Monitoring for cytomegalovirus and Epstein-Barr virus infection in chronic lymphocytic leukemia patients receiving i.v. fludarabine-cyclophosphamide combination and alemtuzumab as consolidation therapy.

The combination of fludarabine and cyclophosphamide (FC) has become the standard of care in chronic lymphocytic leukemia (CLL) patients. Due to the well-recognized F-related immunosuppression,[1][1] a higher risk of opportunistic infections could be expected by adding another immunosuppressive agen

A Single-Center Experience With 1400 Patients

To assess whether the pattern of presentation and the outcome of monoclonal gammopathy of undetermined significance (MGUS) have changed over the last 3 decades, we evaluated 1400 patients, divided into 3 groups: group I (1975-1987), group II (1988-1997), and group III (1998-2007). We observed a significant increase in age (p = 0.001), IgM and biclonal MGUS (p = 0.003), hemoglobin (p < 0.0001), and albumin (p = 0.0001), and a significant reduction of monoclonal (M)-protein concentration (p < 0.0001), percentage of bone marrow plasma cells (p < 0.0001), and beta2-microglobulin (p = 0.0001) over the 3 decades. The proportion of patients with M-protein <1.5 g/dL was significantly higher in group III (66%) than in group II (44%) and group I (26%) (p < 0.0001). By Kaplan-Meier analysis, group III had a significantly lower 5-year probability of transformation (5%) compared to group II (12%) and group I (22%) (p = 0.003). Patients with M-protein <1.5 g/dL had the same life expectancy as the general population (standardized mortality ratio 1.09; p = 0.41). In conclusion, we found that the pattern of presentation of MGUS has changed over time and now includes a higher proportion of patients with more favorable presenting features and probably a better outcome compared to patients presenting in the past. This changing scenario calls for revising the current concepts of the clinical significance of MGUS and the management of patients

Long-term Events in Adult Patients with Clinical Stage IA-IIA Nonbulky Hodgkin's Lymphoma Treated with Four Cycles of Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine and Adjuvant Radiotherapy: A Single-Institution 15-Year Follow-up

Abstract Purpose: To report on long-term events after short doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy and adjuvant radiotherapy in favorable early-stage Hodgkin's lymphoma. Experimental Design: We monitored late events and causes of death over 15 years (median follow-up, 120 months) in 120 patients with nonbulky stage IA-IIA Hodgkin's lymphoma, treated with four cycles of ABVD and limited radiotherapy. Pulmonary and cardiac function tests were done throughout the follow-up. Outcome measures included cause-specific mortality, standardized mortality ratio, and standardized incidence ratio for secondary neoplasia. Results: Projected 15-year event-free and overall survival were 78% and 86%, and tumor mortality was 3%. Standardized mortality ratio was significantly higher than 1 for both males (2.8; P = 0.029) and females (9.4; P = 0.003). The risk of cardiovascular events at 5 and 12 years was 5.5% and 14%, with a median latent time of 67 months (range: 23-179 months) from the end of radiotherapy. Pulmonary toxicity developed in 8% of patients; all had received mediastinal irradiation and the median time from radiotherapy to pulmonary sequelae was 76 weeks (range: 50-123 weeks). The risk of secondary neoplasia at 5 and 12 years was 4% and 8%, respectively, with no cases of leukemia. Fertility was preserved. Conclusions: Long-term events were mostly related to radiotherapy; the role of short ABVD chemotherapy was very limited, as documented by fertility preservation and lack of secondary myelodysplasia/leukemia. A proportion of patients died from causes unrelated to disease progression and the excess mortality risk was mostly due to the occurrence of secondary neoplasms and cardiovascular diseases. A moderate dose reduction of radiotherapy from 40-44 Gy to 30-36 Gy did not decrease the risk of late complications; abolishing radiotherapy in nonbulky early-stage Hodgkin's lymphoma is being evaluated

Increased risk of pregnancy complications in patients with essential thrombocythemia carrying the JAK2 (617V>F) mutation

Abstract Essential thrombocythemia (ET) may occur in women of childbearing age. To investigate the risk of pregnancy complications, we studied 103 pregnancies that occurred in 62 women with ET. The 2-tailed Fisher exact test showed that pregnancy outcome was independent from that of a previous pregnancy. The rate of live birth was 64%, and 51% of pregnancies were uneventful. Maternal complications occurred in 9%, while fetal complications occurred in 40% of pregnancies. The Mantel-Haenszel method showed that fetal loss in women with ET was 3.4-fold higher (95% confidence interval [CI]: 3-3.9; P F) mutation, and a multivariate logistic regression model identified this mutation as an independent predictor of pregnancy complications (P = .01). Neither the platelet count nor the leukocyte count was a risk factor. JAK2 (617V>F)–positive patients had an odds ratio of 2.02 (95% CI: 1.1 - 3.8) of developing complications in comparison with JAK2 (617V>F)–negative patients. Aspirin did not prevent complication in JAK2 (617V>F)–positive patients and appeared to worsen outcome in JAK2 (617V>F)–negative patients. A relationship was found between JAK2 (617V>F) and fetal loss (P = .05). This study indicates that patients carrying the JAK2 (617V>F) mutation have higher risk of developing pregnancy complications

exaggerated insect bite like reaction in patients affected by oncohaematological diseases

Sir,Patients affected by chronic B-cell lymphatic leukaemia(CBLL) and, more rarely, other oncohaematologicaldiseases may present with papules, plaques, nodules andvesico-bullous lesions on exposed areas (1–3). Theselesions are usually considered an exaggerated reaction toinsect bites, although the patients not always had ahistory (except for the seasonal presentation of cuta-neous findings), the clinical picture, and response totreatment suggestive of insect bite (3, 4). This phenom-enon has been described in about 40 patients affected bylymphoproliferative disorders, 95% of whom had CBLL(1–7). Weed (1) first gave the definition of 'exaggerateddelayed hypersensitivity to mosquito bites' and reportedthis condition only in patients affected with CBLL.Later, Houston & Keene (2) described a case ofexaggerated insect bite-like reaction also in a patientwith lymphocytic lymphoma. In 1986, Rosen et al. (3)studied 10 patients and suggested that the cutaneouslesions could be linked, in some way, to the onco-haematological conditions, without explaining the exactpathway.Five patients affected by different B lymphoprolifera-tive disorders, who presented with pruritic papules,nodules and vesico-bullous lesions on exposedareas during spring and summer time, are reported.We discuss an immuno-allergic mechanism, involvingboth allergic reaction to insect bite and the impair-ment of the immune response in oncohaematologicalpatients.CASE REPORTSFrom 1995 to 2001, three patients affected by CBLL andtwo by non-Hodgkin B-cell lymphomas attended ourdepartment with polymorphous, erythematous cuta-neous papules and plaques, some of them evolving intobullous lesions. During spring-summer all the patientsdeveloped very itchy lesions, plaques (Fig. 1) andsometimes bullae, mainly localized on upper and/orlower limbs and on the face. Three patients referred tohave been bitten by mosquitoes, the other two deniedthis occurrence. At the time of the clinical examination,all the patients were living in or close to the area ofPavia, Italy, where seasonal infestations of mosquitoes(Aedes) are particularly widespread. All the patientsunderwent a 4-mm punch biopsy, necessary for ahistopathologic evaluation; a direct immunofluores-cence test was carried out for four patients, to excludeautoimmune bullous diseases.At the time of the eruption, one patient was ontreatment with VACOP-B protocol (adriblastina, cyclo-phosphamide, etoposide, vincristine, bleomycin, predni-sone), two patients with chlorambucil and one withcyclophosphamide. An 87-year-old patient was notunder treatment. Blood analysis revealed peripheraleosinophilia in three patients out of five. Stool analysissearching for parasites was carried out in those threepatients and proved negative. IgE was in the normalrange in all the patients. Serum protein electrophoresisrevealed that total immunoglobulins were in the normalrange or little lower in all the patients, while all of thempresented a different degree of decrease of IgG, IgMand/or IgA in sera. The other clinical and serologicalfindings were unremarkable or consistent with theirhaematological condition.The histopathology was characterized by a variety offindings, all of which were consistent with an arthropodbite reaction. In particular, a wedge-shaped, superficialor superficial-deep perivascular and often also inter-stitial infiltrate was present. It was mainly composed ofeosinophils in association with lymphocytes and rarelyneutrophils. The density or the depth of the infiltratevaried from case to case, also according to the age of thelesion. An oedema of the subpapillary dermis wasalways evident. One patient presented a subepidermalvesicle. In another patient spongiosis could be seen an

Prognostic factors for thrombosis, myelofibrosis, and leukemia in essential thrombocythemia: a study of 605 patients

Background Essential thrombocythemia is a chronic myeloproliferative disorder; patients with this disorder have a propensity to develop thrombosis, myelofibrosis, and leukemia. Design and Methods We studied 605 patients with essential thrombocythemia (follow-up 4596 person-years) with the aim of defining prognostic factors for thrombosis, myelofibrosis, and leukemia during follow-up. Results Sixty-six patients (11%) developed thrombosis with a 10-year risk of 14%. Age >60 years ( p 60 years ( p =0.02) was significantly correlated with the development of leukemia. Cytotoxic treatment did not imply a higher risk of leukemia. At the time of the analysis, 64 of the 605 patients (10.6%) had died. The 10-year probability of survival was 88%, with a median survival of 22.3 years. Age >60 years ( p <0.001) and history of thrombosis ( p =0.001) were independent risk factors for survival. Conclusions The findings from this study on a large series of patients treated according to current clinical practice provide reassurance that essential thrombocythemia is an indolent disorder and affected patients have a long survival. The main risk is thrombosis, while myelofibrosis and leukemia are rare and late complications

Supplementation with cactus pear (Opuntia ficus-indica) fruit decreases oxidative stress in healthy humans: A comparative study with vitamin C

Background: Cactus pear (Opuntia ficus-indica) fruit contains vitamin C and characteristic betalain pigments, the radical-scavenging properties and antioxidant activities of which have been shown in vitro. Objective: We investigated the effects of short-term supplementation with cactus pear fruit compared with vitamin C alone on total-body oxidative status in healthy humans. Design: In a randomized, crossover, double-treatment study, 18 healthy volunteers received either 250 g fresh fruit pulp or 75 mg vitamin C twice daily for 2 wk, with a 6-wk washout period between the treatments. Before (baseline) and after each treatment, 8-epiprostaglandin F2α (8-epi-PGF2α) and malondialdehyde in plasma, the ratio of reduced to oxidized glutathione (GSH:GSSG) in erythrocytes, and lipid hydroperoxides in LDL were measured as biomarkers of oxidative stress; plasma Trolox-equivalent antioxidant activity (TEAC) and vitamins A, E, and C were evaluated as indexes of antioxidant status. Results: Both treatments caused comparable increases compared with baseline in plasma concentrations of vitamin E and vitamin C (P < 0.05); vitamin A and TEAC did not change significantly. After supplementation with cactus pear fruit, 8-epi-PGF2α and malondialdehyde decreased by ≈30% and 75%, respectively; GSH:GSSG shifted toward a higher value (P < 0.05); and LDL hydroperoxides were reduced by almost one-half. Supplementation with vitamin C did not significantly affect any marker of oxidative stress. Conclusions: Consumption of cactus pear fruit positively affects the body's redox balance, decreases oxidative damage to lipids, and improves antioxidant status in healthy humans. Supplementation with vitamin C at a comparable dosage enhances overall antioxidant defense but does not significantly affect body oxidative stress. Components of cactus pear fruit other than antioxidant vitamins may play a role in the observed effects. © 2004 American Society for Clinical Nutrition

A single dose of pegfilgrastim compared with daily filgrastim for supporting neutrophil recovery in patients treated for low-to-intermediate risk acute myeloid leukemia: results from a randomized, double-blind, phase 2 trial

Background: Patients with acute myeloid leukemia (AML) are often neutropenic as a result of their disease. Furthermore, these patients typically experience profound neutropenia following induction and/or consolidation chemotherapy and this may result in serious, potentially life-threatening, infection. This randomized, double-blind, phase 2 clinical trial compared the efficacy and tolerability of pegfilgrastim with filgrastim for assisting neutrophil recovery following induction and consolidation chemotherapy for de novo AML in patients with low-to-intermediate risk cytogenetics. Methods: Patients (n = 84) received one or two courses of standard induction chemotherapy (idarubicin + cytarabine), followed by one course of consolidation therapy (high-dose cytarabine) if complete remission was achieved. They were randomized to receive either single-dose pegfilgrastim 6 mg or daily filgrastim 5 μg/kg, beginning 24 hours after induction and consolidation chemotherapy. Results: The median time to recovery from severe neutropenia was 22.0 days for both pegfilgrastim (n = 42) and filgrastim (n = 41) groups during Induction 1 (difference 0.0 days; 95% CI: -1.9 to 1.9). During Consolidation, recovery occurred after a median of 17.0 days for pegfilgrastim versus 16.5 days for filgrastim (difference 0.5 days; 95% CI: -1.1 to 2.1). Therapeutic pegfilgrastim serum concentrations were maintained throughout neutropenia. Pegfilgrastim was well tolerated, with an adverse event profile similar to that of filgrastim. Conclusion: These data suggest no clinically meaningful difference between a single dose of pegfilgrastim and multiple daily doses of filgrastim for shortening the duration of severe neutropenia following chemotherapy in de novo AML patients with low-to-intermediate risk cytogenetics

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p &lt; .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p &lt; .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come