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

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

Blood ◽

10.1182/blood.v108.11.3956.3956 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3956-3956

Author(s):

Antonio Julia ◽

Lidia Kovaleva ◽

Ignacio Alberca ◽

Fernando Hernandez ◽

Svetlana Loria ◽

...

Keyword(s):

Blood Pressure ◽

Platelet Count ◽

Intravenous Immunoglobulin ◽

Immune Thrombocytopenic Purpura ◽

Study Drug ◽

Efficacy And Safety ◽

Thrombocytopenic Purpura ◽

Platelet Counts ◽

Chronic Itp

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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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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Demographics and Long-Term Outcome of Incident Immune Thrombocytopenic Purpura: A Twelve-Years Nationwide Population-Based Study in Taiwan

Blood ◽

10.1182/blood.v126.23.3259.3259 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3259-3259

Author(s):

Bor-Sheng Ko ◽

Grace Hui-Min Wu ◽

Yu-Chiao Wang ◽

Ming Yao ◽

Churn-Shiouh Gau ◽

...

Keyword(s):

General Population ◽

Immune Thrombocytopenic Purpura ◽

Population Based ◽

Male Gender ◽

Term Outcome ◽

Thrombocytopenic Purpura ◽

Long Term Outcome ◽

Chronic Itp

Abstract Background and Objectives Immune thrombocytopenic purpura (ITP) is a rare disease, and the epidemiology and long-term outcome are still rarely characterized. This study is then aimed to provide a population-based assessment for the demographics and outcome about ITP in Taiwan, an island in Southeastern Asia with around 23 million inhabitants. Material and Methods This study used claims data from Taiwan's National Health Insurance Research Database (NHIRD). The database included information from a nationwide, mandatory-enrollment and single-payer healthcare system with more than 99% coverage rate in Taiwan since March, 1995. To address adequate medical history tracking and outcome follow-up, only those patients with the first ITP diagnosis from Jan 1st, 2001 to Dec 31st, 2012 were included. Incident ITP was identified first with ICD-9 codes; but those cases with codes for potential ITP-confounding diseases within 6 months from the first ITP code were excluded. Next, only those patients with meaningful pharmacological treatment or splenectomy within 3 months were included in the final analysis. Chronic ITP was defined for those with ICD-9 ITP codes and continuous drug exposure for more than 3 months, or with rituximab or splenectomy. Sex- and age-matched cohorts with 1:10 ratio were selected from Taiwan general population for survival comparison. Results Of the 30673 patients with ITP codes from Jan 1st, 2001 to Dec 31st, 2012, 11437 were identified as incident ITP. The mean age was 42.9+/-27.5 y/o, and 5445 (47.6%) cases had Charlson Comorbidity Index (CCI) score more than 2. The average incidence was 4.16 per 100,000 person-year, and the details are shown in Table 1. The incidence for female was higher than that for male (4.97 vs. 3.38 per 100,000 person-year), and the incidences across the age represented a U-shape distribution, with the highest ones in those aged 0-9 y/o and more than 70 y/o (7.21 and 13.3 per 100,000 person-year, respectively). Some geographic distribution of the incidences existed, with the highest in central part and the lowest in Eastern part of Taiwan (5.33 and 2.64 per 100,000 person-year, respectively). Secondary causes could be identified in 3560 (31.0%) cases, and malignant neoplasma (1743, 49.0%) were most frequently noted. Viral hepatitis B or C were found in 785 (22.1%) cases. Chronic ITP was diagnosed during follow-up in 29.1% (n=3324) of incident ITP patients. Those incident ITP patients aged 0-9 y/o (431/2169 vs. 2893/9268, p<0.001) or male gender (1118/4697 vs. 2206/6740, p<0.001) had a less chance to develop chronic ITP. As compared with the matched cohort from general population, the 10-yr survival rate was significantly inferior for all ITP patients, no matter in those aged below 20 y/o (96.9+/-0.5% vs. 98.8+/-0.1%, p<0.0001) or above 20 y/o (62.5+/-0.8% vs. 83.2+/-0.2%, p<0.0001), as in Figure 1. For chronic ITP, the disadvantaged 10-yr survival rates persisted (for age below 20 y/o: 96.5+/-1.0% vs. 98.6+/-0.2%, p<0.0001; for age above 20 y/o: 72.7+/-1.3% vs. 86.7+/-0.4%, p<0.0001, as in Figure 2). Elder age, male gender and high CCI scores predicted worse survival in multi-variate analysis. Conclusions This study is the largest population-based epidemiology report at nationwide scale till now. Not only the results can provide a valuable demographic description for ITP in Eastern Asia, but also they confirm an inferior long-term outcome for ITP patients, which necessitates more attention to their health care. SD: standard deviation Table 1. Table 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Tang: Novartis: Consultancy, Honoraria.

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One year follow-up of children and adolescents with chronic immune thrombocytopenic purpura (ITP) treated with rituximab

Pediatric Blood & Cancer ◽

10.1002/pbc.21757 ◽

2009 ◽

Vol 52 (2) ◽

pp. 259-262 ◽

Cited By ~ 35

Author(s):

Brigitta U. Mueller ◽

Carolyn M. Bennett ◽

Henry A. Feldman ◽

James B. Bussel ◽

Thomas C. Abshire ◽

...

Keyword(s):

Children And Adolescents ◽

Immune Thrombocytopenic Purpura ◽

Thrombocytopenic Purpura ◽

Chronic Immune Thrombocytopenic Purpura ◽

One Year

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Prognostic Factors for Immune Thrombocytopenic Purpura Remission after Laparoscopic Splenectomy: A Cohort Study

Medicina ◽

10.3390/medicina55040112 ◽

2019 ◽

Vol 55 (4) ◽

pp. 112

Author(s):

Kwiatkowska ◽

Radkowiak ◽

Wysocki ◽

Torbicz ◽

Gajewska ◽

...

Keyword(s):

Platelet Count ◽

Prognostic Factors ◽

Immune Thrombocytopenic Purpura ◽

Laparoscopic Splenectomy ◽

Univariate Analysis ◽

Multivariate Logistic Regression Model ◽

Hemorrhagic Diathesis ◽

Thrombocytopenic Purpura

Background and Objectives: Laparoscopic splenectomy (LS) has become the gold standard for patients with immune thrombocytopenic purpura (ITP). The total remission rate after splenectomy is 70%–90%, of which 66% is long-term. Despite this high response rate, some patients do not benefit from surgery. It is therefore important to try to identify risk factors for an unsatisfactory clinical response. The aim of this study was to assess long-term outcomes of LS for ITP and identify factors associated with increased disease remission rates. Materials and Methods: We retrospectively studied consecutive patients with ITP undergoing LS in a tertiary referral surgical center prospectively recorded in a database. Inclusion criteria were: Elective, laparoscopic splenectomy for diagnosed ITP, and complete follow-up. The cohort was divided into two groups—Group 1 (G1) patients with ITP remission after splenectomy and Group 2 (G2) patients without remission. There were 113 G1 patients and 52 G2 patients. Median follow-up was 9.5 (IQR: 5–15) years. Results: In univariate analysis, patient’s age, body mass index (BMI), preoperative platelet count, the need for platelet transfusions, and presence of hemorrhagic diathesis were shown to be statistically significant factors. Next, we built a multivariate logistic regression model using factors significant in univariate analysis. Age <41 years (odds ratio (OR) 4.49; 95% CI: 1.66–12.09), BMI <24.3 kg/m2 (OR: 4.67; 95% CI: 1.44–15.16), and preoperative platelet count ≥97 × 103/mm3 (OR: 3.50; 95% CI: 1.30–9.47) were shown to be independent prognostic factors for ITP remission after LS. Conclusion: The independent prognostic factors for ITP remission after LS revealed in our study are: age <41 years, BMI <24.3 kg/m2, and preoperative platelet count ≥97 × 103/mm3. Duration of the ITP and the time of treatment are not related to remission after LS.

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A rare presentation of immune thrombocytopenic purpura

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20214721 ◽

2021 ◽

Vol 9 (12) ◽

pp. 3692

Author(s):

Ponvijaya Yadav ◽

Vijayashree S. Gokhale ◽

Rupesh Parati ◽

Keyuri Mehta

Keyword(s):

Platelet Count ◽

Lupus Erythematosus ◽

Immune Thrombocytopenic Purpura ◽

Liver Function Tests ◽

Bone Marrow Examination ◽

Severe Thrombocytopenia ◽

Rare Presentation ◽

Thrombocytopenic Purpura ◽

Hematologic Disorder

Immune thrombocytopenic purpura (ITP) is defined as a hematologic disorder, characterized by isolated thrombocytopenia without any apparent cause. Some patients may be diagnosed during routine blood investigations or may present with bleeding diathesis. Treatment required for moderate to severe thrombocytopenia or those with bleeding manifestations. We present a case of 43 year old male, sputum positive pulmonary tuberculosis on isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E) (HRZE) with persistent thrombocytopenia. He developed hepatitis hence isoniazid (INH) and rifampicin were stopped. He had fever, rash, purpura, hematuria and blood tinged sputum with platelet count of 10,000. 4 random donor platelets (RDPs) given. He suffered from mild COVID-19 infection and recovered in 2 weeks but platelets remained low. Bone marrow examination was suggestive of ITP. Inspite of steroid therapy no improvement was seen. Later was treated with injection romiplostim, and started on systemic lupus erythematosus (SLE) regimen for tuberculosis and discharged with regular follow up. Last platelet count being 1,20000/dl, liver function tests normal and now restarted on HRZE.

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Use of the Platelet Indices for Differential Diagnosis of Pediatric Immune Thrombocytopenic Purpura (ITP)

Blood ◽

10.1182/blood.v112.11.4557.4557 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4557-4557

Author(s):

Hisaya Nakadate ◽

Miho Kaida ◽

Shinsuke Furukawa ◽

Masahiro Ishii ◽

Masaaki Higashihara

Keyword(s):

Differential Diagnosis ◽

Platelet Count ◽

Blood Cell ◽

Immune Thrombocytopenic Purpura ◽

Large Cell ◽

Thrombocytopenic Purpura ◽

Platelet Indices ◽

Cell Parameters ◽

Chronic Itp ◽

Cell Analyzer

Abstract Introduction: The prognosis of pediatric immune thrombocytopenic purpura ( ITP ) has a favorable prognosis, about 80 % of ITP children will be cured in 6 months with or without therapy, the rest of patients develop to chronic ITP. However, it is difficult to predict the course of this disease at the time of diagnosis. Recent advances of automated blood cell analyzer enable to measure various blood cell parameters. Among these parameters, platelet indices such as mean platelet volume (MPV), platelet size deviation width (PDW) and platelet-large cell ratio (P-LCR) has brought about some information for thrombocytopenia. We studied the significance of such platelet indices in the differential diagnosis of immune thrombocytopenic purpura ( ITP ) and their ability to discriminate the clinical courses of ITP. Methods: Ninety-three patients were enrolled this study at our institution from 2004 to 2006. Their ages ranged from 1 to 17 years ( media 4.3 years ). Of 93, patients were divided into two goups for analysis, according to the diagnosis of ITP. 34 were diagnosed as ITP and 59 were diagnosed various blood diseases other than ITP. In these 59 non-ITP patients, five were with thrombocytopenia ( platelet count < 100.0 × 109/L ), the other without thrombocytopenia. Of 34 ITP patients, 29 were acute subtype and 5 were chronic. The Sysmex-XE2100 automated blood cell analyzer (Sysmex, Kobe, Japan) was used to measure the blood parameters, including the platelet indices. Results: According to MPV, PDW and P-LCR, there were no significant differences between ITP patients and non-ITP. In children with ITP, there were significant inverse correlations between the platelet count and evaluated parameters, MPV (R2=0.376), PDW (R2=0.26) and P-LCR(R2=0.338). But no significant correlations were found between the platelet count and these evaluated platelet indices in non-ITP. Also, we have found all platelet indices were significantly higher in chronic ITP than in acute ITP. In particular, PDW (9.910 vs 13.080) and P-LCR (21.071 vs 33.220) showed marked differences between the two groups. Conclusions: ITP is considered as a result of hyper-destruction of platelets. Increase of platelet count is regarded as decrease of destruction of platelets. Our data suggested that platelet indices, MPV, PDW and P-LCR showed the useful information for the degree of platelet destruction and the ability to predict the clinical courses of ITP.

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Safety and Efficacy of Romiplostim in Immune Thrombocytopenia (ITP) in the “real-life” : Result of the French Experience in 72 Adults.

Blood ◽

10.1182/blood.v114.22.3519.3519 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3519-3519 ◽

Cited By ~ 1

Author(s):

Mehdi Khellaf ◽

Philippe Quittet ◽

Jean-Francois Viallard ◽

Magda Alexis ◽

Stéphane Cheze ◽

...

Keyword(s):

Platelet Count ◽

Rescue Medication ◽

Real Life ◽

Sustained Response ◽

Platelet Response ◽

Compassionate Use ◽

Safety And Efficacy ◽

Chronic Itp ◽

One Year

Abstract Abstract 3519 Poster Board III-456 Introduction Romiplostim is a thrombopoietic agent that has been unequivocaly demonstrated as highly effective in adult's ITP in prospective studies and has recently been licensed for adults with chronic ITP in USA, Europe, Canada, and Australia. France has been the only country where romiplostim could be given for a compassionate use outside clinical studies from January 2008. The official indication for obtaining romiplostim in this setting was: chronic ITP according to the international criteria and failure or relapse after at least one previous line of therapy regardless the status towards splenectomy. We report here the data on safety and efficacy of the first consecutive 80 ITP patients who have been registered by the French health authorities as receiving the treatment “off-label” and with at least one-year of follow up. Patients and methods The data were retrospectively reviewed using a standardized form. The protocol was approved by local ethical committee. Patients who did not fulfil official indication criteria of compassionate use were excluded (i.e. secondary-ITP). Platelet count was monitored at least monthly during the follow-up. Platelet response was defined as platelet count of 50×109/L or more and a doubling of the pre-treatment count in the absence of any rescue medication within the last 8 weeks. One-year sustained response was defined as a platelet response on at least 2 of the last 3 platelet determinations at month-10-11 and 12. Patients who received rescue medication at any time during the study could not be counted as having a one-year sustained response. Report of adverse events was captured using a standardized form. Results Among the 80 patients, 8 were actually excluded from the analysis (6 with secondary ITP and 2 have been misdiagnosed as having ITP). The analysis was then conducted on 72 patients (43 females) with a median age of 60 years (20 to 91). The median duration of ITP prior to romiplostim administration was 8.7 years (0.1 to 49) and the patients had received a median of 5 (2 to 12) treatment-lines before romiplostim including: corticosteroids (100%), rituximab (65/72, 90%) and splenectomy (39/72, 54%). Among the 33 non-splenectomized patients, 13 patients were reluctant to undergo splenectomy whereas splenectomy was considered as contra-indicated in 20 of them. At time of romiplostim first administration, median platelet count was 16×109/L (1 to 60) and 48 patients (66%) were receiving a concurrent treatment for ITP, including mainly steroids (n=29) ± immunosuppressive drugs (n=8). A platelet response was observed at least once in 76% (55/72) of the patients. On average, patients who responded at any point during the study had a platelet response during 64% of the time (range: 37 to 100%). Romiplostim was stopped in 28 % (20/72) of patients for either lack of efficacy (n=16), for intolerance (n=1) or because it was administered only transiently in preparation for surgery (n=3). Two patients had died respectively from a septic shock and from an ITP-related intracranial hemorrhage. At one-year of follow up, 52 patients were still receiving romiplostim at a median dose of 6.5 μg/kg per week. This dose remained relatively stable as after the first 12 weeks of treatment, romiplostim could be pursued at a stable dose ± 2 μg/kg in 82% of the cases. Twenty % (14/72) of patients received a rescue medication during the study and 50% (36/72) of the patients had a one-year sustained response. The percentage of one-year sustained response was similar in splenectomized and non splenectomized groups [respectively 54% (21/39) and 45% (15/33), NS)]. Among the 29 patients who responded to romiplostim and who were receiving a treatment at time of romiplostim initiation, 86 % (25/29) had discontinued this medication and a further 7% (2/29) had reduced the dose by at least 25%. Only one patient stopped romiplostim because of an adverse event (headache). The most frequent otherwise reported adverse events were: arthralgia (26%), fatigue (13%) and nausea (7%). A transient thrombocytosis > 400×109/L and > 1000×109/L has been observed in respectively 19% (14/72) and 4% (3/72) of patients. A transient stroke occurred in 2 elderly patients (age > 70 yrs). No deep vein thrombosis occurred. Myelofibrosis was not observed. Conclusion Our study confirms in “real-life” that romiplostim is definitely an effective and safe treatment for severe chronic ITP in both non-splenectomized and splenectomized adults. Disclosures: Godeau: AMGEN: Consultancy.

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