Study of Cyclosporine or Corticosteroids as an Adjunct to Plasma Exchange in Thrombotic Thrombocytopenic Purpura (TTP)

TTP is a rare blood disorder that causes blood clots to form in the small blood vessels
throughout the body, including the kidneys, brain, abdomen, and the heart. Plasma exchange
is the standard treatment for TTP. Plasma exchange is a treatment that removes the plasma
(the liquid portion of the blood without any cells) from a patient and replaces it with
plasma from a donor. With plasma exchange, 90% of patients achieve a remission of the
disease. Unfortunately, up to one half of patient will relapse after the plasma exchange
has stopped, leading to significant complications and added risks to the patient.

This study randomizes patients to receive either prednisone or cyclosporine as an adjunct to
plasma exchange, with the cyclosporine arm being the experimental arm of the study. All
patients will undergo plasma exchange but will be randomized to receive either prednisone or
cyclosporine as an adjunct to plasma exchange. Previous studies suggested that cyclosporine
was superior to prednisone as an adjunct to plasma exchange, and therefore this randomized
study attempts to confirm the findings of two previous single institution studies.

Inclusion Criteria:

- Patients with a clinical diagnosis of idiopathic TTP as defined by a
microangiopathic hemolytic anemia and thrombocytopenia (<100 x 103)

- Additional components of the pentad (fever, renal and neurologic abnormalities) need
not be present.

- Additional explanations for the microangiopathic changes including DIC and malignancy
should be excluded.

- Patients with pregnancy associated TTP will be permitted on this therapeutic trial if
the child is delivered prior to the initiation of therapy for TTP. However, female
patients that are breastfeeding and are unwilling to discontinue breastfeeding at the
time of enrollment will be excluded from this study

- Patients with a previous diagnosis of TTP are eligible to be enrolled provided they
meet eligibility criteria and have not been treated for an TTP in the past 30 days

- Given the potential for nephrotoxicity with CSA, all patients must have a serum
creatinine of < 2.5 mg/dl prior to enrollment

Exclusion Criteria:

- In light of concern for the prompt initiation of PE, all patients with suspected TTP
may be enrolled on this trial. If it is subsequently found that the patient does not
meet enrollment criteria, they will be removed and their spot replaced for study
purposes. Patients removed from the study after enrollment will continue to be
followed longitudinally for 6 months to be monitored for safety and will be included
in the safety database.

- Patients with TTP clinically categorized as secondary to stem cell transplant and
solid organ, bloody diarrhea associated, malignancy associated, and drug associated
will not be enrolled on this therapeutic study.

- Incarcerated patients will be excluded from the study due to the inherent
difficulties in maintaining close follow-up for study purposes in patients who are
incarcerated.

- Any patients already being treated chronically with corticosteroids or cyclosporine
and taking these at the time of their presentation will be excluded from this study.

- Female patients that are breastfeeding and are unwilling to discontinue breastfeeding
at the time of enrollment will be excluded from this study

- Patients taking any medications contraindicated in combination with CSA that cannot
be safely discontinued will be excluded from this study.