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• W1998511009 abstract "Splenectomy is effective in refractory, severe HIV-related thrombocytopenia [1–5]. However, this procedure is still considered with caution by many clinicians because of the operative risks, the subsequent possibility of overwhelming infections, the late relapse of thrombocytopenia in some patients [1,6,7] and, potentially more dreadful, the suggested risk of further immunological impairment [8,9]. For this reason, alternative, less invasive, procedures have been proposed [10,11], including low-dose splenic irradiation [12], which would allow the clinician to obtain a reduction of splenic sequestration/destruction of platelets but simultaneously to retain some residual splenic function, thus reducing the immunological risks. No studies have systematically compared splenectomy and splenic irradiation in severe, refractory, HIV-related thrombocytopenia for their efficacy and immunological impact. We have carried out a retrospective, multicentre, chart-review trial, in which all the patients meeting pre-established inclusion criteria and treated in the three participating centres with either splenectomy [2] or low-dose splenic irradiation [12] were enrolled. Inclusion criteria were: long-lasting, symptomatic, severe thrombocytopenia (< 25 × 109/l), refractory to previous treatments (zidovudine; corticosteroids; vincristine; danazol; high-dose intravenous IgG; high-dose dexamethasone or IFN-α) and a CD4 cell count higher than 50 × 106/l. Exclusion criteria were: reduced bone marrow megakaryocytes; liver cirrhosis; granulocytes lower than 3 × 109/l or haemoglobin lower than 110 g/l; allergy to pneumococcal vaccine or to cephalosporins. Patient records were analysed for a follow-up of 6 months by independent reviewers. Before surgery all patients underwent platelet transfusions; in addition, all patients undergoing splenectomy received anti-pneumococcal vaccination and perioperative antibiotic prophylaxis. Splenic irradiation was administered by a 10 MV linear accelerator, after definition of splenic volume by ultrasonography, by giving a total dose of 10 Gy, using an isocentric parallel pair field technique, in five to 10 fractions over a 1–3 week period. Twelve patients were identified, six treated with splenectomy and six with splenic irradiation. The patients belonging to the two treatment groups were well balanced at recruitment, with no significant difference for any of the clinical or laboratory variables and no imbalance in the severity of disease (Table 1).Table 1: Clinical characteristics at recruitment of the study population. Splenectomy increased the platelet count significantly at 3 and 6 months, whereas low-dose splenic irradiation was ineffective (Fig. 1). One single patient in the splenic irradiation group showed some increase in platelet counts (20 × 109/l at baseline, 39 × 109/l at 3 months and 48 × 109/l at 6 months). One of the patients unresponsive to irradiation was later (after 7 months) splenectomized, with an increase in platelet count from 12 × 109/l (after irradiation) to 195 × 109/l (18 months after splenectomy). The failure of splenic irradiation in this study, which is at variance with some reports [12–14], is not explained by differences in the irradiation procedure, because the dose used in this study (10 Gy) was similar or higher than those (5–10 Gy) used in the majority of the previous case series [12–15]. On the other hand, a careful analysis of previous reports shows that the correction of thrombocytopenia was achieved in only a fraction of patients (in seven out of 25), it was mostly only partial (platelet count < 100 × 109/l) and it was almost always only transient (≤ 6 months) [12–14,16]. This study shows that splenic irradiation is not effective in raising the platelet count in severe, long-lasting, HIV-related thrombocytopenia refractory to medical treatment. Whether this unsatisfactory response to splenic irradiation is peculiar to HIV-related thrombocytopenia compared with immune thrombocytopenia [17] remains to be established. Concerning the immunological parameters, CD4 cell counts increased slightly in the splenectomized group, whereas they decreased in splenic-irradiated patients so that at 3 and 6 months significantly more CD4 T cells were evident in splenectomized patients (Fig. 1). CD8 cell counts increased in splenectomized and decreased slightly, but significantly, in splenic-irradiated patients, thus at 3 and 6 months significantly more CD8 cells were evident in the splenectomized group (Fig. 1). Finally, HIV-RNA copies did not change significantly in either group (Fig. 1).Fig. 1.: Platelet counts, CD4 positive T cell counts, CD8 positive T cell counts, and HIV viral loads at baseline, 3 and 6 months after the therapeutic procedure in the two treatment groups. ▪ Splenectomy; &◆ splenic irradiation. Values represent the mean ± SD (n = 6). Asterisks indicate a significant difference between the two groups (t-test for independent samples, *P < 0.05, **P < 0.005); # indicates a significant difference compared with basaline (analysis of variance for repeated measures followed by Studentized Neuman–Keuls test). All statistical analyses were two tailed. For HIV RNA viral loads below the detection limit, a value equal to the detection limit was arbitrarily assigned.It thus seems that splenic irradiation has a negative impact on immunological status, and indeed this procedure has been reported to reduce the number of circulating normal T lymphocytes in patients with chronic B lymphocytic leukaemia [18]. Splenectomy has a complex impact on immunological parameters which, however, appears to be mostly positive. In fact, CD4-positive T cells, CD8-positive T cells and CD8 cell percentages were all significantly increased at 6 months after surgery compared with baseline, and these value were significantly higher than those observed at the same follow-up in the splenic-irradiated subjects. In conclusion, with the limitations of small numbers and the retrospective collection of data, although involving all patients at the participating centres, this study shows that there is no place for splenic irradiation among the therapeutic options for patients with severe, symptomatic, long-lasting, HIV-related thrombocytopaenia, refractory to medical treatment [19]. Splenectomy is an efficacious and safe treatment that should be reserved for symptomatic patients at high risk of serious bleeding, with severe (< 25 × 109/l) and long-lasting (≥ 12 months) thrombocytopenia unresponsive to medical treatment. Acknowledgements The authors would like to thank the following persons for extracting data from the patients’ records: Drs Giampaolo Bucaneve, Fiorella Mecozzi, Marina Polidori and Laura Stoppini. The help of Dr S. Momi with the analysis of data and the preparation of illustrations is gratefully acknowledged. Massimo Marronia Marina Silva Sinnonec Giuseppe Landoniod Cynthia Aristeie Enrico Boschettib Adriano Lazzarinc Paolo Greseleb" @default.
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• W1998511009 title "Splenic irradiation versus splenectomy for severe, refractory HIV-related thrombocytopenia: effects on platelet counts and immunological status" @default.
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