Better clinical outcomes seen with myeloablative autologous hematopoietic stem-cell transplantation for scleroderma patients

Liz Meszaros, MDLinx | March 16, 2018

In patients with scleroderma, myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation (MASCT) improved both event-free and overall survival, but showed increased toxicity compared with cyclophosphamide, according to results published in The New England Journal of Medicine.


Myeloablative autologous hematopoietic stem-cell transplantation

Researchers found clear benefits in clinical outcomes, but toxicity and the risk of second cancers should be considered when choosing a treatment plan for patients with scleroderma.

“Our trial (Scleroderma: Cyclophosphamide or Transplantation [SCOT]) tests a different therapeutic approach: myeloablation with total-body irradiation followed by reconstitution with a CD34+ selected autograft versus cyclophosphamide. We hypothesized that myeloablative transplantation would result in better long-term outcomes than cyclophosphamide treatment,” wrote these researchers, led by Keith M. Sullivan, MD, James B. Wyngaarden Professor of Medicine, Duke Cancer Institute, Duke University School of Medicine, Durham, NC.

Dr. Sullivan and colleagues compared MASCT with immunosuppression with 12 monthly infusions of cyclophosphamide. They included 36 subjects randomized to MASCT and 39 to cyclophosphamide. Patients were aged 18 to 69 years and had scleroderma for 5 years or less, in addition to pulmonary or renal involvement.

At 54 months in the intent-to-treat population, MASCT showed superiority to cyclophosphamide, with 67% of 1,404 pair-wise comparisons favoring transplantation vs 33% in favor of cyclophosphamide (P=0.01). Event-free survival at 54 months was higher in the transplantation group compared with the group completing nine or more doses of cyclophosphamide (per-protocol population) (79% vs 50%, respectively; P=0.02).

Kaplan-Meier estimations showed that both event-free survival and overall survival favored transplantation. In the transplantation group, event-free survival was 74% vs 47% in the cyclophosphamide group (P=0.03). Overall survival was 86% vs 51%, respectively (P=0.02).

Over 72 months, fewer subjects in the cyclophosphamide group experienced serious adverse events (SAEs) compared with those in the transplantation group (51% vs 74%, respectively). After accounting for follow-up duration, researchers found that the rate of SAEs was 0.38 person-years in the transplantation group and 0.52 in the cyclophosphamide group (P=0.08). The majority of SAEs and adverse events occurred within the first 26 months in both groups.

Varicella zoster infection occurred in 12 subjects in the transplantation group, and 1 in the cyclophophamide group (P < 0.001). Five cases of cytomegalovirus reactivation occurred.

Three subjects in the transplantation group and one in the cyclophosphamide group developed cancers. Infection rates were similar in both groups (0.75 vs 0.79, respectively), but grade 3 or higher infections per person-year occurred more frequently in the transplantation group (0.21 vs 0.13; P=0.09).

Adverse events of grade 3 or higher occurred more frequently in the transplantation group than in the cyclophosphamide group (100% vs 84%, respectively), as did a higher event rate per person-year (2.0 vs 1.2; P < 0.001).

Fewer transplantation subjects had to initiate treatment with disease-modifying antirheumatic drugs compared with the cyclophosphamide group by 54 months (9% vs 44%, respectively; P=0.001).

Treatment-related mortality in the transplantation group was 3% at 54 months and 6% at 72 months, compared with 0% in the cyclophosphamide group.

“In conclusion, at 54 months after randomization, myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation resulted in significantly better clinical outcomes than 12 months of cyclophosphamide. Although there was greater hematopoietic toxicity and an unquantified risk of second cancers from exposure to total body irradiation, toxic effects should be weighed against the beneficial results of treatment and the seriousness of the underlying disease,” concluded the authors.

This study was funded by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health.