High efficacy with five days schedule of oral fludarabine phosphate and cyclophosphamide in patients with previously untreated chronic lymphocytic leukaemia.

A multicentre single-arm study testing the efficacy and toxicity of the oral combination of fludarabine and cyclophosphamide (FC) over 5 d in 75 patients with untreated B cell-chronic lymphocytic leukaemia. Oral FC demonstrated high efficacy with overall (OR) and complete response (CR) rates of 80% and 53%, respectively. Out of the 30 CR patients studied for Minimal Residual Disease (MRD) using 4-colour flow-cytometry and the 22 using Clonospecific polymerase chain reaction, 22 (66%) and 16 (68%), respectively, were MRD negative. Median survival and median treatment-free interval had not been reached at 7 years of follow-up. Median progression-free survival (PFS) was 5 years. Toxicity was acceptable, with 52% and 16% of National Cancer Institute grade 3/4 neutropenia and infections, respectively. Gastrointestinal toxicity was mild. Oral FC demonstrated a high efficacy and an acceptable safety profile and may be considered as the standard first line treatment in chronic lymphocytic leukaemia.

Plasma exchanges do not increase red blood cell transfusion efficiency in severe autoimmune hemolytic anemia: a retrospective case-control study.

Severe autoimmune hemolytic anemia (AIHA) can cause life-threatening hemolysis requiring red blood cell transfusions (RBT). The efficiency of RBT could be improved with the use of plasma exchanges (PEx) before RBT. The objective of this study was to assess the effectiveness of PEx in severe AIHA of adults. All adult patients with severe AIHA requiring RBT were included in this single center retrospective case-control study. The end point was change in hemoglobin (Hb) level after RBT, depending on whether PEx was done (experimental group) or not (control group). Thirty-one sessions of RBT following PEx were performed on the 5 patients of the experimental group and were compared with the 7 sessions of BT without PEx performed on the 4 patients of the control group. Despite a lower mean Hb value before the session of RBT (5.7 g/dl vs. 7.2 g/dl, P = 0.04) in the control group, the mean Hb value 5 (4-7) days following RBT (8.7 g/dl vs. 8.6 g/dl, P = 0.85) was not different in the experimental and in the control group, respectively. In a second analysis in which each patient was his own control (31 sessions of RBT following PEx vs. 51 sessions of RBT alone), the gain in Hb was not different (1.4 g/dl vs. 1.9 g/dl, P = 0.67). When RBT are required in severe AIHA of adults, the use of a single PEx before BT does not increase the efficiency of RBT based on day 5 evaluation.

High-dose therapy followed by autologous purged stem-cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by GOELAMS.

Doxorubicin-based immunochemotherapy, with interferon, has been shown to improve survival in patients with advanced follicular lymphoma. High-dose chemotherapy with stem-cell support is effective in follicular lymphoma in relapse but remains controversial as a first-line therapy. In a randomized study using a purged autologous stem-cell support, we compared these 2 approaches in patients with advanced follicular lymphoma. Newly diagnosed advanced follicular lymphoma patients (172 patients) were randomly assigned either to an immunochemotherapy regimen (cyclophosphamide, doxorubicin, teniposide, prednisone, and interferon) or to a high-dose therapy followed by purged autologous stem-cell transplantation. Compared with the patients who received chemotherapy and interferon, patients treated with high-dose therapy had a higher response rate (69% vs 81%, P = .045) and a longer median event-free survival (not reached vs 45 months). This did not translate into a better survival rate due to an excess of secondary malignancies after transplantation. The Follicular Lymphoma Prognostic Index identified a subgroup of patients with a significantly higher event-free survival rate after high-dose therapy. Autologous stem-cell transplantation cannot be considered as the standard first-line treatment of follicular lymphoma for patients younger than 60 years old with a high tumor burden.

Two new cases of familial hairy cell leukemia associated with HLA haplotypes A2, B7, Bw4, Bw6.

Hairy cell leukemia (HCL) is a rare hematological disorder of unknown origin. Thirteen familial cases of HCL have been reported, with 28 relatives affected. Here we report 2 cases of HCL in a family associated with HLA haplotypes A2, B7 and Bw4/6.

Impact of frontline fludarabine and cyclophosphamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia.

Ongoing studies in B-cell chronic lymphocytic leukemia are evaluating autologous peripheral blood stem cell (PBSC) transplantation in first remission following fludarabine therapy. However, fludarabine could impair PBSC harvest. In 38 patients after frontline oral fludarabine and cyclophosphamide (FDR-CY) therapy, we prospectively evaluated steady state filgrastim- or lenograstim-primed PBSC mobilization to collect 2.0 x 106/kg or more CD34 cells. The first mobilization, performed a median of 178 days (range, 69-377 days) from the last FDR-CY course, was unsuccessful in 32 patients. This result was significantly associated with a low platelet count before mobilization but not with age, interval from last FDR-CY course, initial stage, remission status, or other blood parameters. Finally, after 1, 2, and 3 mobilizations in 27, 10, and 1 patients, 2.0 x 106/kg or more CD34 cells were collected in only 12. Explorations of the mechanism of poor mobilization and adaptation of PBSC harvest policies after fludarabine treatment are therefore warranted.

Molecular evidence of persistent echovirus 13 meningoencephalitis in a patient with relapsed lymphoma after an outbreak of meningitis in 2000.

Enteroviral meningoencephalitis was diagnosed in a patient with an immunodeficiency syndrome acquired after treatment with rituximab for a relapsed primary B-cell lymphoma. A second meningoencephalitic episode was diagnosed 6 months later and was successfully treated with a combination of immunoglobulins and pleconaril. The infection was persistent since the enterovirus genome was detected in five sequential specimens of cerebrospinal fluid collected over 9 months. An echovirus 13 isolate was isolated in the first three samples. The viral sequence encoding the VP1 capsid protein of the three isolates was determined and was compared with that of four control viruses. The virus isolates recovered from the patient shared >99% nucleotide sequence similarity with one another. In a phylogenetic tree, they were directly related to a control virus obtained from a patient hospitalized in 2000 during an outbreak of enterovirus meningitis. The epidemiological origin of a chronic echovirus infection in a patient with immune deficiency suggests that the echovirus had been continuously circulating in the general population after the outbreak that had revealed its emergence.

Enteroviral meningoencephalitis after anti-CD20 (rituximab) treatment.

Treatment with the chimeric anti-CD20 monoclonal antibody rituximab induces rapid and long-lasting depletion of circulating B cells. We report the occurrence of enteroviral meningoencephalitis following rituximab therapy in 1 child with immune thrombocytopenia and in 1 adult patient with relapsed B cell lymphoma.