Autologous Stem Cell Transplant (ASCT) for Autoimmune Diseases

Autologous Hematopoietic Stem Cell Transplant for Children and Young Adults With Life Threatening Autoimmune Diseases

A subset of autoimmune diseases (ADs) in children and young adults are life-threatening and unresponsive to conventional treatments. In these patients, the delivery of high dose immunosuppressive therapy followed by autologous stem cell transplant (ASCT) offers a treatment strategy capable of purging the pathogenic, autoreactive immune system and an opportunity for "immune reset." This strategy has been used in adults across a myriad of indications with evidence for efficacy. This study proposes a pilot study to evaluate this therapeutic strategy in children and young adults with systemic sclerosis (SSc) and systemic lupus erythematosis (SLE), two potentially life threatening autoimmune diseases that may response to this therapeutic approach.

The purpose of this study is to determine the safety and feasibility of CD3/CD19 depleted autologous stem cell transplant for the treatment of life threatening autoimmune disease. We will perform CD3/CD19 depletion using the CliniMACs device as a means of purging autoreactive T and B cells from the transfused autologous stem cell product, while retaining some immune function, namely natural killer cells and monocytes in the product.

o Pulmonary function: Change in forced vital capacity (FVC), total lung capacity (TLC) or diffusing capacity of the lung for carbon monoxide (DLCO) > 10%

o Skin condition: An improvement is indicated by a decrease on modified Rodan Skin Score (mRSS) of > 5 points

o Complete remission off therapy (BILAG D/E only or SLEDAI=0 and no SLE treatment except hydroxychloroquine)

Events include death, and significant persistent organ damage o An event based on organ dysfunction must be documented on at least two occasions, at least three months apart and include: respiratory failure (resting O2 saturation < 88%), renal failure (chronic dialysis) and cardiomyopathy (clinical congestive heart failure New York Class III or IV, left ventricular ejection fraction (LVEF) < 30% by echocardiogram despite therapy)

• Achieving an absolute neutrophil count (ANC) > 500 cells/uL and an unsupported platelet count of > 20,000 cells/uL for three consecutive days

Quality of life will be measured based on the Patient-Reported Outcomes measurement Information System (PROMIS) that evaluates physical, mental and social health in adults and children. patient reported outcome measurement information system (PROMIS) will be administered to each patient (or proxy) prior to autologous stem cell transplant (ASCT) and three times/year for the first two years post-transplant and then annually until five years post-transplant.

Inclusion Criteria: Age 8 ≤ 25 years at time of enrollment. Severe systemic sclerosis or systemic lupus erythematosus based on specific criteria Adequate organ function status No active, untreated infections. Exclusion Criteria: Previous hematopoietic stem cell transplant (HSCT) or solid organ transplant Pregnancy Ongoing participation in a clinical trial testing an investigational drug or ongoing receipt of disallowed disease modifying anti-rheumatic drugs (DMARD) Severe comorbidity that jeopardizes the ability of the subject to tolerate therapy