Results of the Russian Registry of Primary Immune Thrombocytopenia in Pediatric Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4643-4643
Author(s):  
Anastasia Shamardina ◽  
Inna Markova ◽  
Tatyana Sycheva ◽  
Elena Volodicheva ◽  
Alexander Rumyantsev ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Disease Onset ◽  
Specific Treatment ◽  
Complete Response ◽  
Second Line ◽  
Second Line Therapy ◽  
Chronic Itp ◽  
Line Therapy ◽  
Clinically Significant

Abstract Study objectives We aim to evaluate disease characteristics and treatment practices of pediatric pts. with Immune thrombocytopenia (ITP) in Russia. Materials and methods The ITP Registry was a multicenter, prospective, observational cohort study. Inclusion criteria: diagnosis of primary ITP, informed consent of the patient/guardians. Exclusion criteria: secondary or congenital thrombocytopenia. Data from medical records were registered in the e-CRF in average every 3 months. Descriptive statistics were used. Patients were registered since June 2011 till June 2014. Results Ninety-three pediatric pts, 46 male (49.5%) and 47 female (50.5%) with a median age 8.4 yrs (range 0.5-17.8) from 5 centers in various regions of Russia were included. The mean observation period reached 17.1 ± 6.5 mo (range1.4 to 28.6 months). Seventy (75.3%) pts had acute and 24.7% pts had insidious disease onset. The presence of trigger factors for ITP development was found in more than half of the cases (in 61.3% of patients), they are listed in Table 1. Table 1. Triggers N % No triggers 36 38.7% Infection 46 49.5% Vaccination 8 8.6% Other 3 3.2% Total 93 100% Median disease duration at enrollment was 1.07 years (range 0 to 16.7 yrs). ITP duration shorter than 5 years at the enrollment was reported in 89.2% pts, up to 1 year - in 43 (46.2%), 1- 5 years - in 40 (43%), 5-10 years - in 8 (8.6%), >10 years - in 2 (2.2%) pts. Newly diagnosed ITP was reported in 35 (37.6 %) pts, persistent ITP - in 12 (12.9 %), chronic ITP - in 46 (49.5 %) pts.Median platelets count was 12,0 x 109/L (range 0.0 - 72.0 109/L). Ninety-two (98%) pts experienced hemorrhagic manifestations during the course of ITP: skin hemorrhages - in 98.9%, oral bleeding - in 15.1%, epistaxis - in 36.6%, gastrointestinal bleeding - in 1.1%, intracranial bleeding - in 1.1%, hematuria - in 1.1%, and other hemorrhages - in 9.7% of pts. Relationship between hemorrhagic syndrome and platelet count at the enrollment is provided in table 2. Table 2. Relationship between hemorrhagic syndrome and platelet count (at enrollment) Hemorrhage highest grade according to WHO Platelet count (visit 1) Total pts / % < 30,000 30,000 -50,000 >50,000 0 3 5.5% 3 5.5% 49 89.1% 55 100% 1 11 40.7% 5 18.5% 11 40.7% 27 100% 2 5 62.5% 0 0% 3 37.5% 8 100% 3 2 66.7% 1 33.3% 0 0% 3 100% Total 21 22,6% 9 9.7% 63 67.7% 93 100% Severe course of ITP after enrollment was observed in 12 (13%) pts (of whose 6 (6.5%) had clinically significant hemorrhage at the disease onset and 6 (6.5%) had new clinically significant hemorrhages during follow-up period. Refractory ITP at enrollment was reported in 9 (9.7%) pts and was associated with the resistance to the first-, second- and subsequent lines of therapy. At enrollment 42 (45.2%) pts received specific treatment for ITP. Before enrollment, splenectomy was reported in only 1 (1.1%) 14-years old patient who had a complete response. During the study, splenectomy was performed in 6 (6.6%) pts with chronic ITP; the duration of the disease at the time of splenectomy varied from 2 to 10 years, with average duration of 4.69 years (median - 4.5 years). Complete response to splenectomy was observed in 3 (50%) pts, a partial response - in 2 (33.3%), no response - in 1 (16.7%) patient. Loss of response to splenectomy was not reported. During the study, severe ITP was reported in 8 (8.7%) pts, 41 (44.6%) pt had various hemorrhagic manifestations of ITP at least at 1 visit, grade IV hemorrhagic syndrome was not reported. Thirty-eight (41%) pts received 1-st line treatment: glucocorticosteroids (GCS) - 23 (60.5%) pts, IVIG - 5 (13.2%), alfa-interferons -16 pts (42.1%). Twenty-three pts (24.7%) received second-line therapy: GCS - 1 (4.3%), IVIG -1 (4.3%), immunosupression - 1 (4.3%), rituximab - 2 (8.7%), romiplostim - 11 (47.8%), eltrombopag - 14 (60.9%). Conclusion For the first time new information on the features of the disease and patterns of management of pediatric pts with primary ITP in Russia was obtained in a prospective study. Interestingly, the preferred therapy for the 2nd or subsequent lines are TPO receptor agonists used outside the approved indications in research institutions, based on published clinical trial data. Splenectomy rate before and during the study was only 7.5% (7 pts) with chronic ITP; in 1 child (14.3%) splenectomy was ineffective. Low acceptance of splenectomy suggests TPO-mimetics as potential second-line therapy. In total, good disease control is achievable in the majority of pediatric pts with ITP. Disclosures Off Label Use: use of TPO-mimetics in children.

scholarly journals Second Line ITP Therapy in the UK: Results from the UK Paediatric ITP Registry

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3478-3478
Author(s):  
Jenna Lakhani ◽  
Robert J. Klaassen ◽  
Nicholas J Barrowman ◽  
Jason Chan ◽  
John D. Grainger
Keyword(s):  
Platelet Count ◽  
Logarithmic Scale ◽  
Line Treatment ◽  
Second Line ◽  
Second Line Therapy ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Line Therapy ◽  
Bleeding Episodes ◽  
The Uk

Abstract Background: Immune thrombocytopaenia (ITP) is the most common acquired bleeding disorder in children and is typically a self-limiting condition that resolves within six months. Although a 'watch and wait' approach is commonly used in the management of paediatric ITP, treatment options are available to aid in managing complex or severe cases, with the ultimate goal being to maintain health-related quality of life (HRQL) and avoid serious complications. This study aims to understand the use and indications for second-line treatments in persistent and chronic ITP (duration of 3 months or longer) based on an analysis of the UK Paediatric ITP Registry. Methods: The UK Paediatric ITP Registry is a prospective database of children presenting with ITP to over 100 paediatric treatment centres in the UK between 2005 and 2015. Patients with ITP were included if they received any second line ITP treatment: specifically rituximab, thrombopoietin receptor agonists (TPO-RAs), azathioprine, dapsone and splenectomy. Factors including age, sex, bleeding episodes and severity as well as follow-up platelet counts were analysed. Patients receiving second line treatments were then compared to similar patients who did not receive treatment but who also had persistent (> 3 months) or chronic (> 12 months) ITP and at least one platelet count of 30x109/l or less during that time period. Results: Of 938 patients in the database, 537 were identified as having persistent or chronic ITP. 22 of these patients received a form of second line treatment. This is 4% of all persistent and chronic ITP patients and 16% of those with at least one recorded platelet count <30x109/l. Of the patients receiving second line treatment, 77% were female and 59% were age 10 or older when diagnosed, which when compared to the control group, show age (p=0.002) and sex (p=0.019) as significant factors in the use of second line treatment. Bleeding episodes and severity were similar between both groups with 64% of patients in each group having at least one episode of moderate or severe bleeding. Of the 22 patients receiving second line treatment, 59% showed a marked improvement in platelet counts after one course. 32% showed no significant response despite multiple courses (Figure). Conclusion: In the UK Paediatric ITP Registry, teenage girls were more likely to be prescribed second line therapy (50% were females aged 10 or older), and the majority of patients showed a marked improvement in their platelet count with one course of therapy. Future research should look at the impact of TPO-RAs as they become licensed and HRQL outcomes to help select which ITP patients would benefit the most from second line therapy. Figure 1. Graphic representation of platelet counts throughout course of ITP in patients receiving second line treatments using a logarithmic scale Figure 1. Graphic representation of platelet counts throughout course of ITP in patients receiving second line treatments using a logarithmic scale Disclosures No relevant conflicts of interest to declare.

Reassessment of treatment modalities for paediatric patients with chronic immune thrombocytopenia

2009 ◽  
Vol 29 (02) ◽  
pp. 171-176 ◽  
Author(s):  
G. Janssen ◽  
A. Borkhardt ◽  
H. J. Laws
Keyword(s):  
Lupus Erythematosus ◽  
Immune Thrombocytopenia ◽  
Spontaneous Recovery ◽  
Treatment Modalities ◽  
First Line ◽  
Second Line Therapy ◽  
Chronic Itp ◽  
First Line Therapy ◽  
Line Therapy ◽  
Acute Form

SummaryApproximately 70% of children have the acute form of immune thrombocytopenia (ITP), which is defined by recovery within six months of presentation with or without treatment. Chronic ITP is to be reserved for patients with platelets < 100 000/μl for more than twelve months and exclusion of other diagnosis like systemic lupus erythematosus or bone marrow failures. In children, the chance of spontaneous recovery is 52% after diagnosis of chronic ITP. The Intercontinental Childhood ITP Study group recommends that children without bleeding may not require therapy regardless of their platelet count. Whereas in patients with bleeding symptoms first line therapy is defined and includes steroids or immunoglobuline, second line therapy in refractory patients with significant hemorrhagic problems is unclear. Guidelines recommend splenectomy, but for more than 50 years patients and physicians look for pharmacological alternatives. It may be that rituximab is a promising option which has been proven to be effective with few adverse effects. Till now the treatment has focused on immunomodulation. Research has now focused on stimulating platelet production. In this review we discuss old and new therapy modalities for children with cITP.

Genes Influencing the Development and Severity of Chronic ITP Identified through Whole Exome Sequencing

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 73-73 ◽  
Author(s):  
Jenny M. Despotovic ◽  
Linda M. Polfus ◽  
Jonathan M. Flanagan ◽  
Carolyn M. Bennett ◽  
Michele P Lambert ◽  
...  
Keyword(s):  
T Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Second Line ◽  
Second Line Therapy ◽  
Advisory Committees ◽  
Chronic Itp ◽  
Line Therapy ◽  
Whole Exome ◽  
Phenotype Data

Abstract Background: Chronic immune thrombocytopenia (ITP) is a complex autoimmune disease characterized by antibody mediated platelet destruction and impaired production. Sustained autoimmunity in chronic ITP appears to be due to generalized immune dysregulation including altered T cell balance with a shift toward immune activation (increased Th1/Th2 ratio) as well as decreased number and impaired function of regulatory T cells (Treg). The cause of these abnormalities has not been fully elucidated and is likely multifactorial, but genetic factors may be involved in ITP pathogenesis. Improved understanding of genetic influences could lead to novel therapeutic approaches. Aim: To identify genetic variants that may be involved in chronic ITP susceptibility and severity. Methods: Whole exome sequencing (WES) was performed on 262 samples with robust phenotype data on children with chronic ITP from the North American Chronic ITP Registry (NACIR, n= 173) and the Platelet Disorders Center at the Weill-Cornell Medical Center (n=89). All but three patients were ≤19 years old at diagnosis; 83% had primary ITP, 10% had Evans syndrome, 7% had other autoimmune disorders. Sequencing data for ITP cases of European American (EA) ancestry were compared to EA controls with platelets >150 x 109/L sequenced in the Atherosclerosis Risk in Communities (ARIC) Study (N=5664) to identify candidate genes associated with ITP susceptibility. Analyses filtered variants on a minor allele frequency (MAF) <0.01 as well as functionality of nonsynonymous, stop gain, splicing, stop loss, and indel variants. Both Fisher-Exact tests of single variants and Firth logistic regression for gene-based tests, accounting for an unequal proportion of cases compared to controls, were used. A Bonferroni corrected threshold based on 16,532 genes was calculated at 3.0x10-6. In a separate analysis, phenotype data for ITP cases were reviewed and cases stratified by disease severity according to second line treatment needed (Yes =139, No=113) and compared to ARIC EA controls with platelet count >150 x 109/L (N=5664). Results: Several damaging variants identified in genes involved in cellular immunity had a significantly increased frequency in the EA ITP cohort (Table). The most significant associations were detected in the IFNA17 gene, which is involved in TGF-β secretion and could affect number and function of the Treg compartment. IFNA17 rs9298814 (9:21227622 A>C) was identified in 26% of cases in the EA ITP cohort compared to <0.01% of EA controls, and other low frequency but presumed deleterious variants were also identified in IFNA17. IFNA17 gene variants remained significant in the most severely affected patients, specifically those requiring second line therapy, providing further evidence for this gene's functional relevance in the pathogenesis and pathophysiology of ITP. Other genes with known impact on T cell number or function, including DGCR14, SMAD2 and CD83 also contained variants with increased frequency in the EA ITP cohort. IFNLR1 and REL genes were also significantly associated with need for second line ITP therapy. Analysis of this large cohort did not validate any of over 20 variants that have been previously published as candidates for ITP susceptibility or evolution to chronic ITP. Conclusion: Damaging variants in genes associated with cellular immunity have an increased frequency in children with chronic ITP compared to controls, providing further evidence for the role of T cell abnormalities in the pathophysiology of ITP. The IFNA17 and IFNLR1 genes maintained significance when the ITP cohort was stratified according to disease severity, and may be important candidate genes involved in immune regulation and sustained autoimmunity associated with chronic ITP. Table. Genes identified through WES analysis of children with chronic ITP. Gene Function Relevant to ITP Pathophysiology Minor Allele Count (MAC)Cases Controls p value EA Chronic ITP vs. EA ARIC (non-ITP) controls N=172 N=5664 IFNA17 Treg, TGF-β signaling 91 17 3.97x10-13 DGCR14 IL-17 induction 14 3 1.27x10-10 SMAD2 TGF-β signaling 1 0 5.62x10-22 CD83 Th17/Treg balance 2 3 1.67x10-6 EA Chronic ITP requiring Second Line Therapy vs. EA ARIC (non-ITP) controls N=139 N=5664 IFNLR1 Class II cytokine receptor 2 1 3.95x10-15 IFNA17 Treg, TGF-β signaling 75 17 3.40x10-7 REL T and B cell function, inflammation 2 0 1.39x10-14 Disclosures Off Label Use: Off-label use of CliniMACS purified CD34+ cells. Lambert:GSK: Consultancy; NovoNordisk: Honoraria; Hardin Kundla McKeon & Poletto: Consultancy. Recht:Baxalta: Research Funding; Kedrion: Consultancy. Bussel:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; protalex: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; rigel: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Thrombopoietin receptor agonists as second-line therapy in splenectomy-eligible persistent immune thrombocytopenia

2019 ◽  
Vol 30 (6) ◽  
pp. 295-299 ◽  
Author(s):  
Fabrizio Vianello ◽  
Fabio D’Amore ◽  
Anna M. Lombardi ◽  
Ilaria Caputo ◽  
Alberto Friziero ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Second Line ◽  
Second Line Therapy ◽  
Thrombopoietin Receptor Agonists ◽  
Receptor Agonists ◽  
Line Therapy ◽  
Thrombopoietin Receptor

Paclitaxel, Ifosfamide, and Cisplatin Second-Line Therapy for Patients With Relapsed Testicular Germ Cell Cancer

2000 ◽  
Vol 18 (12) ◽  
pp. 2413-2418 ◽  
Author(s):  
Robert J. Motzer ◽  
Joel Sheinfeld ◽  
Madhu Mazumdar ◽  
Manjit Bains ◽  
Tania Mariani ◽  
...  
Keyword(s):  
Germ Cell ◽  
Salvage Therapy ◽  
Complete Response ◽  
Second Line ◽  
Second Line Therapy ◽  
Testicular Germ Cell ◽  
Primary Tumor Site ◽  
Prognostic Features ◽  
Line Therapy ◽  
Response To Chemotherapy

PURPOSE: To evaluate the dose, toxicity, and efficacy of paclitaxel in combination with ifosfamide and cisplatin as salvage therapy for patients with relapsed testicular germ cell tumors (GCTs). PATIENTS AND METHODS: Thirty patients with previously treated GCTs were treated with paclitaxel and ifosfamide plus cisplatin (TIP) as second-line therapy. All had favorable prognostic features for response (testis primary tumor site and prior complete response to first-line chemotherapy program). Four cycles of paclitaxel, ifosfamide 5 g/m2, and cisplatin 100 mg/m2 were given 21 days apart with granulocyte colony-stimulating factor support, followed by resection of radiographic residua. The dose of paclitaxel was increased among cohorts with dose levels of 175, 215, and 250 mg/m2; the largest dose was selected for the phase II part of the trial. RESULTS: Twenty-three (77%) of 30 patients achieved a complete response to chemotherapy alone, and one patient achieved a durable partial response with normal tumor markers. Therefore, 24 (80%) achieved a favorable response. Eleven patients with normalized markers after chemotherapy underwent resection of residual tissue, with only necrosis found in 10 and mature teratoma in one. Two patients relapsed, and 22 (73%) of the favorable responses remain durable at a median follow-up duration of 33 months. Myelosuppression was the major toxicity, and two patients had grade 3 neurotoxicity. CONCLUSION: Four cycles of TIP was associated with a high proportion of patients who achieved a complete response, a lack of relapse, and relative tolerability as an ifosfamide-containing salvage regimen for testicular GCTs. The high durable complete response proportion emphasizes the importance of patient selection according to prognostic factors for a favorable outcome to conventional-dose salvage therapy.

Comparative analysis of the effectiveness of second-line bevacizumab plus chemotherapy in second-line therapy in metastatic colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 619-619 ◽  
Author(s):  
Kaldigul Smagulova
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Complete Response ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Group 2 ◽  
Group 1

619 Background: Advances in molecular biology and a wide introduction to the practice of targeted therapies have improved outcomes and significantly affect the overall survival of patients. To investigate the efficacy and safety of bevacizumab (BEV) beyond first progression combined with chemotherapy (CT) in patients with metastatic colorectal cancer. Methods: 68 patients with mCRC who received chemotherapy treatment at the Department of the Kazakh Research Institute of Oncology and Radiology. Selecting second-line chemotherapy based on oxaliplatin or irinotecan depended of an earlier first-line therapy (FOLFOX, FOLFIRI). The survival rate was calculated by Kaplan-Meier, comparison of survival curves was performed by log-rank. Results: The study included 68 patients, who were randomized from February 2009 to November 2011(to 33 [48.5%] BEV + CT and 35 [51.5%] to CT alone). Analysis of the immediate results of treatment showed that in neither case was not achieved complete response of the tumor. Partial regression in group 1 – 11 (33.3 ± 8.2)%, and group 2 - in 9 (25.7 ± 7.3)%. Stabilization is achieved in 20 (60.6 ± 8.5)% and 23 (6.7 ± 8.0)% of cases, respectively. The progression of the disease was observed in the group 1 in 2 (6.1 ± 4.1)% and 3 (8.6 ± 4.7)% of cases. Median progression-free survival (PFS) and overall survival (OS) was 11.5 months (7-16) and 12.2 months in group 1, and 9.7 months (6-13.2) (PFS), 9.1 months(OS) in group 2, respectively. The adverse event profile was consistent with previously reported data for BEV + CT. BEV-related significant adverse events included bleeding grade 3-4 (1.5 %) and venous thrombosis (2.3 %). Conclusions: Our findings demonstrate that BEV + CT continued beyond progression significantly prolong OS and PFS in second-line therapy mCRC.

scholarly journals Second-Line Therapy for Immune Thrombocytopenia: Real-World Experience in Canada

2020 ◽  
Vol 15 (4) ◽  
pp. 28-35
Author(s):  
Hasmik Nazaryan ◽  
Yang Liu ◽  
Emily Sirotich ◽  
Joanne Duncan ◽  
Ishac Nazy ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Second Line ◽  
Treatment Sequence ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Thrombopoietin Receptor ◽  
Count Response ◽  
Immunosuppressant Medications ◽  
Étude De Cohorte

BackgroundThe sequence of second-line therapy used for the treatment of immune thrombocytopenia (ITP) is variable. This study aimed to describe the types and sequences of second-line therapies for a large cohort of ITP patients in Canada. MethodsWe completed a retrospective cohort study of the McMaster ITP Registry. We included patients with primary or secondary ITP who had received one or more second-line therapies including any of the splenectomy, rituximab, danazol, dapsone, or thrombopoietin receptor agonists (TPO-RAs), or immunosuppressant medications. Immunosuppressant medications included azathioprine, cyclophosphamide, cyclosporine, or mycophenolate given alone or in combination. ResultsWe identified 204 ITP patients who had received one or more second-line therapies. The most common second-line therapies were immunosuppressant medications (n = 106; 52.0%), splenectomy (n = 106; 52.0%), TPO-RAs (n = 75; 36.8%), danazol (n = 73; 35.8%), and rituximab (n = 67; 32.8%). For patients who received only one second-line therapy (n = 88), the most common treatment was splenectomy (n = 28; 31.8%). For patients who received more than one second-line therapy (n = 116), the most common treatment sequence was splenectomy, followed by immunosuppressant medications (n = 7; 6.0%). Of the 154 evaluable patients at the end of follow-up, 69 (44.8%) achieved a complete platelet count response and 101 (65.5%) achieved a partial response. ConclusionImmunosuppressant medications and splenectomy are commonly used as second-line therapies for ITP in Canada. Treatment choices and the sequence of treatments were variable. RESUME Contexte La séquence de la thérapie de deuxième ligne utilisée pour le traitement de la thrombocytopénie immunitaire (PTI) est variable. Cette étude visait à décrire les types et les séquences des thérapies de deuxième ligne pour une large cohorte de patients atteints de PTI au Canada. MéthodesNous avons réalisé une étude de cohorte rétrospective du registre ITP de McMaster. Nous avons inclus des patients atteints de PTI primaire ou secondaire qui avaient reçu une ou plusieurs thérapies de deuxième ligne, y compris une splénectomie, du rituximab, du danazol, de la dapsone ou des agonistes des récepteurs de la thrombopoïétine (AR-TPO), ou des médicaments immunosuppresseurs. Les médicaments immunosuppresseurs comprennent l’azathioprine, le cyclophosphamide, la cyclosporine ou le mycophénolate, administrés seuls ou en combinaison. RésultatsNous avons identifié 204 patients atteints de PTI qui avaient reçu une ou plusieurs thérapies de seconde ligne. Les thérapies de deuxième ligne les plus courantes étaient les immunosuppresseurs (n = 106; 52.0%), la splénectomie (n = 106; 52.0%), les AR-TPO (n = 75; 36.8%), le danazol (n = 73; 35.8%) et le rituximab (n = 67; 32.8%). Pour les patients qui n’ont reçu qu’un seul traitement de deuxième intention (n = 88), le traitement le plus courant était la splénectomie (n = 28; 31.8%). Pour les patients qui ont reçu plus d’un traitement de deuxième ligne (n = 116), la séquence de traitement la plus courante était la splénectomie, suivie par les médicaments immunosuppresseurs (n = 7; 6.0%). Sur les 154 patients évaluables à la fin du suivi, 69 (44.8%) ont obtenu une réponse complète de la numération plaquettaire et 101 (65.5%) une réponse partielle. ConclusionLes médicaments immunosuppresseurs et la splénectomie sont couramment utilisés comme traitements de deuxième intention pour le PTI au Canada. Les choix de traitement et la séquence des traitements sont variables.

scholarly journals Efficacy of Second Line Agents Dapsone & Azathioprine in Children & Adults with Immune Thrombocytopenia: Single Centre Experience from India

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1064-1064
Author(s):  
Venkatesh Shreeganesh Ekbote ◽  
Biju George ◽  
Vikram Mathews ◽  
Kavitha Lakshmi ◽  
Abhijeet Ganapule ◽  
...  
Keyword(s):  
Response Rate ◽  
Complete Response ◽  
Second Line ◽  
Second Line Therapy ◽  
Total N ◽  
Overall Response ◽  
Line Therapy ◽  
Number Of Patients ◽  
Increased Risk ◽  
Azathioprine Group

Abstract There are approximately 10 therapeutic agents listed as second line therapy for steroid refractory or relapsed ITP but there are no clear guidelines for timing & order of their use or that of splenectomy. At our center, we have used dapsone or azathioprine as second line therapy prior to splenectomy in such patients who do not have critical bleeding. This study describes the outcome of that approach. Three hundred patients fulfilling ITP International Working Group definition of steroid non-response & relapse ITP (Rodeghiero et al Blood 2009) were included. Response to treatment was assessed using American Society of Hematology 2011 guidelines (Neunert et al Blood 2011). This analysis was approved by the institutional ethics committee. Patients received either dapsone (n = 170) at 1-2 mg/kg/day or azathioprine (n = 130) at 1-3 mg/kg/day in escalating doses based on physician preferences. Additional intermittent corticosteroids were given in 36 patients. Data was retrieved from individual medical records and electronic database. Statistical analysis was performed using SPSS version 16.0 Results: Baseline characteristics of the patients & outcome are described in Table 1. After 3 months of therapy, overall response was 58.6% while it was 58.8% for the dapsone group and 58.5% for azathioprine group. The number of patients achieving complete & partial response was 46% & 12.7% for overall group, 45.9% & 13% for dapsone group & 46.2% & 12.3% for azathioprine group. The median duration of response was 35 months (2-74 months) and was significantly longer with azathioprine - 60 months (2-60 months) compared to 27 months (5-74 months) with dapsone (p=0.015). Therapy was well tolerated with 4 patients discontinuing dapsone (methemoglobinemia, dapsone syndrome) and 2 discontinuing azathioprine (cytopenia). There were no deaths. At a median follow up of 33 months (24-42 months), 67 (38%) of the 176 responders have relapsed. These included 49 patients that relapsed while on therapy and 18 that relapsed after cessation of therapy. Relapses were significantly more common with dapsone (40.3%) than azathioprine (20.4%) (p=0.002). The median time to relapse while on therapy was 14 months for both agents. Any response to second line therapy less than complete response (p=0.030) & steroid nonresponsive ITP (p=0.042) were significantly associated with increased risk of relapse on therapy. Overall, 59.6% patients responding to dapsone and & 79.5% of patients responding to azathioprine continue to remain in remission both on & off therapy. Patients who switched to dapsone at the time of relapse showed significantly better response rate - 54% than azathioprine - 22.2% (p<0.001). Forty one patients who failed second line therapy eventually underwent splenectomy, with a response rate of 70.7%. In conclusion, the use of dapsone & azathioprine appears to be a safe approach, with need for splenectomy only in a few patients. The optimal dose & duration of therapy for these agents needs further evaluation in prospective studies. Table 1. Patient Characteristics Characteristics Total (%) N = 300 Dapsone (%) n = 170 Azathioprine (%) n = 130 P value Children 104 (34.7) 64(37.7) 40(30.7) ns Adults 196 (65.3) 106(62.3) 90(69.3) ns Male:Female Ratio 0.56:1 0.68:1 0.42:1 0.069 Median ITP Duration (months) 5 (1-262) 4 (1-262) 6 (1-146) ns Steroid Non-responsive 144 90 (52.9) 54 (41.5) 0.062 Relapsed ITP 156 80 (47.1) 76 (58.5) 0.062 Overall Response 176 (58.6) 100 (58.8) 76 (58.5) ns Complete Response 138 (46) 78 (45.9) 60 (46.2) ns Relapse rates 67/176 (38) 40.3% 20.4% 0.002 ns = not significant Disclosures No relevant conflicts of interest to declare.

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