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).

CD2 expression in acute promyelocytic leukemia is associated with microgranular morphology (FAB M3v) but not with any PML gene breakpoint.

In the t(15;17) translocation of acute promyelocytic leukemia (APL) at least three regions of the PML gene are involved in the reciprocal translocation between the PML and the RAR-alpha loci. The chimeric PML/RAR-alpha fusion transcripts can be demonstrated in all cases of APL, by a specific reverse-transcription PCR (RT-PCR). Previous studies found a correlation between expression of CD2 and involvement of the PML bcr3. In this study, we assessed this association in 43 children and adults with APL. A blind morphologic review of all smears was performed by four experienced hemopathologists who agreed the diagnosis of M3 vs M3v APL. CD2 expression on APL was detected by using different monoclonal antibodies (MoAbs) directed against specific CD2 epitopes by flow cytometry and in selected cases by Northern blot by the use of a specific CD2 cDNA probe. Nineteen of 43 cases displayed the typical microgranular features consistent with the diagnosis of M3v. Of these, 12 had the bcr3 breakpoint on chromosome 15, while seven had the bcr1 type. In 16 of the 19 patients, leukemic cells expressed both CD2 protein and the corresponding mRNA. Similarly, in the negative cases, Northern blot analysis failed to demonstrate the presence of specific mRNA. The remaining 24 patients, with the classic morphologic features of M3, were CD3 negative. These results point out that CD2 expression correlates with the FAB M3v and not with the PML breakpoints. During the course of all-trans retinoic treatment a down-modulation of CD2 expression was observed in three M3v cases. Overall, our findings might suggest a role of CD2 epitopes in the regulation of adhesion properties of APL blast cells.

Reciprocal translocation t(12;13)(p13;q14) in acute nonlymphoblastic leukemia: report and cytogenetic analysis of two cases.

Two cases of acute nonlymphoblastic leukemia with a reciprocal translocation t(12;13)(p13;q14) are described. Both patients were male adults with a diagnosis of M0 FAB type. Beside standard cytogenetic analysis, we applied fluorescence in situ hybridization (FISH) in order to investigate the position of the RB gene with respect to the breakpoint at 13q14. Our results showed that the RB gene was proximal to the breakpoint, but, apparently, not split in either case.

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.

Molecular monitoring of the myl/retinoic acid receptor-alpha fusion gene in acute promyelocytic leukemia by polymerase chain reaction.

The acute promyelocytic leukemia (APL) t(15;17) translocation generates a myl/retinoic acid receptor-alpha (RAR-alpha) chimeric gene that is transcribed as a fusion myl/RAR-alpha messenger RNA. Using primer sets derived from RAR-alpha and myl cDNAs, we were able to amplify the breakpoint sites of the fusion transcripts of all 35 APL RNA samples by reverse polymerase chain reaction (PCR) and nested primer approach of two rounds of amplification. DNA fragments of different size were obtained according to the chromosome 15 breakpoints (intron 3-bcr 3; exon 6-bcr 2; and intron 6-bcr 1). bcr 1 and bcr 3 represent the regions of the myl locus most frequently involved among APL (48.5 and 34.2 of cases, respectively); bcr 3 constitutes 62.5% of cases among M3V as compared with 25.9% of M3 cases. The feasibility of monitoring the APL clone by PCR analysis in five APL patients who received different treatment (chemotherapy, all-trans-retinoic acid or bone marrow transplantation) was evaluated. In five of nine bone marrow samples of patients in complete remission, t(15;17)-positive cells could be detected by PCR analysis. We conclude that PCR amplification of the myl/RAR-alpha junctions represents the easiest and rapid method for diagnosis and monitoring of the APL clone.

[Clinical course of refractory anemia. Study of a case series of 56 patients]. / Considerazioni sulla evoluzione clinica delle anemie refrattarie. Studio di una casistica di 56 pazienti.

We analysed the course and clinical features of a series of refractory anaemias (RA, RAEB, RAEBt). We could not find evidence to support the hypothesis that these three MDS classes are inevitably subsequent events of a single disease. Therefore aggressive treatment of RA, aimed at avoiding its evolution to RAEB or RAEBt, does not seem justified.

Non-Hodgkin's lymphoma of the elderly. Prognostic factors and outcome.

The initial features and prognosis of non-Hodgkin's lymphoma (NHL) of the elderly have been variously evaluated in literature. We have examined 190 patients with NHL: most of them received induction therapies containing vincristine, cyclophosphamide and/or anthracyclines (CVP, CHOP, CEOP); age at diagnosis was over 65 for 62 of them (32.63%). Elderly patients had a lower rate of complete remissions, a shorter duration of complete remissions and, consequently, a poorer overall survival. In our patients, prognosis was related also with stage, histology (according to Working Formulation, WF) and performance status at the diagnosis. Elderly patient had not a significantly increased incidence of these unfavourable prognostic factors at the onset. However, patients aged 65 or more received lower doses of drugs during induction therapy (cyclophosphamide: 81%; vincristine: 73%; anthracyclines: 22% of patients under 55). Patients aged 55-65 had induction therapies of intermediate intensity; also proportion of complete remissions and survival were intermediate between the two other groups. Haematological toxicity appeared the most important cause of these reductions: in fact nadirs of neutrophils and platelets during induction therapy were similar in the 3 groups in spite of the different intensity of treatment. Even if statistical correlations are not possible, the incidence of infections has been higher in the elderly.

A survey of the necessity of the hospitalization day in an Italian teaching hospital.

To assess the extent of inappropriate hospital use in an adult in-patients population we used a modified version of the Appropriateness Evaluation Protocol (A.E.P.) to evaluate retrospectively a cross-section of 273 patient-days in a large teaching hospital in the Greater Milan area. Overall, 41% were judged to represent inappropriate hospital use on the basis of the protocol's criteria. The rate of inappropriate hospital use was significantly associated with admitting specialty, ranging from 12% for surgery, to 20% for cardiology and to about 60% in psychiatric, geriatrics and neurology departments (p less than 0.01). Hospital days of patients with longer stays were more frequently inappropriate: a statistically significant trend of inappropriateness emerged ranging from 30% among patients with total length of stay (LOS) of 1-10 days to 60% among those with LOS greater than 30 days (p less than 0.01). This study confirms that there is a substantial rate of unnecessary use of hospitals but that such inappropriateness does not seem in most cases to be easily modifiable through "simple" organizational changes.

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.