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Pulmonary function remained stable -- and in some ways improved -- among patients with sickle cell disease (SCD) who underwent non-myeloablative hematopoietic cell transplant (HCT), a prospective cohort study suggested.

Among 97 patients who underwent HCT, the median percent-predicted forced expiratory volume in 1 second (FEV1) was 68.3% pre-HCT compared with 69.2% at 3 years post-HCT, reported A. Parker Ruhl, MD, MHS, of the National Institute of Allergy and Infectious Diseases and the National Heart, Lung, and Blood Institute, and colleagues.

When using generalized estimation equations (GEE) regression modeling, which adjusted for age and sex, there was no significant change in percent-predicted FEV1 post-HCT, they noted in the .

However, GEE modeling did show a statistically significant improvement in the diffusing capacity of the lungs for carbon monoxide from pre-HCT to 2 years post-HCT (estimated change 3.9%), which was sustained at 3 years (3.7%).

In addition, there was a statistically significant post-HCT increase in the 6-minute walk distance (6MWD) test compared with pre-HCT for each year of follow-up, with an estimated increase of 25.9 m at 3 years, which was "comparable to the minimal clinically important difference in 6MWD for several cardiopulmonary processes ... and is a meaningful patient-centered outcome in these adult patients," Ruhl and colleagues observed.

"These findings support the hypothesis that non-myeloablative transplant is not harmful to lung function in adults with SCD," they wrote. "Moreover, allogeneic HCT for SCD may cease the cycle of vaso-occlusive injury to the lung tissue and airway system and prevent further damage."

"Given that lung function is known to decrease over time in the pediatric SCD population, and that lung function impairment is frequent and also declines in adulthood in SCD, the finding that lung function does not worsen either immediately after or for 3 years in this post-HCT cohort is an important contribution to the field," they added.

In explaining the rationale behind the study, Ruhl and colleagues said that while research has shown that non-myeloablative conditioning regimens are not expected to significantly affect lung function in children and adolescents, "more data are needed to evaluate the long-term health effects of non-myeloablative HCT in the SCD population in adults."

They hypothesized that percent-predicted FEV1 -- a measure associated with early death in SCD -- would be stable after non-myeloablative human leukocyte antigen (HLA)-matched sibling or haploidentical HCT.

All 97 patients in the study had pulmonary function testing performed before HCT, and 91, 72, and 55 patients had follow-up testing data available at years 1, 2, and 3, respectively, after HCT.

Of the overall cohort, 67% underwent HLA-matched sibling transplants, and 33% underwent haploidentical transplants. Pre-HCT, median age was 31.8 years, with four patients under the age of 18; 42% were female, and 90% had hemoglobin SS disease.

The study cohort had significant comorbidities, including a history of acute chest syndrome (ACS; 35%), ACS that required intensive care unit admission or ventilation (29%), asthma (13%), right heart catheterization-defined pulmonary hypertension (9%), receipt of regular exchange transfusions (19%), chronic pain (44%), and a history of venous thrombosis (22%).

The authors acknowledged that the number of patients with significant comorbidities was a limitation to the study, since they may not be representative of all patients undergoing HCT.

"Despite these considerable pre-HCT comorbidities, these patients fared well as a group from a pulmonary perspective," they wrote. "Therefore, these findings suggest that non-myeloablative transplant regimens for sickle cell disease do not carry the same risks of developing pulmonary graft-vs-host disease as other myeloablative regimens used for cancer treatments."

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