Ceftriaxone/Amikacin vs Ceftazidime/Amikacin as Empirical Therapy for Fever in Patients with Haematological Malignancy and Severe Granulocytopenia: Clinical and Economic Outcomes.

To assess the economic outcomes produced when a conventional antibiotic treatment regimen requiring three administrations per day was replaced with a treatment regimen requiring only one daily administration, the efficacy, tolerability and cost of ceftazidime was compared with that of ceftriaxone (both drugs in combination with amikacin) for the empirical treatment of febrile granulocytopenic patients with haematological malignancy. 102 febrile patient-episodes were randomly assigned to receive ceftazidime (6g in three divided doses) or ceftriaxone (2g as a single daily dose), both in combination with amikacin. The response was evaluable in 94 patients (47 in each group). 75 (80%) patients had an absolute granulocyte count lower than 100/mm(3) at the onset of fever or during the first week of antibiotic therapy. 61 (64.9%) were affected by acute leukaemia. Multiple daily ceftazidime plus amikacin was effective in 33 of 47 (70.2%) patients, and single daily ceftriaxone plus amikacin in 31 of 47 (66%) patients (p > 0.2). Among patients successfully treated, median time to defervescence was 3.3 days (range 1 to 11) for ceftazidime plus amikacin and 4.5 days for ceftriaxone plus amikacin (range 1 to 15) [p = 0.14]; study drugs were continued for 12 (range 7 to 26) and 12.3 days (range 7 to 28), respectively. Our study demonstrated that single daily administration of ceftriaxone was as effective and well tolerated as multiple daily administration of ceftazidime when both were administered in combination with amikacin. Cost analysis showed that compared with the thrice daily regimen, administration of single daily doses of ceftriaxone for a 12-day treatment period would result in a net cost saving of $US392 (626 940 Italian lire).

Thrombotic complications in acute promyelocytic leukemia during all-trans-retinoic acid therapy.

A case of acute renal failure, due to occlusion of renal vessels in a patient with acute promyelocytic leukemia (APL) treated with all-trans-retinoic acid (ATRA) and tranexamic acid has been described recently. We report a case of acute renal failure in an APL patient treated with ATRA alone. This case further supports the concern about thromboembolic complications associated with ATRA therapy in APL patients. The patients, a 43-year-old man, presented all the signs and symptoms of APL and was included in a treatment protocol with ATRA. After 10 days of treatment, he developed acute renal failure that was completely reversible after complete remission of APL was achieved and therapy discontinued. We conclude that ATRA is a valid therapeutic choice for patients with APL, although the procoagulant tendency is not completely corrected. Thrombotic events, however, could be avoided by using low-dose heparin.

Alpha interferon as initial treatment of essential thrombocythemia. Analysis after two years of follow-up.

AIMS AND BACKGROUND: Recombinant alpha-interferon has been shown to be effective in essential thrombocythemia and in thrombocytosis associated with other myeloproliferative disorders. PATIENTS AND METHODS: Twenty-five untreated patients were enrolled in our study from May 1989 to April 1992. Recombinant alpha interferon-2b was administered at an initial dose of 2 megaunits (MU)/m2 three times a week at escalating doses to 5 MU/m2 or the maximum tolerated dose. The mean follow-up for patients still in treatment at the time of this report was 35.9 months (range, 24-63). RESULTS: Fourteen patients (56%) had achieved a complete remission by a mean time of 152 days; 6 patients (24%) had achieved a good partial remission by a mean of 180 days. In addition to the favorable effect on platelet count, a marked improvement in clinical symptoms was observed. Treatment had to be discontinued in 9 patients (36%), 5 for toxicity (3 neurologic, 1 anemia and 1 severe hypertriglyceridemia) at a median of 155 days from the beginning of therapy (range, 30-400). Four patients refused to continue therapy because of low tolerance (flu-like syndrome) at mean of 160 days from the beginning of therapy (range, 34-301). CONCLUSIONS: In our study, lower doses were administered compared with previous short-time trials. The present data show that interferon is an effective alternative to cytostatic agents in long-term treatment of patients with essential thrombocythemia, even when used at lower dosages.

Amikacin and ceftazidime as empirical antibiotic therapy in severely neutropenic patients: analysis of prognostic factors.

This study aimed to evaluate the efficacy of amikacine and ceftazidime as an empirical antibiotic therapy for neutropenic patients affected by haematological neoplasms and to investigate the presence of prognostic features suggesting a poor outcome with this antibiotic combination at the onset of infection. This could allow the identification of subgroups of patients with a low rate of response to amikacin/ceftazidime therapy; in these patients different initial empirical therapy may be indicated. The study population comprised 166 severely neutropenic (absolute neutrophil count below 500/microliters) oncohaematological patients with fever or clinical signs of infection. Multivariate analysis confirmed four negative prognostic factors: 3 or more days of hospitalization at the onset of an infectious episode, a diagnosis of acute myelmany factors are present, cases can be stratified into three groups, of significantly different prognosis: favourable (0 or 1 factor) 76% success; intermediate (2 factors) 52% success; unfavourable (3 or 4 factors) 19% success. At the onset of an infectious episode a subgroup of patients with a very low response rate to empirical amikacin/ceftazidime antibiotic therapy is identifiable, for whom a different therapy is indicated. Because of the high rate of proven or probable fungal infections in this group, the immediate administration of a systemic antifungal therapy, in addition to antibacterial agents, could be considered in these high-risk patients. Studies should be specifically addressed to evaluating a stratification of empirical antibiotic therapy according to risk factors present at the onset of infection.

[Multiple myeloma. Role of prognostic factors and staging in a therapeutic program]. / Il mieloma multiplo. Ruolo dei fattori prognostici e della stadiazione in un programma terapeutico.

Patients affected with multiple myeloma constitute an heterogeneous population with very different clinical patterns, varying from asymptomatic to very compromised patients with severe and uncontrolled disease. Most common clinical and biological staging systems have been in use for many years. Recently new prognostic factors have been identified; among them, serum levels of beta-2 microglobulin, C-reactive protein and interleukin-6 employed with already known parameters have been useful in the new staging system, permitting a more focalized therapy. As today is not yet possible to define the best treatment schedule, as the most common treatments are incapable to eradicate myeloma neoplastic clone even in responsive patients. Nevertheless extensive use of biologic response modifiers in the last years, as alpha interferon, have added new powerful and hopeful therapeutic tools even if the results need to be confirmed in future trials. It is important to remind the primary role of bone marrow transplantation associated with high dose polychemotherapy even if just a minority of patients is eligible for this therapeutic chance.

Lymphocyte subsets in patients with idiopathic thrombocytopenic purpura during high-dose gamma globulin therapy.

Peripheral lymphocyte subsets (OKT3+, OKT4+, OKT8+) were studied by monoclonal antibodies in 10 patients with chronic idiopathic thrombocytopenic purpura (ITP), before and after high-dose intravenous gamma globulin therapy at a daily dose of 0.4 g/kg/body weight for 5 consecutive days followed by several boosters every 10-15 days. A stable increase of platelet count was obtained in 5 patients, whereas the other 5 showed a transient improvement of platelet count but then became refractory to the treatment. Phenotypic analysis of T cell subsets showed a decrease of the OKT4+/OKT8+ ratio following therapy, with non change in the percentage of OKT3+ cells. A significant decrease of lymphocyte count and platelet associated IgG was shown in 80% of our patients. These data suggest the possible long term efficacy of repeated iv IgG inchronic ITP patients through a mechanism of specific enhancement of suppressor T cell function.

Surgery and chemotherapy in the treatment of gastric non-Hodgkin's lymphoma.

We have retrospectively examined 35 cases of non-Hodgkin's lymphoma (NHL) with gastric involvement at the onset. All patients have completed induction therapy at the time of this report. Histologic specimens have been classified according to the Working Formulation. Patients have undergone surgery and/or chemotherapy. Twenty out of 22 patients with stage I or II disease had surgery. Seventeen out of 20 gastrectomized patients achieved complete remission (11 with stage I and 6 with stage II): Fifteen of these are in their first complete remission with median follow-up of 24 months (range 8-68). Three patients with stage IV had surgery, two of which achieved CR. These data confirm that combined therapy is useful in gastric NHL presenting with stage I and II; no conclusions can be drawn regarding disseminated disease.

[Non-Hodgkin's lymphomas: staging and therapy]. / I linfomi non-Hodgkin: stadiazione e terapia.

Some problems of non-Hodgkin's lymphomas are examined, with special consideration for those related to treatment. Some questions of staging are also considered, together with some particular presentations, such as bulky diseases, central nervous system localizations, lymphoblastic lymphoma. The unique features of this disease in immunocompromised patients and problems related to the growing numbers of older patients eligible for curative treatment are discussed.