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.

Searching for surrogates for IGHV mutations in chronic lymphocytic leukemia.

Despite a startling separation of chronic lymphocytic leukemia (CLL) into two clinically different diseases with average survivals of 8 years and 25 years, the mutational status of immunoglobulin variable region (IGHV) genes has not entered routine clinical practice to assess prognosis, although its assessment is regarded as an essential for clinical trials. Instead, surrogates that may be measured by flow cytometry have been sought. Measurements of the expression of CD38 and ZAP-70 have been the most popular assays for prognosis although both are in their own ways unsatisfactory.

In vitro response of the natural cadaver knee to the loading profiles specified in a standard for knee implant wear testing.

The purpose of this study was to examine how a natural knee responds to the inputs of a total knee replacement testing standard developed by the International Organization for Standardization (ISO). This load control standard prescribes forces to be used for wear testing of knee replacements independent of implant size or design. A parallel ISO standard provides wear testing inputs that are displacement based instead of force based.

The TCL1 mouse as a model for chronic lymphocytic leukemia.

The TCL1 mouse has been proposed as a mouse model for chronic lymphocytic leukemia. This review details how it resembles the aggressive form of the disease rather than the more common indolent form. Although fulfilled predictions in the human disease based on investigations in the mouse model are at present lacking, there are remarkable similarities between human and mouse leukemias that have led to interesting observations on the pathophysiology of chronic lymphocytic leukemia and have identified putative therapeutic targets.

Fludarabine, cyclophosphamide and rituximab for chronic lymphocytic leukemia: no country for old men?

The combination of fludarabine, cyclophosphamide and rituximab is regarded as the gold-standard treatment for chronic lymphocytic leukemia in many parts of the world, although rituximab has not yet been licensed for this use. To date, no randomized, controlled trials have been fully published that demonstrate the superiority of this regimen over other treatments. The results of an open-label, phase II trial with long-term follow-up data on 300 patients with chronic lymphocytic leukemia treated with this regimen are discussed here.

Non-hemic autoimmunity in CLL.

Non-hemic autoimmune complications of chronic lymphocytic leukemia are very rare compared to autoimmune haemolytic anemia, which occurs in between 10% and 20% of patients and immune thrombocytopenia, which occurs in between 1% and 2% of patients. A clear relationship has only been established with three non-hemic syndromes: acquired angioedema, glomerulonephritis and paraneoplastic pemphigus. The first is a result of a secreted product of the tumor, but the last two seem to be a product of the disordered immune system, and may be triggered by treatment with purine analogues suggesting a mechanism involving regulatory T cells.

The immunodeficiency of chronic lymphocytic leukaemia.

Introduction: Patients with chronic lymphocytic leukaemia (CLL) have progressive immunodeficiency and infection is the commonest cause of death. This review seeks to identify the extent of the abnormality, its cause, clinical significance and any possible remedy.

Sources Of Data: TJH has studied CLL for the past 40 years and has scanned or read every paper he could find published on the topic since 1970 and most of those of historical importance published before that date.

Chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia is the commonest form of leukaemia in Europe and North America, and mainly, though not exclusively, affects older individuals. It has a very variable course, with survival ranging from months to decades. Major progress has been made in identification of molecular and cellular markers that could predict disease progression in patients with chronic lymphocytic leukaemia.

CD38 expression in chronic lymphocytic leukemia is regulated by the tumor microenvironment.

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease with a highly variable outcome. The prognosis of patients with CLL may be predicted using a number of biomarkers, including the level of CD38 expression at the leukemic cell surface. This study investigates the hypothesis that CD38 expression by CLL cells reflects interactions with nonmalignant cells within pseudofollicles in secondary lymphoid tissue where tumor cell proliferation is thought to occur.

Approaches to therapy for children in India with cerebral palsy.

This article describes the approach to intervention programs for children with cerebral palsy in India. It provides an overview of services available in particular in the fields of physiotherapy, speech therapy and AAC.

The prognostic significance of a positive direct antiglobulin test in chronic lymphocytic leukemia: a beneficial effect of the combination of fludarabine and cyclophosphamide on the incidence of hemolytic anemia.

Autoimmune hemolytic anemia (AHA) is a common complication in chronic lymphocytic leukemia (CLL). The UK LRF CLL4 trial is the largest prospective trial in CLL to examine the prognostic impact of both a positive direct antiglobulin test (DAT) and AHA. Seven-hundred seventy-seven patients were randomized to receive chlorambucil or fludarabine, alone or with cyclophosphamide (FC).

Determination of how many immunoglobulin variable region heavy chain mutations are allowable in unmutated chronic lymphocytic leukaemia - long-term follow up of patients with different percentages of mutations.

The choice of 98% sequence homology for immunoglobulin heavy chains to distinguish between mutated and unmutated versions of chronic lymphocytic leukaemia (CLL) was arbitrary and was chosen to account for supposed polymorphisms. Some authors chose 97% or even 95%. This study examined survival curves for cohorts of patients with varying degrees of sequence homology.

Have we been wrong about ionizing radiation and chronic lymphocytic leukemia?

It is almost axiomatic that chronic lymphocytic leukemia (CLL) is not caused by ionizing radiation. This assumption has been challenged recently by a critical re-appraisal of existing data. A recent paper implicated radon exposure in Czech uranium miners as a possible cause of CLL and in this issue of Leukemia Research the first paper examining the incidence of CLL among those exposed to radiation from the accident at the nuclear power plant in Chernobyl is published.

Prognostic markers in chronic lymphocytic leukaemia.

Rai and Binet staging of chronic lymphocytic leukaemia (CLL) is being superseded by new prognostic markers. The mutational status of the immunoglobulin variable region heavy-chain genes segregates the disease into more benign and more malignant versions, and has been confirmed as an important prognostic marker in prospective clinical trials. A search for surrogate markers for this difficult-to-perform assay has led to flow cytometric assays for CD38 and ZAP-70 expression, although in both cases there are problems with standardization and interpretation of the assays.

Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial.

Background: Previous studies of patients with chronic lymphocytic leukaemia reported high response rates to fludarabine combined with cyclophosphamide. We aimed to establish whether this treatment combination provided greater survival benefit than did chlorambucil or fludarabine.

Methods: 777 patients with chronic lymphocytic leukaemia requiring treatment were randomly assigned to fludarabine (n=194) or fludarabine plus cyclophosphamide (196) for six courses, or chlorambucil (387) for 12 courses.

Myocardial iron loading by magnetic resonance imaging T2* in good prognostic myelodysplastic syndrome patients on long-term blood transfusions.

Magnetic resonance imaging (MRI) was used to quantify myocardial iron loading by T2* in 11 transfusion-dependent good prognostic myelodysplastic syndrome (MDS) patients. Myocardial T2*, left ventricular function and hepatic T2* were measured simultaneously. Patients had been on transfusion therapy for 13-123 months and had serum ferritin levels of 1109-6148 microg/l at the time of study.