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As medical therapy for ITP is expanding to include monoclonal antibodies and thrombopoietin mimetic agents, the role and safety profile of surgical therapy needs to be reassessed, taking into consideration the improvements made over the years both in surgical technique and infection prophylaxis and surveillance. For this purpose pts who underwent laparoscopic splenectomy for ITP between July 2000 – when the procedure became standard practice at our Institution - and July 2008 were retrospectively analyzed to evaluate short-term outcome and perioperative complications. Pts were candidate to splenectomy when refractory (platelet counts ≤30 × 109/L) to one or more lines of therapy and/or steroid-dependant. All pts received steroids as first-line treatment. All pts were vaccinated (pneumococcal, haemophilus, meningococcal vaccine) before the procedure. A total of 26 pts (8 females, 18 males) underwent the procedure: 22 had a diagnosis of ITP according to ASH criteria; the remaining 4 had immune thrombocytopenia associated with isolated LAC positivity (1), HCV infection (2), and HCV+HIV co-infection (1). Median age at splenectomy was 46 yrs (range 18–79). At the time when splenectomy was planned, median platelet (plt) count was 19 × 109/L (range 3–197) with 11/26 pts having plt counts ≥ 30 × 109/L either off therapy (3/11) or on chronic steroids (8/11). The remaining 15 pts required pre-operative therapy to improve plt levels: pre-op plt transfusion (1 pt), IVIg (5 pts), HD steroids (dexametasone 40 mg i.v. or metilprednisolone 125 mg i.v.) either alone (3 pts) or combined with IVIg (4 pts); IVIg and plt concentrates (1 pt), HD steroids + IVIg + platelet concentrates (1 pt); 11/15 responded to therapy, while in 4/15 plt counts remained ≤15 × 109/L and received plt concentrates during surgery. At splenectomy median plt count was 62 × 109/L, range 3– 212 × 109/L. Median surgical time was 150′(range 50–240′); in no case the surgical procedure had to be converted to open laparotomy. No significant correlation (Spearman’s rank correlation ρ = − 0.1569; p = 0.4441) was found between plt counts at splenectomy and duration of the surgical procedure. Median post-splenectomy hospital stay was 6 days (range 4–18). All pts received low-molecular weight heparin prophylaxis; no thrombotic complications were recorded. Two pts developed haematoma; pt 1: plts at surgery 4 × 109/L, hospital stay 18 days, no red cell transfusion required; pt 2: platelet at surgery 109 × 109/L, reintervention needed with 4 units of red cells transfused, hospital stay 11 days. Four pts experienced transient post-operative low-grade fever with no concomitant signs of systemic infection. Median platelet counts at discharge from the hospital was 353 × 109/L, range 47–1,056 × 109/L. In our experience no relevant complications followed laparoscopic splenectomy. Open splenectomy in itself is known to be associated with a very low risk of surgical complications, but the laparoscopic technique is nevertheless advantageous to the pts in terms of shorter duration of hospital stay, convalescence and time to return to work. Rituximab (R) and thrombopoietin mimetic agents are being suggested as alternatives to splenectomy in patients failing first line therapy with steroids. However, splenectomy does not compromise the efficacy of R, while administration of R prior to splenectomy may compromise immune response to subsequent pre-surgical vaccination for a long time. This may increase the risk of overwhelming infections in those pts with persistently very low plt counts requiring splenectomy as an emergency procedure. Moreover, potential harmful long-term effects of B-cell depletion in non-oncologic patients need to be considered. Although promising, little information is as yet available on thrombopoietin mimetic agents, but they are a life-long therapy. Therefore it is our belief that the very good safety and long-term efficacy profile of splenectomy still makes this procedure standard second line therapy for ITP.

Introduction Chemotherapy (CHT) administration is a high risk process. In particular, in the Day Hospital (DH) patient setting, the potential toxicity of medications is coupled with some organizational aspects, e.g. rapid patient turnover, multiprofessional involvement, lack of continuity of medical care, which can increase the risk of adverse events. The aim of this study was to evaluate the appropriateness of CHT administration for lymphoprolipherative disease in DH setting and the quality of medical charts, by using clinical audit. Audit is a quality improvement process that allows improvement of patient care and outcome through systematic review of care against explicit criteria and the implementation of change. The following evidence-based criteria were established for reviewing CHT administration: o CHT treatment plan (including histology, stage, goals of therapy, patient’s performance status, co-morbidities, CHT regimen) must be established prior to the initiation of CHT, and reported on medical record o CHT treatment summary (including number of cycles administered, extent of dose reduction and/or delay, reason for treatment delay or discontinuation, major toxicities or unexpected hospitalizations, biochemistry data) must be reported in medical records o Maintaining dose-density and dose-intensity may improve clinical outcome; the appropriate use of G-CSFs, in order to prevent neutropenia-related dose reduction or time delay, is particularly relevant when the intent of treatment is curative or to prolong survival o Inclusion of informed consent form in medical records is recommended, in order to verify the informative process and complete patient identification Patients and methods A random sample of 15% of all CHT courses administered for Lymphoma and Chronic Lymphocitic Leukemia from July 2006 to June 2007 in five Hematological DHs was analysed. A total of 282 courses were examined: 87 ABVD, 122 CHOP(R) and 73 FC(R). We collected data about patients, chemotherapy and medical charts. Patients’ clinical characteristics were similar between participating centres. Dose or time violations were considered significative if exceeding one day or 10% of scheduled timing or dosing, respectively. Results Results are reported in Table 1 and 2 Tab 1: courses with dose reduction or delay CHOP(R) (%) ABVD (%) FC(R) (%) Total (%) Dose reduction 30/122 (24,6) 9/87 (10,3) 5/73 (6,8) 44/282 (15,6) Delay 43/116 36/84 (42,9) 24/73 103/273 (37,7) Tab 2: causes of dose or time violation Dose reduction (%) Delay (%) Extra-hematological toxicity 14/44 (31,8) 6/103 (5,8) Neutropenia 3/44 (6,8) 27/103 (26,2) Infection - 17/103(16,5) Other clinical reasons (age, PS, comorbidity) 17/44 (38,7) 3/103 (2,9) Organizational causes - 25/103 (24,3) Not reported 10/44 (22,7) 25/103 (24,3) Pre-therapy biochemistry was available in 279/282 cycles (99%), while informed consent form was included in 131/282 (46.5%) medical charts. Post-therapy follow up revealed 4 unexpected hospitalizations. Conclusions Three main problems emerged: a lot of patients delayed treatment due to organizational causes (e.g. intermediate radiological restaging, holidays, lack of bed, biochemistry pending); in too many cases medical charts lacked causes of dose reduction (22,7%) or delay (24,3%); could guidelines driven use of G-CSF have prevented neutropenia-related delay? At the end of clinical audit, an action plan should be developed to improve the care process. In our study we induced and supported changes in the CHT administration process by various means: dissemination of educational material (as guidelines), interactive educational interventions, professional reminders, decision support. One year after a re-audit will be performed, in order to assess expected improvement.

Starting from 1980, 182 cases of primary extranodal non-Hodgkin’s lymphoma were diagnosed in our Division. Gastrointestinal NHL were the most frequent: 66 patients (36%), followed by head and neck (42 = 23%), skin(23 =13%), urogenital tract (16 = 9%), CNS (10 =5%), chest (9 = 5%), spleen (7 = 4%), bone (5 = 3%) soft tissues (4 = 2%). Median age was 55,4 (range 20–91); median age was lower in chest, bone and intestinal NHL. 77 patients had stage I disease (48,8%), 74 stage II (46,5%) and 8 patients stage III (5%). In the whole group, 134/182 (73.6%) patients achieved complete remission (CR); CRs were 81.8% in gastroenteric NHL, 75% in urogenital, 69.5% in skin, 66.6% in head and neck. Overall survival in the two most important groups are as follows: head and neck: 61% at 50 months and 55% at 100 months; gastrointestinal tract: at 50 months was 80%, at 100 months 75%. When prognostic factors were considered for the whole group, stage and modified I.P.I. (MIPI) were significantly associated with rate of complete remission and overall survival. Stage I pts had a significantly better rate of complete remission 83.1%, vs. 68.9% for stage II and 37.5% for stage III. Overall survival of stage I pts was significantly better than for patients with stage II or stage III disease (80% vs. 72.5% at 50 months; 80.1% vs. 62.7% at 100 months). Modified International Prognostic Index, MIPI is a score ranging from 0 to 5 according to age (>60), LDH (over normal values), ECOG P.S. (>1), Ann Arbor stage (II or III), extranodal sites (>1). Thirty six patients had a MIPI score of 0, 80 pts MIPI 1, 50 pts MIPI 2 and 16 had a MIPI score of 3 or more. A significant correlation between MIPI and achievement of CR was shown with 88.8% of pts with MIPI 0 achieving CR, 78.5% in MIPI 1, 28% in MIPI 2 and 25% in MIPI 3 or more. Overall survival for the four groups was as follows: 96%, 75%, 62%, 61% at 50 months; 96%, 70%, 54%, 24% at 100 months.