Low-dose subcutaneous alemtuzumab in refractory chronic lymphocytic leukaemia (CLL) : results of a prospective, single-arm multicentre study

Alemtuzumab is active in chronic lymphocytic leukaemia (CLL) patients refractory to alkylators and fludarabine. The aim of this study was to determine the efficacy and safety of subcutaneous alemtuzumab at low dose (10 mg three times per week, for 18 weeks) to 49 patients with pre-treated CLL. The overall response rate was 53%, including 27% of complete responses; it was 42% in patients over 70 years, and 54% in the fludarabine-resistant patients. Forty-five percent of the patients with an unfavourable karyotype responded, including 60% of those with the 17p- aberration. After a median follow-up of 25 months, the median overall time to disease progression was 8 months (responders 12 months, non-responders 4 months). The median overall time to alternative treatment was 9 months (responders 17 months, non-responders 6 months) and median overall survival was 30 months. The treatment was well tolerated: grade IV neutropenia was observed in 17%, and cytomegalovirus (CMV) reactivation in 24% of the patients, with no CMV disease. We observed a total of 30 infections (50% during treatment and 50% during the 12-month follow-up), only one-third of which was severe. This study confirms that low-dose subcutaneous alemtuzumab is effective in poor prognosis CLL, and has a particularly favourable toxicity profile

Use of biosimilar filgrastim compared with lenograstim in autologous haematopoietic stem-cell transplant and in sibling allogeneic transplant.

OBJECTIVES: Biosimilar filgrastim was compared with lenograstim for autologous haematopoietic stem-cell transplant (HSCT) in patients with haematological malignancies. Data from a separate group of sibling donors who underwent allogeneic HSCT are also reported. METHODS: Patients with lymphoma or multiple myeloma (MM) who underwent autologous HSCT with biosimilar filgrastim were compared with a historical control group of patients who received lenograstim. Peripheral blood (PB) cells counts were monitored after 7-8 consecutive days of granulocyte-colony stimulating factor (G-CSF) injection and apheresis was performed on day 8 if PB CD34+ cell count was ⩾10 cells/µl. The target PB CD34+ cell doses were ⩾2.0 × 10(6)/kg (lymphoma), ⩾4.0 × 10(6)/kg (MM ⩾60 years old) or ⩾8.0 × 10(6)/kg (MM <60 years old). RESULTS: A total of 259 patients were included in the autologous HSCT comparison (biosimilar filgrastim, n = 104; lenograstim, n = 155). In patients with lymphoma and older MM patients (⩾60 years old), no significant differences were observed between groups with regard to stem-cell mobilization parameters. However, in MM patients <60 years old, all parameters were significantly superior in the biosimilar filgrastim group, including the need for 1 rather than 2 apheresis procedures. No significant differences were observed between groups in median number of days to absolute neutrophil count (ANC) or platelet recovery. In the allogeneic setting, 47 sibling donors received biosimilar filgrastim. Mean CD34+ count at the first apheresis was 6.1 × 10(6)/kg. A total of 13 donors needed a second apheresis and 4 required a third. Among recipients, median days to ANC recovery was 16 (10-28) and to platelet recovery was 13 (9-54). CONCLUSIONS: Biosimilar filgrastim is as effective as lenograstim for autologous HSCT in patients with lymphoma or MM patients ⩾60 years old. However, mobilization with biosimilar filgrastim appeared to be superior to that with lenograstim in younger MM patients.S.A. has received support for meetings and unrestricted educational grants from Amgen, Chugai and SandozPDF version submitted- requires post print - withdraw

Plerixafor: What we still have to learn

Plerixafor, a hematopoietic stem cell mobilizer, is indicated in combination with G-CSF to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma. Current evidence suggests that the addition of plerixafor with chemotherapy plus G-CSF is safe and effective in the large majority of the patients with low blood CD34+ cell count after mobilization and/or poor yield after the first collection. Nevertheless, there are several questions strongly debated, and in this paper, we would like to identify areas of possible future use and development of the drug

Endothelial nitric oxide synthase gene polymorphisms (G894T and T786C) in essential throbocythemia

Background and Objectives. The occurrence of two or more cases of multiple myeloma (MM) in the same family has been reported from time to time. The current study is the first population- and cancer-registry-based survey to investigate familiality of premalignant or malignant B-cell proliferation. Design and Methods. A family registry of 218 multiple myeloma cases was compared with the records of the Icelandic Cancer Registry in order to analyze the pedigrees for the occurrence of families with multiple cases of paraproteinemia and hematologic malignancies. Results. The relative risk of developing monoclonal gammopathies of unknown significance (MGUS) was not increased among first-degree relatives of MM patients, but there was a significantly increased risk of developing MM for females separately (RR = 3.23, CI 1.17-7.01) and for males and females combined (RR = 2.33, CI 1.12-4.26). Analysis for all hematologic malignancies showed an increased risk for female relatives of MM patients (RR = 1.95, CI 1.10-3.20). Eight families were identified in which the propositus with MM had > 1 relatives with MGUS and > 1 with another hematologic malignancy, including 4 families with another relative with MM. In three families both myeloid and lymphoid malignancies occurred. Interpretation and Conclusions. Although inheritance does not appear to be a major risk factor for the development of paraproteinemias a significant risk of developing MM was found for female relatives. The occurrence of multiple cases of benign and malignant paraproteinemias in a few families does suggest a hereditary contribution. Further studies of such families might reveal clues on pathogenesis