Michele Nobile

Pamidronate Reduces Skeletal Events but does not Improve Progression-free Survival in Early-stage Untreated Myeloma: Results of a Randomized Trial

Abstract Ninety patients with untreated, stage I-II A myeloma, were randomised to receive or not monthly infusions of pamidronate (PMD) for 1 year, without additional therapies. Follow-up ranged from 36 to 72 months (median 51 months). Three years after the start of the treatment, the disease had progressed in 25% of PMD treated patients and in 26.8% of controls (p n.s). Median time-to-progression was 16 and 17.4 months, respectively (p n.s). Among the 21 patients who required chemo-radiotherapy, skeletal events (osteolytic lesions, pathological fractures and/or hypercalcemia) developed in 9/11 (81.8%) controls and in 4/10 (40%) of treated patients (p < 0.01). “Prophylactic” administration of PMD may decrease the development of skeletal events, but does not reduce the rate and the time of disease progression in early-stage myeloma.

Heterogeneity of response to imatinib-mesylate (glivec) in patients with hypereosinophilic syndrome: implications for dosing and pathogenesis.

Four cases of hypereosinophilic syndrome (HES) treated with the tyrosine-kinase inhibitor imatinib-mesylate are reported. The drug was effective in three patients, but a prolonged clinical and hematological remission was obtained only in one patient, due to appearance of resistance or poor tolerability in the other cases. The dose of imatinib necessary to achieve a response ranged from 100 to 600 mg/d. One patient with evidence of a clonal T-cell population did not respond at all. We confirm the efficacy of imatinib in HES, but we also underline that type and duration of response may be variable. This could be due to different pathogenetic mechanisms of the disease in single patients.

Rituximab for allo-SCT-associated thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) may rarely complicate Allo-SCT.1, 2 First-line therapy of TTP is plasma exchange.3 However, other therapeutic approaches, such as steroids, i.v. high-dose Ig and vincristine, are still used. Despite anecdotally, recently, the anti-CD20 monoclonal antibody rituximab has been reported to successfully cure SCT-associated thrombotic microangiopathy.4, 5, 6, 7

Non-pegylated liposomal doxorubicin (Myocet®) in patients with poor-risk aggressive B-cell non-Hodgkin lymphoma

The incidence of non-Hodgkin lymphomas increases with age. Non-pegylated liposomal formulations of doxorubicin (Myocet®) reduce systemic and cardiac toxicity especially in the elderly, who often have cardiac diseases. We treated 80 patients (mean age 70.9 years) with poor-risk diffuse large B-cell lymphoma with the R-COMP 21 regimen (Myocet® 50 mg/m2, cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2, rituximab 375 mg/m2, prednisone 100 mg/day). In all, 82.5% and 13.7% patients showed complete and partial responses, respectively. Sixty-two of the 80 patients are alive and disease-free (77.5%), while 3/80 are alive with active disease and 15 patients (18.7%) have died (median follow-up: 31 months). The estimated probability of overall survival at 12/24 months from admission was 93.5/87.3%, respectively. There were no therapy-related cardiac events and the ejection fraction improved (from 51.6 ± 6.9% to 54.2 ± 3.9%). Grade 3–4 neutropenia occurred in 22% of patients. We concluded that Myocet® shows both efficacy and tolerability, mainly at the cardiac level.

Combination treatment of flag with non-pegylated liposomal doxorubicin (MYOCET(TM)) in elderly patients with acute myeloid leukemia: a single center experience.

The incidence of acute myeloid leukemia (AML) increases with age, but results of intensive chemotherapy in elderly patients are disappointing. Non-pegylated liposomal formulations of doxorubicin (Myocet™) have been developed with the aim of reducing systemic and cardiac toxicity especially in the elderly. We evaluated the efficacy and toxicity profiles of fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG) regimen given in association with Myocet™ in 35 patients with AML, median age 69 years (range 61–83 years). Nineteen (54.3%) had newly-diagnosed AML, twelve (34.3%) patients had secondary AML (ten with Myelodisplastic Syndrome, two with Primary Myelofibrosis) and 4 (11.4%) patients had had a late relapse (> 12 months) of AML. Complete remission (CR) and partial remission (PR) were obtained in twenty-two (63%) and 3 (8.5%) patients, respectively. Seven (20%) patients showed a resistant disease. There were 3 early deaths (8.5%). Six patients (17%) experienced severe cardiovascular toxicity. The median overall survival (OS) was 12 months (range 1–52 months) with a median disease-free survival (DFS) of 20 months (range 1–48 months). One-year and two-year DFS were 78.9% and 26.7%, respectively. This study demonstrates that in elderly patients with AML, FLAG-Myocet™ combination shows promising efficacy response with acceptable toxicity, enabling most patients to receive further treatments, including transplantation procedures.