Trial Information

High-Dose Cyclophosphamide With CD34+ Selected Autologous Hematopoietic Cell Support for Treatment of Refractory Chronic Autoimmune Thrombocytopenia

Autoimmune Thrombocytopenia (AITP) is a disorder of low blood platelet counts in which
platelet destruction is caused by antiplatelet autoantibodies. A large proportion of
patients with chronic AITP are refractory to standard therapies including corticosteroids,
immune globulin and splenectomy. Cyclophosphamide is a cytotoxic immunosuppressive agent
which may induce durable remissions of refractory autoimmune diseases. High-dose
cyclophosphamide with peripheral blood stem cell (PBPC) rescue has been proposed as a
potential definitive therapy for AITP; however, the infusion of autoreactive lymphocytes
could result in relapse. The use of PBPC depleted of T-lymphocytes could circumvent this
limitation.

The purpose of this phase I/II study is to explore the feasibility and safety of this
approach, and to seek preliminary evidence of effectiveness, of using high-dose
cyclophosphamide (50 mg/kg/day x 4) followed by infusion of autologous PBPC enriched for
CD34+ cells (concomitantly depleted of CD3+ cells) for the treatment of patients with
refractory AITP. Safety/feasibility parameters to be examined will include the ability to
mobilize, harvest and purify sufficient PBPC to yield greater than 2 x 10(6) CD34+ cells/kg;
symptomatic acceptability and hematologic toxicities of the mobilization regimen (filgrastim
10 micrograms/kg/day IV); tolerability of the leukapheresis procedure, including the central
line placement and maintenance; depth and duration of blood cell nadirs following
chemotherapy; peritransplant bleeding episodes and transfusion requirements; episodes of
febrile neutropenia, culture-proven infections and antibiotic usage. Effectiveness will be
gauged by the rapidity and number of patients to achieve complete remission (platelet count
greater than 100,000/mm(3) and partial remission (platelet count greater than 50,000/mm(3)
or doubling of the platelet count with resolution of bleeding episodes). Ancillary evidence
of therapeutic effect will be sought by examining changes in titers of platelet surface
glycoprotein antibodies. In addition, alterations in T-lymphocyte subsets will be examined
by flow cytometry. If this treatment approach appears feasible, this study will form the
basis for a larger trial to compare alternate treatment approaches.