Stem-Cell Transplant Improves Outcomes of High-Risk Sickle-Cell Disease

By Reuters Staff

December 12, 2019

NEW YORK (Reuters Health) - Familial haploidentical stem-cell transplant improves outcomes in children and adolescents with high-risk sickle-cell disease, researchers report.

HLA-matched sibling allogeneic stem-cell transplant has been shown to improve event-free survival (EFS) in sickle-cell disease (SCD). But rates of graft failure and chronic graft-versus-host disease (GVHD) have been higher than expected.

Dr. Mitchell S. Cairo of New York Medical College, in Valhalla, and colleagues investigated the feasibility, safety, and one-year EFS following myeloimmunoablative conditioning and familial haploidentical stem-cell transplant with CD34+ enrichment and mononuclear cell addback in 19 patients (mean age, 13.1 years) with high-risk SCD.

The median time to neutrophil engraftment was nine days posttransplant, and the median time to platelet engraftment was 19 days posttransplant.

At one year posttransplant, mean donor chimerism was 97.1% for peripheral blood and 96.4% for red blood cell count, the researchers report in JAMA Pediatrics.

The cumulative incidence of grades-2 to -4 acute GVHD and late acute GVHD was 6.2%, and the cumulative incidence of moderate and/or severe chronic GVHD was 6.7%.

The probability of EFS or overall survival was 90% at one year and 84% at two years, with no patient having residual SCD symptoms.

There were three deaths: one from sinusoidal obstruction syndrome at posttransplant day 59, one from steroid-refractory grade-3 acute GVHD at posttransplant day 141, and one from severe chronic GVHD at posttransplant day 390.

At two years, pulmonary and cardiac functions were stable to improved, and there were significant improvements in emotional functioning, physical functioning and neurocognitive processing speed.

"Long-term follow-up is currently underway to assess future risks of chronic GVHD, neurocognitive function, health-related quality of life, and fertility," the researchers note. "Furthermore, alternative allogeneic donor approaches must be balanced in the future with the safety and efficacy of gene therapy in patients with high-risk SCD."

Dr. Cairo did not respond to a request for comments.

SOURCE: JAMA Pediatrics, online December 9, 2019.