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

Background: Pulmonary graft versus host disease is a common and serious complication of haematopoietic stem cell transplant (HSCT). Early diagnosis is essential for rapid treatment before irreversible changes in lung function occur. The NIH support that a decline in forced expiratory volume in 1 second (FEV₁) of ≥10% from baseline values require further investigation and close monitoring post HSCT-transplant. Previous research demonstrates that a 10-19% and ≥20% reduction in FEV₁, within 6 months of transplant, is associated with higher odds of 1-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.

Objectives: 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 to patients who met the NIH diagnostic criteria for lung GvHD.

Study design: Long-term follow-up data of patients who received an allogeneic HSCT at Westmead was retrospectively audited, 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/FVC ratio of < 0.7, and an FEV1 <75% of predicted normal with ≥10% reduction over less than two years and evidence of gas trapping.

Results: Data from 364 patients who underwent an allogeneic HSCT between 2013 and 2019 were analysed; 173 patients (47.7%) experienced a ≥10% reduction in FEV₁ after transplant. 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 <0.001. 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 (OR = 2.98 [1.64-5.41]). However, in the group who had a decline and then later recovered mortality was still elevated (OR = 2.08 [1.17-3.69]) compared with those who did not experience any FEV₁ decline ≥10%.

Conclusion: 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 pre-transplant value should trigger rapid assessment to identify and treat mortality risks, and to minimise decline in overall respiratory function.