Study on the Efficacy and Safety of IGIV3I Grifols (Human Intravenous Immunoglobulin) in Patients Diagnosed with Chronic Immune Thrombocytopenic Purpura.

Abstract Intravenous immunoglobulin (IVIG) products are considered a useful treatment in patients with chronic idiopathic/immune thrombocytopenic purpura (ITP) to prevent bleeding or prior to surgery, when platelet counts have to be rapidly increased. IGIV3I Grifols is a highly purified, unmodified human IgG product whose manufacturing process follows the same basic principles of Flebogamma® (another IVIG manufactured by Grifols in clinical use since 1992). The main differences between both processes are how purification steps are sequentially arranged, and the introduction of two specific steps to inactivate/remove any potential contaminating pathogen (solvent-detergent treatment and sequential nanofiltration through 35 and 20 nm pore size filters), as additional viral elimination steps to pasteurization, already present in Flebogamma®. An open prospective study was planned to investigate the efficacy and safety of IGIV3I Grifols in 20 adult patients with chronic ITP (at least 6 months after diagnosis). Twenty adult subjects were enrolled and 19 patients with chronic ITP in acute phase (platelet counts <20x109/l) were treated. Patients received 0.4 g/kg body weight for 5 consecutive days. Efficacy endpoints were the proportion of patients who reached a platelet count ≥50x109/l, the time taken for the platelet count to reach the target level and the duration of response. Regression of haemorrhages was documented during the first 14 days of follow-up. Safety parameters including adverse events (AEs), laboratory determinations and vital signs were regularly monitored. The follow-up of patients ended 3 months after first dose of IGIV3I Grifols to determine any change in viral markers for HIV, HCV, HBV and HAV. Results from intention to treat (ITT) population (n=20) and per protocol (PP) population (n=19) are presented. A patient was withdrawn from the study because she did not present an immune idiopathic thrombocytopenic purpura. A total of 14 patients (ITT = 70%; PP = 74%) responded to the study drug. The median time to platelet response was ≥2.5 days and the median number of days in which the platelet count remained ≥50x109/l was ≥7.0 days. For 17 patients (ITT = 85%; PP = 89%) a regression of the bleeding episodes was reported on day 14. Eight out of 20 patients presented 21 AEs potentially related to the study drug (16 mild and 5 moderate). Headache and fever (6 cases each), hypertension (2), decreased blood pressure (2) or hypotension (1), blood pressure fluctuation (1), thrombocythaemia (1), bradycardia (1) and asthenia (1) were AEs potentially related to study drug. No patients experienced clinically significant abnormalities in the laboratory values (haematology and renal and hepatic functions) and no patients changed their virological markers during the follow-up of the study. The results show that IGIV3I Grifols is safe and adequate to achieve a safe platelet count in patients with refractory chronic ITP.

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Efficacy and Safety of a New Intravenous Immunoglobulin Product in Patients with Chronic Immune Thrombocytopenic Purpura.

Blood ◽

10.1182/blood.v110.11.1307.1307 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1307-1307

Author(s):

Tadeusz Robak ◽

Abdulgabar Salama ◽

Lidia Kovaleva ◽

Yaroslava I. Vyhovska ◽

Simon Davies ◽

...

Keyword(s):

Platelet Count ◽

Adverse Events ◽

Intravenous Immunoglobulin ◽

Primary Endpoint ◽

Immune Thrombocytopenic Purpura ◽

Efficacy And Safety ◽

Platelet Response ◽

Thrombocytopenic Purpura ◽

Platelet Counts ◽

Chronic Itp

Abstract Background Intravenous immunoglobulin (IVIG) is an accepted treatment for immune thrombocytopenic purpura (ITP). A new liquid 10% human IgG preparation stabilized with proline at a pH of 4.8 (trade name: Privigen) was recently developed. It can be stored at room temperature and is therefore always ready to use. Here we report its efficacy and safety in patients with chronic ITP. Patients and Methods Fifty-seven patients with chronic ITP and a platelet count below 20 x 109/L were included in this open-label, single arm, multi-center Phase III trial. IVIG was given at a dose of 1 g/kg on 2 consecutive days at a maximum infusion rate of 4 mg/kg/min. A subset (56.1%) of the patients received premedication (acetaminophen or diphenhydramine) to avoid adverse events. The primary endpoint was the platelet response rate, defined as the percentage of patients showing an increase in platelet count to ≥50 x 109/L within 7 days of the first infusion. Secondary endpoints included platelet counts at specified time points, time to platelet response, duration of platelet response, and regression of hemorrhages at different bleeding sites. Safety was evaluated by the frequency and severity of adverse events. Results The primary endpoint, an increase in platelet counts to ≥50 x 109/L, was achieved by 81% of the subjects (95% CI: 69–89%). The highest median platelet count (149 x 109/L) was observed on day 8. Median time to response was 2.5 days, with 43% of subjects responding within 1 day. Median duration of platelet response (days with platelet count ≥ 50 x 109/L) was 15.4 days. Regression rates for various bleeding sites ranged from 78% to 100%. Regression of bleeding correlated with increases in platelet counts. Adverse events were reported in 52 (91%) subjects. The most common adverse event was headache (67%), the incidence and severity of which was attenuated by premedication with acetaminophen/diphenhydramine. There were 3 serious adverse events, one of which (aseptic meningitis) was considered related to the study medication. Conclusions The present study has shown the safety and significant efficacy of a novel, 10% liquid, ready for use IVIG preparation, in patients with chronic ITP. A rapid increase in platelet counts to a level where severe bleeding episodes become more unlikely was seen in the majority of patients, as expected with IVIG given at 1 g/kg on 2 consecutive days. The increase in platelet counts was associated with a regression of bleeding. Adverse events were generally mild to moderate in severity, corresponded to those expected with IVIG, and could be prevented with premedication.

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Rituximab Treatment in Childhood Chronic Immune Thrombocytopenic Purpura (ITP).

Blood ◽

10.1182/blood.v114.22.4461.4461 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4461-4461 ◽

Cited By ~ 1

Author(s):

Ji Yoon Kim ◽

Kun Soo Lee ◽

Hyoung Jin Kang ◽

Hoon Kook ◽

Hong Hoe Koo ◽

...

Keyword(s):

Platelet Count ◽

Immune Thrombocytopenic Purpura ◽

Medical Records ◽

Conflicts Of Interest ◽

Complete Response ◽

Thrombocytopenic Purpura ◽

Chronic Itp ◽

New Treatment ◽

Lost To Follow Up

Abstract Abstract 4461 Background Immune thrombocytopenic purpura (ITP) is characterized by mucocutaneous purpura and thrombocytopenia caused by circulating anti-platelet auto-antibodies. ITP is usually self-limited in children, but around 20% of patients will develop chronic ITP. The conventional treatments for children chronic ITP include intravenous immunoglobulin (IVIG), corticosteroid therapy, anti-D immune globulin, or splenectomy. Some children with chronic ITP are refractory to these treatments and nowadays begun to try new treatment agents such as rituximab. Rituximab as a monoclonal antibody to CD-20, has shown promising reports to these patients with refractory chronic ITP in adults groups and a few children groups. We investigated this study to evaluate the efficacy of rituximab for childhood chronic ITP in Korea. Methods We reviewed the questionnaires and medical records about the clinical progresses and results in thirteen children from eight clinical institutes, retrospectively. Complete response (CR) was considered if the platelet count was > 100,000/uL. Results Thirteen patients with chronic thrombocytopenia who had been treated with rituximab were investigated. Two patients were lost to follow-up after rituximab. Finally eleven patients were evaluated including one patient with Evans syndrome. Median age was 6.5 year (range, 0.5 ∼ 15.4). Median platelet count at baseline was 13,700/uL (3,000∼46,000). All patients had been treated with conventional therapy including IVIG and steroids. One had done splenectomy. Median follow-up duration was 2.8 years (1.1-5.9). Among 11 patients, CR was achieved in 3 patients (27%). Their platelet count prior to rituximab were < 10,000/uL. They were treated as the regimen of 375 mg/m2/dose weekly for 4 doses. Time from the first rituximab dose to achievement of complete response was 3.9, 4.9 and 5.7 weeks respectively. One patient who was relapsed 6months after the first course of rituximab was received second course of rituximab using the same regimen and achieved a new CR at 9.3 weeks after. There were no reports about severe complication or interruption of medication. Conclusions Therefore, we suggest that rituximab is effective treatment choice in childhood refractory chronic ITP and well tolerated. Disclosures: No relevant conflicts of interest to declare.

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Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura: results of a prospective multicenter phase 2 study

Blood ◽

10.1182/blood-2008-01-131029 ◽

2008 ◽

Vol 112 (4) ◽

pp. 999-1004 ◽

Cited By ~ 164

Author(s):

Bertrand Godeau ◽

Raphael Porcher ◽

Olivier Fain ◽

François Lefrère ◽

Pierre Fenaux ◽

...

Keyword(s):

Immune Thrombocytopenic Purpura ◽

Phase 2 ◽

Open Label ◽

Thrombocytopenic Purpura ◽

Platelet Counts ◽

Chronic Immune Thrombocytopenic Purpura ◽

Chronic Itp ◽

Phase 2 Trial ◽

Phase 2 Study

Abstract Whether rituximab could effectively and safely avoid splenectomy for adults with chronic immune thrombocytopenic purpura (ITP) remains unresolved. A multicenter, prospective, open-label, single-arm, phase 2 trial was conducted to assess rituximab safety and efficacy in adult splenectomy candidates with chronic ITP. Sixty patients with chronic (≥ 6 months) ITP and platelet counts less than 30 × 109/L received a weekly intravenous infusion of rituximab (375 mg/m2) for 4 weeks. All other ITP treatments were stopped. A good response was defined as a platelet count 50 × 109/L or more, with at least a doubling of the initial value at 1 and 2 years after the first rituximab infusion. Patients who required another treatment during follow up were considered nonresponders. Sixteen patients experienced transient side effects that necessitated treatment discontinuation for only 1. Good 1-year responses were obtained in 40% of the patients (24/60 [95% confidence interval: 28%-52%]). At 2 years, 33.3% (20/60 patients) had good responses and 6.7% (4/60) had sustained platelet counts of 30 × 109/L or more without treatment. Thirty-six (60%) patients failed to respond; 25 underwent splenectomy. Based on these results, rituximab was an apparently safe and effective splenectomy-avoiding option in some adults with chronic ITP. This trial is registered at http://clinicaltrials.gov as NCT00225875.

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Successful Treatment of An Elderly Patient with Refractory Chronic Immune Thrombocytopenic Purpura with Combination Therapy of Rituximab and Corticosteroids: A Case Report

Blood ◽

10.1182/blood.v116.21.4686.4686 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4686-4686

Author(s):

Yun Ling ◽

Xiangshan Cao ◽

Xinyu Qian

Keyword(s):

Platelet Count ◽

Combination Therapy ◽

Immune Thrombocytopenic Purpura ◽

Conflicts Of Interest ◽

Response Duration ◽

Autoimmune Disorder ◽

Thrombocytopenic Purpura ◽

Platelet Counts ◽

Chronic Itp ◽

Duration Of Response

Abstract Abstract 4686 Immune thrombocytopenic purpura (ITP) is an autoimmune disorder. A corticosteroid, usually prednisone is often the first line treatment for ITP. However, the problem is that about 70 percent of adult patients experience a relapse after discontinuation of corticosteroids. And approximately 20–30% of patients with chronic ITP do not respond to corticosteroids therapy. Rituximab has been proven effective in refractory chronic ITP, but the timing of response is slower than expected, at least three months might be necessary to observe an effect. And the response duration to rituximab remains relatively short in some patients. So, sometimes it is necessary to use combination therapy including rituximab, according to different patient conditions. Here, we report an 82-year-old man with chronic ITP who had thrombocytopenia (platelet count <10 × 109/L) for more than 6 months and relapsed on a prednisone taper. He presented sustaining blood-tinged sputum, bleeding in skin and steroid-induced diabetes, the result of short-term prednisone. He didn't want splenectomy and other immune suppressive drugs. His blood glucose got control after insulin therapy. We gave the patient intravenous infusions of rituximab 375 mg/m2 weekly for 4 weeks combined with dexamethasone (10 mg intravenously weekly for 4 weeks). After first dose of dexamethasone followed by rituximab, within 24 hours his platelet count had increased to 65 × 109/L and bleeding symptoms were significantly improved. During the next 3-week period of treatment, his platelet counts fluctuated between 30 × 109/L and 60 × 109/L. And then the platelet count dropped back to a minimum of 19 × 109/L. Consider the slow responses to rituximab and prevention of bleeding, we still gave the patient maintenance therapy with 15mg prednisone daily and he had been no bleeding. Two months after starting rituximab and dexamethasone, his platelet counts began to gradually recover to normal. Although we need to further observe the patients's duration of response, this case suggests that combination therapy of rituximab and corticosteroids may be a promising treatment for refractory chronic ITP. Disclosures: No relevant conflicts of interest to declare.

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Efficacy and Safety of a New Intravenous Immunoglobulin in Adult Subjects with Chronic Idiopathic Thrombocytopenic Purpura.

Blood ◽

10.1182/blood.v106.11.3984.3984 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3984-3984

Author(s):

Heinz Leibl ◽

Gyula Varga ◽

Zuzana Volkova ◽

Zoltan Gasztonyi ◽

Antonin Hlusi ◽

...

Keyword(s):

Platelet Count ◽

Adverse Events ◽

Intravenous Immunoglobulin ◽

Idiopathic Thrombocytopenic Purpura ◽

Analysis Data ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Data Set ◽

Thrombocytopenic Purpura ◽

Chronic Itp

Abstract Idiopathic thrombocytopenic purpura (ITP) is a common clinical disorder of immune regulation leading to phagocytic destruction of platelets. Intravenous immunoglobulin (IGIV) has been used successfully to increase platelet count in patients with ITP. Baxter has developed a new IGIV (IGIV,10%), a 10% liquid immunoglobulin preparation with 3 dedicated virus reduction steps integrated into the manufacturing process. The efficacy and safety of this product was assessed in a prospective multi-center study in adult chronic ITP patients with platelet counts of 20x109/L or less. A total of 23 subjects were enrolled and treated for 2 to 5 days with a total dose of 2 g/kg. Of 21 subjects included in the per-protocol analysis data set, 15 responded to treatment (71.4%), achieving a platelet count of at least 50x109/L by Day 8. Fourteen of 15 responders reached this level by Day 5. The median duration of platelet response was 25 days and the highest median platelet count in the responders was 182x109/L. A total of 81 infusions were administered to the 23 subjects in the safety analysis data set. Among the 40 non-serious adverse events related to the use of the study drug, 35 were mild, 3 were moderate, and 2 were severe. The most frequent related adverse events were headache and pyrexia. The results of this study demonstrate that IGIV, 10% TVR Solution is effective in the treatment of adult subjects with chronic ITP and has an excellent safety profile.

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Rituximab Is an Alternative to Splenectomy in Adults with Chronic Immune Thrombocytopenic Purpura: Results of a Multicenter Prospective Phase 2 Study.

Blood ◽

10.1182/blood.v108.11.478.478 ◽

2006 ◽

Vol 108 (11) ◽

pp. 478-478 ◽

Cited By ~ 10

Author(s):

Bertrand Godeau ◽

Olivier Fain ◽

Raphael Porcher ◽

Francois Lefrere ◽

Pierre Fenaux ◽

...

Keyword(s):

Platelet Count ◽

Immune Thrombocytopenic Purpura ◽

Single Stage ◽

Phase 2 ◽

Initial Value ◽

Durable Response ◽

Thrombocytopenic Purpura ◽

Chronic Itp ◽

One Year

Abstract Background : Rituximab, a monoclonal anti-CD20 antibody, is a promising therapeutic agent for adults with immune thrombocytopenic purpura (ITP). Pooling results of the published literature suggest that rituximab achieves an initial response in about 50 % of adults with chronic ITP, with a 25–40% rate of sustained response. However, heterogeneity of patient pre-treatment status, short follow up and bias due to retrospective studies limit the interpretation of the data. Objective : To assess the safety and efficacy of rituximab in adults with chronic ITP (duration ≥ 6 months) and platelet count ≤ 30x109/L candidate to splenectomy. Methods : a multicenter prospective open-label single arm phase 2 trial designed according to Fleming’s single stage procedure was conducted. After informed consent, non splenectomized adults received 4 weekly intravenous infusions of rituximab at a dose of 375 mg/m2. All other ITP treatments were stopped. Treatment success was defined as a platelet count ≥ 50 x109/L with at least a 2 fold increase of the initial value at one year after the first rituximab infusion. Patients who received another treatment during follow up were considered as non responders. A sample size of at least 56 patients was calculated by Fleming’s single-stage design to ensure 90 % power for proving lack of efficacy if the true complete response rate was below 25%. Results : Sixty consecutive patients (40F/20M) were included over a 21 months period. Mean age was 48 years (range 18–84). Mean ITP duration was 4.8 years. Mean platelet count at inclusion was 16±10x109/L. All but one patient, in whom reversible serum sickness disease was diagnosed after 2 infusions, received 4 infusions of rituximab. Fifteen other patients experienced transient side effects that did not lead to treatment discontinuation. No patient was lost to follow up. Success was achieved in 40 % (24/60 patients) (95 % confidence interval 28% to 52%) and was found significantly different from 25% (p=0.007). Among the 24 long term responders, platelet count at one year was ≥ 150x109/L in 18 and between 50 and 150 x109/L in 6. Two other patients (3%) had and incomplete response defined as a platelet count at one year between 30 and 50 x109/L but at least 2 fold the initial value. Thirty four (57%) patients failed to respond and amongst them, 18 have already undergone splenectomy. Conclusion: rituximab appears to be a safe and good splenectomy-sparing strategy in adults with chronic ITP leading to a significant and durable response in 40% of the cases.

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Does treatment with intermittent infusions of intravenous anti-D allow a proportion of adults with recently diagnosed immune thrombocytopenic purpura to avoid splenectomy?

Blood ◽

10.1182/blood.v99.6.1922 ◽

2002 ◽

Vol 99 (6) ◽

pp. 1922-1927 ◽

Cited By ~ 60

Author(s):

Nichola Cooper ◽

B. Michael R. Woloski ◽

Erin M. Fodero ◽

Maria Novoa ◽

Melissa Leber ◽

...

Keyword(s):

Platelet Count ◽

Immune Thrombocytopenic Purpura ◽

Maintenance Treatment ◽

Thrombocytopenic Purpura ◽

Platelet Counts ◽

L 14 ◽

Lost To Follow Up ◽

Primary Predictor ◽

All Treatment

Abstract This study explored whether repeated infusions of intravenous anti-D could allow adults with recently diagnosed immune thrombocytopenic purpura (ITP) who had failed an initial steroid course to postpone and ultimately avoid splenectomy. Twenty-eight Rh+, nonsplenectomized adults with ITP diagnosed within 1 to 11 months and platelet counts 30 × 109/L (30 000/μL) or below were enrolled. Anti-D was infused whenever the platelet count decreased to 30 × 109/L (30 000/μL) or below. “Response” was defined as a platelet increase of more than 20 × 109/L (20 000/μL) to more than 30 × 109/L (30 000/μL) within 7 days of treatment. Patients were a median 3.5 months from ITP diagnosis at enrollment and had received a median of 2 previous therapies, including prednisone in 26 of 28 cases. They were followed for a median 26 months. A total of 93% responded to their initial infusion of anti-D, and 68% repeatedly responded with counts maintained above 30 × 109/L (30 000/μL) using anti-D alone. Currently, 12 (43%) of 28 patients have been off all treatment for more than 6 months without undergoing splenectomy, 6 maintaining counts above 100 × 109/L (100 000/μL). Seven continue on treatment, 8 underwent splenectomy, and 1 was lost to follow-up at 10 months. One patient discontinued anti-D because of toxicity. Patients with platelet counts at least 14 × 109/L (14 000/μL) at enrollment were more likely to discontinue treatment (P < .05). Anti-D was an effective maintenance treatment for two thirds of Rh+, nonsplenectomized adults with ITP who had failed an initial steroid course. Intermittent infusions of intravenous anti-D allowed more than 40% of these adults to avoid splenectomy and to achieve stable platelet counts off all therapy, even after many months of treatment. Platelet count at study entry was the primary predictor of outcome.

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Response to Intravenous Immunoglobulin Predicts Splenectomy Response in Children With Immune Thrombocytopenic Purpura

PEDIATRICS ◽

10.1542/peds.111.1.87 ◽

2003 ◽

Vol 111 (1) ◽

pp. 87-90

Author(s):

Derick Holt ◽

Justin Brown ◽

Kelly Terrill ◽

Robert Goldsby ◽

Rebecka L. Meyers ◽

...

Keyword(s):

Intravenous Immunoglobulin ◽

Immune Thrombocytopenic Purpura ◽

Predictive Value ◽

Chart Review ◽

Objective Response ◽

Retrospective Chart Review ◽

Poor Response ◽

Thrombocytopenic Purpura ◽

Excellent Response ◽

Chronic Itp

Objective. Response to intravenous immunoglobulin (IVIG) has been shown to predict response to splenectomy in adults with immune thrombocytopenic purpura (ITP). However, reports in children have been inconsistent. We sought to determine whether response to IVIG is predictive of response to splenectomy in children. Methods. Thirty-two assessable children were identified by a retrospective chart review. Response was graded according to previously published criteria as follows: “excellent” (platelets >150 000 within 1 week), “good” (platelets between 50 000 and 150 000), and “poor” (platelets <50 000). “Response” refers to both splenectomy and IVIG, and response to splenectomy was counted only when it was durable. Results. Twenty-one of 23 patients who had a good or excellent response to IVIG also had an excellent response to splenectomy. Six of 9 patients who had a poor response to IVIG also had a poor response to splenectomy. Response to IVIG was a sensitive predictor of response to splenectomy in 88% of patients. Response to IVIG had a specificity of 75%, a positive predictive value of 91%, and a negative predictive value of 67%. Response to prednisone and length of time to splenectomy were not correlated with splenectomy response. Conclusions. These results suggest that response to IVIG is predictive of response to splenectomy in children with chronic ITP. This correlation may be of value in deciding whether a splenectomy should be performed in children with chronic ITP.

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Quantitation of platelet-associated IgG by radial immunodiffusion

Blood ◽

10.1182/blood.v57.4.809.809 ◽

1981 ◽

Vol 57 (4) ◽

pp. 809-811 ◽

Cited By ~ 24

Author(s):

BS Morse ◽

D Giuliani ◽

M Nussbaum

Keyword(s):

Platelet Count ◽

Immune Thrombocytopenic Purpura ◽

Radial Immunodiffusion ◽

Thrombocytopenic Purpura ◽

Platelet Counts ◽

Normal Platelet ◽

Serum Igg ◽

Acute Itp ◽

Igg Level

Abstract Platelet-associated IgG (PAIgG) was measured by a simple radial immunodiffusion technique using washed solubilized platelets and commercially available immunoplates. Subjects with normal platelet counts had PAIgG levels of 1.5--7.0 fg/platelet. Subjects with idiopathic immune thrombocytopenic purpura (ITP) had levels ranging from 5.7 to 70.5 fg/platelet. All patients with recurrent ITP and 85% of patients with acute ITP had elevated PAIgg. Elevated PAIgG was also found in 17% of patients with recovered ITP, 40% of patients with SLE and thrombocytopenia, 57% of patients with thrombocytopenia occurring during the course of septicemia, and 100% of patients with IgG myeloma in whom the serum IgG level was clearly elevated, regardless of the platelet count. The results are similar to reports that used more complex techniques.

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Safety and Efficacy of Laparoscopic Splenectomy in Patients with Refractory Immune Thrombocytopenic Purpura. A Long-Term Survey

Blood ◽

10.1182/blood.v112.11.4548.4548 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4548-4548

Author(s):

Nicola Cascavilla ◽

Matteo Scaramuzzi ◽

Michele Nobile ◽

Matteo Dell’Olio ◽

Antonietta Pia Falcone ◽

...

Keyword(s):

Platelet Count ◽

Immune Thrombocytopenic Purpura ◽

Laparoscopic Splenectomy ◽

New Drugs ◽

Thrombocytopenic Purpura ◽

Safety And Efficacy ◽

Haematological Response ◽

Short And Long Term

Abstract Background: Despite the popularity of splenectomy has decreased dramatically in the past few years, the surgical approach remains the best therapy for patients with refractory Immune Thrombocytopenic Purpura (ITP) in terms of high and durable rate of response (Vesely et al, Ann Intern Med2004; 140: 112). The recent introduction of anti-CD20 antibodies and thrombopoietins of second generation such as AMG 531 and Eltrombopag may have a relevant role (Kuter et al, Lancet2008; 371: 362) but their long-term safety and efficacy have not been still established. In parallel with new drugs, there has been an evolution in the surgery of splenectomy as well (Dolan et al, Am J Hematol2008; 83: 93). Actually, the laparoscopic surgery is considered the standard approach and the ITP represents the most common indication in 50–80% of all the laparoscopic splenectomies. Methods: The aim of this study is to evaluate the long-term complete and partial haematological response (CR + PR), as well as the short and long-term complications, of 40 patients (30 females and 10 males; median age: 38 years - range 6–71) with unresponsive ITP after one or more medical approaches and underwent laparoscopic splenectomy at our Institution from 1999 through 2006. The 40 patients accounted for 22.2% of 181 patients diagnosed in those years. An abdominal CT scan to evaluate the presence of accessory spleens was performed in all cases. All patients received meningococcal, pneumococcal and haemophilus influenzae vaccine one week before splenectomy. For 4 or 5 days before splenectomy the patients were treated with high doses of intravenous Immunoglobulins. Anti-thrombotic prophylaxis was performed with low molecular weight heparin (LMWH) for 10 days and afterwards with cardioaspirin (ASA) if the platelet count exceeded 500x10E9/L. Results: No cases required conversion to laparotomic splenectomy. An accessory spleen was found in 2 patients (5%). Immediate haematological response rate was of 100%. At date, after a median follow-up of 78 months (range 28–112 months), 36 patients (90%) remain in CR or PR with a platelet count more than 50x10E9/L and 2 patients are taking ASA. Four patients (10%) relapsed; out of which, 2 patients have a platelet count less than 10x10E9/L. Short and long-term mortality rate was 0%. Immediate postoperative complications rate was 5%: we observed 2 cases of hemoperitoneum related to a trocar’s tube and to an active bleeding, respectively, both resolved with new laparoscopic approach. The mean postoperative hospital stay was 4,5 days (range 4–8). Neither cases of bacterial sepsis in the postoperative or during the follow-up time, nor cases of splenic-portal vein thrombosis (SPVT) and no cases of neoplasms occurred. Conclusions: Our experience suggests that laparoscopic splenectomy is an excellent approach to patients with refractory ITP in terms of safety, efficacy and costs. With respect to laparotomic splenectomy, the use of laparoscopy is likely to make the splenectomy even safer and therefore suitable for a larger number of patients. Undoubtedly there is a great expectation for the new drugs (Rodeghiero et al, Am J Hematol2008; 83: 91) and we agree that only controlled comparative clinical trials (Vianelli et al, Haematologica2005; 90: 72) will be able or not to say a final word and to challenge the role of splenectomy.

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