Scleroderma: Cyclophosphamide or Transplantation (SCOT) Substudy 03

The purpose of this mechanistic study is [1] to describe the condition of peripheral T cell
reactivity and repertoire diversity in SSc patients and evaluate evidence for potential
defects prior to randomization, [2] to gain a better understanding of the impact of
cyclophosphamide (CY) and high-dose immunosuppressive therapy with autologous peripheral
blood stem cell transplantation (HDIT-transplantation) on thymopoiesis, and [3] to describe
the kinetics and breadth of T cell immune recovery in SSc patients treated with
HDIT-transplantation.

Recruitment for this study will be limited to participants who have elected to participate
in the SCOT study and have been randomized to one of the SCOT treatment arms. Participants
will be recruited after randomization to ensure balance on the two arms for this mechanistic
study and must agree to participate and sign an informed consent for this mechanistic study
prior to initiation of treatment on either arm. Sixty participants, 30 from each arm, will
be recruited for this sub-study. It will be conducted at the participating SCOT transplant
centers.

Peripheral blood samples will be collected (20 mL) pre-treatment (prior to first infusion
for cyclophosphamide arm or mobilization for transplant arm) and approximately 6, 12, 24,
36, and 48 months post completion of treatment to be aligned with the regularly scheduled
SCOT protocol visits. Specific measures will be the level of peripheral blood T Cell
Receptor Excision Circles (sjTREC) and peripheral blood T cell receptor Vbeta repertoire
diversity before and after completion of randomized therapy.

Inclusion Criteria:

- Participation in DAIT SCSSc-01 (SCOT Trial)

Exclusion Criteria:

- No additional exclusion criteria