Effect of high dose cytosine arabinoside on quantitative EEG in patients with acute myeloid leukemia.

Background EEG activity is considered an index of functional state of brain. Chemotherapy (CT), used for non-central nervous system (CNS) cancer, can cross the blood brain barrier and contribute to changes in the functional state of brain that can alter background EEG activity. Quantitative EEG (qEEG) is superior to conventional EEG in the detection of subtle alterations of EEG background activity and for this reason, the use of qEEG might assist the clinician in evaluating the possible effect of CT on the CNS. The nucleoside analog cytosine arabinoside (Ara-C) is one of the milestone chemotherapeutic agents used for treatment of acute myeloid leukemia (AML). Our observational study evaluates the possible effect of Ara-C on the qEEG of patients with AML, without CNS involvement. We conducted an observational study on newly diagnosed AML patients without CNS involvement, undergoing treatment with Ara-C to analyze the possible effect of Ara-C high doses on EEG background activity using qEEG analyses. A total of nine AML patients, 5 with Ara-C i.v. high dose (≥3 g/m(2) die), 4 with standard dose (100 mg/m(2) die) underwent qEEG (at rest, during hyperpnoea, mental arithmetic task and blocking reaction). We compared the EEG background activity of the two groups at baseline and after 6 months. Statistical analysis showed no significant differences between the two groups in mean relative power for all frequency bands, at rest and during hyperpnoea, mental arithmetic task and blocking reaction. Our data indicate that high dose Ara-C i.v. did not induce significant changes on EEG background activity in our patients. Future research in this area could include prospective studies that would combine qEEG and neuropsychological testing to assess the impact of CT on brain functions.

Long term efficacy and safety of Fludarabine, Cyclophosphamide and Rituximab regimen followed by (90)Y-ibritumomab tiuxetan consolidation for the treatment of relapsed grades 1 and 2 follicular lymphoma.

BACKGROUND: In this retrospective study, we investigated the efficacy and safety of radioimmunotherapy with (90)Yttrium- ibritumomab tiuxetan ((90)Y-RIT) in 9 patients with recurrent follicular lymphoma (FL) who were treated in a consolidation setting after having achieved complete (CR) or partial remission (PR) with Fludarabine, Cyclophosphamide and Rituximab (FCR). METHODS: The median age was 63 years (range 46-77). All patients were relapsed with histologically confirmed CD20-positive (grade 1 or 2) FL, at relapse they received FCR every 28 days: F (25 mg/m(2)x 3 days), C (1 gr/m(2) day 1) and R (375 mg/m(2) day 4) for 4 cycles. Those who achieved at least a PR with <25 % bone marrow involvement were treated with (90)Y-RIT 11.1 or 14.8 MBq/Kg, at 3 months after completing FCR. Patients underwent a further restaging at 12 weeks after (90)Y-RIT with a total body CT scan, FDG-PET/CT and bilateral bone marrow biopsy. RESULTS: Nine patients completed the treatment: FCR followed by (90)Y-RIT (6 patients at 14.8 MBq/Kg, 3 patients at 11.1 MBq/Kg). After FCR, 7 patients obtained CR and 2 PR; after (90)Y-RIT 2 patients in PR converted to CR 12 weeks later. With a median follow up of 95 months (range 20-114) since FCR and 88 months (range 13-104) since (90)Y-RIT 3 deaths were not related to lymphoma; all 3 deceased patients obtained CR before (90)Y-RIT and died still in CR. The median overall (OS) and progression free survival (PFS) have not been reached, in this analysis both OS or PFS are 67 % at 7.5 year. The most common grade 3 or 4 adverse events were hematologic. CONCLUSIONS: These results confirm the long term efficacy and safety of 4 cycles of FCR followed by (90)Y-RIT in relapsed grades 1 and 2 FL and suggest that this regimen could be a therapeutic option for this setting of patients, specially at age of 60-75 with no unexpected toxicities.

Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma.

In a randomized, phase 3 study, superior complete/near-complete response (CR/nCR) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone (VTD) versus thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double autologous stem cell transplantation for newly diagnosed myeloma patients (intention-to-treat analysis; VTD, n = 236; TD, n = 238). This per-protocol analysis (VTD, n = 160; TD, n = 161) specifically assessed the efficacy and safety of consolidation with VTD or TD. Before starting consolidation, CR/nCR rates were not significantly different in the VTD (63.1%) and TD arms (54.7%). After consolidation, CR (60.6% vs 46.6%) and CR/nCR (73.1% vs 60.9%) rates were significantly higher for VTD-treated versus TD-treated patients. VTD consolidation significantly increased CR and CR/nCR rates, but TD did not (McNemar test). With a median follow-up of 30.4 months from start of consolidation, 3-year progression-free survival was significantly longer for the VTD group (60% vs 48% for TD). Grade 2 or 3 peripheral neuropathy (8.1% vs 2.4%) was more frequent with VTD (grade 3, 0.6%) versus TD consolidation. The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation. VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients randomly assigned to the VTD arm of the study. The study is registered at www.clinicaltrials.gov as #NCT01134484.

The potential role of pre-transplant HBcIgG seroposivity as predictor of clinically relevant cytomegalovirus infection in patients with lymphoma undergoing autologous hematopoietic stem cell transplantation: a study from the Rome Transplant Network.

Despite the increased use of intensive immunosuppressive chemo-immunotherapies in patients with lymphoma observed in the last decade, current data on cytomegalovirus (CMV) infection following autologous stem cell transplantation (Auto-SCT) are very limited. To address this peculiar aspect, a retrospective study on a cohort of 128 adult patients consecutively transplanted for lymphoma in three Hematology Institutions was performed with the aim to determine the incidence of and the risk factors for CMV symptomatic infection and/or end-organ disease. Sixteen patients (12.5%) required specific antiviral therapy and 4/16 died (25%); transplant-related mortality (TRM) was significantly influenced by CMV infection (P = 0.005). In univariate analysis, a pre-transplant HBcIgG seropositivity, HBV infection according to clinical-virological definitions, a pre-transplant Rituximab treatment, a diagnosis of B-cell non-Hodgkin lymphoma, and age at transplant were significantly associated with the risk of developing a clinically relevant CMV infection. In multivariate analysis, only a pre-transplant HBcIgG seropositivity (P = 0.008) proved to be an independent predictor of a clinically relevant CMV infection. These results suggest that a pre-transplant HBcIgG seropositivity could be considered as an independent predictor factor of clinically relevant CMV infection after Auto-SCT.

Standard- versus high-dose lenograstim in adults with hematologic malignancies for peripheral blood progenitor cell mobilization.

BACKGROUND: The aim of this retrospective, multicenter study was to compare high- versus standard-dose lenograstim after chemotherapy in collecting target dose of CD34+ peripheral blood progenitor cells (PBPCs) in adult candidates for autologous transplant. STUDY DESIGN AND METHODS: A total of 166 consecutive patients (28 acute leukemias [ALs], 77 lymphomas, 61 multiple myeloma [MM]) underwent 182 mobilization procedures. Only the first were analyzed. The CD34+ cell target was at least 2×10(6) , 4×10(6) , and 8×10(6) /kg and lenograstim started on days +19, +1, and +5 from the end of chemotherapy for AL, lymphomas, and MM, respectively. Eighty-seven and 79 patients, respectively, received 5 and 10µg/kg/day lenograstim subcutaneously (sc). An analysis to evaluate factors predicting satisfactory procedures and outcome of transplants performed with first-mobilization-procedure PBPCs was conducted. Most patients received 6mg of pegfilgrastim or 5µg/kg/day lenograstim sc after transplant. RESULTS: In multivariate analysis, high-dose lenograstim (p=0.053) in MM and male sex (p=0.028) were positive predictive factors for reaching cell target. Fludarabine negatively influenced stimulation length (p=0.002). Apheresis, CD34+ cells mobilized and collected, blood volume processed, side effects, transplants performed, and engraftment time were similar between lenograstim cohorts. Pegfilgrastim versus lenograstim delayed platelet (PLT) recovery times (13 days vs. 11 days, p=0.036). CONCLUSIONS: High-dose lenograstim more efficiently mobilized MM patients requiring the highest PBPC target but did not influence transplants performed and engraftment time. Male patients mobilized more efficiently. Fludarabine negatively influenced stimulation length. Finally, pegfilgrastim seems to delay PLT recovery.