Pulmonary function in children and adolescents with sickle cell disease after nonmyeloablative hematopoietic cell transplantation

Abstract

Background: Pulmonary complications are common in sickle cell disease (SCD). The use of standard myeloablative conditioning regimens may increase the risk of lung injury. We report serial pulmonary function testing (PFT) outcomes in children with SCD who underwent a matched-sibling donor hematopoietic cell transplantation (HCT) using nonmyeloablative (NMA) protocol.Methods: This is a retrospective chart review describing pulmonary outcomes in pediatric patients post HCT. The conditioning regimen consisted of alemtuzumab and a single fraction of 300 cGy of total body irradiation (TBI), and sirolimus for graftversus-host disease (GVHD) prophylaxis. Serial PFT testing was performed pre and post HCT. The evaluated pulmonary measures included: forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1 ), FEV 1 /FVC, and forced expiratory flow (FEF 25-75 ).Results: Twelve subjects were included in the analysis. All had HbSS genotype, and five of the 12 patients had one or more episodes of acute chest syndrome prior to HCT. Serial PFT measures were completed per patient. No patient was diagnosed with chronic GVHD of any organ post HCT. The baseline median FVC, FEV 1 , FEV 1 /FVC, and FEF 25-75 were within the normal range and remained relatively unchanged post HCT.A linear mixed effects model, adjusting for gender and time from HCT, suggested no significant relationship between HCT and PFT parameters, including FVC, FEV 1 , and FEV 1 /FVC. Interestingly, the FEF 25-75 results exhibited a shift in the means post HCT (pre-HCT 86.2% predicted and post-HCT 93.05% predicted, p-value = .018). Conclusion:Our study suggests that HCT in children with SCD may prevent the anticipated decline in pulmonary function over time.

Lung function after matched‐related donor allogeneic hematopoietic stem cell transplantation in children with sickle cell disease

“…Like previous studies, we showed prolonged stability of lung function in most patients who underwent HSCT and very few pulmonary complications, with only one case of acute pulmonary GVHD. 4 In our cohort, the most frequent ventilatory defect in the posttransplant period was RVD, with an estimated prevalence of 24%. This prevalence probably varies with age and has been reported from 20% to 30% in similar studies.…”

Effect of allogeneic hematopoietic stem cell transplantation on sickle cell disease‐related organ complications: A systematic review and meta‐analysis

“…After reviewing the full‐text articles, another five studies were excluded based on study design (two because of missing outcome measure, one because of limited follow‐up, one was a literature review, and one because of different patient population). Finally, 34 studies were eligible for inclusion 8,18–50 . All 34 studies were used for the qualitative synthesis, of which 17 studies were also used in the meta‐analyses comparing organ function before and after HSCT.…”

“…In the meta‐analyses, there was no significant difference in FEV1 (SMD 0.08, p = .49), FVC (SMD 0.13, p = .35), or DLCO (SMD 0.95, p = .30) after HSCT as compared to before HSCT (Figure 2, Figure S1). The timepoint for the post‐HSCT assessment of pulmonary function was +2 years in three studies, 8,19,24 and after +3.2, +2.6, +2.4, and + 9 years in the other four studies 23,30,35,38 …”

“…Ten included studies evaluated pulmonary function before and after HSCT by spirometry, of which seven were included in the meta-analyses (Table S3). 8,19,23,24,30,31,35,38,49,50 Clinical heterogeneity among studies used for the meta-analyses for outcome parameters FEV1, FVC, and DLCO was classified as moderate (score 12) for all three measurements, as assessed with the "Clinical Diversity in Meta-analyses" tool. Only one study comprised adult patients.…”

“…The timepoint for the post-HSCT assessment of pulmonary function was +2 years in three studies, 8,19,24 and after +3.2, +2.6, +2.4, and + 9 years in the other four studies. 23,30,35,38…”