Prognostication of the high-risk WM patient

Waldenström's macroglobulinemia is characterized by a protracted course in most patients and the median survival may be long. However, a subset of patients may present with more aggressive disease that is associated with short survival. In order to better characterize these “poor-risk” patients, we identified patients who died within 2 years from the initiation of front-line treatment. These patients were older and had more often features of aggressive disease, such as elevated LDH and low serum albumin than the standard-risk population. Furthermore, only a minority of poor-risk patient had a response to initial therapy. However, conventional clinical factors or even the lack on response could not adequately identify poor-risk patients, indicating the need for novel molecular or other markers that would be able to effectively recognize patients at greatest need for aggressive therapies.     

Impact of cancer patients' disease awareness on their family members' health‐related quality of life: a cross‐sectional survey

Background: Conflicting results exist concerning disease knowledge and patients' quality of life (QOL) while there is very limited information concerning the impact of awareness on caregivers' health‐related quality of life. The aim of this study was to explore the influence of disease awareness on both cancer patients and their caregivers during the period of chemotherapy. Materials and Methods: Two hundred and twelve cancer patient–caregiver dyads completed the QOL SF‐36 instrument on the day of chemotherapy. Hierarchical multiple linear regression analysis was performed. Results: Physical component parameters were significantly higher in the family members (p<0.001), while their mental component was lower than cancer patients. Younger patients, females, and of higher educational status were more frequently aware of their disease status while patients with gastrointestinal cancer were more likely to be unaware. Disease knowledge seems to exert a negative influence on patients' physical and mental parameters while lack of awareness affects adversely caregivers' vitality, social function, emotional role, and mental health. Multiple regression analysis confirmed disease awareness affected reversely patients' and caregivers' mental QOL while the counter‐influence of the dyad was revealed. Conclusions: A holistic approach to cancer management should be followed. Patient's treatment is the major medical concern, but health system and professionals should be involved in the mental and physical support of caregivers as well. Tailored interventions that focus on the support of the dyad patient–caregiver should be developed. Copyright © 2010 John Wiley & Sons, Ltd.     

Autologous stem-cell transplantation in malignant multiple sclerosis: a case with a favorable long-term outcome

Malignant multiple sclerosis (MS) is a rare but clinically important subtype of MS characterized by the rapid development of significant disability in the early stages of the disease process. These patients are refractory to conventional immunomodulatory agents and the mainstay of their treatment is plasmapheresis or immunosuppression with mitoxantrone, cyclophosphamide, cladribine or, lately, bone marrow transplantation. We report on the case of a 17-year old patient with malignant MS who was treated with high-dose chemotherapy plus anti-thymocyte globulin followed by autologous stem cell transplantation. This intervention resulted in an impressive and long-lasting clinical and radiological response. It is concluded that intensive immunosuppression followed by autologous stem cell transplantation is a viable therapeutic option in patients with malignant MS unresponsive to conventional forms of treatment.     

Serum concentrations of angiogenic cytokines in Waldenstrom macroglobulinaemia: the ration of angiopoietin-1 to angiopoietin-2 and angiogenin correlate with disease severity

Angiogenesis represents an essential step of disease progression in several haematological malignancies. Microvessel density is increased in 30% of patients with Waldenstrom macroglobulinaemia (WM), but there is very limited information regarding the role of angiogenic cytokines in this disease. Serum levels of vascular endothelial growth factor (VEGF), VEGF-A, angiogenin, angiopoietin (Ang)-1 and -2, and basic fibroblast growth factor (bFGF) were evaluated in 56 WM patients at different disease phases (24 untreated, 20 relapsed/refractory and 12 patients at remission) and 11 patients with immunoglobulin M type monoclonal gammopathy of undetermined significance (IgM-MGUS). All patients had increased levels of angiogenin, VEGF, VEGF-A, and bFGF compared with controls. The Ang-1/Ang-2 ratio was reduced in WM but not in IgM-MGUS patients. Angiogenin levels correlated with disease status: when compared with healthy subjects, patients with IgM-MGUS and untreated WM patients had increased angiogenin serum levels, which were higher in untreated WM patients than in MGUS. WM patients at remission had lower angiogenin serum levels compared with untreated patients, but these levels were increased again in active disease post-therapy. Angiogenin also correlated with albumin levels, while VEGF-A correlated with beta(2)-microglobulin (beta2M). Ang-1/Ang-2 ratio showed a strong, negative correlation with beta2M, and positive correlation with albumin, haemoglobin and lymphadenopathy. Our results indicate a potential use of angiogenin levels for follow-up in WM and angiogenic molecules as targets for the development of novel anti-WM agents.     

High-dose methotrexate is beneficial in parenchymal brain masses of uncertain origin suspicious for primary CNS lymphoma

In patients with parenchymal brain masses of uncertain origin responsive to corticosteroids, primary CNS lymphoma (PCNSL) should be considered. PCNSL is a rare but aggressive brain tumor that is highly sensitive to high-dose methotrexate (HDMTX)-based chemotherapy. We report a series of six patients with brain masses without histologic confirmation suspicious for PCNSL based on clinical and radiomorphologic criteria after exclusion of some infectious conditions. All patients were treated with HDMTX. We observed two complete responses, two partial responses, and one stable disease. One patient had progressive disease and received rescue whole-brain irradiation. All patients were alive without disease progression 12-48 months after HDMTX start. No symptoms of late neurotoxicity have occurred so far. The response and survival data in this small series of patients are encouraging and suggest a benefit for patients with suspected PCNSL after initial treatment with HDMTX.     

Radiologic and pathologic features of a posttransplantation primary central nervous system lymphoma demonstrating Epstein-Barr virus-positive Hodgkin lymphoma

Posttransplantation lymphoproliferative disease is the most common malignancy in T-cell immunocompromised patients and often involves extranodal sites including the central nervous system (CNS). Primary posttransplantation CNS lymphomas are rare and, accordingly, are poorly characterized. Herein, for the first time, we describe the radiologic and pathologic features of a primary CNS posttransplantation lymphoproliferative disease that reveals Epstein-Barr virus-positive Hodgkin lymphoma. The lesion showed characteristic Hodgkin-Reed Sternberg cells with a typical immunophenotype, accompanied by numerous nonneoplastic B cells and T cells demonstrating classic Hodgkin lymphoma within the brain. The 65-year-old patient was treated by reduction of immunosuppression and cerebral radiation therapy and remains in remission 18 months after the initial diagnosis.     

Pulsed cyclophosphamide, thalidomide and dexamethasone regimen for previously treated patients with multiple myeloma: long term follow up and disease control after subsequent treatments

There are limited data regarding the long term follow up after thalidomide based regimen and the outcome of patients when they progress and they receive further treatment. We reassessed our original series of 43 patients with previously treated multiple myeloma who had received a pulsed cyclophosphamide, thalidomide, dexamethasone (CTD) regimen. Among the 43 patients, 14 did not respond to pulsed CTD and 29 (67%) achieved at least a partial response. The median PFS for all patients was 10 months. After a median follow up of 24 months (range 1 - 62), the 3 year PFS is 14% and 3 patients remain off treatment and without progression for 55+, 55+ and 56+ months respectively. Moreover, 28% of patients who progressed after CTD achieved a partial response after subsequent treatment which included thalidomide, bortezomib or lenalidomide. The median PFS of these patients was 5 months and the 1 year PFS was 20%. Furthermore, 31% of patients who had responded to CTD and then progressed (CTD sensitive) responded to subsequent treatment. We conclude that some patients enjoy long responses after CTD and that several patients who progress after CTD may respond to treatment with a novel agent-based regimen.