Clinical Study of TJ-137 Tsumura Kami-kihi-to in Patients with Idiopathic Thrombocytopenic Purpura (ITP)

1996 ◽  
Vol 2 (3) ◽  
pp. 213-218
Author(s):  
Nobuo Sakuragawa ◽  
Kojiro Yasunaga ◽  
Takeo Nomura ◽  
Junichi Akatsuka ◽  
Atsushi Kuramoto ◽  
...  
Keyword(s):  
Platelet Count ◽  
Clinical Study ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Adverse Reactions ◽  
Clinical Effect ◽  
Thrombocytopenic Purpura ◽  
New Drug ◽  
Chronic Itp ◽  
Low Incidence

TJ-137 administered to patients with chronic ITP increased the platelet count "slightly" or more in 31.7% of the patients and showed a clinical effect in 40.9% with a rating of "modestly effective" or better. With a low incidence of adverse reactions, TJ-137 is ex pected to be a new drug for the treatment of ITP.

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.

Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura

Blood ◽  
2001 ◽  
Vol 98 (4) ◽  
pp. 952-957 ◽  
Author(s):  
Roberto Stasi ◽  
Adalberto Pagano ◽  
Elisa Stipa ◽  
Sergio Amadori
Keyword(s):  
Monoclonal Antibody ◽  
Platelet Count ◽  
Side Effects ◽  
Partial Response ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Antibody Treatment ◽  
Minor Response ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp

The role of rituximab, a chimeric monoclonal antibody directed against the CD20 antigen, in the treatment of patients with chronic idiopathic thrombocytopenic purpura (ITP) has not been determined. The effectiveness and side effects of this therapeutic modality were investigated in a cohort of 25 individuals with chronic ITP. All patients had ITP that had been resistant to between 2 and 5 different therapeutic regimens, including 8 patients who had already failed splenectomy. Patients were scheduled to receive intravenous rituximab at the dose of 375 mg/m2 once weekly for 4 weeks. Rituximab infusion-related side effects were observed in 18 patients, but were of modest intensity and did not require discontinuation of treatment. A complete response (platelet count greater than 100 × 109/L) was observed in 5 cases, a partial response (platelet count between 50 and 100 × 109/L) in 5 cases, and a minor response (platelet count below 50 × 109/L, with no need for continued treatment) in 3 cases, with an overall response rate of 52%. In 7 cases, responses were sustained (6 months or longer). In 2 patients with relapsed disease, repeat challenge with rituximab induced a new response. In patients with a complete or partial response, a significant rise in platelet concentrations was observed early during the course of treatment, usually 1 week after the first rituximab infusion. No clinical or laboratory parameter was found to predict treatment outcome, although there was a suggestion that women and younger patients have a better chance of response. In conclusion, rituximab therapy has a limited but valuable effect in patients with chronic ITP. In view of its mild toxicity and the lack of effective alternative treatments, its use in the setting of chronic refractory ITP is warranted.

Abstract 171: Acute Sagittal Sinus Thrombosis in an Elderly Patient with Chronic Idiopathic Thrombocytopenic Purpura

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Huimin Wu ◽  
Robert Paulino ◽  
Qi Shi ◽  
Sandhya Samavedam ◽  
Indupriya Pallekonda ◽  
...  
Keyword(s):  
Platelet Count ◽  
Venous Thrombosis ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Sinus Thrombosis ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Platelet Destruction ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Sagittal Sinus ◽  
History Of

INTRODUCTION Chronic idiopathic thrombocytopenic purpura (ITP) is classified as a bleeding disorder that involves autoimmune platelet destruction. Cerebral venous sinus thrombosis in association with chronic ITP is rarely reported in medical literature. CASE PRESENTATION A 70-year-old female with a history of chronic ITP, on prednisone, and coronary artery disease presented with a four-day history of vomiting and diarrhea. Platelet count at the time of admission was 25×10 9 /L. She was treated with i.v normal saline. Platelets fell to 12×10 9 /L and intravenous immunoglobulin (IVIG) was started. Six days later, the patient developed confusion and right sided weakness. Repeat platelet count was 13x10 9 /L. MRI of the brain showed bilateral cortical infarcts suggesting sagittal vein involvement. MRV confirmed thrombosis of the posterior portion of the sagittal sinus. Bone marrow aspirates and core biopsy done to rule out other hematological disorders showed tri-lineage hematopoiesis with adequate marrow megakaryocytes. Hypercoagulable work up was unremarkable. ITP was treated with rituximab and romiplostim. Repeat MRV after 2 weeks showed no new thrombosis or hemorrhage. DISCUSSION ITP is occasionally associated with venous thrombosis. The paradoxical occurrence of venous thrombosis in the setting of ITP is poorly understood. Previous data postulates that platelet destruction releases humoral factors and microparticles, which may increase thrombotic events by the activation of thrombin and other coagulation factors. Other possible mechanisms include endothelial damage by autoantibodies directed against antigens on platelets and endothelial cells. More recently, reports have described IVIG-induced arterial and venous thrombotic complications. Treatment of thrombosis in the setting of ITP is complex and requires in-depth risk/benefit assessment. Our case highlights the dilemma of stroke treatment and prevention predicated on antiplatelet therapies for patients with ITP. Additional studies on chronic ITP associated with thrombosis are needed to establish preventive and treatment guidelines.

Interleukin-10 Gene Polymorphism Reflects the Severity of Chronic Idiopathic Thrombocytopenic Purpura.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2111-2111
Author(s):  
Takayuki Saitoh ◽  
Tetsuhiro Kasamatsu ◽  
Madoka Inoue ◽  
W.H.S. Al-ma’Quol ◽  
Akihiko Yokohama ◽  
...  
Keyword(s):  
Platelet Count ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Response Rate ◽  
Initial Diagnosis ◽  
Control Group ◽  
Severe Thrombocytopenia ◽  
Bleeding Tendency ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Significant Difference

Abstract Introduction: Recent several cytokine studies have shown Th1 polarization of the immune response in Idiopathic thrombocytopenic purpura (ITP) patients. IL–10 is most important factor regulating Th1 and Th2 cytokine synthesis and IL–10 polymorphism has been implicated in autoimmunity and tumorigenesis. We examined the single nucleotide polymorphisms (SNPs) in the promoter regions of the IL–10 genes in patients with ITP, and analyzed the relationship between IL–10 SNPs and clinical features. Patients and methods: Seventy-eight patients (male/female; 19/59, median age; 59.4) diagnosed as chronic ITP and 202 healthy controls were included. ITP with severe thrombocytopenia was defined as thrombocytopenia (platelet count < 10×109/L) at initial diagnosis of ITP. ALL patients gave written informed consent about the study. The platelet count was ranged from 1×109/L to 100×109/L at an initial diagnosis. In addition, 53 patients (67.9%) had bleeding tendency, and 20 patients (25.6%) had severe thrombocytopenia. Steroid treatment was given to 48 patients (61.5%), while splenectomy was applied to only 9 patients (11.5%). Genotyping in IL-10-1082G/A, -819C/T, −592A/C was determined by PCR based technique. Genotype and allele frequencies were compared between the study groups using χ2-test. The characteristics and laboratory features of the ITP patients with each IL-10 promoter polymorphism were compared using X2-tests and student t-tests. Probability values <0.05 were considered statistically significant. Results: The frequencies of the genotypes were as follows: GG (0%), GA (6%), and AA (94%) for −1082; CC (12%), CT (51%), and TT (37%) for −812; CC (12%), CA (51%), and AA (37%) for −592 loci. The frequencies of each haplotype were as follows: ATA/ATA haplotype in 31 patients (40%), ATA/ACC haplotype in 35 patients (45%), ACC/ACC haplotype in 7 patients (9%). No significant differences in the genotype or haplotype frequencies demonstrated between chronic ITP patients and control group. However, patients with −592AA genotypes showed severe thrombocytopenic state at initial diagnosis compared to those with −592CA/CC genotypes (41.4% vs. 16.3%, p=0.01). Furthermore, patients with ATA/ATA haplotype showed severe thrombocytopenic state (38.7% vs. 17%, p=0.03) compared to those without ATA/ATA haplotype. In patients treated with steroids, the overall response rate was 71% with complete response rate of 23.2% and partial response rate of 47.8%. No significant difference was observed in treatment response according to IL-10 polymorphism. Conclusion: In previous investigations, −592AA genotype or ATA/ATA haplotype have been reported to be associated with the lower levels of IL-10 expression. Our data suggest that the group with low IL-10 inducibility (i.e. −592AA genotype, ATA/ATA haplotype) may have more severe thrombocytopenia compared to those with high IL-10 inducibility. It is also reported that low IL-10 inducibility type enhances Th1-type polarization in ITP. Furthermore, Panitsas et al. revealed that higher Th1/Th2 ratio in ITP patients correlate with lower platelet count. Thus, these findings suggest that IL-10 polymorphism reflect the severity of chronic ITP.

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

Blood ◽  
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.

Outcome Measures in Childhood Idiopathic Thrombocytopenic Purpura: Relationship of Bleeding Severity, Quality of Life, and Platelet Count.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1079-1079
Author(s):  
Cindy E. Neunert ◽  
George R. Buchanan ◽  
Victor S. Blanchette ◽  
Dorothy R. Barnard ◽  
Nancy L. Young ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Platelet Count ◽  
Side Effects ◽  
Outcome Measures ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Validation Study ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Bleeding Severity

Abstract Idiopathic thrombocytopenic purpura (ITP) is one of the most common disorders requiring the attention of a pediatric hematologist. The most feared outcome of ITP is intracranial hemorrhage (ICH), which fortunately is a rare occurrence in children. Although a rise in platelet count and presumed reduction in risk of ICH are stated therapeutic aims, it is equally important to identify and understand additional outcome measures which are subject to change in this population. These include health-related quality of life (QoL), treatment side effects, cost, and bleeding severity. A QoL questionnaire for pediatric acute and chronic ITP has recently been developed and validated. During the validation study (Pediatr Blood Cancer, 46:692, 2006), grading of hemorrhage and platelet count were also assessed. This report describes the results of a secondary data analysis using the validation study database. Our purpose was to assess the relationship between bleeding severity and QoL, previously not reported. Ninety children (mean age 9.7 yrs.) with ITP (41 acute, 49 chronic) were prospectively enrolled at six North American centers. Platelet count and bleeding severity were measured at baseline. Bleeding severity was assessed using a modification of a previously published grading instrument (J Pediatr, 141:683–8, 2002) where each patient was assigned a grade of 0 (no bleeding) to 5 (life-threatening bleeding) based on the overall amount of hemorrhage in the previous twenty-four hours. QoL scores were obtained by proxy-report by parents on behalf of their child and self-report by children age seven and older. Parents also reported their own QoL. Using a two- tailed Pearson correlation, the bleeding severity grade was weakly correlated with the platelet count in the children with chronic ITP (r= 0.20, p<0.001), but this relationship did not reach significance for children with acute ITP (r= 0.07, p= 0.09). The severity of bleeding did not correlate with the child’s self-reported QoL in either acute (r= 0.005) or chronic ITP (r=0.03). Parents’ self-assessed QoL did not reflect bleeding severity when their children had either acute (r= 0.03) or chronic ITP (r= 0.006). The parents’ perception of the child’s QoL using a proxy score was also poorly correlated with bleeding severity in acute (r= 0.02) and chronic ITP (r= 0.01). In summary, the bleeding severity score did not correlate with the QoL experienced by either the patient or the family in any setting. These results indicate that many factors in addition to bleeding signs may impact the children and parents, such as anxiety about the disease, length of hospital stay, frequency of visits to the physicians’ office, and medication side effects. These findings suggest that the inclusion of multiple outcome measures enhances the scope of our knowledge and should be used in clinical care and research study design in order to understand the full spectrum of disease impact.

Presentation and Outcome of Idiopathic Thrombocytopenic Purpura in Children: A Single Institution Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4683-4683
Author(s):  
Kari Bradham ◽  
Felicia L. Wilson ◽  
Hamayun Imran
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Conflicts Of Interest ◽  
Laboratory Data ◽  
Bone Marrow Examination ◽  
Published Data ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Increased Risk

Abstract Abstract 4683 PURPOSE: To review the presenting features, response to treatment and outcome in children diagnosed with idiopathic thrombocytopenic purpura (ITP) at the University of South Alabama, Children’s and Women’s Hospital and Specialty Clinic. METHODS: Using ICD code 287.3, data were collected from the specialty clinic’s medical records and hospital database for children diagnosed with ITP between January 2005 and September 2010. Recurrent and chronic ITP were defined as thrombocytopenia recurring within or more than 6 months of diagnosis, respectively. Univariate and multivariate logistic regression analyses were performed to evaluate variables associated with chronic ITP. RESULTS: Eight four patients were identified (M,F 1:1) with an average age of 70 months at diagnosis. Mean platelet count at presentation was 14k. Oral or nasal mucosal bleeding occurred in 19(23%) patients but none experienced a serious hemorrhage. Thirty three (39%) patients had an associated illness prior to diagnosis of ITP. Treatment consisted of intravenous immunoglobulin (IVIG) in 38(45%), WinRho in 11(13%), IVIG or WinRho followed by the other in 20(24%), data not available 8(10%) and no therapy in 7 patients (8%). Average platelet count at discharge and within 2 weeks after IVIG and WinRho was 57k, 337k and 57k, 375 respectively. Forty three (51%) were acute, 17(20%) became recurrent, and 24(29%) became chronic ITP. Bone marrow examination was performed in 26(30%) patients upon subsequent relapse but the diagnosis remained unaltered in all cases. Rituximab therapy was provided to five and splenectomy was performed in 7 patients. Four patients failed both modalities, all of whom currently are IVIG dependant. Age <5year (OR 0.12, 95%CI 0.22, 0.67, p=0.01) was protective against development of chronic ITP while platelet count >20k at presentation (OR 6.50, 95%CI 1.35, 31.30, p=0.02) and race other than white (OR 36.63, 95%CI 4.61, 291.09, p=0.001) were found to be significantly associated with the development of chronic ITP. Gender, mean platelet volume, total white cell count, and absolute lymphocyte count had no significant association. CONCLUSION: Our study supports the published data that patients with an initial platelet count >20k, older age and non-white race have an increased risk of progression to chronic ITP. Other published variables had no significant association in our analyses. Response to IVIG and WinRho was no different in our patients while rituximab or splenectomy did not lead to a complete resolution in refractory cases. Since bone marrow examination did not alter the diagnosis in any patient, we suggest that routine performance of this procedure may be omitted when a diagnosis of ITP is consistent with clinical history, physical examination and laboratory data. Disclosures: No relevant conflicts of interest to declare.

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 --

The Influence of Polymorphisms of Interleukin-17F Genes on the Susceptibility and Clinical Significanse of Chronic Idiopathic Thrombocytopenic Purpura.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3428-3428
Author(s):  
Takayuki Saitoh ◽  
Tetsuhiro Kasamatsu ◽  
Akihiko Yokohama ◽  
Hiroshi Handa ◽  
Norifumi Tsukamoto ◽  
...  
Keyword(s):  
Platelet Count ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Initial Diagnosis ◽  
Severe Thrombocytopenia ◽  
Single Nucleotide ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Genotype Frequencies ◽  
Significant Difference ◽  
And Control

Abstract Introduction: Recent several cytokine studies have shown Th1 polarization of the immune response in idiopathic thrombocytopenic purpura (ITP) patients. Interleukin-17 F(IL-17F) is a relatively new cytokine that regulates the adaptive and innate immune systems. In vivo studies in murine disease indicate that the Th17 lineage plays a pathogenic role in autoimmune disease. IL-17 polymorphism has been implicated in autoimmunity, including ulcerative colitis and asthma. Polymorphisms were studied, including the coding-region sequence variant single nucleotide polymorphism rs763780 (7488T/C), which causes a His-to-Arg substitution at amino acid 161 (H161R). We examined the single nucleotide polymorphisms (SNPs) in the promoter regions of the IL-17 genes in patients with ITP, and analyzed the relationship between IL-17 SNPs and clinical features. Patients and methods: Seventy-eight patients (male/female; 19/59, median age; 59.4) diagnosed as chronic ITP and 202 healthy controls were included. ITP with severe thrombocytopenia was defined as thrombocytopenia (platelet count < 10X109/L) at initial diagnosis of ITP. ALL patients gave written informed consent about the study. The platelet count was ranged from 1X109/L to 100X109/L at an initial diagnosis. Genomic DNA was isolated from peripheral blood using the DNA Kit (QIAGEN, Hilden, Germany). Genotyping in IL-17F was determined by PCR based technique. Genotype and allele frequencies were compared between the study groups using χ2-test. The characteristics and laboratory features of the ITP patients with each IL-10 promoter polymorphism were compared using χ2- tests and student t-tests. Probability values <0.05 were considered statistically significant. Results: The frequencies of the genotypes were as follows: TT (72%), TC (12%), and CC (16%). No significant differences in the genotype frequencies demonstrated between chronic ITP patients and control group. However, patients with TT/TC genotypes showed severe thrombocytopenic state at initial diagnosis compared to those with CC genotypes (42.2% vs. 23.1%, p<0.05). No significant difference was observed in treatment response according to IL-17 polymorphism. Conclusion: No significant differences in the genotype frequencies demonstrated between chronic ITP patients and control. However, homozygosity of the H161R variant was inversely associated with severity of chronic ITP. Thus, these findings suggest that IL-17 polymorphism reflect the severity of chronic ITP.

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