Salvatrice Mancuso

Comprehensive geriatric assessment is an essential tool to support treatment decisions in elderly patients with diffuse large B-cell lymphoma: a prospective multicenter evaluation in 173 patients by the Lymphoma Italian Foundation (FIL)

Abstract We performed a multicenter study to validate the concept that a simple comprehensive geriatric assessment (CGA) can identify elderly, non-fit patients with diffuse large B-cell lymphoma (DLBCL) in whom curative treatment is not better then palliation, and to analyze potential benefits of treatment modulation after further subdividing the non-fit category by CGA criteria. One hundred and seventy-three patients aged > 69 treated with curative or palliative intent by clinical judgement only were grouped according to CGA into fit (46%), unfit (16%) and frail (38%) categories. Two-year overall survival (OS) was significantly better in fit than in non-fit patients (84% vs. 47%; p < 0.0001). Survival in unfit and frail patients was not significantly different. Curative treatment slightly improved 2-year OS in unfit (75% vs. 45%) but not in frail patients (44% vs. 39%). CGA was confirmed as very efficient in identifying elderly patients with DLBCL who can benefit from a curative approach. Further efforts are needed to better tailor therapies in non-fit patients.

Optimal Duration of Low Molecular Weight Heparin for the Treatment of Cancer-Related Deep Vein Thrombosis: The Cancer-DACUS Study

PURPOSE We evaluated the role of residual vein thrombosis (RVT) to assess the optimal duration of anticoagulants in patients with cancer who have deep vein thrombosis (DVT) of the lower limbs. PATIENTS AND METHODS Patients with active cancer and a first episode of DVT treated with low molecular weight heparin (LMWH) for 6 months were eligible. Patients were managed according to RVT findings: those with RVT were randomly assigned to continue LMWH for an additional 6 months (group A1) or to discontinue it (group A2), and patients without RVT stopped LMWH (group B). The primary end point was recurrent venous thromboembolism (VTE) during the 1 year after disconinuation of LMWH, and the secondary end point was major bleeding. Analyses are from the time of random assignment. RESULTS Between October 2005 and April 2010, 347 patients were enrolled. RVT was detected in 242 patients (69.7%); recurrence occurred in 22 of the 119 patients in group A1compared with 27 of 123 patients in group A2. The adjusted hazard ratio (HR) for group A2 versus A1 was 1.37 (95% CI, 0.7 to 2.5; P = .311). Three of the 105 patients in group B developed recurrent VTE; adjusted HR for group A1 versus B was 6.0 (95% CI, 1.7 to 21.2; P = .005). Three major bleeding events occurred in group A1, and two events each occurred in groups A2 and B. The HR for major bleeding in group A1 versus group A2 was 3.78 (95% CI, 0.77 to 18.58; P = .102). Overall, 42 patients (12.1%) died during follow-up as a result of cancer progression. CONCLUSION In patients with cancer with a first DVT, treated for 6 months with LMWH, absence of RVT identifies a population at low risk for recurrent thrombotic events. Continuation of LMWH in patients with RVT up to 1 year did not reduce recurrent VTE.

Bendamustine with or without rituximab in the treatment of relapsed chronic lymphocytic leukaemia: an Italian retrospective study

To retrospectively assess the efficacy of bendamustine alone and with rituximab (R–B), 109 patients with relapsed chronic lymphocytic leukaemia (CLL) were enrolled in 24 Italian centres. The median age was 66 years (range 39–85). Forty‐three percent of patients had relapsed and 57% were resistant (median previous therapies = 3; range 1–8). Twenty‐two patients received bendamustine alone and 87 patients received R–B (median B dosage: 100 mg/m2 per day, range 90–130 mg/m2 per day). The overall response rate was 69·6% (complete response 28·6%; partial response 41%), and was significantly higher in patients treated with R–B (P = 0·014) and in those responsive to the previous treatment (P = 0·04). After a median follow‐up of 7·9 months (range 1–148), the median progression‐free survival was 16 months and the median duration of response was 13 months. Median overall survival (OS) was 16·8 months for the whole cohort; patients not responding to the treatment had a significantly worse outcome than those who attained a response (P = 0·0001). In multivariate analysis, only resistant disease status at start of bendamustine treatment (HR 3·2, 95% CI 1·4–7·3, P = 0·006) had an independent prognostic value for OS. Toxicity was manageable and mostly haematological. In conclusion, in our experience R–B was an effective and well‐tolerated treatment for relapsed/refractory CLL patients, producing a remarkable high CR rate and mild toxicity.

Thrombotic complications in paroxysmal nocturnal haemoglobinuria: a literature review

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, clonal haematopoietic stem cell disease caused by mutations in an X-linked gene called phosphatidylinositol glycan class A (PIG-A). The disease can present with bone marrow failure, haemolytic anaemia, smooth muscle dystonia and thrombosis. The PIG-A gene product is necessary for the first step in the biosynthesis of glycosylphosphatidyinositol (GPI) anchors - the transfer of GlcNAc from UDP-GlcNAc to form N-acetylglucosaminyl phosphatidylinositol (GlcNAc-PI) - where expansion and differentiation of the PIG-A mutant stem cell leads to clinical manifestations of the disease1. PNH may occur de novo (classical PNH) or in the setting of aplastic anaemia (hypoplastic PNH); the absence of GPI-linked complement regulatory proteins on PNH erythrocytes renders these cells susceptible to terminal complement-mediated haemolysis2. The natural history of PNH is highly variable, ranging from indolent to life-threatening. The median survival is 10 to 15 years, but the range is wide. Thrombosis is the leading cause of death, and an initial thrombotic event increases the relative risk of death by 5- to 10-fold in PNH3. Haemolysis most likely contributes to thromboembolism, as patients with larger PNH clones have a higher incidence of thromboembolism and events have been temporally associated with increased haemolysis. Although the mechanism is not fully understood, haemolysis has been implicated in the initiation of platelet activation and aggregation4. This review discusses the underlying mechanisms that lead to thrombosis in PNH and therapeutic approaches.

Synthesis and induction of G0-G1 phase arrest with apoptosis of 3,5-dimethyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4(3H)-one.

The multistep synthesis of 3,5-dimethyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4(3H)-one 15 has been carried out. The compound showed antiproliferative and apoptotic effects against K562, K562-R (imatinib mesilate resistant), HL60 and multidrug resistant (MDR) HL60 cell lines. Compound 15 showed a pro-apoptotic activity against HL60 and K562 resistant cell lines markedly higher than etoposide and busulfan, respectively. Flow cytometry studies carried out on K562 cells allowed to establish that 15 induces G0-G1 phase arrest followed by apoptosis.

Rituximab with cyclophosphamide, vincristine, non-pegylated liposomal doxorubicin and prednisone as first-line treatment for splenic marginal zone lymphoma: a Fondazione Italiana Linfomi phase II study

Rituximab ® provides high response rates and effective disease palliation in patients with splenic marginal zone lymphoma (SMZL). We conducted a phase II trial in patients with SMZL who were either untreated or were splenectomized but had shown disease progression within 1 year after splenectomy. Treatment consisted of six courses of Rituximab with cyclophosphamide, vincristine, non-pegylated liposomal doxorubicin and prednisone (R-COMP). Fifty-one patients were eligible for the analysis. The overall response rate was 84%. The 6-year progression-free survival and overall survival were 54% and 72%, respectively. Toxicity was substantial (grade ≥ 3 neutropenia: 26%; grade ≥ 3 infections: 8%). Of the 15 deaths, two occurred on treatment (one sepsis and one pneumonia). Six deaths were due to lymphoma progression, four to secondary neoplasia, one to sepsis, one to pneumonia and one to splenectomy complications. R-COMP should be restricted to patients with bulky disease associated with symptoms or to patients with possible histological transformation.

Oral Leishmaniasis in an HIV-Infected Patient

As in most countries in the Mediterranean basin, leishmaniasis is endemic in Italy, where it has visceral (VL) and cutaneous (CL) forms caused by viscerotropic and dermotropic strains of Leishmania infantum, respectively. With the spread of the acquired immunodeficiency syndrome (AIDS) epidemic, the number of coinfections with Leishmania and human immunodeficiency virus (HIV) is increasing. Between 35% and 50% of the adult VL cases diagnosed annually in Sicily from 1991 to 1995 were related to HIV [1]; although cases of coinfection have been reported in 28 countries worldwide, the majority of these cases (1440 from 1990 to 1998) have been notified in four countries (Spain, Italy, France, Portugal) [2].

Evaluation of the prognostic role of tumour-associated macrophages in newly diagnosed classical Hodgkin lymphoma and correlation with early FDG-PET assessment

In Hodgkin Lymphoma (HL), about 20% of patients still have relapsed/refractory disease and late toxic effects rate continue to rise with time. ‘Early FDG‐PET’ and tissue macrophage infiltration (TAM) emerged as powerful prognostic predictors. The primary endpoint was to investigate the prognostic role of both early FDG‐PET and TAM; the secondary endpoint was to test if early FDG‐PET positivity could correlate with high TAM score.

Absolute lymphocyte count is unrelated to overall survival in newly diagnosed elderly patients with multiple myeloma treated with immunomodulatory drugs

1 Cattedra ed U.O. di Ematologia con trapianto, Policlinico Universitario di Palermo, Palermo, Sicily, 2 Divisione di Ematologia, Ospedale Ferrarotto, Universit à di Catania, Catania, Sicily, 3 Azienda Ospedaliera “ Ospedali Riuniti Villa Sofi a-Cervello ” , Palermo, Sicily, 4 Cattedra ed U.O. di Ematologia con trapianto, Policlinico Universitario di Bari, Bari, Italy and 5 Istituto Italiano di Statistica (ISTAT)-Palermo, Palermo, Sicily

T Cell Large Granular Lymphocytic Leukemia in Association with Sjögren’s Syndrome

T cell large granular lymphocytic (LGL) leukemia is a rare condition accounting for 2–3% of all mature lymphoid leukemias. Here, we present the case of a 73-year-old woman presenting with neutropenia and anemia (hemoglobin 9.9 g/dl). Hematological assessment revealed the presence of a T cell LGL leukemia. At the time of T cell LGL leukemia diagnosis, the patient developed xerophthalmia and xerostomia, and a diagnosis of Sjögren’s syndrome was made following salivary gland biopsy. The finding of large granular lymphocytes in the context of autoimmune disorders is well-known, though it often occurs with rheumatoid arthritis or in association with a positive autoantibody titer in the absence of an overt clinical picture. The concomitant presentation of T cell LGL leukemia with Sjögren’s syndrome is a rare event which is worth reporting. Our patient was managed with immunosuppressive therapy and is still alive.