Hema e-Chart registry of invasive fungal infections in haematological patients: improved outcome in recent years in mould infections.

The electronic surveillance system Hema e-Chart allowed us to prospectively collect data and to perform an analysis of invasive fungal infections (IFI) diagnosed in febrile patients as well as the procedures allowing their diagnosis and outcome according to the treatment given. Every patient admitted to 26 Italian Haematology Units with a new diagnosis of haematological malignancy and who was a candidate for chemotherapy was consecutively registered between March 2007 and March 2009. In all, 147 haematological patients with mycoses were identified. Yeasts were found in 23 infections; moulds were diagnosed in 17 proven, 35 probable and 72 possible mycoses. Galactomannan (GM) antigen was the most important test to diagnose probable mould infection; it was positive (cut-off >0.5) in 27 (77%) probable and in nine (53%) proven mould infections. Among patients with probable/proven mould infection who received no prophylaxis or non-mould-active prophylaxis with fluconazole, more patients (n = 26, 78.8%) had GM antigen positivity compared with patients (n = 10, 52.6%) given prophylaxis with mould-active drugs (p <0.05). First-line antifungal therapy was effective in 11/23 (48%) yeast infections and in 37/52 (71.2%) proven/probable mould infections. Twenty patients (14%) died within 12 weeks. The fungal attributable mortality was 30.4% and 17.3% in yeast and proven/probable mould infections, respectively. Among risk factors only age was independently associated (p 0.013) with mortality; sex, underlying haematological malignancy, previous prophylaxis and presence of neutropenia at diagnosis were not significant. A diagnosis of mould infection seemed to have a trend for a better outcome than the diagnosis of yeast infection (p 0.064).

Combination of all-trans-retinoic acid and gemtuzumab ozogamicin in an elderly patient with acute promyelocytic leukemia and severe cardiac failure.

All-trans-retinoic acid (ATRA) combined with anthracyclines is currently the standard treatment for acute promyelocytic leukemia (APL). In elderly patients the presence of comorbidities, such as cardiomyopathy or different organ failures, often represents an absolute contraindication to standard chemotherapy. In this particular setting of patients, alternative front-line approaches are needed. Here we report the use of gemtuzumab ozogamicin as consolidation therapy in a 68-year-old patient not eligible for standard dose anthracycline due to severe cardiac failure and chronic anticoagulant therapy, affected by low-risk APL. Induction therapy was started with ATRA alone, at a dose of 45 mg/m2 for 80 days. The patient obtained a complete hematological and molecular remission. At day +170 the patient was treated with 6 mg/m2 gemtuzumab ozogamicin monthly for two months (2 total doses) as a consolidation therapy and then started a maintenance program with ATRA 45 mg/m2 for 15 days every three months, for a total time of two years. No adverse events were observed in every phase of treatment and the patient is still in complete continuous hematological and molecular remission 29 months from diagnosis. This approach represents an intriguing therapeutic option to be investigated in randomized studies in low- and intermediate-risk elderly patients (older than 65 years), aiming to minimize or to eliminate standard chemotherapy in advantage of new non-conventional agents, including ATO.

HCV and cancer: a case-control study in a high-endemic area.

BACKGROUND/AIMS: HCV is a RNA virus that cannot be integrated with the host genome; it can, however, exert its oncogenic potential indirectly by contributing to the modulatory effects of the host immune system, probably through a capacity to elude the immune system. We have carried out a case-controlled study on the different oncological pathologies which have, to date, been shown to have a relationship with HCV. METHODS: We screened 495 patients with different types of cancer: 114 cases of liver cancer, 41 of multiple myeloma, 111 non-Hodgkin's lymphomas, 130 thyroid cancers, 63 cases of Hodgkin's disease. The controls were 226 patients with no history of cancer. The relationship between each cancer and HCV infection was assessed by means of odds ratios (OR) and corresponding 95% confidence intervals. RESULTS: Risks were greater for liver cancer (OR=32.9 95% CI 16.5-65.4, p<0.0001), multiple myeloma (OR=4.5 95% CI 1.9-10.7, p=0.0004) and B-cell non-Hodgkin's lymphoma (OR=3.7 95% CI 1.9-7.4, p=0.0001). For Hodgkin's disease there was no significant association (p=0.3). An association between HCV and thyroid cancer was noted (OR=2.8 95% CI 1.2-6.3, p=0.01). CONCLUSION: Our study is particularly important for public health since the high prevalence of HCV in the South of Italy gives reason to expect increases in not only liver cancer, but also tumors associated with the immune system and thyroid cancer in years to come.

HCV and tumors correlated with immune system: a case-control study in an area of hyperendemicity.

Hepatitis C virus (HCV) is a RNA virus that cannot be integrated with the host genome; it can, however, exert its oncogenetic potential indirectly by contributing to the modulator effects of the host immune system, probably through a capacity to elude the immune system. We have carried out a case controlled study on tumors correlated with the immune system (multiple myeloma, non-Hodgkin lymphoma and Hodgkin disease) and HCV, in a high prevalence area. The relationship between each cancer and HCV infection was assessed by means of odds ratios (ORs) and corresponding 95% confidence intervals. Risks were greater for B-cell non-Hodgkin lymphoma (OR=3.7, 95%CI, 1.9-7.4, P=0.0001) and multiple myeloma (OR=4.5, 95%CI, 1.9-10.7, P=0.0004). Our study is particularly important for public health, since it shows that during the coming years in the South of Italy, because of the high prevalence of HCV, there are good reasons to expect not only an increase of liver cancer, but also an increased incidence of great number of tumors correlated with the immune system.

Recombinant interferon alpha-2b as treatment of essential thrombocythaemia.

We report the disease characteristics and therapeutic results for 25 patients suffering from essential thrombocythaemia (ET), treated with recombinant interferon-alpha-2b (IFN-alpha 2b). ET was diagnosed according to the criteria of the Polycythaemia Vera Study Group. All patients were programmed to receive a subcutaneous induction treatment consisting of 3 MU of IFN-alpha 2b daily for 6 months. In responding patients, treatment was continued for a further 6 months with 3 MU of IFN-alpha 2b three times a week. Complete response was achieved in 13 of 25 patients, partial response in 10 of 25. In 2 cases, therapy was unsuccessful. Side effects were usually mild, consisting of flu-like symptoms in most cases, and were easily controlled by paracetamol. After a median follow-up of 14 months after discontinuation of the treatment, most patients retained the therapeutic response in the absence of toxicity.

Recombinant interferon alpha-2b in the treatment of polycythemia vera.

We studied the effects of recombinant alpha 2-b interferon (alpha 2-b IFN) in a dose of 3 x 10(6)U intramuscularly three times a week for 1 year in 13 patients affected by polycythemia vera (PV) previously treated with phlebotomy only. Response to treatment was evaluated by reduction of the number of phlebotomies required to retain normal hematocrit value. Ten out of 13 patients (77%) responded to treatment; in 4 of them the exigency of phlebotomy was completely eliminated. In all responders a concomitant decrease of platelet count and splenomegaly was obtained. Treatment was well tolerated and side effects were easily controlled. We conclude that alpha-IFN may represent an attractive therapeutic option in the management of the proliferative stages of PV.

Recombinant interferon-alpha 2A as maintenance treatment for patients with advanced stage chronic lymphocytic leukemia responding to chemotherapy.

Forty-five patients suffering from advanced B-CLL were randomized to receive interferon-alpha (IFN alpha) or no treatment after achieving complete remission or partial response, following a chemotherapy protocol called MiNa. The two groups were fully comparable in terms of clinical characteristics and level of response obtained by chemotherapy. IFN alpha was given at a dose of 3 megaunits three times a week intramuscularly for 1 year. The IFN-treated patient group showed a significantly longer duration of response and a less frequent incidence of infections as compared to the no treatment group. A minority of patients who had had partial response to chemotherapy obtained complete remission while on therapy with IFN alpha. Toxicity was mild and patient compliance was excellent. We conclude that IFN alpha may have a role as maintenance therapy in CLL for patients responding to chemotherapy.

Clinical relevance of immunological dissection in T-ALL: a report on 20 cases with stem cell (CD7+, CD4-, CD8-, CD1-) phenotype.

In a prospective study on 44 cases of T-cell origin acute lymphoblastic leukemia, 20 patients were found to display an immature immunophenotype (CD7+, CD4-, CD8-, CD1-) and were classified as T-stem cell leukemia (T-SCL). Twenty-four patients expressed CD4 and/or CD8 antigens on their blast cells, designated T acute lymphoblastic leukemia (T-ALL). The T-SCL subset showed a significantly higher median age, a more frequent incidence of extramedullary leukemia, a morphology L1 in most cases, and a poor response to treatment in terms of either complete remission rate or median survival duration. In addition, significant differences between the two groups were found in evaluating the number of days of blast disappearance from peripheral blood, of CR achievement, and of neutrophils and platelets recovery. We conclude that T-SCL represents a distinct clinical entity, characterized by a poor response to ALL conventional chemotherapy. Alternative therapeutic approaches should be developed for patients suffering from this form of leukemia, to modify its severe prognosis.

Acute Myeloid Leukemia Expressing T-Cell Antigens: Clinico-Hematological Report on Six Cases.

In a series of 107 patients suffering from acute myeloid leukemia (AML), blast cells from six patients were found to simultaneously express CD2 and CD7 antigens along with CD13, CD33, and CDw 65 in various combinations. The frequency of the expression of both lymphoid markers recurred with a higher incidence than that anticipated by multiplying single antigens frequency. The clinical and hematologic features from CD2+/CD7 + AML patients were studied as well as compared with those of CD2-/CD7- AML patients observed in the same period. Morphologically, bone marrow smears from the AML hybrid subset showed a preponderant population of agranular blasts along with a minority of typical myeloid cells, characterized by larger amount of cytoplasm and, in three cases, by rare but distinct Auer Rods. In all cases more than 3% of blast cells were positive for myeloperoxidases and all samples were classified as M1 according to FAB classification. Clinically, CD2 + /CD7 + patients presented with a higher incidence of adenopathy and meningeal leukemia than did patients with CD2 + /CD7 - AML and were characterized by poor response to therapy in terms of both achievement and duration of remission. We conclude that simultaneous expression of CD2 and CD7 in AML is a non random event, recurring in more than 5% of cases and is associated with distinct clinical and hematologic features.

Ocular manifestations in thalassemia minor.

The authors report the results of a study on 96 subjects affected with thalassemia minor. The study was made at the Center for the Study of Microcythemia of the OORR in Naples. Of extreme scientific interest is the finding of ocular involvement in 33.3% of the cases. Therefore, after formulating a pathogenetic hypothesis, the authors plan more involved studies and research on these patients.

[Prognostic evaluation of chronic lymphocytic leukemia in relation to the Rai classification. Critical analysis of 145 personal cases]. / Valutazione prognostica della linfoadenosi cronica in rapporto alla classificazione di Rai. Analisi critica di 145 casi personali.

145 patients suffering from Chronic Lymphocytic Leukemia, observed in the period from 1961 to 1976, were analyzed with regard to prognosis according to following factors: age, sex, Rai staging. Age and sex didn't show to influence median survival. According to Rai staging, and Authors, owing to obtained results, propose a classification in just two stages.