About
What We Do

      The foundation is named after 12-year-old Brittany Balser of Hilliard, who, after a 4-week fight with the disease in Children’s Hospital in Columbus, Ohio, lost her life to TTP. Thrombotic thrombocytopenic purpura is a rare blood disease that afflicts females ages 20–50, but recently has afflicted younger girls ages 12 to 14.

    Fund-raising efforts through the generosity of corporations, music artists (local and national), audio visual companies, and professional athletes, restaurants, hotels are very significant to the future outcome of this endeavor. We will be announcing upcoming benefit concerts with nationally known artists that will be helping out the foundation by playing shows all over the USA with RUSH CONCERTS.  Grammy Award winners, along with and multi-million album selling artists have worked with our foundation including STYX, 38 SPECIAL, ASIA, KUTLESS, FAMILY FORCE 5, SKILLET, PETRA, JARS OF CLAY, NATALIE GRANT, and DISCIPLE and HOUSE OF HEROES.

 

 

Due to the rarity of this fatal disease, the doctors at Children’s Hospital had very little medical information or experience with which to treat and save Brittany's life.  The fact that it is a rare blood disease has meant that little has been done to fund research and development of new and better ways to diagnose and treat it. It is also due to the rarity of the disease that our foundation has NOT benefited from donations from corporations, or grants for research from underwriters.
We do need your help!
 

 
Research

Britt Balser Foundation For TTP Information on Research on TTP
by Dr. Spero Cataland:

The National Blood Foundation (NBF) Announces
Recipients of the 2007 NBF Scientific Research Grants

Bethesda, Md. - The National Blood Foundation (NBF) Board of Trustees recently announced the recipients of the 2007 NBF Scientific Research Grants.  Each grant recipient will receive up to $65,000 to pursue either a one- or two-year research project in the field of blood banking, transfusion medicine or cellular and related biological therapies. To date, NBF has awarded more than $5 million in grants since 1985 to 145 early-career researchers. This year’s recipients are: Spero Cataland, MD; Peiman Hematti, MD; Cheryl Lobo, PhD; Louise McCormick, PhD; Michael Milsom, PhD; Lirong Qu, MD, PhD; Astrid Van Halteren, PhD; Saul Yedgar, PhD; and Gregory Barshetin, PhD.

“The NBF Grants Review Committee received 32 applications for innovative research proposals from professionals in the United States and four other countries,” said Connie Westhoff, PhD, chair of NBF's Grants Review Committee. “This year we saw a marked increase in applications on cellular and related biological therapies, compared to past years.”

Proposals for NBF grants are evaluated on the basis of their scientific merit; relevance to and impact on transfusion medicine and science. NBF scientific research grants are made possible by contributions from NBF's Council on Research and Development (CORD) members and its NBF Partners, along with gifts from individuals, institutions and foundations.

The following are synopses of the eight winning proposals:

Spero Cataland, MD, Ohio State University
Cyclosporine or Corticosteroids with Plasma Exchange in TTP

With an interest in the use of immune-based therapy of thrombotic thrombocytopenic purpura (TTP) and funding from the NBF grant, Cataland will begin a randomized study of the efficacy of cyclosporine or corticosteroids as an adjunct to plasma exchange for the treatment of TTP. Previous studies have indicated that the effectiveness of cyclosporine is related to the suppression of the antibody inhibitor of a disintegrin and metalloprotease with thrombospondin type-1 motif, member 13 (ADAMTS13) and improvement in ADAMTS13 activity and antigen. ADAMTS13 is reduced in TTP. Developing a practical immune-based therapy of TTP potentially could minimize a patient’s exposure to plasma and the complications of the plasma exchange procedure, while also conserving valuable blood bank resources.

 

Effect of Prophylactic Cyclosporine Therapy on ADAMTS13 Biomarkers in Patients with Idiopathic Thrombotic Thrombocytopenic Purpura

Spero R. Cataland,1 Ming Jin,2 Shili Lin,3 Eric H Kraut,1 James N. George,4 and Haifeng M. Wu2

1 Division of Hematology/Oncology, Department of Internal Medicine, Ohio State University, Columbus, OH 43210

2 Department of Pathology, Ohio State University, Columbus, OH 43210

3 Department of Statistics, Ohio State University, Columbus, OH 43210

4 Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190

Corresponding Author: Spero R. Cataland, M.D., Department of Internal Medicine, Ohio State University College of Medicine and Public Health, 320 W. 10th Ave., 306B Starling Loving Hall, Columbus, OH 43210, Telephone: (614) 293-2887; Fax: (614) 293-7529, Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

The publisher's final edited version of this article is available at Am J Hematol

Abstract

Several reports have been published regarding the use of cyclosporine (CSA) in the treatment of idiopathic thrombotic thrombocytopenic purpura (TTP). We hypothesized that prophylactic CSA therapy may prevent recurrences in patients with a history of multiple relapses of TTP. Nineteen patients with idiopathic TTP were enrolled on prospective studies at Ohio State University between September 2003 and May 2007. Patients achieving remission remained on CSA therapy for 6 months, allowing us to evaluate the efficacy of CSA as prophylactic therapy. CSA was administered orally at a dose of 2–3 mg/kg in a twice a day divided dose in all patients and continued for a total of 6 months. Long-term clinical follow-up with serial analysis of ADAMTS13 biomarkers during and after CSA therapy were performed to evaluate the efficacy of CSA as a prophylactic therapy. 17/19(89%) patients completed 6 months of CSA therapy in a continuous remission. Two patients relapsed during therapy with CSA and 7 patients relapsed after discontinuing CSA therapy. Ten patients have maintained a continuous remission a median of 21 months (range, 5 to 46) after discontinuing CSA. The ADAMTS13 data suggest that CSA resulted in a significant increase in the ADAMTS13 activity during therapy with CSA. 8/9(89%) relapsing patients had severely deficient ADAMTS13 activity (< 5%) suggesting this is a significant risk factor for relapse of TTP. These data support the hypothesis that prophylactic CSA improves the ADAMTS13 activity and may be effective at preventing relapses in patients at risk for recurrences of TTP.

Keywords: thrombotic thrombocytopenic purpura, ADAMTS13, cyclosporine, relapse, prophylactic therapy

Introduction

Our group has conducted several clinical studies to evaluate the efficacy of CSA, both as an adjunct to plasma exchange (PE) (1, 2) and alone in the treatment of idiopathic TTP(3). While these data suggest the efficacy of CSA in idiopathic TTP, questions regarding the mechanism of action and the risk of relapse after stopping CSA remain to be answered. Therapy with CSA continued after a patient has achieved a sustained (> 30 days) remission could be viewed as prophylactic, with a goal of preventing relapses (recurrence of TTP > 30 days after the last exchange) of TTP. This analysis is focused over the time period beginning 30 days after remission was achieved, allowing us to study the efficacy and potential mechanisms of action of prophylactic CSA in the prevention of relapses of TTP.

Results

Clinical Efficacy Data

Seventeen out of the 19(89%) patients completed the planned 6 months of CSA therapy in a continuous clinical remission (Figure 1). Two of 19 (11%) patients relapsed during the 6 month course of CSA after 3 and 4 months of CSA respectively, one of which relapsed 2 weeks after a 50% dose reduction of the CSA as mandated by the study for an increased serum creatinine. After discontinuing CSA, 7/17 (41%) patients relapsed a median of 2 months (range, 0.5 to 33) after stopping CSA therapy. An analysis of the risk of relapse both during and after discontinuing CSA therapy in terms of events per month at risk was completed. During therapy with CSA, 3 recurrences (2 patient relapsing as described above during the initial 6 month CSA course, and one additional patient during his extended course of CSA as described below in the section entitled: “Long-Term Prophylactic CSA Therapy) occurred over 61 total months of cumulative CSA therapy for all patients. After discontinuing CSA, 6 recurrences occurred over 263 months of cumulative follow-up for all patients. The difference in the recurrence rate per month at risk during therapy with CSA compared to after discontinuing CSA therapy was not statistically significant (4.9% v. 2.3%, p=0.49). Ten of 17 (59%) patients have maintained a continuous clinical remission a median of 21 months (range, 5 to 46) after discontinuing CSA therapy.

Patients

Nineteen patients with idiopathic TTP previously enrolled on prospective, therapeutic studies at our institution between September 2003 and May 2007 that achieved remission after CSA therapy alone or as an adjunct to PE were included in this analysis. Eligibility criteria for these studies included a clinical diagnosis of idiopathic TTP, defined as a microangiopathic hemolytic anemia and thrombocytopenia (<100·109/L) without an alternative etiology. ADAMTS13 activity and inhibitor status were not known at enrollment and were not eligibility criteria for these studies. The focus of this analysis was the efficacy of CSA at preventing future relapses of TTP, therefore only patients from these previous studies that achieved a sustained remission (clinical remission >30 days after the last exchange procedure) with CSA were included. Fifteen patients achieved remission after treatment with concurrent CSA and PE that are included have been reported previously(2). Four additional patients achieved remission with the use of CSA. Two patients were treated with CSA alone for early recurrences of TTP as reported previously(3), and 2 additional patients had CSA added to PE after their failure to be successfully tapered from PE. Both patients had PE discontinued on at least 2 occasions, only to develop a recurrent thrombocytopenia and rising lactate dehydrogenase levels within 48 hours necessitating the resumption of PE. After the last failed tapering from PE, CSA was started with the resumption of PE and continued for 6 months as with the other patients. These two patients have not been reported previously. Demographic details for all 19 patients are shown in Table I.

Treatment

In the patients that received CSA concurrent with PE to achieve remission, PE was performed and tapered using a uniform protocol that was consistent across all clinical trials as reported previously using cryoprecipitate-poor plasma as the replacement fluid(1, 2). CSA was started concurrently with the initiation of PE and administered orally at a dose of 2–3 mg/kg in a twice a day divided dose and continued for 6 months. Steroids were not administered except for intermittent intravenous doses of hydrocortisone as needed to treat reactions to the infused plasma. The 4 patients that started CSA at later time points (2 for early recurrences of TTP, 2 who failed tapering of PE) were treated with CSA at the same dose (2–3 mg/kg) and duration (6 months) of therapy. Based upon a history of multiple (>2) recurrences of TTP, 5 of the19 patients continued CSA beyond the planned 6 months as long-term prophylactic therapy. Patients were seen monthly during the six month course of CSA and then every 3 months in follow-up after discontinuing CSA therapy for clinical follow-up and to obtain samples to analyze the ADAMTS13 biomarkers.

Measurement of ADAMTS13 Biomarkers (ADAMTS13 Activity, Antigen, and ADAMTS13 Antibody (IgG) Concentration)

Plasma ADAMTS13 activity was determined using a method involving Surface Enhanced Laser Desorption/Ionization Time-of-flight Mass Spectrometry (SELDI-TOF-MS) that has been reported previously(14). SELDI-TOF-MS has the ability to provide rapid protein/peptide analysis. One distinguishing feature of SELDI-TOF-MS involves the surface chemistry of ProteinChips that allows for selective, rapid purification of protein/peptide candidates prior to analysis by mass spectrometry. Determination of the ADAMTS13 activity using the peak area of the peptide generated from the cleavage reaction rather than the peak height of the curve provides greater reproducibility and accuracy for all levels of ADAMTS13 activity, but especially at low levels of ADAMTS13 activity. The mass spectrometer-based assay directly measures the analyte in the sample and therefore is less affected by potential interfering factors such as hemolysis or bilirubin. ADAMTS13 autoantibody and ADAMTS13 antigen levels were determined using ELISA kits developed by American Diagnostica Inc. (Stamford, CT; USA)(® ADAMTS13 Autoantibody ELISA Imubind, IMUBIND® ADAMTS13 ELISA). The results from these tests are reported as micrograms of IgG antibody and nanograms of ADAMTS13 protein per milliliter of patient plasma respectively.

Statistical Methods

We fitted a regression model to compare the profiles (based on serial measurements) of the ADAMTS13 activity during the 6-month course of prophylactic CSA therapy between the group of patients maintaining a continuous remission versus the group who eventually relapsed after discontinuing CSA. Because the serial measurements of each patient are correlated, we included a random effect component in the model to account for such correlations. Analysis to compare the ADAMTS13 antibody inhibitor and antigen between these two groups was carried out similarly, but with the data being log-transformed first to achieve approximate normality. To gauge whether any of the three ADAMTS13 biomarkers could be used to predict whether a patient would benefit from using CSA as a prophylactic treatment therapy, we also compared the 2 patients who relapsed during CSA treatment with the patients that completed 6 months of therapy in a continuous remission. The same analysis strategy used for the first set of comparisons was applied to this comparison.

Acknowledgments

This study is supported in part by grants from National Institutes of Health K08HL03279, grant support from Ohio Biomedical Research and Technology Transfer Commission, and support from the Britt Balser Foundation for TTP.

References

1. Cataland SR, Jin M, Ferketich AK, Kennedy MS, Kraut EH, George JN, Wu HM. An evaluation of ciclosporin and corticosteroids individually as adjuncts to plasma exchange in the treatment of thrombotic thrombocytopenic purpura. Br J Haematol. 2007;136:146–149. [PubMed]

2. Cataland SR, Jin M, Lin S, Kennedy MS, Kraut EH, George JN, Wu HM. Ciclosporin and plasma exchange in thrombotic thrombocytopenic purpura: long-term follow-up with serial analysis of ADAMTS13 activity. Br J Haematol. 2007;139:486–493. [PubMed]

3. Cataland S, Jin M, Zheng X, George JN, Wu HM. An evaluation of cyclosporine alone for the treatment of early recurrences of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2006;4:1162–1164. [PubMed]

4. Howard MA, Williams LA, Terrell DR, Duvall D, Vesely SK, George JN. Complications of plasma exchange in patients treated for clinically suspected thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Transfusion. 2006;46:154–155. [PubMed]

5. Vesely SK, George JN, Lammle B, Studt JD, Alberio L, El-Harake MA, Raskob GE. ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients. Blood. 2003;102:60–68. [PubMed]

6. Mannucci PM, Peyvandi F. TTP and ADAMTS13: When Is Testing Appropriate? Hematology Am Soc Hematol Educ Program. 2007;2007:121–126. [PubMed]

7. Zheng XL, Kaufman RM, Goodnough LT, Sadler JE. Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura. Blood. 2004;103:4043–4049. [PubMed]

8. Ferrari S, Scheiflinger F, Rieger M, Mudde G, Wolf M, Coppo P, Girma JP, Azoulay E, Brun-Buisson C, Fakhouri F, Mira JP, Oksenhendler E, Poullin P, Rondeau E, Schleinitz N, Schlemmer B, Teboul JL, Vanhille P, Vernant JP, Meyer D, Veyradier A. Prognostic value of anti-ADAMTS 13 antibody features (Ig isotype, titer, and inhibitory effect) in a cohort of 35 adult French patients undergoing a first episode of thrombotic microangiopathy with undetectable ADAMTS 13 activity. Blood. 2007;109:2815–2822. [PubMed]

9. Jin M, Casper TC, Cataland SR, Kennedy MS, Lin S, Li YJ, Wu HM. Relationship between ADAMTS13 activity in clinical remission and the risk of TTP relapse. Br J Haematol. 2008;141:651–658. [PubMed]

10. Banno F, Kokame K, Okuda T, Honda S, Miyata S, Kato H, Tomiyama Y, Miyata T. Complete deficiency in ADAMTS13 is prothrombotic, but it alone is not sufficient to cause thrombotic thrombocytopenic purpura. Blood. 2006;107:3161–3166. [PubMed]

11. Medina PJ, Sipols JM, George JN. Drug-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Curr Opin Hematol. 2001;8:286–293. [PubMed]

12. Zarifian A, Meleg-Smith S, O’Donovan R, Tesi RJ, Batuman V. Cyclosporine-associated thrombotic microangiopathy in renal allografts. Kidney Int. 1999;55:2457–2466. [PubMed]

13. Elliott MA, Nichols WL, Jr, Plumhoff EA, Ansell SM, Dispenzieri A, Gastineau DA, Gertz MA, Inwards DJ, Lacy MQ, Micallef IN, Tefferi A, Litzow M. Posttransplantation thrombotic thrombocytopenic purpura: a single-center experience and a contemporary review. Mayo Clin Proc. 2003;78:421–430. [PubMed]

14. Jin M, Cataland S, Bissell M, Wu HM. A rapid test for the diagnosis of thrombotic thrombocytopenic purpura using surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF)-mass spectrometry. J Thromb Haemost. 2006;4:333–338. [PubMed]

 
About the Foundation

      Our foundation is a Nationally recognized 501(c)(3) charity named after 12-year-old Brittany Balser, who, after a 4-week fight with the disease in Children's Hospital in Columbus, Ohio, lost her life to TTP. The foundation is a public charity dedicated to raising funds to work with doctors and medical centers around the United States who are actively using their medical knowledge, and their resources to find a better cure for this horrible disease.

     The foundation is named after 12-year-old Brittany Balser, who, after a 4-week fight with the disease in Children’s Hospital in Columbus, Ohio, lost her life to TTP. Thrombotic thrombocytopenic purpura is a rare blood disease that primarily strikes females ages 20–50, but recently has afflicted younger girls ages 12 to 14. Due to the rarity of the disease, the doctors at Children’s Hospital had very little medical information or experience with which to treat it. The fact that it is a rare blood disease has meant that little has been done to fund research and development of new and better ways to diagnose and treat it.

Our Goals:

  1. To publish and distribute a publication that will describe the mortality rate and risks involved with TTP. The publication will include all medical aspects of the disease and give those that are afflicted with the disease a clear description of the treatment options that are involved with the disease. This publication will be authored by Dr. James George of The Oklahoma Blood Institute together with Dr. Spero Cataland of Ohio State University, and will be distributed to medical facilities across the United State States and Northern America.
  2. To raise funds that will be distributed to the Ohio State Medical Research Foundation that funds Dr. Spero Cataland's research into new advances that will reduce the mortality risks associated with TTP. Dr. Cataland is spear heading the research into fighting this rare and fatal blood disease.
  3. The foundation is dedicated to the promotion of the awareness of organ donation by partnering with Lifeline of Ohio to distribute information at all benefit shows.

The foundation is dedicated to raising funds to work with doctors and medical centers around the United States who are actively using their medical knowledge, and their resources to find a better cure for this horrible disease. Our foundation will be working closely with Dr. James George of The Oklahoma Blood Institute. Dr. George is one of the leading experts involved in the study of the disease. He publishes a TTP newsletter and has had his medical research published in various medical journals.

We hope to become a major force in bringing awareness of the disease and its effect on people who become afflicted with the disease. Many medical centers in the United States do not have adequate medical resources on this disease, and it is often very hard for physicians to diagnose.

The fact remains that thrombotic thrombocytopenic pupura is a dangerous disorder with substantial acute mortality along with uncertain long-term prognosis. This is the reason that this organization will help the medical profession learn more about the TTP so they can provide better diagnostic precision, less perilous treatment, and improved ability for doctors to advise patients about risks for disabilities and possible relapse.

All those involved in the foundation hope that other families will gain more knowledge of the sickness which afflicts their loved one. With new insight into treatment, these families may not have to go through the experience of losing a beautiful daughter at the young age of 12 — or at any age.

Fundraising efforts through the generosity of corporations, music artists (local and national), and athletes at all levels will be very significant to the future outcome of this endeavor.

From our hearts, we personally would like to thank ALL of those sponsors and volunteers that have helped to make this charity a viable source to fight this deadly and rare disease.

 

 


Become a Sponsor

Hundreds of people and organizations have helped support the efforts of the foundation.  We would like extend a special thanks to those involved and acknowledge their participation.  See how to become an event sponsor.

Raising Funds

Hundreds of people and organizations have helped support the efforts of this 501 (c)(3) public charity. We would like extend a special thanks to those involved and acknowledge their participation. See how you can donate to the research of this disease.