV in 68% of cases) that predominantly affects elderly patients (median age 70 years, range: 34–90; male:female ratio 0·9), resulting in poor Eastern Cooperative Oncology Group Performance Status (ECOG-PS>1 in 61%), B symptoms (55%), anaemia (63%) and high serum lactate dehydrogenase level (86%). The brain and skin are the most common sites of disease. In contrast to previous reports, hepatosplenic involvement (26%) and bone marrow infiltration (32%) were found to be common features in IVL, while nodal disease was confirmed as rare (11% of cases). Patients with disease limited to the skin (‘cutaneous variant’; 26% of cases) were invariably females with a normal platelet count, and exhibited a significantly better outcome than the remaining patients, which deserves further investigation. Overall survival was usually poor; however, the early use of intensive therapies could improve outcome in young patients with unfavourable features. ECOG-PS>1,‘cutaneous variant’, stage I and chemotherapy use were independently associated with improved survival. [ABSTRACT FROM AUTHOR]

This article presents information related to high-dose sequential (HDS) chemotherapy for high-risk non-Hodgkin's lymphoma (NHL). High dose chemotherapy with autograft is extensively employed in the management of high-risk lymphoma. This approach is presently first-choice for relapsed high grade NHL and Hodgkin's lymphoma. The original HDS, developed in 1989, includes the sequential delivery of high doses of Cyclophosphamide (CY), Methotrexate and Etoposide given at 15-20 day intervals and finally autograft performed with PBPC collected after CY.

Polychlorinated biphenyls (PCB) have been classified by the International Agency for Research on Cancer (IARC) in Group 1 as carcinogenic to human, based on sufficient evidence in humans of an increased risk of cutaneous malignant melanoma and limited evidence for non-Hodgkin lymphoma (NHL). However present findings on the association of PCB exposure and NHL are still controversial. This study examined the relationship between PCB serum levels and risk of NHL in a Northern Italy area (Brescia province), where a chemical factory produced PCBs from 1938 to 1984, causing human contamination. A case–control study of 215 NHL patients and 215 control subjects was conducted. Cases and controls were assayed for serum levels of 33 PCB congeners. No associations were found between risk of NHL and serum levels of total PCBs (OR = 0.51; 95% CI: 0.25–1.04 for highest vs lowest quartile) or specific PCB congeners. The study confirmed a strong association of NHL with HCV infection (OR = 3.60; 95% CI: 1.30–10.02). This case-control study does not support the hypothesis of an association between current serum levels of PCBs and NHL development in the general population. • No association between current serum levels of PCBs and NHL development in the general population. • Association of NHL with HCV was confirmed. • The present is one of the largest study to examine the relationship between individual PCB levels and risk of NHL. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the effect of adding high-dose cytarabine to methotrexate in patients with newly diagnosed primary central nervous system (CNS) lymphoma. The open, randomized phase two trial was conducted in 24 centers in six countries, and involved 79 patients ages 18 to 75 yeas with non-Hodgkin lymphoma exclusively localized into the CNS, cranial nerves or eyes. The patients were randomly assigned by computer to receive four courses of either methotrexate on day one, or methotrexate on day one combined with cytarabine twice a day on days two to three. Main variable measured was complete remission rate following chemotherapy. Interpretation of the research findings indicate the efficacy of the drug.

Abstract: Plerixafor has been previously reported to improve PBSC collection in pts undergoing PBSC mobilization. Aim of the study was to assess the efficacy of plerixafor and G-CSF in pts with lymphoma who failed previous attempts of PBSC mobilization with conventional schemes of chemotherapy+G-CSF. 35 heavily pre-treated lymphoma pts (29 NHL, 6 HL) classified as “poor mobilizers” were enrolled in a program of compassionate use of plerixafor in 7 Italian centres of REL (Rete Ematologica Lombarda). Median number of previous lines of therapy was 3 and median number of previous attempts of mobilizations was 2. The median number of circulating CD34+ cells/μL following plerixafor was 11/μL. It was ≥10/μL in 17 pts and ≥20/μL in 10 pts; 13 were able to collect ≥2×106 CD34+ cells/kg with a median of 1 apheresis procedure; 4 pts collected ≥4×106 CD34+ cells/kg. A total of 6 pts had proceeded to transplant at the time of analysis. The median dose of PBSCs infused was 4×106/kg and hematopoietic recovery was regular. In conclusion, plerixafor combined with G-CSF allows a collection of adequate number of PBSC in approximately 40% of cases of poor mobilizer, heavily pre-treated pts with lymphoma, who need consolidation with ASCT. [Copyright &y& Elsevier]