Be a part of the ITP community and stay informed.
Login to your account or REGISTER
.

•  Web site Help & Info

Welcome, Guest
Username: Password: Remember me

TOPIC:

Triple Treatment - Update 8-1-15 7 years 4 months ago #50486

  • Sandi
  • Offline
  • Sandi Forum Moderator Diagnosed in 1998, currently in remission. Diagnosed with Lupus in 2006. Last Count - 344k - 6-9-18
  • Posts: 12436
  • Karma: 11
  • Thank you received: 2371
Promising reports of combination immunosuppression with high-dose dexamethasone and rituximab for the treatment of primary immune thrombocytopenia (ITP) have recently emerged. They suggest a potential to further optimize the efficacy of therapy. We investigate the use of a novel combination of conventional therapies in ITP given over 4 weeks. From 2011 to 2014, 20 patients were prospectively enrolled onto a single-arm phase 2b study to describe the safety, efficacy, and tolerability of oral dexamethasone 40 mg for days 1 to 4, oral cyclosporine 2.5 to 3 mg/kg daily for day 1 to 28, and intravenous low-dose rituximab 100 mg for days 7, 14, 21, and 28. There were no therapy-related serious adverse side effects, 6-month response rate was 60%, and treatment was well tolerated. Responders enjoyed relapse-free survivals of 92% and 76%, respectively, at 12 and 24 months. This study highlights the possibility of achieving an enduring remission from 4 weeks of therapy. This study is registered at www.anzctr.org.au (#ANZCTRN12611000015943).

Submitted March 3, 2015.
Accepted May 11, 2015.

© 2015 by The American Society of Hematology



www.bloodjournal.org/content/126/4/500.abstract?ct=
The following user(s) said Thank You: Fervenz

Please Log in or Create an account to join the conversation.

Triple Treatment - Update 8-6-15 7 years 4 months ago #50606

  • Sandi
  • Offline
  • Sandi Forum Moderator Diagnosed in 1998, currently in remission. Diagnosed with Lupus in 2006. Last Count - 344k - 6-9-18
  • Posts: 12436
  • Karma: 11
  • Thank you received: 2371
Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder characterized by autoantibodies targeting platelet surface proteins, most commonly GPIIbIIIa (αIIbβ3 integrin), leading to platelet destruction. Recently, CD8(+) cytotoxic T-lymphocytes (CTLs) targeting platelets and megakaryocytes have also been implicated in thrombocytopenia. Because steroids are the most commonly administered therapy for ITP worldwide, we established both active (immunized splenocyte engraftment) and passive (antibody injection) murine models of steroid treatment. Surprisingly, we found that, in both models, CD8(+) T cells limited the severity of the thrombocytopenia and were required for an efficacious response to steroid therapy. Conversely, CD8(+) T-cell depletion led to more severe thrombocytopenia, whereas CD8(+) T-cell transfusion ameliorated thrombocytopenia. CD8(+) T-regulatory cell (Treg) subsets were detected, and interestingly, dexamethasone (DEX) treatment selectively expanded CD8(+) Tregs while decreasing CTLs. In vitro coculture studies revealed CD8(+) Tregs suppressed CD4(+) and CD19(+) proliferation, platelet-associated immunoglobulin G generation, CTL cytotoxicity, platelet apoptosis, and clearance. Furthermore, we found increased production of anti-inflammatory interleukin-10 in coculture studies and in vivo after steroid treatment. Thus, we uncovered subsets of CD8(+) Tregs and demonstrated their potent immunosuppressive and protective roles in experimentally induced thrombocytopenia. The data further elucidate mechanisms of steroid treatment and suggest therapeutic potential for CD8(+) Tregs in immune thrombocytopenia.

© 2015 by The American Society of Hematology.

www.ncbi.nlm.nih.gov/pubmed/26036802

Please Log in or Create an account to join the conversation.

Triple Treatment - Update 8-6-15 7 years 4 months ago #50616

  • Fervenz
  • Offline
  • Posts: 129
  • Thank you received: 6
Sandi,
I've been reading these with great interest Sandi, and just wanted to thank you for posting the latest news!

Please Log in or Create an account to join the conversation.

Triple Treatment - Update 8-6-15 7 years 4 months ago #50618

  • Sandi
  • Offline
  • Sandi Forum Moderator Diagnosed in 1998, currently in remission. Diagnosed with Lupus in 2006. Last Count - 344k - 6-9-18
  • Posts: 12436
  • Karma: 11
  • Thank you received: 2371
You're welcome. I'm glad someone is benefiting.

Please Log in or Create an account to join the conversation.

Triple Treatment - Update 8-6-15 7 years 4 months ago #50629

  • EmilyK
  • Offline
  • Diagnosed jan 2015 at age 50 with 13,000 platelets.
  • Posts: 454
  • Thank you received: 67
Sandi
Your updates are great even if i understand only a tiny bit of the studies mean! It makes me feel good that they are studying ITP.

Please Log in or Create an account to join the conversation.

Triple Treatment - Update 8-6-15 7 years 4 months ago #50630

  • Sandi
  • Offline
  • Sandi Forum Moderator Diagnosed in 1998, currently in remission. Diagnosed with Lupus in 2006. Last Count - 344k - 6-9-18
  • Posts: 12436
  • Karma: 11
  • Thank you received: 2371
Oh yeah! It's come a long way in the last 15 years. I'm fascinated by the information that has been discovered.

Please Log in or Create an account to join the conversation.

Veltuzumab - Update 10-12-15 7 years 1 month ago #51499

  • Sandi
  • Offline
  • Sandi Forum Moderator Diagnosed in 1998, currently in remission. Diagnosed with Lupus in 2006. Last Count - 344k - 6-9-18
  • Posts: 12436
  • Karma: 11
  • Thank you received: 2371
BACKGROUND: Veltuzumab (hA20), a humanized MAb with significant structurefunction differences from rituximab, has shown clinical activity at low doses in non- Hodgkin’s lymphoma. Since anti-CD20 immunotherapy has demonstrated activity in ITP with standard doses of rituximab, we hypothesized that low-dose veltuzumab would be effective in this disorder, thus also justifying subcutaneous injections. The goal of this first study in ITP is to evaluate the safety and tolerability of veltuzumab administered at low doses either intravenously or by subcutaneous injection, to obtain information on efficacy, pharmacodynamics, pharmacokinetics, and immunogenicity, and to determine feasible doses for further studies.

METHODS: A multicenter, phase I/II study was initiated in adult ITP patients with platelets <30K/μL, and a prior history of platelets <150K/μL for >6 months, who had failed ≥1 standard therapy. Patients were administered 2 doses of veltuzumab 2 weeks apart and evaluated for efficacy over 12 weeks, with responding patients continuing evaluation in long-term follow-up. Efficacy was assessed by platelet level responses with increases confirmed at least 1 week apart classified as complete (CR, >150K/μL), partial (PR, 50–150K/μL), or minor (MR, 30–50K/μL) responses. Adverse events and safety laboratories were evaluated by NCI CTC v3 toxicity grades. Pharmacodynamics were evaluated by B-cell levels (CD19), while pharmacokinetics and immunogenicity were evaluated by serum veltuzumab levels and human anti-veltuzumab antibody (HAHA) titers, respectively, using an ELISA assay performed by the Sponsor.

RESULTS: Seven patients (5F/2M, median age 41, 2 splenectomized) have now received intravenous veltuzumab at doses of 80 mg (N=3), 120 mg (N=3) or 200 mg (N=1). They had ITP for 0.5 – 12 years, had received prior steroids (N=7), IVIG and/or WinRho (N=6), or chemotherapy (N=3), and had 6–27 K platelets/μL and Grade 0–1 bleeding scores at study entry. One patient withdrew after receiving 100 mg and experiencing a Grade 3 infusion reaction, subsequently undergoing splenectomy. Otherwise, the treatment was well tolerated with all infusions completed within 60 – 90 minutes. Of the 6 evaluable patients, all 4 non-splenectomized patients responded to treatment with at least a doubling of their baseline platelet levels, achieving 2 CRs, 1 PR, and 1 MR. At present, both CRs are still continuing with >100 K platelets/μL at 16 and 24 weeks after treatment. The patient with a PR, who was treated at 80 mg, had platelets decreased <30K/μL at 11 weeks, but then achieved a second PR after retreatment at 120 mg, which is now ongoing 6 weeks later. The patient with MR still has platelets at least double the baseline levels at 12 weeks. Although neither of the 2 splenectomized patients responded, one had spontaneously increased platelets >30 K/μL just prior to 1st infusion and has continued to maintain these levels now 12 weeks after treatment, while the other has since been treated with cyclosporine, also without response. Veltuzumab quickly depleted B cells after the first dose, with decreases sustained >12 weeks. Even at these low doses, veltuzumab achieved expected serum levels (mean Cmax, 20.3 and 46.0 μg/mL at 80 and 120 mg, respectively) and remained in circulation without evidence of rapid clearance or sequestration (mean post-treatment half-life ~1 week). Two patients developed low-level positive HAHA results of uncertain clinical significance after treatment.

CONCLUSIONS: These initial results indicate that doses of 80 or 120 mg veltuzumab have acceptable safety and demonstrate promising activity for ITP, including durable complete responses. Based on these findings, the study is proceeding, with patients now being recruited for therapy with low-dose veltuzumab administered by subcutaneous injection.

www.bloodjournal.org/content/112/11/3412.abstract?ct=
The following user(s) said Thank You: Forevertwentyone

Please Log in or Create an account to join the conversation.

IgA levels - Update 10-12-15 7 years 1 month ago #51500

  • Sandi
  • Offline
  • Sandi Forum Moderator Diagnosed in 1998, currently in remission. Diagnosed with Lupus in 2006. Last Count - 344k - 6-9-18
  • Posts: 12436
  • Karma: 11
  • Thank you received: 2371
Background ITP is a disorder of antibody mediated destruction and inhibition of production of platelets. ITP is idiopathic as it is unclear what immune factors relate to disease severity and response to treatment. We hypothesize that immune dysregulation represented by abnormal immunoglobulins especially elevated IgA may increase the risk of disease or failure to respond to treatment.

Methods We performed a retrospective analysis of the Platelet Disorder Center master list, encompassing all of the patients with ITP seen at the Platelet Disorder Center in the past 10 years. The data includes demographics, use of and response to treatments, and certain selected laboratory values including levels of gamma globulins. The subject's serum IgA levels were observed for differences in response to treatment; IgG was not evaluated because of the use of IVIG. The analysis was performed using STATA statistical software and the Chi squared test.

Results In total, data was available for 946 subjects with ITP of which 778 had baseline immunoglobulin data. The population was predominantly female (62%) and young with a mean age of 33.4 (SD 23.1) and ranged from less than 1 year old to 94 years of age. IgA mean was 188mg/dl (SD 136). 109 subjects (14%) had an elevated IgA (normal range 70-312). Subjects with an IgA greater than 312 were older than the general population with a mean age 48 (SD 19.4). Subjects with an IgA level greater than mean had a significantly increased chance of failing to respond to standard treatment (steroids, Win-Rho or IVIG) than patients with an IgA level lower than mean (13% vs. 8% p=0.05) and a trend towards failure to respond to individual treatments (rituxan 46% vs. 38% p =0.193, Win-Rho 27% vs. 21% p =0.25, IVIG 24% vs. 16% p= 0.07). In contrast patients with an IgA greater than mean were more likely to respond to splenectomy than patients with IgA less than mean (32.1% vs. 18.1% p=0.045). Subjects with an IgA greater than mean also had an increased risk of having a major bleed (9% vs. 6% p = 0.037). There was no difference in response to standard treatment in subjects with IgA below the lower limit of normal (70mg/dl) relative to subjects with a normal or elevated IgA (8% vs. 11% p= 0.69). Subjects with an IgA above the upper limit of normal (312mg/dl) did not have a significant increase in their chance to fail standard treatment relative to the rest of the study population (9% vs. 11% p =0.12). Subjects older than 65 were more likely to fail to respond to standard treatment than patients under 65 (20% vs. 8% p =0.01) and have an elevated IgA (20% vs. 13% p =0.034). Subjects older than 65 had a non-significant increase in risk of failure to respond to treatment if IgA was greater than mean (26% vs. 14% p= 0.16). This trend was less pronounced in subjects under 65 (10% vs. 7% p =0.19). Of the 6 patients with known inflammatory bowel disease (IBD), 5 had an IgA greater than mean (mean 255, range 193-395) and one had an undetectable IgA. However of the 30 patients treated for H.pylori the mean IgA level was similar to the general population (mean 188, range 8-498).

Discussion More than 10% of patients with ITP have an elevated serum IgA. Subjects with IgA above mean are less likely to respond to standard treatment but more likely to respond to a splenectomy and more likely to have a major bleed than patients with an IgA below mean. This trend is more pronounced in elderly patients but was also suggested in patients younger than 65. However, those subjects with the highest IgA levels did not have a significantly increased risk of failing to respond to standard treatment and significant elevations in IgA were not obviously related to mucosal inflammation. Minor elevations in serum IgA may represent an inflammatory state not addressed with standard treatments for ITP. Further investigation into the role of IgA in the pathology of refractory ITP is warranted.

Disclosures: Bussel: Sysmex: Research Funding; Eisai, Inc: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genzyme: Research Funding; Scienta: Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees.

www.bloodjournal.org/content/114/22/3503.abstract?ct=
The following user(s) said Thank You: Forevertwentyone

Please Log in or Create an account to join the conversation.

New articles posted here - update 10-12-15 7 years 1 month ago #51502

  • Forevertwentyone
  • Offline
  • Posts: 32
  • Thank you received: 2
Thanks for great articles, Sandi. The article (published in 2008) you posted today described the clinical trials of veltuzumab so I looked up and found out veltuzumab has been approved as an orphan drug for ITP August this year. Have you seen anyone in this forum who tried this new treatment?

Please Log in or Create an account to join the conversation.

New articles posted here - update 10-12-15 7 years 1 month ago #51522

  • Sandi
  • Offline
  • Sandi Forum Moderator Diagnosed in 1998, currently in remission. Diagnosed with Lupus in 2006. Last Count - 344k - 6-9-18
  • Posts: 12436
  • Karma: 11
  • Thank you received: 2371
No, not that I can think of, sorry.

Please Log in or Create an account to join the conversation.

TPO's and APS - update 10-26-15 7 years 1 month ago #51694

  • Sandi
  • Offline
  • Sandi Forum Moderator Diagnosed in 1998, currently in remission. Diagnosed with Lupus in 2006. Last Count - 344k - 6-9-18
  • Posts: 12436
  • Karma: 11
  • Thank you received: 2371
Abstract
INTRODUCTION:

Romiplostim is a thrombopeitin-receptor agonist approved for raising platelet counts in patients with immune thrombocytopenia (ITP). Several hematologic adverse effects have been reported including acute myeloid leukemia, myelofibrosis, and thrombosis.

METHODS:

We report two cases, one pediatric and one adult patient, who had antiphospholipid antibodies and received romiplostim for ITP. Additionally, we conducted medline, Food and Drug Administration (FDA) Adverse Events reports website, and manufacturer׳s adverse events database.

RESULTS:

Both patients developed thrombosis with evidence for catastrophic antiphospholipid syndrome (CAPS) after treatment with romiplostim. No reports or events were found from literature and database searches in regards to thrombosis associated with romiplostim in patients with antiphospholipid syndrome.

CONCLUSION:

These cases illustrate the potential for thrombosis with the administration of romiplostim. The administration of this drug to patients with a history of an autoimmune disease, especially those with positive antiphospholipid antibodies, should be done with caution.

Copyright © 2015 Elsevier Inc. All rights reserved.

www.ncbi.nlm.nih.gov/pubmed/26329147


It really surprises me that this has not really been an assumed risk all along. I wouldn't think it's wise for a patient with APS to attempt to use a TPO. The problem is that patients are not tested for APS prior to TPO use. We've seen blood clots and strokes even in patients who do not have APS.

Please Log in or Create an account to join the conversation.

TPO's and APS - update 10-26-15 7 years 1 month ago #51696

  • Ann
  • Offline
  • Posts: 1895
  • Thank you received: 355
Yes it's funny how we here seem to know or suspect far more than the doctors. It doesn't fill one with confidence!

Please Log in or Create an account to join the conversation.

TPO's and APS - update 10-26-15 7 years 1 month ago #51697

  • Sandi
  • Offline
  • Sandi Forum Moderator Diagnosed in 1998, currently in remission. Diagnosed with Lupus in 2006. Last Count - 344k - 6-9-18
  • Posts: 12436
  • Karma: 11
  • Thank you received: 2371
No, it doesn't. We've been saying this since the TPO's came out. This is only two cases....I'm sure there are many more that were not reported because they either didn't recognize the connection or just didn't bother doing it.

Please Log in or Create an account to join the conversation.

TPO's and APS - update 10-26-15 7 years 1 month ago #51699

  • Ann
  • Offline
  • Posts: 1895
  • Thank you received: 355
When I was at that conference for doctors last year, one of them said that he didn't think that Nplate caused a clotting problem, he said it was negligible so he didn't worry about high counts with Nplate and just continued dosing. I was sitting in the audience thinking "oh my, how scary are you".

Please Log in or Create an account to join the conversation.

TPO's and APS - update 10-26-15 7 years 1 month ago #51700

  • Sandi
  • Offline
  • Sandi Forum Moderator Diagnosed in 1998, currently in remission. Diagnosed with Lupus in 2006. Last Count - 344k - 6-9-18
  • Posts: 12436
  • Karma: 11
  • Thank you received: 2371
Wow - seriously? Sometimes I think that some doctors will do anything to get counts up, even if it compromises the patient in another way.

Please Log in or Create an account to join the conversation.

TPO's and APS - update 10-26-15 7 years 1 month ago #51705

  • mrsb04
  • Away
  • ITP since 2014. Retired nurse. My belief is empower patients to be involved as much as possible in their care. Read, read, read & ALWAYS question medics about the evidence base they use.
  • Posts: 2055
  • Karma: 7
  • Thank you received: 584
Ann. I consider myself lucky that my consultant discussed risks at great length with me before commencing my romiplostim treatment

Please Log in or Create an account to join the conversation.

When it's not ITP - update 11-11-15 7 years 4 weeks ago #51937

  • Sandi
  • Offline
  • Sandi Forum Moderator Diagnosed in 1998, currently in remission. Diagnosed with Lupus in 2006. Last Count - 344k - 6-9-18
  • Posts: 12436
  • Karma: 11
  • Thank you received: 2371
Abstract

Type 2B von Willebrand disease (VWD) is frequently associated with distinct platelet morphology. Here we present a familial case of type 2B VWD with a novel VWF mutation (p.R1308S), which caused neonatal thrombocytopenia. The mother had been treated for refractory immune thrombocytopenia (ITP) for more than 20years. The most important hematological features of this case were large platelets and platelet aggregates detected on peripheral blood smears. Hemostatic tests showed enhanced ristocetin-induced platelet agglutination at low-ristocetin concentrations, absence of high-molecular weight von Willebrand factor (VWF) multimers, and low VWF cofactor activity/antigen ratio. In patients with intractable ITP, family history of ITP and consecutive neonatal thrombocytopenia, the differential diagnosis of congenital thrombocytopenia is mandatory. For this purpose, the identification of large platelets and platelet aggregates on peripheral blood smears is the key aspect of type 2B VWD diagnosis.



www.ncbi.nlm.nih.gov/pubmed/26278967

Please Log in or Create an account to join the conversation.

MTHFR - update 11-21-15 7 years 2 weeks ago #52017

  • Sandi
  • Offline
  • Sandi Forum Moderator Diagnosed in 1998, currently in remission. Diagnosed with Lupus in 2006. Last Count - 344k - 6-9-18
  • Posts: 12436
  • Karma: 11
  • Thank you received: 2371

Please Log in or Create an account to join the conversation.

MTHFR - update 11-21-15 7 years 2 weeks ago #52021

  • Ann
  • Offline
  • Posts: 1895
  • Thank you received: 355
Just for balance..

www.sciencebasedmedicine.org/dubious-mthfr-genetic-mutation-testing/

"As a real geneticist, Charis Eng, MD, PhD, points out, none of this means genetic testing is necessary. For some problems, there are cheaper alternatives that give better information. If high homocysteine levels are suspected, the simple solution is a blood test. If the blood test bears this out, supplementation with vitamins such as B6, B12, and folate or folic acid can be recommended. If the levels are normal, nothing need be done, whether the mutation is present or not."

and

"There are no recommended changes in management that are linked to specific test results."

Please Log in or Create an account to join the conversation.

MTHFR - update 11-21-15 7 years 2 weeks ago #52023

  • Sandi
  • Offline
  • Sandi Forum Moderator Diagnosed in 1998, currently in remission. Diagnosed with Lupus in 2006. Last Count - 344k - 6-9-18
  • Posts: 12436
  • Karma: 11
  • Thank you received: 2371
My homocystine levels are high...just found out. Wonder if I should get tested? I am taking B6, B12 and folic acid.

Please Log in or Create an account to join the conversation.

MTHFR - update 11-21-15 7 years 2 weeks ago #52024

  • Ann
  • Offline
  • Posts: 1895
  • Thank you received: 355
You need to check your B6, B12 and folate levels. If low that needs treating more aggressively. Knowing if there's a genetic reason would be interesting but won't help solve the problem. You have to choose where to spend your money and genetic testing for this isn't it.

Please Log in or Create an account to join the conversation.

MTHFR - update 11-21-15 6 years 11 months ago #52193

  • Sandi
  • Offline
  • Sandi Forum Moderator Diagnosed in 1998, currently in remission. Diagnosed with Lupus in 2006. Last Count - 344k - 6-9-18
  • Posts: 12436
  • Karma: 11
  • Thank you received: 2371
Researchers at Baylor College of Medicine have found genes associated with an autoimmune bleeding disorder called chronic immune thrombocytopenia, or ITP.

Dr. Jenny Despotovic, assistant professor of pediatrics at Baylor and Texas Children’s Cancer and Hematology Centers, presented the research Dec. 5 at the American Society of Hematology 57th Annual Meeting.

ITP is an autoimmune disorder in which antibodies are formed against platelets, resulting in a low platelet count and blood that does not properly clot, increasing the risk of bleeding, which can be severe and even life threatening. The study sought to identify genetic variants associated with susceptibility to and severity of the disease.

Researchers obtained DNA samples from the North American Chronic ITP Registry and the Platelet Disorders Center at the Weill-Cornell Medical Center, and whole exome sequencing was performed at Baylor College of Medicine’s Human Genome Sequencing Center. This work was done as a collaboration with the ITP Consortium of North America, of which Baylor and Texas Children's Hospital have been key participants since its inception.

“Results of the study showed that variants in genes associated with immune cell signaling, including IFNA17, are significantly more common in children with chronic ITP than in the healthy population,” Despotovic said.

Of the 172 ITP patients in the study, more than 40 percent had a variant in IFNA17, including one variant present in 26 percent of the ITP patients compared to about 5 percent of controls. This gene is associated with immune cell activity, and could have an important role in predisposition to ITP or disease severity.

“We also identified genes, including DOK3, that are far more common in children with ITP who required more aggressive treatment than those who did not,” Despotovic said.

“This study is the first of its kind in chronic ITP, and these findings may facilitate improved understanding of the development of this disease and why it becomes a chronic disease in some children,” she said. “In addition, understanding patients’ genetic changes could lead to more personalized approaches to treatment of this disorder.”

Others who contributed to this research included Eric Boerwinkle and Linda Polfus, both of the University of Texas Health Science Center at Houston, Jonathan Flanagan of Baylor and Texas Children’s Hospital, as well as numerous collaborators in ICON.

www.bcm.edu/news/pediatrics/genes-associated-with-bleeding-disorder-found

Please Log in or Create an account to join the conversation.

MTHFR - update 11-21-15 6 years 11 months ago #52195

  • Melinda
  • Melinda's Avatar
Thanks Sandi - this is interesting for sure. Now they are talking children - think this would also apply to those of us adults who show up with ITP in their 40s, 50s, 60s?

Please Log in or Create an account to join the conversation.

MTHFR - update 11-21-15 6 years 11 months ago #52196

  • Rob16
  • Offline
  • Posts: 1125
  • Karma: 2
  • Thank you received: 275
Whatever happened to the promising studies showing successful use of alpha interferon to treat refractory ITP?

Now that there has been shown an association between the alpha17-interferon gene and ITP, perhaps research into treating ITP with interferon might be re-invigorated. Perhaps better targeting of specific variants of interferon, and/or perhaps better patient selection based on genetic testing would make such treatment even more effective.

European Journal of Cancer and Clinical Oncology
Volume 27, Supplement 4, December 1991, Pages S63-S68
International Cancer Update: Focus on Interferon Alfa-2b
Alpha interferon therapy in the treatment of idiopathic thrombocytopenic purpura
Stephen J. Proctor ∗
Abstract
Treatment of patients with idiopathic thrombocytopenic purpura (ITP) varies according to the severity of the condition, the patient's age and the phase of the disease. The mainstay of treatment is corticosteroid therapy, with splenectomy for non-responding patients. For the 5%–10% of patients with refractory disease and bleeding problems, intravenous immunoglobulins are often used. Danazol achieves a response in about 30%–40% of refractory patients. At our centre, we have now treated 13 patients with interferon alfa-2b, all of whom had severe steroid-unresponsive ITP of various durations. All patients received 12 injections of 3 million units (MU) interferon subcutaneously three times a week. The platelet count rose significantly in 10 patients after interferon therapy and in one patient during therapy. Three patients had a complete response and eight a partial response. One complete responder relapsed at 5 months but again responded to retreatment with interferon. Responses were similar in splenectomized and non-splenectomized patients, and platelet-associated immunoglobulin levels remained essentially unchanged. Based on a compilation of data from this and other studies, the positive response rate (platelets at least 30–200 × 109/L for at least 6 weeks) is 69% (2232 patients). The future role and dosage of interferon in ITP remains to be determined and particularly in direct comparison with intravenous IgG therapy.

Please Log in or Create an account to join the conversation.

MTHFR - update 11-21-15 6 years 11 months ago #52198

  • Melinda
  • Melinda's Avatar
A 24 year old study - 13 patients

Please Log in or Create an account to join the conversation.

MTHFR - update 11-21-15 6 years 11 months ago #52200

  • Rob16
  • Offline
  • Posts: 1125
  • Karma: 2
  • Thank you received: 275
You're the first ever to criticize me for too few citations!

scholar.google.com/scholar?start=0&q=interferon+itp&hl=en&as_sdt=0,11


Interferon treatment of refractory idiopathic thrombocytopenic purpura (ITP)
P Dubbeld, HFP Hillen… - European journal of …, 1994 - Wiley Online Library
Abstract: Up to 30% of patients with idiopathic thrombocytopenic purpura (ITP) are refractory
to standard therapy with corticosteroids and splenectomy. The treatment of refractory ITP is
barely effective, but promising results of interferon therapy were reported recently. In a ...
Cited by 37 Related articles All 4 versions Cite Save

INTERFERON ALPHA‐2b THERAPY IN ADULT CHRONIC THROMBOCYTOPENIC PURPURA (ITP)
S Bellucci, D Bordessoulte, B Coiffier… - British journal of …, 1989 - Wiley Online Library
In adults, immune thrombocytopenic purpura (ITP) is characterized by its frequent evolution
towards chronicity (Bellucci et al. 1988). Therapy, at this phase of the disease, remains
difficult and is more often ineffective (Pizzuto & Ambriz, 1984). Recently, Proctor et a1 ( ...
Cited by 30 Related articles All 4 versions Cite Save

Recombinant human interferon α‐2b (rh IFNα‐2b) therapy for steroid resistant idiopathic thrombocytopenic purpura (ITP)
K Fujimura, T Takafuta, S Kuriya, T Abe… - American journal of …, 1996 - Wiley Online Library
Treatment with either administration schedule did not result in sustaining platelet counts above
50 × 10 9 /L for a long time after treatment. The results indicate that once a week administration
schedule of rh IFNα-2b is more efficacious for platelet counts increasing for short period in ...
Cited by 24 Related articles All 4 versions Cite Save

Improvement of platelet counts in steroid-unresponsive idiopathic immune thrombocytopenic purpura after short-course therapy with recombinant alpha 2b interferon [ …
SJ Proctor, G Jackson, P Carey, A Stark, R Finney… - Blood, 1989 - Am Soc Hematology
... In 1 3 patients with severe steroid-refractory idiopathic immune thrombocytopenia (ITP).
a short course of recom- binant a 2b interferon (IFN). given at a dose of 3 MU for 12 doses.
caused a significant increase in platelet count in 11 patients. ...
Cited by 92 Related articles All 6 versions Cite

… of transforming growth factor‐β1 and correlated elevation of interleukin‐17 and interferon‐γ in pediatric patients with chronic primary immune thrombocytopenia (ITP)
JD Wang, TK Chang, HK Lin, FL Huang… - Pediatric blood & …, 2011 - Wiley Online Library
Background Dysregulated T helper (Th) cells are considered important in the
pathophysiology of chronic primary immune thrombocytopenia (ITP). The present study
investigated whether levels of Th cytokines in pediatric patients with chronic ITP were ...
Cited by 24 Related articles All 3 versions Cite Save

[CITATION] Short-course alpha-interferon therapy in severe unresponsive immune thrombocytopenic purpura
SJ Proctor, G Jackson, P Carey, A Stark - The Lancet, 1988 - Elsevier
Cited by 36 Related articles All 4 versions Cite Save

Alemtuzumab more effective than interferon β-1a at 5-year follow-up of CAMMS223 clinical trial
AJ Coles, E Fox, A Vladic, SK Gazda, V Brinar… - Neurology, 2012 - AAN Enterprises
... AE= adverse event; ARR= annualized relapse rate; DMT= disease-modifying therapy; EDSS=
Expanded Disability Status Scale; GBM= glomerular basement membrane; IFNβ-1a= interferon
β-1a; ITP= immune thrombocytopenia; LLN= lower limit of normal; MS= multiple ...
Cited by 132 Related articles All 9 versions Cite Save

Cytokines in idiopathic thrombocytopenic purpura (ITP)
J Andersson - Acta Paediatrica, 1998 - Wiley Online Library
... 4 (IL-4) Low or normal Interleukin-10 (IL-10) Normal or elevated Granulocyte-macrophage colony
stimulating Elevated factor (GM-CSF) Thrombopoietin (TPO) Normal Chronic idiopathic
thrombocytopenic purpura (ITP) Interleukin-2 (IL-2) Increased or normal Interferon-g (IFN-g ...
Cited by 77 Related articles All 4 versions Cite Save
A favourable effect of long‐term α‐interferon therapy in refractory idiopathic thrombocytopenic purpura
S Kumakura, H Ishikura, H Tsumura… - British journal of …, 1993 - Wiley Online Library
... So. a-interferon therapy seems to be beneficial in some cases of refractory ITP in terms
of both remission induction and Kecently ... The mechanism of the induction of an increase
in platelet counts by a-interferon in ITP is unclear. However ...
Cited by 15 Related articles All 4 versions Cite Save

Alpha interferon therapy in the treatment of idiopathic thrombocytopenic purpura
SJ Proctor - European Journal of Cancer and Clinical Oncology, 1991 - Elsevier
... The future role and dosage of interferon in ITP remains to be determined and particularly in direct
comparison with intravenous IgG therapy. References. ... Interferon alfa-2b therapy in adult chronic
thrombocytopenic purpura (ITP). Br J Haematol, 73 (1989), p. 578. ...
Cited by 16 Related articles All 6 versions Cite Save

Continuous, low‐dose therapy with interferon‐α for human immunodeficiency virus (HIV)‐related immune thrombocytopenic purpura
DW Northfelt, LD Kaplan… - American journal of …, 1991 - Wiley Online Library
... Page 2. Brief Report: Continuous Interferon-a for HIV-Related ITP 239 mm3 following 12 weeks
of therapy. ... Toxicities observed when interferon-a and zidovudine are administered at higher doses
[7] did not occur. Treatment of ITP with interferon-a has been de- scribed. ...
Cited by 10 Related articles All 4 versions Cite Save

Interferon therapy in intravenous drug users with HIV-associated idiopathic thrombocytopenic purpura.
R Stellini, G Rossi, G Paraninfo - Haematologica, 1991 - europepmc.org
... recombinant alpha interferon (rIFN) has been used in classic ITP with conflicting results.
We have tested its activity in a group of intravenous drug users (IVDUs) with HIV-associated
ITP, who also had a high prevalence of chronic liver disease. ...
Cited by 10 Related articles All 3 versions Cite Save More

α‐interferon therapy for severe chronic idiopathic thrombocytopenic purpura in children
RJ Cohn, R Schwyzer, JE Poole… - American journal of …, 1993 - Wiley Online Library
... South Africa. Page 2. Interferon Therapy for Childhood ITP 247 ... Splenectomy Splenectomy
Asymptomatic Asymptomatic Asymptomatic ”ITP Interferon Response Scale (51: Type I. complete
response, with a return of platelet count to >200 K lO'/liter for >3 months; Type Ila. ...
Cited by 20 Related articles All 4 versions Cite Save

Gene expression profile of idiopathic thrombocytopenic purpura (ITP)
R Sood, W Wong, M Jeng… - Pediatric blood & …, 2006 - Wiley Online Library
... q-value <1.8%, that best distinguish ITP from control samples and this ITP gene signature is shown
in Figure 1. The most prominent finding in our data is the elevated expression of several genes
previously known to be induced by Interferon (IFN) specifically in the ITP samples. ...
Cited by 18 Related articles All 4 versions Cite Save

[HTML] Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response
FP Panitsas, M Theodoropoulou, A Kouraklis… - Blood, 2004 - Am Soc Hematology
... of adult chronic ITP patients and attempted to correlate cytokine polarization with the degree
of thrombocytopenia. We used semiquantitative reverse-transcriptase–polymerase chain reaction
(RT-PCR) to measure the expression of type-1 (interleukin-2 [IL-2], interferon γ [IFN-γ ...
Cited by 240 Related articles All 8 versions Cite Save

Management of chronic immune thrombocytopenic purpura in children and adults.
V Blanchette, J Freedman, B Garvey - Seminars in hematology, 1998 - europepmc.org
... Several therapies that have been reported, but that are rarely used in chronic ITP, include
cyclosporine A, interferon-alpha (IFN-alpha), plasma exchange, staphylococcal protein A
immunoadsorption, combination chemotherapy, dapsone, ascorbic acid, and colchicine. ...
Cited by 105 Related articles All 4 versions Cite Save

Please Log in or Create an account to join the conversation.

MTHFR - update 11-21-15 6 years 11 months ago #52202

  • Melinda
  • Melinda's Avatar

You're the first ever to criticize me for too few citations!

Not the case - it was the 24 year old study :)

Please Log in or Create an account to join the conversation.

IVIG and coronary syndrome - update 1-9-16 6 years 11 months ago #52576

  • Sandi
  • Offline
  • Sandi Forum Moderator Diagnosed in 1998, currently in remission. Diagnosed with Lupus in 2006. Last Count - 344k - 6-9-18
  • Posts: 12436
  • Karma: 11
  • Thank you received: 2371
Abstract

Intravenous immunoglobulin (IVIG) is a therapeutic preparation of pooled polyspecific IgG used effectively in immune thrombocytopenic purpura (ITP), autoimmune diseases, and inflammatory diseases. We present a case of a 67-year-old male who presented with diffuse petechiae and was diagnosed with immune thrombocytopenic purpura with platelet count less than 10,000 per milliliter. Treatment was initiated with IVIG. When the third dose of IVIG was being administered he developed hypertensive urgency and non-ST segment elevation myocardial infarction. He was deemed not to be a candidate for cardiac catheterization and was treated conservatively. IVIG can cause major thrombotic adverse events such as deep vein thrombosis, myocardial infarction and stroke, which are attributed to thrombosis and hyperviscocity. Decreasing the dosage of IVIG, administration of anticoagulants are proposed treatments for such events. We propose that patients receiving high-dose IVIG with previous coronary artery disease require meticulous cardiac monitoring. Further research is needed to determine the true adverse effects of high-dose IVIG and prophylaxis regimens to decrease the risk.

www.ncbi.nlm.nih.gov/pubmed/26720165

Please Log in or Create an account to join the conversation.

Thrombosis and ITP - update 1-27-16 6 years 10 months ago #52822

  • Sandi
  • Offline
  • Sandi Forum Moderator Diagnosed in 1998, currently in remission. Diagnosed with Lupus in 2006. Last Count - 344k - 6-9-18
  • Posts: 12436
  • Karma: 11
  • Thank you received: 2371
Abstract

Antiphospholipid antibodies (aPL) are common in ITP, but their role for the occurrence of ITP-related thrombosis is controversial. We performed a systematic review and a meta-analysis to investigate the risk of thrombosis associated with lupus anticoagulant (LA), anticardiolipin (aCL) and anti-β2GP-I antibodies in primary ITP. The literature search was run on Medline, Cochrane and ISI Web of Science from January 1st 1980 to December 31st 2014. Unpublished studies were searched in meeting abstracts. The main analysis assessed the risk of all thromboses (arterial or venous) associated with the presence of LA, aCL or anti-β2GP-I antibodies. Random-effect models were used to calculate odds ratios (OR) and their 95% confidence intervals (CI). Searches in electronic databases retrieved 776 citations. Twelve additional studies from unpublished literature were added. Eventually, 10 cohort studies totalizing 1574 patients were included in the analysis. The pooled OR for the risk of all thromboses associated with LA was 6.11, 95% CI [3.40-10.99]; it was 2.14, 95% CI [1.11-4.12] with aCL. The ORs were similar when stratifying on the type of thrombosis (arterial vs. venous). Only two studies assessed the risk of thrombosis associated with anti-β2GP-I antibody positivity; consequently, no pooled OR was computed for these antibodies. This meta-analysis highly suggests that LA positivity, and to a less extent aCL antibodies, are associated with an enhanced risk of thrombosis in primary ITP patients. Further prospective studies are needed to identify the factors associated with the risk of thrombosis among LA patients before assessing prevention strategies.

Copyright © 2015. Published by Elsevier B.V.

www.ncbi.nlm.nih.gov/pubmed/26708169

Please Log in or Create an account to join the conversation.

Pseudothrombocytopenia - update 1-29-16 6 years 10 months ago #52855

  • Sandi
  • Offline
  • Sandi Forum Moderator Diagnosed in 1998, currently in remission. Diagnosed with Lupus in 2006. Last Count - 344k - 6-9-18
  • Posts: 12436
  • Karma: 11
  • Thank you received: 2371
BACKGROUND:

Pseudothrombocytopenia (PTCP) is a well-known phenomenon. However, confusion may occur due to unusual characteristics.
CASE REPORTS:

Two patients with autoimmune thrombocytopenia (ITP) and long-lasting PTCP are described. Initially, only the diagnosis of ITP was confirmed. During observation, discrepancies were recognized between clinical findings and platelet counts. Re-examination resulted in the additional diagnosis of EDTA-dependent PTCP. Subsequently, the latter diagnosis was changed to citrate-dependent PTCP in both cases. Interestingly, PTCP was observed to change again and became recognizable in citrate or heparin, and only during the first 20-30 min following phlebotomy in EDTA specimens.
CONCLUSION:

The incidence of concomitant ITP with PTCP might be higher than previously reported, and PTCP may have variable dynamics and characteristics.

www.ncbi.nlm.nih.gov/pubmed/26696805

Please Log in or Create an account to join the conversation.

Charity NavigatorGuideStar Seal NORD Member BadgeTHSNA logo