Precise measurement of the e+e- --> pi+pi-(gamma) cross section with the initial state radiation method at BABAR.

A precise measurement of the cross section of the process e(+)e(-) --> pi(+)pi(-)(gamma) from threshold to an energy of 3 GeV is obtained with the initial state radiation (ISR) method using 232 fb(-1) of data collected with the BABAR detector at e(+)e(-) center-of-mass energies near 10.6 GeV. The ISR luminosity is determined from a study of the leptonic process e(+)e(-) --> mu(+)mu(-)gamma(gamma). The leading-order hadronic contribution to the muon magnetic anomaly calculated using the pipi cross section measured from threshold to 1.8 GeV is (514.1 +/- 2.2(stat) +/- 3.1(syst)) x 10(-10).

Mitoxantrone in elderly patients with advanced breast cancer: pharmacokinetics, marrow and peripheral hematopoietic progenitor cells.

The aims of this study were to evaluate the pharmacokinetics, tolerability and hematopoietic toxicity of mitoxantrone in elderly women. Thirteen patients with advanced breast cancer, median age of 73 years, received escalating doses of mitoxantrone 8, 10, 12 and 14 mg/m2 on day 1, q 21. There was a linear relationship between the mitoxantrone dose administered and the mitoxantrone exposure (AUC) in plasma (r = 0.856, pc0.001). After 4 courses of treatment, a significant decrease in bone marrow cellularity (p = 0.0067), and HPC content (BFU-E p = 0.0077) was observed. A remarkable, though not statistically significant decrease in circulating HPCs was observed after 4 courses and was still present 8-12 months after the termination of treatment. Therapy with mitoxantrone in elderly women was well tolerated at the dose of 12 mg/m2 for four courses. The significant hematological toxicity observed in marrow cellularity and HPC content warrant further studies.

Mobilization and transplantation of Philadelphia-negative peripheral-blood progenitor cells early in chronic myelogenous leukemia.

PURPOSE: Mobilization of Philadelphia (Ph) chromosome-negative progenitors is now possible in many Ph1-positive chronic myelogenous leukemia (CML) patients who had received interferon alfa (IFN-alpha) with no cytogenetic response. In this pilot study, we used this approach in patients without prior IFN-alpha therapy to determine if the number and quality of mobilized progenitors would be increased and to evaluate the potential effect of these cells as autografts. PATIENTS AND METHODS: Twenty-two untreated patients were mobilized within 12 months of diagnosis. The treatment regimen consisted of the mini-ICE protocol. Beginning on day +8, granulocyte colony-stimulating factor (G-CSF) was used in all patients. Leukophoresis was performed as the patients were recovering from aplasia, when WBC count exceeded 0.8 x 10(9)/L. RESULTS: In 14 patients, (63%) the leukophoresis product was entirely Ph1-negative and in four patients the Ph1-positive cell rate was < or = 7%. Significant numbers of long-term culture-initiating cells (LTC-IC) and CD34+ Thy1+Lin- cells were found in most of the Ph1-negative collections that were tested. Twelve patients underwent autografting with their mobilized peripheral-blood progenitor cells (PBPC) (Ph1-negative collections, 10 patients; major cytogenetic response, two patients). All patients engrafted and are alive; six have Ph1-negative marrow 7 to 15 months after autografting. Posttransplant treatment was IFN-alpha combined with interleukin (IL)-2 because of the recent demonstration of synergistic activity in augmenting cytolytic activity. CONCLUSION: Intensive chemotherapy given in early chronic phase of CML is well tolerated and results in high numbers of circulating Ph1-negative precursor cells.

In vivo mobilization of karyotypically normal peripheral blood progenitor cells in high-risk MDS, secondary or therapy-related acute myelogenous leukaemia.

We have previously reported that mobilization of Philadelphia (Ph) chromosome-negative progenitors is possible in a significant number of Ph1-positive acute lymphoblastic leukaemia (ALL) and chronic myelogenous leukaemia (CML) patients. In this pilot study we employed the same approach for patients with RAEB-t, secondary AML (sAML) and therapy-related AML (t-AML). All patients except one had double or complex cytogenetic abnormalities in marrow cells before mobilization therapy. All patients received an idarubicin-containing regimen (mini-ICE protocol) followed by rh-G-CSF and the first leukapheresis was performed as they were recovering from aplasia. In six out of nine patients the leukapheresis product was entirely karyotypically normal, combined with a significant number of CFU-GM. CD34+ cells and LTC-IC. Recovery time from mobilization therapy was short and no patient died as a result of the procedure. To date, three patients have undergone autografting using their karyotypically normal collections, of which two (sAML) are alive with karyotypically normal marrow a few months after autografting.

Multiple myeloma in the elderly: clinical features and response to treatment in 113 patients.

BACKGROUND: Considering the conflicting results of the few reports on geriatric MM patients and the increasing relevance of the problem, we analyzed a series of 113 patients over 64 years of age treated with conventional chemotherapy. PATIENTS AND METHODS: The median age was 71 (range 65-92). Stage IA, IIA, IIIA and IIIB patients numbered 28, 33, 45 and 7, respectively. The M component was IgG in 73 patients (65%), IgA in 30 (26%), IgD in 3 (3%), light chain in 5 (4%); no monoclonal component was detected in 2 (2%) cases. Sixty-three patients showed symptomatic skeletal disease. Melphalan/prednisone (MP) was the first-line treatment in 84 patients (74%). Patients were grouped according to age (> 64 < or = 74; > or = 75) in order to carry out analysis. RESULTS: Seventy-eight cases (69%) showed a sizable reduction in the tumor mass; objective and partial response was achieved in 57 (50%) and 21 (19%) patients, respectively. Patients with stage I-II disease fared significantly better than stage III patients (median survival: 70 vs 38 months; p = 0.017). Response to first-line treatment correlated with overall survival; patients with responsive or refractory disease had median survival rates of 64 and 20 months, respectively (p = 0.0001). CONCLUSIONS: Neither patients above nor below 75 years of age showed any difference in presentation features or in response to treatment. These results suggest that advanced age should not be considered a major obstacle to active treatment.

Twelve years experience with high-dose therapy and autologous stem cell transplantation for high-risk Hodgkin's disease patients in first remission after MOPP/ABVD chemotherapy.

High-dose therapy followed by autografting can cure patients with aggressive Hodgkin's disease (HD) refractory or with early relapse to first-line combination chemotherapy. On the other hand, the eradication of the disease is rarely achieved in heavily pretreated patients. It has been suggested that patients with HD with very high risk characteristics at diagnosis, often relapse despite appropriate therapy with 7-8 drugs combination. Thus it seems to us that such patients are potential candidates for early autografting during first remission. Twelve years ago, we initiated a pilot study to investigate whether patients with very high risk characteristics, would benefit from early autografting. The application of early autografting was compared with our historical group of patients in complete remission after receiving MOPP/ABVD, who had the same negative prognostic characteristics, refused autografting and who did not receive other treatment after achieving complete remission. Among the 22 consecutive patients entered into the pilot study and autografted, 18 are alive and 17 (77%) remain alive in unmaintained remission at a median of 86 months. One patient (4%) died of interstitial pneumonitis in the transplantation group. Only 8/24 (33%) patients, who did not receive an autograft, are currently alive and disease free at a median of 89 months. In conclusion, the early application of autografting appears to improve the outcome in patients with very high risk HD who achieved remission with MOPP/ABVD.

High-dose chemo-radiotherapy followed by autologous Philadelphia chromosome-negative blood progenitor cell transplantation in patients with chronic myelogenous leukemia.

Twenty-three patients with chronic myelogenous leukemia in early chronic phase (ECP) and not previously treated with alpha-interferon (IFN-alpha) (10 patients), in ECP but pretreated with IFN-alpha (<12 months) (seven patients) and in late chronic phase (LCP) pretreated with IFN-alpha (>12 months) (six patients) underwent autografting with Philadelphia (Ph) chromosome-negative blood progenitor cells (BPCs) (20 patients), or partially/totally Ph-positive BPCs (three patients), previously mobilized during the early phase of recovery after aplasia induced by intensive chemotherapy. The conditioning regimen consisted of high-dose chemotherapy alone or followed by total body irradiation (TBI). Recombinant G-CSF was given after BPCs infusion on day +8. All patients in ECP not pretreated with IFN-alpha are alive and five of them are Ph-negative in the marrow after autografting. Six of seven patients autografted with Ph-negative BPCs in the group of ECP pretreated with IFN-alpha (<12 months) are alive and two of them are still Ph-negative in the marrow. In the same group, the only patient transplanted with partially Ph-positive BPCs, died of blastic transformation 2 months after reinfusion. Three patients (two patients autografted with Ph-negative BPCs and one patient with Ph-positive BPC) in the group of LCP pretreated with IFN-alpha >12 months are alive but Ph-positive after autografting. The other three patients of the same group died of procedure-related toxicity (two patients) and blastic transformation (one patient). Seventeen patients (10/10 ECP not pretreated with IFN-alpha; 5/7 ECP pretreated with IFN-alpha and 2/6 LCP pretreated with IFN-alpha) of 23 autografted patients were treated with IFN-alpha +/- IL-2. Toxicities after autografting were mostly related to myelosuppression, particularly thrombocytopenia. All patients of the two groups pretreated with IFN-alpha developed febrile episodes during the aplastic phase following BPCs reinfusion. No patient autografted in ECP and those not pretreated with IFN-alpha developed febrile episodes. This is also probably due to the use of i.v. antibiotic and antimicotic prophylaxis when neutrophils were < or = 1 x 10(9)/l after autografting. Greater toxicity was observed in patients pretreated with IFN-alpha, being lethal in two cases in LCF. In conclusion, the "in vivo' manipulation approach employed in our institution is a safe procedure and it results in a high collection of Ph-negative cells in the blood if the cells are harvested: (1) in early chronic phase; (2) in early phase of recovery after chemotherapy-inducing aplasia; (3) in patients not extensively pretreated with IFN-alpha. The data presented here have shown encouraging trends in chronic phase of CML and offer new perspective for patients without an HLA-identical donor or for patients who do not respond to IFN-alpha.

[Autotransfusion in elective surgery. Preliminary report on 215 cases]. / L'autoemotrasfusione in chirurgia elettiva. Rapporto preliminare su 215 casi.

Two-hundred and fifteen number of patients are presented, who underwent surgical procedures with the support of autologous blood transfusions. The latter have many advantages over traditional allogenic transfusions, such as diminished risk of infections, absence of blood compatibility problems and deep venous thrombosis prophylaxis, through a preoperative controlled state of hemodilution. We have opted for a pre-operative technique, with harvest of blood, obtained before surgery, at quantity of 350 ml each 4 to 5 days. No early, nor late complications occurred, nor any postoperative hemoglobin or hematocrit decrease. The above data, together with a relevant reduction of cost per blood unit, to encourage a wide use of autologous blood transfusion, whenever feasible.

[Effect of pulmonary reventilation on gas exchange after cryolytic removal of obstruction in endobronchial tumors]. / Effetti sullo scambio gassoso della reventilazione polmonare dopo disostruzione criolitica nei tumori endobronchiali.

Blood gas analysis was used to assess the value of cryolytic endobronchial disobstruction in functional recovery of the reventilated lung parenchyma, with particular reference to the real improvement brought about in blood gas equilibrium by reventilation. Blood gas analysis was carried out in 5 cases of malignant tracheobronchial neoplasia (3 with atelectasis or subatelectasis) before and after disobstruction. Improved gas exchange, primarily in the form of better blood oxygen values, was noted in all cases, with a mean improvement of 28% in 3 cases and 7% in 2. It should be noted, however, that there was no correspondence between the results and the presence or otherwise of radiological evidence of atelectasis prior to the treatment.

[Initial observations on the use of levamisole in the immunostimulation treatment of patients operated on for lung cancer]. / Prime osservazioni sull impiego del Ievamisolo nel trattamento immunostimolante dei pazienti operati di resezione per carcinoma polmonare.

The results obtained with levamisole in the immunostimulating of 59 resected and non-resected lung carcinoma patients are presented. The effectiveness of the treatment was assessed in terms of survival, length of the free interval, etc. Cutireaction to the drug was repeatedly monitored. It is felt that the overall results were insufficient evidence of the true effectiveness of this manner of treatment, even though some data indicative of the therapeutic action of the drug were obtained.