Inhibiting Dickkopf-1 (Dkk1) removes suppression of bone formation and prevents the development of osteolytic bone disease in multiple myeloma.

Multiple myeloma (MM) is associated with the development of osteolytic bone disease, mediated by increased osteoclastic bone resorption and impaired osteoblastic bone formation. Dickkopf-1 (Dkk1), a soluble inhibitor of wingless/int (Wnt) signaling and osteoblastogenesis, is elevated in patients with MM and correlates with osteolytic bone disease. In this study, we investigated the effect of inhibiting Dkk1 on the development of osteolytic lesions in the 5T2MM murine model of myeloma.

Ovarian failure following cancer treatment: current management and quality of life.

Background: There is a lack of evidence regarding current screening practices for incipient ovarian failure in young women following gonadotoxic therapy and the most appropriate form of estrogen replacement. This study examined the (i) prevalence and management of ovarian failure and (ii) quality-of-life implications of early menopause (EM).

Methods: A medical case note audit for 288 women with a history of gonadotoxic therapy (aged 18-50 years) was conducted.

Follow-up care for young adult survivors of cancer: lessons from pediatrics.

Introduction: Recent advances in treatment of childhood cancer have resulted in overall survival rates approaching 75%, but approximately two-thirds experience late-effects related to the disease or treatment. Consequently, recommendations for comprehensive follow-up have been made. As the number of survivors of adult cancers increase, similar concerns about how to provide follow-up and achieve optimal quality of life are being raised.

Thalidomide maintenance following high-dose therapy in multiple myeloma: a UK myeloma forum phase 2 study.

Thalidomide maintenance has unresolved issues regarding dosage and toxicity. We evaluated this in five dose cohorts in 100 patients. At a median follow-up of 32.

Haemopoietic stem cell transplantation--an evolving treatment for severe autoimmune and inflammatory diseases in rheumatology, neurology and gastroenterology.

The concept of haemopoietic stem cell transplantation (HSCT) to treat severe autoimmune diseases has been around for several decades. Advances in the safety of HSCT have made it a clinical reality since 1995. Databases have registered around a thousand patients treated specifically for a wide range of diseases, predominantly multiple sclerosis (MS), systemic sclerosis (SSc), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).

Long-term outcomes of myeloablation and autologous transplantation of relapsed acute myeloid leukemia in second remission: a British Society of Blood and Marrow Transplantation registry study.

Relapsed acute myeloid leukemia (AML) in adults has a poor prognosis if treated with chemotherapy alone. Case series have previously supported the role of myeloablation and autologous transplantation as a potentially curative treatment. This study aimed to use the large numbers and extended follow-up data in the British Society of Blood and Marrow Transplantation (BSBMT) registry database to establish long-term outcomes and relate these to biological and procedural factors.

The clinical outcome and toxicity of high-dose chemotherapy and autologous stem cell transplantation in patients with myeloma or amyloid and severe renal impairment: a British Society of Blood and Marrow Transplantation study.

The outcome of high-dose chemotherapy (HDT) was evaluated retrospectively in 27 patients with myeloma and four patients with AL amyloidosis with severe renal impairment. Twenty-three patients were receiving dialysis and the rest had a creatinine clearance of <20 ml/min. The median melphalan dose was 140 mg/m2 (range: 60-200 mg/m2), but 10 patients (37%) received 200 mg/m2.

Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia.

We previously demonstrated prolonged, profound CD4+ T-lymphopenia in rheumatoid arthritis (RA) patients following lymphocyte-depleting therapy. Poor reconstitution could result either from reduced de novo T-cell production through the thymus or from poor peripheral expansion of residual T-cells. Interleukin-7 (IL-7) is known to stimulate the thymus to produce new T-cells and to allow circulating mature T-cells to expand, thereby playing a critical role in T-cell homeostasis.

Autologous hemopoietic stem cell transplantation in severe rheumatoid arthritis: a report from the EBMT and ABMTR.

Objective: Since 1996, autologous hemopoietic stem cell transplantation (HSCT) has been used to treat severe rheumatoid arthritis (RA). To date, published reports have been individual cases or series containing small numbers. This study combined the worldwide experience in a single analysis.

A pilot randomized trial comparing CD34-selected versus unmanipulated hemopoietic stem cell transplantation for severe, refractory rheumatoid arthritis.

Objective: Evidence from animal studies, case reports, and phase I studies suggests that hemopoietic stem cell transplantation (HSCT) can be effective in the treatment of rheumatoid arthritis (RA). It is unclear, however, if depletion of T cells in the stem cell product infused after high-dose chemotherapy is beneficial in prolonging responses by reducing the number of infused autoreactive T cells. This pilot multicenter, randomized trial was undertaken to obtain feasibility data on whether CD34 selection (as a form of T cell depletion) of an autologous stem cell graft is of benefit in the HSCT procedure in patients with severe, refractory RA.