Data on the long-term treatment of myeloma bone disease with bisphosphonates are scanty. In a prospective pilot trial we evaluated the effect of long-term parenteral administration of dichloromethylene bisphosphonate (Clodronate), in addition to standard chemotherapy, in 30 patients with active myeloma bone disease. Patients were treated with a mean of 4 courses (range 2-8) of Clodronate: 300 mg/day i.v. for seven days followed by 100 mg/day i.m. for 10 days, administered at a mean interval of 4 months (range 3-6). The median follow-up was 24 months (range 8-36). Clodronate reduced bone pain rapidly and significantly, and reduced the mean values of the biochemical indices of bone resorption to within normal limits; these effects were maintained throughout the follow-up. In three hypercalcemic episodes serum calcium became normal after 2-5 days of treatment with Clodronate. No toxic or side effects were noticed. The occurrence of skeletal morbidity in patients treated with Clodronate was compared with that observed in the control group of myeloma patients (p less than 0.001) in severe bone pain as well as in the incidence of new osteolytic lesions and pathological fractures (p less than 0.001). Supportive Clodronate therapy contributes significantly in controlling the progression of myeloma bone disease.

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107 determinations of α₁-acid-glycoprotein (α₁S), haptoglobin (Hp) and complement fraction 3 (C₃) were made in 85 consecutive patients with Hodgkin’s disease, both in acute phase (77 measurements) and in complete remission (30 measurements). Only α₁S and Hp showed much higher levels in untreated disease than in remission, and elevation of α₁S in activity of the disease is correlated to advanced stages and – less significantly – to severe histology. The ability of α₁S, Hp and C₃ to discriminate between activity and remission was compared with that of erythrocyte sedimentation rate (ESR), α₁S-globulinaemia (α₂), fibrinogen-aemia (Fb), plasma copper (Cu) and iron (Fe), all data being collected at the same point in time in each patient. The well-known discrimination ability of combined Cu and Fe (75%) can be further improved by α₁S (81%) much more than by Hp, C₃, ESR, α₂ and Fb singly computed and nearly up to the maximum allowed by the eight indexes together (82%).

Purpose. To report on the risk of interstitial pneumonia (IP) in newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated with dose-dense CHOP-14 plus rituximab supported with pegfilgrastim. Patients and Methods. In this phase II study of feasibility and toxicity, 50 patients with DLBCL, aged 18–70, with no major co-morbidities were treated with standard-dose CHOP every 14 days, preceded on day 1 by rituximab at the dose of 375 mg/m2 (R-CHOP-14) and followed on day 3 by pegfilgrastim (6 mg per cycle). No cotrimoxazole prophylaxis had been devised. In patients developing symptoms of possible pulmonary complications, standard chest X-ray, high-resolution CT scan and broncho-alveolar lavage (BAL) were performed, together with complete blood count, serum immunoglobulins level and CD4 lymphocytes determination. Cytomegalovirus (CMV) infection was investigated, as well, by either CMV-antigen or CMV-IgM determination. Results. Overall, 7 patients (14%) developed IP within 120 days from the start of therapy; their median age was 60 years (range: 22–65). Four patients developed IP after the end of therapy and no patient was neutropenic at the onset of pulmonary symptoms; the median absolute neutrophil count was 5.7x109/l (range: 3.0–11.1). Moderate or severe dyspnea and fever were constant. Diagnosis was made in all patients through high-resolution chest CT scan which documented bilateral interstitial damage, while standard chest X-ray was apparently normal in 5 of 7 cases. Clinical conditions did allow for BAL in 5 patients; Pneumocystis carinii (PC) infection was microbiologically documented in three patients, while hemorragic bronchiolitis and lymphocytic diffuse pneumonia were diagnosed in one case, each. CMV infection tests were invariably negative. Patients developing PC infection had low serum gammaglobulin levels (390, 790, and 200 mg/dL) and a lower than 400/mL number of circulating CD4+ lymphocytes (168, 359 and 190/mL, respectively). Wide spectrum antibiotics were administered in all cases until documentation of the etiology; PC infection was then treated with cotrimoxazole and low-dose steroids and lymphocytic pneumonia with high-dose steroids. The outcome was favorable in all patients, with no sequelae. Conclusions. Our data indicate a significant risk of IP in patients with DLBCL treated with R-CHOP-14 and supported with pegfigrastim; most worrisome is the risk of PC infection in the absence of cotrimoxazole prophylaxis. The risk of IP does not correlate with neutropenia, but it correlates with a low level of gammaglobulins and of circulating CD4+ lymphocytes. In this setting of patients, cotrimoxazole prophylaxis is mandatory and high-resolution CT scan and BAL should be done as early as possible at the onset of respiratory symptoms.

Background The early identification of Raynaud’s phenomenon (RP) suspected secondary to a connective tissue disease (CTD) is fundamental to treat promptly the related organ manifestations. Among the potential clinical complications, eye involvement is often overlooked, even if it is known that systemic vascular dysregulation is able to induce vasospasm in the retinal vessels and retinal blood flow abnormalities. Objectives To evaluate the presence of vascular eye involvement measuring the choroidal and macular thickness in a cross-sectional cohort of RP suspected secondary to a CTD. Methods Consecutive RP suspected secondary to a CTD were enrolled. Inclusion criteria were: 1) RP; 2) nosymptoms/signs suggesting a CTD; 3) major capillary abnormalities at nailfold capillaroscopy and/or positive anti-nuclear antibodies (ANA) by IFF and blotting; 4) no visual symptoms. Patients underwent a complete ocular examination including: best corrected visual acuity, slit lamp biomicroscopy, intraocular pressure measurements and fundus examination. Choroidal thickness (CT) was assessed using the Zeiss Cirrus Spectral Domain Optical Coherence Tomography (SD-OCT) with enhanced depth imaging (EDI) scan system at the fovea and up to 1 mm at intervals of 2 mm from the fovea in the superior, inferior, nasal and temporal choroid; central fovea thickness (CFT) was also measured. 26 healthy, sex and aged-matched, subjects were analysed as control group. Statistical analysis was performed by Mann-Whitney test. Results 20 subjects were included in the study (mean age 51.85 years, 18 females), 75% (15 out of 20) had positive ANA test, of whom 11 (55%) with anti-centromere pattern. 13 out of 20 (65%) showed scleroderma pattern at nailfold capillaroscopy. Slit lamp biomicrocopy was within normal limits in all patients and fundus examination revealed normal arterial and venous vessels with no capillary abnormalities. The mean best corrected visual acuity was 20/40 and the mean intraocular pressure measurement was 14 mmHg. Choroidal thickness measurements were significantly thinner than healthy control in the subfoveal region (mean 256.82 µm vs 313.22 µm; p=0.0031). Similar results were observed in the superior, temporal and nasal sectors of the retina at 1 and 2 mm from the fovea: inner superior (mean 250.48 vs 293.22; p=0.0014), outer superior (mean 241.77 vs 293.3; p= 0.016); inner nasal (mean 231.97 vs 297.44; p= 0.0003), outer nasal (mean 185.12 vs 289; p= 0.0001); inner temporal (mean 262.91 vs 313.22; p=0.0031), outer temporal (mean 241.21 vs 282.56; p= 0.045). Choroidal thickness was overall thinned in the inferior sectors: inner inferior (mean 258.29 vs 293.15; p= 0.0003), outer inferior (mean 252.29 vs 289.89; p= 0.067). CFT was also thinner in RP suspected secondary to a CTD than in healthy controls (mean 257.44 vs 275.18; p=0.0061). Conclusions Thinner choroidal thickness was observed in RP suspected secondary to a CTD without evident visual symptoms. This suggests a compromisedchoroidal perfusion, and the presence of an early ...