Single-dose palonosetron for prevention of chemotherapy-induced nausea and vomiting in patients with aggressive non-Hodgkin's lymphoma receiving moderately emetogenic chemotherapy containing steroids: results of a phase II study from the Gruppo Italiano per lo Studio dei Linfomi (GISL)

PURPOSE: The control of nausea and vomiting induced by chemotherapy is paramount for overall treatment success in cancer patients. Antiemetic therapy during chemotherapy in lymphoma patients generally consists of anti-serotoninergic drugs and dexamethasone. The aim of this trial was to evaluate the efficacy of a single dose of palonosetron, a second-generation serotonin type 3 (5-HT(3)) receptor antagonist, in patients with aggressive non-Hodgkin's lymphoma receiving moderately emetogenic chemotherapy (MEC) containing steroids. METHODS: Patients received a single intravenous bolus of palonosetron (0.25 mg) before administration of chemotherapy. Complete response (CR) defined as no vomiting and no rescue therapy during overall phase (0-120 h) was the primary endpoint. Complete control (CC) defined as CR and only mild nausea was a secondary endpoint. RESULTS: Eighty-six evaluable patients entered in the study. A CR was observed in 74 patients (86.0%) during the overall phase; the CR during the acute (0-24 h) and delayed (24-120 h) phases was 90.7% and 88.4%, respectively. CC was 89.5% during the acute and 84.9% during the delayed phase; the overall CC was 82.6%. CONCLUSIONS: This was the first trial, which demonstrated the efficacy of a single dose of palonosetron in control CINV in patients with aggressive non-Hodgkin's lymphoma receiving MEC regimen containing steroids

Results of a Multicenter, Controlled, Randomized Clinical Trial Evaluating the Combination of Piperacillin/Tazobactam and Tigecycline in High-Risk Hematologic Patients With Cancer With Febrile Neutropenia.

PURPOSE: Empiric antibiotic monotherapy is considered the standard of treatment for febrile neutropenic patients with cancer, but this approach may be inadequate because of the increasing prevalence of infections caused by multidrug resistant (MDR) bacteria. PATIENTS AND METHODS: In this multicenter, open-label, randomized, superiority trial, adult, febrile, high-risk neutropenic patients (FhrNPs) with hematologic malignancies were randomly assigned to receive piperacillin/tazobactam (4.5 g intravenously every 8 hours) with or without tigecycline (50 mg intravenously every 12 hours; loading dose 100 mg). The primary end point was resolution of febrile episode without modifications of the initial allocated treatment. RESULTS: Three hundred ninety FhrNPs were enrolled (combination/monotherapy, 187/203) and were included in the intention-to-treat analysis (ITTA). The ITTA revealed a successful outcome in 67.9% v 44.3% of patients who had received combination therapy and monotherapy, respectively (127/187 v 90/203; absolute difference in risk (adr), 23.6%; 95% CI, 14% to 33%; P < .001). The combination regimen proved better than monotherapy in bacteremias (adr, 32.8%; 95% CI, 19% to 46%; P < .001) and in clinically documented infections (adr, 36%; 95% CI, 9% to 64%; P < .01). Mortality and number of adverse effects were limited and similar in the two groups. CONCLUSION: The combination of piperacillin/tazobactam and tigecycline is safe, well tolerated, and more effective than piperacillin/tazobactam alone in febrile, high-risk, neutropenic hematologic patients with cancer. In epidemiologic settings characterized by a high prevalence of infections because of MDR microorganisms, this combination could be considered as one of the first-line empiric antibiotic therapies

INCLUSION OF TOTAL BODY CT SCAN IN THE INITIAL WORK-UP OF CLL PATIENTS WITH EARLY-STAGE ON CLINICAL GROUNDS: PRELIMINARY RESULTS OF A PROSPECTIVE, MULTICENTER O-CLL1-GISL STUDY

Background. The clinical staging systems proposed by Rai and Binet represent the backbone for assessing prognosis in patients with Chronic Lymphocytic Leukemia (CLL). However, staging systems are not devoid of some limitations, among the most significant of which is the lack of recognition of early-stage patients who will progress. Unlike the guidelines for assessing the response to therapy for most other types of non-Hodgkin’s lymphomas, the widely-used NCI-WG guidelines for patients with CLL do not incorporate use of computed tomography (CT) scans in the algorithm. However, two recent retrospective study challenged this notion. highlighting the importance of prospective validation of CT scans before routine inclusion in CLL work up. Aims. In the present study, we investigated whether total body CT scan allowed to individuate among Binet stage A CLL patients, included in the prospective multicenter O-CLL01 GISL study, cases in more advanced stage and whether this subgroup showed a different expression of clinical and biological prognostic markers. Patients. Up to date, 275 patients have been enrolled in the trial started in April 2007 and total body CT scan were available in 87 patients. Fifty-two patients (60%) were male and the median age was 61 years (range, 33 to 71 years). All patients are in Binet stage A, while 83 patients were at low risk (0-I stages) and 4 at intermediate risk (II stage) by Rai classification. LDH was elevated in 11.5% of cases and B2-microglobulin in 24%. Twenty-eight patients (33%) were IgVH unmutated, 31 patients (36%) had a high ZAP-70 expression, 17 patients (20%) were CD38 positive (>30%). Fluorescence in situ hybridization (FISH) data are available in 61/87 cases; the most frequent abnormality was del(13)(q14) (29 pts 33%), followed by trisomy 12 (5 pts, 6%), del(17p13) (4 pts 5%) and del(11q22.3) (2 pts 2%), 21 cases (24%) were normal. Cytogenetic abnormalities were clustered in 3 risk groups [i.e. low (del(13q14) and normal), intermediate (trisomy 12) and high risk (del(11q22) and del(17p13)] as suggested by others. Results. Considering total body CT scan, 22 out of 83 analyzed (25%) patients were converted into Binet stage B. Notably, 64% were male, LDH was elevated in 18% of cases and B2-microglobulin in 18%, 41% were IgVH unmutated, 27% had a high ZAP-70 expression, 27% were CD38 positive, 4,5% showed a high-risk FISH. Both main clinical characteristics and biological prognostic markers failed to correlate with a more advanced stage. In fact, no statistically different distribution of gender, age, LDH and b2-microglobulin, such as IgVH mutational status, CD38 and ZAP-70 expression and cytogenetic abnormalities were observed between Binet A cases and Binet B. According the Rai classification 14/83 (17%) low risk patients became at intermediate risk with the integration of total body CT scan. Also this subset of patients did not show a statistically different expression of all prognostic markers, but a higher rate of cases with elevated B2-microglobulin (p=0.003), than patients at low risk. Finally, total body CT scan allowed to early individuate a second neoplasia in 2 cases (lung cancer 1 pt, renal cell carcinoma 1 pt). Conclusions. In line with literature information, our preliminary data indicate that the integration of total body CT scans in the clinical staging allowed to individuate among Binet A CLL cases on clinical grounds 25% of cases with a more advanced stage. Although a more advanced stage did not correlate with both clinical and biological variables reflecting bad prognosis. A longer follow-up will allow to demonstrate whether the inclusion of total body CT scan in the initial work-up of patients with early-stage on clinical grounds provide relevant prognostic information

Results of a multicenter, controlled, randomized clinical trial evaluating the combination of piperacillin/tazobactam and tigecycline in high-risk hematologic patients with cancer with febrile neutropenia.

Empiric antibiotic monotherapy is considered the standard of treatment for febrile neutropenic patients with cancer, but this approach may be inadequate because of the increasing prevalence of infections caused by multidrug resistant (MDR) bacteria. In this multicenter, open-label, randomized, superiority trial, adult, febrile, high-risk neutropenic patients (FhrNPs) with hematologic malignancies were randomly assigned to receive piperacillin/tazobactam (4.5 g intravenously every 8 hours) with or without tigecycline (50 mg intravenously every 12 hours; loading dose 100 mg). The primary end point was resolution of febrile episode without modifications of the initial allocated treatment. Three hundred ninety FhrNPs were enrolled (combination/monotherapy, 187/203) and were included in the intention-to-treat analysis (ITTA). The ITTA revealed a successful outcome in 67.9% v 44.3% of patients who had received combination therapy and monotherapy, respectively (127/187 v 90/203; absolute difference in risk (adr), 23.6%; 95% CI, 14% to 33%; P < .001). The combination regimen proved better than monotherapy in bacteremias (adr, 32.8%; 95% CI, 19% to 46%; P < .001) and in clinically documented infections (adr, 36%; 95% CI, 9% to 64%; P < .01). Mortality and number of adverse effects were limited and similar in the two groups. The combination of piperacillin/tazobactam and tigecycline is safe, well tolerated, and more effective than piperacillin/tazobactam alone in febrile, high-risk, neutropenic hematologic patients with cancer. In epidemiologic settings characterized by a high prevalence of infections because of MDR microorganisms, this combination could be considered as one of the first-line empiric antibiotic therapies

Hairy cell leukemias with unmutated IGHV genes define the minor subset refractory to single-agent cladribine and with more aggressive behavior.

Hairy cell leukemia (HCL) is generally responsive to single-agent cladribine, and only a minority of patients are refractory and with poor prognosis. HCLs generally express mutated (M) and, in a minority, unmutated (UM) IGHV. In a multicenter clinical trial in newly diagnosed HCL, we prospectively investigated clinical and molecular parameters predicting response and event-free survival after single-agent cladribine. Of 58 HCLs, 6 expressed UM-IGHV (UM-HCL) and 52 M-IGHV (M-HCL). Beneficial responses were obtained in 53 of 58 patients (91%), whereas treatment failures were observed in 5 of 58 patients (9%). Failures were associated significantly with UM-IGHV (5 of 5 failures vs 1 of 53 beneficial responses had UM-IGHV, P < .001), leukocytosis (3 of 5 vs 3 of 53, P = .006), and bulky spleen (4 of 5 vs 4 of 53, P < .001). The UM-HCL not benefiting from cladribine characteristically had bulky spleen (4 of 5, 80%), leukocytosis (3 of 5, 60%), and TP53 defects (2 of 5, 40%), and progressed rapidly after first treatment (median event-free survival, 7.5 months). Our data suggest that UM-HCLs identify the minor subgroup failing cladribine treatment and with more aggressive disease. High incidence of TP53 dysfunction indicates a potential mechanism of resistance to cladribine in the UM-HCL group. Overall, our data provide new molecular elements relevant for treatment concerns in HCL