Epidemiology and environmental aspects of marginal zone lymphomas.

Marginal zone lymphomas (MZLs) account for between 5% and 17% of all non-Hodgkin's lymphomas. MZLs consist of 3 different subtypes with extranodal being the most commonly reported, representing 50-70% of MZL, followed by splenic (20%) and nodal (10%). Median age at presentation varies between these lymphoma sub-types, ranging between 50 and 69 years, with an overall greater incidence noted in males compared to females.

Long-term follow-up after purine analogue therapy in hairy cell leukaemia.

Since 2006 when we last reviewed the literature concerning the use of purine analogues in hairy cell leukaemia (HCL), results from several new and updated series have been published. Here we examine these reports and consider their implications for patient management. The two purine analogues pentostatin and cladribine remain the first-line treatments of choice for all patients with HCL.

An unusual indication for splenectomy in hairy cell leukaemia: a report of three cases with persistent splenomegaly after chemoimmunotherapy.

We describe three cases of relapsed hairy cell leukaemia (HCL) treated with pentostatin plus rituximab. All three achieved bone marrow complete remission but had persistent splenomegaly and hypersplenism. Because of the clinical uncertainty of its significance, they were all splenectomized.

Rituximab plus chlorambucil as first-line treatment for chronic lymphocytic leukemia: Final analysis of an open-label phase II study.

Purpose: Most patients with chronic lymphocytic leukemia (CLL) are elderly and/or have comorbidities that may make them ineligible for fludarabine-based treatment. For this population, chlorambucil monotherapy is an appropriate therapeutic option; however, response rates with chlorambucil are low, and more effective treatments are needed. This trial was designed to assess how the addition of rituximab to chlorambucil (R-chlorambucil) would affect safety and efficacy in patients with CLL.

Improved relapse-free survival after autologous stem cell transplantation does not translate into better quality of life in chronic lymphocytic leukemia: lessons from the randomized European Society for Blood and Marrow Transplantation-Intergroup study.

In chronic lymphocytic leukemia (CLL) medical progress is driven by clinical studies with relapse-free survival (RFS) as the primary endpoint. The randomized EBMT-Intergroup trial compared high-dose therapy and autologous stem cell transplantation (ASCT) to observation and demonstrated a substantial improvement of RFS without showing improved overall survival for the transplant arm. Here we report quality of life (QoL) information of the first 3 years following randomization from that study.

High readmission rates are associated with a significant economic burden and poor outcome in patients with grade III/IV acute GvHD.

Graft-versus-host disease (GvHD) is a common complication following haematopoietic stem cell transplant but little is published about the impact of this condition on hospital readmission rates. We report a retrospective analysis of readmission rates and associated costs in 187 consecutive allogeneic transplant patients to assess the impact of GvHD. The overall readmission rate was higher in patients with GvHD (86% (101/118) vs.

Rituximab, used alone or in combination, is superior to other treatment modalities in splenic marginal zone lymphoma.

Splenic marginal zone lymphoma (SMZL) is a rare B-cell malignancy, with no standard treatment other than splenectomy. Rituximab has shown encouraging results. We therefore retrospectively assessed 43 patients from two centres, who received rituximab, either alone or with chemotherapy.

Alemtuzumab in combination with methylprednisolone is a highly effective induction regimen for patients with chronic lymphocytic leukemia and deletion of TP53: final results of the national cancer research institute CLL206 trial.

Purpose: In chronic lymphocytic leukemia (CLL), TP53 deletion/mutation is strongly associated with an adverse outcome and resistance to chemotherapy-based treatment. In contrast, TP53 defects are not associated with resistance to the anti-CD52 monoclonal antibody alemtuzumab or methylprednisolone. In an attempt to improve the treatment of TP53-defective CLL, a multicenter phase II study was developed to evaluate alemtuzumab and methylprednisolone in combination.

Alemtuzumab therapy in T-cell prolymphocytic leukemia: comparing efficacy in a series treated intravenously and a study piloting the subcutaneous route.

Intravenous alemtuzumab is an effective and well-tolerated treatment for T-cell prolymphocytic leukemia (T-PLL). Alemtuzumab given intravenously as first-line treatment in 32 patients resulted in an overall response rate of 91% with 81% complete responses. Studies in B-cell chronic lymphocytic leukemia have shown subcutaneous alemtuzumab to be equally as effective as intravenous alemtuzumab.

A comparison of the efficacy and safety of oral and intravenous fludarabine in chronic lymphocytic leukemia in the LRF CLL4 trial.

Background: An oral formulation of fludarabine was introduced for use in chronic lymphocytic leukemia in 2001 following studies demonstrating the bioequivalence of a 40 mg/m(2) oral dose with a 25 mg/m(2) intravenous dose. We assessed retrospectively the efficacy of these two routes of administration in the LRF CLL4 trial.

Methods: A total of 777 patients were randomized from 1999-2004 to receive fludarabine, alone or with cyclophosphamide, or chlorambucil.

Long-term results for pentostatin and cladribine treatment of hairy cell leukemia.

Over the past 25 years we have collected data at our institution from 242 patients with hairy cell leukemia (HCL), treated with pentostatin (n = 188) or cladribine (n = 54), with a median follow-up of 16 years. From this we have been able to conclude that there is no significant difference in outcome between the two agents either at first or subsequent lines of therapy. Overall, the complete response (CR) rate is 81% and the median disease-free survival (DFS) is 16 years.

Rituximab with pentostatin or cladribine: an effective combination treatment for hairy cell leukemia after disease recurrence.

The purine analogs pentostatin and cladribine are effective treatments for hairy cell leukemia (HCL). However, alternative treatments are needed for patients with recurrent disease. We reviewed retrospectively data from 18 patients who were retreated with either pentostatin (n = 12) or cladribine (n = 6) in combination with rituximab, after 1-6 (median 2) previous treatments with either purine analog as a single agent.

Mutational status of the TP53 gene as a predictor of response and survival in patients with chronic lymphocytic leukemia: results from the LRF CLL4 trial.

Purpose: TP53 mutations have been described in chronic lymphocytic leukemia (CLL) and have been associated with poor prognosis in retrospective studies. We aimed to address the frequency and prognostic value of TP53 abnormalities in patients with CLL in the context of a prospective randomized trial.

Patients And Methods: We analyzed 529 CLL samples from the LRF CLL4 (Leukaemia Research Foundation Chronic Lymphocytic Leukemia 4) trial (chlorambucil v fludarabine with or without cyclophosphamide) at the time of random assignment for mutations in the TP53 gene.

Guidelines for the management of mature T-cell and NK-cell neoplasms (excluding cutaneous T-cell lymphoma).

The peripheral T-cell neoplasms are a biologically and clinically heterogeneous group of rare disorders that result from clonal proliferation of mature post-thymic lymphocytes. Natural killer (NK) cell neoplasms are included in this group. The World Health Organization classification of haemopoietic malignancies has divided this group of disorders into those with predominantly leukaemic (disseminated), nodal, extra-nodal or cutaneous presentation.

T-cell prolymphocytic leukemia.

T-cell prolymphocytic leukemia is a rare postthymic malignancy with distinctive clinical, morphologic, immunophenotypic, and cytogenetic features. The clinical course is typically aggressive with poor response to conventional chemotherapy and short survival. Treatment with purine analogues and alemtuzumab has resulted in significantly higher response rates and improved survival.

Drug cross-resistance and therapy-induced resistance in chronic lymphocytic leukaemia by an enhanced method of individualised tumour response testing.

Previous results with individualised tumour response testing (ITRT) in vitro in chronic lymphocytic leukaemia (CLL) have consistently shown good correlation with patient response and survival. We describe here an improved test and report its use with samples from the Leukaemia Research Fund CLL4 randomised clinical trial and previously treated patients. ITRT was performed by the tumour response to anti-neoplastic compounds (TRAC) assay, a modification of the differential staining cytotoxicity (DiSC) assay.

Long-term follow-up of 233 patients with hairy cell leukaemia, treated initially with pentostatin or cladribine, at a median of 16 years from diagnosis.

Hairy cell leukaemia (HCL) was first described 50 years ago. Median survival was then 4 years. The purine analogues, introduced in the 1980s, transformed this prognosis.

Alemtuzumab in the treatment of chronic lymphocytic lymphoma.

Alemtuzumab was the first monoclonal antibody to be humanized, a process which embeds rodent sequence fragments in a human IgG framework. The antibody target is CD52, an antigen expressed on normal lymphocytes as well as many T- and B-cell neoplasms. It therefore has a potential broad application across a spectrum of B- and T-cell malignancies as well as use as an immunosuppressant drug in, for example, bone marrow transplantation.

Role of antibody therapy in lymphoid malignancies.

Introduction: Over the past decade, the potential for delivering targeted therapy against malignant disease by the use of monoclonal antibodies (MoAbs) has begun to be realized. The development of human or chimeric antibodies and protein engineering to combine MoAbs with other biologically active molecules, such as radio-isotopes, toxins, chemotherapy and cytokines, has made available a new range of agents with clinical activity.

Discussion: This article will review the requirements and strategies for successful MoAb therapy and the clinical experience in a range of lymphoid malignancies.

Alemtuzumab in T-cell lymphoproliferative disorders.

The humanized monoclonal antibody alemtuzumab binds to the CD52 antigen, a glycoprotein which is widely expressed on normal and malignant B and T lymphocytes. Recently it has been demonstrated in a number of clinical trials that alemtuzumab has clinical activity in mature T-cell diseases such as T-prolymphocytic leukaemia and cutaneous T-cell lymphoma, inducing responses in up to two thirds of heavily pre-treated relapsed/refractory patients. Response was associated with improved survival.