Autologous Hematopoietic Stem Cell Transplant for the Treatment of Children and Young Adults with Systemic Sclerosis or Systemic Lupus Erythematosus

Inclusion Criteria

• Patient age must be 8-25 years, inclusive, at time of enrollment (NOTE: The first two subjects treated on this trial must be >= 18 years of age and at least two additional subjects must be 12-17.99 years of age before subjects < 12 years can enroll)
• Patients of both sexes and all ethnic backgrounds will be eligible
• All patients must be deemed a candidate for ASCT for the treatment of their autoimmune disease by their clinician based on the suggested criteria
• Systemic sclerosis cohort * Diagnosis of diffuse cutaneous systemic sclerosis according to Pediatric Rheumatology European Society/American College of Rheumatology/European League Against Rheumatism classification criteria for juvenile systemic sclerosis (SSc) * Subjects at high risk for a fatal outcome based on the presence of SSc-related pulmonary disease within 30 days prior to enrollment defined as at least one of: ** Total lung capacity (TLC) < 70% ** Forced vital capacity (FVC) < 70% ** Hemoglobin corrected diffusion lung capacity (DLCO) < 70% ** Evidence of alveolitis by high-resolution chest CT scan * Duration of disease < 5 years from first non-Raynaud’s symptoms
• Systemic lupus erythematosus cohort * Meeting at least 4 of 11 American College of Rheumatology criteria for systemic lupus erythematosus (SLE), or meeting Systemic Lupus International Collaborating Clinics (SLICC) criteria for lupus nephritis (requiring only biopsy-proven nephritis with positive antinuclear antibody [ANA] or anti-double stranded deoxyribonucleic acid [anti-dsDNA]) * Presence of anti-nuclear antibody * Active (refractory) disease despite at least six months of conventional therapy: ** Active disease may be defined by: *** British Isles Lupus Assessment Group (BILAG-A) *** Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) ≥ 8 , or *** Inability to decrease prednisone below 7.5mg/day due to active disease ** Conventional therapy defined as: *** Prior treatment with cyclophosphamide at doses of 500-1000 mg/m^2, or *** Mycophenolate mofetil * At least one organ dysfunctions, for example: ** Lupus nephritis with biopsy showing glomerulonephritis and potential reversible/non-fibrotic component ** Parenchymal disease of heart or lung ** Neuropsychiatric lupus ** Autoimmune cytopenias ** Vasculitis (ulceration, gangrene, tender finger nodules, periungual infarction, splinter hemorrhages, or biopsy/angiogram proven vasculitis) ** Antiphospholipid syndrome: visceral organ thrombotic or embolic event despite anticoagulation
• Serum creatinine > 1.5 x upper limit of normal for age unless attributable to autoimmune disease. If attributable to autoimmune disease, estimated glomerular filtration rate (eGFR) must be >= 30
• Transaminases > 5x upper limit of normal
• Serum conjugated (direct) bilirubin > 1.5x upper limit of normal unless attributable to autoimmune disease. If attributable to autoimmune disease, Child-Pugh score must be class A or class B. Child-Pugh score cannot be class C
• Shortening fraction < 27%, left ventricular ejection fraction < 50%, or evidence of severe pulmonary hypertension * Patients with pulmonary artery pressure > 55 mmHg will be excluded * Patients with Peak tricuspid regurgitation velocity > 2.8 m/s and/or a single finding in two of the three echocardiographic categories suggestive of hypertension (below) require assessment by cardiology of severity of hypertension and safety of ASCT ** Ventricles *** Right ventricle/left ventricle basal diameter ratio > 1.0 *** Flattening of intraventricular septum ** Pulmonary artery *** Right ventricular outflow Doppler acceleration time < 105 ms or mid-systolic notching *** Early diastolic pulmonary regurgitation velocity > 2.2 m/s ** Inferior vena cava *** Inferior vena cava diameter with decreased inspiratory collapse (< 50%)
• Diffusion capacity of the lung for carbon monoxide (DLCO) =< 40% (corrected for hemoglobin) in patients old enough to comply with pulmonary function tests (PFTs); baseline oxygen requirement for younger patients
• Lansky or Karnofsky performance < 60
• No active, untreated infections
• Negative for human immunodeficiency virus (HIV) by serology
• Patients with likely bacterial infections must be receiving appropriate antibacterial therapy and demonstrating therapy response. Patients with active tuberculosis infection will not be treated until infection resolves
• Patients with likely fungal infections must have had at least 2 weeks of appropriate anti-fungal antimicrobials (anti-mold if presumed or documented mold infection or anti-yeast if presumed or documented yeast infection), be asymptomatic, and have clinical/radiographic evidence of stable/improved disease
• For patients with symptoms consistent with active viral infection (including coronavirus disease [COVID]-19 or influenza) initiation of the transplant procedure will be delayed until symptoms are resolved. For patients with documented cytomegalovirus (CMV), Epstein-Barr virus (EBV) or other known viremia, initiation of the transplant procedure will be delayed until viremia has resolved with or without treatment. EBV that is positive by polymerase chain reaction (PCR) but not quantifiable is acceptable if repeated and same result is seen x 2 over a 2 week period
• Signed consent by parent/guardian or able to give consent if >= 18 years

Exclusion Criteria

• Patients who do not meet disease, organ or infectious criteria
• Previous hematopoietic stem cell transplant (HSCT) or solid organ transplant
• Pregnant females. All females of childbearing potential must have negative pregnancy test
• Lactating women who want to continue breastfeeding
• Participation in a clinical trial in which the patient receives an investigational drug within a time period equal or less than 5.5 half-lives of the investigational agent prior to study enrollment
• Given the potential risks of additive immunosuppression and unknown effects of DMARDs on the stem cell graft, DMARDS are standardly discontinued prior to any autologous stem cell transplant. Subjects who are unwilling or unable to discontinue disallowed DMARDs at time of enrollment will be excluded from this study * In general, disallowed DMARDs include any therapy (drugs, biologics or other treatments) clearly given for the purpose of treating the underlying autoimmune disease. This will include any Food and Drug Administration (FDA)-approved or experimental agents not currently available but that become available during the period of the trial. The only exception is anti-malarials for the treatment of SLE. Steroids at doses > 7.5mg/day (prednisone or prednisone equivalent) without clearly defined non-autoimmune disease indication will be considered a DMARD
• Any comorbidity that in the opinion of the investigators would jeopardize the ability of the subject to tolerate therapy (e.g. cannot safely undergo anesthesia for placement of central venous catheter, cannot tolerate periods of moderate to severe thrombocytopenia due to risk of bleeding)