Does Myeloablative HSCT Impact Pulmonary Outcomes in Pediatric Patients With Sickle Cell Disease?

Myeloablative hematopoietic stem cell transplantation (HSCT) “resulted in stable pulmonary function” among pediatric patients with sickle cell disease (SCD), according to findings from a recent study.

Cynthia Joseph, MD, of Children’s Hospital Colorado, and colleagues conducted the study and published their findings in Transplantation and Cellular Therapy.

The investigators explained that it was important to explore the effects of transplantation on pulmonary function in pediatric patients because “the unique pathophysiological features of SCD contribute to widespread vascular dysfunction and end-organ damage,” which predominantly affect the pulmonary system.

Moreover, the investigators highlighted the “spectrum of chronic complications” that can affect patients in this population after transplantation, including pulmonary hypertension, asthma and recurrent acute chest syndrome. In addition, they emphasized that “access to curative therapies including hematopoietic stem cell therapy and gene therapy remains low for patients living with SCD.”

The retrospective analysis evaluated pediatric patients with SCD who underwent HSCT “at a single-center institution.” Investigators identified the baseline characteristics gathered among participants such as, age, genotype and disease severity. They analyzed disease severity “by the number and frequency of acute chest syndrome episodes and prior disease complications.”

The researchers also assessed for transplant-related variables, including pulmonary function before and after transplant, occurrence of graft-versus-host disease (GVHD), conditioning regimens and chimerism.

Pulmonary function among eligible participants (n=27) “was followed for up to three years post-transplant to evaluate long-term pulmonary outcomes and transplant-related complications.” Longitudinal assessments were also conducted during the study and included “review of imaging with CT scans and pulmonary function tests (PFTs) at defined intervals” before and after transplant.

According to the results, three patients in the cohort received gene therapy and one patient received two transplants due to graft failure. A total of four patients in the cohort “did not have baseline PFTs available due to young age.” The investigators explained that “varying degrees of lung disease along with the comorbidity of asthma were noted pre-transplant, as evidenced by PFT abnormalities and imaging findings.”

The results also showed that after transplant “pulmonary function remained stable or showed improvement in the majority of patients,” despite one patient who demonstrated “worsened pulmonary function at 1-year post-transplant, although older age at [the] time of transplant may have contributed to [a] poorer outcome.”

In reflecting on the findings, the investigators also highlighted that “no patients experienced recurrence of acute chest syndrome during the post-transplant follow-up period, even in patients with mixed chimerism.”

“Overall transplantation resulted in stable pulmonary function,” the researchers concluded. “Further research is warranted to better understand long-term organ function and to optimize outcomes in this population.”