The initial study-procedure period for stem cell transplant includes outpatient and hospital care and will last approximately 3 months. Below is an overview of the autologous stem cell transplant procedure.

Stem Cell Mobilization

Peripheral blood stem cells will be mobilized from the bone marrow using injections of granulocyte colony stimulating factor (G-CSF).

Leukapheresis

Stem cells will be removed from the peripheral blood stream and stored for future use. Depending on the CD34+ progenitor cell count yield, between 1–5 collections will be needed. Each leukapheresis collection will take approximately 4 hours.

CD34 Selection

CD34+ cells will be selected using a cell-separator machine. This is done in an effort to remove lymphocytes that are potentially scleroderma disease causing from the collection.

Cryopreservation

The cells are stored in a freezer until the time of transplant. After completion of high-dose immunosuppressive therapy (HDIT), the blood stem cells are thawed and reinfused through a central line.

High-dose Immunosuppressive Therapy (HDIT)

A conditioning regimen of HDIT using total body irradiation (TBI) and cyclophosphamide was chosen to provide high-dose immunosuppression. Pre- and post-transplant antithymocyte globulin (ATGAM) will be administered to eliminate lymphocytes that survive the preparative regimen and stem cell selection process. The fractionated TBI dose of 800 cGy is lymphocyte destructive, but it is a reduced dose compared with most TBI-containing regimens used in treatment of malignancy (> 1200 cGy). This dose is similar to that used in pilot and phase II HDIT transplantation studies of SSc. When combined with cyclophosphamide and ATGAM, TBI is expected to provide maximal immunosuppression with acceptable toxicity.(62) Bilateral lung and kidney shielding will be employed to prevent possible renal or pulmonary toxicities.

Stem Cell Transplantation

The autologous CD34- selected hematopoietic progenitor cells will be infused after completion of HDIT to repopulate the immunologic and hematologic blood systems.

In the high-dose cyclophosphamide arm, participants will receive IV pulse cyclophosphamide at 28- to 32-day intervals for 12 months.