Autologous hematopoietic stem cell transplantation (HSCT) is based on the assumption that autoimmune diseases like systemic sclerosis occur when the white blood cells of the immune system attack the body. In this treatment, stem cells from the patient's blood are extracted and stored to preserve them. The patient's white blood cells are destroyed with cyclophosphamide and rabbit antibodies against the white blood cells. Then the stored blood is returned to the patient's bloodstream to reconstitute a healthy blood and immune system which will not attack the body. The results of a phase 3 trial, the Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, with 156 patients were published in 2014. HSCT itself has a high treatment mortality, so in the first year, the survival of patients in the treatment group was lower than the placebo group, but at the end of 10 years, the survival in the treatment group was significantly higher. The authors concluded that HSCT could be effective, if limited to patients who were healthy enough to survive HSCT itself. Therefore, HSCT should be given early in the progression of the disease, before it does damage. Patients with heart disease, and patients who smoked cigarettes, were less likely to survive.   Another trial, the Stem Cell Transplant vs. Cyclophosphamide (SCOT) trial, is ongoing. 
Corticosteroids have been used as drug treatment for some time. Lewis Sarett of Merck & Co. was the first to synthesize cortisone, using a complicated 36-step process that started with deoxycholic acid, which was extracted from ox bile .  The low efficiency of converting deoxycholic acid into cortisone led to a cost of US $200 per gram. Russell Marker , at Syntex , discovered a much cheaper and more convenient starting material, diosgenin from wild Mexican yams . His conversion of diosgenin into progesterone by a four-step process now known as Marker degradation was an important step in mass production of all steroidal hormones, including cortisone and chemicals used in hormonal contraception .  In 1952, . Peterson and . Murray of Upjohn developed a process that used Rhizopus mold to oxidize progesterone into a compound that was readily converted to cortisone.  The ability to cheaply synthesize large quantities of cortisone from the diosgenin in yams resulted in a rapid drop in price to US $6 per gram, falling to $ per gram by 1980. Percy Julian's research also aided progress in the field.  The exact nature of cortisone's anti-inflammatory action remained a mystery for years after, however, until the leukocyte adhesion cascade and the role of phospholipase A2 in the production of prostaglandins and leukotrienes was fully understood in the early 1980s.
There have been no randomized trials examining the effect of hydrocortisone given after the first week of life or used to treat infants with prolonged ventilator dependence. One retrospective cohort study compared infants who required assisted ventilation and oxygen after the first one to two weeks of age and received hydrocortisone with a group of healthier infants who did not receive hydrocortisone.  Infants treated with hydrocortisone experienced decreasing oxygen requirements and were successfully weaned from assisted ventilation. After seven days of treatment, there were no differences in oxygen requirements between the two groups. On follow-up, there were no differences in head circumference, neurological outcome, psychomotor development or school performance. Magnetic resonance imaging performed at eight years of age on a similar cohort of infants treated with hydrocortisone showed that although, overall, children born preterm had significantly reduced grey matter volumes compared to term children, there were no differences in the intracranial volumes, grey matter volumes or white matter volumes between children who did and did not receive hydrocortisone for treatment of CLD.  There were also no differences in neurocognitive outcomes, assessed using the Wechsler Intelligence Scales for Children.