New articles posted here - update 6-28-17

The trigger of what causes ITP is still elusive. Researchers know oxidative stress, caused by free radicals, plays a role in many autoimmune disorders. This study of children and adolescents looked at a possible direct link between platelets in ITP and oxidative stress. Researchers assessed oxidant–antioxidant systems and evaluated effect of antioxidant therapy on platelet count (PC) and bleeding score (BS) in ITP patients. In the six-month prospective, randomized double blind study 39 patients were newly diagnosed with ITP (ND), Group 1 (G1), and 39 patients had chronic ITP, Group 2 (G2). Both groups were compared with 39 healthy controls. Half of each group, G1A and G2A, each received daily antioxidant therapy, while Groups G1B and G2B received placebo. Key primary endpoints were the difference in change from baseline to six months in ITP-specific bleeding assessment and total antioxidant capacity (TAC).

Results showed TAC was significantly lower in newly diagnosed ITP patients compared to chronic ITP patients. Both groups showed lower levels than the healthy controls. At the end of the study both BS and PC improved a great deal in patients who received antioxidant compared to placebo. Researchers concluded there were reduced antioxidant mechanisms in ITP patients. Antioxidant therapy reduced the oxidative stress in both the newly diagnosed and chronic ITP patients. Some well-known antioxidants include Vitamins A, C, and E. Eating an anti-inflammatory diet also helps reduce oxidative stress.

Elalfy MS, Elhenaway YI, Deifalla S, et al. “Oxidant/antioxidant status in children and adolescents with immune thrombocytopenia (ITP) and the role of an adjuvant antioxidant therapy.” Pediatr Blood Cancer 2015, Feb 7: doi: 10.1002/pbc.25434 [Epub ahead of print]
www.ncbi.nlm.nih.gov/pubmed/25663642
informahealthcare.com/doi/abs/10.3109/09537104.2011.610909

Antibody-mediated platelet destruction in fetal or neonatal alloimmune thrombocytopenia (FNAIT) and ITP occurs primarily through engagement of immunoglobulin (Ig)G opsonized platelets with activating Fc receptors (FcRs) on the surface of phagocytes in the spleen and liver, resulting in phagocytosis and thrombocytopenia.2 In FNAIT, for example, the antiplatelet IgG antibodies cross the placenta and target the fetal platelets, which can result in serious complications such as intracerebral hemorrhage. Antibody titer has been shown to be related to fetal platelet counts3; however, this correlation is far from perfect, as there are many cases not attributed to antibody titer alone,4 suggesting other factors such as IgG Fc-fucosylation may be involved.5 Even more striking, in ITP, there is no test that reliably predicts bleeding outcomes or severity of bleeding. Thus, a tool for the prediction of both FNAIT and ITP severity is highly warranted.

See more....

www.bloodjournal.org/content/125/11/1690?sso-checked=true

This is a very interesting article and I'd love to see the long-term outcome on this. The very last sentence says it all, "Controlled trials with extended follow-up are needed to determine whether these intensive regimens induce more cures compared with standard treatment or merely delay relapse at the expense of potentially greater toxicity". The latter part of the sentence is the part that truly bothers me.


Abstract
Primary immune thrombocytopenia (ITP) in adults often assumes a chronic course that requires persistent monitoring and treatment. Medical therapy has traditionally been viewed as a means of temporarily raising the platelet count with little or no potential to induce long-term platelet responses off treatment. However, several recent studies have tested the hypothesis that intensive medical therapy administered early in the disease course may ameliorate or even cure ITP. In this review, we propose a biological rationale for medical intervention that simultaneously targets the innate and adaptive immune responses administered early in the course of disease. We also critically examine data on long-term outcomes after single-agent and multi-agent medical therapy. Intensive regimens that target inflammation and adaptive immunity (e.g., combination high-dose dexamethasone and rituximab) appear to improve response rates at 6 to 12 months compared with standard first-line therapy (e.g., prednisone, high-dose dexamethasone alone) in newly diagnosed patients. Controlled trials with extended follow-up are needed to determine whether these intensive regimens induce more cures compared with standard treatment or merely delay relapse at the expense of potentially greater toxicity.

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.


www.ncbi.nlm.nih.gov/pubmed/25793364


*One person on the FB page used the combo and had a six year remission.

I agree with the authors:
Long term controlled studies are certainly called for if the results of the following study hold up to further scrutiny.
50% of patients receiving a remission of 5 years (or more) is pretty impressive.

www.bloodjournal.org/content/122/21/2310
Rituximab Combined With Three Cycles Of High Dose Dexamethasone Provides a Long Term Response Rate Similar To That Of Splenectomy In Patients With Immune Thrombocytopenia (ITP) Of Duration Less Than 2 Years
Methods
Combination of standard-dose rituximab (weekly x 4) and usually 3 4-day cycles of 28mg/m2 (max. 40mg) dex at 2-week intervals (R+3Dex) was explored in 67 pediatric and adult pts with ITP at WCMC. ...
Conclusions
R+3Dex provides clearly superior results to rituximab alone. Notably, there was a 75% response rate overall (50/67 pts) compared to 50% with R alone. The 5 year response rate was almost 50% of all patients and 3/5 of responders. In patients who had had ITP for ≤ 2 years, the response is comparable to what has been reported with splenectomy...

Totally agree..long term trials are needed. Anything that allows people to retain their spleens has to be worth looking at

But toxicity needs to be considered. That's a potent start.

Long term trials will highlight any toxicities.. patients always have the choice to discontinue a trial if it isn't suiting them

That's not quite what I mean.

Some toxicities do not show up for years or are cumulative. Both of those (Rituxan and Dex) are potent treatments that have risks. If I knew it would cure me, I'd go for it. But if I knew that it might not, I would not want to try that first.

Reactions/side effects to drugs do occur and some are not temporary. If you end up with one or more, it's already too late.

Oh I agree Sandi but without trials we will never know what does and doesn't work so treatment options will never advance. This is why I volunteered for fostamatinib trial. The long term effects of prednisolone are very detrimental plus I have a perfectly healthy spleen doing its job properly and am exceedingly reluctant to part with it.

Sandi as we learned from my sister rituxan can be very potent and in my opinion dangerous if you are allergic. Is it typical to try rituxan right after pred or does that also change from person to person?

Mrsb - I realize that clinical trials are needed and I applaud the people who volunteer for them. Having been harmed by treatments for autoimmune disorders though, I tend to lean more towards an "the less drugs, the better" attitude. I'm all for saving the spleen (still have mine), but when the drugs cause permanent bodily damage, you begin to question and regret your choices.

Mac - there is no set order for treatments, but yes, it is common to try Rituxan after Prednisone.

Just read a fascinating article in the march 2015 edition of scientific america. My law partner was reading it at her eye doctor's office. "Electric Cures; bioelectronic cures could create an "off switch" for arthritis, diabetes even cancer." The author is Kevin Tracey who is a brain surgeon. I will not do it justice, but the idea is to stimulate the right part of the body to let it work to produce its own non toxic and appropriate response to resolve the issue. It does not sound like science fiction and maybe something that could be available in our lifetimes.

Sandi, I agree that it is important to test whether the combination therapy is worth the added risk of having both treatments at the same time, when one or the other alone might do the job, especially if one has the option of following up with the alternative treatment if the first one fails.

I know there were some studies a while back showing that Rituxan with high dose dexamethasone was more effective than HD-DXM alone, but I don't remember by how much, and I don't remember that the HD-DXM was done in multiple pulses.

The data from the following two studies may be comparing apples to oranges, especially regarding duration of response. Still, these studies seem to show that multiple pulses of HD-DXM may be nearly as good as the combination of Rituxan with multiple pulses of HD-DXM.

If this is correct, then it might be more prudent to try the treatments sequentially rather than combined. And if the first treatment works forego the second treatment along with the added risk.

I hope these issues will be taken into account when designing future studies.

www.bloodjournal.org/content/122/21/2310
Rituximab Combined With Three Cycles Of High Dose Dexamethasone Provides a Long Term Response Rate Similar To That Of Splenectomy In Patients With Immune Thrombocytopenia (ITP) Of Duration Less Than 2 Years

www.bloodjournal.org/content/109/4/1401
Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience

Wow.


Abstract
OBJECTIVE:

To determine the efficacy and safety of oral caffeic acid (CA) tablet in management of primary immune thrombocytopenia(ITP).
METHODS:

One hundred and three ITP patients with PLT>10×10⁹/L and no serious bleeding symptoms from three centers were enrolled. According to their platelet count before CA treatment, these patients were divided into group A (PLT<30×10⁹/L), including 24 females and 27 males with median age 48(18-84)years; and group B (PLT≥30×10⁹/L), including 33 females and 19 males with median age 43(18-83)years. Patients in both groups took CA tablets orally of 300 mg three times per day for 12 consecutive weeks. Combined medicine treatment such as corticosteroids, danazol, TPO and Rituximab, which might increase the platelet count of these patients, were not allowed during CA therapy.
RESULTS:

In group A, the overall response rate was 51.0%(26/51), with 2 patients achieving complete response (CR) and 24 patients achieving response(R). Of 26 patients achieving response (CR+R), the median platelet count before CA therapy was 20.5(15-28)×10⁹/L , and the median peak platelet count after CA therapy was 63(38-112)×10⁹/L. The median time to achieving response was 4(2-10) weeks. Patients with pretreatment PLT>20×10⁹/L showed significantly better response than those PLT<20×10⁹/L (68.0% vs 34.6%, P=0.017). In group B, the CR rate was 40.4%(21/52). Frequency of CA-related adverse events was 1.94%(2/103), including mild nausea in 1 case and elevation of liver enzymes in 1 case. Both were grade 1 and transient.

CONCLUSION:

Caffeic acid was effective in patients with ITP with few and mild adverse effects.



www.ncbi.nlm.nih.gov/pubmed/25778883

Ha! So it's my wine and chocolate diet that's keeping my count up! I knew I was doing something right.

Hate to disappoint you Ann but they are doing nothing for my count

Caffeic acid is UNRELATED to caffeine, but it is naturally found in certain foods and herbs:
en.wikipedia.org/wiki/Caffeic_acid

Edit:
"Even though caffeic acid can be found in coffee, it is unrelated to caffeine."
www.wisegeek.com/what-is-caffeic-acid.htm

Edited to provide Sandi a more reliable source.

Hey, it's a reliable source. What can I say?

Ha ha - sitting here with my 'real' coffee, momentarily got excited.
Thanks for all the time & effort Sandi & Rob.
mj

PS Sounds like a Mediterranean diet is the go with herbs, cinnamon, red wine etc.

Think I prefer the Wiki article: it has scientific references

(Caffeic acid) "It is also found in barley grain and in rye grain." WIKI

That's all I needed to know.....it's in my beer.


.

Caffeic acid is found in coffee, wine and chocolate. That's all we need to know!

FLORHAM PARK, N.J.--(BUSINESS WIRE)--Protalex, Inc. (OTCQB:PRTX), a clinical-stage biopharmaceutical company, announced today that it has received notice from the Office of Hematology and Oncology Products of the U.S. Food and Drug Administration (FDA) that it has reviewed the Investigational New Drug Application (IND) submitted under section 505(i) of the Federal Food, Drug, and Cosmetic Act for PRTX-100 and concluded that clinical studies with PRTX-100 in patients with Immune Thrombocytopenia (ITP) may be initiated. PRTX-100, Protalex’s lead drug, is a highly purified form of Staphylococcal Protein A and is the subject of ongoing clinical development in rheumatoid arthritis (RA) under a separate IND previously submitted to the FDA’s Division of Pulmonary, Allergy, and Rheumatology Products.

See more....

www.businesswire.com/news/home/20150331005154/en/Protalex-Announces-FDA-Acceptance-Investigational-Drug-Application#.VTfOCpOacSV

Abstract
BACKGROUND:

Mental stress and daily crises comprise a part of physical and mental threats. Perceived stress is a physical and mental threat, as well. Perceived stress is a psychological process during which the individual considers his/ her physical and psychological welfare as being threatened. Since idiopathic thrombocytopenic purpura (ITP) is one of the chronic diseases being able to affect patients' perceived stress, this study was conducted to compare perceived stress in ITP patients and healthy people.
MATERIALS AND METHODS:

This is a descriptive-comparative study with control and case groups. In this study, 64 ITP patients referring Seyed Al-Shohada Hospital and the same number of healthy individuals from the patients' neighborhood, as the control group, were selected randomly and compared. The Kohen Perceived Stress Standard Questionnaire was used to collect the data. The data were analyzed by SPSS and Student's independent t-test, chi-square, and Mann-Whitney test. Results : 64.1%, 59.4% and 53.1% of participants in case group were older than 35 years old, female and had elementary education. 78.1% of case group had severe perceived stress. 70.3% of participants in control group experienced mild perceived stress. Mann-Whitney test showed significant difference between two groups in level of stress (p<0.001).

CONCLUSION:

In ITP patients, perceived stress was considerable. Planning interventional measures to determine stress-making agents and subside or at least control them is very essential.

www.ncbi.nlm.nih.gov/pubmed/25922646

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 IIb study to describe the safety, efficacy and tolerability of oral dexamethasone 40mg Day 1-4, oral cyclosporine 2.5-3mg/kg/daily Day 1-28 and intravenous low-dose rituximab 100mg Day 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 survival 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).

www.bloodjournal.org/content/early/2015/05/13/blood-2015-03-631937?sso-checked=true

Two earlier studies of Rituxan + HD-DXM APPEAR to show better results than the triple therapy study does here.
HOWEVER: the triple study was done on "chronic" ITP patients whereas one of the other studies was done on "newly diagnosed" patients, and the other was done on a mixed group of patients, some up to to 2 years diagnosed and others longer. This makes a huge difference. Nonetheless, here are the comparisons, for what it's worth:

The 4 weeks standard dose Rituxan + 3 cycles X 4 days HD-DXM of the earlier study shown below gives better relapse free survival rates at 60 months than this triple therapy study of 4 weeks Low dose Rituxan + 1 cycle HD-DXM + 28 days cyclosporine at 24 months.

www.bloodjournal.org/content/122/21/2310
[Standard dose] Rituximab Combined With Three Cycles Of High Dose Dexamethasone Provides a Long Term Response Rate Similar To That Of Splenectomy In Patients With Immune Thrombocytopenia (ITP) Of Duration Less Than 2 Years

The study also claims a 60% 6 month response rate (does that mean CR? or CR+PR?), while an earlier study of 4 weeks low-dose (100 mg) Rituxan + 1 cycle x 4 days HD-DXM claims a 76.2% 6 month sustained response rate. So the triple therapy with cyclosporine APPEARS to have fared less well than the Gómez-Almaguer study.

High response rate to low‐dose rituximab plus high‐dose dexamethasone as frontline therapy in adult patients with primary immune thrombocytopenia
David Gómez-Almaguer, et al First published: 2 April 2013
N=21 Complete sustained response at 6 month 76.2%
onlinelibrary.wiley.com/enhanced/doi/10.1111/ejh.12102/#author1
www5.medicine.wisc.edu/~williams/ld_ritux_dex_itp.pdf

The fact that the triple therapy got such good results with CHRONIC ITP patients is extremely promising.

Rob16 wrote: Two earlier studies of Rituxan + HD-DXM APPEAR to show better results than the triple therapy study does here.
HOWEVER: the triple study was done on "chronic" ITP patients whereas one of the other studies was done on "newly diagnosed" patients, and the other was done on a mixed group of patients, some up to to 2 years diagnosed and others longer. This makes a huge difference.

Yes, that would make a big difference.

Abstract

Persistent or chronic immune thrombocytopenias (P/C-ITP) are acquired blood disorders lasting more than 3 months or 1 year, respectively. The pathogenesis of these disorders is thought to be immunological. We hypothesized that some patients with P/C-ITP might have an intrinsic megakaryopoiesis defect. We identified a group of P/C-ITP patients with acquired isolated mild thrombocytopenia (30-100 × 109 /l), undetectable anti-platelet antibodies, negative autoimmune investigations and no need for treatment. We examined in vitro megakaryocyte differentiation and compared these patients' results with those of acute-ITP patients and healthy controls. No difference in proliferation, ploidy or expression of surface markers was found. In contrast, P/C-ITP patients had significantly fewer proplatelet-forming megakaryocytes. This novel observation demonstrated that some patients diagnosed with P/C-ITP have an intrinsic megakaryopoiesis defect independent of the bone-marrow environment. Further investigations are needed to dissect mechanisms underlying this impaired proplatelet formation in these patients.

© 2015 John Wiley & Sons Ltd.

www.ncbi.nlm.nih.gov/pubmed/25873418

A 71-year-old female patient followed primary immune thrombocytopenia (ITP) was admitted to endocrinology unit with excessive sweating. We started methimazole for Graves' disease. Without any additional immunosuppressive treatment, at week 12 of methimazole therapy, thyroid stimulating hormone (TSH) levels returned to normal, and platelet counts rose to tolerable levels. When her hospital records were analyzed, they revealed that a year ago, when she had been diagnosed with ITP, her TSH values had been suppressed. After immunosuppressive therapy, her platelet values were maintained at normal levels, and during her control visits, her TSH levels were measured twice and were within normal limits. We think that immunosuppressive therapy for ITP without considering thyroid function tests may result in a transient euthyroid state, which potentially masks Graves' disease accompanying immunosuppressive therapy and associated recurrent ITP attacks.

www.ncbi.nlm.nih.gov/pubmed/25949982

Everyone should have a thyroid panel with their yearly physical - thankfully my MD did that, know my thyroid was just fine when the platelets started being destroyed.