Low Dose Rituximab in Adult Patients with Idiopathic Thrombocytopenic Purpura.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1305-1305 ◽  
Author(s):  
Francesco Zaja ◽  
Marta L. Battista ◽  
Maria T. Pirrota ◽  
Salvatore Palmieri ◽  
Michela Montagna ◽  
...  
Keyword(s):  
Platelet Count ◽  
B Cell ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Low Dose ◽  
Standard Dose ◽  
Adult Patients ◽  
Fixed Dose ◽  
Stepwise Logistic Regression ◽  
Significant Activity ◽  
Thrombocytopenic Purpura

Abstract Rituximab 375 mg/sqm weekly for 4 weeks has significant activity in patients with idiopathic thrombocytopenic purpura (ITP). In this setting, different biological and clinical evidence suggests the possible use of lower doses of Rituximab. Twenty-eight adult patients, median age 43 years (range 16–71 years), with previously treated, active and symptomatic ITP were treated prospectively with Rituximab at the fixed dose of 100 mg iv weekly for 4 weeks. Exclusion criteria were positive HIV, HBsAg and pregnancy test, any B-cell lymphoprolipherative disease or other malignancies. Response assessment was evaluated considering the rate of overall and complete responses (OR = platelet count ≥ 50 x 109/L; CR= platelet count ≥ 100 x 109/L and discontinuation of steroid therapy, if present), the time to response (TTR; time necessary to reach a platelet count ≥ 50 x 109/L), the time to complete response (TCR; time necessary to reach a platelet count ≥ 100 x 109/L) and the duration of response. B-cell count and pharmacokinetics (PK) were monitored and related with clinical outcome. Stepwise logistic regression was used to assess whether response was associated with age, gender, diagnosis-Rituximab interval and basal CD20+ve lymphocytes. Results were considered statistical significant when P ≤ 0.05. All patients completed the therapeutic program receiving the four infusions of Rituximab as scheduled, none experiencing short term toxicity. All patients achieved B-cell depletion. OR and CR were achieved in 21/28 (75%) and 12/28 (43%) patients, respectively. CR rate was associated with younger age (OR=0.92 CI95%[0.85;0.99]). The median TTR and TCR were 31 and 44 days, significantly longer then those observed with standard dose in patients with similar characteristics (Haematologica2003;88:538). After a median follow-up of 11 months (range 3–18), 7/21 (33%) patients relapsed, and 3 needed further treatments. PK data showed a concentration time-course profile of Rituximab that was super-imposable, once corrected for the difference in the dose, to that observed previously in patients treated with standard dose, diseases with a median value of 4.1 micrograms/milliliter (range 0–11.9), 12 weeks after the start of treatment. In patients with ITP, low dose Rituximab led to short and mid-term response rates similar to standard dose but with slower timing of response.

A Multi-Centre, Single-Arm, Open-Label Study Evaluating the Safety and Efficacy of Fixed Dose Rituximab in Patients with Refractory, Relapsing or Chronic Idiopathic Thrombocytopenic Purpura (R-ITP1000 Study) and Exploring Rituximab Response with the FcGammaR3A Polymorphisms

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1157-1157
Author(s):  
Huyen Tran ◽  
Jamie P Nourse ◽  
Rod Lea ◽  
Timothy A. Brighton ◽  
Andrew Grigg ◽  
...  
Keyword(s):  
Platelet Count ◽  
B Cells ◽  
Autoimmune Disease ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Response Rate ◽  
Fixed Dose ◽  
Contingency Table Analysis ◽  
Open Label ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp

Abstract Abstract 1157 Background: Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by low platelet count and mucocutaneous bleeding. Approximately 25–30% of adult patients with acute ITP develop chronicity; 30% of chronic ITP patients become refractory to corticosteroids and require additional therapy. As B-cells play an important pathophysiological role in autoimmune disease, rituximab, a chimeric anti-CD20 monoclonal antibody which depletes CD20+ B-cells has been used in chronic ITP. A dosing regimen based on lymphoma therapy (375 mg/m2 weekly × 4) has shown efficacy (∼38% Overall Response Rate-ORR) in adults in this context. Whether this schedule is optimal in autoimmune disease, in which the burden of pathological B-cells is low, is unknown. In this study we explored an abbreviated rituximab schedule, consistent with the approved rheumatoid arthritis dosing. We also explored inherited polymorphisms in FcGammaR3A (FCGR3A) as it has been shown to correlate with response to rituximab. AIM: The primary objective of this study was to determine the ORR, at week 8, among adults (≥ 18 years) with chronic or relapsing ITP (platelet count > 10 × 109/L and ≤ 50 × 109/L) according to the ASH guidelines, who received rituximab 1000 mg intravenous (IV) on days 1 and 15. A laboratory sub-study investigated the relationship between the FCGR3A-V/F158 polymorphisms and response to rituximab. METHOD: Patients received planned doses of rituximab and were followed-up for a minimum of 12 weeks. Assessments and procedures at mandatory follow-up visits occurring on weeks 8, 12, 26, 39 and 52 included physical examination, vital signs, FBC and serum chemistry. ORR was defined as the proportion of patients achieving a Complete Response (CR, platelet count > 150×109/L) or Partial Response (PR, > 50 × 109/L) at weeks 8 and 12 with 2 consecutive measurements, confirmed at least 2 weeks apart. Simon's 2-stage design was used to determine if the ORR was more likely to be ≤ 38% or ≥ 50%. At least 50 out of 108 responders (46%) were required to conclude, with 95% confidence and 80% power, that the ORR was likely to be ≥ 50%. FCGR3A-V/F158 genotyping was performed using allele specific polymerase chain reaction (PCR) techniques previously described (Koene HR, et al. Blood 1997;90:1109–1111). Distribution of polymorphisms was correlated according to response rate, as pre-defined in the study protocol and the frequencies compared using the standard chi-squared test for independence via contingency table analysis. Results: Out of the 124 patients recruited, 2 did not receive study medication and 14 did not have a platelet count ≤ 50 × 109/L within 7 days of first rituximab dose and were excluded from analysis. At week 8, the confirmed ORR was 44% (47/108 patients); 9% and 34% of whom achieved CR and PR respectively. At week 12, 9 patients had a missing platelet count value and therefore response rate data was available for 99 patients; ORR=46% (45/99). Treatment was well tolerated with no safety signals reported. Genotyping data was available for 87 patients. Correlations between FCGR3A-V/F158 polymorphisms and response to rituximab showed that 32% (16/50) non-responders [minor or no response] and 19% (7/37) responders [CR or PR] were homozygous for the FCGR3A-F/F158 genotype; p=0.21. Conclusion: The ORR is comparable with published studies using a more frequent rituximab schedule. Although not statistically significant, non-responders were more likely to be homozygous for the FCGR3A-F/F158 genotype than responders. Further investigations are warranted to determine whether the same response can be achieved with single/lower dosing rituximab, if longer/ more intense dosing might improve ORR and if maintenance rituximab may improve durability of responses. Disclosures: Thurley: ROche Products Australia: Employment.

Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications

Blood ◽  
2004 ◽  
Vol 104 (9) ◽  
pp. 2623-2634 ◽  
Author(s):  
Kiarash Kojouri ◽  
Sara K. Vesely ◽  
Deirdra R. Terrell ◽  
James N. George
Keyword(s):  
Platelet Count ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Surgical Complications ◽  
Current Knowledge ◽  
Case Series ◽  
Complete Response ◽  
Adult Patients ◽  
Complication Rates ◽  
Thrombocytopenic Purpura

AbstractSplenectomy has been a standard treatment for adult patients with idiopathic thrombocytopenic purpura (ITP) for more than 50 years. However, the durability of responses, the ability to predict who will respond, and the frequency of surgical complications with splenectomy all remain uncertain. To better interpret current knowledge we systematically identified and reviewed all 135 case series, 1966 to 2004, that described 15 or more consecutive patients who had splenectomy for ITP and that had data for 1 of these 3 outcomes. Complete response was defined as a normal platelet count following splenectomy and for the duration of follow-up with no additional treatment. Forty-seven case series reported complete response in 1731 (66%) of 2623 adult patients with follow-up for 1 to 153 months; complete response rates did not correlate with duration of follow-up (r = -0.103, P = .49). None of 12 preoperative characteristics that have been reported consistently predicted response to splenectomy. Mortality was 1.0% (48 of 4955 patients) with laparotomy and 0.2% (3 of 1301 patients) with laparoscopy. Complication rates were 12.9% (318 of 2465) with laparotomy and 9.6% (88 of 921 patients) with laparoscopic splenectomy. Although the risk of surgery is an important consideration, splenectomy provides a high frequency of durable responses for adult patients with ITP. (Blood. 2004; 104:2623-2634)

Rituximab Induces High Response Rate and Prolonged Remission in Chronic Idiopathic Thrombocytopenic Purpura (ITP): A Retrospective Analysis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3956-3956 ◽  
Author(s):  
Salahattin M. Sanal ◽  
Melissa J. Hanson ◽  
Morris S. Dees ◽  
Linda S. Sylvester ◽  
Joseph W. Sullivan ◽  
...  
Keyword(s):  
Platelet Count ◽  
Partial Response ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Response Rate ◽  
Complete Response ◽  
Significant Activity ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Hodgkin's Lymphomas

Abstract Background: Rituximab is a chimeric monoclonal antibody targeting CD 20+ B lymphocytes (Rastetter et al, 2004). Combination of rituximab with conventional chemotherapeutic agents has become the mainstay of treatment for B-cell Non-Hodgkin’s Lymphomas. The role of rituximab in treatment of immune mediated disorders is currently under investigation. Earlier studies have reported significant responses to rituximab in chronic idiopathic thrombocytopenic purpura patients, who are refractory to steroids and in some cases to splenectomy. (Cooper et al, 2004). Methods: We retrospectively reviewed charts of 15 patients who received rituximab treatment for chronic ITP. All patients had clinical features consistent with chronic ITP and no other etiology was discovered to cause thrombocytopenia; diagnosis of ITP was confirmed by bone marrow examination in 8 patients. Previous treatments for patients in our series included: prednisone (80%), splenectomy (53%), Rho D immune globulin (40%), IV immunoglobulin (33%), danazole (27%), and vincristine (20%). Rituximab dose was 325mg/m2 for all patients, although the number of treatments varied between patients (Table 1). Complete or partial responses to therapy were defined as follows: Platelet count ≥ 150x10(9)/L at 12 weeks following first infusion was a complete response (CR). Platelet count 50–149x10(9)/L at 12 weeks following first infusion was a partial response (PR). Platelet count < 50x10(9)/L was defined as no response (NR). Response at the 12 week interval was not possible in 2 patients; therefore response was defined at the 8 week interval (Table 1). Results: Patient demographics consist of 5:10 male to female ratio with mean age=49.7, median age= 46 and age range=19–83. 10 patients attained a complete response, 3 patients attained a partial response, and 2 patients failed to show any response to treatment. It was possible to follow 12 patients in our series for a sustained duration of rituximab response; 9 patients (75%) showed a response of >6 months in this group. The most significant factor associated with response to rituximab was age, independent of all other variables when logistic regression analysis was utilized (p=0.003, α=0.05, df=1). Additionally, bivariate analysis was significant for age and number of days lapsed (following first infusion) until platelets increase ≥ 100x10(9)/L and was independent of baseline platelet count (p=0.047, α=0.05, df=1). Conclusion: Rituximab has shown significant activity in our series of ITP patients, with an overall response rate of 93%. Our results indicate a direct relationship between younger age and response. The availability of this agent provides another treatment option for chronic ITP, short of splenectomy. Guidelines for ITP may need further modification in view of the promising results with rituximab therapy. Clinical and hematologic characteristics of ITP patients. Age Gender Duration ITP, months No. Rituximab treatments Baseline Plts x10 9 /L Plts, wk 12 Response Duration of response, wks *=platelet count at 8 week timepoint 83 F 122 8 38 50 PR 104 54 F 33 1 10 603 CR 150 31 F 6 2 78 290 CR 25 20 F 6 4 67 264 CR 26 46 F 42 4 22 194 CR 148 26 F 21 4 24 371 CR 33 25 M 18 4 51 297 CR 81 40 F 9 4 72 169 CR 16 19 F 6 4 45 328 CR 13 46 M 109 4 76 150 CR 21 75 M 108 8 57 93 PR 31 75 F 4 3 30 72* PR 8 78 F 21 8 42 25 NR -- 72 M 25 2 74 479 CR 110 55 M 31 2 16 36* NR --

Apoptosis in platelets from adult patients with chronic idiopathic thrombocytopenic purpura

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Long Xie ◽  
Da-Ming Xu ◽  
Xin-Jian Cai ◽  
Ze-Wen Zhang ◽  
Wen-Jun Yu ◽  
...  
Keyword(s):  
Idiopathic Thrombocytopenic Purpura ◽  
Adult Patients ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura
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