Mortality Is Increased in Those with a ≥10% Reduction in Spirometry Following Allogeneic Hematopoietic Stem Cell Transplant: A Retrospective 5-Year Follow-up Study from a Single Transplant Service

Abstract

Pulmonary graft versus host disease (GVHD) is a common and serious complication of hematopoietic stem cell transplantation (HSCT). Early diagnosis is essential for rapid treatment before irreversible changes in lung function occur. The National Institutes of Health (NIH) support that a decline in forced expiratory volume in 1 second (FEV₁) of ≥10% from baseline values requires further investigation and close monitoring post HSCT. Previous research demonstrates that a 10% to 19% and ≥20% reduction in FEV₁ within 6 months of transplantation is associated with higher odds of 1-year mortality. However, to the authors’ knowledge, there is no long-term follow-up data of FEV₁ decline with an onset after the first 6-month period. We aimed to investigate the clinical significance of a ≥10% decrement in FEV₁ measured by spirometry for predicting all-cause mortality in HSCT recipients over a period of 5 years. A comparison was made with patients who met the NIH diagnostic criteria for lung GVHD. Long-term follow-up data of patients who received an allogeneic HSCT at Westmead was audited retrospectively using a censoring period of 5 years. A decrease in lung function was defined as a change in FEV₁ by ≥10% from their best value, usually at the beginning of the transplant process. Recovery was defined as a ≥10% increase in FEV₁ from the patient’s maximum decline in lung function. A diagnosis of lung GVHD was made when the following criteria were met: FEV₁/forced vital capacity (FVC) ratio of <0.7, and an FEV₁ <75% of predicted normal with ≥10% reduction over less than 2 years and evidence of gas trapping. Data from 364 patients who underwent an allogeneic HSCT between 2013 and 2019 were analyzed; 173 patients (47.7%) experienced a ≥10% reduction in FEV₁ after transplantation. Ninety-five patients experienced an FEV₁ decline lasting <6 months and were likely to recover over half their lost lung function (median % FEV recovered = 68.7%). Seventy-eight patients experienced an FEV₁ decline lasting >6 months and were unlikely to recover any lost lung function (median % FEV recovered = 0%). There was a significant relationship between ≥10% FEV₁ decline and death, X²(1, 364) = 15.67, P < .001. All-cause mortality was doubled in those who experienced ≥10% FEV₁ decline (34%) compared with those without any decline (16%). Mortality was highest in those who experienced decline without any recovery (odds ratio [OR], 2.98; 95% confidence interval [CI], 1.64-5.41). However, in the group who had a decline and then later recovered, mortality was still elevated (OR, 2.08; 95 CI, 1.17-3.69) compared with those who did not experience any FEV₁ decline ≥10%. Mortality risk is elevated from the first ≥10% reduction in FEV₁ and remains elevated even if FEV₁ recovery occurs. Individuals whose FEV₁ declines for longer than 6 months are unlikely to experience FEV₁ recovery despite treatment. An FEV₁ decline of at least ≥10% from pretransplant value should trigger rapid assessment to identify and treat mortality risks and to minimize decline in overall respiratory function.