Multiple myeloma and paget disease with abnormal skull lesions and intracranial hypertension.

We report a 73 years old man with a diagnosis of Paget Disease (PD) and symptomatic Multiple Myeloma (MM). Coexistence of MM and PD has rarely been described. PD mimics many of the features of bone destructive process in MM, making differential diagnosis more complicated. In addition, the presence of serious muscolo-skeletal and metabolic complications in both diseases makes management of patients difficult, worsening the prognosis.The comparison of these two diseases has led to the characterization of a common molecular mechanism represented by the receptor activator of nuclear factor-kB ligand (RANKL)/Osteoprotegerin signaling pathway. The improved comprehension of these mechanisms led to the development of new pharmacologic agents (bisphosphonates, cytokines inhibitors) effective for the treatment of these bone diseases.

[Adhesion the vaccination against HPV in ASL of L'Aquila]. / Adesione alla vaccinazione contro l'HPV nella ASL dell'Aquila.

Sexually transmitted human papillomaviruses (HPVs) are responsible for anogenital infections and tumours. Types 16 and 18 cause 70% of cervical carcinomas, the incidence of which is higher among young women. The aim of this study was to evaluate the propensity of mothers to have their 12-year-old daughters vaccinated against HPV and identify the variables that may influence their agreement, such as their kowledge of HPV and its relationship with cervical cancer. A 17-item questionnaire was anonymously administered to 312 mothers of girls born in 1997 who were invited to undergo vaccination by their local health authority. The results were analysed using the chi-squared test and STATA 9 statistical software. The analysis showed that 69% of the mothers had had their daughters vaccinated, that most of them know about HPV but only 20% clearly understood the relationship between HPV and cancer Acceptance of the vaccination seems to be associated more with a general predisposition to vaccinate than with a knowledge of HPV and its causal relationship with cervical carcinoma. This indicates a need for educational/ information programmes before and during the vaccination cycle.

[Evaluation of cognitive requirements of parents consumers attending vaccination offices]. / Valutazione dei fabbisogni conoscitivi dei genitori utenti degli Uffici di Vaccinazione.

To vaccinate the majority of population it is essential a strong cooperation with parents (users) which have to be correctly informed through an efficient communication system. The present analysis aims at elucidating parental background knowledge and information sources on vaccination problems. We selected 387 parents from ASL vaccination offices in L'Aquila, Avezzano-Sulmona and Pescara. Two groups have been identified: the first group included parents dealing with the first vaccination of their child, parents in the second group already experienced the vaccination tool. The two groups have been tested with a 17 items questionnaire. Results analysis evidenced a reasonable trust in the validity of received information and a fair level of topic knowledge. Our results show that the organizative and cultural effort put on by Public health operators improved awareness and participation to vaccination program. Still a big effort has to be devoted to disadvantage group of population's mainly low-level education groups and new immigrants. Thus it would be wise to promote informative actions even through the media to increase the basic knowledge on vaccine strategies

Pain syndromes in the setting of haematopoietic stem cell transplantation for haematological malignancies.

Severe pain syndromes may be recorded during all phases of haematopoietic stem cell transplantation (HSCT) for haematological malignancies: from stem cell mobilization to the long-term post transplant period. Although the major cause of pain in the setting of HSCT is injury to mucosal tissues induced by the conditioning regimen, pain from several other causes has been reported. In this paper, we review pain and its management in the setting of HSCT.

Prolonged survival and low incidence of late toxic sequelae in advanced follicular lymphoma treated with a TBI-free autografting program: updated results of the multicenter consecutive GITMO trial.

This study provides an updated report of the consecutive multicenter Gruppo Italiano Trapianto Midollo Osseo trial employing an intensified, purging-free, total body irradiation-free, high-dose sequential chemotherapy schedule with peripheral blood stem cell autograft (i-HDS) in advanced-stage follicular lymphoma (FL). Special interest has been devoted to late toxicities and outcome in terms of molecular status. Ninety-two untreated FL patients aged

Phase III comparative trial using CHOP vs CIOP in the treatment of advanced intermediate-grade non-Hodgkin's lymphoma.

Until now, literature data support the fact that the CHOP regimen represents the standard first line treatment for patients with advanced intermediate-grade non-Hodgkin's lymphoma. Recently, idarubicin has been introduced in clinical trials because of its favourable preclinical profile: it is more active than daunorubicin and doxorubicin against a number of experimental tumour systems and is significantly less cardiotoxic in animal models. From March 1991 to June 1993, 115 previously untreated patients with stage II to IV intermediate-grade non-Hodgkin's lymphoma, according to the Kiel classification, were enrolled in a phase III comparative trial. The objectives of the study were to compare the efficacy and safety of using idarubicin instead of doxorubicin in the polychemotherapeutic regimen CHOP (cyclophosphamide, doxorubicin, vincristine, and dexamethasone). Of the 115 patients registered for the trial, 103 were evaluable: 52 received CH (doxorubicin)OP and 51 received CI(Idarubicin)OP. Known prognostic factors were equally distributed among the two groups. There were no significant differences between the 2 groups in the rates of partial and complete response. The overall response rate was 87%, with complete response in 62%: 63% in the CHOP group, and 59% in the CIOP group. At 30 months (median 20 months), 86% of all CR patients were alive without disease in the CHOP group and 85% in the CIOP group. Patients treated with CHOP experienced severe alopecia more frequently (P = .004). Only three patients in the CIOP group showed cardiac adverse events (1 moderate and 2 mild), while in the CHOP group 4 mild, 2 moderate and 1 severe were recorded. LVEF monitoring was carried out in 31 patients of the CHOP group and in 27 of the CIOP group. A median drop of 8.3% of the LVEF was observed in patients treated with CHOP regimen as compared to 4.8% in patients with CIOP regimen (P = .0001). In this trial, the "idarubicin arm" (CIOP regimen) was found to have an equivalent therapeutic efficacy and, slightly, reduced clinical toxicity in comparison to the standard doxorubicin-containing CHOP regimen in patients with intermediate-grade non-Hodgkin's lymphoma.

Long-term observation of 208 adults with chronic idiopathic thrombocytopenic purpura.

PURPOSE: To define response to therapy and ultimate outcome of adults with idiopathic thrombocytopenic purpura (ITP). PATIENTS AND METHODS: We retrospectively analyzed patients with ITP diagnosed between 1978 and 1988, and reexamined them between June 1992 and March 1993. Data from 208 cases were collected. Median patient age was 44 years (range 14 to 78) at the time of diagnosis, and 51 years (range 19 to 86) at reexamination. Length of follow-up ranged from 48 to 151 months (median 92) and was longer than 10 years in 26 patients (12.5%). Reexamination included a careful interview, physical examination, complete blood count, screening for HIV infection, determination of platelet-bound IgG, and, in persistently thrombocytopenic patients, autoimmunity markers and routine laboratory investigations. RESULTS: A total of 121 patients with fewer than 50 x 10(9) platelets per liter received an initial treatment with prednisone (PDN) at a dosage of 1 mg/kg of body weight for 1 month. Refractory or relapsed cases underwent splenectomy and/or other therapeutic modalities. In 87 patients with greater than 50 x 10(9) platelets per liter, no therapy was scheduled. An initial complete response to PDN was observed in 38.8% cases. A sustained complete remission (CR) lasting more than 6 months with no maintenance therapy was attained in 18.7%. At the time of last follow-up only 11 of these patients remained in CR. Sixty-three patients underwent splenectomy. Forty-seven (74.6%) had a CR, with 41 achieving a prolonged recovery (> 6 months). Twelve other cases attained a sustained partial remission. Long-lasting recoveries were observed in 7 other cases following alternative treatments. Spontaneous remissions occurred in 8 of 87 untreated cases after observation periods of 6 months or more. Eleven deaths were recorded (6 women and 5 men, median age 73), but only 5 were attributable to thrombocytopenia. At last control, 43 patients were in complete remission and free from therapy, and 52 were still on therapy. Four thrombocytopenic patients had laboratory features and a clinical history consistent with an autoimmune disease. CONCLUSIONS: This analysis of ITP in adults suggests that splenectomy remains the most effective treatment. The majority of patients who undergo splenectomy can have a CR for many years, while only a minority of those who do not have this therapeutic modality or fail it are likely to attain similar results. The long-term prognosis of ITP is benign even in refractory cases. Spontaneous remissions can be observed in a significant percentage of untreated patients (about 9%). The development of overt autoimmune diseases is relatively uncommon. Particular attention should be given to the management of ITP in the elderly, where bleeding episodes of the central nervous system tend to occur more frequently.

[Antiphospholipid antibodies: their prevalence, clinical significance and correlation with cytokine levels in acute myeloid leukemia and non-Hodgkin's lymphoma]. / Anticorpi anti-fosfolipidi: prevalenza, significato clinico e correlazione con i livelli di citochine nella leucemia mieloide acuta e nel linfoma non-Hodgkin.

Forty-five patients with de novo acute myeloid leukemia (AML) and 22 patients with newly-diagnosed non-Hodgkin lymphoma (NHL) were investigated. Tests for antiphospholipid antibodies (APA) included the measurement of anticardiolipin antibodies (aCL) with a solid-phase immunoassay, and the detection of the lupus-like anticoagulant (LA) activity. Fifteen patients with AML (33.3%) and 9 patients with non-Hodgkin lymphoma (40.9%) presented elevated APA at diagnosis, as compared to 3 out of 174 persons of the control group (p < 0.0001). APA titles became normal in all patients responding to treatment, whereas non-responders retained elevated levels. In addition, 2 patients (1 with AML and 1 with NHL) who had normal APA at diagnosis and were either refractory to treatment or in relapse, subsequently developed LA and/or aCL positivity. At presentation, the mean levels of IgG- and IgM-aCL in patients were not significantly different from controls, and concordance between aCL and LA results reached just 12%. With regard to the clinical course, we were not able to detect any statistically significant difference between patients with normal and elevated APA. Pretreatment concentrations of IL-6 and TNF-alpha in AML, and soluble form of the receptor for interleukin-2 (sIL-2r) in NHL were found significantly elevated compared to controls (p < 0.001, p = 0.011 and p = 0.016 respectively). In addition, the levels of these cytokines correlated with IgG-aCL at the different times of laboratory investigations. These results demonstrate that APA may have a role as markers of disease activity and progression in some haematological malignancies.

Prevalence and clinical significance of elevated antiphospholipid antibodies in patients with idiopathic thrombocytopenic purpura.

Antibodies against phospholipid antigens (APA) have been demonstrated in idiopathic thrombocytopenic purpura (ITP), but their clinical and pathogenetic significance has remained elusive. In this study we analyzed the prevalence and clinical features of ITP patients with elevated APA. In addition, we prospectively evaluated APA levels after treatment with corticosteroids and compared them with platelet-associated immunoglobulin (PAIgG) titers. We studied 149 patients with newly diagnosed ITP. Of these, 78 had a platelet count less than 50 x 10(9)/L and received an initial treatment with oral prednisone (PDN). In 71 asymptomatic cases with platelet counts between 50 x 10(9)/L and 120 x 10(9)/L, no therapy was scheduled. However, in five of them, the platelet count fell below 50 x 10(9)/L after more than 12 months; these patients were treated with PDN. Tests for APA included the measurement of anticardiolipin antibodies (ACA) with a solid-phase immunoassay and the detection of the lupus-like anticoagulant (LA) activity with coagulation tests that included kaolin-clotting time, dilute Russel's Viper venom time, activated partial thromboplastin time (aPTT), and dilute aPTT. Controls consisted of 174 apparently healthy subjects. Either LA or elevated ACA was seen in 69 patients (46.3%) at diagnosis. LA and ACA were both elevated in 24 cases (16.1% of the overall patient population and 34.8% of patients with high APA concentrations). No correlation was found between LA ratio values and ACA-IgG or -IgM titers, or between ACA-IgG and ACA-IgM levels. The presence of these antibodies was not associated with sex, age, platelet count, or the severity of hemorrhages. PAIgG was detected in 106 of 127 cases (83%). Again, no relationship was observed with clinical parameters or with APA levels. However, all cases with elevated APA also had increased PAIgG. With regard to the clinical course, we were not able to detect any significant difference between patients with normal and elevated APA. An initial complete response to prednisone treatment was observed in 43 of 83 cases (51.8%), with 13 (15.7%) achieving a prolonged complete remission. APA levels were not significantly modified after PDN therapy and on relapse. We conclude that APA positivity is a common finding in patients with ITP and does not select a category with different clinical features. APA levels are not influenced by immunosuppressive therapy with steroids and are not related to the activity of the disease. Therefore, we do not support a role for APA in the pathogenesis of ITP.

Erythema multiforme during GM-CSF therapy.

A 52-year-old Caucasian man treated with granulocyte-macrophage colonystimulating factor (GM-CSF) developed a cutaneous eruption on legs and ankles with clinical and histologic features of erythema multiforme. Laboratory studies indicated that the eruption occurred at the time of peripheral blood lymphocyte recovery and that it was coincidental with serum peaks of interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6) and tumour necrosis factor-alpha. We postulate that GM-CSF provoked erythema multiforme in a predisposed individual as a consequence of either an inappropriate cytokine secretion or of an abnormal amplification mechanism following lymphocyte recovery.

Antiphospholipid antibodies: prevalence, clinical significance and correlation to cytokine levels in acute myeloid leukemia and non-Hodgkin's lymphoma.

This study was designed to explore the prevalence and clinical significance of elevated antiphospholipid antibodies (APA) titres in patients affected by acute myeloid leukemia (AML) and high-grade non-Hodgkin's lymphoma (NHL). We also analyzed possible correlations with circulating levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and the soluble form of the receptor for interleukin-2 (sIL-2r). Nineteen patients with de novo AML and 14 patients with newly-diagnosed NHL were investigated. Tests for APA included the measurement of anticardiolipin antibodies (ACA) with a solid-phase immunoassay, and the detection of the lupus-like anticoagulant (LA) activity. Five patients with AML (26.3%) and 5 patients with NHL (35.7%) presented elevated APA at diagnosis, as compared to 3 of 174 persons of the control group (p < 0.0001). APA titres became normal in all patients responding to treatment, whereas non-responders retained elevated levels. In addition, 6 patients (4 with AML and 2 with NHL), who had normal APA at diagnosis and were either refractory to treatment or in relapse, subsequently developed LA and/or ACA positivity. At presentation, the mean levels of IgG- and IgM-ACA in patients were not significantly different from controls, and concordance between ACA and LA results reached just 30%. With regard to the clinical course, we were not able to detect any statistically significant difference between patients with normal and elevated APA. Pretreatment concentrations of IL-6 and TNF-alpha in AML, and sIL-2r in NHL were found significantly elevated compared to controls (p = 0.003, p = 0.009 and p = 0.024 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Soluble factors levels in the initial staging of high-grade non-Hodgkin's lymphomas.

Plasma levels of several soluble factors were assayed in 31 untreated patients with high-grade non-Hodgkin's lymphomas (NHL). The results showed statistically significant higher average levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-2 receptor (IL-2r) and transferrin receptor (TF-r) in NHL patients compared to controls (p = 0.045, p = 0.047, p = 0.020, p = 0.026 and p = 0.033 respectively). IL-2, IL-2r and TF-r levels were found more elevated in Stages III/IV than in Stages I/II (p = 0.031, p = 0.016 and p = 0.048 respectively), whereas IL-6 concentrations were higher in patients presenting B symptoms (p = 0.011). Significant correlations were found between the erythrocyte sedimentation rate (ESR) and IL-6 (r = 0.681), and between beta 2 microglobulin (B2-m) and IL-2r (r = 0.622).